bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Pheromone trap against the melon fly (Miopardalis pardalina Big.) in Agriculture
Authors: Yuldashev Laziz , Djumakulov Turgunboy , Turdibaev Zhakhongir , Rifky Mohamed
Published: June 2024

The intensive development of agricultural production currently requires an expansion of the use of chemicals to protect plants from insect pests, which in turn leads to environmental pollution and irreparable losses in biocenosis. The use of sex pheromones in integrated plant protection systems requires the development of a convenient pheromone trap. This article describes a method of controlling the melon fly using the pheromone component 4 (4-methoxyphenyl)-2-butanone, 1,4-benzyl dicarboxylate. A pheromone trap is a design with bait and a rubber capsule dispenser treated with a mixture of pheromone substances. The results of using pheromone traps to monitor the melon fly in open ground are presented.
Environmental Philosophy: Exploring Sustainable Development and Humanity's Ethical Responsibilities to the Environment and Future Generations
Authors: Kalmamatova Zamira , Mamaturaimova Gulgaky , Bakieva Saken
Published: June 2024

In this journey through environmental philosophy, we try to understand how we can sustainably develop our world while also respecting the environment and safeguarding the well-being of future generations. We stick with questions of ethics and responsibility, seeking to make a harmonious balance between human progress and the preservation of our planet’s natural resources. Through thoughtful exploration and introspection, we aim to cultivate a deeper understanding of our interconnectedness with the environment and our moral obligations towards it to develop a sustainable environment.
Organization of primary health care as a factor in the effective development of rural areas
Authors: Oshkordina Alla , Goncharova Nadezhda , Makarova Elena , Esina Ekaterina
Published: June 2024

The gist of this article boils down to modern methodological approaches to organizing the provision of primary health care in order to improve the quality of life of the rural population in the Sverdlovsk region. The authors reflect the need for reorganization of domestic healthcare towards a focus on the preventive focus of the treatment and diagnostic process, as well as early detection of severe forms of diseases, which is associated with the provision of high-quality, affordable medical care to the population of rural areas. During the analysis of information and analytical material reflecting the activities of primary health care, the authors identified positive and negative trends in its development within a single subject of the Russian Federation. The main directions for the further development of primary medical and social care to the population have been identified in order to improve the medical and demographic indicators of rural areas.
Organic agriculture as a sustainable approach to food security
Authors: Stikhina Irina , Skopova Ludmila , Lapina Valentina
Published: June 2024

The present article discusses the development of organic agriculture in the Russian Federation and abroad. Organic agriculture is a sustainable approach to agricultural land use and can contribute to producing sufficient amount of environmentally friendly agricultural products, while lessening environmental impacts from agricultural activities. The authors conclude on the importance of government support through legislation, action plans and funding for organic agriculture to be economically viable and contribute to producing sufficient amount of healthy food for future generations.
Application of Accelerated Shelf-Life Testing for Determination of Bioactive Emulsion Food Systems’ Shelf Life
Authors: Feofilaktova Olga , Zavorokhina Nataliya , Makarova Elena
Published: June 2024

Determination of the shelf life of food systems involves time consuming and labor-intensive studies. Application of Accelerated Shelf Life Testing (ASLT) allows to determine the degree of time influence and assess environmental conditions’ impact on a food system as well as establish its shelf life in a short time span. This method is extensively applied in various areas, including food industries and scientific research. However, identifying of such dependencies for particular types of food systems is essential. The purpose of the research is to determine shelf life of bioactive emulsion food systems, namely emulsion food systems additionally enriched with biologically active substances, applying ASLT. The studies in this field, which had been conducted at 45±1°C, 40±1°C and 35±1°C temperature control, demonstrated acceleration of chemical processes by 12, 11 and 9 times compared to the control sample with the storage temperature of +4°±2°C. Shelf life of bioactive emulsion food systems was established in compliance with the requirements and absence of significant differences in the values of organoleptic and physicochemical parameters of the samples, tested at higher temperatures in comparison to the control sample. A three-month period was proved to be the shelf life of bioactive emulsion food systems. This conclusion was made on the basis of the time of emerging of crucial differences, taking into consideration the safety factor.
The impact of educational digitalization on the creativity of students with special needs: the role of study crafting and creative self-efficacy
Authors: Zhang Qi , Shi Boxuan , Liu Yuchao , Liang Zhou , Qi Liangqun
Published: June 2024

Special needs are of paramount importance in international equitable education. The focus on students with special needs has become the basis of current special education and education reform. The world is currently undergoing a pivotal phase of digital transformation, with educational digitalization gradually developing. However, only a few studies have focused on the effect of educational digitalization on the creativity of students with special needs, and most of them have ignored its internal mechanism. This study therefore aims to explore the manner in which and the circumstances under which educational digitalization affects the creativity of students with special needs. Building upon information theory, this study proposes a mediated moderating framework to examine the effects of educational digitalization on the creativity of students with special needs, considering the mediating role of studying crafting and the moderating effect of creative self-efficacy. A survey methodology was employed to collect empirical data on the interrelationships among educational digitalization, study crafting, creative self-efficacy, and the creativity of students with special needs. The results demonstrated a significant positive relationship between educational digitalization and the creativity of students with special needs through study crafting. Furthermore, creative self-efficacy was found to play a moderating role in this process. The findings provide educators and policymakers with practical guidance on how to optimize the implementation of digital technologies in educational environments in order to promote education equity.
IgG and IgM differentiation in a particle-based agglutination assay by control over antigen surface density
Authors: Gandhi Shanil , Shaulli Xhorxhina , Fock Jeppe , Scheffold Frank , Marie Rodolphe
Published: June 2024

Point-of-care (POC) testing offers fast and on-site diagnostics and can be crucial against many infectious diseases and in screening. One remaining challenge in serological POC testing is the quantification of immunoglobulin G (IgG) and immunoglobulin M (IgM). Quantification of IgG/IgM can be important to evaluate immunity and to discriminate recent infections from past infections and primary infections from secondary infections. POC tests such as lateral flow immunoassays allow IgG and IgM differentiation; however, a remaining limitation is their incapacity to provide quantitative results. In this work, we show how samples containing IgG or IgM can be distinguished in a nanoparticle-based agglutination biosensing assay by tuning the density of antigens on the nanoparticles' surface. We employ direct STochastic Optical Reconstruction Microscopy to quantify the accessible SARS-CoV-2 trimeric spike proteins conjugated to magnetic nanoparticles at a single-particle level and gain insight into the protein distribution provided by the conjugation procedure. Furthermore, we measure the anti-SARS-CoV-2 IgG/IgM induced agglutination using an optomagnetic readout principle. We show that particles with high antigen density have a relatively higher sensitivity toward IgM compared to IgG, whereas low antigen density provides a relatively higher sensitivity to IgG. The finding paves the way for its implementation for other agglutination-based serology tests, allowing for more accurate disease diagnosis.
Control of biofilm formation by an
Agrobacterium tumefaciens
pterin-binding periplasmic protein conserved among diverse
Proteobacteria
Authors: Greenwich Jennifer L. , Eagan Justin L. , Feirer Nathan , Boswinkle Kaleb , Minasov George , Shuvalova Ludmilla , Inniss Nicole L. , Raghavaiah Jakka , Ghosh Arun K. , Satchell Karla J. F. , Allen Kylie D. , Fuqua Clay
Published: June 2024

Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogen
Agrobacterium tumefaciens
produces a UPP adhesin, which is regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP). Prior studies revealed that DcpA, a diguanylate cyclase-phosphodiesterase, is crucial in control of UPP production and surface attachment. DcpA is regulated by PruR, a protein with distant similarity to enzymatic domains known to coordinate the molybdopterin cofactor (MoCo). Pterins are bicyclic nitrogen-rich compounds, several of which are produced via a nonessential branch of the folate biosynthesis pathway, distinct from MoCo. The pterin-binding protein PruR controls DcpA activity, fostering c-di-GMP breakdown and dampening its synthesis. Pterins are excreted, and we report here that PruR associates with these metabolites in the periplasm, promoting interaction with the DcpA periplasmic domain. The pteridine reductase PruA, which reduces specific dihydro-pterin molecules to their tetrahydro forms, imparts control over DcpA activity through PruR. Tetrahydromonapterin preferentially associates with PruR relative to other related pterins, and the PruR-DcpA interaction is decreased in a
pruA
mutant. PruR and DcpA are encoded in an operon with wide conservation among diverse Proteobacteria including mammalian pathogens. Crystal structures reveal that PruR and several orthologs adopt a conserved fold, with a pterin-specific binding cleft that coordinates the bicyclic pterin ring. These findings define a pterin-responsive regulatory mechanism that controls biofilm formation and related c-di-GMP-dependent phenotypes in
A. tumefaciens
and potentially acts more widely in multiple proteobacterial lineages.
AMBRA1 levels predict resistance to MAPK inhibitors in melanoma
Authors: Di Leo Luca , Pagliuca Chiara , Kishk Ali , Rizza Salvatore , Tsiavou Christina , Pecorari Chiara , Dahl Christina , Pacheco Maria Pires , Tholstrup Rikke , Brewer Jonathan Richard , Berico Pietro , Hernando Eva , Cecconi Francesco , Ballotti Robert , Bertolotto Corine , Filomeni Giuseppe , Gjerstorff Morten Frier , Sauter Thomas , Lovat Penny , Guldberg Per , De Zio Daniela
Published: June 2024

Intrinsic and acquired resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma remains a major therapeutic challenge. Here, we show that the clinical development of resistance to MAPKi is associated with reduced tumor expression of the melanoma suppressor Autophagy and Beclin 1 Regulator 1 (AMBRA1) and that lower expression levels of AMBRA1 predict a poor response to MAPKi treatment. Functional analyses show that loss of AMBRA1 induces phenotype switching and orchestrates an extracellular signal-regulated kinase (ERK)-independent resistance mechanism by activating focal adhesion kinase 1 (FAK1). In both in vitro and in vivo settings, melanomas with low AMBRA1 expression exhibit intrinsic resistance to MAPKi therapy but higher sensitivity to FAK1 inhibition. Finally, we show that the rapid development of resistance in initially MAPKi-sensitive melanomas can be attributed to preexisting subclones characterized by low AMBRA1 expression and that cotreatment with MAPKi and FAK1 inhibitors (FAKi) effectively prevents the development of resistance in these tumors. In summary, our findings underscore the value of AMBRA1 expression for predicting melanoma response to MAPKi and supporting the therapeutic efficacy of FAKi to overcome MAPKi-induced resistance.
Quantum information splitting among N-quantum nodes within a quantum network by using Bell states
Authors: Verma Vikram
Published: June 2024

In quantum information processing, it is essential to ensure the security of quantum information so that it cannot be stolen and interrupted by an eavesdropper. For ensuring the security of information, quantum information splitting (QIS) method is used in which quantum communication is made more secure by splitting the quantum information among the various quantum nodes within a quantum network in such a way that any one node can retrieve the quantum information completely with the collaboration of remaining quantum nodes. In this paper, by using Bell states as the quantum channel we present a simple and precise scheme for quantum information splitting of an arbitrary single-qubit quantum information state among N (N ≥ 2) recipient nodes which are separately entangled with the sender node only and not with one another. We also generalize our scheme to the splitting of multi-qubit quantum information state among the N recipient nodes by using 2-qubit Bell states as the quantum resource. In comparison to the previous existing QIS schemes which require multi-qubit entangled states as the quantum resource, our proposed QIS scheme is very simple and feasible.
Investigating the properties of co-precipitated nickel cobalt phosphate (NiCoP) nanoparticles for energy storage applications
Authors: Alshoaibi Adil , Nkele Agnes C , Getaneh Seyoum A , Awada Chawki , Islam Shumaila , Ezema Fabian I
Published: June 2024

Nickel cobalt phosphate (NiCoP) nanoparticles were synthesized by a co-precipitation method at concentrations of 0.1 M, 0.2 M, 0.3 M, 0.4 M, and 0.5 M. Drop-casting method was utilized in depositing the nanoparticles on the substrate surface to ensure uniform distribution on the substrate surface. Various analytical techniques including XRD, SEM, EDX, Raman spectroscopy, and electrochemical measurements were employed to comprehensively understand the structural, morphological, elemental, vibrational, and electrochemical properties of the synthesized nanoparticles. Results indicate amorphous phases for all samples, with nanoflake-like morphology observed via SEM, and constituent elements confirmed through EDX analysis. Raman spectroscopy validates the composition, while electrochemical measurements demonstrate the NiCoP electrodes’ promising utility in energy storage, particularly with the 0.1 M electrode exhibiting a maximum specific capacitance of 91.2 F g−1 and stability over 3000 cycles. Overall, the findings highlight the potential applications of NiCoP nanoparticles in energy storage and electrochemical devices, providing valuable insights for researchers in the field.
Holographic timelike entanglement entropy from Rindler method*
Authors: He 贺 Peng-Zhang 鹏璋 , Zhang 张 Hai-Qing 海青
Published: June 2024

For a Lorentzian invariant theory, the entanglement entropy should be a function of the domain of dependence of the subregion under consideration. More precisely, it should be a function of the domain of dependence and the appropriate cut-off. In this study, we refine the concept of cut-off to make it applicable to timelike regions and assume that the usual entanglement entropy formula also applies to timelike intervals. Using the Rindler method, the timelike entanglement entropy can be regarded as the thermal entropy of the CFT after the Rindler transformation plus a constant

, where c denotes the central charge. The gravitational dual of the 'covariant' timelike entanglement entropy is presented following this method.
Topology of charged AdS black hole in restricted phase space*
Authors: Wang 王 Han 菡 , Du 杜 Yun-Zhi 云芝
Published: June 2024

The local topological properties of black hole systems can be expressed through winding numbers as defects. To date, AdS black hole thermodynamics are often depicted by the dual parameters of

in the extended phase space, while there have been several studies on the black hole thermodynamics in the restricted phase space. In this paper, we analyze the topological properties of charged AdS black holes in the restricted phase space under the higher-dimension and higher-order curvature gravity frame. The results show that the topological number of the charged black hole in the same canonical ensembles is a constant and is independent of the concrete dual thermodynamical parameters. However, the topological number in the grand canonical ensemble is different from that in the canonical ensemble for the same black hole system. Furthermore, these results are independent of dimension d and highest order k of the Lanczos-Lovelock densities.
Flexures for Kibble balances: minimizing the effects of anelastic relaxation
Authors: Keck Lorenz , Schlamminger Stephan , Theska René , Seifert Frank , Haddad Darine
Published: June 2024

We studied the anelastic aftereffect of a flexure being used in a Kibble balance, where the flexure is subjected to a large excursion in velocity mode after which a high-precision force comparison is performed. We investigated the effect of a constant and a sinusoidal excursion on the force comparison. We explored theoretically and experimentally a simple erasing procedure, i.e. bending the flexure in the opposite direction for a given amplitude and time. We found that the erasing procedure reduced the time-dependent force by about 30%. The investigation was performed with an analytical model and verified experimentally with our new Kibble balance at the National Institute of Standards and Technology employing flexures made from precipitation-hardened Copper Beryllium alloy C17200. Our experimental determination of the modulus defect of the flexure yields

1.2
×

10

−
4

. This result is about a factor of two higher than previously reported from experiments. We additionally found a static shift of the flexure’s internal equilibrium after a change in the stress and strain state. These static shifts, although measurable, are small and deemed uncritical for our Kibble balance application at present. During this investigation, we discovered magic flexures that promise to have very little anelastic relaxation. In these magic flexures, the mechanism causing anelastic relaxation is compensated for by properly shaping and loading a flexure with a non-constant cross-section in the region of bending.
A simple and effective method for smartphone-based detection of polyamines in oral cancer
Authors: Mojumdar Asmita , B S Unnikrishnan , Packirisamy Gopinath
Published: June 2024

Oral cancer accounts for 50%–70% of all cancer-related deaths in India and ranks sixth among the most frequent cancers globally. Roughly 90% of oral malignancies are histologically arise from squamous cells and are therefore called oral squamous cell carcinoma. Organic polycations known as biogenic polyamines, for example, putrescine (Put), spermidine (Spd), and spermine (Spm), are vital for cell proliferation, including gene expression control, regulation of endonuclease-mediated fragmentation of DNA, and DNA damage inhibition. Higher Spm and Spd levels have been identified as cancer biomarkers for detecting tumour development in various cancers. The current study utilises tannic acid, a polyphenolic compound, as a reducing and capping agent to fabricate AuNPs via a one-step microwave-assisted synthesis. The fabricated TA@AuNPs were utilised as a nanoprobe for colourimetric sensing of polyamines in PBS. When TA@AuNPs are added to the polyamine, the amine groups in polyamines interact with the phenolic groups of TA@AuNPs via hydrogen bonding or electrostatic interactions. These interactions cause the aggregation of TA@AuNPs, resulting in a red shift of the Surface Plasmon Resonance band of TA@AuNPs from 530 nm to 560 nm. The nanoprobe was found to be highly specific for Spm at low concentrations. TA@AuNPs were able to detect Spm successfully in artificial saliva samples. On recording the RGB values of the sensing process using a smartphone app, it was found that as the nanoparticles aggregated due to the presence of Spm, the intensity of the R-value decreased, indicating the aggregation of TA@AuNPs due to interaction with the polyamine.
Strengthened impact of late autumn Arctic sea ice on Asian winter cold extremes after 1999/2000
Authors: Wang Cen , Su Hui , Zheng Jianqiu , Yu Shiwei , Jiang Linwei , Mo Huisi
Published: June 2024

Winter cold extremes (WCEs) frequently plague densely populated areas of Asia, leading to substantial economic losses and even fatalities. It has been found that the late autumn sea ice concentration (SIC) anomalies in the northern (SICN) and southern Arctic (SICS) are significantly positively and negatively correlated with the occurrence frequency of WCE in Asia, respectively (Wang and Su 2024). Our study demonstrates that the impacts of SICN and SICS have strengthened after 1999/2000. Specifically, before 1999/2000, the influences of SICN and SICS on the Asian WCE (AWCE) were relatively weak, possibly related to the weak intensity of SICS and the limited correlation between SICN and SICS. After 1999/2000, the interannual variability of SICS became larger and anti-correlated with that of SICN, resulting in a stronger teleconnection between the Arctic SIC and AWCE. It is revealed that after 1999/2000, the greater loss of SICS modified atmospheric stability through changes in surface heat fluxes and surface upward longwave radiation fluxes. This alteration weakened the magnitudes of westerly winds and increased the frequency of blocking events over the northern Eurasian continent, leading directly to a higher occurrence of cold extremes in Asia. These interdecadal differences in the influence of Arctic SIC on AWCE may be associated with long-term climate change.
Reducing hardware requirements for entanglement distribution via joint hardware-protocol optimization
Authors: Labay Mora Adrià , Ferreira da Silva Francisco , Wehner Stephanie
Published: June 2024

We conduct a numerical investigation of fiber-based entanglement distribution over distances of up to 1600 km using a chain of processing-node quantum repeaters. We determine minimal hardware requirements while simultaneously optimizing over protocols for entanglement generation and entanglement purification, as well as over strategies for entanglement swapping. Notably, we discover that through an adequate choice of protocols the hardware improvement cost scales linearly with the distance covered. Our results highlight the crucial role of good protocol choices in significantly reducing hardware requirements, such as employing purification to meet high-fidelity targets and adopting a swap as soon as possible policy for faster rates. To carry out this analysis, we employ an extensive simulation framework implemented with NetSquid, a discrete-event-based quantum-network simulator, and a genetic-algorithm-based optimization methodology to determine minimal hardware requirements.
Engineering intelligent motion control protocol for dual-resolution linear actuator with unified coupled drive system
Authors: Agrawal Gagan , Patel Naimesh , Mathur Neeraj , Joshi Shaunak R , S Shri Hari
Published: June 2024

Actuators with high resolution and high range are always in demand for critical applications such as space applications, machining, and medical equipment. A dual-resolution actuator that has a coarse motion segment and a fine motion segment in itself that runs through a common drive system was designed. A coupling mechanism is employed to engage and disengage with the coarse motion of the actuator, enabling the use of coarse motion only when required. The actuator can achieve the target in any of three methods: (1) directly through fine motion, (2) utilizing a combination of fine and coarse motion without the need to overshoot the target value, and (3) employing both fine and coarse motion with a need for overshoot of the target value. An intelligent algorithm employing multiple techniques to address sensor-induced delays and enhance runtime efficiency was developed and tested on the realized actuator. This paper describes the techniques adopted and the sequence of conditions used to enable the actuator to reach the target in the shortest time and minimum possible steps.
GaAs-on-insulator ridge waveguide nanobeam cavities with integrated InAs quantum dots
Authors: Zhou Yueguang , Yang Yuhui , Wang Yujing , Koulas-Simos Aris , C Palekar Chirag , Limame Imad , Li Shulun , Liu Hanqing , Ni Haiqiao , Niu Zhichuan , Yvind Kresten , Gregersen Niels , Pu Minhao , Reitzenstein Stephan
Published: June 2024

This study investigates nanobeam cavities on a GaAs-on-insulator (GaAsOI) chip with InAs quantum dots (QDs), including design, fabrication, and experimental characterization. The nanobeam cavities are optimized for high photon coupling efficiency and pronounced light-matter interaction. Numerical studies yield Q factors up to about 1400, a coupling efficiency of nearly 70

%

and a maximum Purcell factor of approximately 100. Experimentally, these devices have a Q factor of about 1300, and comparing the lifetime of QDs in on-resonance and off-resonance conditions, a Purcell factor of

10.46
±
0.14

is obtained. Moreover, in the single-emitter regime, we observe strong multiphoton suppression with

g

(
2
)

(
0
)
=
0.297

. Our results demonstrate the high potential of nanobeam cavities on a GaAsOI platform for quantum photonic applications.
Late Acceleration
Authors: Chatterjee Elizabeth
Published: June 2024

The energy crisis of the early 1970s briefly opened up a radically new horizon of energetic possibilities that played out differently around the world. For India, that energy crisis did not begin with the famous Arab oil embargo of 1973. Instead, like many poor oil-importing nations, it experienced the first oil shock as merely one component of a broader climate-food-energy emergency that reverberated throughout the political system. This crisis brought a twinned set of fateful changes. By June 1975, Prime Minister Indira Gandhi had resorted to imposing a constitutional dictatorship—the Emergency—for the first and only time in independent India’s existence, one among a series of coups and authoritarian takeovers that swept the Global South. Less noticed was a second transformation with planetary ramifications. Rising popular expectations collided with the energy crisis to impel a state-led embrace of coal, despite elite reservations about the environmental damage that would follow. Analyzing these dynamics is crucial to understanding India’s intensifying coal dependence, and its rapidly rising carbon emissions, in the decades that followed. Only when we accurately recognize the forces that created and hold carbon-intensive energy regimes in place can we begin to see how they might be dislodged.
A Prospective, Randomized, Double-Blind, Split-Face, Comparative Study to Evaluate the Efficacy and Safety of DKL23 and Juvéderm Volift for Correcting Moderate-to-Severe Nasolabial Folds
Authors: Alimohammadi Mohammad , Furman-Assaf Sharon , Nilsson Johan
Published: June 2024

Background

Hyaluronic acid dermal fillers are used for multiple indications, including wrinkle correction and restoration of volume/fullness.

Objectives

The aim of this study was to compare the efficacy and safety of 2 hyaluronic acid products for correcting moderate to severe nasolabial folds (NLFs).

Methods

A prospective, randomized, double-blind, split-face study was undertaken. The subjects’ left and right NLFs were randomly allocated for treatment with DKL23 or Juvéderm Volift. Follow-up was conducted at 1, 3, 6, and 9 months. The changes from baseline on the Wrinkle Severity Rating Scale and the Global Aesthetics Improvement Scale were evaluated. Posttreatment adverse events (AEs) were recorded.

Results

Forty-eight women (median age, 57.0 years) with Type I to VI skin were enrolled. Both treatments showed statistically significant improvement (P < .0001) in NLFs according to the Wrinkle Severity Rating Scale score from baseline to each of the time points assessed. The improvement in NLFs was maintained until the end of the study (9 months). Furthermore, the change from baseline to each of the time points assessed was similar between DKL23 and Juvéderm Volift. Investigator- and subject-rated Global Aesthetics Improvement Scale scores showed similar rates of improvement (indicated by the sum of responses of improved, much improved, or very much improved) between the 2 products. The AEs reported in the study were in line with previous and expected experience after injection of hyaluronic acid dermal fillers. The types of AEs, their rates, intensity, and duration were comparable between the 2 products.

Conclusions

DKL23 improved NLF severity from baseline and for up to 9 months, and the results were comparable to the improvement shown by Juvéderm Volift. Treatment was safe and well tolerated.

Level of Evidence: 2
HELM-GPT: de novo macrocyclic peptide design using generative pre-trained transformer
Authors: Xu Xiaopeng , Xu Chencheng , He Wenjia , Wei Lesong , Li Haoyang , Zhou Juexiao , Zhang Ruochi , Wang Yu , Xiong Yuanpeng , Gao Xin
Published: June 2024

Motivation

Macrocyclic peptides hold great promise as therapeutics targeting intracellular proteins. This stems from their remarkable ability to bind flat protein surfaces with high affinity and specificity while potentially traversing the cell membrane. Research has already explored their use in developing inhibitors for intracellular proteins, such as KRAS, a well-known driver in various cancers. However, computational approaches for de novo macrocyclic peptide design remain largely unexplored.

Results

Here, we introduce HELM-GPT, a novel method that combines the strength of the hierarchical editing language for macromolecules (HELM) representation and generative pre-trained transformer (GPT) for de novo macrocyclic peptide design. Through reinforcement learning (RL), our experiments demonstrate that HELM-GPT has the ability to generate valid macrocyclic peptides and optimize their properties. Furthermore, we introduce a contrastive preference loss during the RL process, further enhanced the optimization performance. Finally, to co-optimize peptide permeability and KRAS binding affinity, we propose a step-by-step optimization strategy, demonstrating its effectiveness in generating molecules fulfilling both criteria. In conclusion, the HELM-GPT method can be used to identify novel macrocyclic peptides to target intracellular proteins.

Availability and implementation

The code and data of HELM-GPT are freely available on GitHub (https://github.com/charlesxu90/helm-gpt).
Ragas: integration and enhanced visualization for single cell subcluster analysis
Authors: Balaji Uthra , Rodríguez-Alcázar Juan , Balasubramanian Preetha , Smitherman Cynthia , Baisch Jeanine , Pascual Virginia , Gu Jinghua
Published: June 2024

Subcluster analysis is a powerful means to improve clustering and characterization of single cell RNA-Seq data. However, there are no existing tools to systematically integrate results from multiple subclusters, which creates hurdles for accurate data quantification, visualization, and interpretation in downstream analysis. To address this issue, we developed Ragas, an R package that integrates multi-level subclustering objects for streamlined analysis and visualization. A new data structure was implemented to seamlessly connect and assemble miscellaneous single cell analyses from different levels of subclustering, along with several new or enhanced visualization functions. Moreover, a re-projection algorithm was developed to integrate nearest-neighbor graphs from multiple subclusters in order to maximize their separability on the combined cell embeddings, which significantly improved the presentation of rare and homogeneous subpopulations.

Availability and implementation

The Ragas package and its documentation can be accessed through https://github.com/jig4003/Ragas and its source code is also available at https://zenodo.org/records/11244921.
Integrative profiling of untreated primary membranous nephropathy at the single-cell transcriptome level
Authors: Gu Qiuhua , Wen Yuchen , Cheng Xi , Qi Yan , Cao Xin , Gao Xiqian , Mao Xiaoming , Shang Wenya , Wei Li , Jia Junya , Yan Tiekun , Cai Zhigang
Published: June 2024

Background

Primary membranous nephropathy (PMN) is an autoimmune kidney disease. Despite the identification of certain autoantigens, the etiology and pathophysiology of PMN are still largely unknown.

Methods

Five patients with biopsy-proven PMN were enrolled in this study. Their blood, kidney and urine samples were collected respectively to profile cellular, molecular and immunological alterations by using single-cell RNA sequencing (scRNA-seq). Experimental verifications were also implemented in kidney tissue.

Results

In the peripheral blood mononuclear cell (PBMC) samples, portions of B cells and plasma cells were increased in PMN patients. Cell–cell communication analysis suggests that APRIL (a proliferation-inducing ligand from B cells) might be a potential molecule that regulates the activity of plasma cells. In the kidney samples, scRNA-seq analysis showed that the infiltration of T cells, as well as the myeloid cells, appears abundant compared with healthy controls, suggesting that immune cells are actively recruited to kidney. Furthermore, we observed an enhanced interaction between inflammatory cells and podocytes, which might contribute to kidney injury. Accordingly, scRNA-seq analysis of urinary samples is partially reminiscent of the kidney cell landscape, especially T cells and myeloid cells, suggesting monitoring urinary samples is a promising method to monitor PMN development. Additionally, integrative analysis across the blood, kidney and urine identified LTB, HERP1, ANXA1, IL1RN and ICAM1 as common regulators of PMN. Finally, immune repertoire in PBMC also showed an elevated diversity of clonal type, implying the existence of autoreactive T-cell receptor/B-cell receptor.

Conclusion

Our study comprehensively profiled the transcriptomic landscapes of blood, kidney and urine in patients with PMN using scRNA-seq. We depicted the alterations including cell compositions and cell–cell communication in PMN. These results offer important clues with regard to the diagnosis and pathogenesis of PMN and potential intervention of PMN progression.
Cold mountain stream chironomids (Diptera) of the genus Diamesa indicate both historical and recent climate change
Authors: Dočkalová Kateřina , Stuchlík Evžen , Hamerlík Ladislav , Bitušík Peter , Turek Jan , Svitok Marek , Novikmec Milan , Lackner Reinhard , Dvorak Martin , Kopáček Jiří , Tátosová Jolana , Camarero Lluís , Füreder Leopold , Vondrák Daniel
Published: June 2024

Chironomids of the genus Diamesa (Meigen, 1835, Diptera: Chironomidae) inhabit cold, oxygen-rich running waters. We have investigated the presence of Diamesa and other freshwater macroinvertebrates at 22 stream sampling sites in 3 European high mountain regions (the Central Pyrenees, the Ötztal Alps, and the Tatra Mountains) to establish suitable temperature conditions for Diamesa dominance. It has been generally accepted that their high abundance was linked to the presence of glaciers; however, we have shown that in the Tatra Mountains, where there are no glaciers, the conditions for the dominance of Diamesa species are created due to permanent snowfields, the geographical orientation of the valley and shading by the surrounding high peaks. The historical connection of Diamesa to glaciers was investigated from the paleolimnological records of subfossil chironomid assemblages from the Bohemian Forest, where glaciers disappeared before or during the Late Glacial period.

As expected, water temperature seems to be the main driver of Diamesa distribution, and we determined that the relative abundance of Diamesa species was significantly higher at the sites with a mean July water temperature below 6.5 °C. The Diamesa-dominated stream communities seems to be endangered due to ongoing climate warming and this assumption is supported by our paleolimnological results from the Bohemian Forest lakes, where Diamesa has disappeared due to warming of lake inflows at the beginning of the Holocene. These findings strengthen the former suggestions that some Diamesa species could be used as an indicator for tracking recent environmental changes in vulnerable ecosystems of cold mountain streams.
PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome
Authors: Rudd Garces Gabriela , Farke Daniela , Schmidt Martin J , Letko Anna , Schirl Katja , Abitbol Marie , Leeb Tosso , Lyons Leslie A , Lühken Gesine
Published: June 2024

This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from 2 different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included 10 blue-eyed animals. A brainstem auditory evoked response test revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the 8 examined DBE animals. We sequenced the genome of 2 affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded 9 private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2, and TYRP1. The genotype–phenotype cosegregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate—a heterozygous nonsense single base pair substitution in exon 6 of PAX3 (NC_051841.1:g.205,787,310G>A, XM_019838731.3:c.937C>T, XP_019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory–pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness, and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat.
Generalized open-source workflows for atomistic molecular dynamics simulations of viral helicases
Authors: Raubenolt Bryan , Blankenberg Daniel
Published: June 2024

Viral helicases are promising targets for the development of antiviral therapies. Given their vital function of unwinding double-stranded nucleic acids, inhibiting them blocks the viral replication cycle. Previous studies have elucidated key structural details of these helicases, including the location of substrate binding sites, flexible domains, and the discovery of potential inhibitors. Here we present a series of new Galaxy tools and workflows for performing and analyzing molecular dynamics simulations of viral helicases. We first validate them by demonstrating recapitulation of data from previous simulations of Zika (NS3) and SARS-CoV-2 (NSP13) helicases in apo and complex with inhibitors. We further demonstrate the utility and generalizability of these Galaxy workflows by applying them to new cases, proving their usefulness as a widely accessible method for exploring antiviral activity.
The genomes of Dahlia pinnata, Cosmos bipinnatus, and Bidens alba in tribe Coreopsideae provide insights into polyploid evolution and inulin biosynthesis
Authors: Wang Hengchao , Xu Dong , Jiang Fan , Wang Sen , Wang Anqi , Liu Hangwei , Lei Lihong , Qian Wanqiang , Fan Wei
Published: June 2024

Background

The Coreopsideae tribe, a subset of the Asteraceae family, encompasses economically vital genera like Dahlia, Cosmos, and Bidens, which are widely employed in medicine, horticulture, ecology, and food applications. Nevertheless, the lack of reference genomes hinders evolutionary and biological investigations in this tribe.

Results

Here, we present 3 haplotype-resolved chromosome-level reference genomes of the tribe Coreopsideae, including 2 popular flowering plants (Dahlia pinnata and Cosmos bipinnatus) and 1 invasive weed plant (Bidens alba), with assembled genome sizes 3.93 G, 1.02 G, and 1.87 G, respectively. We found that Gypsy transposable elements contribute mostly to the larger genome size of D. pinnata, and multiple chromosome rearrangements have occurred in tribe Coreopsideae. Besides the shared whole-genome duplication (WGD-2) in the Heliantheae alliance, our analyses showed that D. pinnata and B. alba each underwent an independent recent WGD-3 event: in D. pinnata, it is more likely to be a self-WGD, while in B. alba, it is from the hybridization of 2 ancestor species. Further, we identified key genes in the inulin metabolic pathway and found that the pseudogenization of 1-FEH1 and 1-FEH2 genes in D. pinnata and the deletion of 3 key residues of 1-FFT proteins in C. bipinnatus and B. alba may probably explain why D. pinnata produces much more inulin than the other 2 plants.

Conclusions

Collectively, the genomic resources for the Coreopsideae tribe will promote phylogenomics in Asteraceae plants, facilitate ornamental molecular breeding improvements and inulin production, and help prevent invasive weeds.
Diagnosis-based design of electric power steering system considering multiple degradations: role of designable generative adversarial network anomaly detection
Authors: Kim Jeongbin , Yang Dabin , Lee Jongsoo
Published: June 2024

Recently, interest in functional safety has surged because vehicle technology increasingly relies on electronics and automation. Failure of certain system components can endanger driver safety and is costly to address. The detection of abnormal data is crucial for enhancing the reliability, safety, and efficiency. This study introduces a novel anomaly-detection method of designable generative adversarial network anomaly detection (DGANomaly). DGANomaly combines the data augmentation method of a designable generative adversarial network (DGAN) with a generative adversarial network anomaly-detection data classification technique. DGANomaly not only generates virtual data that are challenging to obtain or simulate but also produces a range of statistical design variables for normal and abnormal data. This approach enables the specific identification of normal and abnormal design variables. To demonstrate its effectiveness, the DGANomaly method was applied to an electric power steering (EPS) model when multiple degradations of gear stiffness, gear friction, and rack displacement were considered. An EPS model was constructed and validated using simulation programs such as Prescan, Amesim, and Simulink. Consequently, DGANomaly exhibited a higher classification accuracy than the other methods, allowing for more accurate detection of abnormal data. Additionally, a clearer range of statistical designs can be obtained for normal data. These results indicate that the statistical design variables that are less likely to fail can be obtained using minimal data.
(208) ENDOVASCULAR TREATMENT OF ERECTILE DYSFUNCTION
Authors: Redondo Maria Consuelo Conde , Velasco Javier , Castroviejo-Royo Fatima , Calvo Raul , Cuellar Luis , Herranz Ana , Martin Nicolas Sierrasesumaga , D'Angelo Giovanna , Escudero Jesus Calleja
Published: June 2024

Objectives

Endovascular treatments for refractory patients vasculogenic erectile dysfunction have increased in popularity, including angioplasty or stenting for insufficiency arterial. We attempted to validate whether dilation plus stenting of the pudendal arteries, as described for coronary arteries, is useful for the ED treatment.

Methods

We evaluated 6 patients diagnosed with ED due to arterial insufficiency

Inclusion criteria:

IIEF < 10

ED refractory to oral pharmacotherapy and intracavernous prostaglandin

Diagnosis of stenosis or occlusion of pelvic and penile arteries: using penile Doppler (peak systolic velocity < 30cm/) and confirmed by CT angiography.

Technique: 6-F sheath was placed at the origin of theinternal pudendal for selective angiography. Revascularization was indicated if the stenosis was >50%. Balloon angioplasty drug coated from 2 to 5 mm. If the dilation was not satisfactory, a drug-eluting stent was implanted. The revascularization of bilateral lesions was performed in 2 stages. All patients were treated by the same operator.

Patients were premedicated with acetylsalicylic acid (100 mg/d). And then with tadalafil (5 mg/day) for 3 weeks

Technical success was ultimately defined by patency on angiography after successful deployment of a stent or of the dilation balloon.

Clinical success was defined as an improvement >4 points on the IIEF, the ability to perform penetrative sex, or subjective improvement.of erectile function.

Results

The average age of our patients was 62 years. The follow-up time of 12 months. In one patient it was not posible dilate the problem artery.

In one patient the internal iliac had to be previously dilated with a stent.

Only one patient achieved improved erection helped with IPD5.

Conclusions

Data defend that angioplasty of the penile artery is safe and improves erectile function in 60% of patients with isolated penile artery stenosis.

Our results are very poor, not achieving the desired cost-effectiveness.

Conflicts of Interest

None.
(413) LINGUAL MUCOSAL GRAFT (LMG) FOR PENILE CURVATURES: OUR INITIAL EXPERIENCE
Authors: Pozo Dr Carmen , Kollitsch Dr Lisa , Mock Dr Karl , Marszalek Dr Martin
Published: June 2024

Objectives

Penile curvatures (PC) exceeding 60 degrees typically require surgical treatment. Surgical approaches involving plaque incision/excision with grafting are preferred in these cases to avoid penile shortening. Buccal mucosa graft (BMG), particularly Lingual Mucosa Graft (LMG), is not typically emphasized in many review articles, and clinical series remain limited. Our aim was to evaluate our initial cases with LMG in the treatment of PC.

Methods

From February 2022 until November 2022, three patients, reporting normal erectile function but with PC exceeding 60 degrees that interfered with sexual function, underwent plaque incision and grafting with LMG. Postoperative erectile function, penile deformity, and postoperative complications were assessed.

Results

Median age was 56 (SD ±14.2) years, with a median angle of deformity of 80° (SD ±15.3). One of the patients had a congenital penile curvature (CPC). Two patients reported Peyronie Disease (PD) with a median time since presentation of 3.5 years (range from 3-4). The mean follow-up was 12 months (range 11-20). No donor site complications were reported. De novo mild erectile dysfunction was reported by one patient, who responded to a low-dose phosphodiesterase type 5 inhibitor. One patient presented seven months after surgery an abnormal growth tissue at the graft site, which did not interfere with sexuality. Recurrent curvature was observed in two patients, with a median of 20 degrees (range 20-45). All patients reported satisfactory intercourse.

Conclusions

Although based on a small series, LMG appears to be a valuable substitute for the tunica albuginea in cases of PC. It is readily available without complications at the donor site. However, a larger number of patients is needed to draw any definitive conclusion related to the elasticity of the graft.

Conflicts of Interest

None.