From Static to Dynamic: A Continual Learning Framework for Large Language Models

The vast number of parameters in large language models (LLMs) endows them with remarkable capabilities, allowing them to excel in a variety of natural language processing tasks. However, this complexity also presents challenges, making LLMs difficult to train and inhibiting their ability to continuously assimilate new knowledge, which may lead to inaccuracies in their outputs. To mitigate these issues, this paper presents DynaMind, a novel continual learning framework designed for LLMs. DynaMind incorporates memory mechanisms to assimilate new knowledge and modular operators to enhance the model inference process with the newly assimilated knowledge, consequently improving the accuracies of LLMs' outputs. Benchmark experiments demonstrate DynaMind's effectiveness in overcoming these challenges. The code and demo of DynaMind are available on GitHub: https://github.com/Elfsong/DynaMind

Neutron-proton scattering at next-to-next-to-leading order in Nuclear Lattice Effective Field Theory

We present a systematic study of neutron-proton scattering in Nuclear Lattice Effective Field Theory (NLEFT), in terms of the computationally efficient radial Hamiltonian method. Our leading-order (LO) interaction consists of smeared, local contact terms and static one-pion exchange. We show results for a fully non-perturbative analysis up to next-to-next-to-leading order (NNLO), followed by a perturbative treatment of contributions beyond LO. The latter analysis anticipates practical Monte Carlo simulations of heavier nuclei. We explore how our results depend on the lattice spacing a, and estimate sources of uncertainty in the determination of the low-energy constants of the next-to-leading-order (NLO) two-nucleon force. We give results for lattice spacings ranging from a = 1.97 fm down to a = 0.98 fm, and discuss the effects of lattice artifacts on the scattering observables. At a = 0.98 fm, lattice artifacts appear small, and our NNLO results agree well with the Nijmegen partial-wave analysis for S-wave and P-wave channels. We expect the peripheral partial waves to be equally well described once the lattice momenta in the pion-nucleon coupling are taken to coincide with the continuum dispersion relation, and higher-order (N3LO) contributions are included. We stress that for center-of-mass momenta below 100 MeV, the physics of the two-nucleon system is independent of the lattice spacing.Comment: 22 pages, 8 figure

Sustainable floods: Exploring stakeholder perceptions of sedimentation strategies for the sinking Mekong delta

The Mekong delta in Vietnam, home to over 17 million people, is rapidly losing elevation due to groundwater-extraction-induced subsidence, natural compaction and global sea-level rise. These combined processes result in salinity intrusion, erosion and land loss. The delta has been extensively poldered for agri- and aquaculture, largely cutting off the land from the dwindling supplies of fluvial sediment which would otherwise accumulate on the delta during seasonal floods and increase land elevation. Considering the current state of the Mekong delta and sediment delivery from upstream, the future sustainability of the delta cannot rely on natural delta-building processes and instead must be planned and managed to prevent major degradation of the system. Sedimentation strategies are methods of ensuring that the limited sediment available is retained to increase elevation where it is desirable for the population and sustainability of the delta. Considering the potential disruption to land uses and livelihoods caused by sedimentation strategies, it is vital to discuss the possibilities for sedimentation strategies with stakeholders to ensure that people, particularly vulnerable groups, are not disadvantaged, and ensure that delta management is sustainable from all perspectives. In this research we engage with stakeholders to start an explorative dialogue on the potential of sedimentation strategies in the Mekong delta considering physical, socio-institutional, governance and legal aspects. We resent an analysis of interviews and workshop discussions with farmers, officials, and regional experts in the provinces of Soc Trang (coastal, the most downstream part of the delta) and An Giang (inland, the most upstream part of the delta) to gain insights into local perspectives in different areas of the delta, with different physical environments, land use histories and constraints. Preliminary findings suggest that the perceived role of sediment varies across different stakeholders e.g. farmers focus more on the role of sediment for their agricultural activities while experts also express their concerns on the elevation of the delta. Interestingly, while sediment is perceived to be important in the upstream area, it is considered an inconvenience in the downstream part of the delta due to, among other factors, different types of livelihoods. It is therefore recommended that the sedimentation strategies need to be designed based on the typical livelihoods of locals and communication strategies need to be enhanced to raise the awareness of local actors on the role of sediment

DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity

DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq, and Hi-C, we show that genome-wide methylation loss is associated with both concordant loss of replication timing precision and deregulation of 3D genome organization. Notably, we find distinct disruption in 3D genome compartmentalization, striking gains in cell-to-cell replication timing heterogeneity and loss of allelic replication timing in cancer hypomethylation models, potentially through the gene deregulation of DNA replication and genome organization pathways. Finally, we identify ectopic H3K4me3-H3K9me3 domains from across large hypomethylated domains, where late replication is maintained, which we purport serves to protect against catastrophic genome reorganization and aberrant gene transcription. Our results highlight a potential role for the methylome in the maintenance of 3D genome regulation

Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter

Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tumors, contains two such stretches of guanine-rich tracts, designated c-kit1 and c-kit2. Our previous nuclear magnetic resonance (NMR)-based studies reported on the novel G-quadruplex scaffold of the c-kit1 promoter in K+-containing solution, where we showed for the first time that even an isolated guanine was involved in G-tetrad formation. These NMR-based studies are now extended to the c-kit2 promoter, which adopts two distinct all-parallel-stranded conformations in slow exchange, one of which forms a monomeric G-quadruplex (form-I) in 20 mM K+-containing solution and the other a novel dimeric G-quadruplex (form-II) in 100 mM K+-containing solution. The c-kit2 promoter dimeric form-II G-quadruplex adopts an unprecedented all-parallel-stranded topology where individual c-kit2 promoter strands span a pair of three-G-tetrad-layer-containing all-parallel-stranded G-quadruplexes aligned in a 3′ to 5′-end orientation, with stacking continuity between G-quadruplexes mediated by a sandwiched A•A non-canonical pair. We propose that strand exchange during recombination events within guanine-rich segments, could potentially be mediated by a synapsis intermediate involving an intergenic parallel-stranded dimeric G-quadruplex

The association between diabetes and gastric cancer

Background: Prior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity. Objective: To investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis. Methods: We included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs. Results: We did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls. Conclusion: This study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk

Evaluation of awake prone positioning effectiveness in moderate to severe COVID-19

Evidence mainly from high income countries suggests that lying in the prone position may be beneficial in patients with COVID-19 even if they are not receiving invasive ventilation. Studies indicate that increased duration of prone position may be associated with improved outcomes, but achieving this requires additional staff time and resources. Our study aims to support prolonged (≥ 8hours/day) awake prone positioning in patients with moderate to severe COVID-19 disease in Vietnam. We use a specialist team to support prone positioning of patients and wearable devices to assist monitoring vital signs and prone position and an electronic data registry to capture routine clinical data