bluuebunny/crossref_metadata_2025 huggingface dataset:
Semiotics Analysis of Tempo and Gatra Magazine Cover for September 2020 Edition
Authors: Karina Kusuma WIjaya  , Ruslan Ramli  , Sumartono Sumartono
Published: January 2024

This study discusses symbols or signs related to the coronavirus (Covid-19) pandemic that are found on the covers of Tempo and Gatra magazines edition September 2002. The two magazines has front cover to show the pandemic situation in Indonesia. At the time Indonesia was in a very serious pandemic with a number of victims every day both ordinary people or medical officer. The purpose of this study is to determine the meaning contained on cover of Tempo and Gatra by using semiotics analysis of the Charles Sanders Peirce model. It consists of three points namely sign, object, and interpretant. The research method uses a descriptive qualitative approach. The data obtained in this study were sourced from documentation and literature study such as books, literatures, notes, and a number of other related websites. The result of the research is they differ each other. Tempo tries to portray The Minister of The Health of Republic of Indonesia Terawan Agus Putranto as a character who has fun and takes unilateral advantage of the policies he makes. While on the cover of Gatra, Terawan Agus Putranto is described as overwhelmed and incompetent in fulfilling his duties as minister of health.
Political Communication and Gender: An Analysis of Public’s Perceptions Toward the Election of the 2017 Mayoral Candidates of Banda Aceh
Authors: Nur Anisah  , Zakirah Azman  , Rahmat Saleh  , Lia Monita  , Nadia Muharman  , Maini Sartika
Published: January 2024

This research attempted to describe the public's perception toward political communication ofcertain gender in winning the mayoral election of Banda Aceh in 2017 and to find outpeople's perceptions on whether gender is able to influence the candidacy in winning themayoral election of Banda Aceh in 2017. This research was conducted by using qualitativemethod and took place in Banda Aceh. The process of retrieving data and information of theresearch is obtained from the review of literature. This research employed structured-interview on expert informants from the Independent Election Commission, the Head ofIslamic Shari'a Office of Banda Aceh and the voting community (male and female) selectedby using purposive sampling. The theory used in this research is the theory of socialcognition, a learning theory explaining the patterns of behavior. This theory was developedby Albert Bandura since 1960 and emphasized the tendency to imitate or emulate whatpeople see through the media or other people. There are interrelationships betweenindividuals, environment and behavior. In this case, the political communication carried outby the two mayor candidates of Banda Aceh stemmed a new problem since one of thecandidates was female. As the result, this issue triggered a controversy in the community interms of contradicting the teachings of Islamic Shari'a among candidates and within thecommunity regarding gender. In terms of political participation, women have been givenspecial proportion in both management of political parties and legislative candidacy (30%).Meanwhile, this arrangement is still not well-considered because there are no strict sanctionsfor political parties. In respect of sociological aspects, there are still many serious problems, starting from women's interest which is still low in the political sphere as well as theproblems of gender bias experienced by women. Furthermore, the urgency of women'srepresentation in the political sphere is hampered due to negative stereotypes towards womenand the level of patriarchal knowledge which still sticks on people's lives.
The Political Public Relations of Muhammadiyah Leader in the Covid-19 Pandemic Era
Authors: Harmonis Harmonis , Diah Febrina
Published: January 2024

The purpose of the study on Political Public Relations (PRP) of Muhammadiyah Leaders in the era of the covid-19 pandemic is to find out about the relationship in the political context between the leadership of the Muhammadiyah Branch and the public or stakeholders in their respective branches, especially in the era of the covid-19 pandemic. The concepts used are political public relations and political public relations activities. This study uses qualitative methods with data collection techniques through interviews and document analysis. The results of the study show that although administratively branch leaders have not mapped or recorded data based on modern and professional administrative guidelines and stored in a complete data and documentation center (Pusdatin) about stakeholders, in general branch leaders have understood that those who are stakeholders or those who are interested and who The interests of the Muhammadiyah Branch in East Jakarta are the community around the branch, community leaders or opinion leaders, the sub-district government and political parties and the media. With regard to political public relations activities, the leadership of Muhammadiyah branches throughout East Jakarta varies widely, both internally (relationships within the Muhammadiyah organization, fellow members or fellow administrators), and external (with outside members and administrators). In conclusion, the leadership of Muhammadiyah branches throughout East Jakarta, still really needs to increase data collection and carry out various activities related to political public relations, specifically conducting data collection and activities that are well documented through the data and information center (Pusdatin) in each branch. The benefit is that when there are parties who need information, especially regarding stakeholders and political public relations activities of branch leaders, it can be easily provided to those in need.
Superiority and Mimicry in Korea Reomit
Authors: Tanjung Sumekar
Published: January 2024

This study aims to describe the hegemonic relationship between Jang Hansol and the other who initiate superiority and mimicry issues on the Korea Reomit channel. Jang Hansol's popularity clearly complements the hegemonic discourse of Korean colonialism in Indonesia, as obviously seen in the form of hybrid culture. The importance of this research lies in the absence of previous studies that examined the relationship between the colonized and the colonizer on YouTube. The researcher sees the presence of binary opposition between Jang Hansol and three content creators who play a role in their respective areas of subordination. This study uses a qualitative descriptive method by dissected three collaborative videos between Jang Hansol and Jerome Polin Sijabat, Alphiandi, and Natya Shina. It is readily apparent that the three videos serve as Jang Hansol's colonial strategy in maintaining his power as the superior while at the same time subjugating the position of the colonized. The findings show two hegemonic relations. First, the hierarchical relation shows that the colonizer expresses speech through native languages to strengthen his position as superior. Second, conflicting relations of the other show that the attempts to imitate the colonizer only produce imperfect imitation. These two relations show the Korean hegemony that has been built between Jang Hansol and the other along the surgin Korean Wave.
Deconstructing Collywood: A Conceptual Discourse on the Camerooness and Nigerianisation of Cameroon’s Video Film Industry
Authors: Floribert Patrick C. Endong
Published: January 2024

Since its inception in 2008, the Cameroonian video film industry (codenamed Collywood) has attracted mitigated criticism from both Cameroonian and foreign commentators. This criticism has partly bordered on the “camerooness” versus the “foreignness” of Collywood. While a number of critics are of the persuasion that the above-mentioned cinematic movement is not only nigerianised but one of the multiple vectors of the nigerianisation of the Cameroonian cinema industry, others instead think that, by copying the Nollywood model, Cameroonian cineastes may boost their film production and ultimately inundate the local market with movies that speak to local cultures and reflect the quotidian experiences of Cameroonians. Using three methods of data collection (namely secondary sources, unofficial interviews with cineastes and critical observations), this paper revisits the above-mentioned debate and some of the thorny issues that have stemmed from the emergence, evolution, and enculturation of Collywood. The paper aims specifically at examining the camerooness versus the nigerianess of the Collywood movement. The paper attains four principal objectives: in the first place, it critically examines the creation and vision of Collywood, as well as its representativeness of Cameroon’s socio-cultural dynamics. In the second place, it explores the extent to which Collywood may be said to capture the aspirations of Cameroonian cineastes. Thirdly, the paper critically examines the extent to which Collywood is a nigerianised movement and an agent of the Nollywoodisation of the Cameroonian film industry. In the last place, it shows how the idea of copying the Nollywood model may enable or has been enabling the success of Collywood. Among other findings, the paper argues that Collywood is majorly a Nollywoodised Anglophone movement. Its Nigerianisation is just an inevitable outcome of the globalization/transnationalisation of the Nollywood model.
Local Product Promotional Content on President Joko Widodo’s Instagram
Authors: Wenny Maya Arlena  , Rasyid Mohammad Ichsan
Published: January 2024

So far, Indonesia has only been known as a big market for global products. So positioning Indonesia as a country that making domestically produced products as well as a producer country becomes a very important nation step. President Jokowi through his Instagram often promotes products that made in the country, and the domestic consumers often responded positively. This study seeks to understand how President Jokowi promoted locally made products through his Instagram. Using literature study as a data collection method, content analysis as an analytical technique, and the AIDA Model as a theoretical framework to describe how the uploaded promotional content was being rolled out. This study found that the President's promotional posts are in line with the AIDA framework, and in his posts, the president not only creates awareness and interest, but also seeks to build a sense of pride and confidence towards the locally made products and the nation production capabilities amongst the audiences, particularly the followers. From this research, researchers can further discuss the effects and how audiences interpret the promotional content of President Jokowi.
Global Times’ Framing for China’s Noopolitics in the South China Sea
Authors: Maulaya Mahbi , Wafi Fadhlil
Published: January 2024

The South China Sea (SCS) is an area of water endowed with rich natural resources and a strategic location for geopolitical interests. As the consequence, China has put the SCS in its list of the Great Rejuvenation Goals. China's modus operandi to attain its SCS ambition has been various in the way. It ranges from making land reclamation and artificial islands, sending citizens to artificial islands and further applying its jurisdiction and administration, conducting military activities, and wielding diplomacy efforts. Another path China undergoes to manifest its maritime empire in the SCS is media framing. This study highlights how China employs Global Times, its state-owned media, to construct the mind frame that the SCS belongs to China. To achieve the objective of the study, this paper use Zhongdang Pan and M Kosicky's framing analysis to identify Global Times' type of framing and qualitative method to seek the intention of the frame. This paper finds that Global Times assist the Chinese government in claiming the SCS by syntactic and rhetorical framing; dominantly quoting pro-China experts/academics/statesman, emphasising 'sovereignty' words and displaying a narration that the SCS belongs to China, using Chinese to name the islands in the SCS, and echoing 'no conflict in the SCS' rhetoric. This study proves that China is also pursuing its South China Sea Dream by exercising noopolitics.
APPLICATION OF PSO-LSSVM IN PREDICTION AND ANALYSIS OF SLOW DRILLING (RATE OF PENETRATION)
Authors: Latuny Wilma
Published: January 2024

The benefits of drilling include reducing the total time, maintaining the lowest possible risk, saving costs, and increasing efficiency, which occurs in (the planning and exploration stages). Slow drilling refers to a rate of penetration (ROP) that is not at the desired level. ROP characterizes the speed at which the drill bit penetrates the underlying rock to deepen the borehole, as it is directly related to controlling the speed and efficiency of drilling which ultimately impacts development costs. Predicting ROP is a very important step to optimize drilling with Machine Learning that can assist in solving complex problems with maximum possible efficiency. The model used is PSO-LSSVM treats the penetration drill bit as a continuous process. It takes drilling data sequentially, continuously predicts ROP, and achieves better ROP prediction results. In this case, Hole Depth, weight on bit (WOB), Bit Rotation per minute (RPM), Torque, Bit Depth, Time of Penetration, Hook Load, and Standpipe Pressure, demonstrated influence in keeping ROP at a high level. According to the results, the PSO-LSSVM algorithm can be used for the prediction of ROP in well X. thus providing a solution for prediction and control of operating effects which can result in a fast penetration rate and better efficiency in drilling.
Insight into selectivity differences of glycerol electro-oxidation on Pt(111) and Ag(111)
Authors: Meng Zhe , Tran David , Hjelm Johan , Kristoffersen Henrik , Rossmeisl Jan
Published: January 2024

Electro-oxidation is a way to utilize glycerol, a byproduct of biodiesel production, to produce fuels and feedstock chemicals for the chemical industry. A significant challenge is to get products with high selectivity, so it is desirable to understand the glycerol oxidation mechanisms in further details. Using density functional theory calculations, we investigate possible glycerol oxidation intermediates on Pt(111) and Ag(111). We find that the different adsorption preferences of the intermediates on Pt (adsorption via carbon atoms) and on Ag (adsorption via oxygen atoms) lead to different preferred reaction pathways, resulting in different products. The reaction pathways on both surfaces involve glyceraldehyde as a key intermediate, however, upon further oxidation, Pt(111) preferentially produces glyceric acid (CH2OH-CHOH-COOH), while on Ag(111) C-C bonds are broken and leads to production of glycolaldehyde and formic acid (CH2OH-CHO and HCOOH). These predictions agrees well with the experimental outcome of electro-oxidation of glycerol on Pt and Ag surfaces. Our study therefore provides useful insights for optimizing the selectivity of glycerol oxidation and improving the utilization of glycerol.
Scoring Methods in Lead Optimization of Molecular Glues
Authors: Jia Lei , Weiss Dahlia , Shields Benjamin , Claus Brian , Shanmugasundaram Veerabahu , Johnson Stephen , Riggs Jennifer , Zapf Christoph
Published: January 2024

Efficiency metrics are a simple and effective medicinal chemistry tool to track small molecule progress toward a preferred profile in lead optimization. Targeted protein degradation can be mediated by small molecules that act as a molecular glue between an E3 ligase and a protein target. Molecular glue compounds are characterized by the potency and the depth of their protein degradation dose response measurement, representing additional complexity toward identifying drug candidates. We developed degradation efficiency metrics that are based on both potency and depth of degradation. They serve as basic scoring functions to effectively track lead optimization objectives. In recent years, applying machine learning (ML) has effectively accelerated lead optimization. We established a comprehensive scoring function to guide molecular glue design. This manuscript describes how such a merit score was retrospectively applied to track optimization of a clinical molecular glue degrader series that resulted in the identification of Golcadomide (CC-99282). The application of these efficiency metrics in conjunction with a ML based merit score may accelerate identification of glue molecules development candidates.
Rapid glycan labelling with fluorogenic molecular rotor dyes and nucleic acid stains responding to changes of the cell surface
Authors: Kocak Alen , Homer Amal , Feida Antonia , Telschow Florian , Gorenflos Jacob , Baydaroglu Cihan , Gradzielski Michael , Hackenberger Christian , Alexiev Ulrike , Seitz Oliver
Published: January 2024

Herein, we introduce a dual-labelling technique for covalent modification of cell surfaces with fluo-rescent molecular rotor (FMR) dyes and environmentally insensitive fluorescent dyes. For this pur-pose, we combined an improved method for chemical reactions on sialic acid residues with FMR-dye hydrazides including dyes commonly used to stain nucleic acids. Fluorescence of FMR dyes increases upon molecular crowding and with increasing viscosity providing options for fluorogenic labelling of cell surfaces and detecting changes of cell surfaces that, for example, affect molecular crowding or local viscosity. The method involves mild periodate oxidation of cell surface glycans followed by or-ganocatalyzed dye conjugation. Both steps are performed within a total of 15 min at 25 °C, avoiding cold stress of cells. We show labelling glycans with FMR dyes such as 9-(2-carboxy-2-cyanovinyl)julolidine (CCVJ) or Cyanine 3 (Cy3) and the nucleic acid stain thiazole orange (TO) pro-vides sufficiently strong signals to allow fluorescence microscopy imaging of surfaces of A549, HeLa and CEM cells. Measurements with mucin suggest that the close proximity to glycans induced upon formation of covalent bonds is very efficient in hindering FMR torsional motions. We demonstrate that the fluorescence of CCVJ and TO on cell surface glycans and isolated mucin is influenced by the action of the disulfide-cleaving agent TCEP. Co-labelling of cells with CCVJ and an environmentally insensitive AF568 dye revealed a TCEP-induced decrease in the intensity CCVJ fluorescence, which did not occur when the dye was studied in glycerol solution, consistent with a decrease of the fluores-cence lifetime determined by fluorescence lifetime imaging microscopy (FLIM). This indicates that glycan-bound FMR dyes respond to changes in friction that hinder dye intramolecular rotation, poten-tially enabling the detection of changes occurring to surfaces of epithelial cells during disease and therapeutic intervention.
NMR Analyses of-1,3-Bridged Calix[4]arene Conformations
Authors: Madigan Ryan P , Fulton Brandon B , Gerro Whitney E , Nino Paula F , Vilaysane Bryce , Dominguez Narda R , Carlson Austin J , Jones Benjamin J P , Lovely Carl J , Foss Jr. Frank W
Published: January 2024

Calix[4]arenes are cyclic oligomers known for their unique molecular architecture that provides a versatile platform for various applications in supramolecular chemistry. When strategically coupled with fluorescent molecules, their molecular recognition enables highly selective and sensitive chemosensors. The introduction of bridging groups at 1,3 phenolic positions within the calix[4]arene framework has the potential to yield distinctive structural features and enhanced functional properties. Despite their opportunities, calix[4]arene preparation requires careful characterization of conformationally restricted rotomers. We used a combination of experimental and computational techniques to elucidate the three-dimensional structure and conformational dynamics of a 1,3-bridged calix[4]arene derivative. Nuclear magnetic resonance (NMR) spectroscopy, Density Functional Theory (DFT) based optimization, and Boltzmann-weighted NMR chemical shift calculations are used to determine the precise molecular structure of the binding domain in our novel calix[4]arene derivative, including conformation, bond distance, and angle details.
Molecular O2 Dimers and Lattice Instability in a Perovskite Electrocatalyst
Authors: Bosse Jan , Gu Jian , Choi Jaewon , Roddatis Vladimir , Zhuang Yong-Bin , Kani Nagaarjhuna A. , Hartl Anna , Garcia-Fernandez Mirian , Zhou Ke-Jin , Nicolaou Alessandro , Lippert Thomas , Cheng Jun , Akbashev Andrew
Published: January 2024

Structural degradation of oxide electrodes during electrocatalytic oxygen evolution reaction (OER) is a major challenge in water electrolysis. Although the OER is known to induce changes in the surface layer, little is understood about its effect on the bulk of the electrocatalyst and the overall phase stability. Here, we show that under OER conditions a highly active SrCoO3-x electrocatalyst develops bulk lattice instability, which results in the formation of molecular O2 dimers in the bulk and nanoscale amorphization induced via chemo-mechanical coupling. Using high-resolution resonant inelastic X-ray scattering (RIXS) and first principles calculations, we unveil the potential-dependent evolution of lattice oxygen inside the perovskite and demonstrate that O2 dimers are stable in a densely packed crystal lattice, thus challenging the assumption that O2 dimers require sufficient inter-atomic spacing. We also show that SrCoO3-x develops unusual amorphous bands under intercalation-induced stress that indicates the lattice requires a remarkably low energy to undergo the order-disorder transition. As a result, we propose the amorphization energy as a descriptor of the electrocatalyst stability that can be calculated from the first principles. Our study demonstrates that extreme oxidation of electrocatalysts under OER can intrinsically destabilize the lattice and result in bulk anion redox and disorder, suggesting why some oxide materials are unstable and develop a thick amorphous layer under water electrolysis conditions.
How 2D nanoflakes improve transport in mixed matrix membranes: insights from a simple lattice model and dynamic mean field theory
Authors: Yuan Tianmu , Sarkisov Lev
Published: January 2024

Mixed matrix membranes (MMMs), incorporating graphene and graphene oxide structural fragments, have emerged as promising materials for challenging gas separation processes. What remains unclear is the actual molecular mechanism responsible for the enhanced permeability and perm- selectivity of these materials. With the fully atomistic models still unable to handle the required time and length scales, here we employ a simple qualitative model based on the lattice representa- tion of the physical system and Dynamic Mean Field theory. We demonstrate that the performance enhancement results from the flux-regularization impact of the 2D nanoflakes, and that this effect sensitively depends on the orientation of the nanoflakes and the properties of the interface between the nanoflakes and the polymer.
Quantitative and rapid detection of nanoplastics labeled by luminescent metal phenolic networks using surface enhanced Raman scattering
Authors: Ye Haoxin , Gao Guang , Yang Tianxi
Published: January 2024

The rising incidence of nanoplastics contamination in environmental ecosystems has led to substantial health risks. Traditional analysis methods are suboptimal due to their inability to efficiently analyze nanoplastics at low concentrations and time-consuming operations. Herein, we developed an innovative strategy, employing luminescent metal–phenolic networks (L-MPNs) coupled with surface-enhanced Raman spectroscopy (SERS) to separate and label nanoplastics, thus facilitating rapid, sensitive and quantitative detection of nanoplastics. We used L-MPNs composed of zirconium ions, tannic acid and rhodamine B, to uniformly label diverse sizes (50-500 nm) and types of nanoplastics (i.e., polystyrene, polymethyl methacrylate, polylactic acid). Rhodamine B, serving as a Raman reporter in L-MPNs-based SERS tags can offer sufficient sensitivity for trace measurement of nanoplastics and L-MPNs labeling can also facilitate separation of nanoplastics from liquid medium. By using a portable Raman instrument, our method offers cost-effective, rapid, and field-deployable detection features with excellent sensitivity in nanoplastic analysis with a limit of detection of 0.1 ppm. Moreover, this study provides a highly promising strategy for the robust and sensitive analysis of a wide range of particle analytes through the effective labeling performance of L-MPNs when coupled with SERS techniques.
A lysate-based TR-FRET approach for the facile quantification of cellular drug concentration
Authors: Payne N. Connor , Mazitschek Ralph
Published: January 2024

Many pharmacologically relevant drug targets are located inside cells. The development of therapeutically active small molecule modulators for intracellular targets requires that successful drug candidates can efficiently pass through the plasma membrane at higher rates than their metabolic inactivation or expulsion by drug efflux pumps. Such knowledge is invaluable for correlating biochemical and cellular activity, and for guiding ligand optimization. Despite the critical im-portance of this metric, current methodologies for measuring the intracellular concentration of non-fluorescent small molecules have many limitations, significantly restricting the ability of medicinal chemists to readily and routinely measure cellular drug concentration. We here introduce a straightforward, high-throughput TR-FRET assay platform based on CoraFluor technology to readily quantify the abundance of biologically active small molecules in whole cell lysates. Our approach builds on existing homogenous ligand displacement assays and does not require any additional reagents or equipment, enabling the comprehensive biochemical and cellular characterization of small molecule ligands.
Machine learning based knowledge discovery and modeling of silicon content of molten iron from a blast furnace
Authors: Nistala Sri Harsha , Biswas Jayasree , Kumar Rajan , Pandya Rohan , Rathore Pradeep , Mynam Mahesh , Runkana Venkataramana , Raj Sristy , Ganguly Adity
Published: January 2024

It is necessary to maintain the silicon content of hot metal in a stipulated range to improve the productivity and energy consumption of a blast furnace. Significant research therefore went into the development of data-driven models to predict hot metal silicon content in real-time. However, these models use only a small subset of blast furnace variables that are chosen using prior process knowledge. As each blast furnace is unique in its operation, using pre-selected variables would lead to sub-optimal models. To address this, a machine learning based ensemble feature selection and modeling approach is proposed. In this approach, all the available furnace variables are ranked using multiple feature selection techniques based on their impact on silicon content. The individual ranks are combined to obtain an ensemble ranking of variables and the top variables in the ranking are used to build data-driven silicon prediction models. This approach is applied to an industrial blast furnace wherein 374 variables are used to obtain the ensemble ranking. While some of the top 100 variables in the ensemble ranking matched those that are commonly used in silicon predictions models, several new variables have also been identified. Silicon prediction models trained using the top 100 variables resulted in a hot rate of ~90% demonstrating the efficacy of the proposed approach. Real-time predictions from the models will enable blast furnace operators to control the silicon content without having to wait for laboratory results.
Mechanism of Plasmon-Driven Molecular Jackhammers in Mechanical Opening and Disassembly of Membranes
Authors: Orozco Ciceron , Vardanyan Vardan , Lopez-Jaime Katherine , Wang Zicheng , Seminario Jorge , Kolomeisky Anatoly , Tour James
Published: January 2024

Plasmon-driven molecular jackhammers (MJH) are a type of molecular machine that converts photon energy into mechanical energy. Upon insertion into lipid bilayers followed by near infrared light activation, plasmon-driven MJH mechanically open cellular membranes through a process that is not inhibited by reactive oxygen species (ROS) inhibitors and does not induce thermal heating. The molecular mechanism by which the plasmon-driven MJH open and disassembles cellular membranes has not hitherto been established. Here we differentiate the mechanical mechanism in MJH from the ROS-mediated chemical effects in photodynamic therapy or thermal effects in photothermal therapy. We further present a detailed molecular mechanism for the plasmon-driven MJH disassembly of lipid bilayers. The mechanical effects in plasmon-driven MJH disassembly processes on artificial lipid bilayers is done using ROS-unreactive saturated phytanoyl phospholipids. We were able to capture in real-time the lipid bilayer disassembly by MJH using fluorescence confocal microscopy on saturated phospholipids in giant unilamellar vesicles.
Sampling Chemical Space: Activity Cliffs, Extended Similarity, and ML Performance
Authors: Lopez-Perez Kenneth , Miranda-Quintana Ramon
Published: January 2024

The presence of Activity Cliffs (ACs) has been known to represent a challenge for QSAR modeling. With its data high dependency, Machine Learning QSAR models will be highly influenced by the activity landscape of the data. We propose several extended similarity and extended SALI methods to study the implications of ACs distribution on the training and test sets on the model’s errors. Non-uniform ACs and chemical space distribution tends to lead to worse models than the proposed uniform methods. ML modeling on AC-rich sets needs to be analyzed case-by-case. Proposed methods can be used as a tool to study the dataset, with random and uniform splitting being the better overall data splitting alternatives.
Optimized 13C-TrEnDi enhances the sensitivity of plasmenyl ether glycerophospholipids and demonstrates compatibility with other derivatization strategies
Authors: Shields Samuel , Canez Carlos , Rosales Christian , Roberts Joshua , Bourgaize Hillary , Pallister Peter , Manthorpe Jeffrey , Smith Jeffrey
Published: January 2024

The identification and quantitation of plasmalogen glycerophospholipids is challenging due to their isobaric overlap with plasmanyl ether-linked glycerophospholipids, susceptibility to acid degradation, and their typically low abundance in biological samples. Trimethylation enhancement using diazomethane (TrEnDi) can be used to significantly enhance the signal of glycerophospholipids through the creation of quaternary ammonium groups producing fixed positive charges using 13C-diazomethane in complex lipid extracts. Although TrEnDi requires a strong acid for complete methylation, we report an optimized protocol using 9.6 mM HBF4 with the subsequent addition of a buffer solution that prevents acidic hydrolysis of plasmalogen species and enables the benefits of TrEnDi to be realized for this class of lipids. These optimized conditions were applied to aliquots of bovine liver extract (BLE) to achieve permethylation of plasmalogen lipids within a complex mixture. Treating aliquots of unmodified and TrEnDi-derivatized BLE samples with 80% formic acid and comparing their liquid chromatography mass spectrometry (LCMS) results to analogous samples not treated with formic acid, enabled the identification of 29 plasmalogen species. On average, methylated plasmalogen species from BLE demonstrated 2.81-fold and 28.1-fold sensitivity gains over unmodified counterparts for phosphatidylcholine and phosphatidylethanolamine plasmalogen species, respectively. Furthermore, the compatibility of employing 13C-TrEnDi and a previously reported iodoacetalization strategy was demonstrated to effectively identify plasmenyl-ether lipids in complex biological extracts at greater levels of sensitivity. Overall, we detail an optimized 13C-TrEnDi derivatization strategy that enables the analysis of plasmalogen glycerophospholipids with no undesired cleavage of radyl groups, boosting their sensitivity in LCMS and LCMS/MS analyses.
The interplay between calcite crystal nucleation on polydiacetylene template and its amorphization by phosphoserine
Authors: Tah Bidisha , Berman Amir , Nasser Saja , Jopp Jürgen , Goobes Gil , Stepansky Anna , Glick Yehonatan
Published: January 2024

Organisms use a diverse range of organic-inorganic hybrid materials for a variety of purposes, including mechanical support, navigation and protection. These materials are mostly crystalline and are characterized by unique composition, polymorph, crystallite size, shape and crystallographic orientation. The crystalline biominerals are generally formed through amorphous, hydrated transient minerals, but in some, the amorphous phases are stable and persist. Using a biomimetic approach, we address aspects of biological mineralization in vitro and gain insight into the processes and interactions that play roles in the natural systems, in-vivo. In this work, we demonstrate two essential but conflicting methods that are likely to act simultaneously in many mineralizing systems. These are directed crystal nucleation on organic templates, and on the other hand, crystal inhibition to produce the transient amorphous phase. The experimental method in this project mimics aspects of biomineralization processes of calcium carbonate (CaCO3) nucleation. Polydiacetylene (PDA) – a robust, linear conjugated polymer, made from amphiphilic long-chain diacetylene monomers, which upon surface compression, followed by UV polymerization form an ultrathin, stable monolayer structure. PDA simulates the organic template for the CaCO3 crystallization in our experimental system in that it exposed a dense array of acidic groups in well-defined orientation and being a semi-rigid template surface. On PDA templates, calcite crystals nucleate from a (01.2) face and in every single domain of the PDA film they are all coaligned with the crystals' a-axes oriented parallel to the polymer backbone. Supersaturated solutions for CaCO3were prepared either by mixing CaCl2 and Na2CO3, or by bubbling CO2 into CaCO3 suspension, or by slow diffusion of ammonium carbonate into CaCl2 solution in a desiccator. Phosphoserine (P-ser) was added to CaCO3 deposition systems as a crystallization inhibitor, which results in amorphous calcium carbonate (ACC) deposition. The phosphate groups substitute a part of the carbonate groups during the deposition and this way, inhibit the crystallization process. Various concentrations of P-ser in deposition system on PDA templates result in different morphologies and degrees of crystallinity of CaCO3. In this biomimetic system, we demonstrate the conflicting, yet simultaneous influences on biological crystal formation, namely the ordered template and crystal nucleation and crystal inhibition.
Trivalent Cations Slow Electron Transfer to Macrocyclic Heterobimetallic Complexes
Authors: Karnes Joseph , Kumar Amit , Hopkins Leseberg Julie , Day Victor , Blakemore James
Published: January 2024

Incorporation of secondary redox-inactive cations into heterobimetallic complexes is an attractive strategy for modulation of metal-centered redox chemistry, but quantification of the consequences of incorporating strongly Lewis acidic trivalent cations has received little attention. Here, a family of seven heterobimetallic complexes that pair a redox-active nickel center with La3+, Y3+, Lu3+, Sr2+, Ca2+, K+, and Na+ (in the form of their triflate salts) have been prepared on a heteroditopic ligand platform to understand how chemical behavior varies across the comprehensive series. Structural data from X-ray diffraction analysis demonstrate that the positions adopted by the secondary cations in the crown-ether-like site of the ligand relative to nickel are dependent primarily on the secondary cations’ ionic radii, and that the triflate counter-anions are bound to the cations in all cases. Electrochemical data, in concert with electron paramagnetic resonance (EPR) studies, show that nickel(II)/nickel(I) redox is modulated by the secondary metals; the heterogeneous electron transfer (ET) rate is diminished for the derivatives incorporating trivalent metals, an effect that is dependent on steric crowding about the nickel metal center and that was quantified here with a topographical free-volume analysis. As related analyses carried out here on previously reported systems bear out similar relationships that were not noted in prior work, we conclude that the placement and identity of both the secondary metal cations and their associated counter-anions can afford unique changes in the (electro)chemical behavior of heterobimetallic species.
Visualization of membrane localization and functional state of CB2R pools by matched agonist and inverse agonist probe pairs
Authors: Wasinka-Kalwa Malgorzata , Omran Anahid , Mach Leonard , Bouma Jara , Scipioni Lucia , Li Xiaoting , Radetzki Silke , Mostinski Yelena , Schippers Maria , Gazzi Thais , Horst van der Cas , Brennecke Benjamin , Hanske Annaleah , Kolomeets Yuliya , Guba Wolfgang , Sykes David , von Kries Jens Peter , Broichhagen Johannes , Hua Tian , Veprintsev Dmitry , Heitmann Laura , Oddi Sergio , Maccarrone Mauro , Grether Uwe , Nazare Marc
Published: January 2024

The diversity of physiological roles of the endocannabinoid system has turned it into an attractive yet elusive therapeutic target. However, chemical probes with various functionalities could pave the way for a better understanding of the endocannabinoid system at the cellular level. Notably, inverse agonists of CB2R – a key receptor of the endocannabinoid system - lagged behind despite the evidence regarding the therapeutic potential of its antagonism. Herein, we report a matched fluorescent probe pair based on a common chemotype to address and visualize both the active and inactive states of CB2R, selectively. Alongside with extensive cross-validation by flow cytometry and confocal microscopy, we successfully visualize the intracellular localization of CB2R pools in live cells. The synthetic simplicity together with the high CB2R-selectivity and specificity of our probes, turn them into valuable tools in chemical biology and drug development that can benefit the clinical translatability of CB2R-based drug.
How Low can you Go? Nanoscale Membranes for Efficient Water Electrolysis
Authors: Cohen Lucas A. , Weimer Matthew S. , Yim Kyungmin , Jin Jingjing , Fraga Alvarez Daniela V. , Dameron Arrelaine A. , Capuano Christopher B. , Ouimet Ryan J. , Fortiner Serafina , Esposito Daniel V.
Published: January 2024

Motivated by the need to lower the cost of hydrogen (H2) production by water electrolysis, significant research efforts are focused on making proton (H+) exchange membrane (PEM) water electrolyzers more efficient and capable of operating at higher current densities. These aims can be met by making H+ conducting membranes thinner, which has the effect of lowering ohmic drops across the membrane that represent the largest efficiency loss at high current densities (>2 A cm-2). However, decreasing membrane thickness below 50 microns is not trivial due to trade-offs between membrane resistance, H2 cross-over (safety), membrane degradation, and manufacturing throughput. Herein, descriptions of key processes, limitations, and trade-offs that arise in thin membranes are provided that can be used to guide the design of ultrathin (i.e., sub-micron thick), low-resistance membrane materials that have potential to transform the field of clean H2 production.
A robust “bottom up” proteomics pipeline is integral for assessing protein structure using hydroxyl radical protein footprinting mass spectrometry.
Authors: Jain Rohit , Jeon Nayeon , Kiselar Janna , Chance Mark R.
Published: January 2024

Hydroxyl Radical Protein Footprinting (HRPF) monitors macromolecular structure and dynamics by utilizing hydroxyl radicals to probe the solvent-accessible side chains of proteins. Hydroxyl radicals form irreversible covalent bonds with protein side chains based on their solvent accessibility and intrinsic reactivity. Following labeling, bottom-up proteomics which involves protease digestion and liquid chromatography (LC-MS/MS) coupled with mass spectrometry, is routinely employed to detect and quantify the modified protein side chains. The HRPF technique has been a breakthrough in the field of structural biology, enabling the assessment of structures and interrelationships between proteins, protein-drug complexes or such macromolecular mixtures. It is now being extended to complex applications such as in-cell and in-vivo studies. This perspective focuses on detailing aspects of peptide separations technology in HRPF, with a particular emphasis on chromatography. The discussion further encompasses the HRPF methodology, its current limitations, recent developments, and proposed ideas for future developments for selected research fields.
Chaperone-derived Cu(I)-binding peptide nanofibers disrupt copper homeostasis in cancer cells
Authors: Thekkeyil Jeena M. , Link Julian , Zhang Jian , Baptista Luis Andre , Jonker Hendrik R. A. , Harley Iain , Turunen Petri , Cui Liyang , Lieberwirth Ingo , Landfester Katharina , Graf Robert , Wagner Manfred , Rao Jianghong , Ng David , Weil Tanja
Published: January 2024

Copper (Cu) is a transition metal that plays crucial roles in the human cellular metabolism. Cu+ homeostasis is upregulated in many cancers and contributes to tumorigenesis. However, therapeutic strategies to target Cu+ homeostasis of cancer cells are rarely explored because small molecule Cu+ chelators have poor binding affinity in comparison to the intracellular Cu+ chaperons, enzymes, or ligands. To address this challenge, we introduce a Cu+ chaperon-inspired supramolecular approach to disrupt Cu+ homeostasis in cancer cells that induces programmed cell death. The Nap-FFMTCGGCR peptide self-assembles into nanofibers inside cancer cells with high binding affinity and selectivity for Cu+ due to the presence of the unique MT/CGGC peptide motif, which is conserved in u+ binding intracellular proteins. Nap-FFMTCGGCR exhibits cytotoxicity towards triple negative breast cancer cell lines (MDA-MB-231), impairs the activity of Cu+-dependent co-chaperon super oxide dismutase 1 (SOD1) and induces overproduction of reactive oxygen species (ROS) to initiate apoptosis. In contrast, Nap-FFMTCGGCR has minimal impact on normal HEK 293T cells. Control peptides show that the self-assembly and Cu+ binding properties must work in synergy to successfully disrupt Cu+ homeostasis. We show that assembly-enhanced affinity for metal ions opens new therapeutic strategies to address disease-relevant metal ion homeostasis.
Low-toxicity nanoMolar scaffolds with hundreds of variants generated by computational co-evolution into prokaryotic potassium channel cavities
Authors: coll julio
Published: January 2024

Human potassium channels (Kir) are implicated in numerous dysfunction diseases genetically affecting cardiovascular, skeletal-muscle and/or synaptic-neuronal functions. Variations in Kir sequences, organ distribution differences and toxicity of some of their known inhibitors, require alternative drugs to interfere specifically with each human Kir molecular species. In this work, a prokaryotic asymmetric transmembrane homotetramer potassium (K+) channel protein highly homologous to Kirs has been used as their model. Computational methods combining molecular parent co-evolutions confirmed by consensus docking, were explored as possible prove-of-concept to generate rather than screen for numerous KcsA docking-ligands. The explorations of the KcsA central cavity and of their interface lipid-binding shallow-grooves, predicted highly specific novel scaffolds with low-toxicity risks, displaying hundreds of molecular variations of new scaffolds within nanoMolar-ranged affinities. Experimental validation and/or additional computational research on human Kirs could be attempted in the future.
Evaporative drying of sessile droplets as a means of monitoring UiO-66 MOF synthesis and quality
Authors: Kar Salini , Basu Nandita , Sk Mostakim , Chowdhury Mithun
Published: January 2024

We demonstrate a simple droplet drying based diagnostic approach to monitor the UiO-66 MOF (metal organic framework) synthesis and it’s quality using the sessile drop drying phenomenon. Drying a sessile droplet involves evaporation-driven hydrodynamic ﬂow and particle nature-dependent self-assembled deposition. In general, the MOF synthesis process involves diﬀerent sizes and physicochemical natures of particles in every stage of the synthesis. Equivalent quantities of each of purifed pore-activated UiO-66 MOF, yet to be purifed pore-inactivated UiO-66 MOF, and reaction precursors of UiO-66 MOF give diﬀerent deposition patterns when a well-dispersed aqueous droplet of these materials undergo drying over substrates of varying stiﬀness and wettability. Yet to be purifed pore-inactivated UiO-66 MOF nanoparticles undergo transport towards the droplet periphery leading to a thick ring-like deposition at the dried droplet edge. Under appropriate condition of drying, such deposit leads to desiccationtype mud-like reticular cracking. We study the origin of such ring-like deposits and cracks to understand how it get inﬂuenced by the presence of thermal Marangoni ﬂow feld and the addition of salts contributing to surface charge density of UiO-66 particles controlling their stability. We clearly demonstrate ZrOCl2 salt trapped in non-purifed pore-inactivated UiO-66 MOF moiety is the principal reason for ring-like deposit formation and subsequent cracking in its drying aqueous droplet edge. In general, Lewis acid salts (like FeCl3, SnCl2, ZrOCl2), those also act as Brønsted-acid upon hydrolysis, inﬂuence surface charge density and colloidal stability of dispersed UiO-66 MOF particles. As a result immediate particle coagulation gets avoided, so those travel to the droplet edge leading to the formation of ring-like deposition and subsequent cracking upon drying. Further we show crack patterns on such deposit are highly dependent on the stiﬀness and temperature of depositing substrates via a competition between axial and lateral strain at the deposit-substrate interface.
INNOVATIVE SUSTAINABILITY IN AN EMERGING ECONOMY: NIGERIA’S ECONOMIC DIVERSIFICATION AND HISTORY WITH DEVELOPMENT GOALS
Authors: Onyeka Chimdiya , Onyeka Paulina
Published: January 2024

Nigeria’s emerging economy has gone through a number of phases and dependencies since independence in 1960 and is currently Africa’s largest economy. The majority of government revenue comes from oil but the oil economy presents a lot of challenges not least from a sustainability perspective. Partly to address some of these challenges, Nigeria has also gone through various internal and global development programmes including the Millennium Development Goals and currently the Sustainable Development Goals – with varying degrees of performance recorded. This study systematically reviews Nigeria’s history with these targets and makes economic diversification recommendations based on the findings. Specifically, the study uniquely and chronologically evaluates the evolution history of the Nigerian economy and for the first time, presents a much-needed analysis of rapid diversification potentials for Nigeria underpinned by an established and innovative sustainability framework.