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Proposing the enriched strain-based gradient as a general implicit method to solve time-independent constitutive equation
No full textThis paper describes deriving a novel implicit solution for the constitutive material model based on the flow theory and the strain hardening behaviour for both isotropic and kinematic cases. The explicit approach was applied in solving the equations, and the limitations of the method that led to the introduction of the implicit approaches were explained. Based on the common numerical instability experienced in the proposed solutions for both explicit and implicit approaches. The General Implicit Method, GIM, is proposed for the current research.
The numerical evaluation was applied in the general strain space to include any combinations of the strain and the increments of the strain. The reliability error concept that guarantees the uniqueness of the results is proposed and, in this paper, is used as a measure for each analysis. This approach reveals the error accumulation due to numerical instability caused by the increment ratio for all the approaches discussed. Eventually, it was demonstrated that the GIM is a novel approach that can satisfy both criteria defined for the convergence and reliability error and the computational efficiency as well
Expanding the scope of sustainable peptide synthesis through post-linear synthesis reactions
Get PDFThe replacement of N,N-dimethylformamide (DMF) in solid-phase peptide synthesis (SPPS) is critical for improving the sustainability and safety of peptide research. While N-butyl-2-pyrrolidinone (NBP) has emerged as a viable alternative for linear peptide synthesis, its applicability to post-linear synthesis modifications remains underexplored. Here, we demonstrate the use of NBP as an alternative solvent for key on-resin transformations required in peptidomimetic synthesis. Orthogonal protecting group strategies were successfully implemented, enabling selective removal of Cys(SIT), Cys(Acm), Cys(Trt), and Lys(Dde) under mild conditions. Notably, SIT deprotection achieved 92% conversion in a single 4-hour treatment, while Acm and Trt were selectively removed using iodine or N-halosuccinimides, respectively. Lys(Dde) was efficiently cleaved in the presence of Cys(Acm) using 4% hydrazine in NBP. Furthermore, on-resin cyclisation via disulfide bond and 1,4-disubstituted triazole formation proceeded effectively in NBP, as did N-terminal acetylation under mild conditions. These findings establish NBP as a practical and greener alternative to DMF for diverse post-linear synthesis modifications, supporting the development of sustainable SPPS protocols
Mechanistic insights into heart failure progression and therapeutic target discovery through plasma microRNA profiling: findings from HOMAGE
No full textBackground:
Identifying early pathobiological mechanisms associated with the onset and progression of heart failure (HF) could guide development of preventive strategies.
Objective:
To elucidate molecular pathways driving HF pathogenesis and identify potential therapeutic targets by profiling plasma microRNAs (miRNAs).
Methods:
Multicenter study including 799 elderly patients from HOMAGE. Incident HF was defined as the first hospitalization for HF. A panel of miRNAs implicated in HF was analyzed using RT-qPCR. Two machine learning-based feature selection methods were employed to identify contributors for HF onset. Associations between miRNA targets and HF were explored using publicly available datasets. Bioinformatic analyses were performed using the intersected targets, including functional and single-cell enrichment analyses and drug–gene interaction assessment.
Results:
After adjusting for confounders, four miRNAs (miR-21–5p, miR-24–3p, miR-132–3p, miR-221–3p) were significantly associated with incident HF in univariate analyses (FDR < 0.05). The feature selection process identified miR-21–5p, miR-24–3p and miR-221–3p as the most informative miRNAs linked to HF onset. The predicted targetome of these miRNAs encompassed 1293 transcripts, of which 32 demonstrated cardiac expression and differential levels between HF cases and controls across six different datasets. Pathway enrichment analysis revealed five key biological processes associated with HF progression: i) calcium homeostasis and signaling; ii) cell proliferation; iii) stress response and remodeling; iv) metabolic dysregulation; and v) neurohormonal activation. Drug–gene interaction analysis identified five FDA-approved agonists of the target GABBR2.
Conclusions:
The identified miRNAs provide a rationale for future longitudinal and mechanistic studies and potentially inform the development of novel strategies for HF prevention
The effectiveness of online mental health resources in university students: a qualitative study
No full textObjectives:
This study explored how university students perceive and experience online mental health resources, and the extent to which such resources support their mental well-being and help-seeking behaviours.
Design:
A qualitative, exploratory research design was used to gain rich, in-depth insights into students' lived experiences and evaluations of digital mental health support.
Method:
Ten university students across the UK participated in semi-structured interviews. Participants were recruited through convenience and snowball sampling methods to ensure variation in gender, ethnicity, and subject area. The data were analysed using Braun and Clarke's reflexive thematic analysis, allowing for a detailed examination of recurring patterns and individual perspectives.
Results:
Six overarching themes were identified: (1) Empowerment through Digital Access reflected how online tools offered autonomy, convenience, and a sense of agency; (2) Personal Growth and Skill Development captured the educational value of these resources; (3) Balancing Academic Pressures and Mental Well-being revealed how digital tools helped manage stress amidst academic demands; (4) The Double-Edged Sword of Online Anonymity explored both safety and disconnection in anonymous platforms; (5) Technological Challenges and Adaptations highlighted usability issues and platform fatigue; and (6) The Evolution of Help-Seeking Behaviours addressed how digital tools influenced when and how students reached out for further support.
Conclusion:
Online mental health resources offer accessible, non-intimidating avenues for support, especially during early stages of distress. However, their limitations suggest the need for thoughtful integration with in-person services and greater emphasis on emotional depth and interactivity in digital interventions
Cops and robbers on multi-layer graphs
Get PDFWe generalise the popular cops and robbers game to multi-layer graphs, where each cop and the robber are restricted to a single layer (or set of edges). We demonstrate that initial intuition about the best way to allocate cops to layers is not always correct, and prove that the multi-layer cop number is neither bounded from above nor below by any increasing function of the cop numbers of the individual layers. We show that it is NP- hard to decide if k cops are sufficient to catch the robber, even if every cop layer is a tree and a set of isolated vertices. However, we give a polynomial time algorithm to determine if k cops can win when the robber layer is a tree. Additionally, we investigate a question of worst-case divisions of a simple graph into layers: given a simple graph G, what is the maximum number of cops required to catch a robber over all multi-layer graphs where each edge of G is in at least one layer and all layers are connected? For cliques, suitably dense random graphs, and graphs of bounded treewidth, we determine this parameter up to multiplicative constants. Lastly we consider a multi-layer variant of Meyniel’s conjecture, and show the existence of an infinite family of graphs whose multi-layer cop number is bounded from below by a constant times n/ log n, where
n is the number of vertices in the graph
First observation of CP violation and measurement of polarization in B+ → ρ(770)0K*(892)+ decays
Get PDFAn amplitude analysis of the B + → ( π + π − ) ( K S 0 π + ) decay is performed in the mass regions 0.30 < m π + π − < 1.10 GeV / c 2 and 0.75 < m K S 0 π + < 1.20 GeV / c 2 , using p p collision data recorded with the LHCb detector corresponding to an integrated luminosity of 9 fb − 1 . The polarization fractions and C P asymmetries for B + → ρ ( 770 ) 0 K * ( 892 ) + decays are measured. Violation of the C P symmetry in the decay B + → ρ ( 770 ) 0 K * ( 892 ) + is observed for the first time, with a significance exceeding 9 standard deviations. The C P asymmetry is measured to be A C P = 0.507 ± 0.062 ( stat ) ± 0.024 ( syst ) and the C P -averaged longitudinal polarization fraction of f L = 0.720 ± 0.028 ( stat ) ± 0.009 ( syst ) . The measurements help to shed light on the polarization puzzle of B mesons decaying to two vector mesons
Dear Brand; This is why I Love or Hate you
Get PDFRecent research highlights that many brands are polarizing, attracting both passionate supporters and strong detractors. Managers often deliberately cultivate strategies that embrace this diversity,
nurturing intense brand passion and involvement, which in turn helps clarify the brand’s positioning and strengthen audience engagement. However very little is known about brand polarization. Using qualitative data from 317 informants, this study focuses on brand polarization
and seeks to classify the boundary conditions that cause consumers to perceive a brand as polarizing. While there is an extensive list of reasons presented in the data, preliminary findings confirm the existence of brand polarization and demonstrate that identical brand stimuli can elicit opposed responses from different consumers, resulting in the formation of contradictory yet strong feelings toward a brand. They suggest that brand polarization may stem from (a) brand
characteristics or features, (b) associations with the brand and related entities, (c) current or past consumer experiences, or (d) critical brand incidents that carry symbolic or emotional significance
Characterisation and stabilisation of 2 µm external cavity diode lasers for gravitational wave detection
No full textWe present characterisation and stabilisation results for three prototype tuneable external cavity diode lasers (ECDLs), low-cost compact laser sources operational at 1925 – 1955 nm central wavelength with a 150 nm tuning range. The ECDL free-running relative intensity noise shows good performance in the range of 10⁻⁶ /√Hz up to 1 kHz and below 10−7 /√Hz at higher frequencies. The frequency noise drops as 1/√︁ f up to 1 kHz and, as seen in other diode laser sources, flattens off at a level of 40 Hz/√Hz at higher frequencies. Signal injections onto the laser diode current and the angle of the Littrow grating in the laser housing allow modulation of the intensity and frequency of the laser light. Transfer functions were taken of these feedback mechanisms to characterise laser performance and stabilisation. We present measurements of stabilised intensity noise and stabilised frequency noise for a 2 μm ECDL. The relative intensity noise between 10 Hz – 50 kHz is reduced to a level of 2 × 10⁻⁸ /√Hz. Frequency noise suppression was achieved by Pound-Drever-Hall locking of the laser to a 10 cm rigid cavity, giving a noise reduction across 1 Hz – 100 kHz. From 10 Hz – 1 kHz, there is a 200× suppression to below 10 Hz/√Hz
Exploring the relationship between ADHD symptoms and suicide risk through the lens of the Integrated Motivational-Volitional model of suicidal behaviour
No full textIntroduction:
Attention Deficit-Hyperactivity Disorder (ADHD) is associated with increased vulnerability to suicide. However, understanding of the psychological factors associated with increased risk is limited. Therefore, we investigated the extent to which psychological factors from the Integrated Motivational–Volitional (IMV) model of suicidal behaviour were associated with suicide risk.
Methods:
696 adults who were recruited to a study on ADHD, mental health and suicide risk completed validated measures that assessed components of the IMV model, ADHD symptoms and mental health history.
Results:
642 (92.2%) participants scored 4 or more on the Adult ADHD Self-Report screener (ASRS; Kessler et al., 2005), indicating recent ADHD symptoms. Analyses of IMV model factors were conducted in this subgroup. More than nine out of ten (93%) participants reported lifetime suicidal thoughts (n= 597), and 41.7% (n=268) reported a history of suicide attempts. Multivariable analyses showed higher defeat, internal entrapment and perceived burdensomeness were associated with recent suicidal thoughts, while mental imagery distinguished those with suicide attempt from suicidal thought histories. Perceived burdensomeness moderated the entrapment-to-suicidal thoughts relationship. Exploratory mediation analysis indicated entrapment may mediate the defeat-to-suicidal thoughts relationship.
Conclusions:
This is the first study to apply the IMV model to understanding the ADHD-suicide risk relationship. Psychological factors from the IMV model warrant investigation longitudinally as potentially targets for suicide prevention in people with ADHD
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