bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual feature decomposition and multi-task learning-based variation-invariant face recognition
Authors: Haider Abbas , Wu Guanfeng , Spence Ivor , Wang Hui
Published: August 2024

Facial identity is subject to two primary natural variations: time-dependent (TD) factors such as age, and time-independent (TID) factors including sex and race. This study aims to address a broader problem known as variation-invariant face recognition (VIFR) by exploring the question: “How can identity preservation be maximized in the presence of TD and TID variations?" While existing state-of-the-art (SOTA) methods focus on either age-invariant or race and sex-invariant FR, our approach introduces the first novel deep learning architecture utilizing multi-task learning to tackle VIFR, termed “multi-task learning-based variation-invariant face recognition (MTLVIFR)." We redefine FR by incorporating both TD and TID, decomposing faces into age (TD) and residual features (TID: sex, race, and identity). MTLVIFR outperforms existing methods by 2% in LFW and CALFW benchmarks, 1% in CALFW, and 5% in AgeDB (20 years of protocol) in terms of face verification score. Moreover, it achieves higher face identification scores compared to all SOTA methods. Open source code.
The striking influence of solubility on the nuclearity of cobalt NCN pincer complexes
Authors: Käfer Matthias G. , Pecak Jan , Stöger Berthold , Kirchner Karl
Published: August 2024

The synthesis and characterization of two Co(II) complexes stabilized by NCN pincer ligands are described. The paramagnetic Co(II) complex [Co(κ3NCN-NCNCH2-iPr)Br] is obtained via a transmetalation protocol from CoBr2 and NC(C–Br)NCH2-iPr in THF. Surprisingly, the dinuclear complex [Co2(κ3NCN-μ2-NCNCH2-iPr)(μ-Cl)(Cl)2] was synthesized following the same synthetic protocol but using an ultrasonicated CoCl2 suspension instead of CoBr2 in the same solvent. Both complexes are paramagnetic species exhibiting solution magnetic moments of 1.9(1) and 5.8(3) μB, respectively. This corresponds to low-spin and high-spin d7 configurations featuring one and three unpaired electrons at the metal centers. X-ray structures of both complexes are presented.

Graphical abstract
Power utility maximization with expert opinions at fixed arrival times in a market with hidden Gaussian drift
Authors: Gabih Abdelali , Kondakji Hakam , Wunderlich Ralf
Published: August 2024

In this paper we study optimal trading strategies in a financial market in which stock returns depend on a hidden Gaussian mean reverting drift process. Investors obtain information on that drift by observing stock returns. Moreover, expert opinions in the form of signals about the current state of the drift arriving at fixed and known dates are included in the analysis. Drift estimates are based on Kalman filter techniques. They are used to transform a power utility maximization problem under partial information into an optimization problem under full information where the state variable is the filter of the drift. The dynamic programming equation for this problem is studied and closed-form solutions for the value function and the optimal trading strategy of an investor are derived. They allow to quantify the monetary value of information delivered by the expert opinions. We illustrate our theoretical findings by results of extensive numerical experiments.
Preclinical efficacy of oral and nasal rivastigmine-loaded chitosan nano-particles on AlCl3-induced Alzheimer’s-like disease in rats
Authors: ElMosbah Dina E. , Khattab Marwa S. , Ibrahim Marwa A. , El-Asssal Mona I. , Miniawy Hala M. F. El
Published: August 2024

The successful treatment of Alzheimer’s disease (AD) is still a big challenge. Rivastigmine is one of the most used drugs for the treatment of AD. The short half-life, lower bioavailability, and less concentration of the drug in the brain after oral delivery are considered the main drawbacks of rivastigmine. To improve these drawbacks, nanostructure-mediated drug delivery has gained more attention. This study investigates the effect of rivastigmine-loaded in optimized chitosan nano-particles (RS-CSNPs) as polymeric nano-carriers by different administration routes (oral and intranasal) on aluminum chloride (AlCl3)-induced Alzheimer-like disease in rat. The model was established by giving rats 100 mg/kg/b.wt of AlCl3 orally for 3 months. Then the experimental rats were treated with RS-CSNPs either orally or intranasally for 75 days. Histopathology, immunohistochemistry of Tau expression in brain tissue, and gene expression of Caspase-3, NF-κB, and Nrf-2 were carried out. The therapeutic agents used decreased the alterations observed in AlCl3 group with improvement in the neuronal viability. In addition to low expression of tau protein, down-regulation of caspase-3 and NF-κB genes and up-regulation of Nrf-2. RS-CSNPs alleviated the progression of AD presumably via blocking the inflammatory cascade and decreasing the oxidative stress process. The intranasal route is superior to the oral one and promising in AD management.
Genetic proxies for therapy of insulin drug targets and risk of osteoarthritis: a drug-target Mendelian randomization analysis
Authors: Cao Ziqin , Li Qiangxiang , Wu Jianhuang , Li Yajia
Published: August 2024

Background

The potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.

Methods

Mendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.

Results

Genetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810–1.4675] and HOA (OR:1.4218; 95%CI:1.1240–1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.

Conclusion

There was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA.
Parent-led Communication Therapy for Young Bilingual Autistic Children: A Scoping Review
Authors: Oudet Sarah , Howard Katie , Gilhuber Christina , Robert Marie , Zimmerli Joanna , Katsos Napoleon , Durrleman Stephanie
Published: August 2024

A scoping review of the literature was undertaken using JBI guidelines to map the evidence of parent-led therapy (PLT) for young autistic children (≤ 6 years) raised in bilingual environments. Reviewers used Covidence to screen located sources. Sixteen papers met inclusion criteria. A strong acceleration of reports of PLT for young autistic children measured in bilingual environments was observed, with 93.8% of papers (n = 15) published since 2015. Reporting of participants’ language environments (home language(s)/L1s and societal language(s)/L2s) was inconsistent. A large majority of these studies, 87.5% (n = 14) were conducted in North America or in collaboration with a North American institution. Diverse PLT programs and methodologies were identified. There is variation in demographic information collected and outcomes reported. Evidence gaps in the literature are identified and the value of undertaking systematic review on this topic is considered. This scoping review points to the necessity of further empirical research and practice that centres parents in early and specific support for autistic children raised in bilingual environments. Suggestions for improving reporting standards of language profiles are provided.
The Predictive Power of Religious Coping on Care Burden, Depression, Stress, and Anxiety of Parents of Pediatric Oncology Patients in Turkey
Authors: Semerci Remziye , Uysal Gülzade , Açikgöz Ayfer , Demirer Pınar
Published: August 2024

This study aimed to determine the predictive power of religious coping of parents of children with cancer on caregiver burden, depression, anxiety, and stress in Turkey. It was designed as a descriptive and cross-sectional study, utilizing correlational analysis and regression models to explore associations between variables. Data were collected from 164 parents in the pediatric hematology-oncology clinics of a university hospital between November 2023 and March 2024. There was a negative correlation between caregiver burden score and negative and positive religious coping scores. Caregiver burden scores were positively correlated with depression, anxiety, and stress scores. Results indicated that caregiver burden, education level, employment status, family structure, family income, and age at diagnosis significantly predicted positive religious coping. For negative religious coping, caregiver burden, education level, family structure, and family income were significant predictors. This suggests that religious coping may help reduce caregiver burden, underscoring the importance of promoting constructive coping strategies to support caregivers' well-being.
Uncertainty Quantification in Mineral Resource Estimation
Authors: Lindi Oltingey Tuya , Aladejare Adeyemi Emman , Ozoji Toochukwu Malachi , Ranta Jukka-Pekka
Published: August 2024

Mineral resources are estimated to establish potential orebody with acceptable quality (grade) and quantity (tonnage) to validate investment. Estimating mineral resources is associated with uncertainty from sampling, geological heterogeneity, shortage of knowledge and application of mathematical models at sampled and unsampled locations. The uncertainty causes overestimation or underestimation of mineral deposit quality and/or quantity, affecting the anticipated value of a mining project. Therefore, uncertainty is assessed to avoid any likely risks, establish areas more prone to uncertainty and allocate resources to scale down potential consequences. Kriging, probabilistic, geostatistical simulation and machine learning methods are used to estimate mineral resources and assess uncertainty, and their applicability depends on deposit characteristics, amount of data available and expertise of technical personnel. These methods are scattered in the literature making them challenging to access when needed for uncertainty quantification. Therefore, this review aims to compile information about uncertainties in mineral resource estimation scatted in the literature and develop a knowledge base of methodologies for uncertainty quantification. In addition, mineral resource estimation comprises different interdependent steps, in and through which uncertainty accumulates and propagates toward the final estimate. Hence, this review demonstrates stepwise uncertainty propagation and assessment through various phases of the estimation process. This can broaden knowledge about mineral resource estimation and uncertainty assessment in each step and increase the accuracy of mineral resource estimates and mining project viability.
A generalized Bouc–Wen model for simulating the quasi-static and dynamic shear responses of helical wire rope isolators
Authors: Capuano Raffaele , Vaiana Nicoló , Carboni Biagio
Published: August 2024

This research investigates the mechanical behavior of a helical wire rope isolator deforming along its shear direction. In particular, we present the results of an extensive experimental campaign including both quasi-static and dynamic tests. The former provide hysteresis loops characterizing the device quasi-static behavior; the latter, performed by using an electro-mechanical shaker, furnish frequency response curves describing the dynamic behavior of a rigid block supported by the tested device. To simulate such a complex behavior, we adopt a generalized Bouc–Wen model and identify its parameters on the basis of the quasi-static test results. Subsequently, such a model is employed to reproduce the frequency response curves of the isolated rigid block. Since the results of the dynamic tests suggest the presence of rate-dependent hysteresis phenomena in the isolated system, the generalized Bouc–Wen model is enhanced by introducing a linear viscous component. Finally, to substantiate the model validation, the experimental results obtained by applying a series of white noise signals are compared with those obtained numerically to demonstrate the model capability of reproducing the device behavior in non-stationary response conditions.
Crop stress detection from UAVs: best practices and lessons learned for exploiting sensor synergies
Authors: Chakhvashvili Erekle , Machwitz Miriam , Antala Michal , Rozenstein Offer , Prikaziuk Egor , Schlerf Martin , Naethe Paul , Wan Quanxing , Komárek Jan , Klouek Tomáš , Wieneke Sebastian , Siegmann Bastian , Kefauver Shawn , Kycko Marlena , Balde Hamadou , Paz Veronica Sobejano , Jimenez-Berni Jose A. , Buddenbaum Henning , Hänchen Lorenz , Wang Na , Weinman Amit , Rastogi Anshu , Malachy Nitzan , Buchaillot Maria-Luisa , Bendig Juliane , Rascher Uwe
Published: August 2024

Introduction

Detecting and monitoring crop stress is crucial for ensuring sufficient and sustainable crop production. Recent advancements in unoccupied aerial vehicle (UAV) technology provide a promising approach to map key crop traits indicative of stress. While using single optical sensors mounted on UAVs could be sufficient to monitor crop status in a general sense, implementing multiple sensors that cover various spectral optical domains allow for a more precise characterization of the interactions between crops and biotic or abiotic stressors. Given the novelty of synergistic sensor technology for crop stress detection, standardized procedures outlining their optimal use are currently lacking.

Materials and methods

This study explores the key aspects of acquiring high-quality multi-sensor data, including the importance of mission planning, sensor characteristics, and ancillary data. It also details essential data pre-processing steps like atmospheric correction and highlights best practices for data fusion and quality control.

Results

Successful multi-sensor data acquisition depends on optimal timing, appropriate sensor calibration, and the use of ancillary data such as ground control points and weather station information. When fusing different sensor data it should be conducted at the level of physical units, with quality flags used to exclude unstable or biased measurements. The paper highlights the importance of using checklists, considering illumination conditions and conducting test flights for the detection of potential pitfalls.

Conclusion

Multi-sensor campaigns require careful planning not to jeopardise the success of the campaigns. This paper provides practical information on how to combine different UAV-mounted optical sensors and discuss the proven scientific practices for image data acquisition and post-processing in the context of crop stress monitoring.
A bibliometric study of positive psychological capital: investigating intellectual foundations through co-citation and content analyses
Authors: Reichard Rebecca J. , Smith Daniel J. , Avey James B. , Mhatre Ketan H.
Published: August 2024

Since its inception in the early 2000s, the growing popularity of positive psychological capital (i.e., PsyCap) has been accompanied by robust debates. Critics assert that PsyCap research is plagued by suboptimal theoretical foundations, disregard for rigorous methodologies, and cult-like cronyism. Leveraging bibliometric data based on 937 primary documents, 28,428 secondary documents, 9714 sources, and 18,247 authors, we conduct document, source, and author co-citation analyses to examine the intellectual foundations of PsyCap and, thus, the veracity of these critiques. We extend this comprehensive scientific mapping of the PsyCap field with an in-depth content analysis of the 100 most frequently co-cited secondary documents. Results suggest that the PsyCap field is built upon solid theoretical foundations in psychology published in reputable, peer-reviewed journals. The authors of secondary documents consider the typical organizational behavior methodological approaches, emphasizing correlational designs. And, although somewhat insular, the research that underlies the PsyCap field consists of a distribution of contributing authors and journals. Finally, we discuss implications for the practical application of positive psychology tenets and prescriptions for scholars researching PsyCap.
Effect of Heat Treatments on the Microstructure and Mechanical Properties of SS317L/ASTM SA516 GR60 Steel Clad Plate Fabricated Through Hot Roll Bonding
Authors: Gupta Laxya , Keskar Nachiket , Maji Bikas C. , Singh R. N. , Krishnan Madangopal
Published: August 2024

Triple-layer stainless-steel clad plate having 317L stainless steel (SS317L) as cladding layer and ASTM SA516 GR60 (GR60) as backing layer was successfully fabricated through vacuum hot roll bonding (VHRB) at 1373 K (1100 °C) temperature and strain rate regime of 1–5 s−1, which were identified through process efficiency maps of the base materials (SS317L and GR60). The process efficiency maps were constructed by conducting isothermal compression tests within the temperature range of 1173 K (900 °C)–1473 K (1200 °C) and 0.1–50 s−1strain rate regime. Effect of post-rolling heat treatments on the mechanical properties of clad plate was studied after solutionization at 1173 K (900 °C) for 1 h followed by cooling at different rates, i.e., water quenching, air cooling, and furnace cooling. As compared to other post-rolling heat treatments, the ultimate tensile strength, uniform plastic elongation, and maximum shear strength showed a significant change from 524 MPa, 0.46 and 519 MPa to 652 MPa, 0.36 and 410 MPa, when the normalized clad plate was solutionized at 1173 K (900 °C) and water quenched. A drastic change in shear fracture mode from gradual failure in normalized condition to catastrophic failure was also noticed after water quenching. These changes are essentially manifestation of the microstructural change in GR60 layer which led to the change in mechanical properties.
Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy
Authors: Joshi Deepak Chandra , Sharma Anurag , Prasad Sonima , Singh Karishma , Kumar Mayank , Sherawat Kajal , Tuli Hardeep Singh , Gupta Madhu
Published: August 2024

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vaccines, utilizes the host’s immune system to selectively target and eradicate malignant cells while minimizing harm to normal tissue. The development of targeted medicines like kinase inhibitors and monoclonal antibodies has allowed for more targeted and less harmful approaches to treating cancer. With the help of genomics and molecular profiling, “precision medicine” customizes therapies to each patient’s unique genetic makeup to maximize therapeutic efficacy while minimizing unwanted side effects. Epigenetic therapies, metabolic interventions, radio-pharmaceuticals, and an increasing emphasis on combination therapy with synergistic effects further broaden the therapeutic landscape. Multiple-stage clinical trials are essential for determining the safety and efficacy of these novel drugs, allowing patients to gain access to novel treatments while also furthering scientific understanding. The future of cancer therapy is rife with promise, as the integration of artificial intelligence and big data has the potential to revolutionize early detection and prevention. Collaboration among researchers, and healthcare providers, and the active involvement of patients remain the bedrock of the ongoing battle against cancer. In conclusion, the dynamic and evolving landscape of cancer therapy provides hope for improved treatment outcomes, emphasizing a patient-centered, data-driven, and ethically grounded approach as we collectively strive towards a cancer-free world.
The role of the ALKBH5 RNA demethylase in invasive breast cancer
Authors: Woodcock Corinne L. , Alsaleem Mansour , Toss Michael S. , Lothion-Roy Jennifer , Harris Anna E. , Jeyapalan Jennie N. , Blatt Nataliya , Rizvanov Albert A. , Miftakhova Regina R. , Kariri Yousif A. , Madhusudan Srinivasan , Green Andrew R. , Rutland Catrin S. , Fray Rupert G. , Rakha Emad A. , Mongan Nigel P.
Published: August 2024

Background

N6-methyladenosine (m6A) is the most common internal RNA modification and is involved in regulation of RNA and protein expression. AlkB family member 5 (ALKBH5) is a m6A demethylase. Given the important role of m6A in biological mechanisms, m6A and its regulators, have been implicated in many disease processes, including cancer. However, the contribution of ALKBH5 to invasive breast cancer (BC) remains poorly understood. The aim of this study was to evaluate the clinicopathological value of ALKBH5 in BC.

Methods

Publicly available data were used to investigate ALKBH5 mRNA alterations, prognostic significance, and association with clinical parameters at the genomic and transcriptomic level. Differentially expressed genes (DEGs) and enriched pathways with low or high ALKBH5 expression were investigated. Immunohistochemistry (IHC) was used to assess ALKBH5 protein expression in a large well-characterised BC series (n = 1327) to determine the clinical significance and association of ALKBH5 expression.

Results

Reduced ALKBH5 mRNA expression was significantly associated with poor prognosis and unfavourable clinical parameters. ALKBH5 gene harboured few mutations and/or copy number alternations, but low ALKBH5 mRNA expression was seen. Patients with low ALKBH5 mRNA expression had a number of differentially expressed genes and enriched pathways, including the cytokine-cytokine receptor interaction pathway. Low ALKBH5 protein expression was significantly associated with unfavourable clinical parameters associated with tumour progression including larger tumour size and worse Nottingham Prognostic Index group.

Conclusion

This study implicates ALKBH5 in BC and highlights the need for further functional studies to decipher the role of ALKBH5 and RNA m6A methylation in BC progression.
On the spaces introduced by N. K. Karapetyants and B. S. Rubin, and their connection with Lorentz–Zygmund spaces
Authors: Doktorski Leo R. Ya.
Published: August 2024

We consider spaces introduced by N. K. Karapetyants and B. S. Rubin in 1982, to characterize, in particular, the image of the fractional integral Riemann–Liouville operator. These spaces lie near $${L}^{\infty }$$

L

∞

. We show that they coincide with well-known Lorentz–Zygmund spaces. This allows us to reformulate one result from N. K. Karapetyants and B. S. Rubin dealing with Riemann–Liouville fractional integral operator $${J}_{0+}^{\alpha }$$

J

0
+

α

defined on $${L}^{p}\left(\text{0,1}\right)$$

L

p

0,1

($$1<p<\infty$$

1
<
p
<
∞

) in the borderline case $$\alpha =1/p$$

α
=
1
/
p

. Using of the well-developed theory of Lorentz–Zygmund spaces leads to new results on the fractional integral Riemann–Liouville operator.
From competencies to strengths: exploring the role of character strengths in developing twenty-first century-ready leaders: a strengths-based approach
Authors: Advani Alexandra , Mergenthaler Jens
Published: August 2024

A substantial amount of research, resources, and effort has been invested in the search for a 'holy grail' of twenty-first century leadership competencies. Ironically, despite the increasing significance of leadership and the substantial investments in uncovering the attributes of successful leaders, concerns persist regarding the quality of leadership worldwide. While the literature extensively outlines 'what' twenty-first century-ready leaders should embody, there remains a gap in outlining 'how' to nurture such leaders. We contrast existing practices that have focused on teaching functional content and relying on retrospective and deficit-based competency models by advocating for a strengths-based perspective. While there has been an increasing interest in positive psychology, which promotes a shift away from prevalent deficit correction approaches towards a framework that emphasises social-emotional and meta-cognitive strengths, character strengths have received little attention in corporate leader development programmes. We argue that nurturing character strengths offers a more sustainable, self-reinforcing process for twenty-first century leader development to overcome the limitations of short-lived leadership training results that fade over time. The Values in Action Classification of Character Strengths and Virtues provides a robust framework for identifying and nurturing these strengths. However, character strengths have traditionally been viewed as personal attributes, rather than leadership competencies. We challenge traditional views on leader development by arguing that character strengths reflect the competencies required of twenty-first century-ready leaders, as these more 'humane' characteristics remain relevant over time and valued across cultures because they represent qualities that are universally appreciated in defining 'what makes a good person'.
New Expression of the Field‐Line Integrated Rayleigh‐Taylor Instability Growth Rate
Authors: Huang Chun‐Yen , Fang Tzu‐Wei , Richmond Arthur D. , Fuller‐Rowell Timothy J. , Liu Jann‐Yenq
Published: August 2024

An expression of Rayleigh‐Taylor (R‐T) instability growth rate based on the field‐line integrated theory is newly established. This expression can be directly utilized in ionosphere models with magnetic flux tube structure based on Modified Apex Coordinates. The R‐T instability growth rates are calculated using the thermospheric and ionospheric conditions based on the coupled Whole Atmosphere Model and Ionosphere Plasmasphere Electrodynamic model (WAM‐IPE). The parameters used in this calculation include the field‐line integrated conductivities and currents, which consider the Quasi‐Dipole Coordinates and the modifications to the equations of electrodynamics. Detailed description of the new formulas and comprehensive analyses of diurnal, longitudinal, and seasonal variations of the R‐T instability growth rate are carried out. The dependencies of growth rates on pre‐reversal enhancement (PRE) vertical drifts and solar activity are also examined. The results show that pronounced R‐T growth rates are captured between 18 and 22 local time (LT) when strong PRE occurs in the equatorial ionosphere. The simulated R‐T growth rate increases with increasing solar activity levels and demonstrates strong correlations with the angle between the sunset terminator and the geomagnetic field line. These results are consistent with plasma irregularity occurrence rates shown in various satellite observations, suggesting that the newly developed R‐T growth rate calculation can effectively capture the probability of irregularities by considering the changes along magnetic flux‐tubes in the ionosphere. Since the WAM‐IPE is running in operation at National Oceanic and Atmospheric Administration Space Weather Prediction Center, the new calculations can be potentially implemented in the near future to provide forecasted information of the R‐T growth rate.
Melatonin: A potential nighttime guardian against Alzheimer’s
Authors: Zhang Zefan , Xue Pei , Bendlin Barbara B. , Zetterberg Henrik , De Felice Fernanda , Tan Xiao , Benedict Christian
Published: August 2024

In the context of the escalating global health challenge posed by Alzheimer’s disease (AD), this comprehensive review considers the potential of melatonin in both preventive and therapeutic capacities. As a naturally occurring hormone and robust antioxidant, accumulating evidence suggests melatonin is a compelling candidate to consider in the context of AD-related pathologies. The review considers several mechanisms, including potential effects on amyloid-beta and pathologic tau burden, antioxidant defense, immune modulation, and regulation of circadian rhythms. Despite its promise, several gaps need to be addressed prior to clinical translation. These include conducting additional randomized clinical trials in patients with or at risk for AD dementia, determining optimal dosage and timing, and further determining potential side effects, particularly of long-term use. This review consolidates existing knowledge, identifies gaps, and suggests directions for future research to better understand the potential of melatonin for neuroprotection and disease mitigation within the landscape of AD.
Genetically- and spatially-defined basolateral amygdala neurons control food consumption and social interaction
Authors: Lim Hansol , Zhang Yue , Peters Christian , Straub Tobias , Mayer Johanna Luise , Klein Rüdiger
Published: August 2024

The basolateral amygdala (BLA) contains discrete neuronal circuits that integrate positive or negative emotional information and drive the appropriate innate and learned behaviors. Whether these circuits consist of genetically-identifiable and anatomically segregated neuron types, is poorly understood. Also, our understanding of the response patterns and behavioral spectra of genetically-identifiable BLA neurons is limited. Here, we classified 11 glutamatergic cell clusters in mouse BLA and found that several of them were anatomically segregated in lateral versus basal amygdala, and anterior versus posterior regions of the BLA. Two of these BLA subpopulations innately responded to valence-specific, whereas one responded to mixed - aversive and social - cues. Positive-valence BLA neurons promoted normal feeding, while mixed selectivity neurons promoted fear learning and social interactions. These findings enhance our understanding of cell type diversity and spatial organization of the BLA and the role of distinct BLA populations in representing valence-specific and mixed stimuli.
Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans
Authors: Kutzner Carl Elias , Bauer Karen Carolyn , Lackmann Jan-Wilm , Acton Richard James , Sarkar Anwesha , Pokrzywa Wojciech , Hoppe Thorsten
Published: August 2024

Mechanical stress during muscle contraction is a constant threat to proteome integrity. However, there is a lack of experimental systems to identify critical proteostasis regulators under mechanical stress conditions. Here, we present the transgenic Caenorhabditis elegans model OptIMMuS (Optogenetic Induction of Mechanical Muscle Stress) to study changes in the proteostasis network associated with mechanical forces. Repeated blue light exposure of a muscle-expressed Chlamydomonas rheinhardii channelrhodopsin-2 variant results in sustained muscle contraction and mechanical stress. Using OptIMMuS, combined with proximity labeling and mass spectrometry, we identify regulators that cooperate with the myosin-directed chaperone UNC-45 in muscle proteostasis. One of these is the TRIM E3 ligase NHL-1, which interacts with UNC-45 and muscle myosin in genetic epistasis and co-immunoprecipitation experiments. We provide evidence that the ubiquitylation activity of NHL-1 regulates myosin levels and functionality under mechanical stress. In the future, OptIMMuS will help to identify muscle-specific proteostasis regulators of therapeutic relevance.
Variability in interseismic strain accumulation rate and style along the Altyn Tagh Fault
Authors: Shen Lin , Hooper Andrew , Elliott John R. , Wright Tim J.
Published: August 2024

Major strike-slip faults that develop between strong and weaker regions are thought to focus along narrow shear zones at the rheological boundary. Here we present the InSAR-derived velocity field spanning almost the entire length of one such fault, the 1600 km-long Altyn Tagh Fault (ATF), and analyse the strain distribution. We find that localisation of strain is actually variable, in contrast to other major strike-slip faults that show little variation, with strain concentrated at the fault for some sections and distributed over broad (>100 km) shear zones for others. Slip rate along the ATF is also variable, decreasing along the fault from 11.6 ± 1.6 mm/yr in the west to 7.2 ± 1.4 mm/yr in the central portion, before increasing again to 11.7  ± 0.9 mm/yr over the eastern portion. We show that the variable shear zone width may be linked to geological variability and the influence of heat flow, and the results imply that sub-parallel faults play an important role in the overall deformation field. This demonstrates the significance of accurately characterising strain rates over a broad region when assessing seismic hazard.
Differential stability of task variable representations in retrosplenial cortex
Authors: Franco Luis M. , Goard Michael J.
Published: August 2024

Cortical neurons store information across different timescales, from seconds to years. Although information stability is variable across regions, it can vary within a region as well. Association areas are known to multiplex behaviorally relevant variables, but the stability of their representations is not well understood. Here, we longitudinally recorded the activity of neuronal populations in the mouse retrosplenial cortex (RSC) during the performance of a context-choice association task. We found that the activity of neurons exhibits different levels of stability across days. Using linear classifiers, we quantified the stability of three task-relevant variables. We find that RSC representations of context and trial outcome display higher stability than motor choice, both at the single cell and population levels. Together, our findings show an important characteristic of association areas, where diverse streams of information are stored with varying levels of stability, which may balance representational reliability and flexibility according to behavioral demands.
Rethinking simultaneous suppression in visual cortex via compressive spatiotemporal population receptive fields
Authors: Kupers Eline R. , Kim Insub , Grill-Spector Kalanit
Published: August 2024

When multiple visual stimuli are presented simultaneously in the receptive field, the neural response is suppressed compared to presenting the same stimuli sequentially. The prevailing hypothesis suggests that this suppression is due to competition among multiple stimuli for limited resources within receptive fields, governed by task demands. However, it is unknown how stimulus-driven computations may give rise to simultaneous suppression. Using fMRI, we find simultaneous suppression in single voxels, which varies with both stimulus size and timing, and progressively increases up the visual hierarchy. Using population receptive field (pRF) models, we find that compressive spatiotemporal summation rather than compressive spatial summation predicts simultaneous suppression, and that increased simultaneous suppression is linked to larger pRF sizes and stronger compressive nonlinearities. These results necessitate a rethinking of simultaneous suppression as the outcome of stimulus-driven compressive spatiotemporal computations within pRFs, and open new opportunities to study visual processing capacity across space and time.
OTUD6 deubiquitination of RPS7/eS7 on the free 40 S ribosome regulates global protein translation and stress
Authors: Villa Sammy , Dwivedi Pankaj , Stahl Aaron , Hinkle Trent , Rose Christopher M. , Kirkpatrick Donald S. , Tomchik Seth M. , Dixit Vishva M. , Wolf Fred W.
Published: August 2024

Ribosomes are regulated by evolutionarily conserved ubiquitination/deubiquitination events. We uncover the role of the deubiquitinase OTUD6 in regulating global protein translation through deubiquitination of the RPS7/eS7 subunit on the free 40 S ribosome in vivo in Drosophila. Coimmunoprecipitation and enrichment of monoubiquitinated proteins from catalytically inactive OTUD6 flies reveal RPS7 as the ribosomal substrate. The 40 S protein RACK1 and E3 ligases CNOT4 and RNF10 function upstream of OTUD6 to regulate alkylation stress. OTUD6 interacts with RPS7 specifically on the free 40 S, and not on 43 S/48 S initiation complexes or the translating ribosome. Global protein translation levels are bidirectionally regulated by OTUD6 protein abundance. OTUD6 protein abundance is physiologically regulated in aging and in response to translational and alkylation stress. Thus, OTUD6 may promote translation initiation, the rate limiting step in protein translation, by titering the amount of 40 S ribosome that recycles.
Laser harmonic generation with independent control of frequency and orbital angular momentum
Authors: Trines Raoul , Schmitz Holger , King Martin , McKenna Paul , Bingham Robert
Published: August 2024

The non-linear optical process of laser harmonic generation (HG) enables the creation of high quality pulses of UV or even X-ray radiation, which have many potential uses at the frontiers of experimental science, ranging from lensless microscopy to ultrafast metrology and chiral science. Although many of the promising applications are enabled by generating harmonic modes with orbital angular momentum (OAM), independent control of the harmonic frequency and OAM level remains elusive. Here we show, through a theoretical approach, validated with 3D simulations, how unique 2-D harmonic progressions can be obtained, with both frequency and OAM level tuned independently, from tailored structured targets in both reflective and transmissive configurations. Through preferential selection of a subset of harmonic modes with a specific OAM value, a controlled frequency comb of circularly polarised harmonics can be produced. Our approach to describe HG, which simplifies both the theoretical predictions and the analysis of the harmonic spectrum, is directly applicable across the full range of HG mechanisms and can be readily applied to investigations of OAM harmonics in other processes, such as OAM cascades in Raman amplification, or the analysis of harmonic progressions in nonlinear optics.
Diet modifies the association between alcohol consumption and severe alcohol-related liver disease incidence
Authors: Petermann-Rocha Fanny , Zhou Ziyi , Mathers John C. , Celis-Morales Carlos , Raubenheimer David , Sattar Naveed , Pell Jill P. , Forrest Ewan , Ho Frederick K.
Published: August 2024

It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcohol consumption and diet were self-reported. The diet score was created from 4 items selected using LASSO. Cox proportional hazard model showed that the diet score was monotonically associated with severe ALD risk, adjusted for sociodemographics, lifestyle factors, and alcohol consumption. Relative excess risk due to interaction analysis indicated that having a higher ALD diet score and a higher alcohol consumption simultaneously confers to 2.44 times (95% CI: 1.06-3.83) higher risk than the sum of excess risk of each factor. In this work, we show that people who have a poor diet might be more susceptible to severe ALD due to alcohol consumption.
Citrate polymer optical fiber for measuring refractive index based on LSPR sensor
Authors: Arefnia Fatemeh , Zibaii Mohammad Ismail , Layeghi Azam , Rostami Soroush , Babakhani-Fard Mohammad-Mahdi , Moghadam Fatemeh Mortazavi
Published: August 2024

Fiber optic localized surface plasmon resonance (LSPR) sensors have become an effective tool in refractive index (RI) detection for biomedical applications because of their high sensitivity. However, using conventional optical fiber has caused limitations in implanting the sensor in the body. This research presents the design and construction of a new type of polymer-based LSPR sensors to address this issue. Also, finite element method (FEM) is used to design the sensor and test it theoretically. The proposed polymer optical fiber (POF) based on citrate is biocompatible, flexible, and degradable, with a rate of 22% and 27 over 12 days. The step RI structure utilizes two polymers for light transmission: poly (octamethylene maleate citrate) (POMC) as the core and poly (octamethylene citrate) (POC) as the cladding. The POF core and cladding diameters and lengths are 700 µm, 1400 µm, and 7 cm, respectively. The coupling efficiency of light to the POF was enhanced using a microsphere fiber optic tip. The obtained results show that the light coupling efficiency increased to 77.8%. Plasma surface treatment was used to immobilize gold nanoparticles (AuNPs) on the tip of the POF, as a LSPR-POF sensor. Adsorption kinetics was measured based on the pseudo-first-order model to determine the efficiency of immobilizing AuNPs, in which the adsorption rate constant (k) was obtained be 8.6 × 10–3 min−1. The RI sensitivity of the sensor in the range from 1.3332 to 1.3604 RIU was obtained as 7778%/RIU, and the sensitivity was enhanced ~ 5 times to the previous RI POF sensors. These results are in good agreement with theory and computer simulation. It promises a highly sensitive and label-free detection biosensor for point-of-care applications such as neurosciences.
Punicalagin increases follicular activation, development and activity of superoxide dismutase 1, catalase, and glutathione peroxidase 1 in cultured bovine ovarian tissues
Authors: Bezerra Vitória S. , Costa Francisco C. , Caetano Filho Francisco F. , Costa José J. N. , de Lima Neto Miguel F. , Furtado Cristiana L. M. , Ceccatto Vânia M. , Araújo Valdevane R. , Silva José R. V.
Published: August 2024

Context The overproduction of reactive oxygen species (ROS) during in vitro culture of ovarian tissues impairs follicular development and survival. Aims To evaluate the effects of punicalagin on the development and survival of primordial follicles, stromal cell and collagen fibres, as well as on the levels of mRNA for nuclear factor erythroid 2-related factor 2 (NRF2), superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1) and perirredoxin 6 (PRDX6), and activity of antioxidant enzymes in cultured bovine ovarian tissues. Methods Bovine ovarian cortical tissues were cultured for 6 days in α-MEM+ alone or with 1.0, 10.0, or 100.0 μM punicalagin at 38.5°C with 5% CO2. Follicle morphology and growth, stromal cell density, and collagen fibres were evaluated by classical histology, while the expression of mRNA was evaluated by real-time PCR. The activity of enzymes was analysed by the Bradford method. Key results Punicalagin improved follicle survival and development, reduced mRNA expression for SOD1 and CAT, but did not influence stromal cells or collagen fibres. Punicalagin (10.0 μM) increased the levels of thiol and activity of SOD1, CAT, and GPX1 enzymes. Conclusions Punicalagin (10.0 μM) promotes follicle survival and development and activates SOD1, CAT, and GPX1 enzymes in bovine ovarian tissues. Implications Punicalagin improves follicle development and survival in cultured ovarian tissues.
Has genomic selection fulfilled its promise?
Authors: Banks Robert G.
Published: August 2024

Genomic selection has been increasingly implemented since its initial description in 2001. The initial focus of activity was in the dairy industry in the developed world but it has now been adopted in all major livestock species, and adoption is underway in most agronomically important plants. The promise of genomic selection includes increased accuracy of estimation of genetic merit, earlier estimation of genetic merit, the capacity to make improvements in traits previously less tractable to genetic change, and the capacity to estimate genetic merit in animals without phenotypic records.

Each of these benefits has been realised in practice, with the significance of the opportunity varying with species.

At the same time, ease of adoption and realisation of benefits has varied, based on three broad parameters: the availability of suitable (and sufficiently cheap) genotyping tools, the prior extent of systematic recording of phenotypes, and the use of estimates of genetic merit in selection.

The effectiveness of genomic selection depends on the existence and composition of a genomic reference population, and this is the most significant challenge for any industry, breed or breeding program seeking to achieve the available benefits. The challenge is two-fold: first, to ensure that sufficient of the right phenotypes are recorded on the right animals, and second, flowing directly from the first, is to fund the phenotyping effort – and challenges aspects are ongoing. “Right” in the context of both phenotypes and animals means most informative, or relevant to the breeding objective or goal.

No standard approach has been outlined for addressing these challenges, but the review presents some simple conceptual thinking that can assist.

Genomic selection also heightens the importance of ensuring maintenance of genetic diversity, and of monitoring changes in both selected and non-selected traits.

Genomic selection has fulfilled its promise where applied effectively and is increasing scope for genetic improvement both in rate of progress and trait coverage. At the same time, its dependencies must be addressed in order to the potential benefits to be realised, and this will likely require new organisational and funding arrangements in many situations.
Introduction to the concept of effective albumin concentration
Authors: Erstad Brian L
Published: August 2024

Purpose

The purpose of this article is to discuss how the structural and presumably functional integrity of albumin, as described by the concept of effective albumin concentration (eAlb), has potentially important clinical implications beyond the total albumin concentration (tAlb) routinely reported by clinical laboratories.

Albumin has several functions beyond its oncotic effects, including molecule binding, substance transport, detoxification actions, and serving as an antioxidant. However, there are conformational changes that occur during or following the manufacture of albumin and during its administration to patients with various disease states, such as decompensated liver disease, that often impair these functions. Such impairments are not reflected in tAlb values reported by clinical laboratories and might explain the disconnect often seen between albumin’s proposed beneficial mechanistic functions and its less-than-predicted clinical effectiveness as noted in published studies. The concept of eAlb has been introduced to describe albumin with structural and functional integrity. Limited studies have found associations between eAlb values and patient prognostic indicators, but the techniques used to decide these effective concentrations to date are complicated and require specialized equipment and experienced researchers for proper interpretation.

Conclusion

Estimation of eAlb may provide valuable information on the functional ability of albumin beyond the tAlb reported by clinical laboratories, but more research is needed to decide how this information is best used in the clinical setting.