bluuebunny/crossref_metadata_2025 huggingface dataset:
Entrepreneurial Incentives Among University Students in Georgia and Portugal
Authors: Taktakishvili Tengiz , Charaia Vakhtang , Moutinho Nuno , Alves Jorge Manuel Afonso
Published: June 2024

The study of entrepreneurial incentives among students is a highly relevant issue because it is of utmost importance for the economic development of the country to cultivate generations of entrepreneurs who will create high-value technological startups and contribute to the transformation of Georgia into a technological hub, a goal that we have been calling a priority for years. In recent years, there has been a tendency among young adults to show entrepreneurial initiative, although this is modest compared to what could truly change the image of the country. Funds and angel investors have emerged in the country, ready to invest in interesting business projects with global potential. In this process, the role of universities could be invaluable. The primary obstacle that Georgia’s and Portugal’s education systems are still facing is incorporating entrepreneurial skills into formal and vocational education. Scant is the rundown of colleges that have coordinated this new test in their educational programs.

The region is characterized by precarious and unsystematic skill-based professional schooling, reflecting inadequate funding initiatives lacking sustainability. The article studies the factors influencing students’ entrepreneurial incentives in Georgia and Portugal, identifies the interests and opportunities of Georgian and Portuguese university students in starting a business, and discusses the best foreign practices for encouraging students’ entrepreneurial activity. The article reports a study, based on a survey, which identified the main facilitating and hindering factors that influence students’ entrepreneurial incentives. The paper also analyzes the environment supporting students’ entrepreneurial activities in Georgia and Portugal, discusses the possibilities of finding financing, and identifies the main obstacles that students face when starting a business.
Sexual Violence: Comparative Overview of German and Georgian Legal Perspectives
Authors: Kherkheulidze Irine
Published: June 2024

The issue of sexual violence that this article was tasked to deal with is neither new nor devoid of a regulating legislative framework. Moreover, a number of scientists from diff erent countries and institutions of the world have devoted their works to the topic under discussion, which has repeatedly been subjected to discussions in the European Court of Human Rights, International Criminal Court, and ad hoc tribunals.

However, this article aspires to analyze the normative framework for the regulation of sexual violence in line with Article 36 of the Istanbul Convention in Germany and Georgia after the ratifi cation of the Convention in the last decade. The main focus of the study is the contentious interpretation of consent in sexual off ences. Due to the inevitable legislation reforms concerning sexual violence, this academic work examines new trends on regulating this issue in Western countries, especially in Germany, considering the historical ties of Georgian Criminal Code to German law. The article discusses sexual violence in general, providing a brief review of sexual violence legislation, where it is mainly presented by considering the international legal framework. Sexual violence and other sexual off ences according to Georgian and German criminal codes are presented in general terms and in a comparative manner. The article also explains rape in the light of its re-conceptualization, encompassing an analysis on sexual violence, including rape, especially in relation to consent. This, in turn, can prompt amendments to Georgian Criminal Code on the related issue, which currently does not comply with the standards on interpreting sexual violence, established by the Istanbul Convention and other important related international acts.
Representation in International Relations, Impeachment of the President of Georgia, and European Integration
Authors: Gegenava Dimitry , Goradze George
Published: June 2024

The 2017–2018 constitutional reform amended the Constitution of Georgia and changed the political system of the country. The president has the responsibility to represent the country in international relations, but only with the approval of the government. Constitutional norms are not specific, leaving room for different interpretations. Article 78 of the Constitution obliges constitutional bodies to use all measures for European integration. Under this constitutional obligation, the president met with European colleagues, though without governmental approval. This provoked the ruling party to initiate the process of impeachment. The Constitutional Court of Georgia concluded that the president breached the Constitution, but the parliament could not impeach the president. The paper analyses the role of presidential representation in international relations and its constitutional responsibility in the light of Georgia’s European aspirations.
Extension of Vedic mathematics sutras for square calculation
Authors: Asrani Komal , Gupta Anuradha , Asrani Deepak
Published: June 2024

Square is one of the basic arithmetic operations. Referring to the earlier contributions provided by ancient Indian mathematicians concerning square calculation, various techniques have been suggested by Arybhata, Bhaskara I, Sridhara, Mahavira and Bhaskara II to quote a few. Besides, P. Swami Bharati Krishna Tirthji discussed various techniques for square calculating based on various sutras. In this paper, we summarise the works done by ancient Indian mathematicians and discuss the applications of calculating squares using different sutras. In addition, we propose a new method of calculating square based on the drawbacks identified and that can be applied for the square calculation of any number. Our method splits the number and hence makes the calculation simpler. Moreover, for bigger values, nested calculations can also be applied.
A comparison of the convergence rates of Hestenes’ conjugate Gram-Schmidt method without derivatives with other numerical optimization methods
Authors: Raihen Md Nurul
Published: June 2024

This article describes an approach known as the conjugate Gram-Schmidt method for estimating gradients and Hessian using function evaluations and difference quotients, and uses the Gram-Schmidt conjugate direction algorithm to minimize functions and compares it to other techniques for solving ∇f = 0. Comparable minimization algorithms are also used to demonstrate convergence rates using quotient and root convergence factors, as described by Ortega and Rheinbolt to determine the optimal minimization technique to obtain results similar to the Newton method, between the Gram-Schmidt approach and other minimizing approaches. A survey of the existing literature in order to compare Hestenes’ Gram-Schmidt conjugate direction approach without derivative to other minimization methods is conducted and further analytical and computational details are provided.
Petri nets for Adaptive learning scenarios in Serious games
Authors: Hosťovecký M. , Korečko Š. , Sobota B.
Published: June 2024

Serious games are becoming a more commonly utilized tool in training, education, and learning. On the other hand, Petri nets, a well-known formalism for process modeling, seem to be a promising tool for describing learning activity scenarios for serious games and virtual environments. Thanks to their graphical form and easy-to-understand nature, it can be assumed that participants from different backgrounds should be able to understand and use Petri nets for their scenarios. A present study presented here investigates how this assumption corresponds to reality. In the study, a short explanation of Petri nets and a set of related tasks were given to a sample of 31 participants (n = 31). The participants were students of Computer Science (16) and Humanities (15). The results collected and statistically analyzed demonstrate both similarities and distinctions in the reactions to problem-solving assignments among individuals in the two groups. These findings and their analysis have been condensed and presented in visual form.
Financial Development-International Trade Nexus in Ghana: The Role of Sectoral Effects
Authors: Prempeh Kwadwo Boateng , Frimpong Joseph Magnus
Published: June 2024

This study investigates the role of sectoral effects in the financial development-international trade nexus using time series data from Ghana for the period 1960 to 2017. Our evidence from the autoregressive distributed lag (ARDL) estimates indicates that while the effect of sectoral value additions on trade is conditional on the proxy of financial development, financial development significantly promotes trade in both the long- and short-run, regardless of the proxy. Moreover, even after accounting for sectoral value additions, finance positively affected international trade. On the moderation front, we observe that increased agricultural value additions mitigate the beneficial impact of financial development on international trade, whereas increased service value additions magnify the beneficial effects. Thus, to boost international trade in Ghana, policymakers should prioritise fostering complementarity between the industrial, agricultural, service, manufacturing, and financial sectors.
Do Exchange Rates Respond Asymmetrically to Crude Oil Market Shocks? Insights from BRICS and Pakistan
Authors: Rashid Abdul , Jehan Zainab , Tahira Maria , Javed Amir
Published: June 2024

The shocks in the crude oil market are unlikely to have symmetric impacts on exchange rates, especially over various time periods. Furthermore, in low- and high-volatility regimes, exchange rates are predicted to respond differently to oil market shocks. By employing Markov-switching model and state-space model, this research empirically investigates whether oil market shocks exert asymmetric impacts on exchange rates, across the time and across different levels of volatility. In doing so, the study utilizes monthly data from January 1994-September 2017 for BRICS countries and Pakistan. The findings indicate that although oil supply shocks are mostly insignificant, oil price shocks appear statistically significant to affect the exchange rates whereas aggregate demand shocks are most volatile and are more likely to cause exchange rate fluctuations. The study concludes that various forms of oil shocks have a wide range of consequences on exchange rate determinations. Nonetheless, exchange rates’ response to oil shocks differ dramatically through low- and high-volatility states, implying that oil shocks exert a time-varying impact on exchange rates. Finally, the findings provide credence to the phenomenon of asymmetry in exchange rate responses to oil market shocks.
Sunda Borangan dalam Karya Video Art
Authors: Ramadhan Muhammad Rizky , Sintowoko Dyah Ayu Wiwid , Zen Adrian Permana
Published: June 2024

Borangan merupakan istilah Sunda yang berarti penakut. Borangan adalah gambaran dari sifat manusia yang kerap menghantui pikiran manusia dimana konsep Borangan ini menjadi dasar penciptaan film ekperimental. Penelitian ini bertujuan untuk memvisualisasikan bagaimana sifat Borangan kepada khalayak melalui medium video art. Rumusan masalahnya adalah bagaimana proses penciptaan Borangan dengan menggunakan medium Video Art. Adapun metode yang digunakan adalah practice-based study. Hasil penelitian tidak terlepas dari dua hal, yaitu : (1) Borangan sebagai budaya Sunda secara konseptual diciptakan sebagai sebuah refleksi diri orang Sunda dalam melawan rasa takut, sehingga penciptaan karya dalam penelitian ini dilakukan berbasis tiga babak permasalahan, pemecahan, dan penyadaran; dan (2) medium Video Art menekankan pada eksplorasi pengkarya tanpa harus mementingkan sisi komersialisasi. Oleh sebab itu, berbeda dengan medium film yang kental akan penekanan formalis film teori, video art pada karya Borangan lebih menggambarkan aspek kejujuran dan kesan apa adanya yang ditampilkan secara visual.
Crime Dynamics in Russia - Model Analysis
Authors: Artyushkin V. F. , Tokareva V. I. , Zvyagintsev M. M.
Published: June 2024

Introduction. The article proposes a mathematical model of the dynamics of one of the indicators of crime ― the number of persons who have committed crimes. The indicator is aggregated, so it is considered as a generalized characteristic of the behavior of crime in general. The analysis of the dynamics of the indicator in the context of the political, economic and legal situation in the country and the world is carried out.Materials and methods. As a statistical base for the crime indicator, data from the statistical yearbook "Russia in figures" has been used. For global oil demand, data from the monthly review of the International Energy Agency (Monthly Oil Market Report // International Energy Agency) has been used. To build mathematical models, time series analysis and modeling methods were used, and correlation analysis methods were used when comparing models. General scientific research methods were also used - systematic and historical approaches.Results of the study. A mathematical model is proposed, which is the sum of periodic functions and a trend. The functions have several settings and only one argument – time. The model adequately describes the behavior of the indicator therefore it can be used to obtain short-term forecasts. The historical period is highlighted, in which the correlation between the dynamics of crime and the dynamics of the global economic situation is traced. The stabilization of crime dynamics in recent years has been noted, when the processes of restoring Russia's economic sovereignty accelerated.Discussion and conclusion. The proposed mathematical model gives good results of fitting the crime indicator to a time series on the entire observation period. And this period covers very different historical situations: from unlimited entry into the global economic system to strengthening economic sovereignty. The reliability of the model over the entire interval indicates the validity of its use even with new economic benchmarks. The result of demonstrating a rapid decrease in the amplitude of fluctuations in the crime rate while strengthening the sovereignty of the Russian economy in recent years is indicative. The processes that were analyzed in the work have many differences, but they are well described by models of the same type. A possible explanation for this invariance is the hypothesis that some complex socio-economic processes not only affect each other's condition, but synchronize their dynamics.
Responsibility of Minors in the History of Criminal Law in Russia (before 1845)
Authors: Trapaidze K. Z.
Published: June 2024

Introduction. The main purpose of the work is to show how the criminal legislation of the Russian Empire has evolved in the matter of the age of a person capable of being responsible or serving the sentences imposed on him. To achieve this goal, the paper analyzes the legislative norms of different eras (before 1845) using the scientific works of pre-revolutionary Russian legal scholars on the subject of the study.Materials and methods. The methods applied in the course of the study (historical, formal-legal, logical, dialectical) showed that for several centuries in the criminal law of Russia, the age of the person who committed the crime had no legal significance. The situation changed with the adoption of New Proof Articles in 1669, which for the first time established the exact age at which a person could be responsible for what he had done – 7 years. Subsequently, this age changed many times – the legislator then raised it, then restored it.Results of the study. The analysis showed that, during the period under study, the question of the age of responsibility for crimes was resolved inconsistently, often contradictory.Discussion and conclusion. The study showed that, most importantly, age was not considered as an independent criminal-legal sign, but only within the framework of the sign of sanity.
The Main Directions of Supranational Regulation of the Digital Space in the EAEU at the Present Stage
Authors: Lyu K. A.
Published: June 2024

Introduction. The study of the main directions of supranational regulation of the digital space is an important task in the context of the constant complication and expansion of social relations in the digital sphere. The creation of effective and progressive regulation in the relevant area can become the basis for increasing the competitiveness of the EAEU on the world stage. At the same time, the corresponding issues have been practically not studied in the domestic academic literature. Within the framework of this article, an attempt has been made to comprehensively assess the system of supranational regulation of the digital space in the EAEU, to identify its strengths and weaknesses.Materials and methods. The methodological basis of the study was made up of general scientific and special scientific methods. General scientific methods are presented: analysis, synthesis, inductive-deductive method, systematic method. Special scientific methods include: the method of systemic analysis of law, the comparative legal method, the formal legal method. The research materials are presented by supranational acts of the EAEU (primarily the Treaty on the EAEU and its protocols), official documents and statements, as well as doctrinal concepts and approaches.Results of the study. The article analyzes and evaluates the key areas of supranational regulation of the digital space in the EAEU at the present stage. The conceptual and legal foundations of the relevant regulation are identified (including in comparison with the EU approach to supranational regulation of the digital space) and their role and significance for the development of supranational regulation of the digital space in the EAEU is analyzed. Changes in the customs legislation of the EAEU in terms of supranational regulation of external (with the participation of residents of third countries) electronic trade are involved in scientific circulation.Discussion and conclusion. Based on the results of the study, it was concluded that currently the system of supranational regulation of the digital space in the EAEU is at the stage of its formation and extends only to four main areas: the circulation of non-personal data, public procurement, intellectual property protection and external electronic commerce. At the same time, recent initiatives in the field of supranational regulation of external electronic commerce represent an important step towards a new stage in the development of digital aspects of Eurasian integration.
RAGAM METODE PEMBELAJARAN MENARIK UNTUK ANAK USIA DINI : KONSEP DAN PRAKTEK
Authors: Azizah Nur Azizah
Published: June 2024

Penelitian ini bertujuan untuk mengidentifikasi metode pembelajaran yang menarik bagi anak usia dini serta memberikan referensi bagi para pendidik PAUD. Melalui tinjauan literatur yang komprehensif, penelitian ini menganalisis berbagai model pembelajaran, menyoroti keunggulan, tantangan, dan implikasi praktisnya. Hal ini penting untuk meningkatkan kemampuan anak dalam berbagai aktivitas seperti bercerita, bermain, dan berwisata, serta untuk memberikan alternatif pembelajaran yang berkualitas bagi peserta didik PAUD. Hasilnya menunjukkan bahwa pembelajaran yang menarik, efektif dalam meningkatkan minat belajar anak, menciptakan lingkungan belajar yang kondusif, dan merangsang kreativitas mereka. menurut para ahli pembelajaran pada PAUD harus di sertakan dengan beberapa metode yang sesuai dengan kemampuan anak dalam belajar. pada metode ini anak mampu meningkatkan kreativitas anak usia dini, pada pendekatan ini dapat memungkinkan anak untuk belajar secara aktif dan eksploratif, sehingga dapat mendorong mereka untuk menyampaikan ide-ide kreatif mereka, salah satu nya yaitu menggunakan metode tanya jawab. Kata Kunci : metode, pembelajaran, anak usia dini, kegunaan.
Direct-Contact and Contact-free Treatment of a DBD-like Non-thermal Atmospheric Pressure Plasma Jet on Pseudomonas aeruginosa
Authors:   Department of Physics, Faculty of Science and Letters, Eskisehir Osmangazi University, TR-26040 Eskisehir, Turkey, AKAN TAMER , CABUK AHMET ,   Department of Biology, Faculty of Science and Letters, Eskisehir Osmangazi University, TR-26040 Eskisehir, Turkey, CELIK PINAR AYTAR ,   Graduate School of Natural and Applied Sciences, Eskisehir Osmangazi University, TR-26040 Es¬kisehir, Turkey, YAVAS E. SERHAT ,   Graduate School of Natural and Applied Sciences, Eskisehir Osmangazi University, TR-26040 Es¬kisehir, Turkey, DURMUS CAGRI ,   Graduate School of Natural and Applied Sciences, Eskisehir Osmangazi University, TR-26040 Es¬kisehir, Turkey
Published: June 2024

In this study, a Dielectric Barrier Discharge (DBD)-like non-thermal atmospheric pressure plasma jet (NTAPPJ) was exposed to the Pseudomonas aeruginosa planktonic bacteria. The P. aeruginosa bacteria were treated by the NTAPPJs in both Ar and He at the non-contact distance (contact-free) and the contact distance (direct-contact). The contact of the NTAPPJs with the bacteria has generated spark discharges in both filamentary mode and diffuse mode. The antibacterial efficacy of the Ar and He NTAPPJs for various treatment times (60, 120, 180, and 300 sec) were investigated by treatment on the bacteria without contact and with contact in both filamentary mode and diffuse mode. The NTAPPJs in both Ar and He caused erosion on the agar surface when treated in direct-contact with the bacteria in the filamentary mode, while the NTAPPJs in Ar in the diffuse mode produced the greatest antibacterial efficacy without damage.
Assessment of the antimicrobial activity of some essential oils against multi-resistant bacterial strains
Authors:   University of Bucharest, Faculty of Biology, Bucharest, Romania, MIHAI (BĂȘA) DANIELA-CRISTINA , DIȚU LIA-MARA ,   University of Bucharest, Faculty of Biology, Bucharest, Romania, GHEORGHE IRINA ,   University of Bucharest, Faculty of Biology, Bucharest, Romania, BANU OTILIA ,   Institute of Cardiovascular Diseases Prof. C.C. Iliescu, Bucharest, Romania, MIHAESCU GRIGORE ,   University of Bucharest, Faculty of Biology, Bucharest, Romania
Published: June 2024

Volatile oils, also called essential oils, are secreted by plant-specific secretory cells and tissues. These components are a mixture of different substances, primarily mono and sesquiterpenes. Our aim was to assess the antimicrobial activity of different essential oils, i.e. lavender, cloves, eucalyptus, rosemary, thyme and oregano against multidrug resistant bacterial strains belonging to the ESKAPE group. The most effective oils proved to be the thyme and oregano which induced the occurrence of the largest diameters of the growth inhibition zones against all tested bacterial species. Oregano oil showed the best inhibitory activity against Pseudomonas aeruginosa, followed by clove, while thyme oil was the most effective against Staphylococcus aureus strains.
Impact of ligustrazine on chondrocyte apoptosis in knee osteoarthritis through FAK/PI3K/Akt pathway
Authors:   Department of Orthopaedics, Liuzhou Traditional Chinese Medical Hospital, Liuzhou City, Guangxi Province, 545001, China, SHENG GUANYUN , YANG JING ,   Department of Intensive Care Unit, Liuzhou Traditional Chinese Medical Hospital, Liuzhou City, Guangxi Province, 545001, China, RONG PENG ,   Guangxi University of Chinese Medicine, graduate school, Nanning City, Guangxi Province, 530000, China, YANG XUEYI ,   Department of Orthopaedics, Liuzhou Traditional Chinese Medical Hospital, Liuzhou City, Guangxi Province, 545001, China
Published: June 2024

Objective: To probe into the impact of ligustrazine on chondrocyte apoptosis in knee osteoarthritis (OA) and its pos¬sible mechanism. Methods: Our team extracted the human primary chondrocytes to construct the IL-113-induced chondrocyte damage model, detected the impact of ligustrazine on chondrocyte apoptosis through TUNEL and Western blot, applied Western blot to detect the impact of ligustrazine on matrix-degrading enzymes, matrix-associated proteins, as well as FAK/PI3K/ Akt pathway, using ELISA detected the impact of ligustrazine on MCP-1, IL8, PEG2 and NO levels, applied FAK/PI3K/ Akt pathway inhibitor PF573228 to inhibit FAK/PI3K/Akt pathway to detect whether the chondroprotective impact of ligustrazine was inhibited, constructed a New Zealand rabbit osteoarthritis model, applied HE staining to evaluate the impacts of ligustrazine and ligustrazine+PF573228 on cartilage histomorphology, and applied Western blot to detect the impacts of ligustrazine and ligustrazine+PF573228 on apoptotic proteins, matrix-degrading enzymes and matrix-related proteins in cartilage tissue. Results: Ligustrazine signally inhibited IL-113-induced chondrocyte apoptosis, reduced Bax, caspase-9, caspase-3, caspase-7, MMP3, MMP13, collagen X protein expression levels, and reduced MCP-1, IL8, PEG2, and MCP-1. NO contents, promoted collagen II and aggrecan protein expression. Additionally, ligustrazine activated the FAK/PI3K/ Akt pathway, and applying PF573228 to inhibit the FAK/PI3K/Akt pathway abolished the chondroprotective impact of ligustrazine. At the in vivo level, ligustrazine activated the FAK/PI3K/Akt pathway to inhibit Bax, caspase-9, caspase-3, caspase-7, MMP3, MMP13, collagen X protein expression levels, promoted collagen II and aggrecan protein expression, and improved cartilage histomorphology. Conclusion: Ligustrazine exerts chondroprotective impact through FAK/PI3K/Akt pathway
Authors: Farida Ariesa , Amalia Kiki Putri , Liritantri Widyanesti , Budiono Irwana Zulfia , Laksitarini Niken
Published: June 2024

Hunian merupakan kebutuhan dasar manusia, semakin padatnya perkotaan mengakibatkan efektifitas lahan sebagai kawasan hunian harus dilakukan. Saat ini berkembangnya hunian tipe 33 mengakibatkan kebutuhan akan furniture yang multifungsi agar dapat menghemat ruang untuk beraktivitas menjadi tren yang berkembang. Berdasarkan hasil diskusi dengan pihak developer pada hunian tipe 33 direncanakan perlunya perencanaan dan penelitian yang seusai akan penggunaan furniture multifungsi sebagai solusi space saving. Objek studi yang akan diteliti terletak di Kota Bogor Provinsi Jawa Barat dengan luas hunian 33m2 dan luas lahan 60m2 yang terdiri dari ruang keluarga, ruang makan dan pantry, dua kamar tidur dan satu kamar mandi. Berdasarkan permasalahan diatas maka tujuan penelitian ini adalah mengkaji desain furniture multifungsi yang dapat mengakomodasi aktifitas dan perilaku penghuni hunian, dimana furniture multifungsi merupakan salah satu solusi untuk memaksimalkan ruang terbatas pada hunian. Tujuan penelitian ini untuk menghasilkan solusi yang tepat akan pilihan furniture multifungsi yang dirasa paling dibutuhkan dalam mengakomodasi dan memaksimalkan ruang. Metode penelitian yang digunakan adalah metode kualitatif dengan mengkaji data primer dari hasil survey dan kuesioner juga data sekunder dari studi literatur untuk dapat menghasilkan desain furniture multifungsi yang tepat pada hunian.
IDENTIFIKASI KERAGAMAN GENETIK SORGUM LOKAL HASIL IRADIASI MENGGUNAKAN PENANDA MOLEKULER RPAD
Authors: Arum Laras Sekar , Ramadhan Moch. Alfian Rizky , Hazmi Muhammad , Murtiyaningsih Hidayah
Published: June 2024

Sorgum (Sorghum bicolor L. Moench) termasuk komoditas pangan alternatif yang memiliki potensi cukup besar untuk dikembangkan di Indonesia. Namun tingkat keragaman genetiknya di Indonesia masih terbilang rendah. Rendahnya keragaman genetik sorgum memicu untuk memperbaiki dan mencari sumber-sumber genetik yang baru, upaya yang dapat dilakukan diantaranya melalui pemuliaan tanaman. Mutasi induksi radiasi merupakan pemuliaan tanaman yang bertujuan untuk mendapatkan sifat-sifat baru dan memiliki sifat yang tidak dimiliki oleh induknya. Irradiasi sinar gamma dapat merusak DNA dan selama proses perbaikan, DNA akan mengalami mutasi baru yang diinduksi secara acak. Penelitian ini bertujuan untuk mengetahui bagaimana tampilan karakter agronomis, keragaman geneitk, dan hubungan kekerabatan dari tanaman yang telah diiradiasi sinar gamma berdasarkan penanda molekuler Random Amplified Polymorphic DNA (RAPD), Pada penelitian ini sorgum lokal bandung, demak, dan jember di induksi keragaman genetiknya dengan iradiasi sinar gamma dosis 0 Gy, 300 Gy, dan 500 Gy. Pemberian dosis iradiasi sinar gamma memberikan pengaruh nyata pada parameter viabilitas  vigoritas, dan morfologi Hasil isolasi DNA dianalisis dengan teknik Random Amplified Polymorphic DNA (RAPD). OPA-12 memiliki tingkat polimorfisme tertingi daripada ketiga primer lainnya. Pita yang dihasilkan dari empat primer diskoring dan dianalisis menggunakan program NTSYSpc untuk mengetahu tingkat kekerabatan antar genotip. Jarak genetik antar genotip terbilang jauh berkisar antara 0.1-0.46 sehingga berpotensi untuk dilakukan persilangan
Mupirocin/hydroxyapatite composite suspended in transcutol P-spiked hydrogel: In vitro characterization and in vivo wound healing assessment
Authors: Ojo Olusola Emmanuel , Ilomuanya Margaret Okonawan , Cardoso-Daodu Ibilola Mary , Sekunowo Olatunde Israel , Gbenebor Oluwashina Philips , Oladimeji Islamiyat Kanyinsola , Falodun Tomiwa Thomas , Adeosun Samson Oluropo
Published: June 2024

Objectives:

Natural hydroxyapatite (HAP) has been utilized as a drug carrier owing to its excellent bioactivity and biocompatibility. This study is aimed at formulating mupirocin/hydroxyapatite composite suspended in hydrogel. The appropriate quantity of the penetration enhancer (Transcutol-P®) was also investigated.

Materials and Methods:

The HAP was isolated from bovine bone by hydrothermal treatment, calcined at 1000oC and held for 2 hours in an electric furnace to remove the organic contents. The bones were milled, sifted using 150 µm mesh sieve and characterized. Olive oil, which contains oleic acid, was utilized as a natural capping agent to prevent agglomeration of the particles in the formulation. The quantity of Transcutol-P® was varied with mupirocin used as the active pharmaceutical ingredient for the management of acute wound in Wistar rats. In this animal study, the wound closure rate was evaluated.

Results:

The formulation with the 0.6%v/v, of Transcutol-P® gave the best wound closure rate of 30.05 mm2/day. The in-vitro study showed that the formulation containing 0.6%v/v Transcutol-P® released 63.9% of the drug after 75 minutes while 42.4% was released at the same time interval when the concentration of the penetration enhancer was increased to 1.2%v/v. The mupirocin-encapsulated HAP hydrogel composite showed high resistance against staphylococcus saprophyticus with inhibition zone of 37.3 mm.

Conclusion:

The mupirocin encapsulated in HAP allows for sustained release of the antibiotic and thus serves as a veritable drug carrier suitable for wound healing applications. Transcutol-P® (0.6%v/v) is effective in facilitating drug release, which is reflected in the increased wound closure rate in Wistar rats.
Experience of rigorous practice of antimicrobial stewardship program and its impact on antibiotic consumption
Authors: Kumar Shweta , Khadanga Sagar , Haq Rehan Ul , Saxena Pradeep , Sampath Ananyan , Tadepalli Karuna
Published: June 2024

Objectives:

Antimicrobial resistance (AMR) is the next pandemic with a huge global economic burden. A customized antimicrobial stewardship program (AMSP) is a well-recognized tool for containment of AMR. The current study was undertaken to identify the impact of AMSP measures on the trends of antibiotic consumption rates, e.g., defined daily dose (DDD) and days of therapy (DOT) per 100 patient days in pre-identified areas of the hospital.

Materials and Methods:

The present study was a case-record-based extended cross-sectional study carried out in a tertiary care institute in central India from January 2021 to September 2021. Time-bound feasible sampling was undertaken, and all cases were included without any exclusion criteria. The study was approved by the Ethics Committee of the Institute and funded by the Indian Council of Medical Research (ICMR).

Statistical Analysis:

The data was entered into a spreadsheet. The calculation of DDD and DOT was performed individually for each antibiotic as per WHO tool per 100 patient days.

Results:

In high-priority areas such as intensive care unit and high dependency unit, the top three DDD/100 days were meropenem (77.9), colistin (41.4), and piperacillin-tazobactam (13.5) versus the top 3 DOT/100 patient days were meropenem (40.5), colistin (20.9), and piperacillin-tazobactam (15.7). In low-priority areas such as general wards, the top 3 DDD/100 patient days were meropenem (45.4), piperacillin-tazobactam (22.6), and cefoperazone (5.0) versus the top three DOT/100 patient days were meropenem (45.4), cefoperazone (44.9), and piperacillintazobactam (22.6). There was a downward trend of consumption of almost all these antibiotics when measured at baseline and the next two quarters. DDD and DOT per 100 patient days had a positive linear correlation during the study period.

Conclusions:

The present study demonstrates about 50% reduction in consumption of ICMR priority antibiotics with a yearlong AMSP. DDD and DOT per 100 patient days can be calculated with minimal effort, even in extremely busy hospitals. DOT tools are less labor-intensive and, hence, should be the pivotal tool for antibiotic exposure measurement.
The movement potentiation scale and movement therapy – A study of three cases
Authors: Williams Brogan , Horschig Aaron , Lock Andrew , Johnson David
Published: June 2024

A study of three separate female volunteers was conducted. The movement potentiation scale™ (MPS) was used as a movement evaluation and pain levels were determined using a Visual Analog Scale (VAS) for pain. The six core movement challenges in the MPS evaluation have a combined point value of 26. After the evaluation, every subject underwent a consecutive five-day functional movement training program, which had an emphasis on movement quality, proprioception, balance, coordination, and optimal biomechanics under suitable stimuli. Provocative daily triggers were determined, and participants were educated on movement. Post-intervention data, including the repeated MPS and VAS pain rating findings, were gathered on the day six. Every participant showed a marked improvement in their MPS score and pain. On day one, participant 1, who was awaiting surgery for ongoing severe lower back pain, had a low MPS score of 5/26. On day six, following the intervention, she reported 0/10 discomfort and a 15/26 MPS score. Participant 2 began the trial with a low MPS score of 7/26, chronic shoulder pain, and paresthesia down her left arm. On day six, she reported 0/10 discomfort, no paresthesia, and an improved 14/26 MPS score. Participant 3 had an MPS score of 8/26; the predominant complaint was urinary incontinence. On day six, she showed an improved MPS score of 18/26, with a 10-day follow-up of nil urine incontinence.
Chemical Exposomics in Human Plasma by Lipid Removal and Large Volume Injection Gas Chromatography High-Resolution Mass Spectrometry
Authors: Xie Hongyu , Sdougkou Kalliroi , Papazian Stefano , Bonnefille Bénilde , Bergdahl Ingvar , Rantakokko Panu , Martin Jonathan
Published: June 2024

For comprehensive chemical exposomics in blood, analytical workflows are evolving through advances in sample preparation and instrumental methods. We hypothesized that gas chromatography high-resolution mass spectrometry (GC-HRMS) workflows could be enhanced by minimizing lipid co-extractives, thereby enabling larger injection volumes and lower matrix interference for improved sensitivity and molecular discovery. A simple protocol was developed for small plasma volumes (100-200 µL) by using isohexane (H) to extract supernatants of acetonitrile-plasma (A-P). The HA-P method was quantitative for a wide range of hydrophobic multiclass target analytes (i.e. log Kow >3.0), and the extracts were free of major lipids, thereby enabling robust large-volume injections (LVI; 25 µL) in long sequences to a GC-Orbitrap HRMS. Without lipid removal, LVI was counter-productive because method sensitivity suffered from the abundant matrix signal, resulting in low ion injection times to the Orbitrap. The median method quantification limit was 0.08 ng/mL (range 0.005–4.83 ng/mL), and good accuracy was shown for a certified reference serum. Applying the method to plasma from a Swedish cohort (n=32; 100 µL), 51 of 103 target analytes were detected. Simultaneous nontarget analysis resulted in 112 structural annotations (12.8% annotation rate), and Level 1 identification was achieved for 7 of 8 substances in follow-up confirmations. The HA-P method is potentially scalable for application in cohort studies and is also compatible with many liquid-chromatography-based exposomics workflows.
An ex situ gaseous reagent for multicomponent amine bioconjugation
Authors: Ding Yuxuan , Pedersen Simon , Wang Yixian , Xiao Han , Ball Zachary
Published: June 2024

Bioconjugation is a large field with many diverse goals, needs, and challenges, that requires a broad toolbox of fundamentally different synthetic approaches. As nucleophilic groups are prevalent in biomolecules, the ability to crosslink two nucleophilic sites offers an attractive approach to construct useful bioconjugates. New technologies for crosslinking with gaseous reagents and with minimal perturbation of natural structure could provide new ways to think about bioconjugation in complex environments. We report a minimalist gaseous sulfonyl chloride-derived reagent for multicomponent bioconjugation with amine, phenol, or aniline reagents to afford urea or carbamate products. In utilizing a gas-phase reagent for a reaction mediated by metal ions, a variety of biologically relevant molecules such as saccharide, PEG, fluorophore, and affinity tag can be efficiently crosslinked to the N-terminus or lysine side chain amines on natural polypeptides or proteins. The application of this method to the production of functional, modified proteins was demonstrated by fluorescence imaging of a cancer cell line and by the facile preparation of a peptide–protein conjugate.
High-Spin State of a Ferrocene Electron Donor Revealed by Optical and X-ray Transient Absorption Spectroscopy
Authors: Burke John , Bae Dae Young , Wallick Rachel , Dykstra Conner , Rossi Thomas , Smith Laura , Leahy Clare , Schaller Richard , Mirica Liviu , Vura-Weis Josh , van der Veen Renske
Published: June 2024

Ferrocene is one of the most common electron donors, and mapping its ligand-field excited states is critical to designing donor-acceptor (D-A) molecules with long-lived charge transfer states. Although 3(d-d) states are commonly invoked in the photophysics of ferrocene complexes, mention of the high-spin 5(d-d) state is scarce. Here, we provide clear evidence of 5(d-d) formation in a bimetallic D-A molecule, ferrocenyl cobaltocenium hexafluorophosphate ([FcCc]PF6). Femtosecond optical transient absorption (OTA) spectroscopy reveals two distinct electronic excited states with 30 ps and 500 ps lifetimes. Using a combination of ultraviolet, visible, nearinfrared, and short-wave infrared probe pulses, we capture the spectral features of these states over an ultrabroadband range spanning 320 nm to 2200 nm. Time-dependent density functional theory calculations of the lowest triplet and quintet states, both primarily Fe(II) (d-d) in character, qualitatively agree with the experimental OTA spectra, allowing us to assign the 30 ps state as the 3(d-d) state and the 500 ps state as the high-spin 5(d-d) state. To confirm the ferrocene-centered high-spin character of the 500 ps state, we performed X-ray transient absorption (XTA) spectroscopy at the Fe and Co K edges. The Fe K-edge XTA spectrum at 150 ps shows signatures of bond-length expansion and a Jahn-Teller distortion, consistent with an Fe(II) high-spin state. No transient signal is detected at the Co K-edge, confirming the ferrocene-centered character of the excited state. Altogether, these results demonstrate that the high-spin state of ferrocene should be considered when designing donor-acceptor assemblies for photocatalysis and photovoltaics.
Total synthesis of twenty-five picrotoxanes by virtual library selection
Authors: Li Chunyu , Shenvi Ryan
Published: June 2024

Strong-bond activation refers to the conversion of typically inert functional groups (FG) into reactive ones: e.g. C–H or C–C into C–X. Its application in retrosynthetic analysis requires evaluation of strategy (is it simplifying?) and feasibility (will it work?). However, the feasibility of strong bond cleavage can be difficult to predict due to competing low barrier pathways (e.g. 5–8 kcal/mol) in complex molecular environments. If strong bond activation can be strategically evaluated, accurately calculated and experimentally validated, it can simplify the synthesis of complex molecules. Here we build a virtual library of strategic late-stage intermediates en route to diverse picrotoxanes, calculate C–H vs. C–C oxidation preference and experimentally interrogate the predictions. Costly transition state calculations are then simplified to faster parameterizations to explain remote effects on strong bond activation and to devise concise routes to the picrotoxanes .
Electrochemical Kinetics of Multistep Reactions in General and the HOR/HER on Platinum in Particular
Authors: Brandes Benedikt Axel , Chatzichristodoulou Christodoulos
Published: June 2024

While multistep reactions in electrochemistry are ubiquitous, their analytical treatment has been incomplete and at times misleading. Several misconceptions have led to incorrect conclusions, derailing the analysis of electrochemical processes. In this work we present a rigorous application of the Butler-Volmer model and develop a coherent nomenclature and methodology on how to analyze multistep reactions. We discuss how a universal definition of the exchange current density does not exist for multistep reactions, clarify the meaning of the Tafel slope, often misinterpreted in the electrochemical literature. Eventually we discuss the classically proposed HOR/HER mechanisms on platinum, briefly discuss their origin, show how mass transport effects should be correctly analyzed by introduce a new equation that complements the Koutecký-Levich equation in the micropolarization region. We then perform a thorough experimental investigation of the HOR/HER kinetics over a wide range of combination of cations, anions, concentration, and buffers. There we reveal that buffers seem to take directly part in the HOR/HER and discuss the supposed “cation-effect”. Through the analysis of the micropolarization, Tafel region, and kinetics of the H-upd we propose a new mechanistic description of the HOR/HER with substantial experimental agreement and discuss how anions in the interface play a deciding role in the HOR/HER and H-upd on polycrystalline platinum.
Dynamic Nuclear Polarization Enhanced Multiple Quantum Spin Counting of Molecular Assemblies in Vitrified Solutions
Authors: Nowotarski Mesopotamia , Potnuru Lokeswara Rao , Straub Joshua , Chaklashiya Raj , Shimasaki Toshihiko , Pahari Bholanath , Coffaro Hunter , Jain Sheetal , Han Songi
Published: June 2024

Crystallization pathways are essential to various industrial, geological, and biolog- ical processes. In nonclassical nucleation theory, prenucleation clusters (PNCs) form, aggregate and crystallize to produce higher order assemblies. Microscopy and X-Ray techniques have limited utility for PNC analysis due to small size (0.5 - 3 nm) and time stability constraints. We present a new approach for analyzing PNC formation based on 31P NMR spin counting of vitrified molecular assemblies. The use of glassing agents en- sures that vitrification generates amorphous aqueous samples, and offers conditions to perform dynamic nuclear polarization (DNP) amplified NMR spectroscopy. We demon- strate that molecular adenosine triphosphate, along with crystalline, amorphous, and clustered calcium phosphate materials formed via a non-classical growth pathway can be differentiated from one another by the number of dipolar coupled 31P spins. We also present an innovative approach to examine spin counting data, demonstrating that a knowledge based fitting of integer multiples of cosine wave functions, instead of the traditional Fourier transform, provides a more physically meaningful retrieval of the ex- isting frequencies. This is the first report of multi-quantum spin counting of assemblies formed in solution as captured under vitrified DNP conditions, which can be useful for future analysis of PNCs and other aqueous molecular clusters.
Reduction in the need for glucocorticoids on the background of therapy with biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors in rheumatoid arthritis: evidence from real clinical practice
Authors: Potapova Alena S. , Karateev Andrey E. , Polishchuk Elena Yu. , Filatova Ekaterina S. , Amirdzhanova Vera N. , Lila Aleksander M.
Published: June 2024

Background. Clinical guidelines for the treatment of rheumatoid arthritis (RA) recommend reducing the use of glucocorticoids (GCs) due to the high risk of associated complications.
Aim. To determine the frequency of GC cancellations and dose reductions in real clinical practice, while taking into account active RA therapy.
Materials and methods. The study group consisted of 303 patients with RA reliable according to ACR/EULAR criteria (women 79.9%, age 52.8±13.3, disease duration 9 [4; 16] years, DAS-28-CRP 4.9±1.0, RF seropositivity 77.4%, ACPA seropositivity 70.3%), who were prescribed or changed therapy with disease-modifying antirheumatic drugs (DMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (iJAK) due to disease exacerbation and ineffectiveness of previous treatment. All patients initially received GC (7.7±3.8 mg/day equivalent of prednisolone). After adjustment of therapy, 42.9% of patients received methotrexate, 27.6% leflunomide, 2.5% sulfasalazine, hydroxychloroquine, or a combination with an Non-steroidal anti-inflammatory drugs, 63.7% bDMARDs, and 7.2% iJAK. The need for GC intake was assessed by a telephone survey conducted 6 months after the start of follow-up.
Results. Telephone survey was possible in 274 (90.4%) persons. There was a significant decrease in pain intensity (numerical rating scale, NRS 0–10) from 6.3±1.4 to 4.3±2.4 (p0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 (p0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 (p0.001). A positive PASS index (symptom status acceptable to patients) was noted in 139 (50.7%) patients. GC cancellation was noted in 19.7%, dose reduction in 25.9%, maintaining the same dose in 42.7%, and dose increase in 11.7%.
Conclusion. Against the background of intensive RA therapy, including combination of DMARDs with bDMARDs or iJAK, complete withdrawal or reduction of GC dose was achieved in less than half (45.6%) of patients after 6 months.