University of Surrey - Research Portal

Recent advancements in Artificial Intelligence have yielded promising results in addressing complex challenges within Natural Language Processing (NLP), serving as a vital tool for expediting judicial proceedings in the legal domain. This study focuses on the detection of similarity among judicial documents within an inference group, employing eight NLP techniques grounded in transformer architecture, specifically applied to a case study of legal proceedings in the Brazilian judicial system. The transformer-based models utilised - BERT, GPT-2, RoBERTa, and LlaMA - were pre-trained on general-purpose corpora of Brazilian Portuguese and subsequently fine-tuned for the legal sector using a dataset of 210,000 legal cases. Vector representations of each legal document were generated based on their embeddings, facilitating the clustering of lawsuits and enabling an evaluation of each model's performance through the cosine distance between group elements and their centroid. The results demonstrated that transformer-based models outperformed traditional NLP techniques, with the LlaMA model, specifically fine-tuned for the Brazilian legal domain, achieving the highest accuracy. This research presents a methodology employed in a real case involving substantial documentary content that can be adapted for various applications. It conducts a comparative analysis of existing techniques focused on a non-English language to quantitatively explain the results obtained with various NLP transformers-based models. This approach advances the current state of the art in NLP applications within the legal sector and contributes to the achievement of Sustainable Development Goals.

Children with attention-deficit/hyperactivity disorder show deficits in processing speed, as well as aberrant neural oscillations, including both periodic (oscillatory) and aperiodic (1/f-like) activity, reflecting the pattern of power across frequencies. Both components were suggested as underlying neural mechanisms of cognitive dysfunctions in attention-deficit/hyperactivity disorder. Here, we examined differences in processing speed and resting-state-Electroencephalogram neural oscillations and their associations between 6- and 12-year-old children with (n = 33) and without (n = 33) attention-deficit/hyperactivity disorder. Spectral analyses of the resting-state EEG signal using fast Fourier transform revealed increased power in fronto-central theta and beta oscillations for the attention-deficit/hyperactivity disorder group, but no differences in the theta/beta ratio. Using the parameterization method, we found a higher aperiodic exponent, which has been suggested to reflect lower neuronal excitation-inhibition, in the attention-deficit/hyperactivity disorder group. While fast Fourier transform-based theta power correlated with clinical symptoms for the attention-deficit/hyperactivity disorder group only, the aperiodic exponent was negatively correlated with processing speed across the entire sample. Finally, the aperiodic exponent was correlated with fast Fourier transform-based beta power. These results highlight the different and complementary contribution of periodic and aperiodic components of the neural spectrum as metrics for evaluation of processing speed in attention-deficit/hyperactivity disorder. Future studies should further clarify the roles of periodic and aperiodic components in additional cognitive functions and in relation to clinical status.

DNA is held together by hydrogen bonding between nucleobases (adenine-thymine, guanine-cytosine) and van der Waals interactions between adjacent base pairs' π orbitals. Intercalating molecules with quasi-planar structures utilize van der Waal in- teractions to bind between DNA base pairs. Experimental studies have shown that Cryptolepine preferentially intercalates between non-alternating cytosine and guanine base pairs. However, an atomic scale mechanism that can explain the selective inter- calation is still missing. Using molecular dynamics and density functional theory, we demonstrate how Cryptolepine binds to DNA base pairs, rationalizing its selectivity by analyzing the intermolecular bonding strength predicted by Umbrella Sampling and Free Energy Perturbation calculations. Cryptolepine is stable in all DNA base confor- mations studied, and the binding is a combination of van der Waals interactions with the nucleobases surrounding its π system and hydrogen bonds with the DNA back- bone and nucleobases. Our model predicts a preference for cytosine and guanine base pairs, with a more prominent preference for alternating cytosine and guanine base pairs. These findings illustrate Cryptolepine’s binding mechanism to DNA and highlight the importance of hydrogen bonds and van der Waals interactions.

Neuroinflammation is the foremost defense reaction of the nervous system to most if not all insults. Injuries to the central and peripheral nervous system (CNS and PNS) are followed by immediate activation of innate immune cells and infiltration of peripheral immune cells, amid waves of upregulation of numerous inflammatory mediators. Prolonged inflammation can lead to secondary tissue damage and prohibit regeneration of the injured nervous system. The regulation of inflammation and neuroregeneration are orchestrated through a complex network of signal transduction. Interestingly, many molecules play pleiotropic roles in both processes. Growing evidence implicates a handful of axon regeneration regulators in the processes of neuroinflammation, among which are the myelin and glial scar associated axon growth inhibitors and their axonal receptors. In this article, we will review the roles of these canonical axon regeneration regulators in neuroinflammation.

Chemotherapy-induced peripheral neuropathy (CIPN) remains a major reason for cancer patients to withdraw from their lifesaving therapy. CIPN results in irreversible sensory and motor impairments; however, the epidemiology is largely unknown. Here, we report for the first time that chemotherapy drug vincristine not only reduced axonal regeneration in primary dorsal root ganglion neuron but also induced substantial changes in cell mechanical properties detected by atomic force microscopy (AFM). Confocal imaging analysis revealed vincristine-induced microtubule depolymerization. By using AFM for high-resolution live cell imaging and quantitative analysis, we observed significant changes in cell surface roughness and stiffness of vincristine-treated neurons. Elastic modulus was decreased (21-45%) with increasing dosage of vincristine. Further study with paclitaxel, another well-known CIPN drug, confirmed the link between cell mechanics and cytoskeleton organization. These data support that our system can be used for probing potential CIPN drugs that are of enormous benefit to new chemotherapy drug development.
This study concludes that reduced cell elasticity in dorsal root ganglion neurons accompanies the development of chemotherapy-induced peripheral neuropathy, providing a model system that enables testing of upcoming chemotherapy agents for this particularly inconvenient and often treatment-limiting complication.
Patients withdraw from their life-saving treatment for cancer due to the development of chemotherapy-induced peripheral neuropathy (CIPN). There is an urge to establish a screening tool to identify chemotherapy drugs that could cause peripheral neuropathy. Here, we tested the effects of some well-known CIPN drugs on mouse primary peripheral sensory neurons by using atomic force microscopy (AFM). CIPN drugs significantly change the cell morphology and mechanical properties of sensory neurons, which was detected by AFM. We proposed that our in vitro system can serve as a cell-based screening tool for future chemotherapy drug discovery. [Display omitted]

Real-time tracking of fast axonal transport of acidic vesicles in live adult mouse dorsal root ganglion (DRG) and cortical neurons in brain slices was visualized by the use of binuclear cycloplatinated complexes, {[Pt(L-1)](2)(mu-dppm)}(2+) (1) and {[Pt(L-2)](2)(mu-dppm)}(2+) (2), as lysosome-specific two-photon imaging probes.

Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

Microglia are immune cells in the central nervous system (CNS) that contribute to primary innate immune responses. The morphology of microglia is closely associated with their functional activities. The majority of microglial studies have focused on the ramified or amoeboid morphology; however, bipolar/rod-shaped microglia have recently received much attention. Bipolar/rod-shaped microglia form trains with end-to-end alignment in injured brains and retinae, which is proposed as an important mechanism in CNS repair. We previously established a cell culture model system to enrich bipolar/rod-shaped microglia simply by growing primary microglia on scratched poly-D-lysine (PDL)/laminin-coated surfaces. Here, we investigated the role of laminin in morphological changes of microglia. Bipolar/rod-shaped microglia trains were transiently formed on scratched surfaces without PDL/laminin coating, but the microglia alignment disappeared after 3 days in culture. Amoeboid microglia digested the surrounding laminin, and the gene and protein expression of laminin-cleaving genes Adam9 and Ctss was up-regulated. Interestingly, lipopolysaccharide (LPS)-induced transformation from bipolar/rod-shaped into amoeboid microglia increased the expression of Adam9 and Ctss, and the expression of these genes in LPS-treated amoeboid-enriched cultures remained unchanged. These results indicate a strong association between laminin and morphological transformation of microglia, shedding new light on the role of bipolar/rod-shaped microglia in CNS repair.