bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineered Deregulation of Expression in Yeast with Designed Hybrid‐Promoter Architectures in Coordination with Discovered Master Regulator Transcription Factor
Authors: Ergün Burcu Gündüz , Demir İrem , Özdamar Tunçer H. , Gasser Brigitte , Mattanovich Diethard , Çalık Pınar
Published: March 2020

Engineered promoters are key components in the cell‐factory design, allowing precise and enhanced expression of genes. Promoters having exceptional strength are attractive candidates for designing metabolic engineering strategies for tailoring de novo production strategies that require directed evolution methods by engineering with de novo synthetic biology tools. Here, the custom‐designed AOX1 hybrid‐promoter architectures in coordination with targeted transcription factors are shown, transcriptionally rewired the expression over methanol‐free substrate‐utilization pathway(s) and converted methanol‐dependent Pichia pastoris alcohol oxidase 1(AOX1) promoter (PAOX1) expression into a non‐toxic carbon‐source‐regulated system. AOX1 promoter variants are engineered by replacing specified cis‐regulatory DNA elements with synthetic Adr1, Cat8, and Aca2 cis‐acting DNA elements for Mxr1, Cat8, and Aca1 binding, respectively. Applications of the engineered‐promoters are validated for eGFP expression and extracellular human serum albumin production. The hybrid‐promoter architecture designed with single Cat8 cis‐acting DNA element deregulates the expression on ethanol. Compared with PAOX1 on methanol, the expression on ethanol is increased with i) PAOX1/Cat8‐L3 (designed with single Cat8 cis‐acting element) to 74%, ii) PAOX1/Adr1‐L3/Cat8‐L3 (designed with single‐ Cat8 and Adr1 cis‐acting elements) to 85%, and for further consolidation of deregulated expression iii) PeAOX1 (designed with triplet‐ Cat8 and Adr1 cis‐acting elements) 1.30‐fold, at t = 20 h of batch cultivations.
Photoassisted Electroforming Method for Reliable Low‐Power Organic–Inorganic Perovskite Memristors
Authors: Zhao Xiaoning , Wang Zhongqiang , Li Wentong , Sun Shaowu , Xu Haiyang , Zhou Peng , Xu Jiaqi , Lin Ya , Liu Yichun
Published: March 2020

Organic–inorganic hybrid perovskite memristors with high resistive‐switching (RS) reliability and low power consumption are crucial for high‐density storage and high‐efficiency neuromorphic computing. However, the current overshoot in the electroforming process generally induces overgrowth of conductive filaments (CFs) and degrades the RS performance. Here, a simple photo‐assisted electroforming (PAE) method to suppress the current overshoot, in which the visible light irradiation is introduced into the initial electroforming process, is proposed for the first time. As a result, a reliable memristor with reduced RS fluctuation and enhanced cycling endurance is obtained, and also, the low operating current of 0.06 mA and low powerconsumption of 0.12 mW are achieved, which are about one order of magnitude lower than those of most reported hybrid perovskite‐based memristors. Further experimental evidence indicates that light irradiation plays dual roles: 1) the light‐induced lowering of iodide migration barrier leads to a significant reduction of overshoot current and forming voltage; 2) the enhanced local photoconductivity of the perovskite film shares the overshoot current through the CFs. Both factors limit the total quantity of vacancy defects generated in the electroforming process, thus preventing undesirable overgrowth of the CFs. The present PAE strategy has promise for developing high‐performance memristors.
Films Stoichiometry Effects on the Electronic Transport Properties of Solution‐Processed Yttrium Doped Indium–Zinc Oxide Crystalline Semiconductors for Thin Film Transistor Applications
Authors: Afouxenidis Dimitrios , Halcovitch Nathan R. , Milne William I. , Nathan Arokia , Adamopoulos George
Published: March 2020

Spray‐coated crystalline InZnOx‐based semiconductors are investigated as a function of [In3+]:[Zn2+] and their performance as TFTs semiconducting channels. More precisely, it is demonstrated that optical, structural, and electron transport properties show a high degree of sensitivity to the films' stoichiometry; that is, the [In3+]:[Zn2+] atomic ratio that equally determines the amorphous or crystalline structure of the film. Yttrium co‐doping of InZnOx with [In3+]:[Zn2+] atomic ratio of 6:4 shows that the YInZnOx structure and the key TFT parameters can further be engineered and improved in terms of the on‐to‐off current modulation ratio and, most importantly, the field effect mobility. It is finally demonstrated that the latter is in excess of 52 cm2 V‐1 s‐1 by combining crystalline YInZnOx and spray‐coated MgO dielectrics. These results identify spray‐coated crystalline YInZnOx as a viable TFT semiconducting channel material with respect to enhanced electrical performance and processing requirements in terms of simplicity and cost.
Programmable Spin–Orbit‐Torque Logic Device with Integrated Bipolar Bias Field for Chirality Control
Authors: Lim Gerard Joseph , Chua Daniel , Gan Weiliang , Murapaka Chandrasekhar , Lew Wen Siang
Published: March 2020

Driven by the need to address both the von Neumann bottleneck and scaling limits predicted by Moore's law, spintronic devices have been shown to be strong contenders for logic‐in‐memory applications. While several field‐free spin–orbit torque (SOT)‐driven logic devices have been proposed, their operation typically requires additional initialization or reset pulses, the exchange‐coupled canted spins reduce both anomalous Hall sign‐to‐noise ratio as well as thermal stability of the ferromagnetic layer, and device‐to‐device variation in exchange coupling strength is expected. A reconfigurable SOT‐driven logic device using a double Hall cross structure with an integrated bias field line for the generation of a local bias field is experimentally demonstrated. The on‐chip bipolar bias field can be toggled to flip the SOT‐induced switching chirality, and to assist with deterministic SOT magnetization switching, thereby enabling on‐the‐fly reconfigurability of the logic device to function as one of the several possible logic gates, e.g., AND, NOR, XNOR, XOR, NIMP, and converse NIMP. It is then shown through compact‐modeling and circuit simulation that the applications of such reconfigurable logic devices can be further expanded to build half‐adders.
Indium–Gallium–Zinc Oxide Schottky Diodes Operating across the Glass Transition of Stimuli‐Responsive Polymers
Authors: Guerrero Edgar , Polednik Alexander , Ecker Melanie , Joshi‐Imre Alexandra , Choi Wooyeol , Gutierrez‐Heredia Gerardo , Voit Walter E. , Maeng Jimin
Published: March 2020

Implementing stable electronic components on smart, soft materials can facilitate increasingly complex functionality in body‐worn and implanted devices for biomedical applications. The fabrication and characterization of indium–gallium–zinc oxide (IGZO)‐based Schottky diodes on a thiol–ene/acrylate shape memory polymer (SMP) that softens in response to physiological stimuli, including temperature and moisture, are presented. A platinum–IGZO Schottky junction is formed on the softening polymer assisted by ultraviolet‐ozone (UV‐O3) surface treatment. The effects of the UV‐O3 treatment conditions on the Schottky barrier properties are examined. The diode operation is evaluated in dry and wet conditions with varying temperatures up to 75 °C, revealing that the fabricated diodes preserve their performance even after the softening effect (i.e., an orders‐of‐magnitude modulus change) is induced in the polymer substrate. Additionally, high‐frequency diode operation up to 1 GHz is demonstrated for devices with an active area of 10 000 µm2 at 0 V bias. These devices can serve as building blocks for high‐frequency rectifying circuits and in more sophisticated arrangements toward applications in, for example, wireless bioelectronic implants.
A Silicon Nanowire Ferroelectric Field‐Effect Transistor
Authors: Sessi Violetta , Simon Maik , Mulaosmanovic Halid , Pohl Darius , Loeffler Markus , Mauersberger Tom , Fengler Franz P. G. , Mittmann Terence , Richter Claudia , Slesazeck Stefan , Mikolajick Thomas , Weber Walter M.
Published: March 2020

The design and characterization of a Schottky‐type ferroelectric field‐effect transistor based on a nominally undoped silicon nanowire are reported. The nanowire transistor is fabricated by top‐down technology starting from a silicon‐on insulator wafer. A thin ferroelectric Hf0.38Zr0.62O2 layer is integrated via a gate‐first approach. Abrupt Schottky source/drain contacts to the undoped silicon are provided by NiSi2 formation. Two distinct nonvolatile transistor states (programmed and erased) are observed in correspondence to negative and positive polarization in the ferroelectric layer, delivering a memory window of ≈1.5 V and, differently to conventional ferroelectric field effect transistors, yielding an on‐current difference of up to 30%. These results are interpreted as a combination of effects, arising from the proximity of the ferroelectric layer to both the channel and the Schottky‐junction regions. The threshold voltage shift, due to a polarization field acting on the channel, adds up to a polarization field‐driven tuning of the current injection through the Schottky‐source junction. This provides a strategy for manufacturing Schottky‐type nanoscale transistors with the add‐on nonvolatile option, following a complementary metal‐oxide‐semiconductor compatible process. In particular, the device concept is of great interest for achieving nonvolatile polarity modification in reconfigurable field‐effect transistors.
Effects of trees and nitrogen supply on macronutrient cycling in integrated crop–livestock systems
Authors: Carpinelli Sandoval , da Fonseca Adriel Ferreira , Assmann Tangriani Simioni , Pontes Laíse da Silveira
Published: March 2020

Residue decomposition from pastures and crops plays an important role in nutrient cycling in integrated crop–livestock systems (ICLS). The objective of this research was to quantify dry matter decomposition and nutrient release—nitrogen, phosphorus, and potassium (N, P, and K, respectively), the most commonly required nutrients in tropical and subtropical agriculture—from pasture and soybean (Glycine max) residues of stocking and crop seasons in two ICLS (with and without trees, CLT and CL, respectively) and two N fertilization levels (90 vs. 180 kg N ha−1, N90 and N180, respectively, applied during the pasture phase). Litter bag incubations were set out in the December 2014 (soybean phase) and May 2015 (pasture phase), and retrieved after 7, 15, 30, 60, 90, and 120 d in each season. The total N, P, and K released from the pasture or soybean residues were related to the initial quantity of plant residues, which was reduced in the CLT systems, mostly for pasture residue (−60%), probably due to light reduction (−55%), rather than changes in litter quality and dynamics. Significant amounts of N (∼57 kg ha−1), P (∼11 kg ha−1), and K (∼58 kg ha−1) were cycled, particularly in CL and N180 treatments. The quantities of K released from pasture residues were enough to restore the quantity of K exported by soybean grains. Therefore, results reinforce the need to understand nutrient release patterns from residues to improve fertilization management.
Leaf area development and yield of cassava in response to pruning of shoots and the late supply of nitrogen and potassium
Authors: Mota Lydia Helena S.O. , Fernandes Adalton M. , Assunção Natália S. , Leite Hugo M.F.
Published: March 2020

This study evaluated leaf area development, leaf nutritional content, and yield of pruned/unpruned cassava supplied with nitrogen (N) and potassium (K) during its second vegetative cycle. Two field experiments were conducted in a randomized complete‐block design with split‐plots and four replications. The treatments consisted of four management approaches that combined pruning/not pruning with or without K as the main plot and four N application rates (0, 50, 100, and 200 kg ha−1 N) as the subplots. The results revealed that an evaluation of the nutritional status of cassava during its second vegetative cycle should be considered if shoot pruning has been conducted because pruned plants had higher concentrations of N, P, and K in their leaves, and unpruned plants exhibited leaves with higher Ca, Fe, and Mn concentrations. Pruning of cassava shoots during the autumn/winter resting phase did not negatively affect root yield and may represent a recommended management practice for cassava cultivation. In soils with a medium level of K availability, K provision during the second cassava growth cycle is unnecessary because the application of K did not increase leaf reconstitution or yield components in either pruned or unpruned plants. The late application of N improved the nutritional status of cassava plants and increased their leaf area during the second growth cycle. Cassava root, starch, and flour yields increased in a linear fashion in response to the late application of N.
Long‐term influence of phosphorus fertilization on organic carbon and nitrogen in soil aggregates under no‐till corn–wheat–soybean rotations
Authors: Bansal Sangeeta , Yin Xinhua , Savoy Hubert J. , Jagadamma Sindhu , Lee Jaehoon , Sykes Virginia
Published: March 2020

The role of P availability on soil C sequestration is poorly understood in no‐tillage production. The objective of this study was to examine the long‐term phosphorus (P) fertilization effect on soil organic C (SOC), N, and C:N ratio in soil aggregates at different depths in no‐till corn (Zea mays L.)‐wheat (Triticum aestivum L.)‐soybean (Glycine max L.) rotations. The experiment was conducted on low to medium P soils at Springfield and Milan, TN during 2013–2015 from 0–15 cm and from 0–5, 5–10, 10–15, and 15–30 cm in 2018 using Latin square design with five replications of five P rates (0, 29, 59, 88, and 117 kg P ha−1) applied annually. Bulk soil and aggregate sizes > 2, 0.25–2, 0.053–0.25, and < 0.053 mm were analyzed for SOC and N. Phosphorus rate of 88 kg ha−1 resulted in high soil testing P and had higher SOC and N than all other treatments on low P soil. However, over‐application of P at 117 kg ha−1 decreased SOC on low P soil. No response of SOC or N to P fertilization was observed on medium P soil. Application of 29 kg P ha−1 increased large macroaggregate (> 2 mm) weight. Concentrations of SOC and N were higher in microaggregates (0.053–0.25 mm) than the other aggregates. In conclusion, SOC and N stocks are increased on low P soils with appropriate P application, which is crucial for simultaneous improvements of soil C sequestration and crop yield.
Utilizing multiparametric flow cytometry in the diagnosis of patients with primary plasma cell leukemia
Authors: Evans Laura A. , Jevremovic Dragan , Nandakumar Bharat , Dispenzieri Angela , Buadi Francis K. , Dingli David , Lacy Martha Q. , Hayman Suzanne R. , Kapoor Prashant , Leung Nelson , Fonder Amie , Hobbs Miriam , Hwa Yi Lisa , Muchtar Eli , Warsame Rahma , Kourelis Taxiarchis V. , Go Ronald , Russell Stephen , Lust John A. , Lin Yi , Siddiqui Mustaqeem , Kyle Robert A. , Gertz Morie A. , Rajkumar S. Vincent , Kumar Shaji K. , Gonsalves Wilson I.
Published: March 2020

The diagnosis of primary plasma cell leukemia (pPCL) has been made by quantifying circulating plasma cells (cPCs) morphologically on a peripheral blood (PB) smear. However, this technique is not sufficiently sensitive. Multiparametric flow cytometry (MFC) provides a readily available and highly sensitive method to identify and quantify cPCs that could complement PB smear assessment. However, an optimal quantitative cutoff for cPCs by MFC to identify pPCL has not been established. Thus, a total of 591 patients newly diagnosed multiple myeloma (NDMM) patients who had their PB samples evaluated morphologically by PB smear, and immunophenotypically by MFC prior to beginning therapy were evaluated. The presence of ≥200 cPCs/μL by MFC (N = 25 or 5% of the total population) was chosen to identify patients with ≥5% cPCs by PB smear with a specificity of 99% and a sensitivity of 77%. For patients with ≥200 cPCs/μL by MFC compared to the remainder of the cohort, the median Time to next therapy (TTNT) was 18 vs 30 months and the median OS was 38 vs 70 months respectively. Thus, MFC assessment of PB can be utilized in conjunction with the morphological assessment of a PB smear to aid in improving the identification of pPCL among NDMM patients.
Safety and efficacy of self‐administered romiplostim in patients with immune thrombocytopenia: Results of an integrated database of five clinical trials
Authors: Kuter David J. , Arnold Donald M. , Rodeghiero Francesco , Janssens Ann , Selleslag Dominik , Bird Robert , Newland Adrian , Mayer Jiri , Wang Kejia , Olie Robert
Published: March 2020

Romiplostim self‐administration by patients or caregivers may offer time/cost savings to healthcare professionals (HCPs) and convenience for patients who avoid weekly clinic visits. We performed an integrated analysis of five clinical trials to evaluate the efficacy and safety of romiplostim self‐administration. Data were analyzed from adults with immune thrombocytopenia (ITP) who received weekly romiplostim via self‐administration or from an HCP. Patients who achieved a stable romiplostim dose for ≥3 weeks (HCP group ≥5 weeks to provide an appropriate index date to enable comparisons with the self‐administration group) with platelet counts ≥50 × 109/L were eligible. In the self‐administration (n = 621) vs HCP (n = 133) groups, respectively, median age was 53 vs 58 years, median time since primary ITP diagnosis was 3.7 vs 2.5 years, and median baseline platelet count at ITP diagnosis was 19.0 vs 20.0 × 109/L. In the self‐administration and HCP‐dosed groups, median romiplostim treatment duration was 89 vs 52 weeks and median total number of doses was 81 vs 50, respectively. In the self‐administration and HCP groups, respectively: 95.0% and 100.0% of patients achieved ≥1 platelet response (defined as weekly platelet count ≥50 × 109/L without rescue medication in previous 4 weeks); the median percentage of weeks with a response was 94.5% and 95.9%; and rescue medication was used in 36.7% and 39.8% of patients. Self‐administration did not adversely affect safety; duration‐adjusted rates for all treatment‐emergent adverse events (TEAEs) and bleeding TEAEs were numerically lower with self‐administration. Romiplostim self‐administration appears effective and well tolerated in eligible patients with ITP.
Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome
Authors: Bernardo Pia , Cobb Stuart , Coppola Antonietta , Tomasevic Leo , Di Lazzaro Vincenzo , Bravaccio Carmela , Manganelli Fiore , Dubbioso Raffaele
Published: March 2020

Objective

Rett syndrome (RTT) is an X‐linked dominant neurodevelopmental disorder due to pathogenic mutations in the MECP2 gene. Motor impairment constitutes the core diagnostic feature of RTT. Preclinical studies have consistently demonstrated alteration of excitation/inhibition (E/I) balance and aberrant synaptic plasticity at the cortical level. We aimed to understand neurobiological mechanisms underlying motor deficit by assessing in vivo synaptic plasticity and E/I balance in the primary motor cortex (M1).

Methods

In 14 patients with typical RTT, 9 epilepsy control patients, and 11 healthy controls, we applied paired‐pulse transcranial magnetic stimulation (TMS) protocols to evaluate the excitation index, a biomarker reflecting the contribution of inhibitory and facilitatory circuits in M1. Intermittent TMS‐theta burst stimulation was used to probe long‐term potentiation (LTP)‐like plasticity in M1. Motor impairment, assessed by ad hoc clinical scales, was correlated with neurophysiological metrics.

Results

RTT patients displayed a significant increase of the excitation index (p = 0.003), as demonstrated by the reduction of short‐interval intracortical inhibition and increase of intracortical facilitation, suggesting a shift toward cortical excitation likely due to GABAergic dysfunction. Impairment of inhibitory circuits was also confirmed by the reduction of long‐interval intracortical inhibition (p = 0.002). LTP‐like plasticity in M1 was abolished (p = 0.008) and scaled with motor disability (all p = 0.003).

Interpretation

TMS is a method that can be used to assess cortical motor function in RTT patients. Our findings support the introduction of TMS measures in clinical and research settings to monitor the progression of motor deficit and response to treatment. ANN NEUROL 2020;87:763–773
Intelligentes Design von Nanomaterialien für Mitochondrien‐gerichtete Nanotherapeutika
Authors: Liew Si Si , Qin Xiaofei , Zhou Jia , Li Lin , Huang Wei , Yao Shao Q.
Published: March 2020

Mitochondrien sind die Kraftwerke der Zelle. Sie sind überlebenswichtige Organellen, die zelluläre Funktionen und den Metabolismus aufrechterhalten. Eine Dysfunktion der Mitochondrien führt zu verschiedenen Krankheiten mit einer großen Diversität klinischer Erscheinungen. In der Vergangenheit wurden Strategien zur Herstellung subzellulär angreifender Nanowirkstoffcarrier entwickelt, die zunächst die zelluläre Internalisierung und schließlich die Lokalisierung der Organelle ermöglichen. Seit einiger Zeit zeichnen sich innovative Strategien für das intelligente Design multifunktionaler Nanocarrier ab. Hierarchisches Targeting erlaubt es diesen, verschiedenste Barrieren auf dem Wege der Verabreichung in vivo zu umgehen oder zu überwinden und das Organell mit guter Bioverfügbarkeit zu erreichen. Stimuli‐responsive Nanocarrier erlauben die kontrollierte Freisetzung der Therapeutika unmittelbar am gewünschten Target. Synergetische Therapien können durch die Verwendung einer Ansatzkombination erzielt werden, wie etwa aus Chemo‐, Gen‐ und Phototherapie. In diesem Aufsatz untersuchen wir dieses Feld auf neuste Entwicklungen und Strategien im intelligenten Design von Nanocarriern für Mitochondrien‐gerichtete Therapeutika. Überdies werden bestehende Herausforderungen sowie bisher unerforschte therapeutische Möglichkeiten aufgezeigt und diskutiert, um die nächste Generation mitochondrial‐gerichteter Nanotherapeutika zu inspirieren.
Dimeric Manganese‐Catalyzed Hydroarylation and Hydroalkenylation of Unsaturated Amides
Authors: Wang Dongping , Dong Jie , Fan Wenjing , Yuan Xiang‐Ai , Han Jian , Xie Jin
Published: March 2020

An unprecedented Mn(I)‐catalyzed selective hydroarylation and hydroalkenylation of unsaturated amides with commercially available organic boronic acids is reported. Alkenyl boronic acids have been successfully employed for the first time in Mn(I)‐catalyzed carbon–carbon bond formation. A wide array of β‐alkenylated amide products can be obtained in moderate to good yields, which offers practical access to five‐ and six‐membered lactams. This protocol has predictable regio‐ and chemoselectivity, excellent functional group compatibility and ease of operation in air, representing a significant step‐forward towards manganese‐catalyzed C−C coupling.
Enhancing the Acceptor Character of Conjugated Organoborane Macrocycles: A Highly Electron‐Deficient Hexaboracyclophane
Authors: Baser‐Kirazli Nurcan , Lalancette Roger A. , Jäkle Frieder
Published: March 2020

We introduce a new boron‐doped cyclophane, the hexabora[16]cyclophane B6‐FMes, in which six tricoordinate borane moieties alternate with short conjugated p‐phenylene linkers. Exocyclic 2,4,6‐tris(trifluoromethyl)phenyl (FMes) groups serve not only to further withdraw electron density but at the same time sterically shield the boron atoms, resulting in a macrocycle that is both highly electron‐deficient and stable. The optical and electronic properties are compared with those of related linear oligomers and the electronic structure is further evaluated by computational methods. The studies uncover unique properties of B6‐FMes, including a low‐lying and extensively delocalized LUMO and a wide HOMO–LUMO gap, which arise from the combination of a cyclic π‐system, strong electronic communication between the closely spaced borons, and the attachment of electron‐deficient pendent groups. The binding of small anions to the electron‐deficient macrocycle and molecular model compounds is investigated and emissive exciplexes are detected in aromatic solvents.
Smart Design of Nanomaterials for Mitochondria‐Targeted Nanotherapeutics
Authors: Liew Si Si , Qin Xiaofei , Zhou Jia , Li Lin , Huang Wei , Yao Shao Q.
Published: March 2020

Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular‐targeting drug‐delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli‐responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this Review, we survey the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria‐targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondrial‐targeting nanotherapeutics.
Semi‐Rationally Designed Short Peptides Self‐Assemble and Bind Hemin to Promote Cyclopropanation
Authors: Zozulia Oleksii , Korendovych Ivan V.
Published: March 2020

The self‐assembly of short peptides gives rise to versatile nanoassemblies capable of promoting efficient catalysis. We have semi‐rationally designed a series of seven‐residue peptides that form hemin‐binding catalytic amyloids to facilitate enantioselective cyclopropanation with efficiencies that rival those of engineered hemin proteins. These results demonstrate that: 1) Catalytic amyloids can bind complex metallocofactors to promote practically important multisubstrate transformations. 2) Even essentially flat surfaces of amyloid assemblies can impart a substantial degree of enantioselectivity without the need for extensive optimization. 3) The ease of peptide preparation allows for straightforward incorporation of unnatural amino acids and the preparation of peptides made from d‐amino acids with complete reversal of enantioselectivity.
Aggregation‐Induced Emission: Recent Advances in Materials and Biomedical Applications
Authors: Cai Xiaolei , Liu Bin
Published: March 2020

The concept of aggregation‐induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image‐guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.
Catalytic reduction of 4‐nitrophenol by means of nanostructured polymeric Schiff base complexes
Authors: Aghaei Marjan , Kianfar Ali Hossein , Dinari Mohammad
Published: March 2020

Polymeric Schiff base ligands were synthesized using 2‐hydroxybenzaldehyde (L2), 4‐hydroxy‐3‐methoxybenzaldehyde (L4), and 5‐aminoisophthalic acid. The nanostructured complexes were then synthesized using Ni2+, Cu2+, and Mn3+. The ligands and complexes thus synthesized were characterized using Fourier‐transform infrared spectroscopy, X‐ray diffraction, thermogravimetric analysis (TGA), and field‐emission scanning electron microscopy. The thermal stability of the complexes was confirmed using TGA. The synthesized complexes were used as catalysts in the reduction of 4‐nitrophenol (4‐NP) to 4‐aminophenol in an aqueous phase in the presence of sodium borohydride. In this work, the catalytic reactivity of nanostructured complexes was compared using the rate constant (k) of the reaction. The reaction time for the reduction of 4‐NP was 5–14 min for different complexes. The catalytic system based on Ni2+/2‐hydroxybenzaldehyde was the most active and displayed reusability in the reduction of 4‐NP.
Factors Affecting the Thermal Comfort of Perioperative Personnel in the OR
Authors: Karahan Azize , Budak Ertürk Elif , Uğurlu Ziyafet , Ünlü Hayriye , Akovalı Nükhet , Tepe Aylin , Özhan Elbaş Nalan
Published: March 2020

Thermal comfort is an important component of any work setting and can be difficult to achieve in the complex OR environment. This comparative descriptive study sought to identify factors affecting the thermal comfort of perioperative personnel in the OR (N = 68). Researchers used the American Society of Heating, Refrigerating and Air‐Conditioning Engineers Thermal Sensation Scale and researcher‐developed surveys to collect data. The mean reported thermal comfort level was −0.44 (standard deviation 1.3), which is within acceptable parameters. Factors affecting thermal comfort were gender, professional role, and wearing additional clothing. Additionally, participants who complained about temperature or ventilation were less likely to report thermal comfort levels in the normal range. Health care facility leaders should consider the comfort needs of perioperative personnel when making purchasing decisions about ventilation systems and surgical clothing; however, they also should consider other factors (eg, surgeon comfort, permeability of protective clothing to blood and other body fluids).
Clinical Issues—March 2020
Authors: deKay Karen
Published: March 2020

THIS MONTH

Laundering microfiber cleaning supplies

Key words: cloth, mop, microfiber, laundering, microorganisms.

Significance of contact time during cleaning

Key words: disinfectant, contact time, cleaning, bactericidal efficacy.

Mask use during cystoscopy and tonsillectomy procedures

Key words: surgical mask, splash, exposure, barrier level, blood‐contaminated aerosols.

Use of radiopaque towels

Key words: radiopaque towels, radiopaque markers, soft goods, towel retention.

Personal fragrances in the perioperative setting

Key words: fragrances, fragrance sensitivity, asthma, disability.
Determinants of private school participation: All about the money?
Authors: Anders Jake , Green Francis , Henderson Morag , Henseke Golo
Published: March 2020

For those who grew up in Britain in the latter half of the twentieth century, there is known to be a strong association between social class or family income and attending a private school. However, increasing private school fees and promotion of school choice in the state sector have potential implications for the predictors of participation in private schooling in the twenty‐first century. In this article, through analysis of rich, longitudinal data from a recent, representative birth cohort study, we provide new evidence on this issue. Given the high and rising fees required to send a child to private school, one might think that the decision is entirely connected with financial resources. However, while these remain an important factor, we argue that other determinants are also important. In particular, we highlight the importance of parental values and geographical proximity to high‐quality state school alternatives: a one standard deviation increase in levels of parental traditional values is associated with a 2.5 percentage point higher probability of their child attending a private school, while each minute of additional travel time to the nearest state school judged ‘Outstanding’ by England’s schools inspectorate is associated with a 0.2 percentage point higher probability of attending a private school. We also examine the characteristics of those who ‘mix and match’ state and private schooling, noting their similarity to private school attendees in terms of their values but lower levels of financial resources.
Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics
Authors: Dragani Tommaso A. , Matarese Valerie , Colombo Francesca
Published: March 2020

Thousands of candidate cancer biomarkers have been proposed, but so far, few are used in cancer screening. Failure to implement these biomarkers is attributed to technical and design flaws in the discovery and validation phases, but a major obstacle stems from cancer biology itself. Oncogenomics has revealed broad genetic heterogeneity among tumors of the same histology and same tissue (or organ) from different patients, while tumors of different tissue origins also share common genetic mutations. Moreover, there is wide intratumor genetic heterogeneity among cells within any single neoplasm. These findings seriously limit the prospects of finding a single biomarker with high specificity for early cancer detection. Current research focuses on developing biomarker panels, with data assessment by machine‐learning algorithms. Whether such approaches will overcome the inherent limitations posed by tumor biology and lead to tests with true clinical value remains to be seen.
Systematic and Comparative Evaluation of Software Programs for Template‐Based Modeling of Protein Structures
Authors: Jang Woo Dae , Lee Sang Mi , Kim Hyun Uk , Lee Sang Yup
Published: March 2020

Modeling protein structures is critical for understanding protein functions in various biological and biotechnological studies. Among representative protein structure modeling approaches, template‐based modeling (TBM) is by far the most reliable and most widely used approach to model protein structures. However, it still remains as a challenge to select appropriate software programs for pairwise alignments and model building, two major steps of the TBM. In this paper, pairwise alignment methods for TBM are first compared with respect to the quality of structure models built using these methods. This comparative study is conducted using comprehensive datasets, which cover 6185 domain sequences from Structural Classification of Proteins extended for soluble proteins, and 259 Protein Data Bank entries (whole protein sequences) from Orientations of Proteins in Membranes database for membrane proteins. Overall, a profile‐based method, especially PSI‐BLAST, consistently shows high performance across the datasets and model evaluation metrics used. Next, use of two model building programs, MODELLER and SWISS‐MODEL, does not seem to significantly affect the quality of protein structure models built except for the Hard group (a group of relatively less homologous proteins) of membrane proteins. The results presented in this study will be useful for more accurate implementation of TBM.
Simultaneous increases in the levels of compatible solutes by cost‐effective cultivation of Synechocystis sp. PCC 6803
Authors: Iijima Hiroko , Watanabe Atsuko , Sukigara Haruna , Shirai Tomokazu , Kondo Akihiko , Osanai Takashi
Published: March 2020

Synechocystis sp. PCC 6803, a cyanobacterium widely used for basic research, is often cultivated in a synthetic medium, BG‐11, in the presence of 4‐(2‐hydroxyethyl)‐1‐piperazine ethanesulfonic acid (HEPES) or 2‐[[1,3‐dihydroxy‐2‐(hydroxymethyl)propan‐2‐yl]amino]ethanesulfonic acid buffer. Owing to the high cost of HEPES buffer (96.9% of the total cost of BG‐11 medium), the biotechnological application of BG‐11 is limited. In this study, we cultured Synechocystis sp. PCC 6803 cells in BG‐11 medium without HEPES buffer and examined the effects on the primary metabolism. Synechocystis sp. PCC 6803 cells could grow in BG‐11 medium without HEPES buffer after adjusting for nitrogen sources and light intensity; the production rate reached 0.54 g cell dry weight·L−1·day−1, exceeding that of commercial cyanobacteria and Synechocystis sp. PCC 6803 cells cultivated under other conditions. The exclusion of HEPES buffer markedly altered the metabolites in the central carbon metabolism; particularly, the levels of compatible solutes, such as sucrose, glucosylglycerol, and glutamate were increased. Although the accumulation of sucrose and glucosylglycerol under high salt conditions is antagonistic to each other, these metabolites accumulated simultaneously in cells grown in the cost‐effective medium. Because these metabolites are used in industrial feedstocks, our results reveal the importance of medium composition for the production of metabolites using cyanobacteria.
Surveillance and outcomes after curative resection for gastroesophageal adenocarcinoma
Authors: Jiang Di M. , Suzuki Chihiro , Espin‐Garcia Osvaldo , Lim Charles H. , Ma Lucy X. , Sun Peiran , Sim Hao‐Wen , Natori Akina , Chan Bryan A. , Moignard Stephanie , Chen Eric X. , Liu Geoffrey , Swallow Carol J. , Darling Gail E. , Wong Rebecca , Jang Raymond W. , Elimova Elena
Published: March 2020

Background

The goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance.

Methods

A single‐site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease‐free survival ≥2 years. Time‐to‐event data were analyzed using the Kaplan‐Meier method and log rank tests.

Results

Between 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow‐up of 38.3 months, 5‐year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance‐detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time‐to‐recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance‐detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P < .001), but similar TTR (16.2 vs 13.3 months, P = .40) and duration of palliative chemotherapy (3.9 vs 3.3 months, P = .64).

Conclusions

Among patients surveyed, 96% of recurrences were distant, and salvage therapy was successful in only 1.9% of patients. Longer OS in patients with surveillance‐detected compared to symptomatic recurrences was not associated with significant earlier disease detection, and may be contributed by differences in disease biology. Further prospective data are warranted to establish the benefit of surveillance testing in gastroesophageal adenocarcinoma.
MicroRNA targeting of the non‐canonical planar cell polarity pathway in the developing neural tube
Authors: Mukhopadhyay Partha , Greene Robert M. , Pisano M. Michele
Published: March 2020

MicroRNAs (miRNAs) provide context‐dependent transcriptional regulation of genes comprising signalling networks throughout the developing organism including morphogenesis of the embryonic neural tube (NT). Using a high‐sensitivity, high‐coverage microarray analysis platform, miRNA expression in the murine embryonic NT during the critical stages of its formation was examined. Analysis of a number of differentially expressed (DE) miRNAs enabled identification of several gene targets associated with cellular processes essential for normal NT development. Using computational pathway analysis, interactive biologic networks and functional relationships connecting DE miRNAs with their targeted messenger RNAs (mRNAs) were identified. Potential mRNA targets and a key signal transduction pathway governing critical cellular processes indispensable for normal mammalian neurulation were also identified. RNA preparations were also used to hybridize both miRNA arrays and mRNA arrays allowing miRNA‐mRNA target analysis using data of DE miRNAs and DE mRNAs – co‐expressed in the same developing NT tissue samples. Identification of these miRNA targets provides key insight into the epigenetic regulation of NT development as well as into potential mechanistic underpinning of NT defects.

Significance of the study

This study underscores the premise that microRNAs are potential coordinators of normal neural tube (NT) formation, via regulation of the crucial, planar cell polarity pathway. Any alteration in their expression during neurulation would result in abnormal NT development.
Hypoxia‐induced apoptosis of astrocytes is mediated by reduction of Dicer and activation of caspase‐1
Authors: Kang Yeo Wool , Kim Yoon Suk , Park Jun Young , Chu Ga‐eul , Yang Young Chul , Choi Byung Young , Cho Won Gil
Published: March 2020

Hypoxia is a condition in which the whole body or a region of the body is deprived of oxygen supply. The brain is very sensitive to the lack of oxygen and cerebral hypoxia can rapidly cause severe brain damage. Astrocytes are essential for the survival and function of neurons. Therefore, protecting astrocytes against cell death is one of the main therapeutic strategies for treating hypoxia. Hence, the mechanism of hypoxia‐induced astrocytic cell death should be fully elucidated. In this study, astrocytes were exposed to hypoxic conditions using a hypoxia work station or the hypoxia mimetic agent cobalt chloride (CoCl2). Both the hypoxic gas mixture (1% O2) and chemical hypoxia‐induced apoptotic cell death in T98G glioblastoma cells and mouse primary astrocytes. Reactive oxygen species were generated in response to the hypoxia‐mediated activation of caspase‐1. Active caspase‐1 induced the classical caspase‐dependent apoptosis of astrocytes. In addition, the microRNA processing enzyme Dicer was cleaved by caspase‐3 during hypoxia. Knockdown of Dicer using antisense oligonucleotides induced apoptosis of T98G cells. Taken together, these results suggest that astrocytic cell death during hypoxia is mediated by the reactive oxygen species/caspase‐1/classical caspase‐dependent apoptotic pathway. In addition, the decrease in Dicer levels by active caspase‐3 amplifies this apoptotic pathway via a positive feedback loop. These findings may provide a new target for therapeutic interventions in cerebral hypoxia.
Solvent‐Free Synthesis of Nano Zirconium Phenylphosphonates with Molten Phenylphosphonic Acid
Authors: Contreras‐Ramirez Aida , Tomlin Bryan E. , Day Gregory S. , Clearfield Abraham , Zhou Hong‐Cai
Published: March 2020

Nanosized α‐zirconium phenylphosphonate particles were successfully prepared by the reaction between different zirconium sources and molten phenylphosphonic acid in the absence of solvent. The resultant nanoplates exhibit particle sizes in the range of 15 to 30 nm. The use of a topotactic anion exchange method starting from α‐zirconium phosphate instead resulted in the generation of 15 to 180 nm plates, while also resulting in nanoparticles with a higher degree of crystallinity. The topotactic anion exchange of the phosphate groups by phenylphosphonate groups could be performed to completion when performed in molten phenylphosphonic acid. Characterization of both the final products as well as the individual steps in the anion exchange were performed by powder XRD, fast neutron activation analysis, TGA, FTIR spectroscopy, TEM, solid‐state NMR and XPS.
A Silane‐Based Bipolar Host with High Triplet Energy for High Efficiency Deep‐Blue Phosphorescent OLEDs with Improved Device Lifetime
Authors: Ko Soo‐Byung , Kang Sunwoo , Kim Taekyung
Published: March 2020

A high triplet energy host is developed using a silane moiety, 9‐(4‐(triphenylsilyl)dibenzo[b,d]furan‐2‐yl)‐9H‐carbazole (SiDBFCz), is designed through extensive density functional theory (DFT) calculations to obtain appropriate hole and electron injection barriers. The chemical hardness and the charge transport characteristics are comprehensively investigated to realize a bipolar host with high triplet energy over 2.9 eV for deep blue phosphorescent organic light‐emitting diodes (PHOLEDs). The synthesized SiDBFCz clearly exhibits the bipolar characteristics especially with emitter molecules doped. An external quantum efficiency over 19 % without any microcavity optimization is achieved thanks to the good charge balance in the SiDBFCz PHOLED. The device lifetime of the SiDBFCz PHOLED is improved more than 1000 %, compared to the unipolar control devices at an initial luminance of 500 cd m−2. The dramatic enhancement of the operational stability of the deep blue PHOLED is also thoroughly investigated in terms of electrochemical stability of host molecules in charged or excited states. The results clearly indicate that the device lifetime is strongly correlated with the bond dissociation energy and the activation energy for the bond dissociation reaction in triplet excited state.
Probing the Water Stability Limits and Degradation Pathways of Metal–Organic Frameworks
Authors: Safy Mohamed E. A. , Amin Muhamed , Haikal Rana R. , Elshazly Basma , Wang Junjun , Wang Yuemin , Wöll Christof , Alkordi Mohamed H.
Published: March 2020

A comprehensive model to describe the water stability of prototypical metal–organic frameworks (MOFs) is derived by combining different types of theoretical and experimental approaches. The results provide an insight into the early stages of water‐triggered destabilization of MOFs and allow detailed pathways to be proposed for the degradation of different MOFs under aqueous conditions. The essential elements of the approach are computing the pKa values of coordinated water molecules and geometry relaxations. Variable‐temperature and pH infrared spectroscopy techniques are used to corroborate the main findings. The model developed herein helps to explain stability limits observed for several prototypical MOFs, including MOF‐5, HKUST‐1, UiO‐66, and MIL‐101‐Cr, in aqueous solutions, and thus, provides an insight into the possible degradation pathways in acidic and basic environments. The formation of a metal hydroxide through the autoprotolysis of metal‐coordinated water molecules and the strength of carboxylate–metal interactions are suggested to be two key players that govern stability in basic and acidic media, respectively. The methodology presented herein can effectively guide future efforts, which are especially significant for in silico screening, for developing novel MOFs with enhanced aqueous stability.
Sulfonation of 3,3′‐Diformyl‐BINOL for Enantioselective Fluorescent Recognition of Amino Acids in Water
Authors: Zhao Feng , Wang Yalin , Wu Xuedan , Yu Shanshan , Yu Xiaoqi , Pu Lin
Published: March 2020

Reaction of (R)‐3,3′‐diformyl‐1,1′‐bi‐2‐naphthol with concentrated sulfuric acid gives the corresponding 6,6′‐disulfonated compound (R)‐2 selectively. This provides a simple and efficient method to convert a water‐insoluble compound to a water‐soluble fluorescent probe. It is found that (R)‐2 in combination with Zn2+ shows a highly enantioselective fluorescent response toward various amino acids in the aqueous HEPES buffer solution at pH 7.4. For example, an enantioselective fluorescence enhancement ratio [ef=ΔID/ΔIL] up to 35.8 is observed for the recognition of asparagine. NMR and mass spectroscopic investigations are conducted to explore the reaction of (R)‐2 with asparagine.