bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Student-Paced Pragmatics Instruction through Nearpod on EFL Learners’ Request Performance
Authors: Civelek Mustafa , Karatepe Çiğdem
Published: February 2022

Although the use of technology for pragmatics instruction has attracted significant attention from scholars, the number of studies regarding the impact of self-access materials to this end is limited. Nearpod is a useful cloud-based application to support self-paced learning. This paper aims to probe the effect of learning through Nearpod on EFL learners’ request performance. Researchers designed seven self-access courses to teach requests. The data was collected from 11 EFL learners through Online Oral Discourse Completion Tasks before and after the treatment. The post-test results revealed that the participants significantly improved their request performance after the treatment. The learners’ responses in the pre-test and the post-test were also qualitatively analyzed for an in-depth investigation of the changes in their requesting behavior. The findings revealed that the learners stopped modality generalization and started using a variety of modal verbs according to the context of situation after the treatment. Additionally, it was indicated that self-paced pragmatics instruction helped learners overcome the pragmatic failures regarding the main verb use in request head acts. Furthermore, the differences regarding the learners’ use of internal and external modifiers were also documented. After the treatment, they performed various internal modifiers that were either absent or uncommon in the pre-test data. Alerters and grounders were found to be the most frequent external modifiers in both the pre-test and the post-test data set. In summary, the results indicated that self-paced learning helped learners improve strategies for performing appropriate requests.
Wei2GO: weighted sequence similarity-based protein function prediction
Authors: Reijnders Maarten J.M.F.
Published: February 2022

Background

Protein function prediction is an important part of bioinformatics and genomics studies. There are many different predictors available, however most of these are in the form of web-servers instead of open-source locally installable versions. Such local versions are necessary to perform large scale genomics studies due to the presence of limitations imposed by web servers such as queues, prediction speed, and updatability of databases.

Methods

This paper describes Wei2GO: a weighted sequence similarity and python-based open-source protein function prediction software. It uses DIAMOND and HMMScan sequence alignment searches against the UniProtKB and Pfam databases respectively, transfers Gene Ontology terms from the reference protein to the query protein, and uses a weighing algorithm to calculate a score for the Gene Ontology annotations.

Results

Wei2GO is compared against the Argot2 and Argot2.5 web servers, which use a similar concept, and DeepGOPlus which acts as a reference. Wei2GO shows an increase in performance according to precision and recall curves, Fmax scores, and Smin scores for biological process and molecular function ontologies. Computational time compared to Argot2 and Argot2.5 is decreased from several hours to several minutes.

Availability

Wei2GO is written in Python 3, and can be found at https://gitlab.com/mreijnders/Wei2GO.
A Study of Toxic Effects of Formalin on Health of First Year Medical and Dental Students
Authors: Fernandes Refli , Anturlikar Vaishali , Patil Dhaval
Published: February 2022

Introduction: Formalin is widely and commonly used as a fixative for microscopy, histology, preservative and disinfectant, etc. Despite formalin being extensively used in different fields, its toxicity is frequently ignored. It can be allergenic, carcinogenic or toxic to many organs such as pancreas, liver, kidney and brain. Aim: To study the toxic effects of formalin on health of first year medical and dental students. MaterialsandMethods:Thecross-sectionalstudywasconducted over a period of one year (February 2019 to January 2020) in the Department of Anatomy, SMBT Institute of Medical Sciences and Research Center, Dhamangaon, Nashik, Maharashtra. This questionnaire based study was conducted on 200 first year medical and dental students. The percentage distribution of incidence of toxic effects of formalin pertaining to symptoms was calculated using Microsoft Excel 2019 spreadsheet software. The data were presented as frequency and percentage. Results: Out of 200 students, 180 students (85 females and 95 males) completed and returned the questionnaire. The toxic effects of formalin with symptoms such as lacrimation in 63.33%, itching of eyes in 81.67%, running nose in 51.11%, redness of eyes in 55%, burning of eyes in 80.5%, and headache in 42.22% of subjects were observed. The results were compared with previous studies conducted. Conclusion: Formalin toxicity is of concern to people working closely with it including embalmers, anatomists, medical and dental students. Awareness will bring a positive effect on their health. Also, through research, we will be able to contribute towards prevention of occupational hazards, rehabilitation of affected persons and dissemination of knowledge.
Analysis of Foramina of the Middle Cranial Fossa with Special Emphasis on Morphology and Morphometry of Foramen Ovale- An Observational Study
Authors: Santhosh S , Showri R , Sreekanth C
Published: February 2022

Introduction: Foramen Ovale (FO) is an important aperture present in the middle cranial fossa which transmits delicate neurovascular structures, especially the mandibular nerve. Morphological and morphometrical variations of this foramen are seen in literature and this knowledge is important as it is used for cannulation in rhizotomy for trigeminal neuralgia. Aim: To analyse the foramina of the middle cranial fossa by emphasising on morphometry and morphology of FO as mandibular nerve passes through it. Materials and Methods: This observational study was conducted in the Department of Anatomy, Vydehi Institute of Medical Sciences and Research,Banglore, Karnataka,India from January 2020 to June 2020. Fifty-one fully ossified adult skulls were utilised for this observational study. Antero-Posterior (AP) diameter, transverse diameter, area, and different shapes of the FO, distance between FO and other foramina, presence of foramen of Vesalius and accessory bony structures were studied. Independent sample t-test was done to compare the mean values of all the diameters. Results: The AP and transverse diameter of FO on the right and left side was found to be almost symmetrical. AP diameter on the right and left side was found to be 6.79±1.4 mm and 6.78±1.3 mm, respectively and transverse diameter was 3.58±0.90 mm on the right and 3.45±0.99 on left side. Distance between FO and Foramen Spinosum (FS), foramen lacerum and Meckel’s cave were similar on both the sides. The distance between FO and rotundum was greater on the right side i.e., 11.09±1.9 mm than left side which showed a diameter of 10.68±1.6 mm. The different shapes of the FO observed were oval, almond, D-shaped, elongated, round, slit and irregular. Oval shape (22 skulls on the left side and 27 skulls on the right) was the most common type. Foramen of Vesalius was observed in four skulls and accessory bony structures like bony septum, plate and spurs were also seen in the current study. Conclusion: The knowledge regarding the shape and distance between the FO and various foramina might benefit the neurosurgeons and radiologists during surgical procedures.
Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy
Authors: D'Silva Arlene M. , Holland Sandra , Kariyawasam Didu , Herbert Karen , Barclay Peter , Cairns Anita , MacLennan Suzanna C. , Ryan Monique M. , Sampaio Hugo , Smith Nicholas , Woodcock Ian R. , Yiu Eppie M. , Alexander Ian E. , Farrar Michelle A.
Published: February 2022

Objective

To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real‐world practice, in a broad population of infants with spinal muscular atrophy (SMA).

Methods

A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described.

Results

21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment‐related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge.

Interpretation

This study provides real‐world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.
TRPV4 mutations causing mixed neuropathy and skeletal phenotypes result in severe gain of function
Authors: Taga Arens , Peyton Margo A. , Goretzki Benedikt , Gallagher Thomas Q. , Ritter Ann , Harper Amy , Crawford Thomas O. , Hellmich Ute A. , Sumner Charlotte J. , McCray Brett A.
Published: February 2022

Objective

Distinct dominant mutations in the calcium‐permeable ion channel TRPV4 (transient receptor potential vanilloid 4) typically cause nonoverlapping diseases of either the neuromuscular or skeletal systems. However, accumulating evidence suggests that some patients develop mixed phenotypes that include elements of both neuromuscular and skeletal disease. We sought to define the genetic and clinical features of these patients.

Methods

We report a 2‐year‐old with a novel R616G mutation in TRPV4 with a severe neuropathy phenotype and bilateral vocal cord paralysis. Interestingly, a different substitution at the same residue, R616Q, has been reported in families with isolated skeletal dysplasia. To gain insight into clinical features and potential genetic determinants of mixed phenotypes, we perform in‐depth analysis of previously reported patients along with functional and structural assessment of selected mutations.

Results

We describe a wide range of neuromuscular and skeletal manifestations and highlight specific mutations that are more frequently associated with overlap syndromes. We find that mutations causing severe, mixed phenotypes have an earlier age of onset and result in more marked elevations of intracellular calcium, increased cytotoxicity, and reduced sensitivity to TRPV4 antagonism. Structural analysis of the two mutations with the most dramatic gain of ion channel function suggests that these mutants likely cause constitutive channel opening through disruption of the TRPV4 S5 transmembrane domain.

Interpretation

These findings demonstrate that the degree of baseline calcium elevation correlates with development of mixed phenotypes and sensitivity to pharmacologic channel inhibition, observations that will be critical for the design of future clinical trials for TRPV4 channelopathies.
Sodium Metal Anodes with Self‐Correction Function Based on Fluorine‐Superdoped CNTs/Cellulose Nanofibrils Composite Paper
Authors: Xiao Jian , Xiao Nan , Li Kai , Zhang Lipeng , Ma Xiaoqing , Li Yong , Leng Changyu , Qiu Jieshan
Published: February 2022

Despite much efforts to stabilize sodium metal anodes for promoting their commercial applications, achieving a safe cycling process without intrinsic dendrite growth remains difficult owing to the unstable reaction interface and irregular sodium metal propagation. Herein, fluorine‐superdoped carbon nanotubes with a fluorine content of 14.38 at% are achieved using a new oxidation‐assisted plasma strategy, and then alternately assembled with cellulose nanofibrils to form periodical conductive/dielectric composite paper with outstanding mechanical properties. The superdoping of fluorine facilitates the construction of a NaF‐dominated solid electrolyte interphase layer, while the periodical conductive/dielectric network re‐homogenizes electric field distribution around irregular sodium protrusions, realizing a “bottom‐up” sodium orientation deposition and the “self‐correction” functionality during sodium plating/stripping process. Density functional theory calculations reveal that the specific oxygen species (CO/CO) and fluorine species (semi‐ionic CF/covalent CF2) on the surface of carbon matrix, could remarkably trap active fluorine fragments and generate NaF with sodium metal, respectively, which promotes the superdoping of fluorine and forms dendrite‐free sodium anodes. This delicate structure renders the sodium anodes a low nucleation overpotential of ≈7 mV, high Coulombic efficiency of 99.5% over 300 cycles at 3 mA cm−2, stable operation for up to 2100 h under ≈16 mV, and excellent full battery performance.
Bistable and Multistable Actuators for Soft Robots: Structures, Materials, and Functionalities
Authors: Chi Yinding , Li Yanbin , Zhao Yao , Hong Yaoye , Tang Yichao , Yin Jie
Published: February 2022

Snap‐through bistability is often observed in nature (e.g., fast snapping to closure of Venus flytrap) and the life (e.g., bottle caps and hair clippers). Recently, harnessing bistability and multistability in different structures and soft materials has attracted growing interest for high‐performance soft actuators and soft robots. They have demonstrated broad and unique applications in high‐speed locomotion on land and under water, adaptive sensing and fast grasping, shape reconfiguration, electronics‐free controls with a single input, and logic computation. Here, an overview of integrating bistable and multistable structures with soft actuating materials for diverse soft actuators and soft/flexible robots is given. The mechanics‐guided structural design principles for five categories of basic bistable elements from 1D to 3D (i.e., constrained beams, curved plates, dome shells, compliant mechanisms of linkages with flexible hinges and deformable origami, and balloon structures) are first presented, alongside brief discussions of typical soft actuating materials (i.e., fluidic elastomers and stimuli‐responsive materials such as electro‐, photo‐, thermo‐, magnetic‐, and hydro‐responsive polymers). Following that, integrating these soft materials with each category of bistable elements for soft bistable and multistable actuators and their diverse robotic applications are discussed. To conclude, perspectives on the challenges and opportunities in this emerging field are considered.
Flexible Interconnected Cu‐Ni Nanoalloys Decorated Carbon Nanotube‐Poly(vinylidene fluoride) Piezoelectric Nanogenerator
Authors: Badatya Simadri , Kumar Anil , Srivastava Avanish Kumar , Gupta Manoj Kumar
Published: February 2022

Herein, high‐performance flexible and stable Cu‐Ni nanoalloy decorated carbon nanotube (CNT) reinforced poly(vinylidene fluoride) (PVDF) based piezoelectric nanogenerator is presented for the first time with very high current and power density. The formation of crystalline β‐phase is confirmed using FT‐IR and Raman spectra analysis. HR‐TEM study reveals the formation of Cu‐Ni nanoalloys with well‐defined interconnected structure with CNT. The Cu‐Ni nanoalloy decorated CNT‐PVDF nanogenerator device exhibits a high output voltage of 12 V and high current density of 0.3 µA cm−2 compared to pristine PVDF nanogenerator (4 V and 10 nA cm−2). Very high power density of 204 µW cm−3 is obtained from the nanocomposite nanogenerator. Piezoelectric force microscopy study reveals very high piezoelectric charge coefficient (d33) of about 160 pm V−1 from Cu‐Ni decorated CNT‐PVDF. Very stable output performance with almost no degradation till 1500 cycles is observed from the Cu‐Ni nanoalloy CNT‐PVDF nanogenerator. Such high stability is due to its dramatic improved high tensile strength of 60 MPa. Very high dielectric constant of 500 is observed from Cu‐Ni decorated CNT‐PVDF as compared to pristine PVDF (ε’ ≈ 20). The dramatic increase in output performance even under without electrical poling is discussed in light of self‐dipole alignment, in‐situ poling, high d33, interfacial polarization, and enhanced dielectric properties.
Hybrid Nanogenerator for Biomechanical Energy Harvesting, Motion State Detection, and Pulse Sensing
Authors: Du Minxing , Cao Yu , Qu Xuecheng , Xue Jiangtao , Zhang Weiyi , Pu Xiong , Shi Bojing , Li Zhou
Published: February 2022

Harvesting biomechanical energy to power wearable electronic devices shows great potential in the field of the Internet of Things. An insole hybrid nanogenerator (IHN) has been designed based on a combination of multilayered triboelectric nanogenerator and arched piezoelectric nanogenerator. The IHN not only can convert the mechanical energy of the footsteps into electricity, but also distinguishes three kinds of motion states: walking, stepping, and jumping. A maximum open‐circuit voltage of 150 V and a short‐circuit current of 4.5 µA are achieved from human body motions. After walking for 8 min, the IHN can charge a 100 μF capacitor to 2.5 V. Then, a self‐powered dorsalis pedis artery monitoring system is designed, which can detect the pulse signals of the dorsalis pedis artery in real‐time. The integrated design of energy collection, storage, and utilization has important application potential in future self‐powered monitoring of patients and intelligent analysis of blood supply to the lower limbs in a professional athlete.
Thread‐Based Wristwatch Sensing Device for Noninvasive and Simultaneous Detection of Glucose and Lactate
Authors: Promphet Nadtinan , Thanawattano Chusak , Buekban Chatchai , Laochai Thidarut , Rattanawaleedirojn Pranee , Siralertmukul Krisana , Potiyaraj Pranut , Hinestroza Juan P. , Rodthongkum Nadnudda
Published: February 2022

An electrochemical sensing device based on a cotton‐thread electrode for real‐time and simultaneous detection of sweat glucose and sweat lactate is reported. The cotton thread surfaces are simply modified by cellulose nanofibers/carbon nanotube ink‐Prussian blue/chitosan to enhance liquid adsorption, bioreceptor immobilization, and sensor performance in addition to minimize potential irritation and allergies on the wearer's skin. The modified thread surfaces are characterized by laser scanning confocal microscopy, scanning electron microscopy, and Fourier transform Raman spectroscopy. Amperometry is carried out via hydrogen peroxide detection for electrochemical characterization of the modified thread electrodes. A circuit and digital readout of this wearable sensor are customized designed to be integrated with thread electrodes for real‐time and simultaneous detection of sweat glucose and sweat lactate. The wristwatch sensing device provides a linear range of 0.025–3 × 10−3 m with a detection limit of 0.025 × 10−3 m for glucose and a linear range of 0.25–35 × 10−3 m with a detection limit of 0.25 × 10−3 m for lactate. This device can effectively determine the cut‐off levels of both glucose and lactate, which can distinguish between a normal individual and one with a diabetic condition. This platform opens a new avenue for noninvasive and real‐time detection of other sweat biomarkers.
Comparison of eddy covariance and automatic chamber‐based methods for measuring carbon flux
Authors: Shi Rui , Su Peixi , Zhou Zijuan , Yang Jianping , Ding Xinjing
Published: February 2022

An automatic chamber (AC) is an alternative method to the eddy covariance (EC) technique for estimating of CO2 fluxes. However, few direct comparisons between two techniques have been performed on nature alpine meadows. In order to determine diurnal pattern of net ecosystem exchange (NEE) of CO2 in summer on alpine meadows, and test the NEE measurement performance of AC under site conditions, we conducted simultaneous measurements of NEE using both EC and AC methods. The NEEAC can be estimated with the information from the initial slope of the time series of CO2 mixing ratio. We found that the application of linear regression, when photosynthesis processes were considered, could lead to serious deviations, even if closure times were short. The linear regression, however, was adequate for estimating CO2 fluxes when photosynthesis processes were not involved in, at least for short chamber closing times. Using appropriate fitting method, the fluxes of AC were relatively close to that of EC, but presented a daytime underestimation and nighttime overestimation. With the subsequent friction velocity (u*) filtering (<m s–1), the nighttime overestimation was eliminated, and the fluxes of AC showed a similar diurnal pattern of NEE with that of EC, but an overall underestimation all day long. Here, we may provide a side evidence of the overestimation of chamber fluxes at low atmospheric turbulence. Finally, we assume that the overall underestimation of AC is caused by the absence of detection of effective volume of chamber.
Emerging polymeric biomaterials and manufacturing techniques in regenerative medicine
Authors: Xia Dan , Chen Jiatian , Zhang Zhongyang , Dong Mingdong
Published: February 2022

The current demand for patients’ organ and tissue repair and regeneration is continually increasing, where autologous or allograft is the golden standard treatment in the clinic. However, due to the shortage of donors, mismatched size and modality, functional loss of the donor region, possible immune rejection, and so forth, the application of auto‐/allo‐grafts is frequently hindered in many cases. In order to solve these problems, artificial constructs structurally and functionally imitating the extracellular matrix have been developed as substitutes to promoting cell attachment, proliferation, and differentiation, and ultimately forming functional tissues or organs for better tissue regeneration. Particularly, polymeric materials have been widely utilized in regenerative medicine because of their ease of manufacturing, flexibility, biocompatibility, as well as good mechanical, chemical, and thermal properties. This review presents a comprehensive overview of a variety of polymeric materials, their fabrication methods as well applications in regenerative medicine. Finally, we discussed the future challenges and perspectives in the development and clinical transformation of polymeric biomaterials.
Risk stratification for relapsed/refractory classical Hodgkin lymphoma integrating pretransplant Deauville score and residual metabolic tumor volume
Authors: Yhim Ho‐Young , Eshet Yael , Metser Ur , Lajkosz Katherine , Cooper Matthew , Prica Anca , Kukreti Vishal , Bhella Sita , Lang Noémie , Xu Wei , Rodin Danielle , Hodgson David , Tsang Richard , Crump Michael , Kuruvilla John , Kridel Robert
Published: February 2022

Pretransplant Deauville score (DS) is an imaging biomarker used for risk stratification in relapsed/refractory classical Hodgkin lymphoma (cHL). However, the prognostic value of residual metabolic tumor volume (rMTV) in patients with DS 4–5 has been less well characterized. We retrospectively assessed 106 patients with relapsed/refractory cHL who underwent autologous stem cell transplantation. Pretransplant DS was determined as 1–3 (59%) and 4–5 (41%), with a markedly inferior event‐free survival (EFS) in patients with DS 4–5 (hazard ratio [HR], 3.14; p = .002). High rMTV41% (rMTVhigh, ≥4.4 cm3) predicted significantly poorer EFS in patients with DS 4–5 (HR, 3.70; p = .014). In a multivariable analysis, we identified two independent factors predicting treatment failure: pretransplant DS combined with rMTV41% and disease status (primary refractory vs. relapsed). These two factors allow to stratify patients into three groups with divergent 2‐year EFS: 89% for low‐risk (51%; relapsed disease and either pretransplant DS 1–3 or DS 4–5/rMTVlow; HR 1), 65% for intermediate‐risk (28%; refractory disease and either DS 1–3 or DS 4–5/rMTVlow; HR 3.26), and 45% for high‐risk (21%; DS 4–5/rMTVhigh irrespective of disease status; HR 7.61) groups. Pretransplant DS/rMTV41% combination and disease status predict the risk of post‐transplant treatment failure and will guide risk‐stratified approaches in relapsed/refractory cHL.
Microscale Concert Hall Acoustics to Produce Uniform Ultrasound Stimulation for Targeted Sonogenetics in hsTRPA1‐Transfected Cells
Authors: Vasan Aditya , Allein Florian , Duque Marc , Magaram Uri , Boechler Nicholas , Chalasani Sreekanth H. , Friend James
Published: February 2022

Ultrasound neuromodulation has rapidly developed over the past decade, a consequence of the discovery of strain‐sensitive structures in the membrane and organelles of cells extending into the brain, heart, and other organs. A key limitation to its use in the brain is the formation of standing waves within the skull. In standing acoustic waves, the maximum ultrasound intensity spatially varies from near zero to double the mean in one‐half of a wavelength, and has led to localized tissue damage and disruption of normal brain function while attempting to evoke a broader response. This phenomenon also produces a large spatial variation in the actual ultrasound exposure in tissue, leading to heterogeneous results. One approach to overcome this limitation is presented here: transducer‐mounted diffusers that result in spatiotemporally incoherent ultrasound. It is shown through experiment and analysis that adding a diffuser to the transducer leads to a twofold increase in ultrasound responsiveness of transient receptor potential ankyrin 1 (TRPA1)‐transfected human embryonic kidney cells. Furthermore, it is shown that the diffuser produces a uniform spatial distribution of pressure within the rodent skull. The approach offers uniform ultrasound delivery into irregular cavities for sonogenetics.
Fully Conjugated Tetraoxa[8]circulene‐Based Porous Semiconducting Polymers
Authors: Fritz Patrick W. , Chen Tianyang , Ashirov Timur , Nguyen Anh‐Dao , Dincă Mircea , Coskun Ali
Published: February 2022

Tetraoxa[8]circulenes (TOCs) are a class of hetero[8]circulenes featuring a planar cyclooctatetraene core with a mixed aromatic/antiaromatic motif that governs their electronic properties. Polymeric TOCs (pTOCs) have been the subject of several computational simulations because they are predicted to be low‐band‐gap semiconductors, but they have not been available synthetically yet. Here, we report the first example of pTOCs, a new family of porous semiconductors, synthesized under ionothermal conditions through the intermolecular cyclization of 1,4,5,8‐anthracene tetrone. pTOCs are porous, with surface areas up to 1656 m2 g−1, and exhibit light‐switchable and tunable semiconducting properties.
Co‐Assembly Induced Solid‐State Stacking Transformation in Amino Acid‐Based Crystals with Enhanced Physical Properties
Authors: Ji Wei , Yuan Hui , Xue Bin , Guerin Sarah , Li Hui , Zhang Lei , Liu Yanqing , Shimon Linda J. W. , Si Mingsu , Cao Yi , Wang Wei , Thompson Damien , Cai Kaiyong , Yang Rusen , Gazit Ehud
Published: February 2022

The physical characteristics of supramolecular assemblies composed of small building blocks are dictated by molecular packing patterns in the solid‐state. Yet, the structure–property correlation is still not fully understood. Herein, we report the unexpected cofacial to herringbone stacking transformation of a small aromatic bipyridine through co‐assembly with acetylated glutamic acid. The unique solid‐state structural transformation results in enhanced physical properties of the supramolecular organizations. The co‐assembly methodology was further expanded to obtain diverse molecular packings by different bipyridine and acetylated amino acid derivatives. This study presents a feasible co‐assembly approach to achieve the solid‐state stacking transformation of supramolecular organization and opens up new opportunities to further explore the relationship between molecular arrangement and properties of supramolecular assemblies by crystal engineering.
Distale Ruthenaelektro‐katalysierte meta‐C−H‐Bromierung mit wässriger HBr
Authors: Wang Yulei , Simon Hendrik , Chen Xinran , Lin Zhipeng , Chen Shan , Ackermann Lutz
Published: February 2022

Während elektrochemische ortho‐selektive C−H‐Aktivierungen bereits etabliert sind, bleiben die distalen C−H‐Aktivierungen weiterhin unterrepräsentiert. Hiermit beschreiben wir eine meta‐C−H‐Aktivierung. Die Bromierung der abgelegenen C−H‐Bindung wurde in einer ungeteilten Zelle unter Verwendung von RuCl3⋅3 H2O und wässriger HBr realisiert. Die Elektrohalogenierung verläuft ohne die Zugabe eines zusätzlichen Liganden und unter elektrolytfreien Bedingungen. Bemerkenswerterweise wurden Pyrazolylarene zum ersten Mal meta‐selektiv am Benzoidfragment und nicht am elektronenreichen Pyrazolring funktionalisiert. Mechanistische Studien legen die Bildung eines Ruthenazyklus nahe mit nachfolgendem Ligand‐zu‐Ligand‐Wasserstoff‐Transfer (LLHT), welcher schließlich das bromierte Produkt bildet.
Non‐parametric local capability indices for industrial planar manufacts: An application to the etching phase in the microelectronic industry
Authors: Borgoni Riccardo , Farace Vincenzo Emanuele , Zappa Diego
Published: February 2022

Process capability indices are routinely used to estimate the mean‐variability performance of industrial products with respect to both targets and specification limits. However, when the target variable is defined over a planar surface of a manufact, it is relevant to assess the capability of the production process locally, that is, at any spatial location of the surface, in particular if the manufact has to be split into pieces to obtain single production items. In this article, focusing on the specification introduced by Clements [Qual Prog., 22, 95–100], we suggest an approach based on additive quantile models to estimate, in a Bayesian paradigm, the index locally. We demonstrate its use in the context of the etching phase of the integrated circuit fabrication process. Since capability of etching processes is typically assessed for batches of wafers, we also propose two algorithms based on resampling to perform local capability analysis at the lot level.
Process monitoring framework for cross‐flow diafiltration‐based virus‐like particle disassembly: Tracing product properties and filtration performance
Authors: Hillebrandt Nils , Vormittag Philipp , Dietrich Annabelle , Hubbuch Jürgen
Published: February 2022

Virus‐like particles (VLPs) are an emerging biopharmaceutical modality with great potential as a platform technology. VLPs can be applied as gene therapy vectors and prophylactic or therapeutic vaccines. For non‐enveloped VLPs, recombinant production of the protein subunits leads to intracellular self‐assembly. The subsequent purification process includes VLP dis‐ and reassembly which aim at removing encapsulated impurities and improving particle properties. Filtration‐based separation and processing has proven successful for VLPs but requires large product quantities and laborious experiments in early development stages. Both challenges can be tackled by implementation of process analytical technology (PAT) to efficiently obtain extensive process information. In this study, an existing PAT setup was extended to comprehensively monitor the diafiltration‐based disassembly of hepatitis B core antigen (HBcAg) VLPs. Process‐related signals were monitored in‐line, while product‐related signals, such as ultraviolet light (UV) spectra as well as static and dynamic light scattering (SLS and DLS), were monitored on‐line. The applicability of the sensors for disassembly monitoring was evaluated under varying processing conditions. HBcAg VLP subunit concentrations were accurately predicted based on UV data using ordinary and partial least squares regression models (Q2 from 0.909 to 0.976). DLS data were used for aggregation monitoring while the SLS intensity qualitatively reflected the disassembly progress.
Optimized prodigiosin production with Pseudomonas putida KT2440 using parallelized noninvasive online monitoring
Authors: Brehl Carl , Brass Hannah U. C. , Lüchtrath Clara , Böckmann Lukas , Ihling Nina , Classen Thomas , Pietruszka Jörg , Büchs Jochen
Published: February 2022

The red pigment prodigiosin is of high pharmaceutical interest, due to its potential applications as an antitumor drug and antibiotic agent. As previously demonstrated, Pseudomonas putida KT2440 is a suitable host for prodigiosin production, as it exhibits high tolerance toward the antimicrobial properties of prodigiosin. So far, prodigiosin concentrations of up to 94 mg/L have been achieved in shake flask cultivations. For the characterization and optimization of the prodigiosin production process, the scattered light of P. putida and fluorescence of prodigiosin was measured. The excitation and emission wavelengths for prodigiosin measurement were analyzed by recording 2D fluorescence spectra. The strongest prodigiosin fluorescence was obtained at a wavelength combination of 535/560 nm. By reducing the temperature to 18 °C and using 16 g/L glucose, the prodigiosin concentration was more than doubled compared with the initial cultivation conditions. The obtained results demonstrate the capabilities of parallelized microscale cultivations combined with noninvasive online monitoring of fluorescence for rapid bioprocess development, using prodigiosin as a molecule of current biotechnological interest.
Comparative Study of the Essential Oil and Hydrosol Composition of Sweet Wormwood (Artemisia annuaL.) from Serbia
Authors: Aćimović Milica , Jeremić Jovana Stanković , Todosijević Marina , Kiprovski Biljana , Vidović Senka , Vladić Jelena , Pezo Lato
Published: February 2022

The most abundant volatile compounds of sweet wormwood (Artemisia annua L.) essential oil were artemisia ketone (25.4 %) andtrans‐caryophyllene (10.2 %), followed by 1,8‐cineole, camphor, germacrene D andβ‐selinene. The major volatile compounds in the hydrosol were camphor (25.1 %), 1,8‐cineole (20.5 %) and artemisia ketone (10.7 %), followed bytrans‐pinocarveol and yomogi alcohol. Tested essential oil was rich in oxygenated monoterpenes and sesquiterpene hydrocarbons, while the former were identified as the major class of volatile compounds in the hydrosol, due to higher water solubility. Classification of all sweet wormwood chemotypes, according to essential oil composition, in available literature (17 studies and 61 accessions) could be done according to four chemotypes: artemisia ketone+artemisia alcohol (most abundant), artemisia ketone, camphor and nonspecific chemotype. According to this classification, essential oil of sweet wormwood from this study belongs to artemisia ketone (content varied between 22.1 and 55.8 %). Bearing in mind that hydrosols are a by‐product of industrial production of essential oils, and the fact that sweet wormwood hydrosol has high contents of camphor, 1,8‐cineole and artemisia ketone, there is a great potential for the use of this aromatic plant primary processing waste product as a water replacement in cosmetic industry, beverages flavoring, for food preservation, as well as in post‐harvest pre‐storage treatments in organic agriculture.
Case report of penile cancer recurrence treated with cetuximab combined with anlotinib
Authors: Dai Shuang , Liu Yan‐Yang , Liu Tao , Zhang Yu , Luo De‐Yun
Published: February 2022

Penile squamous cell carcinoma with pelvic lymph node metastases/recurrence has a poor prognosis. We reported a case with recurrent pSCC was administered cetuximab and anlotinib after failure of first‐line treatment and achieved an effective response. Cetuximab combined with anlotinib may be a new choice for relapsed pSCC.
Coordination and Hydroboration of Ru(II)‐Borate Complexes: Dihydridoborate vs. Bis(dihydridoborate)
Authors: Pathak Kriti , Gayen Sourav , Saha Suvam , Nandi Chandan , Mishra Shivankan , Ghosh Sundargopal
Published: February 2022

Treatment of [Cp*RuCl2]2, 1, [(COD)IrCl]2, 2 or [(p‐cymene)RuCl2]2, 3 (Cp*=η5‐C5Me5, COD= 1,5‐cyclooctadiene and p‐cymene=η6‐iPrC6H4Me) with heterocyclic borate ligands [Na[(H3B)L], L1 and L2 (L1: L=amt, L2: L=mp; amt=2‐amino‐5‐mercapto‐1,3,4‐thiadiazole, mp=2‐mercaptopyridine) led to the formation of borate complexes having uncommon coordination. For example, complexes 1 and 2 on reaction with L1 and L2 afforded dihydridoborate species [LAM(μ‐H)2BHL] 4–6 (4: LA=Cp*, M=Ru, L=amt; 5: LA=Cp*, M=Ru, L=mp; 6: LA=COD, M=Ir, L=mp). On the other hand, treatment of 3 with L2 yielded cis‐ and trans‐bis(dihydridoborate) species, [Ru{(μ‐H)2BH(mp)}2], cis‐7 and trans‐7. The isolation and structural characterization of fac‐ and mer‐[Ru{(μ‐H)2BH(mp)}{(μ‐H)BH(mp)2}], 8 from the same reaction offered an insight into the behaviour of these dihydridoborate species in solution. Fascinatingly, despite having reduced natural charges on Ru centres both at cis‐and trans‐7, they underwent hydroboration reaction with alkynes that yielded both Markovnikov and anti‐Markovnikov addition products, 10 a–d.
New Insight into Dearomatization and Decarbonylation of Antitubercular 4H‐Benzo[e][1,3]thiazinones: Stable 5H‐ and 7H‐Benzo[e][1,3]thiazines
Authors: Richter Adrian , Seidel Rüdiger W. , Graf Jürgen , Goddard Richard , Lehmann Christoph , Schlegel Tom , Khater Nour , Imming Peter
Published: February 2022

8‐Nitro‐4H‐benzo[e][1,3]thiazinones (BTZs) are potent in vitro antimycobacterial agents. New chemical transformations, viz. dearomatization and decarbonylation, of two BTZs and their influence on the compounds’ antimycobacterial properties are described. Reactions of 8‐nitro‐2‐(piperidin‐1‐yl)‐6‐(trifluoromethyl)‐4H‐benzo[e][1,3]thiazin‐4‐one and the clinical drug candidate BTZ043 with the Grignard reagent CH3MgBr afford the corresponding dearomatized stable 4,5‐dimethyl‐5H‐ and 4,7‐dimethyl‐7H‐benzo[e][1,3]thiazines. These methine compounds are structurally characterized by X‐ray crystallography for the first time. Reduction of the BTZ carbonyl group, leading to the corresponding markedly non‐planar 4H‐benzo[e][1,3]thiazine systems, is achieved using the reducing agent (CH3)2S ⋅ BH3. Double methylation with dearomatization and decarbonylation renders the two BTZs studied inactive against Mycobacterium tuberculosis and Mycobacterium smegmatis, as proven by in vitro growth inhibition assays.
Design, Synthesis and X‐Ray Structural Studies of Potent HIV‐1 Protease Inhibitors Containing C‐4 Substituted Tricyclic Hexahydro‐Furofuran Derivatives as P2 Ligands
Authors: Ghosh Arun K. , Kovela Satish , Sharma Ashish , Shahabi Dana , Ghosh Ajay K. , Hopkins Denver R. , Yadav Monika , Johnson Megan E. , Agniswamy Johnson , Wang Yuan‐Fang , Hattori Shin‐Ichiro , Higashi‐Kuwata Nobuyo , Aoki Manabu , Amano Masayuki , Weber Irene T. , Mitsuya Hiroaki
Published: February 2022

The design, synthesis, X‐ray structural, and biological evaluation of a series of highly potent HIV‐1 protease inhibitors are reported herein. These inhibitors incorporate novel cyclohexane‐fused tricyclic bis‐tetrahydrofuran as P2 ligands in combination with a variety of P1 and P2′ ligands. The inhibitor with a difluoromethylphenyl P1 ligand and a cyclopropylaminobenzothiazole P2′ ligand exhibited the most potent antiviral activity. Also, it maintained potent antiviral activity against a panel of highly multidrug‐resistant HIV‐1 variants. The corresponding inhibitor with an enantiomeric ligand was significantly less potent in these antiviral assays. The new P2 ligands were synthesized in optically active form using enzymatic desymmetrization of meso‐diols as the key step. To obtain molecular insight, two high‐resolution X‐ray structures of inhibitor‐bound HIV‐1 protease were determined and structural analyses have been highlighted.
Binary Transition Metal NiFeOx and CoFeOx Cocatalysts Boost the Photodriven Water Oxidation over Fe2TiO5 Nanoparticles
Authors: Melo Mauricio A. , Centurion Higor A. , Machado Giovanna , Souza Flavio L. , Gonçalves Renato V.
Published: February 2022

Although achieving a perfect match between a cocatalyst and a photocatalyst is challenging, it is a key factor to maximize the production of solar fuels. Herein, the nanostructured binary transition metal oxides NiFeOx and CoFeOx, loaded through magnetron sputtering deposition, were employed as cocatalysts for Fe2TiO5 nanoparticles, applied to the oxygen production from solar water splitting. After the coverage of Fe2TiO5 with exceptionally small CoFeOx and NiFeOx nanoparticles, the O2 evolution boosted from 7.0 (pure Fe2TiO5) to 56.0 and 63.0 μmol, respectively, under visible light irradiation. To the best of our knowledge, these performance enhancements are the highest reported for the particulate Fe2TiO5 photocatalyst, so far. The improvements result from the alleviation of charge transfer resistance at the solid/liquid interface, as the binary metal oxides aid the charge carriers separation at the heterojunctions and improve the kinetics of the water oxidation reaction.
Pharmacokinetics and Macrophage Inhibitory Cytokine‐1 Pharmacodynamics of the Murine Double Minute 2 Inhibitor, Navtemadlin (KRT‐232) in Fed and Fasted Healthy Subjects
Authors: Wong Shekman , Krejsa Cecile , Lee Dana , Harris Anna , Simard Emilie , Wang Xiaohui , Allard Martine , Podoll Terry , O'Reilly Terry , Slatter J. Greg
Published: February 2022

This single 60‐mg dose, 4‐period crossover study assessed the effect of food and formulation change on navtemadlin (KRT‐232) pharmacokinetics (PK) and macrophage inhibitory cytokine‐1 (MIC‐1) pharmacodynamics. Healthy subjects (N = 30) were randomized to 3 treatment sequences, A: new tablet, fasted (reference, dosed twice); B: new tablet, 30 minutes after a high‐fat meal (test 1); C: old tablet, fasted (test 2). PK/pharmacodynamic parameters were measured over 0 to 96 hours. Adverse events were mild without any discontinuations. No serious adverse events or deaths occurred. In treatment A, navtemadlin mean (coefficient of variation) maximum concentration (Cmax) was 525 (66) ng/mL, at median time to maximum concentration (tmax) of 2 hours. Mean (coefficient of variation) area under the plasma concentration–time curve from time 0 to time t (AUC0‐t) was 3392 (63.3) ng • h/mL, and arithmetic mean terminal half‐life was 18.6 hours. Acyl glucuronide metabolite (M1)/navtemadlin AUC0‐t ratio was 0.2, and urine excretion of navtemadlin was negligible. After a meal (B vs A), navtemadlin tmax was delayed by 1 hour. Geometric least squares means ratios (90%CI) for navtemadlin Cmax and AUC0‐t were 102.7% (87.4‐120.6) and 81.4% (76.2‐86.9), respectively. Old vs new tablet fasted formulations (C vs A) had geometric least squares means ratios (90%CI) of 78.4% (72.0‐85.3) for Cmax and 85.9% (80.5‐91.7) for AUC0‐t. MIC‐1 Cmax and AUC were comparable across groups; tmax was delayed relative to navtemadlin tmax by ≈8 hours. Navtemadlin AUC0‐t and MIC‐1 AUC0‐t correlated significantly. In conclusion, navtemadlin can be administered safely with or without food; the new formulation does not affect navtemadlin PK. The 60‐mg navtemadlin dose elicited a reproducible and robust MIC‐1 response that correlated well with navtemadlin exposure, indicating that murine double minute 2 target engagement leads to p53 activation.
A novel Frei‐Chen based fragile watermarking method for authentication of an image
Authors: Renklier Ayhan , Öztürk Serkan
Published: February 2022

In recent years, the protection of the intellectual property rights of digital media has become a considerable issue. Especially using digital image editing tools has made it very easy and fast to manipulate images. Therefore, manipulation detection of digital images has become a necessity. This article presents a novel Frei‐Chen based self‐embedding fragile watermarking technique implemented to blocks for image manipulate detection. The block key and the Frei‐Chen based block feature are calculated from the non‐overlapping image blocks of size . Exclusive‐OR operations are applied to the Frei‐Chen based block feature and the block key. After, a nine bit block authentication key is generated from the Frei‐Chen based block feature and the block key. Then the generated authentication key is embedded in the least significant bits of each block. Experimental results prove the effectiveness of the proposed method through the detection of the various attacks and obtain the excellent visual quality of watermarked images. Also, the results demonstrate that the proposed method detects all of the manipulated areas plainly.
Advances in the Catalytic Reductive Amination of Furfural to Furfural Amine: The Momentous Role of Active Metal Sites
Authors: Saini Ms. Kanika , Kumar Sahil , Li Hu , Babu Srinivasarao Arulananda , Saravanamurugan Shunmugavel
Published: February 2022

One‐pot synthesis of sustainable primary amines by catalytic reductive amination of bio‐based carbonyl compounds with NH3 and H2 is emerging as a promising and robust approach. The primary amines, especially furfuryl amine (FUA) derived from furfural (FUR), with a wide range of applications from pharmaceuticals to agrochemicals, have attracted much attention due to their versatility. This Review is majorly comprised of two segments on the reductive amination of FUR to FUA, one with precious (Ru, Pd, Rh) and the other with non‐precious (Co, Ni) metals on different supports and in various solvent systems in the presence of NH3 and H2. The active metal sites generated on multiple supports are accentuated with experimental evidence based on CO‐diffuse reflectance infrared Fourier‐transform spectroscopy, H2 temperature‐programmed reduction, X‐ray photoelectron spectroscopy, and calorimetry. Moreover, this Review comprehensively describes the role of acidic and basic support for the metal on the yield of FUA. Overall, this Review provides an insight into how to design and develop an efficiently robust catalyst for the selective reductive amination of a broad spectrum of carbonyl compounds to corresponding amines.
CO2‐Einbindung in Porenbeton und Kalksandstein durch Recarbonatisierung
Authors: Walther Hartmut B.
Published: February 2022

Die Reduzierung von Treibhausgasemissionen ist gegenwärtig eine der größten Herausforderungen für die Menschheit. Neue Daten zur Freisetzung und Fixierung von CO2 finden deshalb Eingang in Ökobilanzen und Umweltproduktdeklarationen (EPD) von Bauprodukten und betreffen gem. der gültigen DIN EN 15804:2020‐03 nicht nur die Produktherstellung, sondern den gesamten Produktlebenszyklus. Bindemittelgebundene Baustoffe nehmen über dessen Verlauf CO2 wieder auf, das bei der Herstellung von Zement und Branntkalk freigesetzt wurde. Für Porenbeton und Kalksandstein kann diese Menge aus dem Rohstoffeinsatz errechnet werden. Die Reduzierung ist absolut und auf die eingesetzte Bindemittelmasse bezogen. Damit kann sie umfassend und ohne Einfluss des verwendeten Datenbanksystems der Hintergrunddaten in EPD Anwendung finden.