Dual Route Research Articles

Development of Dual Practical Manufacturing Routes to Cognate Pyrrolobenzodiazepine-Based Linker-Drugs

Development of Dual Practical Manufacturing Routes to Cognate Pyrrolobenzodiazepine-Based Linker-Drugs

Nonclinical Pharmacokinetic Evaluation of Desidustat: a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.

Desidustat is a novel prolyl hydroxylase domain(PHD) inhibitor for the treatment of anemia. The objective of this study was to investigate the pharmacokinetics and drug-drug interaction properties of desidustat using invitro and invivo nonclinical models. Invitro, Caco2 cell permeability, plasma protein binding, metabolism, cytochrome P450 (CYP) inhibition, and CYP induction were examined. In vivo, pharmacokinetic studies of oral bioavailability in mice, rats, dogs and monkeys, dose linearity, tissue distribution, and excretion in rats were conducted. In Caco-2 cells, the apparent permeability of desidustat was high at low pH and low at neutral pH. The oral bioavailability (%F) of desidustat was 43-100% with a mediantime to reach peak concentration (Tmax)of about 0.25-1.3h across species. Desidustat displayed a low mean plasma clearance (CL) of 1.3-4.1mL/min/kg (approximately 1.8-7.4% of hepatic blood flow), and the mean steady-state volume of distribution (Vss) was 0.2-0.4L/kg (approximately 30-61% of the total body water). Desidustat showed a dose-dependent increase in exposures over the 15-100mg/kg dose range. It was rapidly distributed in various tissues, with the highest tissue-to-blood ratio in the liver (1.8) and kidney (1.7). Desidustat showed high plasma protein binding and was metabolically stable in human liver microsomes, hepatocytes, and recombinant CYPs. It did not show significant inhibition of major drug-metabolizing CYP enzymes (IC50>300µM) or the potential to induce CYP1A2 and CYP3A4/5 (up to 100µM) in HepG2 cells. It may have minimal potential of clinical drug-drug interaction when used in combination with iron supplements or phosphate binders. Desidustat was primarily excreted unchanged in urine (25% of the oral dose) and bile (25% of the oral dose) in rats. The mean elimination half-life of desidustat ranged from 1.0 to 5.3h and 1.3 to 5.7h across species after intravenous and oral administration, respectively. Taken together, desidustat is well absorbed orally. It showed a dose-dependent increase in exposure, did not accumulate in tissue, and was eliminated via dual routes. It is metabolically stable, has minimal potential to cause clinical drug-drug interactions (DDIs), and demonstrates discriminable pharmacokinetic properties for the treatment of anemia.

MM-Wave HetNet in 5G and beyond Cellular Networks Reinforcement Learning Method to improve QoS and Exploiting Path Loss Model

This paper presents High density heterogeneous networks (HetNet) which are the most promising technology for the fifth generation (5G) cellular network. Since 5G will be available for a long time, previous generation networking systems will need customization and updates. We examine the merits and drawbacks of legacy and Q-Learning (QL)-based adaptive resource allocation systems. Furthermore, various comparisons between methods and schemes are made for the purpose of evaluating the solutions for future generation. Microwave macro cells are used to enable extra high capacity such as Long-Term Evolution (LTE), eNodeB (eNB), and Multimedia Communications Wireless technology (MC), in which they are most likely to be deployed. This paper also presents four scenarios for 5G mm-Wave implementation, including proposed system architectures. The WL algorithm allocates optimal power to the small cell base station (SBS) to satisfy the minimum necessary capacity of macro cell user equipment (MUEs) and small cell user equipment (SCUEs) in order to provide quality of service (QoS) (SUEs). The challenges with dense HetNet and the massive backhaul traffic they generate are discussed in this study. Finally, a core HetNet design based on clusters is aimed at reducing backhaul traffic. According to our findings, MM-wave HetNet and MEC can be useful in a wide range of applications, including ultra-high data rate and low latency communications in 5G and beyond. We also used the channel model simulator to examine the directional power delay profile with received signal power, path loss, and path loss exponent (PLE) for both LOS and NLOS using uniform linear array (ULA) 2X2 and 64x16 antenna configurations at 38 GHz and 73 GHz mmWave bands for both LOS and NLOS (NYUSIM). The simulation results show the performance of several path loss models in the mmWave and sub-6 GHz bands. The path loss in the close-in (CI) model at mmWave bands is higher than that of open space and two ray path loss models because it considers all shadowing and reflection effects between transmitter and receiver. We also compared the suggested method to existing models like Amiri, Su, Alsobhi, Iqbal, and greedy (non adaptive), and found that it not only enhanced MUE and SUE minimum capacities and reduced BT complexity, but it also established a new minimum QoS threshold. We also talked about 6G researches in the future. When compared to utilizing the dual slope route loss model alone in a hybrid heterogeneous network, our simulation findings show that decoupling is more visible when employing the dual slope path loss model, which enhances system performance in terms of coverage and data rate.

Photocatalytic oxidation of p-xylene coupled with hydrogen evolution over MOFs-based bifunctional catalyst

Photocatalytic oxidation of organic small molecules accompanied by the release of hydrogen is considered to be a dual optimal route to obtain green energy and high value-added oxidation products through a green way. A TiO2-CdS/Ni bi-functional catalyst combining the advantages of MOFs, semiconductor materials and metal nanoparticles was prepared by using MIL-125 as a precursor. The prepared composite catalyst has strong photoresponsiveness, abundant catalytic sites and the ability to oxidize aromatic compounds. The hydrogen evolution capacity can reach 6.6 mmol·g−1·h−1 over TiO2-CdS/Ni in the presence of hole sacrificial agent. The hydrogen production was 81.9 μmol·g−1 h−1 in the system with PX instead of hole sacrificial agent, and 521.2 μmol·g−1 of TALD oxidation products can be obtained with high selectivity. The high activity of the catalytic system can also be extended to the oxidation of toluene and benzyl alcohol, which can generate hydrogen of 33.3 μmol·g−1·h−1 and 1.6 mmol·g−1·h−1, and 620.3 μmol·g−1 and 4.2 mmol·g−1 of benzaldehyde were produced at the same time, respectively. This study successfully extends the strategy of photocatalytic oxidation of organic small molecule coupled with hydrogen evolution to PX and other compounds.

Enhanced photocatalytic antibacterial performance by hierarchical TiO2/W18O49 Z-scheme heterojunction with Ti3C2Tx-MXene cocatalyst

Construction of multiple electronic transmission channels in a photocatalytic system is in favor of boosting the charge separation to realize a high photocatalytic antibacterial property. Herein, a novel hierarchical ternary photocatalyst consisting of TiO2/W18O49 Z-scheme heterojunction and Ti3C2Tx-MXene cocatalyst was synthesized via a simple two-step solvothermal method. Dual charge transfer routes were realized in this TiO2/W18O49/Ti3C2Tx-MXene composite. The electrons on TiO2 can transfer either through the Z-scheme mode to combine with the holes of W18O49, or through the Schottky-junction to Ti3C2Tx-MXene cocatalyst. The TiO2/W18O49/Ti3C2Tx-MXene composite maintained high photooxidation-reduction capacity and possessed fast charge separation behavior. As a result, the TiO2/W18O49/Ti3C2Tx-MXene heterojunction had a high photocatalytic bactericidal rate of 93.7% for Escherichia coli (E. coil) under light (λ ≥ 365 nm, 6 h), which was 3.3, 5.5, 3.1 and 2.9 times that of MXene (28.6%), TiO2 (17.0%), W18O49 (30.0%) and TiO2/MXene (32.8%), respectively. In addition, the ternary heterojunction illustrated good biocompatibility. This work provides a simple method of constructing multiple electronic transmission channels for high bactericidal performance and proves the effectiveness of photocatalytic materials in the biological field.

Understanding special requests as drivers of customer citizenship behaviors: the mediating role of gratitude and satisfaction

ABSTRACT Customer special requests are requests that fall outside frontline employees’ (FLE) normal job duties, requiring them to adapt to fit customer’s needs. Adopting the customer perspective, this study aims to understand how can service firms benefit from an efficient reply to these requests. Two hundred and eighty customers were surveyed regarding a plethora of self-selected requests. Results show that FLE’s adaptive behaviors promote customer citizenship behaviors (CCB) through gratitude and satisfaction, revealing a dual route to CCB according to request type. The study contributes a better understanding of the mechanisms underlying the FLE–customer reciprocal relationship, showing that special requests produce value for both parts.

Exploring Consumer Adoption of Mobile Shopping Apps From a Perspective of Elaboration Likelihood Model

This study aims to integrate perceived risk into elaboration likelihood model, develop a comprehensive research model to explain dual routes of persuasive communication through various factors affecting individual acceptance and usage of mobile shopping apps, and identify the antecedents of consumers’ perceived risk in the context of mobile shopping. Structural equation modeling is adopted to test the proposed model. Information quality has a negative effect on perceived risk (central route), while source credibility has a positive impact on perceived usefulness (peripheral route). The antecedents of perceived risk including information quality, source credibility, familiarity, and personal innovativeness which are divided into four categories: cognition-based, affect-based, experience-based, and personality-oriented. The four antecedents significantly affect consumer’s perceived risk in adopting mobile shopping apps. The results show that consumers’ perceived usefulness and perceived risk affect consumers’ behavioral intentions of mobile shopping apps adoption.

Specific predictors of length and frequency effects in German beginning readers: testing component processes of sublexical and lexical reading in the DRC

Reading a word requires several component processes. The dual route cascaded (DRC) model provides a characterization of these component processes and their involvement in different reading routes. We tested how relevant precursor skills associated with these component processes predict the use of the sublexical and lexical route in beginning readers of a transparent orthography. More than 100 German first graders performed a battery of tasks tapping into precursor skills associated with the DRC components. Using factor analysis, we first verified that the tasks can be attributed to three sets of skills, capturing visual, sublexical, and lexico-semantic components, as the DRC suggests. We then used these sets of skills to predict differences in the reliance on sublexical and lexical reading in second grade as indicated by length and frequency effects. Results show that the set of sublexical skills in first grade especially predicts differences in the recognition of long frequent words at the end of second grade, whereas the set of lexico-semantic skills predicts differences in the reading of long infrequent words. The findings corroborate the attribution of specific precursor skills to the sublexical and lexical route and reveal their distinct impact on sublexical and lexical reading in beginning readers. The work thus empirically informs the developmental version of the DRC, especially regarding variability in trajectories of reading acquisition.

Efficacy of gene therapy in a CLN5 sheep model using a dual route of administration supports a first-in-human clinical trial

Efficacy of gene therapy in a CLN5 sheep model using a dual route of administration supports a first-in-human clinical trial

Synergistic photocatalytic dye mitigation and bacterial disinfection using carbon quantum dots decorated dual Z-scheme Manganese Indium Sulfide/Cuprous Oxide/Silver oxide heterojunction

A novel CQDs decorated MnIn2S4/Cu2O/Ag2O dual Z-scheme tandem hybrid is fabricated via hydrothermal method for MO removal and E. coli disinfection under visible light illumination. CQDs shuttle electrons in CQDs-MnIn2S4/Cu2O/Ag2O interface via dual Z-scheme electron transferal route which lead to upgrade in charge separation and visible light absorption. The Z-scheme hybrid displayed best catalytic inactivation performance of E. coli and degradation of MO which totally disinfect bacteria within 3 h and displayed 98.6% of MO degradation in 70 min in visible light radiation. The unique dual Z-scheme junction supports enhanced redox capabilities, prolong lifespan of photo-excitons, stability, spatial separation and enhanced visible light absorption.

Reading Development, Word Length and Frequency Effects: An Eye-Tracking Study with Slow and Fast Readers

Research on reading development attempts to explain differences in the reading patterns of adults and children. Previous studies, which typically analyzed word length and frequency effects in developing readers, often focused on dyslexic or dysfluent readers. Similar to previous studies, we investigated the effects of word length and word frequency on the eye movements of children and added several novel aspects: We tested 66 typically developing German-speaking children. Children’s oral reading fluency was used as measure of reading ability. Only fast readers (n = 34, mean age 10.9 ± 0.9 years) and slow readers (n = 32, 11.2 ± 0.9 years) participated in an eye-tracking experiment and silently read an age-appropriate original narrative text from a children’s book. The analysis of silent reading of the entire text confirmed the earlier group classification. To analyze word length and frequency, we selected 40 nouns as target words in the text. We found significant effects of word length and word frequency for all children in the expected direction. For fast readers, we detected significant interactions of word length and frequency in first fixation duration, gaze duration, and total reading time. These revealed a frequency effect for long, but not short words. This suggests lexical whole-word processing with a fast activation of the word’s lexical entry for shorter words and an application of the nonlexical route of the dual route cascaded model (DRC) with a slower lexical access to whole word forms for long words. Slow readers demonstrated a strong sensitivity to word length, indicating a slower or delayed lexical access to orthographic word forms. Additionally, they exhibited weaker word frequency effects. These findings suggest a developmental view of reading in typically developing children in accordance with the DRC, with nonlexical serial decoding as the seemingly prominent reading strategy of slow readers and lexical whole-word recognition as the prominent reading strategy of fast readers.

Use of EGR e-pump for Dual-Mode Dual-Fuel engines in mild hybrid architectures

Highway transport sector is still expected to be dominated by internal combustion engines in the future, especially due to limitations in the introduction and applicability of full electrification for heavy-duty propulsive systems. Nonetheless, this sector is still under the objectives imposed in the roadmap towards carbon neutrality. For this, engine efficiency and low-emission combustion modes must be improved, and the introduction of synthetic fuels, low electrification levels and devices for engine optimization and energy management have proven to be a great advance towards these objectives. This work studies the application of an EGR e-pump for energy recovery and combustion optimization on a powertrain running on Dual-Mode Dual-Fuel combustion mode as a substitute of a complex dual route EGR system. The results include the evaluation of the impact of using energy recovery devices on combustion performance and emissions levels, as well as a numerical evaluation of driving conditions considering a medium-duty application in the transport sector under different driving scenarios. The results point out that the inclusion of the EGR e-pump can contribute to mitigate the drawbacks of removing the complex dual route system in terms of equivalent fuel consumption without greater impact in terms of emissions. Additionally, its application in mild hybrid platforms can promote a significant improvement in CO2 emissions, especially for urban areas (20% compared to a conventional powertrain based on HP EGR).

Chemiluminescent magnetic nanoparticles with good catalytic activity and rapid separation capability and sensitive sensing for H2O2.

It is of considerable importance to develop chemiluminescent functionalized nanomaterials (CF-NMs) with good catalytic activity, high chemiluminescence (CL) efficiency and good stability, and rapid magnetic separation capability, achieving excellent performance in CL biosensing. In this study, N-(4-aminobutyl)-N-ethylisoluminol (ABEI)-functionalized CuFe2O4 magnetic nanomaterial (ABEI/CuFe2O4) with high catalytic activity was synthesized by virtue of a solvothermal and post-functionalization method. ABEI/CuFe2O4 showed outstanding CL properties, superior to ABEI-CuFe2O4 in liquid phase. This reveals that the immobilization of ABEI on the surface of CuFe2O4 exhibits unique heterogeneous catalytic property. The catalytic ability of CuFe2O4 was better than that of CoFe2O4, ZnFe2O4, MnFe2O4, and NiFe2O4. It is suggested that the peroxide-like activity as well as Cu2+ and Cu0 enriched on the surface of ABEI/CuFe2O4 opened up a dual route for synergistic catalysis of H2O2. ABEI/CuFe2O4 also demonstrated good superparamagnetism and magnetic separation could be carried out in 2 min, which is advantageous for the separation and purification of ABEI/CuFe2O4 during the synthetic procedures and bioassays. Owing to the sensitive response of ABEI/CuFe2O4 to H2O2, an enzyme-free sensor was developed for the detection of H2O2 with a wide linear range over 5 orders of magnitude of H2O2 concentrations and a low detection limit of 5.6 nM. The as-developed sensor is sensitive, stable, and convenient. This work provides a new family member of nanomaterials with good magnetism and CL activity as well as good stability. The developed ABEI/CuFe2O4 shows great prospects in biocatalysis, bioassays, biosensing, and bioimaging, etc.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00216-021-03597-w.

An investigation of idiom processing advantage using translated familiar idioms.

The facilitatory effect shown in native speakers processing idiomatic phrases compared to matched novel phrases may be explained by a dual route model. This postulates that all phrases are processed literally at first, and if a phrase was recognized as familiar during processing, it would then be processed by a faster retrieval-route; if the phrase was not perceived as familiar, it would continue to be processed literally by the slower computation-route. The goals of the current project were to test the dual route model and to decipher the underlying mechanism in retrieval-route activation. English idioms and translated Chinese idioms were presented to both native English speakers and Chinese-English bilinguals in a random order. Participants listened to the idiom up until the last word (e.g., "draw a snake and add"), then saw either the idiom ending (e.g., "feet") or the matched control ending (e.g., "hair"); to which they made lexical decision and reaction times were recorded. We examined the priming effect for idioms compared to controls across the two language groups. The results showed that the two groups processed idioms of different origins differently. Native English speakers' faster responses to English idioms than controls supported a dual route model; however, both native English and bilingual speakers' faster responses to Chinese idioms than controls called for a less straightforward interpretation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Boosting the rate capability and cycle life of Zr-substituted Na3V2(PO4)3/C enwrapped on carbon nanotubes for symmetric Na-ion batteries

Na3V2(PO4)3 (NVP) has been deemed to be an ideal cathode candidate due to the high capacity but suffers from the intrinsic poor conductivity. Herein, we adopt a dual modification route of Zr substitution and carbon nanotubes (CNTs) enwrapping to improve the kinetic characteristics and stabilize the structural framework. The replacement of V3+ by Zr4+ is favorable to expanding the migration channels for Na+ diffusion and supporting the structure. Furthermore, Zr4+ substitution contributes to restraining the particle agglomeration and facilitating the uniform distribution. The evenly intertwined CNTs construct an efficient network and establish the beneficial connections for the adjacent Zr-doped NVP particles to accelerate the electronic conductivity significantly. Distinctively, the modified Na2.9V1.9Zr0.1(PO4)3/C@CNTs (Zr0.1-NVP/C@CNTs) exhibits a superior electrochemical performance: it delivers a capacity of 102.1 mAh g−1 at 20 C with a retention of 86.3% after 1000 cycles. Notably, it still reveals an outstanding capacity of 74.3 mAh g−1 and remains 62.2 mAh g−1 after 2000 cycles at 200 C, indicating a low capacity loss of 0.0081% per cycle. Moreover, the symmetric full cell constituted by Zr0.1-NVP/C@CNTs presents competitive practical applicability. Furthermore, the improved kinetic characteristics are demonstrated by multiple methods, indicating the significant improvement of conductivities resulted from the synergetic utility.

Rare case of intra-oral palatal (soft palate) fibro-lipoma

<p>Amongst various differential diagnoses possible for intra-oral (palatal) mass, possibility of fibro-lipoma is extremely rare but documented in literature, and hence should be a consideration. Such patient requires thorough evaluation and step-wise approach to treat. This case study documents for a 30-year-old male patient presenting with such mass and chief complaints of post nasal drip, nasal obstruction (right side>left side) and intermittent headache for 3 years. After radiological and endoscopic examination, the mass was surgically removed in toto via dual route (trans-oral and endoscopic). Lipomas are uncommon tumors in the oral cavity, and palate being the rarest amongst them as is our case. It would be strongly advocated to keep lipoma in the differential diagnosis when evaluating a palatal mass. Also, it is worth mentioning and recommending that a careful radiological examination of large lesions arising from the palate is a must before approaching for surgery.</p>

Possibilities of using fosinopril in treatment of patients with chronic kidney disease in combination with cardiovascular diseases and diabetes mellitus

Chronic kidney disease is one of the most common diseases in general medical practice, due to their secondary damage to the kidneys in arterial hypertension, chronic heart failure, and diabetes mellitus. The coexistence of hypertension and diabetes increases the likelihood of developing chronic kidney failure tenfold. In turn, chronic kidney disease is an important independent risk factor for the development of cardiovascular complications, including fatal ones, due to the direct relationship of the pathogenetic mechanisms of cardiorenal relationships. Approaches to the treatment of chronic kidney disease should be aimed both at preventing the risks of developing renal dysfunction, and at treating existing pathology. The multifactorial nature of the disease and the complex etiopathogenetic relationships determine the need to optimize existing approaches to the treatment of chronic kidney disease in multimorbidity patients with concomitance cardiovascular diseases and diabetes mellitus. This is also due to the fact that, unlike other target organs, compensation for background disease does not always prevent further deterioration of kidney function. According to the recommendations of the main scientific communities, in such cases, it is advisable to start therapy with the most effective angiotensin-converting enzyme inhibitors that combine nephro-and cardioprotective effects and have a dual route of elimination from the body, which is especially important in multimorbidity, the aim to prevent polypharmacy, reduce the risk of drug interactions and, consequently, side effects. This article reviews the literature data indicating the high efficacy and safety of the angiotensin converting enzyme inhibitor fosinopril in patients with chronic kidney disease in combination with cardiovascular diseases and diabetes mellitus.

Visible-light-driven Cr(VI) reduction by ferrocene-integrated conjugated porous polymers via dual catalytic routes.

Conjugated porous polymers with rapid separation of photogenerated charges and multiple catalytic pathways remain a great challenge. Herein, two ferrocene-based polymers (Fc-CPPs) with high charge separation efficiency and unique dual catalytic routes for Cr(vi) reduction were developed. They exhibited an excellent efficiency, with almost 99% of Cr(vi) readily converted to Cr(iii) under 15 min of visible light illumination (λ > 420 nm).

Efecto de longitud silábica en español

Los modelos cognitivos de doble ruta de lectura apoyan la existencia de dos vías: la léxica que opera con palabras completas y permite el acceso directo desde la ortografía a la semántica y a la pronunciación; y la subléxica que funciona de manera analítica convirtiendo, mediante reglas de correspondencia, cada uno de los grafemas en el fonema correspondiente. Numerosas investigaciones concluyen que el efecto de longitud constituye un índice de gran utilidad para el estudio de los mecanismos que subyacen a la lectura. El objetivo del presente trabajo es estudiar el efecto de longitud a partir del análisis de los tiempos de reacción. Para esto, se evaluaron 84 estudiantes universitarios con una tarea de lectura en voz alta de palabras y no-palabras de distinta longitud. Se llevó a cabo un análisis por sujeto (F1) y un análisis por estímulo (F2) que arrojaron efecto de longitud estadísticamente significativo y, además, se observó una interacción significativa con el tipo de estímulo. Estos hallazgos constituyen evidencias convergentes con la asunción de la existencia de dos procedimientos de lectura en lenguas de ortografía transparente como el español.

How psychology helps us to understand word reading

ABSTRACT This paper presents an overview of evidence from psychological research, which enables us to understand the processes involved in word reading, how children develop word reading skills and how to teach them to read words successfully. Psychological models of reading in alphabetic orthographies propose two routes to word reading: an indirect route requiring mapping of letters and sounds using phonological processes and a direct route, mapping visual identities of words onto meaning using visual processes and memory. The dual route paves the way to an understanding of what children need to achieve to be able to read words. Evidence about how people read words successfully has led to the development of effective teaching programmes and of tests to identify deficits when word reading does not develop optimally.