Terminal Position Research Articles

Dendritic Inhibition by Shh Signaling-Dependent Stellate Cell Pool Is Critical for Motor Learning.

Cerebellar inhibitory interneurons are important regulators of neural circuit activity for diverse motor and nonmotor functions. The molecular layer interneurons (MLIs), consisting of basket cells (BCs) and stellate cells (SCs), provide dendritic and somatic inhibitory synapses onto Purkinje cells, respectively. They are sequentially generated in an inside-out pattern from Pax2+ immature interneurons, which migrate from the prospective white matter to the ML of the cortex. However, little is known about how MLI subtype identities and pool sizes are determined, nor are their contributions to motor learning well understood. Here, we show that GABAergic progenitors fated to generate both BCs and SCs respond to the Sonic hedgehog (Shh) signal. Conditional abrogation of Shh signaling of either sex inhibited proliferation of GABAergic progenitors and reduced the number of Pax2+ cells, whereas persistent Shh pathway activation increased their numbers. These changes, however, did not affect early born BC numbers but selectively altered the SC pool size. Moreover, genetic depletion of GABAergic progenitors when BCs are actively generated also resulted in a specific reduction of SCs, suggesting that the specification of MLI subtypes is independent of Shh signaling and their birth order and likely occurs after Pax2+ cells settle into their laminar positions in an inside-out sequence. Mutant mice with reduced SC numbers displayed decreased dendritic inhibitory synapses and neurotransmission onto Purkinje cells, resulting in an impaired acquisition of eyeblink conditioning. These findings also reveal an essential role of Shh signaling-dependent SCs in regulating inhibitory dendritic synapses and motor learning.SIGNIFICANCE STATEMENT The cerebellar circuit that enables fine motor learning involves MLIs of BCs and SCs, which provide dendritic and somatic inhibitory synapses onto Purkinje cells. Little is known about how their identities and numbers are determined, nor are their specific contributions to motor learning well understood. We show that MLI subtypes are specified independent of Shh signaling and their birth orders but appear to occur in their terminal laminar positions according to the inside-out sequence. This finding challenges the current view that MLI subtypes are specified sequentially at the progenitor level. We also demonstrate that dendritic inhibition by Shh signaling-dependent SC pool is necessary for motor learning.

Synthesis of the precursors of iminosugars with 7-membered ring

d-Glucose was converted into the orthogonally protected open-chain derivative having different blocks at both terminal positions: C1 and C6. Selective deprotection of the C1-position opened a route to intermediate with the D-gluco-configuration, while deprotection at the C6-position gave the L-gulo isomer. In both derivatives, the oxime functionality was installed at the proper terminal position, which produced the corresponding precursors of a family of 7-membered ring iminosugars. One of these oximes was converted into the direct precursor: 6,1-bromonitrile.

Investigation of displacement ventilation performance under various room configurations using computational fluid dynamics simulation

The performance of a ventilation system affects air quality, thermal comfort, and energy consumption in indoor environments. To evaluate the performance of displacement ventilation under various room configurations, steady Reynolds Averaged Navier–Stokes (RANS) Computational Fluid Dynamics (CFD) simulations were used. The CFD model was validated using measurements of a full-scale test room. The age of air concept was used to evaluate the ventilation performance regarding indoor air quality. The PD index was used to control the case studies for draft risk. Twelve cases with different configurations were systematically studied and compared with the reference case. The configurations included plan aspect ratio, exhaust opening position, inlet position and geometry, and internal heat gains. The results showed that the overall ventilation performance of a room is less sensitive to room configurations compared with local ventilation performance around the occupants. However, almost in all cases, the occupants were exposed to better-than-average air quality in most cases. The results also indicated that when internal heat gains are small, displacement ventilation should be used with caution. Practical application: Any HVAC system design is based on assumptions made for ventilation performance. Comprehensive knowledge of the influential factors is critical for an efficient design. Regarding the architecture and interior design, the architects are also involved in the ventilation systems since they have an axial role in decision making for room configuration, including but not limited to room geometry, the position of inlet and outlet air terminals, and heat/pollutant sources. Consequently, the impact of room configuration on ventilation performance is of practical importance in the architecture, engineering, and construction industry.

Design, Synthesis and Biological Evaluation of New 3,4-Dihydro-2(1H)-Quinolinone-Dithiocarbamate Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease.

BackgroundAlzheimer’s disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports.PurposeTo obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1H)-quinolinone and dithiocarbamate.MethodsAll compounds were evaluated for their inhibitory abilities of ChEs and MAOs. Then, further biological activities of the most promising candidate 3e were determined, including the ability to cross the blood-brain barrier (BBB), kinetics and molecular model analysis, cytotoxicity in vitro and acute toxicity studies in vivo.ResultsMost compounds showed potent and clear inhibition to AChE and MAOs. Among them, compound 3e was considered to be the most effective and balanced inhibitor to both AChE and MAOs (IC50=0.28 µM to eeAChE; IC50=0.34 µM to hAChE; IC50=2.81 µM to hMAO-B; IC50=0.91 µM to hMAO-A). In addition, 3e showed mixed inhibition of hAChE and competitive inhibition of hMAO-B in the enzyme kinetic studies. Further studies indicated that 3e could penetrate the BBB and showed no toxicity on PC12 cells and HT-22 cells when the concentration of 3e was lower than 12.5 µM. More importantly, 3e lacked acute toxicity in mice even at high dose (2500 mg/kg, P.O.).ConclusionThis work indicated that compound 3e with a six-carbon atom linker and a piperidine moiety at terminal position was a promising candidate and was worthy of further study.

Iterative Guidance Algorithm for Lunar Soft Landing

A closed-form explicit guidance algorithm for the deceleration, attitude adjustment and final landing phases before lunar probe soft landing is presented in this paper. Guidance with a variable-thrust engine is extended from the iterative guidance mode (IGM) to satisfy the terminal velocity, position, and attitude constraints. The closed form expression, obtained by integrating the acceleration and shutdown time, is analysed to obtain an explicit ex-pression for the velocity and position requirements and vertical touchdown of the spacecraft toward a designated landing site with high terminal accuracy. The influence of the attitude constraint on the motion equation is analysed to calculate the attitude, which is the physical control variable for the guidance loop. The variable thrust IGM formulation ensures the least switch of the thrust magnitude profile based on the analysis result of the residual flight altitude. The simulation results demonstrate that the proposed multi-constrained iterative guidance method can help accomplish an accurate lunar soft landing and that employed the algorithm is simple and easy to implement in engineering practice.

Biochemical and molecular characterization of sialylated cervical mucins in sheep

Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen–thawed semen at both synchronized and natural estrus cycles. These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport.

Inflorescence and floral development of Dipteronia sinensis (Sapindaceae): Demonstration of developmental constraints in the shaping of the flower

The inflorescence, floral structure and ontogeny, and breeding system of the relict woody species Dipteronia sinensis was investigated to understand the developmental basis for its floral Bauplan, more particularly the octandrous androecium, dimerous gynoecium and the occurring flower symmetry in comparison with Sapindaceae.The functionally unisexual flowers arise in thyrses. Structural floral dimorphism was clearly observed in the different lengths of style and filaments and in the presence or absence of fructifications. Functionally pistillate flowers are found in a terminal position of each cincinnus maturing before the functionally staminate flowers. Petals are initiated unidirectionally and there is a time overlap with stamens. No common petal-stamen primordium was observed. There are two empty stamen positions, always opposite the first initiated petal, between sepals 1 and 3, and opposite the second petal between sepals 2 and 4; subsequently stamens are displaced to accommodate to the available space. Two median carpels are almost apocarpous in early stages and produce two parallel ovules each that become later superposed. Floral dimorphism develops as a late event when pollen and ovules are formed.Empty stamen positions are inversely correlated with the sequence of initiation and delayed growth of the petals, suggesting that a subtle heterochronic shift is responsible for the balance between petal and stamen initiation. Although the flower is initially polysymmetric to weakly monosymmetric, the bicarpellate gynoecium causes a shift to disymmetry during the mid-developmental stage as in the sister genus Acer, differently from tricarpellate Sapindaceae. Floral development demonstrates the flexibility in building symmetry in Sapindaceae, which is linked with available space and subtle changes in the sequence of initiation, rate of development and reduction of floral organs. This study underlines the importance of analyzing developmental constraints responsible for the floral diversity of Sapindaceae and provides further support for a monosymmetric ancestry in Sapindaceae.

Reevaluation of the phylogenetic relationships among Neotomini rodents (Hodomys, Neotoma, and Xenomys) and comments on the woodrat classification.

The woodrats or packrats of the genus Neotoma have been the subject of a wide array of research including paleoecology, physiology, morphological evolution, systematics, speciation, and hybridization. In recent years, much work has been done to elucidate evolutionary relationships within and between closely related species of the genus; in particular the addition of newly collected specimens from critical geographic regions has provided new opportunities for taxonomic assessment. Given these new data and their potential, parsimony (PARS), maximum likelihood (ML), and Bayesian inference (BI) analyses were conducted on DNA sequences obtained from nine individual genes (four mitochondrial loci: 12S, 16S, CoII, and Cytb; five nuclear loci: AdhI2, BfibI7, En2, Mlr, and Myh6) to estimate the phylogenetic relationships among 23 species of Neotoma. Results of these analyses depicted a wide array of phylogenetic relationships among taxa; with substantial nodal support recovered in both the ML and PARS analyses at some mid-level and terminal positions. Several individual genes, particularly 12S, AdhI2, BfibI7, CoII, and Cytb, provided support at several basal positions; however, phylogenetic resolution was limited in the other genes. A final BI analysis where the nine genes were concatenated into a single data set produced several supported clades that corresponded to previously recognized species groups (floridana, micropus, mexicana, and lepida) and the subgenus Homodontomys. Levels of genetic divergence for within-species comparisons (estimated from the Cytb data set) ranged from 0.88% (N. magister) to 6.82% (N. fuscipes); for between sister species comparisons ranged from 4.68% (N. devia and N. lepida) to 12.70% (N. angustapalata and N. nelsoni); and for members within closely related clades ranged from 8.70% (N. bryanti and N. lepida) to 12.57% (N. goldmani and N. magister). Evaluations of generic, subgeneric, and species group boundaries were explored using phylogenetic principles on the DNA sequence data presented herein, as well as morphological findings from previous studies. Results obtained suggest that the most conservative taxonomic interpretation involves the abandonment of subgeneric delineations and relies on the recognition of eight species groups (cinerea, floridana, fuscipes, lepida, mexicana, micropus, phenax, and stephensi) as the backbone of the woodrat classification.

Role of Terminal Group Position in Triphenylamine-Based Self-Assembled Hole-Selective Molecules in Perovskite Solar Cells.

The application of self-assembled molecules (SAMs) as a charge selective layer in perovskite solar cells has gained tremendous attention. As a result, highly efficient and stable devices have been released with stand-alone SAMs binding ITO substrates. However, further structural understanding of the effect of SAM in perovskite solar cells (PSCs) is required. Herein, three triphenylamine-based molecules with differently positioned methoxy substituents have been synthesized that can self-assemble onto the metal oxide layers that selectively extract holes. They have been effectively employed in p-i-n PSCs with a power conversion efficiency of up to 20%. We found that the perovskite deposited onto SAMs made by para- and ortho-substituted hole selective contacts provides large grain thin film formation increasing the power conversion efficiencies. Density functional theory predicts that para- and ortho-substituted position SAMs might form a well-ordered structure by improving the SAM's arrangement and in consequence enhancing its stability on the metal oxide surface. We believe this result will be a benchmark for the design of further SAMs.

Newton’s method for reinforcement learning and model predictive control

The purpose of this paper is to propose and develop a new conceptual framework for approximate Dynamic Programming (DP) and Reinforcement Learning (RL). This framework centers around two algorithms, which are designed largely independently of each other and operate in synergy through the powerful mechanism of Newton’s method. We call these the off-line training and the on-line play algorithms; the names are borrowed from some of the major successes of RL involving games. Primary examples are the recent (2017) AlphaZero program (which plays chess), and the similarly structured and earlier (1990s) TD-Gammon program (which plays backgammon). In these game contexts, the off-line training algorithm is the method used to teach the program how to evaluate positions and to generate good moves at any given position, while the on-line play algorithm is the method used to play in real time against human or computer opponents.Both AlphaZero and TD-Gammon were trained off-line extensively using neural networks and an approximate version of the fundamental DP algorithm of policy iteration. Yet the AlphaZero player that was obtained off-line is not used directly during on-line play (it is too inaccurate due to approximation errors that are inherent in off-line neural network training). Instead a separate on-line player is used to select moves, based on multistep lookahead minimization and a terminal position evaluator that was trained using experience with the off-line player. The on-line player performs a form of policy improvement, which is not degraded by neural network approximations. As a result, it greatly improves the performance of the off-line player.Similarly, TD-Gammon performs on-line a policy improvement step using one-step or two-step lookahead minimization, which is not degraded by neural network approximations. To this end it uses an off-line neural network-trained terminal position evaluator, and importantly it also extends its on-line lookahead by rollout (simulation with the one-step lookahead player that is based on the position evaluator).An important lesson from AlphaZero and TD-Gammon is that the performance of an off-line trained policy can be greatly improved by on-line approximation in value space, with long lookahead (involving minimization or rollout with the off-line policy, or both), and terminal cost approximation that is obtained off-line. This performance enhancement is often dramatic and is due to a simple fact, which is couched on algorithmic mathematics and is the focal point of this work:(a) Approximation in value space with one-step lookahead minimization amounts to a step of Newton’s method for solving Bellman’s equation.(b) The starting point for the Newton step is based on the results of off-line training, and may be enhanced by longer lookahead minimization and on-line rollout. Indeed the major determinant of the quality of the on-line policy is the Newton step that is performed on-line, while off-line training plays a secondary role by comparison.Significantly, the synergy between off-line training and on-line play also underlies Model Predictive Control (MPC), a major control system design methodology that has been extensively developed since the 1980s. This synergy can be understood in terms of abstract models of infinite horizon DP and simple geometrical constructions, and helps to explain the all-important stability issues within the MPC context. In this work we aim to provide insights (often based on visualization), which explain the beneficial effects of on-line decision making on top of off-line training. In the process, we will bring out the strong connections between the artificial intelligence view of RL, and the control theory views of MPC and adaptive control. While we will deemphasize mathematical proofs, there is considerable related analysis, which supports our conclusions and can be found in the author’s recent RL books (Bertsekas, 2019; Bertsekas, 2020), and the abstract DP monograph (Bertsekas, 2022).One of our principal aims is to show, through the algorithmic ideas of Newton’s method and the unifying principles of abstract DP, that the AlphaZero/TD-Gammon methodology of approximation in value space and rollout applies very broadly to deterministic and stochastic optimal control problems, involving both discrete and continuous search spaces, as well as finite and infinite horizon.

Flexible manipulation of the onset and terminal positions of femtosecond laser filamentation in fused silica via controlling beam profile before axicon

The flexible control of femtosecond laser filamentation is crucial for many practical and promising applications. We have demonstrated a simple method to control arbitrarily the onset and the terminal positions of femtosecond laser filament in the fused silica by tailoring the profile of the annular Bessel beam. The tailoring of the inner and outer radius of the annular beam is realized by amplitude mask and iris diaphragm respectively before the axicon. Our experiments have shown that the onset of the filamentation can be modulated by changing the inner radius of the laser beam, and the filamentation termination is determined by the outer radius of the annular beam. Moreover, the results show that the onset and terminal positions of the filaments are positively correlated with the inner and outer radius of the beam, respectively, which facilitate the arbitrary start and length control of the filament in the experiment. In addition, this arbitrary regulation of the onset and termination of the filamentation is being negligibly affected by incident laser power that is lower than the damage threshold of fused silica. The flexible control of filamentation enabled by the simple method is beneficial to many applications.

Novel Thienyl DPP derivatives Functionalized with Terminal Electron-Acceptor Groups: Synthesis, Optical Properties and OFET Performance.

Three novel diketopyrrolopyrrole (DPP) based small molecules have been synthesized and characterized in terms of their chemical‐physical, electrochemical and electrical properties. All the molecules consist of a central DPP electron acceptor core symmetrically functionalized with donor bi‐thienyl moieties and flanked in the terminal positions by three different auxiliary electron‐acceptor groups. This kind of molecular structure, characterized by an alternation of electron acceptor and donor groups, was purposely designed to provide a significant absorption at the longer wavelengths of the visible spectrum: when analysed as thin films, in fact, the dyes absorb well over 800 nm and exhibit a narrow optical bandgap down to 1.28 eV. A detailed DFT analysis provides useful information on the electronic structure of the dyes and on the features of the main optical transitions. Organic field‐effect transistors (OFETs) have been fabricated by depositing the DPP dyes as active layers from solution: the different end‐functionalization of the dyes had an effect on the charge‐transport properties with two of the dyes acting as n‐type semiconductors (electron mobility up to 4.4 ⋅ 10−2 cm2/V ⋅ s) and the third one as a p‐type semiconductor (hole mobility up to 2.3 ⋅ 10−3 cm2/V ⋅ s). Interestingly, well‐balanced ambipolar transistors were achieved by blending the most performant n‐type and p‐type dyes with hole and electron mobility in the order of 10−3 cm2/V ⋅ s

Determination of an optimum sampling unit of Ricania shantungensis (Hemiptera: Ricaniidae) eggs in persimmons

Even though the optimum sampling methods for invasive pests are very important in newly invaded areas, the standard sampling unit of Ricania shantungensis is still undeveloped in persimmons. Among all developmental stages of R. shantungensis, the egg has close relationship between its density and subsequent tree damage. Thus, this study was conducted to suggest an optimum sampling unit for R. shantungensis eggs in persimmons based on characteristics of its within-tree distribution pattern. The within-tree distribution pattern was characterized with 60 persimmon trees by cutting 12 branches at three vertical levels (low, middle, and high) in four horizontal criteria (east, west, south, and north) per tree. The sampling units were determined based on coefficient of variation (CV) and coefficient of determination (r2) calculated from egg mass numbers per 10 cm from the tip within a branch. In numbers of R. shantungensis egg masses, there was no significant difference (P > 0.05) horizontally, but significant (P < 0.05) difference vertically. More R. shantungensis eggs were found on terminal branches of each trunk. The 60 cm from the tip of branches in the terminal positions of each trunk was selected as the optimum sampling unit for R. shantungensis in persimmons because this unit has the lowest CV value and more than 0.9 of r2 value. Even though the optimum sample number per tree should be determined field-specifically, it would be acceptable to sample two or three branches by considering this pests’ recognizable damage level. This small sampling unit could make the sampling of R. shantungensis become more economical, precise, and consistent in persimmon fields.

Synthesis of Crosslinked 2'-OMe RNA Duplexes Using 2-Amino-6-Vinylpurine and Their Application for Effective Inhibition of miRNA Function.

Crosslinking reactions to nucleic acids are an effective way to prepare stable complexes formed by covalent bonding. We demonstrated that fully 2'-O-methylated (2'-OMe) RNAs having a 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. Recently, we reported the preparation of crosslinked 2'-OMe RNA duplexes using AVP and the anti-miRNA oligonucleotides (AMOs) containing crosslinked duplexes at the terminal positions. These AMOs exhibited efficient microRNA (miRNA) inhibition at very low concentrations. In this article, we describe the chemical synthesis of 2'-OMe oligonucleotides containing AVP and preparation of the AMOs bearing crosslinked 2'-OMe RNA duplexes using AVP. In addition, we describe in detail the miRNA inhibition assay using these AMOs. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of phosphoramidite of 2-amino-6-vinylguanosine derivative Basic Protocol 2: Synthesis of AVP-2'-OMe RNA Basic Protocol 3: Evaluation of the crosslink reactivity of CFO containing AVP to the 2'-OMe RNA and preparation of AMOs containing crosslinked duplex Basic Protocol 4: miRNA inhibition assays.

A9 SIALIC ACID METABOLISM PLAYS A KEY ROLE IN INTESTINAL FITNESS AND VIRULENCE OF AN ATTACHING/ EFFACING BACTERIAL PATHOGEN

BackgroundThe gastrointestinal (GI) mucus barrier acts as an important interface between the host and luminal gut microbes, beyond its role in limiting direct contact between noxious luminal agents and the underlying intestinal epithelium. Mucus is comprised of highly glycosylated mucin proteins, modified by O-glycan side chains, formed by five sugar monomers, including sialic acid. Sialic acid frequently occupies the terminal position of O-glycans and can be cleaved by microbial sialidases. We hypothesize that upon entering their hosts, enteric pathogens, such as the attaching and effacing (A/E) family (EHEC, EPEC and Citrobacter rodentium) metabolically adapt to their intestinal environment, and express key virulence factors by sensing and metabolizing mucin sugars, such as sialic acid.AimsInvestigate the role of sialic acid in regulating the fitness and virulence strategies of the A/E pathogen C. rodentium within the GI environment.MethodsC57Bl/6 mice were orally infected with either wildtype (WT) or mutant strains of C. rodentium to study bacterial pathogenicity in vivo. Sialic acid was localized in mouse colonic tissue sections through lectin staining, and quantified in mouse feces and mucus scrapings using a commercial kit. Protein secretion by C. rodentium, in the presence or absence of sialic acid was analyzed by SDS-PAGE and mass spectrometry. Intestinal epithelial cell lines were infected with enteropathogenic E. coli (EPEC) or C. rodentium to examine bacterial adherence.ResultsSialic acid was expressed widely in the GI tracts of mice, primarily in the colonic mucus layer and by intestinal goblet cells. Both EPEC and C. rodentium were found to take up and metabolize sialic acid through the transporter NanT. A C. rodentium strain deficient in sialic acid uptake ( ΔnanT) was dramatically impaired in colonizing the intestines of mice and was rapidly cleared. Sialic acid also impacted C. rodentium’s virulence by inducing the secretion of two key virulence factors, which significantly enhanced the pathogen’s adhesion to intestinal epithelial cells. Moreover, sialic acid increased C. rodentium’s ability to degrade mucus, due to the increased production of these two secreted virulence factors.ConclusionsWe demonstrate that sialic acid, a mucin-derived sugar, is an essential nutrient for A/E pathogens to thrive and expand within their host’s intestines. Moreover, sialic acid enhances pathogen virulence by inducing secretion of two important virulence factors, which increase adhesion to the epithelium and promote the degradation of mucus.Funding AgenciesCCC, CIHRCH.I.L.D. Fdn

Photoinduced Bisphosphination of Alkynes with Phosphorus Interelement Compounds and Its Application to Double-Bond Isomerization.

The addition of interelement compounds with heteroatom-heteroatom single bonds to carbon-carbon unsaturated bonds under light irradiation is believed to be an atomically efficient method to procure materials with carbon-heteroatom bonds. In this study, we achieved the photoinduced bisphosphination of alkynes using the phosphorus interelement compound, tetraphenyldiphosphine monosulfide (1), to stereoselectively obtain the corresponding (E)-vic-1,2-bisphosphinoalkenes, which are important transition-metal ligands. The bisphosphination reaction was performed by mixing 1 and various alkynes and then exposing the mixture to light irradiation. Optimization of the conditions for the bisphosphination reaction resulted in a wide substrate range and excellent trans-selectivity. Moreover, the completely regioselective introduction of pentavalent and trivalent phosphorus groups to the terminal and internal positions of the alkynes, respectively, was achieved. We also found that the novel double-bond isomerization reaction of the synthesized bisphosphinated products occurred with a catalytic amount of a base under mild conditions. Our method for the photoinduced bisphosphination of carbon-carbon unsaturated compounds may have strong implications for both organic synthesis and organometallic and catalyst chemistry.

Ultrahigh sensitive and selective triethylamine sensor based on h-BN modified MoO3 nanowires

In this work, a novel structure of 1D MoO3 nanowires wrapped by 2D hexagonal boron nitride (h-BN) was synthesized via a simple solvothermal method with subsequent annealing process for triethylamine (TEA) detection. The samples were characterized by XPS, SEM, HRTEM and N2 adsorption-desorption. Gas sensing performance test results illuminate that the typical 2 wt% h-BN/MoO3 sensor possesses an ultrahigh response (8616) toward 500 ppm TEA. The promoted sensing performance of TEA may be caused by the forming of heterojunction between h-BN and MoO3, the increased specific surface area of h-BN modification, providing a highly active sites for the adsorption of TEA gas, which greatly enhance the response of the sensor. The adsorption energy of a single oxygen molecule on MoO3 (010) surface was calculated by DFT, indicating the most stable site is the terminal oxygen position (Top O-1), with an adsorption energy of −2.075 eV. This work provides an inspiration to design highly efficient TEA gas sensor on basis of h-BN/MoO3 nanocomposites.

Role of sialylation of N-linked glycans in prion pathogenesis.

Mammalian prion or PrPSc is a proteinaceous infectious agent that consists of a misfolded, self-replicating state of the prion protein or PrPC. PrPC and PrPSc are posttranslationally modified with N-linked glycans, which are sialylated at the terminal positions. More than 30years have passed since the first characterization of the composition and structural diversity of N-linked glycans associated with the prion protein, yet the role of carbohydrate groups that constitute N-glycans and, in particular, their terminal sialic acid residues in prion disease pathogenesis remains poorly understood. A number of recent studies shed a light on the role of sialylation in the biology of prion diseases. This review article discusses several mechanisms by which terminal sialylation dictates the spread of PrPSc across brain regions and the outcomes of prion infection in an organism. In particular, relationships between the sialylation status of PrPSc and important strain-specific features including lymphotropism, neurotropism, and neuroinflammation are discussed. Moreover, emerging evidence pointing out the roles of sialic acid residues in prion replication, cross-species transmission, strain competition, and strain adaptation are reviewed. A hypothesis according to which selective, strain-specified recruitment of PrPC sialoglycoforms dictates unique strain-specific disease phenotypes is examined. Finally, the current article proposes that prion strains evolve as a result of a delicate balance between recruiting highly sialylated glycoforms to avoid an "eat-me" response by glia and limiting heavily sialylated glycoforms for enabling rapid prion replication.

Mechanistically Guided Workflow for Relating Complex Reactive Site Topologies to Catalyst Performance in C-H Functionalization Reactions.

Leveraging congested catalyst scaffolds has emerged as a key strategy for altering innate substrate site-selectivity profiles in C-H functionalization reactions. Similar to enzyme active sites, optimal small molecule catalysts often feature reactive cavities tailored for controlling substrate approach trajectories. However, relating three-dimensional catalyst shape to reaction output remains a formidable challenge, in part due to the lack of molecular features capable of succinctly describing complex reactive site topologies in terms of numerical inputs for machine learning applications. Herein, we present a new set of descriptors, "Spatial Molding for Approachable Rigid Targets" (SMART), which we have applied to quantify reactive site spatial constraints for an expansive library of dirhodium catalysts and to predict site-selectivity for C-H functionalization of 1-bromo-4-pentylbenzene via donor/acceptor carbene intermediates. Optimal site-selectivity for the terminal methylene position was obtained with Rh2(S-2-Cl-5-MesTPCP)4 (30.9:1 rr, 14:1 dr, 87% ee), while C-H functionalization at the electronically activated benzylic site was increasingly favored for Rh2(TPCP)4 catalysts lacking an ortho-Cl, Rh2(S-PTAD)4, and Rh2(S-TCPTAD)4, respectively. Intuitive global site-selectivity models for 25 disparate dirhodium catalysts were developed via multivariate linear regression to explicitly assess the contributing roles of steric congestion and dirhodium-carbene electrophilicity in controlling the site of C-H functionalization. The workflow utilizes spatial classification to extract descriptors only for reactive catalyst conformers, a nuance that may be widely applicable for establishing close correspondence between ground-state model systems and transition states. Broader still, SMART descriptors are amenable for delineating salient reactive site features to predict reactivity in other chemical and biological contexts.

Intramolecular charge transfer and molecular flexibility: Key parameters to be considered in the design of highly fluorescent p-phenylene vinylene derivatives

The optoelectronic properties of a series of p-phenylene vinylene derivatives are studied herein to scrutinize their relationship with the molecular flexibility of the peripheral groups induced by the hybridization of the presented nitrogen atoms. All the molecules share a model fluorophore in the core, 1,3,5-tristyrylbenzene, as a structural leitmotif, while TPA and carbazole groups are located in the periphery. The studied compounds showed high luminescence, highlighting the TPA derivative (compound 1) with a fluorescence quantum yield of 91% in dichloromethane solution. In addition, a linear relationship between the fluorescence lifetime and the solvent polarity was found for this compound. The solvent dependence was associated with an intramolecular charge transfer (ICT) upon photoexcitation which leads to a large change of the dipole moment and geometrical modifications mainly involving a single branch of the molecule. The photophysical properties of the carbazole derivatives (compounds 2 and 3) are strongly influenced by the substitution position of the peripheral carbazole groups (C–N or C–C linkage, respectively). Interestingly, a linear relationship between the non-radiative rate constant and the solvent viscosity was found for compound 3. This behavior was associated to the higher rigidity of this compound because the carbazole groups are embedded in the branches of the molecule and not in a terminal position as in compound 2. Finally, the three studied compounds were used as electroluminescent material for non-doped OLEDs (organic light emitting diodes) in a proof-of-concept. This experiment also showed the importance of the molecular packing for having a good device performance.