18 F-Fluorination of a supported 2-(aryl-di-tert-butylsilyl)-N-methyl-imidazole for indirect 18 F-labeling of a VH H single-variable domain.

Anchoring an imidazole-di-tert-butyl-arylsilane possessing an azido group to a polystyrene resin provided a heterogeneous precursor that was radiolabeled easily using aqueous [18 F]fluoride. After optimizing the conditions (i.e., using DMSO as solvent and heating at 160°C for 15 min), the desired [18 F]fluorosilane was obtained in 24% radiochemical yield (RCY) and 78% radiochemical purity (RCP) using solid-phase extraction as sole purification. Then, this compound was conjugated by strain-promoted alkyne-azide cycloaddition to a model single-variable domain possessing a cyclooctyne tag, yielding to the desired 18 F-labeled bioconjugate in 2% RCY and >95% RCP after purification by a size exclusion chromatography.

Deciphering the role of non-Frankia nodular endophytes in alder through in vitro and genomic characterization.

Endophytic bacterial populations are well-positioned to provide benefits to their host plants such as nutrient acquisition and plant hormone level manipulation. Actinorhizal plants such as alders are well known for their microbial symbioses that allow them to colonize harsh environments whether natural or anthropized. Although the nitrogen-fixing actinobacterium Frankia sp. is the main endophyte found in alder root nodules, other bacterial genera, whose roles remain poorly defined, inhabit this niche. In this study, we isolated a diverse panel of non-Frankia nodular endophytes (NFNE). Some NFNE were isolated from alders grown from surface-sterilized seeds and maintained in sterile conditions, suggesting these may have been seed-borne. In vitro testing of 24 NFNE revealed some possessed putative plant growth promotion traits. Their genomes were also sequenced to identify genes related to plant growth promotion traits. This study highlights the complexity of the alder nodular microbial community. It paves the way for further understanding of the biology of nodules and could help improve land reclamation practices that involve alders.

Neighbours in nodules: the interactions between Frankia sp. ACN10a and non-Frankia nodular endophytes of alder.

In the present study, we report the in vitro interactions between Frankia sp. ACN10a and non-Frankia nodular endophytes (NFNE) isolated from alder. The supernatant of NFNE grown in nitrogen-replete medium had neutral or negative effects on Frankia growth; none had a stimulatory effect. Inhibitory effects were observed for supernatants of some NFNE, notably Micromonospora, Pseudomonas, Serratia and Stenotrophomonas isolates. However, some NFNE-Frankia coculture supernatants could stimulate Frankia growth when used as a culture medium supplement. This was observed for supernatants of Frankia cocultured with Microvirga and Streptomyces isolates. In nitrogen-limited conditions, cocultures of Frankia with some NFNE, including some rhizobia and Cytobacillus, resulted in higher total biomass than Frankia-only cultures, suggesting cooperation, while other NFNE were strongly antagonistic. Microscopic observation of cocultures also revealed compromised Frankia membrane integrity, and some differentiation into stress resistance-associated morphotypes such as sporangia and reproductive torulose hyphae (RTH). Furthermore, the coculture of Frankia with Serratia sp. isolates resulted in higher concentrations of the auxinic plant hormone indole-3-acetic acid and related indolic compounds in the culture supernatant. This study sheds new light on the breadth of microbial interactions that occur amongst bacteria that inhabit the understudied ecological niche of the alder nodule.

Data Freshness and End-to-End Delay in Cross-Layer Two-Tier Linear IoT Networks.

The operational and technological structures of radio access networks have undergone tremendous changes in recent years. A displacement of priority from capacity-coverage optimization (to ensure data freshness) has emerged. Multiple radio access technology (multi-RAT) is a solution that addresses the exponential growth of traffic demands, providing degrees of freedom in meeting various performance goals, including energy efficiencies in IoT networks. The purpose of the present study was to investigate the possibility of leveraging multi-RAT to reduce each user's transmission delay while preserving the requisite quality of service (QoS) and maintaining the freshness of the received information via the age of information (AoI) metric. First, we investigated the coordination between a multi-hop network and a cellular network. Each IoT device served as an information source that generated packets (transmitting them toward the base station) and a relay (for packets generated upstream). We created a queuing system that included the network and MAC layers. We propose a framework comprised of various models and tools for forecasting network performances in terms of the end-to-end delay of ongoing flows and AoI. Finally, to highlight the benefits of our framework, we performed comprehensive simulations. In discussing these numerical results, insights regarding various aspects and metrics (parameter tuning, expected QoS, and performance) are made apparent.

Direct Carbon Isotope Exchange of Pharmaceuticals via Reversible Decyanation.

The incorporation of carbon-14 allows tracking of organic molecules and provides vital knowledge on their fate. This information is critical in pharmaceutical development, crop science, and human food safety evaluation. Herein, a transition-metal-catalyzed procedure enabling carbon isotope exchange on aromatic nitriles is described. By utilizing the radiolabeled precursor Zn([14C]CN)2, this protocol allows the insertion of the desired carbon tag without the need for structural modifications, in a single step. By reducing synthetic costs and limiting the generation of radioactive waste, this procedure will facilitate the labeling of nitrile containing drugs and accelerate 14C-based ADME studies supporting drug development.

Biosynthesis of [14 C]-11-De-O-Methyltomaymycin, a Precursor of Radiolabelled Antibody Drug Conjugates.

Antibody drug conjugates (ADCs) are one of the most promising technologies to treat cancer as they combine the specificity of an antibody with the high potency of a cytotoxic molecule such as tomaymycin derivatives, which are DNA-interactive antitumor antibiotics previously isolated from bacterial broth. The multistep chemical synthesis of some tomaymycin derivatives is complicated because their structures contain a reactive imine bond. Therefore, we turned to biosynthesis to obtain 14 C radiolabelled tomaymycin derivative to support ADME studies. Following Hurley's work (J. Antibiotics 1977, 30, 349-370; Antimicrob. Agents Chemother. 1979, 15, 42-45; Acc. Chem. Res. 1980, 13, 263-269), the 14 C radiolabel was incorporated efficiently in one step from radiolabelled tyrosine using the strain Streptomyces sp. FH6421. This process has been further optimized by using anthranilic acid as radiolabelled precursor, leading to one of the highest incorporation levels of radiochemical precursors published to date. This biosynthetic strategy is the fastest way to access such radiolabelled precursors.

Bacillus subtilis Modulates Its Usage of Biofilm-Bound Iron in Response to Environmental Iron Availability.

Iron (Fe) is one of the most important micronutrients for most life forms on earth. While abundant in soil, Fe bioavailability in oxic soil is very low. Under environmental conditions, bacteria need to acquire sufficient Fe to sustain growth while limiting the energy cost of siderophore synthesis. Biofilm formation might mitigate this Fe stress, since it was shown to accumulate Fe in certain Gram-negative bacteria and that this Fe could be mobilized for uptake. However, it is still unclear if, and to what extent, the amount of Fe accumulated in the biofilm can sustain growth and if the mobilization of this local Fe pool is modulated by the availability of environmental Fe (i.e., Fe outside the biofilm matrix). Here, we use a nondomesticated strain of the ubiquitous biofilm-forming soil bacterium Bacillus subtilis and stable Fe isotopes to precisely evaluate the origin of Fe during growth in the presence of tannic acid and hydroxides, used as proxies for different environmental conditions. We report that this B. subtilis strain can accumulate a large quantity of Fe in the biofilm, largely exceeding Fe associated with cells. We also report that only a fraction of biofilm-bound Fe is available for uptake in the absence of other sources of Fe in the vicinity of the biofilm. We observed that the availability of environmental Fe modulates the usage of this pool of biofilm-bound Fe. Finally, our data suggest that consumption of biofilm-bound Fe relates to the efficacy of B. subtilis to transport Fe from the environment to the biofilm, possibly through siderophores.IMPORTANCE Recent pieces of evidence suggest that Fe bound to the biofilm could assume at least two important functions, a local source of Fe for uptake and a support to extracellular metabolism, such as extracellular electron transfer. Our results show that B. subtilis can use biofilm-bound Fe for uptake only if it does not compromise Fe homeostasis of the biofilm, i.e., maintains a minimum Fe concentration in the biofilm for extracellular purposes. We propose a theoretical framework based on our results and recent literature to explain how B. subtilis manages biofilm-bound Fe and Fe uptake in response to environmental Fe availability. These results provide important insights into the management of biofilm-bound and environmental Fe by B. subtilis in response to Fe stress.

Iron Homeostasis in Bacillus subtilis Requires Siderophore Production and Biofilm Formation.

Iron (Fe) is the most important metal in biology. Despite its abundance, Fe is mostly present as a ferric form in soils, strongly limiting its bioavailability. To overcome the challenge of Fe acquisition, many microorganisms produce siderophores to retrieve Fe from natural sources. Another ubiquitous feature of bacteria in natural environments is biofilm formation. Previous studies showed that external Fe strongly influenced biofilm formation in several bacteria, suggesting that this microenvironment plays a mechanistic role in micronutrient acquisition for bacteria. Here, we applied a complementary set of analytical methods and deletion mutants to evaluate the role of biofilm formation, siderophore production, and their interaction in Fe homeostasis in Bacillus subtilis We observed that Fe homeostasis, i.e., active growth at a constant intracellular Fe concentration, requires both siderophore production and biofilm formation. Also, we report that in B. subtilis, both biofilm formation and siderophore production are required to achieve active Fe acquisition from the medium and to sustain normal growth. Furthermore, we provide evidence that the formation of biofilm slightly enhances the kinetics of Fe complexation by catechol siderophores and markedly improves siderophore use efficiency. These results provide new perspectives on the mechanism underlying siderophore-based acquisition of Fe in biofilm-forming bacteria.IMPORTANCE Iron acquisition is of fundamental importance for microorganisms, since this metal is generally poorly bioavailable under natural conditions. In the environment, most bacteria are found tightly packed within multicellular communities named biofilms. Here, using the soil Gram-positive bacterium Bacillus subtilis, we show that biofilm formation and the production of siderophores, i.e., small molecules specifically binding metals, are both essential to ensure Fe uptake from the medium and maintain cellular Fe homeostasis. The biofilm matrix appears to play an important role favoring the efficient usage of siderophores. Taken together, our results demonstrate a close link between biofilm formation and iron acquisition in B. subtilis, allowing a better comprehension of how bacteria can cope with metal limitation under environmental conditions.

Comparative genomics of Rhizophagus irregularis, R. cerebriforme, R. diaphanus and Gigaspora rosea highlights specific genetic features in Glomeromycotina.

Glomeromycotina is a lineage of early diverging fungi that establish arbuscular mycorrhizal (AM) symbiosis with land plants. Despite their major ecological role, the genetic basis of their obligate mutualism remains largely unknown, hindering our understanding of their evolution and biology. We compared the genomes of Glomerales (Rhizophagus irregularis, Rhizophagus diaphanus, Rhizophagus cerebriforme) and Diversisporales (Gigaspora rosea) species, together with those of saprotrophic Mucoromycota, to identify gene families and processes associated with these lineages and to understand the molecular underpinning of their symbiotic lifestyle. Genomic features in Glomeromycotina appear to be very similar with a very high content in transposons and protein-coding genes, extensive duplications of protein kinase genes, and loss of genes coding for lignocellulose degradation, thiamin biosynthesis and cytosolic fatty acid synthase. Most symbiosis-related genes in R. irregularis and G. rosea are specific to Glomeromycotina. We also confirmed that the present species have a homokaryotic genome organisation. The high interspecific diversity of Glomeromycotina gene repertoires, affecting all known protein domains, as well as symbiosis-related orphan genes, may explain the known adaptation of Glomeromycotina to a wide range of environmental settings. Our findings contribute to an increasingly detailed portrait of genomic features defining the biology of AM fungi.

The first radiosynthesis of 2-amino-5-[18F]fluoropyridines via a "minimalist" radiofluorination/palladium-catalyzed amination sequence from anisyl(2-bromopyridinyl)iodonium triflate.

The synthesis of 2-amino-5-[18F]fluoropyridines was achieved in 8-85% yields by palladium-catalyzed reaction of 2-bromo-5-[18F]fluoropyridine with piperidine, dimethylamine, butylamine, methylpiperazine, benzylamine, aniline and 3-aminopyridine. 2-Bromo-5-[18F]fluoropyridine was obtained by radiofluorination of anisyl(2-bromopyridinyl-5)iodonium triflate (88% yield). The radiofluorination step was performed under "minimalist" conditions to guarantee a successful subsequent amination reaction.

Two new convenient syntheses of 14C-squalene from turbinaric acid.

Carbon-14 labeled (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, also known as squalene, was synthesized as a tool for pharmacokinetic studies. Two simple and efficient labeling approaches were developed to give [2-14 C]-squalene and [3-14 C]-squalene from a halogenated precursor derived from turbinaric acid. They were obtained in 13.5% radiochemical yield in 6 steps and in 38% radiochemical yield in 3 steps respectively from carbon-14 labeled potassium cyanide with a radiochemical purity higher than 98% in both cases.

Bmp signaling in colonic mesenchyme regulates stromal microenvironment and protects from polyposis initiation.

In the colon, myofibroblasts are primary contributors in the establishment of the microenvironment involved in tissue homeostasis. Alterations in myofibroblast functions lead to changes resulting in a toxic microenvironment nurturing tumorigenesis. Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in adult gut homeostasis. Studies in genetically-modified mice have shown that Bmp disruption in all cell layers leads to the development of gut polyposis. In contrast, our studies showed that loss of Bmp exclusively in the gastrointestinal epithelium resulted in increased epithelial proliferation without polyposis initiation, thus suggesting a key role for mesenchymal Bmp signaling in polyposis initiation. In order to identify the role of mesenchymal Bmp signaling on the microenvironment and its impact on colonic mucosa, a mouse model was generated with suppression of Bmp signaling exclusively in myofibroblasts (Bmpr1aΔMES). Bmpr1aΔMES mice exhibited increased subepithelial proliferation with changes in cellular composition leading to the development of a primed stroma with modulation of extracellular matrix proteins, immune cells and cytokines as early as 90 days of age. This microenvironmental deregulation was associated with increased polyposis initiation at one year of age. These results are the first to demonstrate that mesenchymal Bmpr1a inactivation alone is sufficient to prompt an expansion of myofibroblasts leading to the development of a reactive mesenchyme that contributes to polyposis initiation in the colon. These findings support the novel concept that inhibition of Bmp signaling in mesenchymal cells surrounding the normal epithelium leads to important changes instructing a toxic microenvironment sufficient to induce colonic polyposis.

Performance of ectomycorrhizal alders exposed to specific Canadian oil sands tailing stressors under in vivo bipartite symbiotic conditions.

Canadian oil sands tailings are predominately sodic residues contaminated by hydrocarbons such as naphthenic acids. These conditions are harsh for plant development. In this study, we evaluated the effect of inoculating roots of Alnus viridis ssp. crispa and Alnus incana ssp. rugosa with ectomycorrhizal fungi in the presence of tailings compounds. Seedlings were inoculated with 7 different strains of Paxillus involutus and Alpova diplophloeus and were grown under different treatments of NaCl, Na2SO4, and naphthenic acids in a growth chamber. Afterwards, seedling survival, height, dry biomass, leaf necrosis, and root mycorrhization rate were measured. Paxillus involutus Mai was the most successful strain in enhancing alder survival, health, and growth. Seedlings inoculated with this strain displayed a 25% increase in survival rate, 2-fold greater biomass, and 2-fold less leaf necrosis compared with controls. Contrary to our expectations, A. diplophloeus was not as effective as P. involutus in improving seedling fitness, likely because it did not form ectomycorrhizae on roots of either alder species. High intraspecific variation characterized strains of P. involutus in their ability to stimulate alder height and growth and to minimize leaf necrosis. We conclude that in vivo selection under bipartite symbiotic conditions is essential to select effective strains that will be of use for the revegetation and reclamation of derelict lands.

A diaminopimelic acid auxotrophic Escherichia coli donor provides improved counterselection following intergeneric conjugation with actinomycetes.

Considering the medical, biotechnological, and economical importance of actinobacteria, there is a continuous need to improve the tools for genetic engineering of a broad range of these microorganisms. Intergeneric conjugation has proven to be a valuable yet imperfect tool for this purpose. The natural resistance of many actinomycetes to nalidixic acid (Nal) is generally exploited to eliminate the sensitive Escherichia coli donor strain following conjugation. Nevertheless, Nal can delay growth and have other unexpected effects on the recipient strain. To provide an improved alternative to antibiotics, we propose a postconjugational counterselection using a diaminopimelic acid (DAP) auxotrophic donor strain. The DAP-negative phenotype was obtained by introducing a dapA deletion into the popular methylase-negative donor strain E. coli ET12567/pUZ8002. The viability of ET12567 and its ΔdapA mutant exposed to DAP deprivation or Nal selection were compared in liquid pure culture and after mating with Streptomyces coelicolor. Results showed that death of the E. coli ΔdapA Nal-sensitive donor strain occurred more efficiently when subjected to DAP deprivation than when exposed to Nal. Our study shows that postconjugational counterselection based on DAP deprivation circumvents the use of antibiotics and will facilitate the transfer of plasmids into actinomycetes with high biotechnological potential, yet currently not accessible to conjugative techniques.

Hemodynamic pressure waveform analysis in predicting fluid responsiveness.

OBJECTIVE: To assess the usefulness of central venous pressure (CVP), diastolic right ventricular pressure, and pulmonary capillary wedge pressure (PCWP) waveform analysis in predicting fluid responsiveness. DESIGN: A prospective observational study. SETTING: Tertiary care university hospital. PATIENTS: Forty-four patients undergoing coronary artery bypass grafting. INTERVENTIONS: Analysis of the a/v wave ratio of the PCWP, CVP, and right ventricular dP/dt to predict an increase in stroke volume >15% after the administration of 500 mL of colloid. MEASUREMENTS AND MAIN RESULTS: Forty-four patients were enrolled in this study and 7 were excluded. There were 24 responders and 13 nonresponders. No differences in mean CVP and PCWP values between the responders and the nonresponders were found. The only parameter associated with a significant response to volume infusion was the ratio of the a/v waves of the PCWP tracing (p = 0.0001). The performance of the a/v wave ratio>1 of the PCWP tracing in predicting fluid responsiveness was evaluated by constructing a receiver operating characteristic curve. The area under the receiver operating characteristic curve was 0.89 (95% confidence interval, 0.79-0.99; p<0.05). CONCLUSIONS: The a/v ratio measured on the PCWP tracing is a predictor of fluid responsiveness in patients with preserved left ventricular function undergoing coronary artery bypass grafting.

Absorption, Metabolism, and Excretion of [14C]-Tolebrutinib After Oral Administration in Humans, Contribution of the Metabolites to Pharmacological Activity.

BACKGROUND AND OBJECTIVE: Tolebrutinib is a covalent inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are thought to be major drivers of inflammation in multiple sclerosis. This excretion balance and metabolism study evaluated the metabolite profile of tolebrutinib in healthy male volunteers. METHODS: Six healthy volunteers received a 60-mg oral dose of [14C]-tolebrutinib, and metabolite profiling of 14C-labeled metabolites was performed using a combination of liquid chromatography, mass spectrometry, and radioactivity assay methods. RESULTS: Tolebrutinib was rapidly and completely absorbed from the gastrointestinal tract, followed by rapid and extensive metabolism. Excretion via feces was the major elimination pathway of the administered radioactivity (78%). Tolebrutinib was highly metabolized, with 19 metabolites identified in human plasma. Phase 1 biotransformations were primarily responsible for the circulating metabolites in plasma. Seven metabolites that achieved exposure in plasma similar to or higher than the parent compound were characterized biochemically for inhibition of Bruton's tyrosine kinase activity. Metabolite M8 exceeded the exposure threshold of 10% (18%) of the total radioactivity but had little if any pharmacological activity. Metabolite M2 (4% of circulating radioactivity) retained the ability to irreversibly and potently inhibit Bruton's tyrosine kinase in vitro, similar to the parent compound. Tolebrutinib and metabolite M2 had short (3.5-h) half-lives but durable pharmacodynamic effects as expected for an irreversible antagonist. CONCLUSIONS: Tolebrutinib was extensively metabolized to multiple metabolites. The hydroxylated metabolite M2 demonstrated similar inhibitory potency toward Bruton's tyrosine kinase as the parent compound. Both tolebrutinib and metabolite M2 likely contributed to pharmacological activity in vivo.

The mycoparasite Pythium oligandrum induces legume pathogen resistance and shapes rhizosphere microbiota without impacting mutualistic interactions.

Pythium oligandrum is a soil-borne oomycete associated with rhizosphere and root tissues. Its ability to enhance plant growth, stimulate plant immunity and parasitize fungal and oomycete preys has led to the development of agricultural biocontrol products. Meanwhile, the effect of P. oligandrum on mutualistic interactions and more generally on root microbial communities has not been investigated. Here, we developed a biological system comprising P. oligandrum interacting with two legume plants, Medicago truncatula and Pisum sativum. P. oligandrum activity was investigated at the transcriptomics level through an RNAseq approach, metabolomics and finally metagenomics to investigate the impact of P. oligandrum on root microbiota. We found that P. oligandrum promotes plant growth in these two species and protects them against infection by the oomycete Aphanomyces euteiches, a devastating legume root pathogen. In addition, P. oligandrum up-regulated more than 1000 genes in M. truncatula roots including genes involved in plant defense and notably in the biosynthesis of antimicrobial compounds and validated the enhanced production of M. truncatula phytoalexins, medicarpin and formononetin. Despite this activation of plant immunity, we found that root colonization by P. oligandrum did not impaired symbiotic interactions, promoting the formation of large and multilobed symbiotic nodules with Ensifer meliloti and did not negatively affect the formation of arbuscular mycorrhizal symbiosis. Finally, metagenomic analyses showed the oomycete modifies the composition of fungal and bacterial communities. Together, our results provide novel insights regarding the involvement of P. oligandrum in the functioning of plant root microbiota.

The C-terminal domains of melanocortin-2 receptor (MC2R) accessory proteins (MRAP1) influence their localization and ACTH-induced cAMP production.

ACTH binding to the human melanocortin-2 receptor (MC2R) requires the presence of the MC2R accessory protein1 isoforms, MRAPα or MRAPß. This study evaluated the role of the isoform-specific C-terminal domains of MRAP with regard to their cellular localization, topology, interaction with MRAP2 and cAMP production. When stably expressed in HEK293/FRT cells or in B16-G4F mouse melanoma cells (an MSH receptor-deficient cell clone), MRAPα and MRAPdCT (truncated MRAP1, N-terminal only) localized mainly around the nuclear envelope and within dense intracellular endosomes, while MRAPß exhibited a strong localization at the plasma membrane, and partially with rapid recycling endosomes. MRAPß and MRAPdCT both exhibited dual-topology (N(cyto)/C(exo) and N(exo)/C(cyto)) at the plasma membrane whereas MRAPα exhibited only N(cyto)/C(exo) topology at the plasma membrane while adopting dual-topology in intracellular compartments. Both MRAPα and MRAP2 colocalized in intracellular compartments, as opposed to weak colocalization between MRAPß and MRAP2. MRAP2 and MC2R enhanced the expression of MRAP1 isoforms and vice versa. Moreover, in both HEK293/FRT and B16-G4F cells, ACTH failed to activate MC2R unless MRAP1 was present. MRAP1 expression enhanced MC2R cell-surface expression as well as concentration-dependent cAMP accumulation. In the presence of human or zebrafish MC2R, MRAPß induced the highest cAMP accumulation while MRAPdCT induced the lowest. Together, the present findings indicate that the C-terminal domains of MRAP dictate their intracellular localization in addition to regulating ACTH-induced cAMP production. These preferential localizations suggest that MRAPα is involved in MC2R targeting to the plasma membrane, while MRAPß may enhance ACTH-MC2R coupling to cAMP production.

Microbial production of phase I and phase II metabolites of midazolam.

Midazolam, a potent benzodiazepine derivative and a typical substrate of CYP3A4/3A5, is essentially metabolized in human into 1'-hydroxymidazolam, then eliminated as the corresponding phase II metabolite, the 1'-O-ß-D-glucuronide derivative. A high yield alternative to the current multistep synthesis of 1'-hydroxymidazolam is described, using a biotransformation of midazolam by a fungal microorganism, Beauveria bassiana. The corresponding phase II metabolite, 1'-hydroxymidazolam-1'-O-ß-D-glucuronide, has been then prepared by chemical synthesis (3 steps, 20% yield), or by microbial glucuronidation (one step, 20% yield) using a Streptomyces sp. strain. The use of the same Streptomyces strain allows a direct and expeditive synthesis of the same glucuronide conjugate from midazolam itself in an advantageous 17% yield.

SmithNet: Strictness on Motion-Texture Coherence for Anomaly Detection.

Anomaly detection is a key functionality in various vision systems, such as surveillance and security. In this work, we present a convolutional neural network (CNN) that supports the detection of anomaly, which has not been defined when building the model, at frame level. Our CNN, named SmithNet, is structured to simultaneously learn commonly occurring textures and their corresponding motion. Its architecture is a combination of: 1) an encoder extracting motion-texture coherence from each video frame and 2) two decoders that separately reconstruct the input as well as predict its typical motion from the estimated coherence. We also introduce an encoding block, which is specifically designed for the task of anomaly detection. The optimization is performed on only data of normal events, and the network is expected to determine the ones that are unusual, i.e., have not been seen before. According to the experiments on eight benchmark datasets of different environments with various anomalous events, the performance of our network is competitive or outperforms current state-of-the-art approaches.