The DNA binding of most Escherichia coli Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of in vivo DNA binding for 139 E. coli TFs using ChIP-Seq. We use these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence. BoltzNet mirrors a quantitative biophysical model and provides directly interpretable predictions genome-wide at nucleotide resolution. We use BoltzNet to quantitatively design novel binding sites, which we validate with biophysical experiments on purified protein. We generate models for 124 TFs that provide insight into global features of TF binding, including clustering of sites, the role of accessory bases, the relevance of weak sites, and the background affinity of the genome. Our paper provides new paradigms for studying TF-DNA binding and for the development of biophysically motivated neural networks.

HbA1c variability and body composition independently predicted cardiovascular outcomes in patients with T2DM. Higher HbA1c variability increased CVD risk by 70%, while higher appendicular muscle mass reduced risk by 25%, and higher total fat percentage increased risk by 10%. Incorporating these parameters into risk stratification models could enhance cardiovascular risk prediction and guide preventive strategies for diabetes management.

The DNA binding of most Escherichia coli Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of in vivo DNA binding for 139 E. coli TFs using ChIP-Seq. We use these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence. BoltzNet mirrors a quantitative biophysical model and provides directly interpretable predictions genome-wide at nucleotide resolution. We use BoltzNet to quantitatively design novel binding sites, which we validate with biophysical experiments on purified protein. We generate models for 124 TFs that provide insight into global features of TF binding, including clustering of sites, the role of accessory bases, the relevance of weak sites, and the background affinity of the genome. Our paper provides new paradigms for studying TF-DNA binding and for the development of biophysically motivated neural networks.

HbA1c variability and body composition independently predicted cardiovascular outcomes in patients with T2DM. Higher HbA1c variability increased CVD risk by 70%, while higher appendicular muscle mass reduced risk by 25%, and higher total fat percentage increased risk by 10%. Incorporating these parameters into risk stratification models could enhance cardiovascular risk prediction and guide preventive strategies for diabetes management.

Bacterial transcription factors (TFs) are widely studied in Escherichia coli. Yet it remains unclear how individual genes in the underlying pathways of TF machinery operate together during environmental challenge. Here, we address this by applying an unbiased, quantitative synthetic genetic interaction (GI) approach to measure pairwise GIs among all TF genes in E. coli under auxotrophic (rich medium) and prototrophic (minimal medium) static growth conditions. The resulting static and differential GI networks reveal condition-dependent GIs, widespread changes among TF genes in metabolism, and new roles for uncharacterized TFs (yjdC, yneJ, ydiP) as regulators of cell division, putrescine utilization pathway, and cold shock adaptation. Pan-bacterial conservation suggests TF genes with GIs are co-conserved in evolution. Together, our results illuminate the global organization of E. coli TFs, and remodeling of genetic backup systems for TFs under environmental change, which is essential for controlling the bacterial transcriptional regulatory circuits.

Dyslipidemia has steadily increased in South Korea over the past two decades, emerging as a major public health concern and key risk factor for cardiovascular disease. Thus, our study aimed to investigate long-term trends in the prevalence, awareness, treatment, and control of dyslipidemia in South Korea, including the COVID-19 pandemic. This study utilized data from nationally representative cross-sectional surveys conducted as part of the Korea National Health and Nutrition Examination Survey from 2005 to 2022, analyzing long-term trends of dyslipidemia among 98,396 individuals aged over 30. Weighted linear and binary logistic regression were performed to calculate the β coefficients, β_diff, and weighted odds ratios with 95% confidence intervals (CIs). Weighted odds ratios were computed for various socioeconomic groups using aggregated data from 2005 to 2022. The prevalence of dyslipidemia increased from 41.30% (95% CI 40.40-42.21) in 2005-2009 to 48.41% (47.36-49.47) in 2020-2022. Awareness increased from 17.87% (16.75-18.99) to 48.90% (47.34-50.47), treatment from 7.10% (6.39-7.80) to 38.19% (36.61-39.76), and control among prevalence from 6.49% (5.79-7.19) to 31.82% (30.33-33.32). Treatment (β_diff, 3.94 [1.97-5.92]) and control among prevalence (β_diff, 3.52 [1.67-5.38]) increased more rapidly during the pandemic. Higher odds of dyslipidemia were associated with male sex, older population, rural residence, high BMI, central adiposity, low education and income levels, smoking, and high-risk alcohol consumption. Lower odds of awareness, treatment, and control among individuals with dyslipidemia were associated with male sex, younger population, rural residence, higher education and income levels, smoking, and high-risk alcohol consumption. Over the past 18 years, the prevalence, awareness, treatment, and control of dyslipidemia have steadily increased, with persistent disparities among socioeconomic groups.

A convex relaxation of a quadratically constrained quadratic program (QCQP) is called exact if it has a rank-$1$ optimal solution that corresponds to an optimal solution of the QCQP. Given a QCQP whose convex relaxation is exact, this paper investigates the incorporation of additional quadratic inequality constraints under a non-intersecting quadratic constraint condition while maintaining the exactness of the convex relaxation of the resulting QCQP. Specifically, we extend existing exact semidefinite programming relaxation, completely positive programming relaxation and doubly nonnegative programming relaxation of various classes of QCQPs in a unified manner. Illustrative examples are included to demonstrate the applicability of the established result.

이 글은 말라부의 변형(plastic) 아나키즘과 필자의 잡일(雜一, Hybrid-One) 아나키즘을 각각 소개하면서, 탈근대 아나키즘이 당면한 여러 이론적 과제를 검토한다. 잡일 아나키즘은 변형 아나키즘이 지닌 서구 이론의 한계를 극복하기 위해, 동아시아 개인주의 아나키즘의 논리를 활용하여 이론적 출구를 제시한다. 변형 아나키즘의 두 핵심 개념은 변형성과 무통치성이다. 변형성은 형태를 수용하고, 생성시키며, 파괴하는 능력을 의미한다. 특히 파괴 능력은 기존 체제를 해체하거나 재구성하는 건설적·창조적 가능성을 내포한다. 이는 아나키즘에 대한 통상적 비난인 ‘파괴성’을 존재의 자연스러운 운동이자 새로운 존재 생성에 필요한 긍정적 수단으로 재해석하며, 아나키즘에 대한 불신과 오해를 완화한다. 한편, (노자의 무위자연을 연상시키는) 무통치는 통치의 틀 내에서 ‘통치불가’의 저항을 하면서 자유를 확보하려는 기존 아나키스트 투쟁의 존재론적 지평을 넓힌다. 무통치는 통치와는 무관한, 통치 이전의 원초적 영역으로서 외부의 명령이나 간섭을 받지 않고, 사람들이 스스로 모든 것을 새롭게 생성하게 한다. 이를 통해 자유와 해방의 새로운 대지가 열리게 된다. 한편 잡일 아나키즘은 존재 구성의 잡종성과 존재 운동으로서 잡종화를 강조하는 필자 고유의 이론이다. 이론적으로 잡일 아나키즘은 필자의 하나논리와 그로부터 파생된 동아시아 개인주의 아나키즘으로부터 직접 도출되었다. 세 가지 핵심적 주장은 ① 존재의 잡종적 구성, ② 존재 운동의 잡종화, ③ 유아유심 개인주의와 자유해방으로서 깨달음과 안락주의이다. 깨달음은 수신과 수행을 통한 개인적 각성으로, 아나키스트가 추구해야 할 최고의 목표이자 가치로 간주한다. 나아가 잡일 아나키즘은 현 문명전환을 선천 물질개벽에서 후천 정신개벽에로의 전환이라는 탈물질주의적 관점에서 이해한다. 그러나 천지불인과 선악병진의 현실 속에서는 중도자비의 원칙아래 행동해야 한다.미래 탈아나키즘의 이론적 지평을 확장하기 위해, 잡일 아나키즘은 변형 아나키즘과의 접합을 세 가지 재인식 차원에서 시도한다. 첫째, 탈이분법·탈본질주의의 음양오행적 재인식: 음양오행의 대대적 관계나 ‘일음일양’이라는 순환론적 관점은 이분법의 단점을 극복하면서 장점을 활용한다. 둘째, 탈급진주의의 중도적·잡종적 재인식: 급진적·전면적 부정보다는 다양한 저항 방식과의 잡종화를 통해 연합전선을 형성할 때 더 큰 효과를 낼 수 있다. 셋째, 탈유토피아주의의 깨달음적 전환과 안락주의적 재인식: 깨달음은 유토피아나 디스토피아에 집착하지 않는 평정심 속에서 안빈낙도, 안분자족, 안심입명 등 개인이 안전하고 즐겁게 살아가는 안락주의를 적극 긍정한다. 결론적으로, 잡일 아나키즘과 변형 아나키즘이 지향하는 탈아나키즘의 이론적·실천적 기반은 존재론적 자유해방이며, 이를 위한 깨달음과 자주인의 문제를 다시 강조한다.

In this study, GLP-1RAs were associated with cardiovascular, renal, and metabolic benefits in type 2 diabetes without increasing cancer risk, though gastrointestinal adverse events were common. Our findings support the clinical use of GLP-1RAs, with attention to individual risk profiles and treatment tolerability.