Miracle-dz/UniFAR-FTUs huggingface dataset:
The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine)

The GO system is an error avoidance pathway devoted to enhancing the fidelity of DNA replication (31, 35). Although the system has been most fully characterized for Eschenchia coli, evidence already exists for similar repair proteins in other prokaryotes (23, 27) and in higher eukaryotes (29, 52). The GO system in E. coli is composed of at least three proteins, MutM, MutT, and MutY. These three proteins are responsible for removing an oxidatively damaged form of guanine from DNA and the nucleotide pool and for the correction of error-prone translesion synthesis. The damaged form of guanine is 7,8-dihydro-8-oxoguanine (also known as 8-hydroxyguanine or a GO lesion [Fig. 1A]). Despite the fact that the GO system appears to be devoted to the prevention of errors emanating solely from the GO lesion, it is one of the more important fidelity-enhancing systems characterized to date, as judged by the mutation rates of strains lacking common error avoidance mechanisms (31). A knockout of the GO system results in mutation rates that are of the same order of magnitude as those in mutants lacking the polymerase III proofreading subunit (mutD) and about an order of magnitude higher than those in mutants lacking the methyl-directed mismatch repair system (dam, mutHLS) (31, 32). The high mutation rate observed in a GO system knockout is attributable in large part to the abundance and miscoding potential of the GO lesion. The GO lesion is one of the most stable products of oxidative damage to DNA (17). Ionizing radiation and other treatments that generate active oxygen species produce GO lesions (17). However, such treatments are not required in order to generate GO lesions in the cell. Mutator strains grown aerobically or anaerobically have equal mutation rates (32), suggesting that endogenous processes, such as electron transport or lipid peroxidation, can produce the active oxygen species that lead to GO lesions. Steady-state levels of this adduct have been estimated to be 104 per cell in humans and 105 per cell in rodents (20). In addition to its high abundance, the GO lesion has miscoding potential. The miscoding potential of the lesion might seem surprising given the adduct's benign appearance-a nondistorting lesion that is situated outside the base-pairing region (40). However, it forms a stable base pair with A, where A is
Mechanistic evidence for tracking the seasonality of photosynthesis with solar-induced fluorescence

Significance Recent advances in satellite remote sensing of solar-induced fluorescence (SIF) are promising for estimating gross primary production (GPP). However, the empirical link between GPP and SIF has mostly been observed at coarse spatial and temporal scales and lacks a direct mechanistic explanation. Here, we compare high-resolution SIF with GPP and needle-scale physiology at a winter-dormant coniferous forest. Needles retained chlorophyll year-round despite cold temperatures and high light in winter; meanwhile SIF tracks GPP at hourly to weekly timescales. We show that both GPP and SIF are regulated by seasonal changes in photoprotective pigments and that SIF is directly related to needle physiology. This highlights the unique ability of SIF compared with traditional remote-sensing methods to capture GPP seasonality. Northern hemisphere evergreen forests assimilate a significant fraction of global atmospheric CO2 but monitoring large-scale changes in gross primary production (GPP) in these systems is challenging. Recent advances in remote sensing allow the detection of solar-induced chlorophyll fluorescence (SIF) emission from vegetation, which has been empirically linked to GPP at large spatial scales. This is particularly important in evergreen forests, where traditional remote-sensing techniques and terrestrial biosphere models fail to reproduce the seasonality of GPP. Here, we examined the mechanistic relationship between SIF retrieved from a canopy spectrometer system and GPP at a winter-dormant conifer forest, which has little seasonal variation in canopy structure, needle chlorophyll content, and absorbed light. Both SIF and GPP track each other in a consistent, dynamic fashion in response to environmental conditions. SIF and GPP are well correlated (R2 = 0.62–0.92) with an invariant slope over hourly to weekly timescales. Large seasonal variations in SIF yield capture changes in photoprotective pigments and photosystem II operating efficiency associated with winter acclimation, highlighting its unique ability to precisely track the seasonality of photosynthesis. Our results underscore the potential of new satellite-based SIF products (TROPOMI, OCO-2) as proxies for the timing and magnitude of GPP in evergreen forests at an unprecedented spatiotemporal resolution.
Ginseng stem‐leaf saponins in combination with selenium enhance immune responses to an attenuated pseudorabies virus vaccine

Pseudorabies, a herpesvirus infection, is mainly controlled by using attenuated live vaccines. In this study, the effect of ginseng stem and leaf saponins (GSLS) in combination with selenium (Se; in the form of sodium selenite) on vaccination against attenuated pseudorabies virus (aPrV) was evaluated. It was found that GSLS and Se have an adjuvant effect and that a combination of GSLS and Se stimulates significantly enhanced immune responses than does GSLS or Se alone. Following oral administration of GSLS, mice immunized with an attenuated PrV vaccine diluted in Se‐containing physiological saline solution (PSS) provoked a significantly stronger gB‐specific serum antibodies response (IgG, IgG1 and IgG2a), enhanced lymphocyte proliferation and cytolytic activity of NK cells, along with higher production of cytokines (IFN‐γ, IL‐12, IL‐5 and IL‐10) by splenocytes. Notably, the combination of GSLS and Se conferred a much higher resistance to fPrV challenge after immunization of the mice with aPrV vaccine. This study offers convincing experimental evidence that an injection of Se with oral GSLS is a promising adjuvant combination that improves the efficacy of vaccination against PrV and deserves further study regarding improvement of responses to other animal vaccines.
Outage-Limit-Approaching Channel Coding for Future Wireless Communications: Root-Protograph Low-Density Parity-Check Codes

A block-fading (BF) channel, also known as a slow-fading channel, is a type of simple and practical channel model that can characterize the primary feature of a number of wireless-communication applications with low to moderate mobility. Although BF channels have received significant research attention in the past 20 years, designing low-complexity, outage-limit-approaching error-correction codes (ECCs) is still a challenging issue. For this reason, a novel family of protograph low-density paritycheck (LDPC) codes, called rootprotograph (RP) LDPC codes, has been conceived recently. The RP codes not only can realize linearcomplexity encoding and highspeed decoding with the help of the quasi-cyclic (QC) structure but can also achieve near-outage-limit performance in different BF scenarios. In this article, we briefly review the design guidelines of such protograph codes with the aim of inspiring further research activities in this area.
Education of Migrant and Nonmigrant Patients Is Associated With Initiation and Discontinuation of Preventive Medications for Acute Coronary Syndrome

Background The benefits of preventive medications after acute coronary syndrome are impeded by low medication persistence, in particular among marginalized patient groups. Patient education might increase medication persistence, but the effect is still uncertain, especially among migrant groups. We, therefore, assessed whether use of patient education was associated with medication persistence after acute coronary syndrome and whether migrant background modified the potential associations. Methods and Results A cohort of patients discharged with a diagnosis of acute coronary syndrome (N=33 199) was identified in national registers. We then assessed number of contacts for patient education during a period of 6 months after discharge and the initiation and discontinuation of preventive medications during a period of up to 5 years. Results were adjusted for comorbidity and sociodemographic factors. Three or more contacts for patient education was associated with a higher likelihood of initiating preventive medications, corresponding to adjusted relative risks ranging from 1.12 (95% CI, 1.06–1.18) for statins to 1.39 (95% CI, 1.28–1.51) for ADP inhibitors. Lower risks of subsequent discontinuation were also observed, with adjusted hazard ratios ranging from 0.86 (95% CI, 0.79–0.92) for statins to 0.92 (95% CI, 0.88–0.97) for β blockers. Stratification and test for effect modification by migrant status showed insignificant effect modification, except for initiation of ADP inhibitors and statins. Conclusions Patient education is associated with higher chance of initiating preventive medications after acute coronary syndrome and a lower long‐term risk of subsequent discontinuation independently of migrant status.
Intensive treatment of hypertension to a SBP <120 mm Hg in patients aged 75 and over reduces mortality and cardiovascular events

Commentary on : Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years. A randomized clinical trial. JAMA 2016;315:2673–82[OpenUrl][1][CrossRef][2][PubMed][3]. There is uncertainty regarding optimal blood pressure (BP) targets in treating hypertension. Most recent guidelines have recommended a systolic target of <140 mm Hg. The Systolic Blood Pressure Intervention Trial (SPRINT) compared cardiovascular (CV) outcomes in non-diabetic hypertensive patients randomised to standard (systolic blood pressure (SBP) <140 mm Hg) or intensive treatment (<120 mm Hg). 1 Composite CV events and total mortality were significantly reduced with intensive treatment. A prespecified analysis evaluated older patients (≥75) and has now been published. SPRINT compared outcomes with treatment targets of <120 mm Hg and <140 mm Hg in hypertensive patients at medium/high CV risk identified by previous CV events (except stroke), high Framingham risk … [1]: {openurl}? query=rft.jtitle%253DJAMA%26rft.volume%253D315%26rft.spage%253D2673%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.2016. 7050%26rft_id%253Dinfo%253Apmid%252F27195814%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref? access_num=10.1001/jama.2016. 7050&link_type=DOI [3]: /lookup/external-ref? access_num=27195814&link_type=MED&atom=%2Febmed%2F22%2F1%2F30.atom
The effect of education and income on need and willingness to undergo total joint arthroplasty.

OBJECTIVE Individuals with lower socioeconomic status (SES) receive less arthritis care, including joint arthroplasty. However, no studies have considered the expectations or needs of the patients. Our objective was to assess the effect of education and income on the potential need for, and the willingness to consider hip and knee arthroplasty. METHODS Through a mail/telephone survey of 48,218 persons ages 55 years or older residing in 2 areas of Ontario, Canada, 3,307 individuals with moderate-to-severe hip/knee problems were identified. These individuals received a questionnaire to assess education, income, arthritis severity, and comorbidity. In a subset of these subjects, we conducted interviews to evaluate the willingness to consider arthroplasty, and we also performed clinical and radiographic examinations of the joints to validate self-reports of arthritis. The potential need for arthroplasty was defined as the presence of severe arthritis (as scored by the Western Ontario and McMaster Universities Osteoarthritis Index), with no absolute contraindications to surgery. Separate logistic regression models examined the independent effects of education and income on the potential need for, and definite willingness to consider arthroplasty, after controlling for age, sex, and region of residence. Potential unmet need was estimated as the proportion of subjects with the need for arthroplasty who were not already on a surgery waiting list, who were definitely willing to consider arthroplasty, and who had evidence of arthritis by examination and radiography. RESULTS Response rates were at least 72% for all questionnaires and interviews. Less education (adjusted odds ratio [OR] 1.57 for less than high school versus postsecondary education, 95% confidence interval [95% CI] 1.17-2.11) and lower income (adjusted OR 1.83 for </=$20,000 versus >$40,000, 95% CI 1.24-2.70) were independently associated with a greater likelihood of having the potential need for arthroplasty. Among the subjects with potential need, neither education nor income was independently associated with a definite willingness to consider arthroplasty. Thus, taking willingness into consideration, individuals with less education and/or lower income were more likely to have potential unmet need for arthroplasty. CONCLUSION Persons with lower SES had a greater need for, and were equally willing to consider arthroplasty, compared with those with higher SES. Thus, observed SES disparities in the rates of performed arthroplasties cannot be explained by a lower need or less willingness to undergo arthroplasty in those with lower SES.
Risk of Vascular Thrombotic Events Following Discontinuation of Antithrombotics After Peptic Ulcer Bleeding

Goals: To evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. Background: Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuing antithrombotics after peptic ulcer bleeding. The aim of this study was to evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. Study: We reviewed the medical records of patients with ulcer bleeding who were taking antiplatelet agents or anticoagulants at the time of ulcer bleeding. Cox-regression model was used to adjust for potential confounders, and analyzed association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke. Results: Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotics and followed up for >2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Thrombotic events developed more often in discontinuation group than in the continuation group [7/32 (21.9%) vs. 1/40 (2.5%), P=0.019]. Hazard ratio for thrombotic event when antithrombotics were continuously discontinued was 10.9 (95% confidence interval, 1.3-89.7). There were no significant differences in recurrent bleeding events between the 2 groups. Conclusions: Discontinuation of antithrombotics after peptic ulcer bleeding increases the risk of cardiovascular events. Therefore, caution should be taken when discontinuing antithrombotics after ulcer bleeding.
Perylene bisimide dimers as fluorescent "glue" for DNA and for base-mismatch detection.

Perylene-3,4:9,10-tetracarboxylic acid bisimide (“PB”) and its derivatives are applied as fluorescent dyes in organic materials owing to their excellent photochemical stability as well as the high fluorescence quantum yields. The strong hydrophobic stacking interactions between the PB chromophores make this dye an important building block for functional supramolecular architectures. Based on these properties, PB in the dimeric form should be also of potential interest as a probe for fluorescent DNA/RNA analytics as well as for functionalized DNA-based architectures. Its noncovalent DNA-binding interactions have been studied with PB derivatives that had been modified with spermine or other amines. Moreover, an increasing number of publications about covalent modifications of oligonucleotides with PB have appeared over the last few years. Recently, we presented a facile route for the synthetic incorporation of PB as an artificial DNA base in order to study the stacking interactions of this dye at specific sites in duplex DNA. Herein, we present the evaluation of fluorescent PB dimers for the optical functionalization of DNA using three representative duplexes (DNA1, DNA3, and DNA4a). For the synthetic modification of the corresponding oligonucleotides with the PB chromophore (Scheme 1), the 2-deoxyribofuranoside moiety was replaced by an acyclic linker system which is tethered to one of the imide nitrogens of the PB dye. This linker allows the chromophore to intercalate in the base stack while providing high chemical stability during the automated phosphoramidite chemistry. DNA1 bears one interstrand PB dimer inside the duplex, whereas DNA3 contains a PB monomer outside the duplex at each 5’ end. Both duplexes contain palindromic sequences. When DNA1 and DNA3 are excited at 505 nm, the fluorescence spectra of both duplexes (Figure 1) are dominated by a broad band at 660 nm without fine structure. This band corresponds to the excimer-type emission of the PB dimer that has been observed in nanoaggregates of perylene bisimides. 15] The UV/Vis spectra of DNA1 and DNA3 (Figure 2) at low temperatures show two major bands that are hyposochromically (506 nm) or bathochromically (545 nm) shifted in comparison to the 0! 1 and 0! 0 vibronic transitions of the PB monomer. This result shows the strong p–p excitonic interactions of the two PB chromophores inside (DNA1) and outside (DNA3) of the duplex. Both the excimer-type fluorescence band and the shifted absorption bands of DNA1 vanish at higher temperatures. It is remarkable that this occurs cooperatively at a temperature (75.9 8C) that corresponds to the cooperative thermal dehybridization of the whole DNA duplex, which is typically measured at 260 nm (Tm = 78.6 8C). Apparently the intact helical duplex is required as a framework for the PB dimer formation. In comparison to the unmodified DNA2 (Tm = 76.2 8C) the duplex DNA1 is stabilized by 2.4 8C through the Scheme 1. PB-modified duplexes DNA1–DNA3 and DNA4a–DNA4e.
Trained Innate Immunity Not Always Amicable

The concept of “trained innate immunity” is understood as the ability of innate immune cells to remember invading agents and to respond nonspecifically to reinfection with increased strength. Trained immunity is orchestrated by epigenetic modifications leading to changes in gene expression and cell physiology. Although this phenomenon was originally seen mainly as a beneficial effect, since it confers broad immunological protection, enhanced immune response of reprogrammed innate immune cells might result in the development or persistence of chronic metabolic, autoimmune or neuroinfalmmatory disorders. This paper overviews several examples where the induction of trained immunity may be essential in the development of diseases characterized by flawed innate immune response.
Analysis of Periodic Steady-States of Non-Linear Circuits Using the Discrete Singular Convolution Method

In this brief, an effective method is introduced to obtain the steady-state response of non-linear circuits. It involves the application of the discrete singular convolution method in the time domain. A cyclic form involving Shannon’s series kernel is used to express the derivatives in the ordinary differential equations representing the circuit’s mathematical model. This leads to a simple matrix expression for the derivatives. The matrix coefficients are independent of the number of unknown signals in the circuit and depend only on the number of sample points chosen in the steady-state analysis. The procedure transforms differential equations into a system of non-linear algebraic equations, that can be solved using the Newton–Raphson method. Several examples illustrate the performance of the developed method.
Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups

Objectives Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. Methods We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. Results We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10–5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10–53 and HLA-DRB1*03:01, p=3.25×10–9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10–26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10–11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10–13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10–6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10–64) and position 9 of HLA-B (p=7.03×10–11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. Conclusions These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
ARM: Adaptive Random-Selected Multi-Beamforming Estimation Scheme for Satellite-Based Internet of Things

In this paper, we focus on the millimeter-wave (mmWave) band multiple-input and multiple-output (MIMO) channel estimation in the satellite-based Internet of Things (S-IoT). At first, we establish a sparse geometric-based mmWave MIMO channel model between a high throughput satellite (HTS) and multiple terrestrial user equipments (UEs) for the S-IoT downlink system. By exploiting the sparsity inherent to the mmWave band channel, we propose an efficient adaptive random-selected multi-beamforming (ARM) estimation scheme, which can simultaneously estimate the mmWave MIMO channel state information (CSI) for multiple UEs in angle domain. The ARM estimation scheme measures of the CSI between the HTS and multiple UEs by utilizing a series of random combinations of transmitting beamforming vectors and receiving UEs’ antennas and the required number of measurements can adaptively reduce as well as the signal-to-noise ratios (SNR) increases. To further improve the performance of ARM estimation scheme, the number of each beamforming been selected for the channel measurement is buffered, and modify the probability of the random selection of beams and UEs. Two improved ARM estimation schemes are proposed, one is ARM forcing adaptation beam selection (ARM-FABS) scheme, and the other is ARM partially estimated beam selection (ARM-PEBS) scheme. The simulation results show that the proposed ARM estimation schemes can reduce the required number of measurements and achieve a better tracking performance over a wide range of SNRs.