213476 research outputs found
Sort by
Design and Performance of a Novel Scalable Core–Sheath Inverted Nozzle Soft Material Pressure Spinner
No full textCore–sheathed inverted nozzle pressurized gyration (CsINPG) is a novel fiber manufacturing process based on gas blowing-assisted rotary coaxial spinning technology, capable of large-scale manufacture of core–sheathed, micropolymeric structures. The CsINPG spinning vessel is constructed from polycarbonate and has a unique nozzle arrangement, which increases uniformity and facilitates the formation of core–sheathed fibers. The CsINPG apparatus functions as a jet generator, ejecting the spinning feedstock under the combined forces of centrifugal force and pressure differentials. The centrifugal force, which is generated by the spinning of the vessel, is powered by a connected electrical motor. This enables the loaded polymeric feedstock to overcome its surface tension, facilitating fluid ejection through the external nozzles on the vessel wall to form spinning jets. These polymeric jets undergo further stretching through the assimilation of the pressure differential, which is powered by introducing nitrogen flows. This further increases the initial velocity and acceleration. In core–sheathed pressurized gyration, the feedstock is present in two different chambers of the core and the sheath. Furthermore, during “inverted” nozzle-pressurized gyration, the entire manufacturing process is carried out on a horizontal axis, facilitating the controlled streaming of these spinning jets into a water bath. This facilitates the usage of “green polymers” such as alginate and cellulose, which require water baths to be converted from soluble streams to insoluble fibrous structures. These fabricated core–sheathed fibers, manufactured under the optimum parameters in this study, produced fibers with average diameters measuring <10 μm. This paper will delve into the development of the novel CsINPG manufacturing process, focusing on the design of the spinning vessel, the parameters used, the optimization of parameters and their consequences, and the potential future applications of the manufactured core–sheathed fibers
Imagining the Future of Politics in Syria through the Constitution: Gender Exclusion and Transformative Pathways
No full textOn December 8, 2024, the Assad government which had ruled Syria since 1971, collapsed unexpectedly during a major offensive campaign. This campaign was led by Hayʾat Tahrir al-Sham (HTS), a jihadist organization led by Mohammad al-Jolani (Ahmad alSharaa), who declared himself president and established a governing authority. This paper examines the post-Assad era in Syria, where contradictory inclinations of authoritarian excluding policies conflict with pathways toward a more prosperous and inclusive future for a country torn by decades of violence and authoritarianism. With Assad’s fall, Syria entered another historical juncture. This phase marks an in-between phase that offers the possibility of a new society and new political relations. This is also a founding moment in which the institutional and legal architecture of a future order is conceived, negotiated, and codified. This episode is formative as it reshapes political relationships, establishes future configurations of power, and may even influence trajectories beyond national borders (Albert et al., 2019). It holds the potential for radical transformation as much as it is equally susceptible to reproducing authoritarian and patriarchal restoration in new forms. Although this paper is about Syria, it addresses a broader concern about the future of political life in the Middle East, where in many cases the old is dying while the new is yet to be born. The concern is the society’s capacity to imagine and create prosperous ways of being
Advances in supply chain operations under uncertainty: game theoretic and global optimisation methods
No full textSupply chains are inherently exposed to uncertainty leading to significant operational disruptions and financial inconsistency. Increasing the resilience and profitability of supply chain operations requires the development of novel methodologies that integrate state-of-the-art optimisation techniques. This thesis addresses this challenge via: (i) the development of global optimisation methodologies to address non-convex problems through the lenses of robust optimisation and (ii) the fair and optimal supply chain planning using a two-stage stochastic framework.
For the first part of the thesis, a novel global optimisation algorithm for Quadratically Constrained Quadratic Programming (QCQP) problems is developed. The proposed Robust spatial Branch-and-Bound (RsBB) algorithm integrates Branch-and-Bound and robust cutting plane algorithms. The research hypothesis for this work is that a concurrent robust and optimality search can lead to computational benefits. The performance of the algorithm is evaluated in benchmark pooling problems. The proposed RsBB algorithm results in computational improvements compared to the state-of-the-art methodologies. To further accelerate the performance of the RsBB algorithm, a multi-parametric programming approach is examined. In the multi-parametric variation of the RsBB algorithm, the inner-maximisation problem is replaced by function evaluations resulting in computational time savings of up to 99\% compared to the original algorithm.
For the second part of the thesis, the fair and optimal supply chain planning of oligopolistic industrial gases market is evaluated. Initially, a deterministic multi-period model for the supply chain is developed, employing contractual agreements of varying duration and pricing mechanisms. A game-theoretic framework is proposed for the fair profit allocation among the oligopoly firms. Oligopoly markets are susceptible to market uncertainty fluctuations. To address this, a two-stage stochastic model is constructed under product demand and electricity price uncertainty. The stochastic customer allocation increases the resilience of the examined supply chains resulting in higher total profits and more effective utilisation of the oligopoly production plants
Exploring Novel ‘Split’ Transketolases: From Discovery to Biocatalytic Scope
No full textBiocatalysis is a major resource for biomanufacturing, offering the possibility to develop more efficient and sustainable processes than purely chemical routes. Transketolases (TKs) are thiamine diphosphate (ThDP)-dependent enzymes that catalyse the stereoselective formation of C-C bonds. Beyond the canonical 600-residue TKs, many prokaryotes encode a split variant made of two 300-residue subunits. It has been hypothesised that this split architecture could confer increased conformational flexibility and allow the accommodation of bulkier substrates, yet split TKs remain largely unexplored from a biocatalytic perspective, and the crystal structure of only one split TK has been solved. To advance our understanding, in this work in-house metagenomic libraries and public genomes from mesophiles and thermophiles were mined, and almost 500 split TK gene pairs were retrieved. Ten representatives were successfully cloned, purified, and assayed, doubling the number of putative split TKs ever produced and tested. These enzymes were investigated for activity with different substrates, stability, and enantioselectivity. sTK2 from the mesophile Fusobacterium nucleatum gave the highest conversion with glycolaldehyde and hydroxypyruvate, and was further biochemically characterised. Site-saturation libraries of its active site residues were prepared, of which some were preliminary tested, indicating residues with potential for future engineering. Thermostability studies showed that sTK4 and sTK7 were able to retain activity after 1 hour at 90 °C and 100 °C, respectively, exceeding the performance of thermostable TKs from the literature. Overall, the thermostable sTK4 and the metagenome-derived sTK23 were the best performing, displaying activity on various nonhydroxylated aliphatic and aromatic acceptors as wild-type. The latter also displayed excellent enantioselectivities. Unlike Escherichia coli TK, sTK23 and two additional metagenomic enzymes showed specificity for cross-coupling when tested with the alternative donor pyruvate. This study shed light on the diversity and biocatalytic potential of split TKs, identifying promising biocatalysts and providing a solid foundation for future optimisation
Frameworks for Fluctuation Analysis in Semi-Markov Systems: Large Deviations, Renewal Theory and Reinforcement Learning
No full textIn recent decades, rigorous frameworks for studying non-equilibrium phenomena, rooted in the theory of stochastic processes and their large deviations have spawned several successful techniques for investigating Markovian (or memoryless) processes. Adaption of these frameworks for fluctuation analysis in non-Markov systems has become an active area of research, with recent works showing analytical and computational results for some types of memory-dependent models. The present thesis reflects this growing interest and is concerned with the analysis of fluctuations in semi-Markov systems, a class of non-Markov processes where memory is encoded via non-exponential waiting-time distributions.
We present contributions towards two complementary frameworks for large deviations in semi-Markov systems, aiming to obtain the scaled cumulant generating function (SCGF); a quantity capturing non-equilibrium fluctuations. The first is a computational framework using advanced neural reinforcement learning, which takes inspiration from recent machine learning trends. The method extends the Markovian method by Rose et al. [New J. Phys. 23 013013 (2021)] to semi-Markov systems and effective SCGF computations are demonstrated for current fluctuations in single and many-body systems. The second contribution uses an analytical framework for calculating the SCGF in certain semi-Markov systems where waiting-time distributions are renewed after a transition occurs. The method combines renewal theory and the pole analysis notably utilized by Poland and Scheraga [J. Chem. Phys. 45 1456–1463 (1966)] for studying DNA denaturation. The method is then applied for computing fluctuations of a special type of ratchet current induced via asymmetry in the shapes of waiting-time distributions having the same mean
Peripheral CD4 T cell differentiation in lung cancer development
No full textLate diagnosis of non-small cell lung cancer (NSCLC) is a major cause of cancer mortality. Current lung cancer screening methods are burdensome and/or ineffective, underscoring the need for improved non-invasive early detection technologies. The T cell response represents a naturally amplified, measurable and specific signal which could be exploited for early cancer detection. We and others recently discovered that neoantigens elicit distinct patterns of T cell differentiation within NSCLC tumours, implying that pre-invasive T cell dynamics could be leveraged to detect pulmonary carcinogenesis. CD4 T cells specifically have been shown to be amongst the earliest and most dynamically remodelled lymphocytes in pre-invasive lung neoplasia. In this thesis, I ask how and when the peripheral immune system senses and responds to the earliest stages of lung carcinogenesis, and whether these changes are measurable in peripheral blood to guide development of immune-focused early detection technologies.
To address this, I profiled systemic immune remodelling across cohorts of pre-invasive lung squamous carcinoma (LUSC) and early-stage lung adenocarcinoma (LUAD), via flow cytometry, TCR sequencing, and DNA methylation. Flow cytometry revealed that early carcinogenesis is associated with skewing of the blood CD4 T cell compartment, including a consistent enrichment of effector CD39+ Tregs across all cohorts. In LUAD, this was concomitant with increases in markers of tissue adaptation and tumour experience (CD103, CCR8, CXCR4, GzmK) and parallel shifts in early to late conventional CD4 T cell differentiation. DNA methylation profiling demonstrated widespread hypomethylation at immune-regulatory and activation-associated loci with stable epigenetic imprinting of effector Treg and recirculating S1PR1+ Treg programmes in LUAD, consistent with an immune state that is activated yet functionally restrained. TCR sequencing indicates clonal reshaping most apparent in pre-invasive and early LUSC. Finally, a multi-omic machine learning framework integrating flow cytometry, methylation and TCR features yielded a compact, highly discriminative signature dominated by effector Treg phenotypes and methylation markers that distinguish early LUAD from high-risk controls.
Together, these results define systemic immune remodelling by CD4 T cell differentiation skewing and effector Treg expansion as hallmarks of early lung cancer. These data support a model in which tumour-derived signals propagate beyond the lesion to reshape circulating immunity, establishing a tolerogenic environment that may constrain anti-tumour responses even before overt invasion. Crucially, these changes are measurable in peripheral blood, highlighting translational potential for non-invasive early detection of not only lung cancer but pre-invasive disease, and reframing early lung cancer development as a systemic immunological process in which CD4 T cell regulatory dominance emerges early and tracks carcinogenesis. These signatures may provide a new window for interception of disease years prior to typical clinical diagnosis
Time-varying partial loudness of noise burst sequences in stationary noise with a similar level
No full textLoudness increases with increasing duration up to 200 ms after sound onset. This temporal integration is well documented in quiet but less understood in the presence of other sounds and for very short durations. The present study investigates the temporal integration of partial loudness for bursts of noise in the presence of equally intense background noise. Level differences required for equal loudness between a reference burst duration of 20 ms and target burst durations of 1, 2, 5, and 10 ms were obtained using a 1-up/1-down staircase procedure in the laboratory and online for burst repetition rates of 5, 10, and 20 Hz and for rectangular and Hann shaped bursts. All results showed that the short duration bursts were perceived as louder than expected from the temporal integration of energy. The difference was equivalent to a change in level up to 6.7 dB and was larger for higher burst repetition rates. The difference was higher when using abrupt onsets and offsets for both target and reference compared to bursts with a Hann window shape. Differences between experiments conducted in the laboratory and online were small (up to 1.2 dB) but were statistically significant
The use of indocyanine green fluorescence dye in adrenal, thyroid, and parathyroid glands surgery: a prospective cohort study
No full textBACKGROUND:
Indocyanine green (ICG) fluorescence imaging is increasingly employed in endocrine surgery to enhance anatomical precision and intraoperative decision-making. This study evaluates its role across thyroidectomy, parathyroidectomy, and laparoscopic adrenalectomy.
METHODS:
A prospective cohort study was conducted over 24 months across two tertiary endocrine surgery centers. A total of 120 patients undergoing elective thyroidectomy (n=60), parathyroidectomy (n=40), or laparoscopic adrenalectomy (n=20) were enrolled and divided into ICG-assisted and control groups. ICG fluorescence was used for real-time visualisation of vascular structures and assessment of tissue viability.
RESULTS:
In the thyroidectomy, group, ICG group demonstrated a significantly lower
rate of transient hypoparathyroidism (16.7% vs. 43.3%, p=0.047), with selective auto-transplantation guided by perfusion scoring. Permanent hypoparathyroidism was also lower (6.7% vs. 16.7%), though not statistically significant. During parathyroidectomy, ICG enabled accurate localisation and vascular confirmation in all patients, with 100% cure rates in both groups.
In adrenalectomy, ICG allowed early adrenal vein identification in 30% of ICG-assisted cases and enhanced anatomical clarity, particularly in complex scenarios like subtotal adrenalectomy.
CONCLUSION:
ICG fluorescence is a safe and effective adjunct in endocrine surgery. It supports real-time intraoperative decision-making by enabling dynamic assessment of tissue perfusion and vascular anatomy. Wider adoption and standardised protocols may further improve safety and surgical precision, particularly in high-risk procedures
Did the COVID-19 pandemic shift the landscape of late HIV diagnosis?
No full textBackground:
The COVID-19 pandemic profoundly disrupted healthcare services. This study assessed the impact of the pandemic on the incidence, characteristics, and outcomes of late HIV diagnosis (LD) in Italy.
//
Methods:
All people with HIV (PWH) enrolled in ICONA during 2016–2019 (pre-pandemic) and 2021–2024 (post-pandemic), and diagnosed with HIV within 3 months before enrolment, were included. LD was defined as CD4 <350 cells/mm³ or an AIDS-defining event (ADE) within three months of HIV diagnosis; AIDS presentation (AIDS-P) was considered an ADE at diagnosis. Annual incidence, socio-demographic determinants, and survival outcomes were compared between periods using Poisson regression, Cox proportional hazards models, and Fine-Gray competing risk models.
//
Results:
Among 5,724 newly diagnosed PWH, 56% were enrolled in pre-pandemic and 44% post-pandemic. Overall, 58% presented late and 13% as AIDS-P, with proportions stable across periods. Risk factors for LD — female sex, older age, foreign nationality, heterosexual transmission, lower education, and unemployment — remained consistent, with no significant interaction by time (p = 0.39). During follow-up, 151 deaths occurred. LD and especially AIDS-P were associated with substantially increased all-cause mortality compared with non-LD, particularly within the first-year post-diagnosis. Adjusted hazard ratios were 2.96 for LD and 6.51 for AIDS-P pre-pandemic, and 8.64 and 17.99 post-pandemic. No excess risk was observed for non-AIDS-related mortality.
//
Conclusions:
The prevalence and determinants of LD and AIDS-P in Italy remained stable before and after the COVID-19 pandemic. However, late presentation continues to carry a heavy mortality burden, underscoring the urgent need to strengthen early testing and prompt linkage to care