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Soil application of herbicides for pre-emergence (PRE) weed control is vital for grain sorghum production. Many soil-applied herbicides can be adsorbed or bound to the soil reducing the amount available for weed control. Extent of adsorption is strongly correlated to soil physical properties of organic matter (SOM) and texture. To overcome adsorption, the rate of herbicide to be applied is dependent on SOM and texture levels. These properties can vary within one field, making it difficult to follow label recommendations and achieve adequate weed control with a uniform rate. Variable rate applications (VRA) can be utilized to maximize herbicide effectiveness by applying the right rate in the right place. In 2016 and 2017, herbicide algorithms were developed for two different tank-mixes to be applied at five locations across Kansas. A Veris MSP3 system was utilized to collect and develop interpolated maps of SOM and of EC values that were correlated with soil texture classes to develop soil texture maps. Three algorithms were evaluated in the field for each tank-mix: based only on SOM (alg-SOM), on SOM and texture (alg-SOMtex), or on a flat rate. Rates for each tank-mix were based on the maximum usage rate (MUR) allowed for each herbicide. VRA based on SOM reduced the amount of herbicide applied while resulting in similar weed control compared to the flat rate. VRA based on SOM and texture greatly reduced the amount of herbicide applied but also resulted in reduced weed control compared to the flat rate at several locations. These findings prove that accurate SOM and texture data at high resolution combined with herbicide algorithms can be utilized by producers for effective VRA of soil-applied herbicides.

Steam oxidation experiments were conducted at 800–1400 °C with boiling water reactor alloy Zircaloy-2 strip specimens. Sample weight gain measurements were performed on the oxidized specimens before and after the test and were compared to oxygen pickup calculations using the Cathcart–Pawel correlation. The results showed that Zircaloy-2 follows the parabolic law at temperatures above 1000 °C. At or below 1000 °C, the oxidation rate was very low when compared to Cathcart–Pawel correlation and can be represented by a cubic expression. Arrhenius expressions are given to describe the parabolic rate constants at temperatures above 1000 °C and cubic rate constants are provided for temperatures at or below 1000 °C. The weight gains calculated by our Arrhenius correlations are in excellent agreement with the measured sample weight gains at all test temperatures.

Author(s): Buckley, AK; Cheng, T; Oh, MH; Su, GM; Garrison, J; Utan, SW; Zhu, C; Toste, FD; Goddard, WA; Toma, FM | Abstract: We report the discovery of a quaternary ammonium surface additive for CO2 reduction on Ag surfaces that changes the Faradaic efficiency for CO from 25% on Ag foil to 97%, while increasing the current density for CO production by a factor of 9 from 0.14 to 1.21 mA/cm2 and reducing the current density for H2 production by a factor of 440 from 0.44 to 0.001 mA/cm2. Using ReaxFF reactive molecular dynamics, we find that the surface additive with the highest selectivity, dihexadecyldimethylammonium bromide, promotes substantial population of CO2 near the Ag surface along with sufficient H2O to activate the CO2. While a critical number of water molecules is required in the reduction of CO2 to CO, the trend in selectivity strongly correlates with the availability of CO2 molecules. We demonstrate that the ordering of the cationic modifiers plays a significant role around the active site, thus determining reaction selectivity. The dramatic improvement by addition of a simple surface additive suggests an additional strategy in electrocatalysis.

Candidate tungsten armor materials in a magnetic confinement fusion device must be able to withstand thermal variation that leads to internal stresses caused by the impinging heat load. In addition...

O-Phenyloximes tethered to alkenes undergo 5-exo-trig iminyl radical cyclizations upon microwave irradiation. Trapping of the resulting cyclic radicals results in C-C, C-N, C-O, C-S, or C-X bond formation. Allylic sulfides undergo a tandem cyclization-thiyl radical β-elimination, affording terminal alkenes. The cyclizations exhibit a broad scope, and in some cases they are highly diastereoselective. The pyrroline adducts are versatile intermediates that can be transformed into a range of different species.

Objective To determine the proportion of chronic low back pain patients who achieve a clinically meaningful response from different pharmacologic and nonpharmacologic treatments. Data sources MEDLINE, EMBASE, Cochrane Library, and gray literature search. Study selection Published randomized controlled trials (RCTs) that reported a responder analysis of adults with chronic low back pain treated with any of the following 15 interventions: oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs), exercise, acupuncture, spinal manipulation therapy, corticosteroid injections, acetaminophen, oral opioids, anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors, cannabinoids, oral muscle relaxants, or topical rubefacients. Synthesis A total of 63 RCTs were included. There was moderate certainty that exercise (risk ratio [RR] of 1.71; 95% CI 1.37 to 2.15; number needed to treat [NNT] of 7), oral NSAIDs (RR = 1.44; 95% CI 1.17 to 1.78; NNT = 6), and SNRIs (duloxetine; RR = 1.25; 95% CI 1.13 to 1.38; NNT = 10) provide clinically meaningful benefits to patients with chronic low back pain. Exercise was the only intervention with sustained benefit (up to 48 weeks). There was low certainty that spinal manipulation therapy and topical rubefacients benefit patients. The benefit of acupuncture disappeared in higher-quality, longer (> 4 weeks) trials. Very low-quality evidence demonstrated that corticosteroid injections are ineffective. Patients treated with opioids had a greater likelihood of discontinuing treatment owing to an adverse event (number needed to harm of 5) than continuing treatment to derive any clinically meaningful benefit (NNT = 16), while those treated with SNRIs (duloxetine) had a similar likelihood of continuing treatment to attain benefit (NNT = 10) as those discontinuing the medication owing to an adverse event (number need to harm of 11). One trial each of anticonvulsants and topical NSAIDs found similar benefit to that of placebo. No RCTs of acetaminophen, cannabinoids, muscle relaxants, selective serotonin reuptake inhibitors, or tricyclic antidepressants met the inclusion criteria. Conclusion Exercise, oral NSAIDs, and SNRIs (duloxetine) provide a clinically meaningful reduction in pain, with exercise being the only intervention that demonstrated sustained benefit after the intervention ended. Future high-quality trials that report responder analyses are required to provide a better understanding of the benefits and harms of interventions for patients with chronic low back pain.

A new series of polymers comprising four terpolymers was synthesized via Mannich polycondensation of benzene-1,4-diamine, formaldehyde and piperazine by varying the benzene-1,4-diamine and piperazine ratio. The new polyamines (labeled Dipip) were characterized using 13C solid-state NMR, FT-IR, TGA, DSC, XRD, SEM and EDX. The adsorptive performances of the synthesized polymers for Erichrome Black T (EBT) uptake from aqueous solution were investigated under batch process. Equilibrium, kinetic, and thermodynamic studies were conducted to determine the influence of different operational parameters of the adsorption process. The two most promising polymers among the series show an excellent EBT removal efficiency of ~100% and ~95% with high adsorption capacities of 775 mg·g−1 and 917 mg·g−1, respectively at a meager dosage of 5 mg. The sorption of EBT on the polymers was well described by Redlich-Peterson & Langmuir model while the kinetic studies indicate that pseudo-second order model was followed. For the thermodynamic studies, the negative ΔG and positive ΔH values obtained suggest a spontaneity of the sorption process which was endothermic in nature. The results of reusability test of the resins were promising even at the fourth cycle, showcasing the potentials of the new polymers in dyes contaminated water treatment.

PREMISE Biological invasions increasingly threaten native biodiversity and ecosystem services. One notable example is the common reed, Phragmites australis, which aggressively invades North American salt marshes. Elevated atmospheric CO2 and nitrogen pollution enhance its growth and facilitate invasion because P. australis responds more strongly to these enrichments than do native species. We investigated how modifications to stomatal features contribute to strong photosynthetic responses to CO2 and nitrogen enrichment in P. australis by evaluating stomatal shifts under experimental conditions and relating them to maximal stomatal conductance (gwmax ) and photosynthetic rates. METHODS Plants were grown in situ in open-top chambers under ambient and elevated atmospheric CO2 (eCO2 ) and porewater nitrogen (Nenr ) in a Chesapeake Bay tidal marsh. We measured light-saturated carbon assimilation rates (Asat ) and stomatal characteristics, from which we calculated gwmax and determined whether CO2 and Nenr altered the relationship between gwmax and Asat . RESULTS eCO2 and Nenr enhanced both gwmax and Asat , but to differing degrees; gwmax was more strongly influenced by Nenr through increases in stomatal density while Asat was more strongly stimulated by eCO2 . There was a positive relationship between gwmax and Asat that was not modified by eCO2 or Nenr , individually or in combination. CONCLUSIONS Changes in stomatal features co-occur with previously described responses of P. australis to eCO2 and Nenr . Complementary responses of stomatal length and density to these global change factors may facilitate greater stomatal conductance and carbon gain, contributing to the invasiveness of the introduced lineage.

Bisphenol A (BPA) is a versatile petrochemical used in the preparation of high volume polymers including polycarbonates and epoxy resins. Unfortunately, BPA is also an endocrine disrupter and has been banned from use in various consumer products by several regulatory agencies. To address this issue, our group evaluated the estrogenic activity of nine bio-based tris/bisphenols derived from resveratrol (1 and 2), anethole (3, 4), eugenol (5), carvacrol (6), and creosol (7–9). Compounds 5–9 were determined to be non-estrogenic, while compound 3 exhibited a response at a lower concentration than BPA, and compounds 1, 2, and 4 exhibited responses similar to BPA. Polycarbonates of the bio-based bisphenols (PC3–PC9) were then synthesized via interfacial polymerization and characterized by SEC, MALDI-MS, DSC, TGA, and UV-VIS spectroscopy. The bio-based polycarbonates exhibited Mn values up to 14 600 Da (SEC) and had a wide range of glass transition temperatures (Tg) with values up to 156 °C (∼25 °C higher than BPA with a similar molecular weight) depending on the monomer structure. The bio-based polycarbonates had high thermal stabilities with Td5% values up to 383 °C under a nitrogen atmosphere. The non-estrogenic properties of 5–9 coupled with the good thermal properties of the derivative polycarbonates suggests that these materials are sustainable, lower toxicity alternatives for BPA-based polycarbonates.

Polymerization-induced self-assembly (PISA) is a facile method to obtain block copolymer aggregates with defined morphologies. However, the transitions between these morphologies have been difficult to monitor directly in real-time during the polymerization. Herein, we describe a straightforward and readily accessible in situ method to monitor the evolution of nanostructure via changes in internal hydrophobicity during the PISA process using a polymer-tethered pyrene fluorescent probe. We were able to correlate morphological transitions with changes of the pyrene emission and gain unprecedented insight into the evolution of core hydrophobicity during PISA.

Polymer bottlebrushes are complex macromolecular nanostructures with polymeric side chains densely grafted to a polymer backbone. In this work, a synthetic strategy for the synthesis of cyclic bott...

Quaternary ammonium compounds (QACs) comprise a large class of surfactants, consumer products, and disinfectants. The recently-isolated QAC natural product tricepyridinium bromide displays potent inhibitory activity against S. aureus but due to its unique structure, its mechanism of action remains unclear. A concise synthetic route to access tricepyridinium analogs was thus designed and four N-alkyl compounds were generated in addition to the natural product. Biological analysis of these compounds revealed that they display remarkable selectivity towards clinically-relevant Gram-positive bacteria exceeding that of commercially-available QACs such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAC) while having little to no hemolytic activity. Molecular modeling studies revealed that tricepyridinium and shorter-chain N-alkyl analogs may preferentially bind to the QacR transcription factor leading to potential activation of the QAC resistance pathway found in MRSA; however, our newly synthesized analogs are able to overcome this liability.

Cysteine palmitoylation (S-palmitoylation) is a reversible post-translational modification that is installed by the DHHC family of palmitoyltransferases and is reversed by several acyl protein thioesterases1,2. Although thousands of human proteins are known to undergo S-palmitoylation, how this modification is regulated to modulate specific biological functions is poorly understood. Here we report that the key T helper 17 (TH17) cell differentiation stimulator, STAT33,4, is subject to reversible S-palmitoylation on cysteine 108. DHHC7 palmitoylates STAT3 and promotes its membrane recruitment and phosphorylation. Acyl protein thioesterase 2 (APT2, also known as LYPLA2) depalmitoylates phosphorylated STAT3 (p-STAT3) and enables it to translocate to the nucleus. This palmitoylation–depalmitoylation cycle enhances STAT3 activation and promotes TH17 cell differentiation; perturbation of either palmitoylation or depalmitoylation negatively affects TH17 cell differentiation. Overactivation of TH17 cells is associated with several inflammatory diseases, including inflammatory bowel disease (IBD). In a mouse model, pharmacological inhibition of APT2 or knockout of Zdhhc7—which encodes DHHC7—relieves the symptoms of IBD. Our study reveals not only a potential therapeutic strategy for the treatment of IBD but also a model through which S-palmitoylation regulates cell signalling, which might be broadly applicable for understanding the signalling functions of numerous S-palmitoylation events. The dynamic and reversible S-palmitoylation of the transcription factor STAT3 enhances its activation and promotes the differentiation of TH17 cells.

Resveratrol is a sustainable and versatile bio-derived phenolic compound that has shown promise as a high glass-transition temperature (Tg), flame-resistant building block for thermoset networks. In this study, three components of epoxy thermoset resins were synthesized from resveratrol: trans-resveratrol trisepoxy (1), dihydroresveratrol trisepoxy (2), and a trifunctional amine, 4,4′-((5-(4-(4-aminophenoxy)phenethyl)-1,3-phenylene)bis(oxy))dianiline (4). The epoxy monomers were low melting solids (mp 2000 mg/L, and no cytotoxicity up to its solubility limit. The epoxy monomers were cured with 4,4′-methylenedianiline (3) and 4 to produce four epoxy–amine networks (A–D). Networks C and D, prepared with the resveratrol-derived aniline, contained up to 52.6% bio-based material. The moisture uptake, thermal stability, and dry/wet thermomechanical properties of the networks were measured. The networks had Tg’s as high as 285 °C, approximately 110 °C higher than networks based on petroleum-derived bisphenol A (BPA). In addition, the resveratrol networks had char yields as high as 51 and 46% in nitrogen and air, respectively, compared to ca. 15 and 5%, respectively, for BPA-based networks. Overall, this study shows the advantages of resveratrol-based epoxy and amine monomers as components of sustainable, low-toxicity, high-temperature resin systems.

In 1957 Glenn T. Seaborg conceived and advocated for the construction of the High Flux Isotope Reactor (HFIR) and the Transuranium Processing Plant (since then renamed the Radiochemical Engineering Development Center, or REDC) at Oak Ridge National Laboratory. Heavily shielded hot cells, glove boxes, and laboratories allow recovery of transuranium elements produced in substantial quantities. Seaborg’s vision of HFIR and REDC producing milligram quantities of berkelium, californium, and einsteinium has been fulfilled beginning in 1966 through May 2019 with 78 production campaigns yielding a cumulative totals of 1.2 g of 249Bk, 10.2 g of 252Cf, 39 mg of 253Es, and 15 pg of 257Fm. Notably, 252Cf is a neutron source used in many industrial applications including oil exploration; process control systems for the cement industry, coal analysis, and power production; sources to start nuclear reactors and perform nondestructive materials analyses; homeland security and national defense detection devices; and medical research. Isotopes made available through transplutonium production at HFIR/REDC have enabled scientists to study the nuclear properties and reactions, chemical properties, optical properties, and solid-state properties of transplutonium elements. Long-lived isotopes have served as targets in heavy ion accelerators to produce heavier elements leading to the discovery of 104Rf, 105Db, 106Sg, 113Nh, 114Fl, 115Mc, 116Lv, 117Ts, and 118Og. This paper reviews the evolution of the processing flowsheets to produce, separate, and purify transplutonium isotopes, which have evolved over 50 years of operation at HFIR and REDC, and summarizes directions of future work to improve the efficiency of the production operations.

Conjugated aromatic macrocycles are attractive due to their unique photophysical and optoelectronic properties. In particular, the cyclic radially oriented π-system of cycloparaphenylenes (CPPs) gives rise to photophysical properties unlike any other small molecule or carbon nanomaterial. CPPs have tunable emission, possess large extinction coefficients, wide effective Stokes shifts, and high quantum yields. However, accessing bright CPPs with emissions beyond 500 nm remains difficult. Herein, we present a novel and bright orange-emitting CPP-based fluorophore showing a dramatic 105 nm red-shift in emission and striking 237 nm effective Stokes shift while retaining a large quantum yield of 0.59. We postulate, and experimentally and theoretically support, that the quantum yield remains large due to the lack of intramolecular charge transfer.

Ortho-substitution with hydrophobic aliphatic groups has shown reduced moisture uptake in a variety of thermoset networks. In this study, the number and size of ortho-substituents were systematical...

We report a photomediated disulfide cross-linking strategy for the generation of adaptable hydrogels from telechelic network precursors containing strained cyclic disulfides. Exploiting the intrica...

Photoreceptors possess ribbon synapses distinct from the conventional synapses in the brain. Little is known about the function of the BBSome, a complex integral in ciliary and intracellular trafficking, in ribbon synaptic formation. We performed immunohistochemistry using retinas from Bardet-Biedl Syndrome (BBS) mouse models and found that BBS mutant animals have significantly fewer ribbon synapses in the outer plexiform layer and increased ectopic synapses in the outer nuclear layer compared to controls. Many ectopic synapses in BBS mutant retinas are associated with horizontal cell axonal processes that aberrantly intrude into the outer nuclear layer. To determine whether this horizontal cell phenotype is a consequence of retinal degeneration, we examined this phenotype in mice with photoreceptor-specific inactivation of the BBSome induced by Cre recombinase driven by the rhodopsin promoter. At three months of age, despite retinal degeneration, Bbs8floxed/floxed; Rho-Cre+ mice lack the aberrant intrusion of horizontal cell processes. At 6 months, some horizontal cell processes intrude into the outer nuclear layer in Bbs8floxed/floxed; Rho-Cre+ mice, but the phenotype does not recapitulate the phenotypic severity observed in young congenital BBS mutant mice. Therefore, the lack of BBSome function negatively impacts retinal synaptogenesis, and causes horizontal cell defects in a potentially cell-autonomous fashion.

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1- specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.

Ibrutinib (Imbruvica; PCI-32765) is an orally administered inhibitor of Bruton's tyrosine kinase that has transformed the treatment of B-cell malignancies. However, ibrutinib has very low oral bioavailability that contributes to significant variability in systemic exposure between patients, and this has the potential to affect both efficacy and toxicity. We hypothesized that the oral bioavailability of ibrutinib is limited by CYP3A isoform–mediated metabolism, and that this pathway can be inhibited to improve the pharmacokinetic properties of ibrutinib. Pharmacokinetic studies were performed in wild-type mice and mice genetically engineered to lack all CYP3A isoforms (CYP3A−/−) that received ibrutinib alone or in combination with CYP3A inhibitors cobicistat or ketoconazole. Computational modeling was performed to derive doses of ibrutinib that, when given after a CYP3A inhibitor, results in therapeutically relevant drug levels. Deficiency of CYP3A in mice was associated with an approximately 10-fold increase in the AUC of ibrutinib. This result could be phenocopied by administration of cobicistat before ibrutinib in wild-type mice, but cobicistat did not influence levels of ibrutinib in CYP3A−/− mice. Population pharmacokinetic and prospectively validated physiologically based pharmacokinetic models established preclinical and clinical doses of ibrutinib that could be given safely in combination with cobicistat without negatively affecting antileukemic properties. These findings signify a dominant role for CYP3A-mediated metabolism in the elimination of ibrutinib, and suggest a role for pharmacologic inhibitors of this pathway to intentionally modulate the plasma levels and improve the therapeutic use of this clinically important agent. Significance: Ibrutinib has limited oral bioavailability, which contributes to significant interindividual pharmacokinetic variability. Using engineered mouse models, we here report a causal relationship between CYP3A-mediated metabolism and ibrutinib's bioavailability and drug–drug interaction with cobicistat. These results offer a mechanistic basis for reported pharmacokinetic interactions with ibrutinib, and in conjunction with a newly developed computational model, allow for the rational design of clinical trials aimed at improving the therapeutic use of ibrutinib.

Lysine fatty acylation in mammalian cells was discovered nearly three decades ago, yet the enzymes catalyzing it remain unknown. Unexpectedly, we find that human N-terminal glycine myristoyltransferases (NMT) 1 and 2 can efficiently myristoylate specific lysine residues. They modify ADP-ribosylation factor 6 (ARF6) on lysine 3 allowing it to remain on membranes during the GTPase cycle. We demonstrate that the NAD+-dependent deacylase SIRT2 removes the myristoyl group, and our evidence suggests that NMT prefers the GTP-bound while SIRT2 prefers the GDP-bound ARF6. This allows the lysine myrisotylation-demyristoylation cycle to couple to and promote the GTPase cycle of ARF6. Our study provides an explanation for the puzzling dissimilarity of ARF6 to other ARFs and suggests the existence of other substrates regulated by this previously unknown function of NMT. Furthermore, we identified a NMT/SIRT2-ARF6 regulatory axis, which may offer new ways to treat human diseases., Lysine fatty acylation is an important protein posttranslational modification but mammalian lysine fatty acyl transferases have remained unknown so far. Here the authors report that the human N-terminal glycine myristoyltransferases 1 and 2 catalyze the addition of myristoyl chains to specific lysine residues and show that they myristoylate ARF6 lysine 3, which explains the unusual membrane binding properties of ARF6.

A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (1), was isolated from laboratory cultures of a marine Chlorophyte, Derbesia sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MS-based molecular networking. Cultures were grown in a light- and temperature-controlled environment and harvested after several months of growth. The planar structure of pagoamide A (1) was characterized by detailed 1D and 2D NMR experiments along with MS and UV analysis. The absolute configurations of its amino acid residues were determined by advanced Marfey’s analysis following chemical hydrolysis and hydrazinolysis reactions. Two of the residues in pagoamide A (1), phenylalanine and serine, each occurred twice in the molecule, once in the d- and once in the l-configuration. The biosynthetic origin of pagoamide A (1) was considered in light of other natural products investigations with coenocytic green algae.

Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through the creation of rod-shaped particles of defined sizes reflective of native LA drugs, theranostic probes can be deployed to measure particle-cell and tissue biodistribution, antiretroviral activities and drug retention. Methods: Herein, we created multimodal rilpivirine (RPV) 177lutetium labeled bismuth sulfide nanorods (177LuBSNRs) then evaluated their structure, morphology, configuration, chemical composition, biological responses and adverse reactions. Particle biodistribution was analyzed by single photon emission computed tomography (SPECT/CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging. Results: Nanoformulated RPV and BSNRs-RPV particles showed comparable physicochemical and cell biological properties. Drug-particle pharmacokinetics (PK) and biodistribution in lymphoid tissue macrophages proved equivalent, one with the other. Rapid particle uptake and tissue distribution were observed, without adverse reactions, in primary blood-derived and tissue macrophages. The latter was seen within the marginal zones of spleen. Conclusions: These data, taken together, support the use of 177LuBSNRs as theranostic probes as a rapid assessment tool for PK LA ARV measurements.

From the viewpoint of inorganic crystal engineering (ICE), the coordination sphere of the metal centre can be affected by two main parts of inorganic and organic units in complexes. Database study can play a significant role in the explanation of the relationship between various parameters related to these parts. For the first time, we have investigated this relationship through the concomitant studies of the inorganic crystal structure database (ICSD) and the cambridge structural database (CSD) for mercury(II) halide compounds. The results of CSD analysis are divided into two categories of metal halide complexes (MHC or mercury halide compounds with ligands) and metal halide only (MHO or mercury halide compounds without ligands). MHC (970, 460, and 521 metal centres as HgCl2, HgBr2, and HgI2, respectively) and MHO (419, 141, and 201 metal centres as HgCl2, HgBr2, and HgI2, respectively) were structurally investigated. The coordination number, polymerization mode, coordination geometry of the metal centre, type of donor atom in ligands, and the chelation mode of the ligand for all MHC and MHO compounds were extracted as effective factors in inorganic and organic units. To rationalize the effect of ICE in the design of the coordination sphere, eleven new mercury halide complexes, including the ester ligands of L1, naphthalene-5-yl nicotinate (complexes 1–3), L2, naphthalene-6-yl nicotinate (complexes 4–6), L3, naphthalene-5-yl pyrazine-2-carboxylate (complexes 7–9), and L4, naphthalene-6-yl pyrazine-2-carboxylate (complexes 10–11) were synthesized and fully characterized. The various parameters of substitution, C–H to nitrogen replacement, counteranion, and symmetry effects were investigated for all of the complexes. The results show that there is a meaningful relationship between inorganic and organic units. According to the findings of the CSD and ICSD analyses, most of the complexes obeyed the same relationship. Despite the predominant role of the inorganic unit in determining the coordination geometry, the organic unit can also change the coordination sphere of complexes with one major effect or the cooperativity of minor effects.

We describe the development of a new palladium-catalyzed method to generate ketones via the oxidative coupling of two arenes and CO. This transformation is catalyzed by simple palladium salts, and is postulated to proceed via the conversion of arenes into high energy aroyl triflate electrophiles. Exploiting the latter can also allow the synthesis of unsymmetrical ketones from two different arenes.

Copper is the most commonly used material for interconnects within microelectronics. However, electromigration and high resistance within the material limit the use of copper in nanoscale applications. New, two-dimensional (2D) materials such as graphene, carbon nanotubes (CNTs), and transition-metal dichalcogenide (TMDs) are being developed for the next generation of interconnects. A composite consisting of a forest of vertically aligned carbon nanotubes within a matrix of copper is a proposed solution to the issues which present themselves in nanoscale copper interconnects. The fabrication of CNTs and graphene often requires high temperatures that exceed the material limitations of copper in microelectronic processing. If these 2D materials are used in conjunction with copper, it is desirable to delay copper deposition to late stages of microfabrication in order to avoid exposing copper to high temperatures. It is proposed that a seed layer be deposited before deposition/growth of CNTs/graphene or other TMD materials, such that later deposition of copper via electroplating is feasible. A conductive seed layer must be introduced underneath the forest of CNTs in order to allow for electroplating to take place. Copper itself may not be used as a seed layer since it migrates at elevated temperatures, which prevents growth of carbon nanotubes. Thus, the seed layer must be able to withstand high temperatures, must not migrate or diffuse into silicon or barrier layers, and must also be a suitable seed layer for copper electroplating. This research focuses on evaluating different metals as potential seed layers for copper electroplating for nanoscale applications. Layers of various metals of 100 A, 275 A, and 1000 A thickness were deposited onto silicon wafers via physical vapor deposition. They were then electroplated with copper and examined visually for quality and consistency. A digital microscope was used for microscopic examination, then a scanning electron microscope was used to examine the development of copper over the seed layers and for elemental mapping to verify copper deposition. Seeds consisting of 1000 A platinum, 1000 A nichrome, and 100 A silver showed strong promise for use as seed layers for nanoscale applications. Platinum and nichrome were found to develop uniform copper coatings and strongly adhere to the silicon wafer. To protect platinum and nichrome from diffusion into silicon during chemical vapor deposition (CVD) CNT growth, a barrier layer may be required. Copper developed uniformly over the 100-A silver seed. Silver is unlikely to diffuse into silicon at the temperatures required during CVD CNT growth. Due to poor adhesion between the silver seed and silicon wafer, an adhesion layer may be used to improve reliability.

Boron nitride nanotubes (BNNTs) have unique thermomechanical properties that make them excellent candidates for use in structural heat resistant composites, but their usage has been limited in the ...

Pavlova sp. 459 has been used as a high-quality liquid live-feed for cultivated bivalves, while this is its first evaluation as a low-trophic dry aquafeed ingredient. Pav459 was batch-cultivated in photobioreactors and prepared as an intact-cell meal (direct freeze-drying) and a cell-ruptured meal (freeze-drying following microfluidic high-pressure homogenization) and evaluated for nutritional characteristics relevant for salmonid aquafeeds. Protein quality was based on essential amino acid (EAA) profiles, chemical scores, and in vitro 2-phase gastric/pancreatic digestion (GPD) for salmonids. Nutrients were well-preserved after processing and meals contained 66% protein, 16% lipid, 7% carbohydrate, 24 MJ kg⁻¹ DW energy, and 11% ash. Protein quality of the meals was good as indicated by their high EAA/non-EAA ratios (0.91), high EAA indices of 0.82–1.06 (relative to egg albumin, premium fish meal, and soy protein), high chemical scores (1.4–2.2) for most EAAs (calculated against published salmonid dietary requirements), and high in vitro GPD (82%), irrespective of cell-rupture. Pav459 meals contained health-promoting compounds (fucoxanthin, 358–368 mg (100 g)⁻¹ DW; lutein, 101–162 mg (100 g)⁻¹ DW; total phenolic compounds, 33 mg gallic acid equivalents g⁻¹ DW) with negligible contaminating heavy metals (< 1 ppm) and anti-nutritional factors (ANFs) (1 TUI mg⁻¹ DW trypsin inhibition; < 10 mg g⁻¹DW phytate). Pav459 lipid was highest in PUFA (> 60% of FAME), most of which was nutritionally superior n-3 series (50–52% of FAME) relative to n-6 series (10% of FAME). In addition, the vast majority of n-3 PUFA (81%) was comprised of essential LC-PUFA, eicosapentaenoic acid (EPA, 20:5n-3) at 3% of the meals and docosahexaenoic acid (DHA, 22:6n-3) at 2% of the meals.

Catalyst deactivation resulting from the hydrothermal leaching of sulfonic acid residues and the deposition of carbonaceous residues was studied using condensed phase flow reactor experiments along...

[Image: see text] Beta-pompilidotoxin (β-PMTX) is a 13-amino acid wasp venom peptide that activates human neuronal sodium channel Na(V)1.1 with weak activity (40% activation at 3.3 μM of β-PMTX). Through rational design of β-PMTX analogs, we have identified peptides with significantly improved activity on human Na(V)1.1 (1170% activation at 3.3 μM of peptide 18). The underlying structure–activity relationship suggests importance of charge interactions (from residue Lys-3) and lipophilic interactions (from residue Phe-7 and Ser-11). Three top-ranked analogs showed parallel activity improvement for other neuronal sodium channels (human Na(V)1.2/1.3/1.6/1.7) but not muscular subtypes (Na(V)1.4/1.5). Finally, we found that analog 16 could partially rescue the pharmacological block imposed by Na(V)1.1/1.3 selective inhibitor ICA-121431 in cultured mouse cortical GABAergic neurons, demonstrating an activating effect of this peptide on native neuronal sodium channels and its potential utility as a neuropharmacological tool.

Receptor-targeted radiopharmaceuticals based on low-molecular-weight carriers offer many clinically advantageous attributes relative to macromolecules but have generally been hampered by their rapid clearance from tumors, thus diminishing tumor-to-nontarget tissue ratios. Herein, we present a strategy using irreversible inhibitors (E-64 derivative) of cysteine cathepsins (CCs) as trapping agents to increase the tumor retention of receptor-targeted agents. Methods: We incorporated these CC-trapping agents into agonistic and antagonistic pharmacophores targeting the gastrin-releasing peptide receptor (GRPR). The synthesized radioconjugates with either an incorporated CC inhibitor or a matching control were examined using in vitro and in vivo models of the GRPR-positive, PC-3 human prostate cancer cell line. Results: From the in vitro studies, multiple techniques confirmed that the CC-trapping, GRPR-targeted constructs were able to increase cellular retention by forming intracellular macromolecule adducts. In PC-3 tumor–bearing xenograft mice, the CC-trapping, GRPR-targeted agonistic and antagonistic constructs led to an approximately 2-fold increase in tumor retention with a corresponding improvement in most tumor-to-nontarget tissue ratios over 72 h. Conclusion: CC endolysosomal trapping provides a pathway to increase the efficacy and clinical potential of low-molecular-weight, receptor-targeted agents.

We explored the approach of using an analog of E−64, a well-known and hydrophilic cysteine cathepsin (CC) inhibitor, as a potent cysteine cathepsin-trapping agent (CCTA) to improve the tumor retention of low-molecular-weight, receptor-targeted radiopharmaceuticals. The synthesized hydrophilic CCTA-incorporated, NTSR1-targeted agents demonstrated a substantial increase in cellular retention upon uptake into the NTRS1-positive HT-29 human colon cancer cell line. Similarly, biodistribution studies using HT-29 xenograft mice revealed a significant and substantial increase in tumor retention for the CCTA-incorporated, NTSR1-targeted agent. The intracellular trapping mechanism of the CCTA-incorporated agents by macromolecular adduct formation was confirmed using multiple in vitro and in vivo techniques. Furthermore, utilization of the more hydrophilic CCTA greatly increased the hydrophilicity of the resulting NTSR1-targeted constructs leading to substantial decreases in most non-target tissues in contrast to our previously reported dipeptidyl acyloxymethyl ketone (AOMK) constructs. This work further confirms that the CCTA trapping approach can make significant improvements in the clinical potential of NTSR1-and other receptor-targeted radiopharmaceuticals.

A heptacyclo[6.6.0.02,6.03,13.04,11.05,9.010,14]tetradecane (HCTD) complex with terminal allylidene groups at the 7- and 12-positions (HCTD-7,12-diallylidene, 2) was generated at the multigram scal...

Neutron irradiation in mixed spectrum reactors is an effective approach to investigate the synergistic effects of solid transmutations and atomic displacement damage in tungsten. In this article the findings and interpretations from a large-scale tungsten irradiation campaign conducted using the High Flux Isotope Reactor of Oak Ridge National Laboratory are summarized. The response of originally-unalloyed tungsten to mixed spectrum neutron irradiation is characterized by enormous hardening, degradation of modulus of toughness eventually leading to embrittlement, and decreased thermal conductivity. These property changes may be attributed primarily to production, segregation, and precipitation of rhenium and osmium and assisted by displacement damage. The stages describing the evolution of the microstructural development and property changes with the neutron dose and the accompanying accumulation of transmutation products are proposed. This manuscript has been co-authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan ( http://energy.gov/downloads/doe-public-access-plan ).

In reactor-relevant fusion divertor conditions, tungsten (W) will be used as an armor material due to its excellent thermal properties. It will be exposed to impurities from numerous sources, inclu...

The United States and Japan have collaborated on fusion materials research in a series of agreements reaching back to 1981. The PHENIX collaboration is the latest U.S.-Japan project which s...

To collect data for fusion applications and understand the basic properties of tungsten, single-crystal tungsten was neutron irradiated in the mixed-spectrum High Flux Isotope Reactor at the Oak Ridge National Laboratory at temperatures of 90–830 °C to fast fluences of 0.01–9 × 1025 n/m2 (E > 0.1 MeV). For tensile tests at room temperature of the irradiated material in both orientations, and tensile orientation, initially there was strengthening that peaked at 0.02 dpa and was followed by progressive modulus of toughness reduction, approaching zero at higher doses. For all irradiation temperatures, in elevated temperature tensile tests there was a distinct transition from ductile-to-brittle behavior between 0.1 and 0.4 dpa, accompanied by an increase in indentation hardness. The ductile-to-brittle transition with increasing dose was particularly critical because it presented as a total loss in elongation and modulus of toughness. The critical transition dose was well below the dose (∼1 dpa) where irradiation-induced precipitates are visible in the TEM. The extent of Vickers microhardness increase was significant at higher doses and did not depend on irradiation temperature or crystal orientation, reaching 12.9 GPa after 2.8 dpa. The significant mechanical property degradation above 0.1 dpa is believed to have been caused by the accumulation of irradiation-induced clusters and eventually precipitates of the transmutation elements Re and Os.

Consumption of dietary lignans has been associated with reduced risk of chronic diseases, although the underlying mechanisms are unclear. We sought to determine if urinary excretion of ENL, the predominant microbial metabolite of dietary lignans, was associated with plasma protein abundance using a cross-sectional design based on data and plasma collected from 80 healthy participants in a randomized crossover, controlled feeding study. Proteomic analysis was performed on plasma samples collected at the end of each of two diet periods (160 samples total) using a customized antibody array corresponding to 2072 unique proteins. GC-MS was used to measure ENL excretion in 24-h urine samples collected in tandem with plasma. Linear mixed models tested the association between urinary enterolignan excretion and plasma protein abundance. Subsequently, over-representation analysis was conducted considering 17 a priori pathways with putative associations with enterolignan bioactivity in an exploratory approach. Controlling the false discovery rate at 10%, ENL excretion was inversely associated with seven proteins (FCRL5, PSCA, GAB1, LAPTM5, CCS, REG4, CEACAM1), and positively associated with two proteins (WAS and FBLN5). Over-representation analysis revealed associations of ENL excretion with estrogen and TNF signaling pathways, which were not significant after adjustment for false discovery. These ENL-associated proteins and pathways have potential implications in cancer prevention.

This work was supported by United States Public Health Service grant R01 AI035739 and funds from the Jacobs School of Medicine and Biomedical Sciences to J.D.B. and from United States Public Health Service grant 1S10OD021719-01A1 to the University of Georgia, which purchased the ImageStreamX Mk II. This work was also supported by the Wellcome Trust (grant 094476/Z/10/Z) for funding the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility. African trypanosomes utilize glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG) to evade the host immune system. VSG turnover is thought to be mediated via cleavage of the GPI anchor by endogenous GPI-specific phospholipase C (GPI-PLC). However, GPI-PLC is topologically sequestered from VSG substrates in intact cells. Recently, A. J. Szempruch, S. E. Sykes, R. Kieft, L. Dennison, et al. (Cell 164:246-257, 2016, https://doi.org/10.1016/j.cell.2015.11.051) demonstrated the release of nanotubes that septate to form free VSG+ extracellular vesicles (EVs). Here, we evaluated the relative contributions of GPI hydrolysis and EV formation to VSG turnover in wild-type (WT) and GPI-PLC null cells. The turnover rate of VSG was consistent with prior measurements (half-life [t1/2] of ∼26 h) but dropped significantly in the absence of GPI-PLC (t1/2 of ∼36 h). Ectopic complementation restored normal turnover rates, confirming the role of GPI-PLC in turnover. However, physical characterization of shed VSG in WT cells indicated that at least 50% is released directly from cell membranes with intact GPI anchors. Shedding of EVs plays an insignificant role in total VSG turnover in both WT and null cells. In additional studies, GPI-PLC was found to have no role in biosynthetic and endocytic trafficking to the lysosome but did influence the rate of receptor-mediated endocytosis. These results indicate that VSG turnover is a bimodal process involving both direct shedding and GPI hydrolysis. IMPORTANCE African trypanosomes, the protozoan agent of human African trypanosomaisis, avoid the host immune system by switching expression of the variant surface glycoprotein (VSG). VSG is a long-lived protein that has long been thought to be turned over by hydrolysis of its glycolipid membrane anchor. Recent work demonstrating the shedding of VSG-containing extracellular vesicles has led us to reinvestigate the mode of VSG turnover. We found that VSG is shed in part by glycolipid hydrolysis but also in approximately equal part by direct shedding of protein with intact lipid anchors. Shedding of exocytic vesicles made a very minor contribution to overall VSG turnover. These results indicate that VSG turnover is a bimodal process and significantly alter our understanding of the "life cycle" of this critical virulence factor. Publisher PDF

Polyphenols, such as flavonoids and phenolic acids, are a group of specialized metabolites in plants that largely aid in plant defense by deterring biotic stressors and alleviating abiotic stress. Polyphenols offer a wide range of medical applications, acting as preventative and active treatments for diseases such as cancers and diabetes. Recently, researchers have proposed that polyphenols may contribute to certain applications aimed at tackling challenges related to the COVID-19 pandemic. Understanding the beneficial impacts of phytochemicals, such as polyphenols, could potentially help prepare society for future pandemics. Thus far, most reviews have focused on polyphenols in cancer prevention and treatment. This review aims to provide a comprehensive discussion on the critical roles that polyphenols play in both plant chemical defense and human health based on the most recent studies while highlighting prospective avenues for future research, as well as the implications for phytochemical-based applications in both agricultural and medical fields.