Prominent Discovery Research Articles

Enzyme Tunnel Dynamics and Catalytic Mechanism of Norcoclaurine Synthase: Insights from a Combined LiGaMD and DFT Study.

This study conducts a systematic investigation into the catalytic mechanism of norcoclaurine synthase (NCS), a key enzyme in the biosynthesis of tetrahydroisoquinolines (THIQs) with therapeutic applications. By integration of LiGaMD and DFT calculations, the reaction pathway of NCS is mapped, providing detailed insights into its catalytic activity and selectivity. Our findings underscore the critical role of E103 in substrate capture and reveal the hitherto unappreciated influence of nonpolar residues M183 and L76 on tunnel dynamics. A prominent discovery is the identification of a high-energy barrier (44.2 kcal/mol) associated with the aromatic electrophilic attack, which pinpoints the rate-limiting step. Moreover, we disclose the existence of dual transition states leading to different products with the energetically favored six-membered ring formation consistent with experimental evidence. These mechanistic revelations not only refine our understanding of NCS but also advocate for a renewed emphasis on enzyme tunnel engineering for optimizing THIQs biosynthesis. The research sets the stage for translating these findings into practical enzyme modifications. Our results highlight the potential of NCS as a biocatalyst to overcome the limitations of current synthetic methodologies, such as low yields and environmental impacts, and provide a theoretical contribution to the efficient, eco-friendly production of THIQs-based pharmaceuticals.

Understanding Hotel Employees’ Perceptions of Guests with Disabilities in Ho Chi Minh City, Vietnam

While previous research has mainly concentrated on understanding the requirements of guests with disabilities, there is a notable gap in exploring the perspectives held by hotel employees. This study endeavors to address this research gap by investigating how hotel employees in Ho Chi Minh City (HCMC) perceive guests with disabilities. Employing a mixed-methods approach, this research seeks to uncover employee attitudes and knowledge, their roles in fostering inclusivity, and the significance of communication between management and staff in elevating service quality. Notably, the study’s key findings underscore a significant link between employee contentment and customer satisfaction within hotels in HCMC, underscoring the pivotal role of effective communication in enhancing service quality. The research’s most prominent discovery indicates that a substantial proportion of hotel staff (88.5%) strongly agree on the importance of providing accessibility for guests with disabilities, as evident from the outcomes of the online survey. This outcome demonstrates a commendable high level of awareness among hotel employees concerning the specific needs of customers with disabilities. In terms of hotels’ overarching outlook towards guests with disabilities, a majority of managers voiced the perspective that hotels do not actively focus on disabled guests as a distinct market segment. These findings provide invaluable insights that can guide hotel managers and employees, contributing to a more comprehensive comprehension of how to establish an inclusive environment within the hospitality industry.

SarS Is a Repressor of Staphylococcus aureus Bicomponent Pore-Forming Leukocidins.

Staphylococcus aureus is a successful pathogen that produces a wide range of virulence factors that it uses to subvert and suppress the immune system. These include the bicomponent pore-forming leukocidins. How the expression of these toxins is regulated is not completely understood. Here, we describe a screen to identify transcription factors involved in the regulation of leukocidins. The most prominent discovery from this screen is that SarS, a known transcription factor which had previously been described as a repressor of alpha-toxin expression, was found to be a potent repressor of leukocidins LukED and LukSF-PV. We found that inactivating sarS resulted in increased virulence both in an ex vivo model using primary human neutrophils and in an in vivo infection model in mice. Further experimentation revealed that SarS represses leukocidins by serving as an activator of Rot, a critical repressor of toxins, as well as by directly binding and repressing the leukocidin promoters. By studying contemporary clinical isolates, we identified naturally occurring mutations in the sarS promoter that resulted in overexpression of sarS and increased repression of leukocidins in USA300 bloodstream clinical isolates. Overall, these data establish SarS as an important repressor of leukocidins and expand our understanding of how these virulence factors are being regulated in vitro and in vivo by S. aureus.

Lagrange Optimization of Shock Waves for Two-Dimensional Hypersonic Inlet with Geometric Constraints

The present paper focuses on the Lagrange optimization of shock waves for a two-dimensional hypersonic inlet by limiting the cowl internal angle and inlet length. The results indicate the significant influences of geometric constraints on the configuration of shock waves and performances of an inlet. Specifically, the cowl internal angle mainly affects the internal compression section; the inlet length affects both the internal and external compression sections where the intensity of internal and external compression shock waves shows a deviation of equal. In addition, the performances of optimized inlets at off-design points are further numerically simulated. A prominent discovery is that a longer inlet favors a higher total pressure recovery at the positive AOA; conversely, a shorter inlet can increase the total pressure recovery at the negative AOA.

Editorial

The earliest research on the siliceous raw materials in the territory of Poland dates back to the first years after World War I. A patriarch of these studies was an archaeologist Stefan Krukowski (1890–1982). Together with Jan Samsonowicz (1888–1959), then a young geologist, they undertook a grand survey focused on flint deposits and prehistoric exploitation sites. The year 2022 brings a centennial celebration of their most prominent discovery: Krzemionki (Fig. 1). Exactly on July 19th, 1922, J. Samsonowicz realized that the unusual landscape of Krzemionki is a remnant of a prehistoric flint mine; he later wrote about this: “It came out that the mentioned pits are prehistoric mining shafts, filled with debris and soil” (Samsonowicz 1923: 22, translation by the Editors).

Teachers’ Perceptions of Distance Education During the COVID-19 Pandemic in Saudi Arabia –Riyadh Educational Area

The Internet is one of the most prominent discoveries in the world today. The move of most businesses and establishment to the online platform has been witnessed increasingly. Education is not left out of this development and the government of Saudi Arabia has been reported in several studies to have dedicated to providing the citizens with the best educational option. Studies have also shown that Saudi Arabia has embraced majorly the on-ground method of education given that most students are not intrigued by the idea of online education even though they find it preferable. Several studies have however been carried out on the perception of students of distance education. This 2020 study brings to light the perception of teachers in schools in Riyadh, Saudi Arabia by obtaining a group data. The study showed that teachers positively perceive the method of education but do not have enough resources and training to properly handle teaching through the method. The government is thereby pleaded with to help improve the accessibility of students and training of staff in necessary basics concerning the method of education.

The role of scientific research on nuclear radiation waste management and preserving environment

On the level of this article, we deal with nuclear radiation (and their residues), which is defined as a physical phenomenon and strong atomic activity that occurs in unstable atoms of elements. We are interested in studying radiation as the emission or diffusion of energy into space in the form of electromagnetic waves or particles. The scientist Fermi (1934 AD) is among the first to present scientific research in this field. Radioisotopes are considered one of the most prominent discoveries of modern science and based on the importance of the topic, scientists and researchers searched for methods and techniques to facilitate the implementation of practical applications for radiation measurement, and among those methods a specialized program was used to simulate radiation dose (digital simulation in a computer through the use of an imaginary model of the radiometric process with technology Monte Carlo using code (Geant 4). We have also highlighted the views of researchers and specialists in the area of disposal of radioactive waste, relying on a field study and a comparison of some of the currently adopted techniques to get rid of the negative consequences that each unreasonable (reckless) management and measure of this radioactive waste may have Among the most prominent results we have reached is highlighting the weakness of dealing with this topic and not giving it the right to research and scientific achievements carried out by researchers, which increases the complexity of the situation and from which it is difficult to control the problem in the future.

LINGUISTIC ANALYSIS ON BUSINESS SALES PITCH SCRIPTS

Many challenges are faced by sales representatives in the effort of closing sales deal of product or service offered to their prospective clients. The goal is to persuade the clients to invest in the offered products or services. To perform this, sales representatives need a well-constructed sales script that can help them in enticing their clients. In relation to this, numerous tips and step-by-step advices are given by business professionals on how to craft a good sales script. However, looking at this situation in linguistic spectrum, it is observed that those tips and advices given are lacking justification from the linguistic perspectives which may provide new insights in the craftsmanship of a well-structured sales script. Hence, this paper serves to provide a steady parameter set to give linguistic guidelines for crafting an excellent pitch script. With reference to the theories developed by scholars like Schffrin (1994), Martin (2012), and Widdowson (1996), an analysis was conducted on 10 samples of sales script taken from one of the most successful international sales companies. Data collected shows that there are 6 different types of key linguistic components embedded within the scripts at a different frequency level. One prominent discovery of this study revealed that the different frequency of these key components leads to a rhythmic patterns and themes that immediately distinguish a good sales script with a successful one.
 
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Specific Targeting of Notch Ligand-Receptor Interactions to Modulate Immune Responses: A Review of Clinical and Preclinical Findings.

Understanding and targeting Notch signaling effectively has long been valued in the field of cancer and other immune disorders. Here, we discuss key discoveries at the intersection of Notch signaling, cancer and immunology. While there is a plethora of Notch targeting agents tested in vitro, in vivo and in clinic, undesirable off-target effects and therapy-related toxicities have been significant obstacles. We make a case for the clinical application of ligand-derived and affinity modifying compounds as novel therapeutic agents and discuss major research findings with an emphasis on Notch ligand-specific modulation of immune responses.

Catalyst: Possible Consequences of the N-Methyl Pyrrolidone REACH Restriction

The authors work at the Green Chemistry Centre of Excellence (GCCE) at the University of York and are all currently involved in the H2020-BBI-funded project ReSolve for the development of safer bio-based solvents. Solvent applications for dihydrolevoglucosenone (Cyrene) and 2,2,5,5-tetramethyloxloane (TMO) are among their prominent discoveries. Dr. James Sherwood leads the Alternative Solvents Technology Platform at the GCCE. His research interests include solvent effects in organic synthesis and the substitution of hazardous solvents with novel bio-based solvents. Dr. Thomas Farmer is leader of the Clean Synthesis Technology Platform in the GCCE. Tom works on the development of greener synthetic methods and the uses of bio-derived platform molecules. Prof. James Clark is the director of the GCCE and winner of the 2018 RSC Green Chemistry Award. He has published over 500 articles and is a member of the UK Government’s Chemical Stakeholder Forum.

Formation and characteristics of large-medium buried-hill hydrocarbon reservoirs in Bohai Sea

There had been a long history of the buried-hill hydrocarbon reservoirs exploration operation in Bohai Sea. Between 1970s and 1990s, based on the onshore exploration experiences in eastern China, many boreholes were drilled in order to detect large-scale carbonate buried-hill hydrocarbon reservoirs in Bohai Sea, but no prominent discoveries was achieved. In-depth re-evaluation and examination were conducted upon these exploration failures, a new understanding that Bohai Sea had unique geological characteristics of buried hills was concluded. Bedrocks on the uplifts of Bohai oil province were mainly granites and migmatitic granites of Archean, Proterozoic and Mesozoic, as well as minor Lower Paleozoic carbonates. Proterozoic algae dolomite was most favorable for buried-hill hydrocarbon reservoirs however which were not developed in Bohai Sea. A large number of faults in Bohai oil province were developed and faults activities were intense in the late period. Thus, conventionally, reservoirs and preservation conditions of the buried hills were believed to be poor in Bohai Sea, and were not favourable for formation of large-scale buried-hill hydrocarbon reservoirs. Through the long-term practices and deep analyses, the coupling between granites, migmatitic granites and intense bedrock faults was favorable for buried-hill reservoirs with high test production and relatively low core recovery rate. Geophysical data could be used for accurate predictions of bedrock lithology and faults. The monadnock buried hills on the low uplifts adjacent to hydrocarbon-rich sags were covered by shallow to semi-deep lacustrine shale, which was favorable for buried-hill hydrocarbon reservoirs. Under the guidance of a series of innovative understandings, the re-exploration of buried hills in Bohai Sea achieved two largest granite buried-hill oil and gas fields with 100 million tons of reserves. The understanding and practice processes might also inspire exploration of other areas.

Eco-friendly high-performance silicide thermoelectric materials

Silicide-based thermoelectrics are examples of cost-efficient and environmentally friendly new energy materials, which can be used for power-generation applications in the range of 500-800 K. We review the research focusing on the exploration of n-type Mg2IV-based solid solutions (IV = Si, Ge and Sn) and summarize the most prominent discoveries achieved so far in their studies. Owing to their superior performance compared to other silicides, including p-type Mg2IV, higher manganese silicides (HMS) are commonly considered as a suitable p-type material to be used in thermoelectric modules in conjunction with n-type Mg2IV-based solid solutions for mid-temperature power-generation applications. We describe the strategies used to improve the thermal and electronic transport properties of n-type Mg2IV-based solid solutions and mention some key features of HMS. We also point out the importance of mechanical properties and thermal stability of this family of materials and offer perspectives on the future research work to further improve their performance.

COX-1 Inhibitors: Beyond Structure Toward Therapy.

Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), which exists as COX-1 and COX-2. AA is in turn released from the cell membrane upon neopathological stimuli. COX inhibitors interfere in this catalytic and disease onset process. The recent prominent discovery involvements of COX-1 are mainly in cancer and inflammation. Five classes of COX-1 inhibitors are known up to now and this classification is based on chemical features of both synthetic compounds and substances from natural sources. Physicochemical interactions identification between such molecules and COX-1 active site was achieved through X-ray, mutagenesis experiments, specific assays and docking investigations, as well as through a pharmacometric predictive model building. All these insights allowed the design of new highly selective COX-1 inhibitors to be tested into those disease models in which COX-1 is involved. Particularly, COX-1 is expressed at high levels in the early to advanced stages of human epithelial ovarian cancer, and it also seems to play a pivotal role in cancer progression. The refinement of COX-1 selective inhibitor structure has progressed to the stage that some of the inhibitors described in this review could be considered as promising active principle ingredients of drugs and hence part of specific therapeutic protocols. This review aims to outline achievements, in the last 5 years, dealing with the identification of highly selective synthetic and from plant extracts COX-1 inhibitors and their theranostic use in neuroinflammation and ovarian cancer. Their gastrotoxic effect is also discussed.

Oxidative theory of atherosclerosis and antioxidants.

Atherosclerosis is a multifactorial process that begins early in infancy and affects all the humans. Early steps of atherogenesis and the evolution towards complex atherosclerotic plaques are briefly described. After a brief history of the 'Lipid theory of atherosclerosis', we report the most prominent discoveries on lipoproteins, their receptors and metabolism, and their role in atherogenesis. The main focus is the 'oxidative theory of atherosclerosis', with emphasis on free radicals and reactive oxygen species, lipid peroxidation and LDL oxidation, biological properties of oxidized LDL and their potential role in atherogenesis. Then, we report the properties of antioxidants and antioxidant systems and their effects invitro, on cultured cells, in animal models and in humans. The surprising discrepancy between the efficacy of antioxidants invitro and in animal models of atherosclerosis and the lack of protective effect against cardiovascular events and death in epidemiological study and clinical trials are discussed. In contrast, epidemiological studies seem to indicate that the Mediterranean diet may protect (in part) against atherosclerosis complications (myocardial infarction and cardiovascular death).

High-resolution mapping of ice-marginal landforms in the Barnim region, northeast Germany

Despite more than a 100-year-long research history, timing and position of the last glacial ice margins in the northeast German lowland are still up for debate. The Barnim region, a till plain in the northeast German young morainic landscape, is traversed by the contradictorily discussed Frankfurt ice marginal position. It is located in a key position to reassess the current state of research with help of a geographic information system (GIS) and field methods.A qualitative geomorphological analysis of a high resolution LiDAR digital elevation model (DEM) in the Barnim area uncovers a variety of landforms that were previously not described. The most prominent discovery is a set of about 10 lobe-shaped ridges in the middle Barnim area. Fieldwork and geophysical measurements were carried out to investigate the structure of the ridges. The ridges are 1000–1500m in length and their widths vary from 10 to 15km. They are raised some 6–10m from their surroundings. The Frankfurt ice marginal position can only partially be traced in the DEM. Sedimentological and geophysical investigations indicate that the ridges are composed of glacial till that was deposited on glaciofluvial sediments. Their formation most probably took place during the ice retreat of the Brandenburg phase (W1B) and hence represents the W1F phase in the region.

Julius Caesar Arantius (Giulio Cesare Aranzi, 1530-1589) and the hippocampus of the human brain: history behind the discovery.

Julius Caesar Arantius is one of the pioneer anatomists and surgeons of the 16th century who discovered the different anatomical structures of the human body. One of his prominent discoveries is the hippocampus. At that time, Arantius originated the term hippocampus, from the Greek word for seahorse (hippos ["horse"] and kampos ["sea monster"]). Arantius published his description of the hippocampus in 1587, in the first chapter of his work titled De Humano Foetu Liber. Numerous nomenclatures of this structure, including "white silkworm," "Ammon's horn," and "ram's horn" were proposed by different scholars at that time. However, the term hippocampus has become the most widely used in the literature.

Low mass gluino within the sparticle landscape, implications for dark matter, and early discovery prospects at LHC-7

We analyze supergravity models that predict a low mass gluino within the landscape of sparticle mass hierarchies. The analysis includes a broad class of models that arise in minimal and in nonminimal supergravity unified frameworks and in extended models with additional $U(1{)}_{X}^{n}$ hidden sector gauge symmetries. Gluino masses in the range (350--700) GeV are investigated. Masses in this range are promising for early discovery at the LHC at $\sqrt{s}=7\text{ }\text{ }\mathrm{TeV}$ (LHC-7). The models exhibit a wide dispersion in the gaugino-Higgsino eigencontent of their lightest supersymmetric particles and in their associated sparticle mass spectra. A signature analysis is carried out and the prominent discovery channels for the models are identified with most models needing only $\ensuremath{\sim}1\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ for discovery at LHC-7. In addition, significant variations in the discovery capability of the low mass gluino models are observed for models in which the gluino masses are of comparable size due to the mass splittings in different models and the relative position of the light gluino within the various sparticle mass hierarchies. The models are consistent with the current stringent bounds from the Fermi-LAT, CDMS-II, XENON100, and EDELWEISS-2 experiments. A subclass of these models, which include a mixed--$w$-ino lightest supersymmetric particle and a Higgsino lightest supersymmetric particle, are also shown to accommodate the positron excess seen in the PAMELA satellite experiment.

Tel Beth Shean During the EB IB Period: Evidence for Social Complexity in the Late 4th Millennium BC

The Early Bronze I (henceforth EB I) is a formative era in the Southern Levant. Modern research has thrown light on many aspects of this period: its long duration, its spatial and temporal subdivisions, its settlement pattern, its socio-economic characterizations, and the phenomenon of Egyptian colonization in southern Palestine (e.g. Stager 1992, 28–34; Joffe 1993, 39–62; Braun 1996). Among the prominent discoveries related to the later part of EB I (denoted here EB IB) are the monumental temple at Megiddo and the notion that certain sites were fortified. These features may require us to change the way in which we conceive of socio-political developments during the late 4th millennium BC, in particular in northern Palestine.In the present paper, we present two phases of an unusual EB IB building excavated at Tel Beth Shean. The stratigraphy, architecture and finds from this building raise intriguing questions concerning architectural traditions, function, economy, social complexity and regionalism in material culture. The evidence also bears on matters of chronology, and the way in which we define the transition from EB I to EB II in the region. While a full account will appear in the final excavation report (Mazar (ed.) forthcoming), some of these issues were felt to warrant more immediate consideration.

Three‐dimensional P‐wave velocity structure of Iwate volcano, Japan from active seismic survey

The three‐dimensional P‐wave velocity structure of the Iwate volcano, northeastern Japan, is determined to depths of 2 km through an active seismic survey conducted in October 2000. Seismic tomography is applied to approximately 2700 travel‐time data. The most prominent discovery is an existing of column‐like high‐velocity body (Vp > 5.4 km/s) that extends vertically for 2 km beneath the caldera. While the western part of the volcano extending from the caldera is characterized by a moderate‐velocity region (4.8 < Vp < 5.4 km/s), the summit and eastern flank of the volcano are covered with very low‐velocity material (Vp < 4 km/s) which represent relatively younger volcanic edifices. The spatial difference in the velocity structures between the western and eastern parts of the volcano is explained by the evolutionary history of the volcano. And we find that the western structure may give constraints on the volcanic activity in 1998.

Search for glueballs at crystal barrel

The present state of the research for glueballs with the Crystal Barrel experiment is summarized. The most prominent discovery is a scalar resonance at 1500 MeV/c 2 which does not fit into a 0 ++ nonet. It is interpreted as the glueball groundstate.