bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid two-mode squeezing of microwave and optical fields using optically pumped graphene layers
Authors: Qasymeh Montasir , Eleuch Hichem
Published: October 2020

A measurable quadrature of a squeezed quantum state manifests a small uncertainty below the Heisenberg limit. This phenomenon has the potential to enable several extraordinary applications in quantum information, metrology and sensing, and other fields. Several techniques have been implemented to realize squeezed electromagnetic states, including microwave fields and optical fields. However, hybrid squeezed modes (that incorporate both microwave and optical fields) have not yet been proposed despite their vital functionality to combine the two worlds of quantum superconducting systems and photonics systems. In this work, for the first time, we propose a novel approach to achieve two-mode squeezing of microwave and optical fields using graphene based structure. The proposed scheme includes a graphene layered structure that is driven by a quantum microwave voltage and subjected to two optical fields of distinct frequencies. By setting the optical frequency spacing equal to the microwave frequency, an interaction occurs between the optical and microwave fields through electrical modulation of the graphene conductivity. We show that significant hybrid two-mode squeezing, that includes one microwave field and one optical field, can be achieved. Furthermore, the microwave frequency can be tuned over a vast range by modifying the operation parameters.
Experimental demonstration of an arbitrary shape dc electric concentrator
Authors: Barati Sedeh Hooman , Fakheri Mohammad Hosein , Abdolali Ali , Sun Fei
Published: October 2020

Coordinate transformation (CT) theory has shown great potentials in manipulating both time-varying and static fields for different physics ranging from electromagnetism and acoustics to electrostatic and thermal science. Nevertheless, as inhomogeneous and anisotropic materials are required to be realized for the implementation of CT-based devices, the applicability of this method is restricted due to difficulties in the fabrication process. In this paper, based on transformation electrostatic (TE) methodology, the design principle of an arbitrary shape dc electric concentrator is established which yields the enhancement of static electric fields in a predefined region with only one homogeneous conductivity, named as dc null medium (DNM). It is shown that one constant DNM is sufficient for localizing steady electric current in any arbitrary shape region, which in turn obviates the tedious mathematical calculations that conventional methods suffer from. In other words, the same DNM can be used for different concentrators regardless of their cross-section geometries, which makes the presented approach suitable for scenarios where reconfigurability is of utmost importance. Several numerical simulations are performed in order to demonstrate the capability of the proposed dc electric concentrator in localizing steady electric fields into the desired region. Moreover, by utilizing the analogy between electrically conducting materials and resistor networks, the attained DNM is realized with low-cost resistors and then exploited for fabricating a square shape dc electric concentrator on a printed circuit board (PCB). It is demonstrated that the measurement results agree well with the theoretical predictions and numerical simulations, which corroborate the effectiveness of the propounded method. The presented idea of this paper could find applications in scenarios where highly confined electric fields/currents are of critical importance such as electronic skin devices and electrical impedance tomography.
Optically induced diffraction gratings based on periodic modulation of linear and nonlinear effects for atom-light coupling quantum systems near plasmonic nanostructures
Authors: Vafafard Azar , Sahrai Mostafa , Siahpoush Vahid , Hamedi Hamid Reza , Asadpour Seyyed Hossein
Published: October 2020

We investigate the quantum linear and nonlinear effects in a novel five-level quantum system placed near a plasmonic nanostructure. Such a quantum scheme contains a double-V-type subsystem interacting with a weak probe field. The double-V-subsystem is then coupled to an excited state by a strong coupling field, which can be a position-dependent standing-wave field. We start by analyzing the first-order linear as well as the third and fifth order nonlinear terms of the probe susceptibility by systematically solving the equations for the matter-fields. When the quantum system is near the plasmonic nanostructure, the coherent control of linear and nonlinear susceptibilities becomes inevitable, leading to vanishing absorption effects and enhancing the nonlinearities. We also show that when the coupling light involves a standing-wave pattern, the periodic modulation of linear and nonlinear spectra results in an efficient scheme for the electromagnetically induced grating (EIG). In particular, the diffraction efficiency is influenced by changing the distance between the quantum system and plasmonic nanostructure. The proposed scheme may find potential applications in future nanoscale photonic devices.
Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity
Authors: Zaborska Beata , Sygitowicz Grażyna , Smarż Krzysztof , Pilichowska-Paszkiet Ewa , Budaj Andrzej
Published: October 2020

Galectin-3 is a biomarker of fibrosis, inflammation and oxidative stress, and its role in heart remodelling and exercise intolerance has not been conclusively proven in heart failure (HF) patients with reduced ejection fraction (rEF). We prospectively assessed 67 consecutive patients with symptomatic HF and left ventricular (LV) EF ≤ 35% during optimal medical therapy, with a mean serum galectin-3 concentration of 15.3 ± 6.4 and a median of 13.5 ng/mL. The group with galectin-3 concentrations greater than or equal to the median had significantly worse right ventricular (RV) systolic function parameters (s′, TAPSE), higher pulmonary artery systolic pressure, more advanced tricuspid regurgitation and lower RV-to-pulmonary circulation coupling index, while no significant differences were found in LV parameters. Moreover, this group achieved significantly lower parameters in cardiopulmonary exercise testing. Significant negative correlations were found between galectin-3 concentration and RV parameters and exercise capacity parameters and have persisted after adjustment for glomerular filtration rate, but not all of them have persisted after adjustment for NT-proBNP. Multivariate regression analysis revealed that TAPSE (β coefficient: − 0.605; p < 0.001) and heart rate at peak exercise (β coefficient: − 0.98; p = 0.009) were independently related to galectin-3 concentration. Elevated galectin-3 concentration in patients with HFrEF might indicate concomitant RV dysfunction and exercise intolerance.
Association between body mass index and prognosis of patients hospitalized with heart failure
Authors: Seko Yuta , Kato Takao , Morimoto Takeshi , Yaku Hidenori , Inuzuka Yasutaka , Tamaki Yodo , Ozasa Neiko , Shiba Masayuki , Yamamoto Erika , Yoshikawa Yusuke , Yamashita Yugo , Kitai Takeshi , Taniguchi Ryoji , Iguchi Moritake , Nagao Kazuya , Kawai Takafumi , Komasa Akihiro , Nishikawa Ryusuke , Kawase Yuichi , Morinaga Takashi , Toyofuku Mamoru , Furukawa Yutaka , Ando Kenji , Kadota Kazushige , Sato Yukihito , Kuwahara Koichiro , Kimura Takeshi
Published: October 2020

The prognostic implications of very low body mass index (BMI) values remain unclear in patients with acute decompensated heart failure (ADHF). This study aimed to investigate the prognostic impact of BMI classification based on the World Health Organization criteria in patients with ADHF. Among 3509 patients with ADHF and available BMI data at discharge in 19 participating hospitals in Japan between October 2014 and March 2016, the study population was divided into five groups; (1) Severely underweight: BMI < 16 kg/m2, (2) Underweight: BMI ≥ 16 kg/m2 and < 18.5 kg/m2, (3) Normal weight: BMI ≥ 18.5 kg/m2 and < 25 kg/m2, (4) Overweight: BMI ≥ 25 kg/m2 and < 30 kg/m2 (5) Obese: BMI ≥ 30 kg/m2. The primary outcome measure was all-cause death. The median follow-up duration was 471 days, with 96.4% follow up at 1-year. The cumulative 1-year incidence of all-cause death was higher in underweight groups, and lower in overweight groups (Severely underweight: 36.3%, Underweight: 23.9%, Normal weight: 14.4%, Overweight: 7.9%, and Obese: 9.0%, P < 0.001). After adjusting confounders, the excess mortality risk remained significant in the severely underweight group (HR, 2.32; 95%CI, 1.83–2.94; P < 0.001), and in the underweight group (HR, 1.31; 95%CI, 1.08–1.59; P = 0.005) relative to the normal weight group, while the lower mortality risk was no longer significant in the overweight group (HR, 0.82; 95%CI, 0.62–1.10; P = 0.18) and in the obese group (HR, 1.09; 95%CI, 0.65–1.85; P = 0.74). Very low BMI was associated with a higher risk for one-year mortality after discharge in patients with ADHF.
PET amyloid in normal aging: direct comparison of visual and automatic processing methods
Authors: Haller Sven , Montandon Marie-Louise , Lilja Johan , Rodriguez Cristelle , Garibotto Valentina , Herrmann François R. , Giannakopoulos Panteleimon
Published: October 2020

Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. Whether the different amyloid processing methods impacts on the quality of clinico-radiological correlations is still unclear. We directly compared in 155 elderly controls with extensive neuropsychological testing at baseline and 4.5 years follow-up three approaches: (i) operator-dependent standard visual reading, (ii) operator-independent automatic SUVR with four different reference regions, and (iii) novel operator and region of reference-independent automatic Aβ-index. The coefficient of variance was used to examine inter-individual variability for each processing method. Using visually-established amyloid positivity as the gold standard, the area under the receiver operating characteristic curve (ROC) was computed. Linear regression models were used to assess the association between changes in continuous cognitive score and amyloid uptake values. In SUVR analyses, the coefficient of variance varied from 1.718 to 1.762 according to the area of reference and was of − 3.045 for the Aβ-index method. Compared to the visual rating, Aβ-index method showed the largest area under the ROC curve [0.9568 (95% CI 0.9252, 0.98833)]. The best cut-off score was of − 0.3359 with sensitivity and specificity values of 0.97 and 0.83, respectively. Only the Aß-index was related to more severe decrement of cognitive performances [regression coefficient: 9.103 (95% CI 1.148, 17.058)]. The Aβ-index is considered as preferred option in asymptomatic elders, since it is operator-independent, avoids the selection of reference area, is closer to established visual scoring and correlates with the evolution of cognitive performances.
Common origin of ornithine–urea cycle in opisthokonts and stramenopiles
Authors: Horák Aleš , Allen Andrew E. , Oborník Miroslav
Published: October 2020

Eukaryotic complex phototrophs exhibit a colorful evolutionary history. At least three independent endosymbiotic events accompanied by the gene transfer from the endosymbiont to host assembled a complex genomic mosaic. Resulting patchwork may give rise to unique metabolic capabilities; on the other hand, it can also blur the reconstruction of phylogenetic relationships. The ornithine–urea cycle (OUC) belongs to the cornerstone of the metabolism of metazoans and, as found recently, also photosynthetic stramenopiles. We have analyzed the distribution and phylogenetic positions of genes encoding enzymes of the urea synthesis pathway in eukaryotes. We show here that metazoan and stramenopile OUC enzymes share common origins and that enzymes of the OUC found in primary algae (including plants) display different origins. The impact of this fact on the evolution of stramenopiles is discussed here.
Engineering of impact ionization characteristics in In0.53Ga0.47As/Al0.48In0.52As superlattice avalanche photodiodes on InP substrate
Authors: Lee S. , Winslow M. , Grein C. H. , Kodati S. H. , Jones A. H. , Fink D. R. , Das P , Hayat M. M. , Ronningen T. J. , Campbell J. C. , Krishna S.
Published: October 2020

We report on engineering impact ionization characteristics of In0.53Ga0.47As/Al0.48In0.52As superlattice avalanche photodiodes (InGaAs/AlInAs SL APDs) on InP substrate to design and demonstrate an APD with low k-value. We design InGaAs/AlInAs SL APDs with three different SL periods (4 ML, 6 ML, and 8 ML) to achieve the same composition as Al0.4Ga0.07In0.53As quaternary random alloy (RA). The simulated results of an RA and the three SLs predict that the SLs have lower k-values than the RA because the electrons can readily reach their threshold energy for impact ionization while the holes experience the multiple valence minibands scattering. The shorter period of SL shows the lower k-value. To support the theoretical prediction, the designed 6 ML and 8 ML SLs are experimentally demonstrated. The 8 ML SL shows k-value of 0.22, which is lower than the k-value of the RA. The 6 ML SL exhibits even lower k-value than the 8 ML SL, indicating that the shorter period of the SL, the lower k-value as predicted. This work is a theoretical modeling and experimental demonstration of engineering avalanche characteristics in InGaAs/AlInAs SLs and would assist one to design the SLs with improved performance for various SWIR APD application.
Effect of post-treatment process of microalgal hydrolysate on bioethanol production
Authors: Seon Gyeongho , Kim Hee Su , Cho Jun Muk , Kim Minsik , Park Won-Kun , Chang Yong Keun
Published: October 2020

Microalgae accumulate abundant lipids and are a promising source for biodiesel. However, carbohydrates account for 40% of microalgal biomass, an important consideration when using them for the economically feasible production of biodiesel. In this study, different acid hydrolysis and post-treatment processing of Chlorella sp. ABC-001 was performed, and the effect of these different hydrolysates on bioethanol yield by Saccharomyces cerevisiae KL17 was evaluated. For hydrolysis using H2SO4, the neutralization using Ca(OH)2 led to a higher yield (0.43 g ethanol/g sugars) than NaOH (0.27 g ethanol/g sugars). Application of electrodialysis to the H2SO4 + NaOH hydrolysate increased the yield to 0.35 g ethanol/g sugars, and K+ supplementation further enhanced the yield to 0.41 g ethanol/g sugars. Hydrolysis using HNO3 led to the generation of reactive species. Neutralization using only NaOH yielded 0.02 g ethanol/g sugars, and electrodialysis provided only a slight enhancement (0.06 g ethanol/g sugars). However, lowering the levels of reactive species further increased the yield to 0.25 g ethanol/g sugars, and K+ supplementation increased the yield to 0.35 g ethanol/g sugars. Overall, hydrolysis using H2SO4 + Ca(OH)2 provided the highest ethanol yield, and the yield was almost same as from conventional medium. This research emphasizes the importance of post-treatment processing that is modified for the species or strains used for bioethanol fermentation.
Risk of recurrent stroke and antiplatelet choice in breakthrough stroke while on aspirin
Authors: Kim Joon-Tae , Kim Beom Joon , Park Jong-Moo , Lee Soo Joo , Cha Jae-Kwan , Park Tai Hwan , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Lee Byung-Chul , Kim Dong-Eog , Choi Jay Chol , Kwon Jee-Hyun , Shin Dong-Ick , Sohn Sung Il , Lee Ji Sung , Lee Juneyoung , Bae Hee-Joon
Published: October 2020

Uncertainty regarding an optimal antiplatelet regimen still exists in patients with breakthrough acute ischemic stroke (AIS) while on aspirin. This study provides an analysis of a prospective multicenter registry between April 2008 and April 2014. Eligible patients were on aspirin at the time of AIS and treated with antiplatelet regimens (aspirin, clopidogrel, or clopidogrel-aspirin). Potential factors associated with the choice of each antiplatelet regimen were explored and included a predictive risk score for future vascular events, the Essen Stroke Risk Score (ESRS). A total of 2348 patients (age, 69 ± 11 years; male, 57.7%) were analyzed, and 55.3%, 25.3% and 19.4% were treated with clopidogrel-aspirin, aspirin and clopidogrel, respectively. While the likelihood of choosing clopidogrel-aspirin increased as the ESRS increased, the likelihood of choosing aspirin decreased as the ESRS increased (Ptrend < 0.001). The ESRS category (0–1/2–3/ ≥ 4) modified the effect of antiplatelet regimens for 1-year vascular events (Pinteraction < 0.01). Among patients with ESRS ≥ 4, clopidogrel-aspirin (HR 0.47 [0.30–0.74]) and clopidogrel (HR 0.30 [0.15–0.60]) significantly reduced the risk of outcome events. Our study showed that more than half of the patients with aspirin failure were treated with clopidogrel-aspirin. In particular, a higher ESRS, which indicates an increased risk of recurrent stroke, was associated with the choice of clopidogrel-aspirin rather than aspirin.
Tuning magnetic properties of penta-graphene bilayers through doping with boron, nitrogen, and oxygen
Authors: Santos Ramiro Marcelo dos , da Cunha Wiliam Ferreira , de Sousa Junior Rafael Timóteo , Giozza William Ferreira , Ribeiro Junior Luiz Antonio
Published: October 2020

Penta-graphene (PG) is a carbon allotrope that has recently attracted the attention of the materials science community due to its interesting properties for renewable energy applications. Although unstable in its pure form, it has been shown that functionalization may stabilize its structure. A question that arises is whether its outstanding electronic properties could also be further improved using such a procedure. As PG bilayers present both sp$$^2$$

2

and sp$$^3$$

3

carbon planes, it consists of a flexible candidate for functionalization tuning of electromagnetic properties. In this work, we perform density functional theory calculations to investigate how the electronic and structural properties of PG bilayers can be tuned as a result of substitutional doping. Specifically, we observed the emergence of different magnetic properties when boron and nitrogen were used as dopant species. On the other hand, in the case of doping with oxygen, the rupture of bonds in the sp$$^2$$

2

planes has not induced a magnetic moment in the material.
Contrast medium administration with a body surface area protocol in step-and-shoot coronary computed tomography angiography with dual-source scanners
Authors: Jin Liang , Gao Yiyi , Sun Yingli , Li Cheng , Gao Pan , Zhao Wei , Li Ming
Published: October 2020

We evaluated the feasibility and image quality of prospective electrocardiography (ECG)-triggered coronary computed tomography angiography (CCTA) using a body surface area (BSA) protocol for contrast-medium (CM) administration on both second- and third-generation scanners (Flash and Force CT), without using heart rate control. One-hundred-and-eighty patients with suspected coronary heart disease undergoing CCTA were divided into groups A (BSA protocol for CM on Flash CT), B (body mass index (BMI)-matched patients; BMI protocol for CM on Flash CT), and C (BMI-matched patients; BSA protocol for CM on Force CT). Patient characteristics, quantitative and qualitative measures, and radiation dose were compared between groups A and B, and A and C. Of the 180 patients, 99 were male (median age, 62 years). Average BSA in groups A, B, and C was 1.80 ± 0.17 m2, 1.74 ± 0.16 m2, and 1.64 ± 0.17 m2, respectively, with groups A and C differing significantly (P < 0.001). Contrast volume (50.50 ± 8.57 mL vs. 45.00 ± 6.18 mL) and injection rate (3.90 ± 0.44 mL/s vs. 3.63 ± 0.22 mL/s) differed significantly between groups A and C (P < 0.001). Groups A and C (both: all CT values > 250 HU, average scores > 4) achieved slightly lower diagnostic image quality than group B. The BSA protocol for CM administration was feasible in both Flash and Force CT, and therefore may be valuable in clinical practice.
Deep tuning of photo-thermoelectricity in topological surface states
Authors: Huang Shouyuan , Miotkowski Ireneusz , Chen Yong P. , Xu Xianfan
Published: October 2020

Three-dimensional topological insulators have been demonstrated in recent years, which possess intriguing gapless, spin-polarized Dirac states with linear dispersion only on the surface. The spin polarization of the topological surface states is also locked to its momentum, which allows controlling motion of electrons using optical helicity, i.e., circularly polarized light. The electrical and thermal transport can also be significantly tuned by the helicity-control of surface state electrons. Here, we report studies of photo-thermoelectric effect of the topological surface states in Bi2Te2Se thin films with large tunability using varied gate voltages and optical helicity. The Seebeck coefficient can be altered by more than five times compared to the case without spin injection. This deep tuning is originated from the optical helicity-induced photocurrent which is shown to be enhanced, reduced, turned off, and even inverted due to the change of the accessed band structures by electrical gating. The helicity-selected topological surface state thus has a large effect on thermoelectric transport, demonstrating great opportunities for realizing helicity control of optoelectronic and thermal devices.
SP prevents T2DM complications by immunomodulation
Authors: Baek Sang-Min , Kim Kiyoung , Kim Suna , Son Youngsook , Hong Hyun Sook , Yu Seung-Young
Published: October 2020

Type 2 diabetic mellitus (T2DM) is characterized by systemic inflammation and insulin resistance due to obesity, and this leads to critical complications, including retinopathy and nephropathy. This study explored the therapeutic effect of substance-p (SP), a neuropeptide, on T2DM progression and its complications. To examine whether SP affects glucose metabolism, lipid metabolism, systemic inflammation, and retinopathy, Otsuka Long-Evans Tokushima Fatty rats (OLETF, 27 weeks old) with chronic inflammation, obesity, and impaired bone marrow stem cell pool was selected. SP was intravenously injected and its effect was evaluated at 2 and 4 weeks after the SP injection. OLETF had typical symptoms of T2DM, including obesity, chronic inflammation, and poor glycemic control. However, SP treatment inhibited the body-weight gain and reduced circulating levels of free fatty acid, cholesterol, and triglyceride, ameliorating the obese environment. SP could suppress inflammation and rejuvenate bone marrow stem cell in OLETF rats. SP-mediated metabolic/immunological change could resolve hyperglycemia and insulin resistance. Histopathological analysis confirmed that SP treatment alleviated the dysfunction of target tissue with insulin resistance. OLETF rats have retinal damage from 27 weeks of age, which was reliably aggravated at 31 weeks. However, SP treatment could restore the damaged retina, sustaining its structure similarly to that of non-diabetic rats. In conclusion, systemic application of SP is capable contribute to the inhibition of the progression of T2DM and diabetic retinopathy.
Valley-polarized domain wall magnons in 2D ferromagnetic bilayers
Authors: Ghader Doried
Published: October 2020

Valleytronics is a pioneering technological field relying on the valley degree of freedom to achieve novel electronic functionalities. Topological valley-polarized electrons confined to domain walls in bilayer graphene were extensively studied in view of their potentials in valleytronics. Here, we study the magnonic version of domain wall excitations in 2D honeycomb ferromagnetic bilayers (FBL) with collinear order. In particular, we explore the implications of Dzyaloshinskii-Moriya interaction (DMI) and electrostatic doping (ED) on the existence and characteristics of 1D magnons confined to layer stacking domain walls in FBL. The coexistence of DMI and ED is found to enrich the topology in FBL, yet the corresponding domain wall magnons do not carry a well-defined valley index. On the other hand, we show that layer stacking domain walls in DMI-free FBL constitute 1D channels for ballistic transport of topological valley-polarized magnons. Our theoretical results raise hope towards magnon valleytronic devices based on atomically thin topological magnetic materials.
Catechol-containing Polymers for Electrochemical Energy Storage
Authors: Patil Nagaraj , Marcilla Rebeca
Published: October 2020

The development of redox-active polymers (RAPs) as organic electrode materials is foreseen as a promising solution for safe, sustainable and high-performance electrochemical energy storage technologies. Among the different families of RAPs, poly(catechol)s are especially interesting due to their remarkable degree of physicochemical and electrochemical versatility. This chapter describes their intriguing and unique properties and details the different routes towards poly(catechol)s, including bioresources (e.g., lignins, tannins, eumelanins, etc.) and other advanced synthetic strategies. Moreover, their application as active materials in different types of electrochemical energy-storage systems such as capacitors, rechargeable static batteries and redox flow batteries is also discussed. Poly(catechol)s were first applied as pseudocapacitive electrodes, either combined with carbon additives or with intrinsically conducting polymers, in hybrid capacitors. Lately, poly(catechol)s were also investigated as electrode materials, both cathode and anode, in numerous rechargeable static batteries. As anode materials, they were first used to obtain activated carbons or, in a more interesting approach, designed to undergo superlithiation (or sodiation) reactions in alkali metal-ion batteries. Taking advantage of the reversible redox couples involving catecholate/ortho-quinone transformations and their propensity for the metal-ion coordination/uncoordination reactions, poly(catechol)s have been also recently proposed as “universal” cathodes in monovalent Li-ion, Na-ion, multivalent Mg-ion, Zn-ion and all-polymer batteries. The use of lignin as an abundant and extremely low-cost biopolymer for sustainable redox flow battery is also discussed here.
Conducting Polymers as Redox Electroactive Materials for Soft Microelectromechanical Systems
Authors: Rohtlaid K. , Nguyen T. M. G. , Soyer C. , Cattan E. , Vidal F. , Plesse C.
Published: October 2020

This chapter focuses on conducting polymers as redox electroactive materials for the development of soft actuators and microactuators. General properties and working principles are first presented as well as the different configurations for operation in liquid electrolyte and air operation. An overview of past, recent and present works on the synthesis, fabrication and integration approaches of soft microactuators based on conducting polymers is finally presented, highlighting the future challenges for the development of fully integrated soft microelectromechanical systems.
PROTAC-mediated Target Degradation: A Paradigm Changer in Drug Discovery?
Authors: Cromm Philipp M. , Crews Craig M. , Weinmann Hilmar
Published: October 2020

The recent successes of small-molecule-induced target degradation have generated considerable excitement in the pharmaceutical industry, which will be watching carefully as the first two assets progress through clinical trials. Proteolysis-targeting chimeras (PROTACs), a technology surfacing not more than a couple of decades ago, is in the process of revolutionizing drug discovery. This chapter will provide an introductory overview of the technology, highlighting some key milestones and speculating about future opportunities as well as challenges ahead.
Developing Pharmacokinetic/Pharmacodynamic Relationships With PROTACs
Authors: Harling John D. , Scott-Stevens Paul , Gaohua Lu
Published: October 2020

Many examples of PROTACs possessing in vivo efficacy in pre-clinical studies have now been disclosed. While building pharmacokinetic (PK)/pharmacodynamic (PD) relationships is recognized as a key activity in small-molecule drug discovery to support translation from the research to clinical phases, there has been a paucity of reports describing this for PROTACs despite their huge potential as therapeutics. In this chapter we consider the unique mechanism of action of PROTACs and how this introduces additional factors which may need to be considered in the development of PK/PD relationships. We discuss this in the context of a series of PROTACs for the kinase RIPK2, which is a protein with a long half-life. Finally, we discuss how physiologically based pharmacokinetic (PBPK)/PD modeling can be used to deliver human dose predictions with PROTACs.
Structure-based PROTAC Design
Authors: McConnell Darryl B.
Published: October 2020

Structure-based drug design allows medicinal chemists to see, at atomic resolution, how a drug ligand binds to its target in three dimensions and has expedited the discovery of therapeutics against the most recalcitrant of drug targets. PROTACs, with their increased size and complexity, stand to equally gain from a structure-based design approach. While small molecules and PROTACs both require the design of ligands which bind potently, PROTAC design involves the additional step of stabilizing the interaction between two proteins, the E3-ligase and the protein of interest. This second protein–protein interaction stabilization step of PROTAC design is where PROTACs gain their potency and selectivity advantages over classical small molecules. It is the structural insights gained from the practice of structure-based PROTAC design which promises to accelerate the discovery of highly potent and selective PROTAC drugs.
Plate-based High-throughput Cellular Degradation Assays to Identify PROTAC Molecules and Protein Degraders
Authors: Carter Nikki
Published: October 2020

A growing body of literature and clinical evidence shows that newly evolving therapeutic modalities resulting in targeted protein degradation hold promise where catalytic, event-driven mechanisms of target modulation are intractable or exquisite selectivity is challenging, thereby offering new therapeutic potential to drug the “undruggable.” PROTACS (PROteolysis-TArgeting Chimeras) are hetero-bifunctional molecules comprising a ligand that binds the target protein, a chemical linker and a E3 ligase recognition moiety. The resulting PROTAC molecule then specifically recruits the E3 ligase ubiquitin machinery to the target protein of interest (POI) and exploits the cellular ubiquitin proteasome system (UPS) or lysosomal degradation pathways to degrade the protein. PROTAC design to subsequent degradation of the POI is a multifaceted process, requiring cellular assays that interrogate and provide both structure–activity relationship (SAR) data at high-throughput scale and mechanistic data to elucidate target binding, ternary complex formation, ubiquitination and ultimately degradation. In this chapter we will discuss how this approach to PROTAC discovery and optimization has been developed within AstraZeneca and focus on the plate-based cellular assays utilized to enable this evolving modality.
An Efficient Approach Toward Drugging Undruggable Targets
Authors: Gamo Kanae , Kitamoto Naomi , Kanemaki Masato T. , Tominari Yusuke
Published: October 2020

Targeted protein degradation (TPD) is under intensive focus with respect to the next-generation drugs to target currently undruggable proteins. Bivalent type degraders, known as proteolysis-targeting chimeras (PROTACs), are an attractive but challenging novel modality. As drug discovery for TPD involves time-consuming and costly processes, it is important to establish a platform for not only the identification and validation of the targets but also rapid and efficient drug discovery. Herein, two processes were proposed: (1) target validation by a ligand-induced genetic degradation system, especially the Auxin-Inducible Degron (AID) system and (2) degrader drug discovery by Rapid Protein Proteolysis Inducer Discovery System (RaPPIDSTM). Moreover, a strategy was developed for the discovery of TPD drugs against novel target proteins.
Phosphinoborane interception at magnesium by borane-assisted phosphine-borane dehydrogenation
Authors: Morris Louis J. , Rajabi Nasir A. , Hill Michael S. , Manners Ian , McMullin Claire L. , Mahon Mary F.
Published: October 2020

Ph2PBH2is generated and trapped on-metal by addition of B(C6F5)3to a β-diketiminato magnesium phospidoborane complex, similar reactivity is meanwhile prevented for the analogous calcium-based system by formation of a stable η6-toluene complex.
Structure dependent photostability of ITIC and ITIC-4F
Authors: Ciammaruchi Laura , Zapata-Arteaga Osnat , Gutiérrez-Fernández Edgar , Martin Jaime , Campoy-Quiles Mariano
Published: October 2020

ITIC photostability is markedly dependent on the specific polymorph phase and end-group decoration. Fluorination grants stronger chemical stability upon degradation.
Antibacterial efficacy from NO-releasing MOF–polymer films
Authors: Duncan Morven J. , Wheatley Paul S. , Coghill Emma M. , Vornholt Simon M. , Warrender Stewart J. , Megson Ian L. , Morris Russell E.
Published: October 2020

Sufficient concentration of nitric oxide is released from metal organic framework loaded polymer films to impart antibacterial efficacy.
Resonant tip-enhanced Raman scattering by CdSe nanocrystals on plasmonic substrates
Authors: Milekhin I. A. , Rahaman M. , Anikin K. V. , Rodyakina E. E. , Duda T. A. , Saidzhonov B. M. , Vasiliev R. B. , Dzhagan V. M. , Milekhin A. G. , Latyshev A. V. , Zahn D. R. T.
Published: October 2020

We demonstrated resonant/non-resonant gap-mode TERS on CdSe nanocrystals analyzing of LO (up to 3rd order), SO/TO phonons, as well as Se vibrational modes.
Development of label-free gold nanoparticle based rapid colorimetric assay for clinical/point-of-care screening of cervical cancer
Authors: Appidi Tejaswini , Mudigunda Sushma V. , Kodandapani Suseela , Rengan Aravind Kumar
Published: October 2020

“C-ColAur” technique for colorimetric detection of cervical cancer by in situ formation of gold nanoparticles.
Evaluation of the site-unspecified peptide identification method for proteolytic peptide mapping
Authors: Wang H. B. , Zeng F. , Wang Y. Y. , Li X. , S. H.  , Li Y. M. , Wang Y. F. , Liu Y. H. , Lu F. P.
Published: October 2020

The site-unspecific method could successfully identify most of the peptides from tryptic hydrolysates revealed by site-specific identification.
Gold nanochannels oxidation by confined water
Authors: Batista André M. , de Queiroz Thiago B. , Antunes Renato A. , Lanfredi Alexandre J. C. , Benvenho Adriano R. V. , Bonvent Jean J. , Martinho Herculano
Published: October 2020

We investigate the properties of confined water on Au 〈111〉 nanochannels. We report an unique oxidation process was also observed in the nanochannels driven by first wetting layer of the surface.
Lead-free cesium tin halide nanocrystals for light-emitting diodes and color down conversion
Authors: Mahesh K. P. O. , Chang Che-Yu , Hong Wei-Li , Wen Tzu-Hsiang , Lo Pei-Hsuan , Chiu Hao-Zhe , Hsu Ching-Ling , Horng Sheng-Fu , Chao Yu-Chiang
Published: October 2020

Organometal halide perovskites are attracting a great deal of attention because of their long carrier diffusion lengths, wide wavelength tunability, and narrow-band emission.
Multicomponent crystals of anti-tuberculosis drugs: a mini-review
Authors: Batisai Eustina
Published: October 2020

Pharmaceutical co-crystals of isoniazid and pyrazinamide could improve the stability of fixed-dose combinations used in TB treatment.
A fluorescent target-guided Paal–Knorr reaction
Authors: Wagh Sachin B. , Maslivetc Vladimir , La Clair James J. , Kornienko Alexander
Published: October 2020

A pocket-templated Paal–Knorr reaction delivers fluorescent COX-2 probes.
α-Hydroxy acid as an aldehyde surrogate: metal-free synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and other N-heterocyclesviadecarboxylative oxidative annulation reaction
Authors: Viji Mayavan , Vishwanath Manjunatha , Sim Jaeuk , Park Yunjeong , Jung Chanhyun , Lee Seohu , Lee Heesoon , Lee Kiho , Jung Jae-Kyung
Published: October 2020

A TBHP mediated, metal-free approach for the synthesis of quinoxalines, quinazolinones, and indolo quinoxaline was developed from alpha hydroxy acidsviadecarboxylation followed by condensation.
Photochlorination of toluene – the thin line between intensification and selectivity. Part 1: intensification and effect of operation conditions
Authors: Taştan Ümit , Ziegenbalg Dirk
Published: October 2020

Intensification of photochlorination of toluene in microstructured reactors by up to a factor of 10 was achieved, but also caused an unexpected decrease of selectivity. Dynamic irradiation suppressed side reactions and increased energy efficiency.
Photochlorination of toluene – the thin line between intensification and selectivity. Part 2: selectivity
Authors: Taştan Ümit , Seeber Phillip , Kupfer Stephan , Ziegenbalg Dirk
Published: October 2020

The selectivity of the photochlorination of toluene was found to decrease under intensified conditions. This was traced back to the formation of a toluene–chlorine complex, that activates the ring upon irradiation and causes ring chlorination.
Digitising chemical synthesis in automated and robotic flow
Authors: Hardwick Tomas , Ahmed Nisar
Published: October 2020

Automated flow chemistry: humans and machines working together to create faster, safer, more efficient laboratories of the future where computers help to design and control experiments, allowing researchers to focus on other scientific pursuits.
Applications of microwave energy in gas production and tar removal during biomass gasification
Authors: Guo Feiqiang , Dong Yichen , Tian Beile , Du Shilin , Liang Shuang , Zhou Nan , Wang Yunpu , Chen Paul , Ruan Roger
Published: October 2020

Microwave heating has the potential to promote gas production and tar removal during biomass pyrolysis or gasification based on its advantageous characteristics such as rapid heating and selective heating.
Variable pitch hydrodynamic electro-optic gratings utilising bent liquid crystal dimers
Authors: Morris R. , Jones J. C. , Nagaraj M.
Published: October 2020

Electrohydrodynamic Instabilities in nematic liquid crystals cause uniform and continuously variable pitch diffraction gratings. Liquid crystal dimers allow greater range of elastic constants, allowing wider angle diffraction to be achieved.
Graphene quantum dots as a highly efficient electrocatalyst for lithium–oxygen batteries
Authors: Wu Yuanguo , Zhu Xingbao , Ji Xin , Liu Weilong , Wan Weihua , Wang Yu , Pan Xingyu , Lu Zhe
Published: October 2020

Herein, we successfully synthesized glucose-derived graphene quantum dots (GQDs) through a hydrothermal process, which were further employed as an efficient cathodic catalyst in a non-aqueous lithium–oxygen battery for the first time.
How ribbons make ‘sense’ for vision
Authors: Thoreson Wallace B. , Hays Cassandra L.
Published: October 2020

The processing of light by the retina and brain provides the basis for visual perception. Photons are captured and converted to electrical signals by rod and cone photoreceptor cells in the retina. These electrical signals are converted to chemical signals for transmission to downstream neurons. This article provides an overview of the mechanisms involved in transmitting light responses from rods and cones. Chemical signalling occurs at synapses between neurons. In keeping with many other neurons, the chemical messenger released by photoreceptors is the amino acid glutamate, which is packaged into small spherical vesicles. Each photoreceptor synaptic terminal has thousands of synaptic vesicles. Some of these vesicles are attached to the face of planar structures known as ribbons. Ribbons capture and deliver vesicles to release sites at the bottom of the ribbon. Upon stimulation, vesicles fuse with the cell membrane and release their contents. Glutamate molecules diffuse through the extracellular space to reach specialized receptors that regulate the activity of downstream neurons. We discuss how rates of vesicle attachment to ribbons, delivery of vesicles down the ribbon and the release of glutamate shape the information provided to downstream neurons in the visual system.
Der „schwierige“ Patient in der Tierphysiopraxis – Maßnahmen zur Stressreduktion
Authors: Wiese Nina , Voigt Katrin
Published: October 2020

Immer häufiger kommen Hunde in die Praxis, die Verhaltensprobleme mit sich bringen: Sie lassen sich nicht gerne anfassen, kommen nicht zur Ruhe oder zeigen sogar Aggressionsverhalten. Eines steht fest – die Behandlung wird dadurch nicht einfacher. Die permanente Anspannung macht eine Befundung und Behandlung schwierig.
Kritisches Outcome und Hypoxisch-Ischämische Enzephalopathie
(HIE) – Ein Thema der Qualitätssicherung
Authors: Schmidt Stephan , Misselwitz Björn , Schuster Roxanne , Schrod Lothar
Published: October 2020

Ziel dieser Studie ist es, ein kritisches postnatales Outcome als
Prädiktor für die Entwicklung einer hypoxisch
ischämischen Enzephalopathie (HIE) zu evaluieren.

Methodik Auf Basis der Daten der hessischen Perinatalerhebung aus dem
Jahr 2016 mit 52 122 Geburten (Lebendgeborene Einlinge,
≥ 37+0 Schwangerschaftswochen) wurden die
Fälle mit kritischem Outcome identifiziert. Kriterien waren ein
APGAR-Score <5 nach 5 Minuten in Kombination mit einem pH
<7,00 bzw. Basendefizit >16,0 mmol/L. Diese
Fälle wurden mit den HIE-Fällen aus der Neonatalerhebung
zusammengeführt. Es wurden die Odds Ratio sowie
Sensitivität/Spezifität und positiver
(ppW)/negativer(npW) Vorhersagewert berechnet. Durch Evaluation des
Geburtsverlaufes und des subpartalen CTG wurde die potentielle
Vermeidbarkeit des Kritischen Outcomes/hypoxisch
ischämischen Enzephalopathie überprüft.

Ergebnisse Die Inzidenz der Fälle mit kritischem Outcome
(n=11) und derer mit hypoxisch ischämischen Enzephalopathie
(n=29) ist gering. Nach Zusammenführung der Daten aus der
Perinatal- respektive Neonatalerhebung ergaben sich eine
Sensitivität von 10,34%, eine Spezifität von
99,98%, ein positiver bzw. negativer prädiktiver Wert von
27,35, bzw. 99,95%. In nahezu einem Drittel der Fälle mit
kritischem Outcome (4/11) oder hypoxisch ischämischen
Enzephalopathie (9/29) fanden sich Hinweise auf eine potentielle
Vermeidbarkeit.

Schlussfolgerungen Ein postnataler Depressionszustand führt
häufiger zur Diagnose einer HIE als eine schwere Azidose im
Nabelschnurblut. Da ein Drittel der Fälle vermeidbar erscheinen,
kann die fachübergreifende Einzelfallanalyse bei kritischem
Neugeborenenstatus zur Optimierung der Geburtshilfe auch im Rahmen der
externen Qualitätssicherung (QS) zielführend sein.
The Potential Role of Coagulation Factor Xa in the Pathophysiology of COVID-19: A Role for Anticoagulants as Multimodal Therapeutic Agents
Authors: Frydman Galit H. , Streiff Michael B. , Connors Jean M. , Piazza Gregory
Published: October 2020

SARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19.
Enhancing the sensitivity in measuring nanoparticle sizes
Authors: McConnon Aili
Published: October 2020

A theoretical investigation of integrated nanoparticle sensors may help guide the exploration of exceptional points (EPs) for nanoparticle sensing applications in photonic systems
Unraveling crystal symmetry and strain effects on electronic band structures of SiC polytypes
Authors: Kuroiwa Yuichiro , Matsushita Yu-ichiro , Oba Fumiyasu
Published: October 2020

The modulations of the electronic band structures of hexagonal (2H, 4H, and 6H) and cubic (3C) SiC under biaxial (0001) and (111) in-plane strain are investigated by using first-principles calculations including spin–orbit coupling effects. We have clarified that the strain dependency of the valence bands is closely related to the crystal symmetry and hexagonality. Specifically, tensile strain induces hybridization and crossover between the heavy-hole and light-hole bands in the hexagonal polytypes. On the other hand, the degeneracy between the heavy-hole and light-hole bands breaks in the cubic polytype under tensile strain. Consequently, the hole effective masses change significantly under certain tensile strain in all four polytypes. The values of the critical tensile strain are approximately proportional to the energy differences between the heavy-hole and crystal-field splitting bands under no strain and, in turn, show a correlation with the hexagonality. In contrast to the case of the valence bands, the band structures around the conduction band minima and, therefore, the electron effective masses are insensitive to the strain, except for the ML direction in 6H–SiC. The present study provides principles for elucidating and designing the crystal structure and strain dependency of the electronic band structures and transport properties of SiC.
Single-domain formation of SrMnBi2 films on polar LaAlO3 substrate
Authors: Takahashi K. , Shiogai J. , Inoue H. , Ito S. , Kimura S. , Awaji S. , Tsukazaki A.
Published: October 2020

By considering the crystal symmetry of the Dirac semimetal candidate SrMnBi2, it is expected that a substrate based on a square lattice is preferred to form a single-domain growth of a thin film. In this study, however, we observed different schemes of interface formation of SrMnBi2 using molecular-beam epitaxy on two oxide substrates of SrTiO3(001) and LaAlO3(001), both of which are often applied to the growth of the films with square lattices. Although antiphase domains appear in the SrMnBi2 film on SrTiO3(001), a single domain develops on LaAlO3(001) with an abrupt interface. The distinct difference indicates that the surface of the LaAlO3(001) substrate plays a crucial role in the selection of the initial growth plane. Judging from the abrupt interface image in scanning transmission electron microscopy and the four-fold symmetric in-plane x-ray diffraction pattern representing the orientation relationship of SrMnBi2 film [110]//LaAlO3 [100], the polar surface termination with (AlO2)− or (LaO)+ probably promotes the interface formation of the ionic Sr or Bi plane on the surface, respectively. According to the semimetallic electronic structure of SrMnBi2, the electrical transport properties of the films can be consistently evaluated by the two-carrier model with high-mobility electrons and low-mobility holes. Our demonstration of the single-domain growth of the Dirac semimetal provides a key technique toward the future engineering of heterostructures composed of topological materials.