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Upon treatment with Cs2CO3, S-methyl-N-ynonylsulfoximines undergo 5-exo-dig cyclizations to give three-dimensional heterocycles. The reactions proceed at ambient temperature with a wide range of substrates affording the corresponding products in good to excellent yields.

"If You're Woke You Dig It" is a research article and elegy for the popular AAVE term, "woke." I attempt to illustrate woke's early uses in the Black Atlantic in connection to its resurgence in the 21st century. I discuss it's usage among non-Black people and the absorption of Black Vernacular Englishes into popular consciousness and its usage by non-Black people. I argue that the "death" of woke is indicative of the lack of possession Black people have over cultural production and the importance of Black Vernacular English as a counter- hegemonic tactic. Black cultural production should be understood as key to global black liberation.

A novel sp 3 carbon-rich tricyclic 3D scaffold-based peptide mimetic compound library was constructed to target protein-protein interactions. T ricyclic framework 6 was synthesized from 9-azabicyclo[3,3,1]nonan-3-one 9 via a gold (I)-catalyzed Conia-ene reaction. The electron-donating group on the pendant alkyne of cyclization precursor 11b-e was the key to forming 6- endo - dig cyclized product 6 with complete regioselectivity. Using the synthetic strategy for regioselective construction of bridged tricyclic framework 6 , a diazatricyclododecene 3D-scaffold 7a , which enables the introduction of substituents into the scaffold to mimic amino acid side chains, was designed and synthesized. The peptide mimetics 20a-h were synthesized via step-by-step installation of three substituents on diazatricyclododecene scaffold 7a . C o mpounds 20a-h were synthesized as α-helix peptide mimics of hydrophobic ZZxxZ and ZxxZZ sequences (Z = Leu or Phe) and subjected to cell-based assays: antiproliferative activity, HIF-1 transcriptional activity which is considered to affect cancer malignancy , and antiviral activity against rabies virus. Compound 20a showed the strongest inhibitory activity of HIF-1 transcriptional activity (IC 50 = 4.1 ± 0.8 μM), whereas compounds 20a-g showed antiviral activity with IC 50 values of 4.2-12.4 μM, suggesting that the 3D-scaffold 7a has potential as a versatile peptide mimic skeleton.

International audience; Vibsatin A is a new neurotrophic vibsane-type diterpenoid comprising a bridged bicyclo[4.2.1]nonane skeleton. Inspired by Sawamura’s works, we generated the bicyclic backbone through a Conia-ene-derived 7-exo-dig cyclization from an enantiomerically enriched TIPS-based silyl enol ether. The reaction, catalyzed by a sensitive gold(I) complex, was efficiently performed on a large scale by glovebox free techniques. Furthermore, the shape of this system was exploited for subsequent installation of all of the stereogenic centers.

Background Drug-induced glaucoma (DIG) is a kind of serious adverse drug reaction that can cause irreversible blindness. Up-to-date, the molecular mechanism of DIG largely remains unclear yet due to the medical complexity of glaucoma onset. Methods In this study, we conducted data mining of tremendous historical adverse drug events and genome-wide drug-regulated gene signatures to identify glaucoma-associated drugs. Upon these drugs, we carried out serial network analyses, including the weighted gene co-expression network analysis (WGCNA), to illustrate the gene interaction network underlying DIG. Furthermore, we applied pathogenic risk assessment to discover potential biomarker genes for DIG. Results As the results, we discovered 13 highly glaucoma-associated drugs, a glaucoma-related gene network, and 55 glaucoma-susceptible genes. These genes likely played central roles in triggering DIGs via an integrative mechanism of phototransduction dysfunction, intracellular calcium homeostasis disruption, and retinal ganglion cell death. Further pathogenic risk analysis manifested that a panel of nine genes, particularly OTOF gene, could serve as potential biomarkers for early-onset DIG prognosis. Conclusions This study elucidates the possible molecular basis underlying DIGs systematically for the first time. It also provides prognosis clues for early-onset glaucoma and thus assists in designing better therapeutic regimens.

A convenient, transition-metal-free access to a series of unprecedented saccharin substituted 2,5-dihydropyrroles is reported. This approach employs a post-Ugi–Smiles 5-endo-dig Conia–ene cyclization sequence under mild conditions while incorporating a series of readily available precursors and sodium azide substrate as a catalyst for the cyclization step. The method provides a broad scope of 2,5-dihydropyrrole derivatives in good yields.

Designing antibody-powered DNA nanodevice switches is crucial and fascinating to perform a variety of functions in response to specific antibodies as regulatory inputs, achieving highly sensitive detection by integration with simple amplified methods. In this work, we report a unique DNA-based conformational switch, powered by a targeted anti-digoxin mouse monoclonal antibody (anti-Dig) as a model, to rationally initiate the hybridization chain reaction (HCR) for enzyme-free signal amplification. As a proof-of-concept, both a fluorophore Cy3-labeled reporter hairpin (RH) in the 3' terminus and a single-stranded helper DNA (HS) were individually hybridized with a recognition single-stranded DNA (RS) modified with Dig hapten, while the unpaired loop of RH was hybridized with the exposed 3'-toehold of HS, isothermally self-assembling an intermediate metastable DNA structure. The introduction of target anti-Dig drove the concurrent conjugation with two tethered Dig haptens, powering the directional switch of this DNA structure into a stable conformation. In this case, the unlocked 3'-stem of RH was implemented to unfold the 5'-stem of the BHQ-2-labeled quench hairpin (QH), rationally initiating the HCR between them by the overlapping complementary hybridization. As a result, numerous pairs of Cy3 and BHQ-2 in the formed long double helix were located in spatial proximity. In response to this, the significant quenching of the fluorescence intensity of Cy3 by BHQ-2 was dependent on the variable concentration of anti-Dig, achieving a highly sensitive quantification down to the picomolar level based on a simplified protocol integrated with enzyme-free amplification.

We herein report a chemo- and regioselective 6-exo-dig catalytic cyclization of Ugi adducts N-substituted 2-alkynamides to access functionalized morpholinone glycoconjugates in the presence of triphenylphosphine. This array allows an interesting multicomponent access to a library of functionalized morpholinone glycoconjugates under mild reaction conditions with regeneration of catalyst triphenylphosphine, supported by 31P nuclear magnetic resonance studies. Density functional theory shows the 6-exo-dig oxocyclization pathway is preferred, which supports our experimental observation.

A robust method toward the synthesis of diastereomerically pure methyl (2S)-2-(1-benzyl-3-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-methylbutanoate has been described. The key reactions in the synthesis are: HATU-mediated coupling, Pd-catalyzed Sonogashira coupling, base-mediated 5-exo-dig cyclization, and catalytic hydrogenation. The diastereomeric mixture is subjected to trituration with heptane to furnish both diastereomers in moderate yields. The relative stereochemistry was confirmed by the single crystal X-ray diffractometry. The key feature of the method is the simplicity of the diastereomeric separation.

Garlic, Allium sativum L., is a culinary herb that has been employed medicinally since ancient times. Garlic has been regarded as the oldest of all cultivated plants. Various experimental as well as human studies have demonstrated that garlic is used in preventing the initiation and evolution of several ailments such as hypertension, atherosclerosis, diabetes mellitus, cancer, microbial infections, arthritis, thrombosis, and Alzheimer’s disease. It can also act as an anti-oxidant. The preclinical toxicity study gives an impression that garlic is safe, although allergic reactions may occur. Recently, there has been systematic research regarding garlic, and positive results have been attained in healing many diseases. For centuries many countries of different civilizations and continents protected their populations and healed themselves using garlic. Therefore, there is an augmented necessity of investigation on the history of garlic for the sake of strengthening the ability of physicians and pharmacists to deal with the challenges arising in the provision of specialized facilities to serve mankind. The present review provides morphological, pharmacological, and toxicological insight regarding garlic. Further studies are required to explicate the therapeutic mode of action of garlic along with its potency, effectiveness, and clinical wellbeing in the management of different ailments.

Autori predstavljaju projekt nastao suradnjom Konzervatorskog odjela u Trogiru Ministarstva kulture i medija te Javne vatrogasne postrojbe Grada Trogira. Iako je inicijalno zamišljen kao jednogodišnji projekt s primarnim ciljem revidiranja postojeće procjene ugroženosti za povijesnu jezgru, projekt je nadišao prvotno zamišljene okvire i u smislu aktivnosti i broja uključenih partnera. Vatrogasci i konzervatori radili su zajedno kako bi uključili cijeli sektor civilne zaštite grada i aktivirali lokalnu zajednicu kroz DIG (disaster imagination game) i InSight radionice. Štoviše, projekt je prerastao u nacionalni program smanjivanja rizika od požara na baštini koji podupiru Ministarstvo kulture i medija te Hrvatska vatrogasna zajednica., This paper presents a project delivered in collaboration between the Conservation Department of the Ministry of Culture and the Trogir Fire Department. Although originally planned as a one-year project, with the aim of revising the existing Fire Risk Assessment for the historic city core of Trogir, it surpassed its initial framework, both in terms of activities and the partners involved. Fire-fighters and conservators worked together to engage the entire civil protection sector in the city, and to involve the local community through a disaster imagination game and InSight workshops. Moreover, the project has grown into a national programme for fire mitigation in heritage sites, supported by both the Ministry of Culture and the Croatian Fire Association.

Made available in DSpace on 2022-04-29T08:37:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Twelve dose-response trials were conducted to estimate lysine (Lys) and arginine (Arg) requirements of male and female broilers in the starter (1–14 days of age), grower (15–28 days of age), and finisher (29–42 days of age) phase. In each trial, 640 birds were randomly assigned to one of eight treatments (Lys or Arg levels) with four replicates of 20 birds. In Lys trials, for both sexes, digestible (dig) Lys concentration in feeds ranged from 8.73 to 17.5 g/kg in the starter phase, 7.80–15.7 g/kg in the grower phase, and 6.40–12.8 g/kg in the finisher phase. In Arg trials, for both sexes, the dietary dig Arg concentrations investigated ranged from 10.9 to 18.7 g/kg in the starter phase, 8.38 a 16.8 g/kg in the grower phase, and 6.85–13.7 g/kg in the finisher phase. Performance and protein gain (PG) data were fitted to linear-response plateau (LRP), curvilinear-response plateau (CRP), and quadratic polynomial (QP) regression models to estimate the dig Lys and Arg intake required to optimize the responses assessed. For each phase, average daily gain (ADG) was maximized at 0.415, 1.38, 1.79 g dig Lys/day and 0.457, 1.48, and 2.11 g dig Arg/day in male broiler chickens and 0.415, 1.21, and 1.40 g dig Lys/day and 0.446, 1.34, and 1.89 g dig Arg/day in female. For male birds, PG was maximum at 0.496, 1.63, and 1.72 g dig Lys/day, whereas for female birds, maximum values were 0.528, 1.30, and 1.80 g dig Lys/day. In Arg trials, maximum protein gain was reached at 0.518, 1.36, and 2.29 g dig Arg/day in male, and 0.474, 1.28, and 2.03 g Arg/day in female, respectively. The Lys and Arg values reported in this study may be used as a reference to formulate feeds and achieve a maximum response. Department of Animal Science Faculty of Agrarian and Veterinary Science (FCAV) São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N Aquaculture Center of São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N Production Systems Natural Resources Institute Finland (Luke) Department of Animal Science Faculty of Agrarian and Veterinary Science (FCAV) São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N Aquaculture Center of São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N CNPq: 142222/2018-6 FAPESP: 2013/25761-4

We demonstrate a facile approach for the synthesis of gem-disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols be...

An efficient and practical one-pot strategy to produce highly substituted 1-naphthylamines via sequential palladium-catalyzed decarboxylative amination/intramolecular 6-endo-dig benzannulation reactions has been described. In this reaction, a broad range of electron-rich, electron-neutral, and electron-deficient o-alkynylarylketones react well with N-hydroxyl aryl/alkylamides to give a diversity of 1-naphthylamines in good to excellent yields under mild reaction conditions. The gram-scale synthesis, with benefits such as undiminished product yield and easy transformation, illustrated the practicality of this method.

An InCl3-catalyzed atom-economic intramolecular 5-exo-dig cyclization/1,6-conjugate addition/aromatization of N-propargylamides with p-QMs to produce oxazoles tethering diarylmethane has been successfully developed. InCl3 not only served as Lewis acid to catalyze the cyclization of propargylic amides but also activated the carbonyl of p-QMs to achieve the 1,6-addition process in a one-pot manner. The reaction has attractive features, including mild reaction conditions, broad scope of substrates, good yields, and scalability.

Mouse-mouse hybridoma cell lines producing stable, highly specific monoclonal antibodies with good affinity for the cardiac glycoside digoxin (DIG) were established to construct an indirect enzyme-linked immunosorbent assay and lateral-flow immunochromatographic strip to detect DIG in human blood. The hapten DIG was coupled to bovine serum albumin or chicken ovalbumin by sodium periodate oxidation. The highest sensitivity and specificity antibody had a median inhibitory concentration (IC50) of 0.45 ng/mL, a linear range of detection of 0.293-0.7 ng/mL, and low cross-reactivity with several DIG analogues. The cut-off value of the lateral-flow immunochromatographic strip was 5 ng/mL when the strip was tested with human blood. The immunochromatographic lateral flow strip test provides a quick and convenient method for determining DIG in plasma which can be visually observed in only 5 min to promote rational drug use.

An efficient approach for the synthesis of immobilized copper (triazole-5-yl)methanamine complexes onto MCM-41 (Cu@TZMA@MCM-41), as a novel recyclable nanocatalyst, is described. This nanocatalyst was used for the synthesis of pyridine-containing pseudopeptides through a sequential Ugi/nucleophilic addition/1,5-enyne cyclization reaction and elicited good-to-excellent yields. The nanocatalyst was fully characterized by SEM, EDS, TEM, BET, ICP-OES, TGA, and XRD techniques. Furthermore, the catalyst was recovered by simple filtration and could be used for at least 5 cycles without significant loss of activity.

The paper features linguistic and creative foundations in the German comic book "Dig, Dag, Digedag". Modern linguacultural, cognitive studies, and discursive practices are aimed at studying comics, which are a series of drawings with brief accompanying texts. However, comic books consist of two components – verbal and nonverbal, which means that graphic novels and strips have linguacreative foundations. The author performed philological and semiotic analyzes to identify the linguistic and creative foundations of the German comic book. The algorithm of the philological analysis included literary description of the time and place, the most original and interesting scenes in several editions, lexical expressive means and stylistic devices. The semiotic analysis featured the graphics related to the non-verbal component. The linguistic and creative foundations of the comic are manifested in original plots that allow its readers to escape from everyday and political problems through fun, exciting, and informative trips to Ancient Rome, Sicily, ancient Arab countries, the Moon and Mars, as well as to an uninhabited island. The carefully selected scientific and mundane knowledge is transmitted through verbal means and comic book graphics, making young readers expand their horizon. The use of such tools as hyperbole, metaphor, pun, as well as diverse vocabulary within the text of the comic, also suggests linguistic creativity of the German comic book "Dig, Dag, Digedag".

Proton-beam irradiation (1, 2, and 4 Gy, 150 MeV) of hybrid male mice F1 (CBA × C57BL/6J) has changed their adaptive behavior in a different ways. The irradiated mice performed significantly less successfully than control ones in the puzzle-box test at those stages when the underpass to the safe box compartment was masked by wood shavings, and they had to dig to get to it. At the same time, they were significantly more successful at the stages when the underpass was masked by a light plug, which should be removed as it blocked the entrance. A reduction in neurogenesis in two proliferative forebrain zones had been demonstrated in irradiated mice.

MAPK pathway activation has been recurrently observed in desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) with reported disproportionally low mutation allele frequencies relative to the apparent high tumor content, suggesting that MAPK pathway alterations may be subclonal. We sought to expand the number of molecularly profiled cases and investigate if tumor cell composition could account for the observed low mutation allele frequencies. Molecular (targeted neuro-oncology next-generation sequencing/RNA sequencing and OncoScan microarray) and immunohistochemical (CD68-PGM1/CD163/CD14/CD11c/lysozyme/CD3/CD20/CD34/PD-L1) studies were performed in 7 DIG. Activating MAPK pathway alterations were identified in 4 (57%) cases: 3 had a BRAF mutation (V600E/V600D/V600_W604delinsDQTDG, at 8%–27% variant allele frequency) and 1 showed a TPM3-NTRK1 fusion. Copy number changes were infrequent and nonrecurrent. All tumors had at least 30% of cells morphologically and immunophenotypically consistent with microglial/macrophage lineage. Two subtotally resected tumors regrew; 1 was re-excised and received adjuvant treatment (chemotherapy/targeted therapy), with clinical response to targeted therapy only. Even with residual tumor, all patients are alive (median follow-up, 83 months; 19–139). This study further supports DIG as another MAPK pathway-driven neuroepithelial tumor, thus expanding potential treatment options for tumors not amenable to surgical cure, and suggests that DIG is a microglia/macrophage-rich neuroepithelial tumor with frequent low driver mutation allele frequencies.

A study was conducted to determine if increasing digestible (dig) amino acid (AA) density or feed allocation of starter diets fed to broilers receiving coccidiosis vaccination can ameliorate poor cumulative growth performance and reduce meat yield. A total of 1,600 Yield Plus Ross × Ross 708 male broilers were assigned to a 2 × 3 factorial arrangement of dig AA density [moderate (1.15% dig Lys) and high (1.25% dig Lys)] and feed allotment (0.45, 0.73, and 1.00 kg/bird) with 2 positive control treatments during the starter period. Diets were formulated to essential AA ratios relative to dig Lys. Vaccinated birds received a 1x dosage of Coccivac- B52 prior to placement, whereas non-vaccinated birds in the positive control groups were fed diets containing diclazuril. Following consumption of the starter diets, birds were provided common grower and finisher diets. Broilers fed the high AA density diet during the starter period had higher cumulative BW gain and lower cumulative feed conversion ratios (P

Activity level, or the amount of action/interaction with a product, can be an indication of interest in a product category and influences purchases. Our goal was to assess the overall market for landscape plants using consumers’ activity level from the active/passive continuum proposed by Pine and Gilmore (2011). An online survey instrument was administered to invitees from a national online panel from 7 to 13 Sept. 2016 yielding 1543 useful responses. Factor analysis of 23 items adapted from a previous study revealed five factors, including one active factor and a separate passive factor. These two factors were used in the present study as a basis for a k-means cluster analysis. Two clusters emerged and were labeled “Active Engagement” and “Obligatory Passive Engagement” in landscape activities. We compared cluster means for all five factors and found the Active cluster purchased more plants of all types as well as had greater landscape pride and desire for a low (water) input landscape. Members of the Active cluster were from higher income and education households which were slightly larger and more likely to have Caucasian residents compared with the Passive cluster. In practice, retail employees and landscape professionals might initially ask about consumers’ activity level desired in the landscape as a screening question. Subsequent assistance in design and/or plant selection/purchase could then be tailored toward the desired activity level.

A series of 4-exo-dig cyclocarbopalladations has been efficiently used to produce molecular complexity in a straightforward manner. Strained 1,2-cyclobutanediols are rapidly obtained, usually under microwave irradiation, in high yields. In many cases, the cyclocarbopalladation cascade reaction is associated with 6π- or 8π-electrocyclic reactions. Polycyclic skeletons of unnatural or natural products can be prepared in a few steps from simple starting materials. Very strained aromatic polycycles, the taxane framework, cyclooctatrienes, cyclooctatetraenes, fenestranes, and fenestrenes have been obtained using this methodology.