The Shortest Duration Constrained Hidden Markov Model: data denoise and forecast optimization on the country-product matrix for the Fitness-Complexity Algorithm

The Economic Fitness Index describes industrial completeness and comprehensively reflects product diversification with competitiveness and product complexity in production globalization. The Fitness-Complexity Algorithm offers a scientific approach to predicting GDP and obtains fruitful results. As a recursion algorithm, the non-linear iteration processes give novel insights into product complexity and country fitness without noise data. However, the Country-Product Matrix and Revealed Comparative Advantage data have abnormal noises which contradict the relative stability of product diversity and the transformation of global production. The data noise entering the iteration algorithm, combined with positively related Fitness and Complexity, will be amplified in each recursion step. We introduce the Shortest Duration Constrained Hidden Markov Model (SDC-HMM) to denoise the Country-Product Matrix for the first time. After the country-product matrix test, the country case test, the noise estimation test and the panel regression test of national economic fitness indicators to predict GDP growth, we show that the SDC-HMM could reduce abnormal noise by about 25% and identify change points. This article provides intra-sample predictions that theoretically confirm that the SDC-HMM can improve the effectiveness of economic fitness indicators in interpreting economic growth

Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease

Rationale and introductionIt is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system.Materials and methodsPatients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis.ResultsA total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827–0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816–0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720–0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness.ConclusionThe CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages

Heart failure and cognitive impairment: A narrative review of neuroimaging mechanism from the perspective of brain MRI

Both heart failure (HF) and cognitive impairment (CI) have a significant negative impact on the health of the elderly individuals. Magnetic resonance imaging (MRI) can non-invasively detect functional and structural variations in the heart and brain, making it easier to explore the connection between the heart and brain. According to neuroimaging studies, HF patients have a higher chance of developing CI because they have a variety of different types of brain injuries. To examine how HF and CI are influenced by one another, English-language literature was searched in the Web of Science, PubMed EMBASE (OVID), PsycInfo, and Scopus databases. The search terms included “high-frequency,” “brain function,” “brain injury,” “cognition,” “cognitive impairment,” and “magnetic resonance imaging.” Normal brain function is typically impaired by HF in the form of decreased cerebral perfusion pressure, inflammation, oxidative stress, and damage to the BBB, resulting in CI and subsequent HF. Early pathophysiological alterations in patients’ brains have been widely detected using a range of novel MRI techniques, opening up new avenues for investigating the connection between HF and CI. This review aims to describe the pathogenesis of HF with CI and the early diagnostic role of MRI in the heart-brain domain

Inference-Time Policy Adapters (IPA): Tailoring Extreme-Scale LMs without Fine-tuning

Large language models excel at a variety of language tasks when prompted with examples or instructions. Yet controlling these models through prompting alone is limited. Tailoring language models through fine-tuning (e.g., via reinforcement learning) can be effective, but it is expensive and requires model access. We propose Inference-time Policy Adapters (IPA), which efficiently tailors a language model such as GPT-3 without fine-tuning it. IPA guides a large base model during decoding time through a lightweight policy adaptor trained to optimize an arbitrary user objective with reinforcement learning. On five challenging text generation tasks, such as toxicity reduction and open-domain generation, IPA consistently brings significant improvements over off-the-shelf language models. It outperforms competitive baseline methods, sometimes even including expensive fine-tuning. In particular, tailoring GPT-2 with IPA can outperform GPT-3, while tailoring GPT- 3 with IPA brings a major performance boost over GPT-3 (and sometimes even over GPT-4). Our promising results highlight the potential of IPA as a lightweight alternative to tailoring extreme-scale language models

Elucidating the Ticking of an In Vitro Circadian Clockwork

A biochemical oscillator can be reconstituted in vitro with three purified proteins, that displays the salient properties of circadian (daily) rhythms, including self-sustained 24-h periodicity that is temperature compensated. We analyze the biochemical basis of this oscillator by quantifying the time-dependent interactions of the three proteins (KaiA, KaiB, and KaiC) by electron microscopy and native gel electrophoresis to elucidate the timing of the formation of complexes among the Kai proteins. The data are used to derive a dynamic model for the in vitro oscillator that accurately reproduces the rhythms of KaiABC complexes and of KaiC phosphorylation, and is consistent with biophysical observations of individual Kai protein interactions. We use fluorescence resonance energy transfer (FRET) to confirm that monomer exchange among KaiC hexamers occurs. The model demonstrates that the function of this monomer exchange may be to maintain synchrony among the KaiC hexamers in the reaction, thereby sustaining a high-amplitude oscillation. Finally, we apply the first perturbation analyses of an in vitro oscillator by using temperature pulses to reset the phase of the KaiABC oscillator, thereby testing the resetting characteristics of this unique circadian oscillator. This study analyzes a circadian clockwork to an unprecedented level of molecular detail

Intramolecular Regulation of Phosphorylation Status of the Circadian Clock Protein KaiC

KaiC, a central clock protein in cyanobacteria, undergoes circadian oscillations between hypophosphorylated and hyperphosphorylated forms in vivo and in vitro. Structural analyses of KaiC crystals have identified threonine and serine residues in KaiC at three residues (T426, S431, and T432) as potential sites at which KaiC is phosphorylated; mutation of any of these three sites to alanine abolishes rhythmicity, revealing an essential clock role for each residue separately and for KaiC phosphorylation in general. Mass spectrometry studies confirmed that the S431 and T432 residues are key phosphorylation sites, however, the role of the threonine residue at position 426 was not clear from the mass spectrometry measurements.Mutational approaches and biochemical analyses of KaiC support a key role for T426 in control of the KaiC phosphorylation status in vivo and in vitro and demonstrates that alternative amino acids at residue 426 dramatically affect KaiC's properties in vivo and in vitro, especially genetic dominance/recessive relationships, KaiC dephosphorylation, and the formation of complexes of KaiC with KaiA and KaiB. These mutations alter key circadian properties, including period, amplitude, robustness, and temperature compensation. Crystallographic analyses indicate that the T426 site is phosphorylatible under some conditions, and in vitro phosphorylation assays of KaiC demonstrate labile phosphorylation of KaiC when the primary S431 and T432 sites are blocked.T426 is a crucial site that regulates KaiC phosphorylation status in vivo and in vitro and these studies underscore the importance of KaiC phosphorylation status in the essential cyanobacterial circadian functions. The regulatory roles of these phosphorylation sites--including T426--within KaiC enhance our understanding of the molecular mechanism underlying circadian rhythm generation in cyanobacteria

Coupling of a Core Post-Translational Pacemaker to a Slave Transcription/Translation Feedback Loop in a Circadian System

Analysis of the cyanobacterial circadian biological clock reveals a complex interdependence between a transcription/translation feedback loop and a biochemical oscillator

The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.

The circadian clock regulates immune responses to microbes and affects pathogen replication, but the underlying molecular mechanisms are not well understood. Here we demonstrate that the circadian components BMAL1 and REV-ERBα influence several steps in the hepatitis C virus (HCV) life cycle, including particle entry into hepatocytes and RNA genome replication. Genetic knock out of Bmal1 and over-expression or activation of REV-ERB with synthetic agonists inhibits the replication of HCV and the related flaviruses dengue and Zika via perturbation of lipid signaling pathways. This study highlights a role for the circadian clock component REV-ERBα in regulating flavivirus replication