bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A
Authors: Yamagata Atsushi , Ito Kaori , Suzuki Takehiro , Dohmae Naoshi , Terada Tohru , Shirouzu Mikako 
Published: April 2024

AbstractMore than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. Synaptic vesicle glycoprotein 2a (SV2A), a putative membrane transporter in the synaptic vesicles (SVs), has been identified as a target of LEV and BRV. SV2A also serves as a receptor for botulinum neurotoxin (BoNT), which is the most toxic protein and has paradoxically emerged as a potent reagent for therapeutic and cosmetic applications. Nevertheless, no structural analysis on AEDs and BoNT recognition by full-length SV2A has been available. Here we describe the cryo-electron microscopy structures of the full-length SV2A in complex with the BoNT receptor-binding domain, BoNT/A2 HC, and either LEV or BRV. The large fourth luminal domain of SV2A binds to BoNT/A2 HC through protein-protein and protein-glycan interactions. LEV and BRV occupy the putative substrate-binding site in an outward-open conformation. A propyl group in BRV creates additional contacts with SV2A, explaining its higher binding affinity than that of LEV, which was further supported by label-free spectral shift assay. Numerous LEV derivatives have been developed as AEDs and positron emission tomography (PET) tracers for neuroimaging. Our work provides a structural framework for AEDs and BoNT recognition of SV2A and a blueprint for the rational design of additional AEDs and PET tracers.
Perceptography unveils the causal contribution of inferior temporal cortex to visual perception
Authors: Shahbazi Elia , Ma Timothy , Pernuš Martin , Scheirer Walter , Afraz Arash 
Published: April 2024

AbstractNeurons in the inferotemporal (IT) cortex respond selectively to complex visual features, implying their role in object perception. However, perception is subjective and cannot be read out from neural responses; thus, bridging the causal gap between neural activity and perception demands independent characterization of perception. Historically, though, the complexity of the perceptual alterations induced by artificial stimulation of IT cortex has rendered them impossible to quantify. To address this old problem, we tasked male macaque monkeys to detect and report optical impulses delivered to their IT cortex. Combining machine learning with high-throughput behavioral optogenetics, we generated complex and highly specific images that were hard for the animal to distinguish from the state of being cortically stimulated. These images, named “perceptograms” for the first time, reveal and depict the contents of the complex hallucinatory percepts induced by local neural perturbation in IT cortex. Furthermore, we found that the nature and magnitude of these hallucinations highly depend on concurrent visual input, stimulation location, and intensity. Objective characterization of stimulation-induced perceptual events opens the door to developing a mechanistic theory of visual perception. Further, it enables us to make better visual prosthetic devices and gain a greater understanding of visual hallucinations in mental disorders.
Local environment in biomolecular condensates modulates enzymatic activity across length scales
Authors: Gil-Garcia Marcos , Benítez-Mateos Ana I. , Papp Marcell , Stoffel Florence , Morelli Chiara , Normak Karl , Makasewicz Katarzyna , Faltova Lenka , Paradisi Francesca , Arosio Paolo 
Published: April 2024

AbstractThe mechanisms that underlie the regulation of enzymatic reactions by biomolecular condensates and how they scale with compartment size remain poorly understood. Here we use intrinsically disordered domains as building blocks to generate programmable enzymatic condensates of NADH-oxidase (NOX) with different sizes spanning from nanometers to microns. These disordered domains, derived from three distinct RNA-binding proteins, each possessing different net charge, result in the formation of condensates characterized by a comparable high local concentration of the enzyme yet within distinct environments. We show that only condensates with the highest recruitment of substrate and cofactor exhibit an increase in enzymatic activity. Notably, we observe an enhancement in enzymatic rate across a wide range of condensate sizes, from nanometers to microns, indicating that emergent properties of condensates can arise within assemblies as small as nanometers. Furthermore, we show a larger rate enhancement in smaller condensates. Our findings demonstrate the ability of condensates to modulate enzymatic reactions by creating distinct effective solvent environments compared to the surrounding solution, with implications for the design of protein-based heterogeneous biocatalysts.
Position- and scale-invariant object-centered spatial localization in monkey frontoparietal cortex dynamically adapts to cognitive demand
Authors: Taghizadeh Bahareh , Fortmann Ole , Gail Alexander 
Published: April 2024

AbstractEgocentric encoding is a well-known property of brain areas along the dorsal pathway. Different to previous experiments, which typically only demanded egocentric spatial processing during movement preparation, we designed a task where two male rhesus monkeys memorized an on-the-object target position and then planned a reach to this position after the object re-occurred at variable location with potentially different size. We found allocentric (in addition to egocentric) encoding in the dorsal stream reach planning areas, parietal reach region and dorsal premotor cortex, which is invariant with respect to the position, and, remarkably, also the size of the object. The dynamic adjustment from predominantly allocentric encoding during visual memory to predominantly egocentric during reach planning in the same brain areas and often the same neurons, suggests that the prevailing frame of reference is less a question of brain area or processing stream, but more of the cognitive demands.
Green moisture-electric generator based on supramolecular hydrogel with tens of milliamp electricity toward practical applications
Authors: Yang Su , Zhang Lei , Mao Jianfeng , Guo Jianmiao , Chai Yang , Hao Jianhua , Chen Wei , Tao Xiaoming 
Published: April 2024

AbstractMoisture-electric generators (MEGs) has emerged as promising green technology to achieve carbon neutrality in next-generation energy suppliers, especially combined with ecofriendly materials. Hitherto, challenges remain for MEGs as direct power source in practical applications due to low and intermittent electric output. Here we design a green MEG with high direct-current electricity by introducing polyvinyl alcohol-sodium alginate-based supramolecular hydrogel as active material. A single unit can generate an improved power density of ca. 0.11 mW cm−2, a milliamp-scale short-circuit current density of ca. 1.31 mA cm−2 and an open-circuit voltage of ca. 1.30 V. Such excellent electricity is mainly attributed to enhanced moisture absorption and remained water gradient to initiate ample ions transport within hydrogel by theoretical calculation and experiments. Notably, an enlarged current of ca. 65 mA is achieved by a parallel-integrated MEG bank. The scalable MEGs can directly power many commercial electronics in real-life scenarios, such as charging smart watch, illuminating a household bulb, driving a digital clock for one month. This work provides new insight into constructing green, high-performance and scalable energy source for Internet-of-Things and wearable applications.
Illuminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans
Authors: Lehrstrand Joakim , Davies Wayne I. L. , Hahn Max , Korsgren Olle , Alanentalo Tomas , Ahlgren Ulf 
Published: April 2024

AbstractPancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis, but critical information regarding their mass, distribution and composition is lacking within a whole organ context. Here, we apply a 3D imaging pipeline to generate a complete account of the insulin-producing islets throughout the human pancreas at a microscopic resolution and within a maintained spatial 3D context. These data show that human islets are far more heterogenous than previously accounted for with regards to their size distribution and cellular make up. By deep tissue 3D imaging, this in-depth study demonstrates that 50% of the human insulin-expressing islets are virtually devoid of glucagon-producing α-cells, an observation with significant implications for both experimental and clinical research.
Palladium anchored to BisPyP@bilayer-SiO2@NMP organic–inorganic hybrid as an efficient and recoverable novel nanocatalyst in suzuki and stille C–C coupling reactions
Authors: Abdalrazaq Eid Ahmed , Mohammed Hala Kh. , Voronkova Daria K. , Joshi Sanjeev Kumar , Saleh Ebraheem Abdu Musad , Kareem Anaheed Hussein , Kumar Abhinav , Alawadi Ahmed , Alslaami Ali , Fathollahi Rohollah 
Published: April 2024

AbstractThe palladium anchored to BisPyP@bilayer-SiO2@NMP organic–inorganic hybrid was employed as an effective and recyclable organometallic catalyst in Suzuki and Stille C–C coupling reactions. The structure of this magnetic nanocatalyst was determined using various techniques such as SEM, TEM, FT-IR, EDS, ICP-OES, VSM, N2 adsorption–desorption isotherms, XRD, and TGA. In both of the mentioned coupling paths, the yields of the products were very favorable and ranged from 90 to 98%. Also, they had significant features compared to previous reports, such as very short reaction time (5–15 and 7–20 min respectively in the Suzuki and Stille reactions), easy work-up, broad substrate scope, ease of separation of the catalyst using a magnet, suitable reproducibility of the catalyst in 6 runs, heterogeneous nature of the catalyst and not washing it during consecutive runs with confirmation of hot filtration and ICP-OES methods.
A novel flexible exponent power-X family of distributions with applications to COVID-19 mortality rate in Mexico and Canada
Authors: Shah Zubir , Khan Dost Muhammad , Khan Imad , Ahmad Bakhtiyar , Jeridi Mouna , Al-Marzouki Sanaa 
Published: April 2024

AbstractThis paper aims to introduce a novel family of probability distributions by the well-known method of the T–X family of distributions. The proposed family is called a “Novel Generalized Exponent Power X Family” of distributions. A three-parameters special sub-model of the proposed method is derived and named a “Novel Generalized Exponent Power Weibull” distribution (NGEP-Wei for short). For the proposed family, some statistical properties are derived including the hazard rate function, moments, moment generating function, order statistics, residual life, and reverse residual life. The well-known method of estimation, the maximum likelihood estimation method is used for estimating the model parameters. Besides, a comprehensive Monte Carlo simulation study is conducted to assess the efficacy of this estimation method. Finally, the model selection criterion such as Akaike information criterion (AINC), the correct information criterion (CINC), the Bayesian information criterion (BINC), the Hannan–Quinn information criterion (HQINC), the Cramer–von-Misses (CRMI), and the ANDA (Anderson–Darling) are used for comparison purpose. The comparison of the NGEP-Wei with other rival distributions is made by Two COVID-19 data sets. In terms of performance, we show that the proposed method outperforms the other competing methods included in this study.
Exploring the prognostic impact of absolute lymphocyte count in patients treated with immune-checkpoint inhibitors
Authors: Conroy M. R. , O’Sullivan H. , Collins D. C. , Bambury R. M. , Power D. , Grossman S. , O’Reilly S. 
Published: April 2024

Abstract
Background
The role of immune checkpoint inhibitors (ICI) expands but affordable and reproducible prognostic biomarkers are needed. We investigated the association between baseline and 3-month absolute lymphocyte count (ALC) and survival for patients on ICI.

Methods
A retrospective study investigated patients who received ICI July 2014—August 2019. Survival probabilities were calculated for lymphocyte subsets. Univariate and multivariate analyses were performed to investigate risk factors for lymphopenia.

Results
Among 179 patients, median age was 62 and 41% were female. The most common diagnoses were melanoma (41%) and lung cancer (40%). Median PFS was 6.5 months. 27% had baseline lymphopenia (ALC < 1 × 109cells/L) and no significant difference in PFS or OS to those with normal ALC. However, 31% had lymphopenia at 3 months and significantly shorter OS than those without (9.8 vs 18.3 months, p < 0.001). Those with baseline lymphopenia who recovered counts at 3 months had no difference in PFS (median NR vs 13.0 months, p = 0.48) or OS (22 vs 18.3 months, p = 0.548) to those never lymphopenic. The strongest risk factor for lymphopenia on multivariable analysis was previous radiation therapy (RT).

Conclusions
3-month lymphopenia is a negative prognostic marker in cancer patients on ICI. Previous RT is significantly associated with lymphopenia.
AgSCF3 Radical Addition Based on an Oxidant-Free α,β-Amide (Trifluoromethyl)sulfanylation Reaction
Authors: Li Yang , Li Zhi-Bo , Zhang Jin , Shi Yi-Ran , Li Hong , Yang Min-Ge , Zhu Wen-Qing , Fan Qiang-Wei 
Published: April 2024

Abstract(Trifluoromethyl)sulfanylamides are an important class of organic compounds that are common among natural products and drug molecules. Here, we report a (trifluoromethyl)sulfanylation reaction using silver(I) (trifluoromethyl)sulfide as a free-radical (trifluoromethyl)sulfanylation reagent for β-amide compounds. This reaction does not require stoichiometric oxidants or additional transition-metal catalysts, and can be achieved by adding common organic acids. This method has excellent applicability and can accommodate several functional groups, including ester groups, acyl groups, and even bromo or iodo groups. Heterocyclic α,β-amides can also be readily converted into the corresponding products. This reaction also provides a new method for the synthesis of deuterated (trifluoromethyl)sulfanylamides.
Brain Wave Oscillations as an Objective Neurophysiological Biomarker of Homeopathic Subjective Well-Being
Authors: Teixeira Marcus Zulian 
Published: April 2024

Abstract
Background Homeopathy uses the “similitude principle” to arouse a therapeutic reaction in the body against its own disorders. For this to occur optimally, the medicinal pathogenetic effects must present similarity with the totality of the individual's symptoms. To assess if this similarity has been successfully achieved, Hahnemann states that “improvement in the disposition and mind”—i.e., subjective well-being—is the most important parameter to consider.
Aim Our aim was to perform a narrative review of the literature, exploring what is known about subjective well-being as a marker of therapeutic action, and to formulate ways in which subjective well-being might be quantifiable and applied in future homeopathy research.
Results The concept of subjective well-being has been extensively studied in the complementary and conventional medical literature. Improved well-being has been observed in clinical trials, including those in the fields of positive psychology and meditation. Positive subjective outcomes of this nature are supported by objective evidence through associated changes in brain oscillatory activity using electroencephalography and/or “brain mapping” by functional magnetic resonance imaging. Neurophysiological responses in the brain have been identified in subjects after they ingested a homeopathic medicine.
Conclusions The concept of subjective well-being is supported by a body of literature and is a measurable entity. When viewed from the perspective of electrophysiological changes, brain activity is an objective neurophysiological biomarker with a potential to quantify individual well-being in the context of homeopathy research.
A uniform step size, low-voltage piezoelectric motor with dual-channel force loop
Authors: Li Hongen , Xia Zhigang , Zhang Liangliang , Zheng Jiaming , Zhang Jingjing 
Published: April 2024

Recently, a variety of piezoelectric motors with remarkable performance have appeared. However, due to the hysteresis effect of piezoelectrics and stress return errors within the mechanical structures, the existing piezoelectric motors still face some challenges, such as inconsistent step size, high working voltage, and considerable speed variances during upward vs downward movements even under identical driving voltage signals. Here, we introduce a novel low-voltage piezoelectric motor with a dual-channel force loop based on piezoelectric stacks, in which each slider has two force loops connected with other sliders and the internal elastic preload element is installed, which can effectively address these issues. This new type of piezoelectric motor has low working voltage (starting voltage is only 0.8 V, significantly lower than that of conventional piezoelectric motors), large driving force, uniform step size, and excellent linearity.
Development of a 50 kV hydrogen–helium mixed ion beam implanter
Authors: Huang W. , Cai S. X. , Wang L. , Su Y. K. , Zhu K. 
Published: April 2024

Ion implanters have extensively been employed to simulate the irradiation effects of neutrons on relevant nuclear materials. In this study, a 50 kV hydrogen–helium mixed ion beam implanter was developed to generate H2+ and He+ ion beams, with a beam current of 20 µA, while keeping the impurity ion content below 2%. The ions are generated by an antenna-type 2.45 GHz electron cyclotron resonance ion source, and the hydrogen-to-helium ion beam ratio was controlled using two gas mass flow controllers to ensure long time stability of the beam current. As a result, the H2+/He+ ratio, beam size, and homogeneity of the beam spot can be maintained at a stable level. The beam line consisted of four Wien filters, a movable dual-slit plate, and an accelerator tube. The experimental results demonstrated successful transport of more than 20 µA of H2+ and He+ ion beams onto the target, with a beam axis deviation of less than 0.5 mm.
Echinococcus multilocularis in the red fox Vulpes vulpes from the East Carpathian region of Poland and the Slovak Republic
Authors: Dubinský P. , Malczewski A. , Miterpáková M. , Gawor J. , Reiterová K. 
Published: April 2024

AbstractThe occurrence of Echinococcus multilocularis in the Poland–Slovak frontier zone of the East Carpathian region was assessed, for comparison with that in adjacent regions in both countries. A total of 392 red foxes from Poland and 427 red foxes from the Slovak Republic were examined from 2001 to 2004. Significant differences in prevalences were observed in foxes captured from the borderland and adjacent zones in both countries. The mean prevalence of E. multilocularis in the Polish borderland reached 45.7±18.6% and in the Slovak border 35.0±10.7%. In both countries, the prevalence of E. multilocularis in red foxes from adjacent districts, outside the frontier Carpathian region, was considerably lower (18.9±9.2% in Poland and 20.8±9.0% in Slovakia). These differences are probably due to geomorphological and ecological factors, which contribute to the survival of the tapeworm eggs and the subsequent spread of infection. The Carpathian regions of northeast Slovakia and southeast Poland are characterized by specific climatic conditions such as low mean annual air temperatures, low temperatures in active soil surfaces, high soil humidities and a high mean annual rainfall.
Reduced interface effect of proton beam irradiation on the electrical properties of WSe2/hBN field effect transistors
Authors: Ko Seongmin , Shin Jiwon , Jang Juntae , Woo Jaeyong , Kim Jaeyoung , Park Jaehyoung , Yoo Jongeun , Zhou Chongwu , Cho Kyungjune , Lee Takhee 
Published: April 2024

Abstract
Two-dimensional transition metal dichalcogenide (TMDC) semiconductors are emerging as strong contenders for electronic devices that can be used in highly radioactive environments such as outer space where conventional silicon-based devices exhibit nonideal characteristics for such applications. To address the radiation-induced interface effects of TMDC-based electronic devices, we studied high-energy proton beam irradiation effects on the electrical properties of field-effect transistors (FETs) made with tungsten diselenide (WSe2) channels and hexagonal boron-nitride (hBN)/SiO2 gate dielectrics. The electrical characteristics of WSe2 FETs were measured before and after the irradiation at various proton beam doses of 1013, 1014, and 1015 cm−2. In particular, we demonstrated the dependence of proton irradiation-induced effects on hBN layer thickness in WSe2 FETs. We observed that the hBN layer reduces the WSe2/dielectric interface effect which would shift the transfer curve of the FET toward the positive direction of the gate voltage. Also, this interface effect was significantly suppressed when a thicker hBN layer was used. This phenomenon can be explained by the fact that the physical separation of the WSe2 channel and SiO2 dielectric by the hBN interlayer prevents the interface effects originating from the irradiation-induced positive trapped charges in SiO2 reaching the interface. This work will help improve our understanding of the interface effect of high-energy irradiation on TMDC-based nanoelectronic devices.
Implementation of modified P&O and an adaptive fuzzy logic controller based MPPT tracking system under partial shading and variable environmental conditions
Authors: Eshete Firdos Ahmed , Samajdar Dip Prakash , Kumar Anil 
Published: April 2024

Abstract
Most of the conventional Maximum Power Point Tracking (MPPT) Algorithms provide the finest efficiency during uniform irradiation conditions, but under variable irradiation or partial shading condition (PSC), the performance deteriorates and the solar PV system is unable to provide the maximum electricity out of the PV Modules. This degradation in performance occurs due to the presence of numerous local maximum power points (LMPP) and a single global maximum power point (GMPP) in the power versus voltage (P-V) characteristics and the perfect tracking of these LMPP is not possible with the prevailing MPPT algorithms. In order to eradicate this shortcoming, we have proposed the implementation of an adaptive Fuzzy Logic Controller (FLC) based on Perturb and Observe (P&O) technique by employing a boost converter with variable resistive load under uniform irradiance condition (UIC), dynamic atmospheric conditions (DAC) and PSC in this article. We also demonstrated the usage of a simple and improved P&O algorithm by employing a buck boost converter for faster tracking time. These two suggested approaches of FLC and P&O incorporate a variable load scenario and a stable load scenario respectively to address the problem of output voltage oscillation in a PV-based system. The FLC is designed to adjust the dynamic change in step size based on the rate of change of the yield power of the PV panel to reduce oscillations in output of the boost converter and the PV system. According to the results of this analysis, the recommended FLC-based P&O (FLC-P&O) algorithm outperforms the proposed P&O algorithm under DAC and PSC with respect to tracking speed, steady-state error, and dynamic response. Apparently, it can be concluded that the proposed FLC-P&O technique can be applicable to real-time systems for reliable and efficient operation of the boost converter and add to the stability and simplicity of the contemporary PV-based systems.