bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractTriple-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

AbstractNovel 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

Abstract
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

AbstractWe 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

AbstractA 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

AbstractAn 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

AbstractIn 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

AbstractThe 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

AbstractMechanical 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

AbstractMajor 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

AbstractCortical 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

AbstractWhen 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

AbstractRibosomes 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

AbstractThe 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

AbstractIt 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.