Direct Route Research Articles

Base Rates of Non‐Proficiency in Reading and Math: Implications for Universal Screening

ABSTRACTSeveral researchers have called for schools to interpret universal screening results using posterior probabilities. Following this recommendation could require schools to move away from direct‐route, single‐measure screening unless base rates of risk fall within a narrow range. In this descriptive study, we investigated two questions surrounding the feasibility of adopting a probability‐based approach in schools. First, how many districts had base rates of risk that would allow educators to classify all students using a single screener? Second, to what extent would yearly fluctuation in base rates require planned flexibility in screening procedures? We used public state test data to estimate base rates of risk for each district in Florida, Oregon, and Wisconsin across four school years. Districts' base rates of risk were rarely within the required range for a single screener to classify all students based on posterior probabilities. Many districts had base rates conducive to direct route screening in at least 1 year but very few had base rates in the required zone across the 4 years. Using posterior probabilities to make screening decisions may require more changes to existing practices than simply interpreting screening results as probabilities. Additional research to promote the use of this approach in schools is needed.

NHC‐Catalyzed Synthesis of 2‐Aroylchromones and Their Application in the Synthesis of Wrightiadione Analogues

AbstractWith a number of biologically active members, 2‐aroylchromones are valuable synthetic targets. A direct route towards 2‐aroylchromones from 2‐(methylsulfonyl)chromones and aldehydes via NHC‐catalyzed C−C bond formation was developed. Yields of the synthesized 2‐aroylchromones were up to 85%. Chromones with angioprotective or antibacterial properties were easily synthesized using the method developed. Additionally, the synthetic utility of the afforded chromones was demonstrated by using them to synthesize the anticancer compound wrightiadione and analogues of it.

Utilitarians, Educators, Poets: The Beginnings of the <em>Westminster Review</em> and the London Mechanics’ Institution

The Westminster Review and the London Mechanics’ Institution were established within months of each other in 1823–24. The prestige periodical, founded on faith in the power of print media to improve lives by the diffusion of knowledge through the social body, and the institution undertaking a more direct and practical route to the same end, were evidently of the same political spirit and historical moment. This article seeks to add texture to the early history of these two initiatives and the radical London milieu that produced them by delving beneath the official documented accounts into the subterranean networks that connected the Westminster and the London Mechanics’ Institution in the mid-1820s. In so doing it complicates a too easy identification of the relationship between them as simply one of shared utilitarian and party political ideology. It looks beyond public manifestos to consider other sources, such as Anna Birkbeck’s album (begun in 1825), which brings familiar figures into different relation, and introduces new names, such as Mary Shelley, into the interwoven threads that represented radical London at this time. Other stories, like that of the Greek Committee, whose secretary John Bowring, also editor of the Westminster, contributed a poem on George Birkbeck to the album, cut across the histories of the journal Bowring edited and the mechanics’ institution he supported. Other actors, such as Lord Byron, and other forms — poems, cartoons — help us to view these years more fully, and resist the binaried accounts of utilitarianism and Romanticism that run through early commentaries and subsequent scholarship. In fact, things were much less clearly defined. Such an approach reminds us that the imaginative arts were an integral part of the conception and practice of both the Westminster Review and Dr Birkbeck’s London Mechanics’ (later Literary and Scientific) Institution.

Active learning for the design of polycrystalline textures using conditional normalizing flows

Generative modeling has opened new avenues for solving previously intractable materials design problems. However, these new opportunities are accompanied by a drastic increase in the required amount of training data. This is in stark juxtaposition to the high expense and difficulty in curating such large materials datasets. In this work, we propose a novel framework for integrating generative models within an active learning loop. This enables the training of generative models with datasets significantly smaller than what has previously been demonstrated, providing a direct route for their application in data constrained environments. The functionality of this framework is then demonstrated by addressing the challenge of designing polycrystalline textures associated with target anisotropic mechanical properties. The developed protocol exhibited a cost reduction between 14 to 18 times over a randomly sampled experimental design.

Delivery of JAL-TA9 to the brain by nasal application

We have reported on two Catalytides (Catalytic peptides), JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMI). Both peptides belong to the Tob/BTG family proteins and cleave Aβ42. Although Catalytides must be delivered to the brain parenchyma to treat Alzheimer's disease, the blood-brain barrier (BBB) limits their entry into the brain from the systemic circulation. Thus, we evaluated the direct route of ANA-TA9 from the nasal cavity to the brain to bypass the BBB. In this study, we present our findings on JAL-TA9. Animal studies using rats and mice clarified that the plasma clearance of JAL-TA9 was more rapid than its in vitro degradation in plasma, whole blood, and cerebrospinal fluid (CSF). After nasal administration of JAL-TA9, brain concentrations were significantly higher than after intraperitoneal administration, despite much lower plasma concentration. This observation strongly suggests direct delivery of JAL-TA9 to the brain from the nasal cavity. Similar findings were observed for its transport to CSF after nasal and intravenous administration. The concentration of JAL-TA9 in the olfactory bulb peaked at 5 ‍min, while those in the frontal brain peaked at 30 ‍min and in the occipital brain at 60 ‍min. In conclusion, JAL-TA9 was efficiently delivered to the brain by nasal application compared to other routes.

Green synthesis of 2-trifluoromethylquinoline skeletons via organocatalytic N-[(α-trifluoromethyl)vinyl]isatins C-N bond activation

The Pfitzinger reaction has long served as a notable synthesis pathway for quinoline-4-carboxylic acids. Although recognized for its synthetic potential since its discovery more than 138 years ago, a truly catalytic variant has remained elusive until now. Herein, we present a novel 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG)-catalyzed Pfitzinger reaction that employs N-[(α-trifluoromethyl)vinyl]isatins with amines and alcohols, providing direct routes to 2-CF3-quinoline-4-carboxamides and carboxylic esters. This method is not only green and environmentally benign but also accommodates the introduction of other functional groups like CF2H and CO2Me at the C2 position of quinoline skeleton. The utility of this methodology was demonstrated by the broad substrate scope, the late-stage modification of commercial drugs, and the diverse derivatization of quinoline framework. More importantly, this work not only opens up a new avenue for the activation of amide C-N bonds in catalytic reaction development, but also unlocks the huge potential of some 2-trifluoromethyl quinolines with strong inhibitory activity against PTP1B or optoelectronic application in organic light-emitting diodes.

Ag‐Catalyzed Asymmetric 1,3‐Dipolar Cycloaddition of N‐2,2,2‐Trifluoroethylisatin Ketimines with Conjugated Exocyclic Double Bonds: Access to Pyrrolidines with Four Consecutive Stereocenters Including Two Adjacent Spiro‐Quaternary Centers

AbstractAg‐catalyzed enantioselective 1,3‐dipolar cycloaddition of N‐2,2,2‐trifluoroethylisatin ketimines with conjugated exocyclic double bonds including α‐alkylidene succinimides and aurone derivatives was developed for the first time. Using a catalyst system consisting of a ferrocenyl P,N‐ligand and AgNO2, the reaction provides a facile method for the construction of chiral pyrrolidines bearing four consecutive stereocenters and two adjacent spiro‐quaternary chiral centers, as well as offers a direct route to structurally diverse enantioenriched CF3‐containing 3,2′‐pyrrolidinyl spirooxindole derivatives.

Increasing the efficiency of operation and management of railroad transport infrastructure based on maximum levels of fault tolerance

This paper considers the optimization of parameters for a railroad transport system. The maximum level of technological reliability and the average time spent by trains on the route are used as optimization criteria. The purpose of the study is to establish the optimal parameters for the operational process of railroad transport systems according to the criterion of the maximum level of technological reliability and the minimum time of trains on the route. Methods of technological reliability research have been proposed. Taking into account that the entire technological process is a sequential set of technological elements, a simulation model of the technological process of the transit transport-technological line along a route direction has been built. A population of agents that simulates the operation of railroad sections of the rotation of train locomotives and is a key subsystem of the simulation model has been developed and configured. The simulation model makes it possible to optimize the parameters of multi-section railroad lines. This approach is provided owing to the agent approach. As a result of the experiments, the optimal parameters of the functioning of railroad lines were established when organizing the passage of transit trains. The coefficient of utilization of the locomotive fleet fluctuates within the optimal range (0.55–0.65), which indicates the sufficiency of traction resources in the railroad system. The optimal parameters of the railroad transport system were established experimentally using the example of a train flow of 85 pairs of trains on a two-track route with five sections. The problem of "abandoned trains" has a solution but, to this end, it is necessary to increase the fleet of train locomotives by 150–200 % relative to existing standards. At the same time, even with an unlimited fleet of train locomotives, there is a fairly high probability (up to 30–50 %) of technological failures

Metal‐ and Additive‐Free One‐Pot Synthesis of 2,3,5‐Trisubstituted 1,3,4‐Thiadiazines Using β‐Ketodithioesters and 2‐Bromohydrazones through a Cross‐Coupling/Cyclization Cascade

AbstractPrivileged 2,3,5‐trisubstituted 1,3,4‐thiadiazines were synthesized from readily accessible β‐ketodithioesters as a two‐atom (CS) synthon and 2‐bromohydrazones as a four‐atom (CCNN) unit through a cross‐coupling/cyclization cascade. The operationally simple metal‐ and additive‐free method shows broad substrate scope as well as high functional‐group tolerance and provides a direct route to functionalized 1,3,4‐thiadiazines that are not easily prepared by other methods. This one‐pot approach features easy‐to‐handle nontoxic reagents, high yields, gram scalability, excellent selectivity and the formation of an exocyclic double bond with Z‐stereoselectivity.

A Rapid, Mild and Direct Route to Sulfonimidoyl Fluoride from Sulfenamide.

We develop a rapid and mild protocol to access sulfonimidoyl fluoride-[S(VI)] from sulfenamide-[S(II)] directly. The transformation occurs via the reaction of sulfenamide with NCS (N-chlorosuccinimide), water, and TBAF in acetonitrile. Water and TBAF act as the source for S═O bond formation and fluoride, respectively. The reaction takes a very short time (within 5 min). The drug molecules, such as Carbamazepine and Levetiracetam attached sulfonimidoyl fluorides are also achieved following this protocol. Furthermore, sulfonimidoyl fluoride is transformed into sulfonimidamide in the presence of AlCl3. To the best of our knowledge, it is the first report detailing the synthesis of sulfonimidoyl fluoride-[S(VI)] directly from S(II)-sulfenamide.

Epoxidation of Chalcone Derivatives under Visible-Light Irradiation: An Organophotoredox Catalytic Approach

AbstractEpoxidation of α,β-unsaturated ketones under visible-light irradiation constitutes a significant chemical transformation with potential applications in the synthesis of epoxypropane derivatives. An organophotoredox catalytic system is herein reported to facilitate efficient aerobic epoxidation. This protocol enables the conversion of α,β-unsaturated ketones into their corresponding epoxy products with moderate to high yields under benign reaction conditions. The methodology demonstrates broad functional-group compatibility, providing a reliable and direct route to a variety of functionalized epoxypropane compounds. Additionally, the absence of heavy metals in this strategy renders it particularly suitable for the pharmaceutical industry, offering a new avenue for the synthesis of epichlorohydrin drugs.

Integrated One-Step Fabrication of Protonic Sensing Devices for Respiratory Monitoring.

The development of direct fabrication routes with seamless integration of both the macro/micropatterning process and nanostructure synthesis is crucial for the commercial realization of cost-effective nanoscale sensor devices. This, if realized, can liberate us from the conventional limitations inherent in nanoscale device manufacturing. Specifically, such fabrication routes can, in principle, address the challenges such as the complexity, multistep nature, and substantial costs associated with existing technologies, which are not suitable for widespread market adoption in everyday-use devices. Herein, we propose a novel yet facile one-step fabrication approach that simultaneously accomplishes both patterning and nanostructure synthesis by employing low-power, cost-effective laser technology with a minimal environmental footprint. Versatile in nature, this approach can enable the incorporation of diverse functionalities spanning a broad spectrum of technologies, encompassing fields such as sensors, catalysts, photonics, energy storage, and biomedical monitoring devices. As a proof of concept, using our approach, we fabricated an ultra responsive, high-speed protonic sensing device for real-time respiratory monitoring. The enhanced temporal characteristics of our as-fabricated device, particularly in the relative humidity levels of interest in breath monitoring (typically over 55%), exhibited a superior response/recovery time in rapid humidity fluctuations. We envisage that the advantages brought by the presented fabrication approach can pave the way to establish a new method for inexpensive large-scale functional-material-based device fabrication.

Pd-Catalyzed 1,4-Difluoromethylative Functionalization of 1,3-Dienes Using Freon-22.

We report a visible-light-driven, palladium-catalyzed 1,4-difluoromethylative functionalization of conjugated dienes using chlorodifluoromethane (ClCF2H, Freon-22) as a cost-effective difluoromethyl source. The excited palladium catalyst efficiently reduces the C-Cl bond, which generates a CF2H radical, followed by regioselective SN2' substitution to afford 1,4-difunctionalized products. This versatile, redox-neutral method accommodates diverse nucleophiles and exhibits broad functional group compatibility, making it suitable for late-stage functionalization in drug discovery and offering a direct route to difluoromethylated molecules.

Hybrid Silica Cage-Type Nanostructures Made from Triply Hydrophilic Block Copolymers Single Micelles.

Controlling the structure and functionality of porous silica nanoparticles has been a continuous source of innovation with important potential for advanced biomedical applications. Their synthesis, however, usually involves passive surfactants or amphiphilic copolymers that do not add value to the material after synthesis. In contrast, polyion complex (PIC) micelles based on hydrophilic block copolymers allow for the direct synthesis of intrinsically functional hybrid materials. While most previous studies have focused on bulk materials made from double-hydrophilic block copolymers (DHBC), in this work we have synthesized a triple-hydrophilic block copolymer (THBC) and demonstrated both its PIC micellization and its potential for hybrid mesoporous silica nanomaterials. Introducing this THBC has allowed to direct the transition from bulk three-dimensional (3D) materials to zero-dimensional (0D) nanomaterials with cage-type structures. The stabilization and isolation of these nanostructures formed around discrete individual micelles has been made possible by the careful design of the three different blocks that each play a key role. These nanostructures could also be synthesized from hybrid PIC micelles based on THBC-multivalent metal ions complexes, offering a direct route to metal/silica composite nanoparticles. This class of THBC polymers therefore creates significant opportunities for the synthesis of nanostructures with complex and functional architectures.

A mathematical model of Cholera–Typhoid coinfection dynamics with a hygiene-driven contact rate

Waterborne infections such as Cholera and Typhoid remain a huge burden on the public health systems of poor countries in Africa and Asia. The highest disease burden is concentrated in sub-Saharan Africa. In most regions, the recent spike in cases of both infections is attributed to dilapidated infrastructure and poor hygiene. This paper examines the role of poor hygiene in the surge of both infections. We use a system of non-linear ordinary differential equations to model the movement of people between the different classes of infections, and we use a sigmoidal function to model the different levels of hygiene in a community. The findings demonstrate that managing hygiene, even if limited to the direct transmission route, can significantly reduce the prevalence of both infections. This paper presents some of the public health implications of these findings.

The Importance of Direct Routes for Air Travel Itinerary Choices: Results from a Stated Preference Choice Experiment

The Importance of Direct Routes for Air Travel Itinerary Choices: Results from a Stated Preference Choice Experiment

Surface Cation Cross‐Locking Enables Non‐Destructive “On‐Demand” Synthesis of Anion‐Exchanged CsPbX3 Perovskite Nanocrystals

AbstractPost‐synthetic halide anion exchange is considered a “double‐edged sword” for perovskite nanocrystals (PNCs), which offer unique access to color tunability while bringing about surface defects. Herein, a novel surface cation cross‐locking (SCCL) strategy is proposed to achieve the anion‐exchanged CsPbX3 PNCs (X is Cl, Br, I) with non‐destructive emissions. This is achieved using a dendritic ligand of Pentaerythritol tetrakis (3‐mercaptopropionate) (PETMP) as a surface cross‐locker, which can form the multiple coordination to the surface Pb cation of octahedral [PbX6]4− during the fast halide anion exchange via four end‐thiolates and four side‐carboxylates. As a result, the red‐ and blue‐emitting anion‐exchanged CsPbX3 PNCs exhibit high photoluminescence quantum yield (PLQY) values of >97%, close to the parent green‐emitting CsPbBr3 PNCs. Moreover, the “on‐demand” synthesis of anion‐exchanged CsPbX3 PNCs is also performed via autonomous robotic in‐flow experimentation. This work provides a new general post‐synthetic way for the full‐color CsPbX3 PNCs with compositions that are inaccessible via direct synthetic routes.

Silica surface modification using cellulose as a renewable organosilane derived from coconut coir fiber for carbon capture

The properties of silica surface modification for carbon capture were studied, utilizing cellulose-amine as a modification agent derived from dissolved coconut coir fiber. To form bonds with NH2 functional groups through amination processes, cellulosic biomass waste is utilized, which is analogous to replacing alkoxy ligands. The dual-function mixture reagents dimethyl sulfoxide (DMSO) and ammonium hydroxide (NH4OH) were employed in the same system as the amine sources and solvents. Waterglass is used as a source of silica, and the modified particles are formed using a one-step consecutive sol-gel spray drying process used in a direct condensation route. Changes in the concentration of sodium lauryl sulfate (SLS) were examined to determine how they affected the essential parameters of the particles. The template is removed during particle formation without further physical or chemical processing. The particle morphology changed from donut-shaped to spherical after SLS application, as evidenced by the increase in SLS concentration. This also shows that the increase in the particle surface area is directly influenced by the increase in the formation of new pore structures with increasing SLS concentration. Through this mechanism, it is possible to extend the pore size distribution to the meso-macropore regime and initiate the formation of new mesopores. This has a direct impact on the capacity to absorb CO2 gas by increasing the cellulose-amine mass fraction that can be grafted to as high as 32.35 %wt. At an operating pressure of 6 bar, a maximum CO2 gas adsorption capacity of 5.32 mmol/g silica was attained by adding SLS 3 CMC to the silica particles. This value is 2.3 times higher than that obtained when using an aminosilane-based modification agent.

Ein Direkter Syntheseweg zu closo‐SBnCln Thiaboranen aus Einfachen Elektronenpräzisen Startmaterialien: Die Unterschiedliche Rolle der Chalkogenbindungen in Kristallinem SB5Cl5 und SB11Cl11

AbstractDie Thiaborane closo‐SB5Cl5 (1) und closo‐1‐SB9Cl9 (2) wurden neben dem bereits bekannten closo‐SB11Cl11 (3) durch Co‐Pyrolyse von B2Cl4 mit S2Cl2 bei 280 °C im Vakuum hergestellt. Die Verbindungen sind sublimierbare, blass‐cremefarbene Feststoffe, deren elementare Zusammensetzung durch hochauflösende Massenspektrometrie bestimmt wurde. Sie wurden ferner durch ein‐ und zweidimensionale 11B NMR‐Spektroskopie und – im Falle von 1 und 3 – mittels Röntgenstrukturanalyse charakterisiert. Ab‐initio/GIAO/NMR‐Rechnungen stimmen mit den für 1, 2 bzw. 3 gefundenen oktaedrischen, doppelt überkappten quadratisch‐antiprismatischen bzw. ikosaedrischen Geometrien überein, wie aufgrund der Anzahl der für polyedrische closo‐Cluster typischen 2n+2 Gerüstelektronenzahl zu erwarten war. Hierbei ist 1 das erste isolierte Beispiel für ein neutrales closo‐Thiaboran mit weniger als zehn Clusterbausteinen und 3 ein seltenes Beispiel für ein ikosaedrisches Heteroboran, welches mittels Röntgenbeugung am Einkristall untersucht werden konnte. Die Kristall‐Packungskräfte in 1 und 3 sprechen für unterschiedliche Rollen der jeweiligen Chalkogen‐Bindung in diesen oktaedrischen und ikosaedrischen Clustern. Darüber hinaus fanden sich massenspektrometrische Hinweise auf die Bildung weiterer Thiaboran‐Homologe der Formel closo‐SBnCln mit n=4, 6, 10 und supra‐ikosaedrischem 12.

A Novel Synthesis of Substituted Benzo[1,2,4]Oxadiazine Derivatives Via Copper‐Catalyzed Intermolecular O‐Arylation of 2‐Iodoaniline and N‐Hydroxyimidoyl Chloride

AbstractIn this work, a rapid and direct route for the synthesis of benzo[1,2,4]oxadiazine derivatives through a copper iodide‐catalyzed intermolecular O‐arylation of 2‐iodoaniline and N‐hydroxyimidoyl chloride has been investigated. The reaction is fast and simple at room temperature and takes place in a reasonable amount of time. No complex ligands or special equipment are required. The use of cheap and available raw materials and catalysts, without column chromatography, performing the reaction in 4 hours, and good efficiency (72–86 %) are notable features of this protocol. The synthesized product is often found in drugs and other bioactive molecules.