Miracle-dz/UniFAR-FTUs huggingface dataset:
Abscisic acid positively regulates L-Arabinose metabolism to inhibit seed germination through ABI4-mediated transcriptional promotions of MUR4 in Arabidopsis thaliana.

L-Ara is a major monosaccharide in plant polysaccharides and glycoproteins, and functions in plant growth and development. However, the potential role of L-Ara during abscisic acid (ABA)-mediated seed germination has been largely ignored. Here, our results showed a function of L-Ara during ABA-mediated seed germination. ABA slowed down the reduction of L-Ara in seed cell wall, and exogenous L-Ara aggravated the inhibition of ABA on germination. We further found that MUR4, encoding UDP-D-XYLOSE 4-EPIMERASE 1, played a vital role in ABA-mediated germination. MUR4 was highly expressed in embryo and induced by ABA in both seeds and seedlings. Overexpression of MUR4 conferred hypersensitive seed germination and early post-germination growth to ABA. Further analysis revealed that ABSCISIC ACID INSENSITIVE (ABI4) positively modulated the MUR4 expression by directly binding the CE1 motif of MUR4 promoter. Consistently, abi4-1 mutant had a lower L-Ara content in seed cell wall, while a higher L-Ara content in seed cell wall was observed in ABI4 overexpressors. Genetic analysis suggested that overexpression of MUR4 in abi4-1 partly restored the ABA sensitivity of abi4-1. We established the link between ABA and L-Ara during ABA-mediated seed germination and cotyledon greening in Arabidopsis, and revealed the potential molecular mechanism. This article is protected by copyright. All rights reserved.
System Analysis of MIRNAs in Maize Internode Elongation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.
Longitudinal Relations between Emotion Restraint Values, Life Stress, and Internalizing Symptoms among Vietnamese American and European American Adolescents

ABSTRACT Objective: Recent research has documented cultural differences in the extent and manner in which various forms of emotion regulation are linked with psychological well-being. Most of these studies, however, have been cross-sectional, nor have they directly examined the values underlying the use of emotion regulation. The present study examined emotion restraint values and their interactions with life stress in predicting internalizing symptoms across time among Vietnamese American and European American adolescents. The study focused on adolescence as a critical developmental period during which life stress and internalizing symptoms increase significantly. Method: Vietnamese American (n = 372) and European American (n = 304) adolescents’ levels of emotion restraint values, internalizing symptoms, and stress were assessed at two timepoints six months apart. Results: Results indicated differential associations between emotion restraint values, stress, and symptoms over time for the two groups. For Vietnamese American adolescents, emotion restraint values did not predict depressive, anxiety, or somatic symptoms. For European American adolescents, emotion restraint values predicted higher somatic symptoms but buffered against the effects of interpersonal stress on anxiety and depressive symptoms. Conclusions: These results provide increased understanding of the role of values related to emotion restraint in shaping adolescent internalizing symptoms and responses to stress across cultural groups. Implications of the findings for guiding intervention efforts are discussed.
Neural coding and perception of auditory motion direction based on interaural time differences.

While motion is important for parsing a complex auditory scene into perceptual objects, how it is encoded in the auditory system is unclear. Perceptual studies suggest that the ability to identify the direction of motion is limited by the duration of the moving sound, yet we can detect changes in interaural differences at even shorter durations. To understand the source of these distinct temporal limits, we recorded from single units in the inferior colliculus of unanesthetized rabbits in response to noise stimuli containing a brief segment with linearly time-varying interaural time difference ("ITD sweep") temporally embedded in interaurally uncorrelated noise. We also tested the ability of human listeners to either detect the ITD sweeps or identify the motion direction. Using a point process model to separate the contributions of stimulus-dependence and spiking history to single-neuron responses, we found that the neurons respond primarily by following the instantaneous ITD rather than exhibiting true direction selectivity. Furthermore, using an optimal classifier to decode the single-neuron responses, we found that neural threshold durations of ITD sweeps for both direction identification and detection overlapped with human threshold durations even though the average response of the neurons could track the instantaneous ITD beyond psychophysical limits. Our results suggest that the IC does not explicitly encode motion direction, but internal neural noise may limit the speed at which we can identify the direction of motion.
Nonpharmacologic Interventions to Prevent or Mitigate Adverse Long-Term Outcomes Among ICU Survivors: A Systematic Review and Meta-analysis.

OBJECTIVE ICU survivors suffer from long-lasting physical, mental, and cognitive health impairments, also called "postintensive care syndrome". However, an overview of the effectiveness of interventions to prevent or mitigate these impairments is lacking. The aim of this study is to assess the effectiveness of nonpharmacologic interventions. DATA SOURCES PubMed, CINAHL, PsycINFO, Embase, and Cochrane Library were systematically searched from inception until July 19, 2018. STUDY SELECTION (Non)randomized clinical trials, controlled before-after studies, and interrupted time series were included. Outcomes of interest included patients physical, mental and cognitive outcomes, quality of life, and outcomes such as social functioning and functional status, measured after hospital discharge. DATA EXTRACTION Two independent reviewers selected studies, extracted data, and assessed the risk of bias. Pooled mean differences and standardized mean differences were calculated using random-effect meta-analyses. DATA SYNTHESIS After screening 17,008 articles, 36 studies, including 10 pilot studies, were included (n = 5,165 ICU patients). Interventions were subdivided into six categories: 1) exercise and physical rehabilitation programs; 2) follow-up services; 3) psychosocial programs; 4) diaries; 5) information and education; and 6) other interventions. Many outcomes favored the interventions, but significant differences were only found for diaries in reducing depression (two studies, n = 88; standardized mean difference, 0.68; 95% CI, 0.14-1.21) and anxiety (two studies, n = 88; standardized mean difference, 0.44; 95% CI, 0.01-0.87) and exercise programs in improving the Short Form Health Survey-36 Mental Component Score (seven studies, n = 664; mean difference, 2.62; 95% CI, 0.92-4.32). CONCLUSIONS There is thin evidence that diaries and exercise programs have a positive effective on mental outcomes. Despite outcomes favoring the intervention group, other commonly used nonpharmacologic interventions in daily ICU practice are not supported by conclusive evidence from this meta-analysis. To improve recovery programs for ICU survivors, more evidence is needed from robust intervention studies using standardized outcomes.
Aalborg Universitet Individual Pitch Control for Mitigation of Power Fluctuation of Variable Speed Wind Turbines

Grid connected wind turbines are the sources of power fluctuations during continuous operation due to wind speed variation, wind shear and tower shadow effects. This paper presents an individual pitch control (IPC) strategy to mitigate the wind turbine power fluctuation at both above and below the rated wind speed conditions. Three pitch angles are adjusted separately according to the generator output power and the azimuth angle of the wind turbine. The IPC strategy scheme is proposed and the individual pitch controller is designed. The simulations are performed on the NREL (National Renewable Energy Laboratory) 1.5MW upwind reference wind turbine model. The simulation results are presented and discussed to show the validity of the proposed control method. Keywords-wind turbine; IPC; power fluctuation; FAST
A single phosphoacceptor residue in BGLF3 is essential for transcription of Epstein-Barr virus late genes

Almost one third of herpesvirus proteins are expressed with late kinetics. Many of these late proteins serve crucial structural functions such as formation of virus particles, attachment to host cells and internalization. Recently, we and others identified a group of Epstein-Barr virus early proteins that form a pre-initiation complex (vPIC) dedicated to transcription of late genes. Currently, there is a fundamental gap in understanding the role of post-translational modifications in regulating assembly and function of the complex. Here, we used mass spectrometry to map potential phosphorylation sites in BGLF3, a core component of the vPIC module that connects the BcRF1 viral TATA box binding protein to other components of the complex. We identified threonine 42 (T42) in BGLF3 as a phosphoacceptor residue. T42 is conserved in BGLF3 orthologs encoded by other gamma herpesviruses. Abolishing phosphorylation at T42 markedly reduced expression of vPIC-dependent late genes and disrupted production of new virus particles, but had no effect on early gene expression, viral DNA replication, or expression of vPIC-independent late genes. We complemented failure of BGLF3(T42A) to activate late gene expression by ectopic expression of other components of vPIC. Only BFRF2 and BVLF1 were sufficient to suppress the defect in late gene expression associated with BGLF3(T42A). These results were corroborated by the ability of wild type BGLF3 but not BGLF3(T42A) to form a trimeric complex with BFRF2 and BVLF1. Our findings suggest that phosphorylation of BGLF3 at threonine 42 serves as a new checkpoint for subsequent formation of BFRF2:BGLF3:BVLF1; a trimeric subcomplex essential for transcription of late genes. Our findings provide evidence that post-translational modifications regulate the function of the vPIC nanomachine that initiates synthesis of late transcripts in herpesviruses.
A Reinforcement Learning–Based Method for Management of Type 1 Diabetes: Exploratory Study

Background Type 1 diabetes mellitus (T1DM) is characterized by chronic insulin deficiency and consequent hyperglycemia. Patients with T1DM require long-term exogenous insulin therapy to regulate blood glucose levels and prevent the long-term complications of the disease. Currently, there are no effective algorithms that consider the unique characteristics of T1DM patients to automatically recommend personalized insulin dosage levels. Objective The objective of this study was to develop and validate a general reinforcement learning (RL) framework for the personalized treatment of T1DM using clinical data. Methods This research presents a model-free data-driven RL algorithm, namely Q-learning, that recommends insulin doses to regulate the blood glucose level of a T1DM patient, considering his or her state defined by glycated hemoglobin (HbA1c) levels, body mass index, engagement in physical activity, and alcohol usage. In this approach, the RL agent identifies the different states of the patient by exploring the patient’s responses when he or she is subjected to varying insulin doses. On the basis of the result of a treatment action at time step t, the RL agent receives a numeric reward, positive or negative. The reward is calculated as a function of the difference between the actual blood glucose level achieved in response to the insulin dose and the targeted HbA1c level. The RL agent was trained on 10 years of clinical data of patients treated at the Mass General Hospital. Results A total of 87 patients were included in the training set. The mean age of these patients was 53 years, 59% (51/87) were male, 86% (75/87) were white, and 47% (41/87) were married. The performance of the RL agent was evaluated on 60 test cases. RL agent–recommended insulin dosage interval includes the actual dose prescribed by the physician in 53 out of 60 cases (53/60, 88%). Conclusions This exploratory study demonstrates that an RL algorithm can be used to recommend personalized insulin doses to achieve adequate glycemic control in patients with T1DM. However, further investigation in a larger sample of patients is needed to confirm these findings.
Novel AChE and BChE inhibitors using combined virtual screening, text mining and in vitro binding assays

Abstract In the current work, we developed a computational pipeline method for predicting the binding affinities of studied compounds at the specific target sites. Since many approved therapeutic compounds involve indole or indole-derivative rings, in the current study we focused compounds including these fingerprints. Initially, 212520 compounds were retrieved from Specs-SC library and after the conversion of IUPAC text file format, compounds that include ‘indol’ keyword (5194 compounds) were used in binary QSAR-based models to screen against a defined therapeutic activity “Alzheimer’s disease” (AD). The molecules that have higher AD therapeutic activity values (>0.5) were then used in the 26 different toxicity-QSAR models. Binary QSAR models resulted 89 hits that have high AD therapeutic activity and no toxicity. Selected 89 molecules were then screened against acetylcholinesterase (AChE) targets using molecular docking and top-docking poses of compounds were used in initially short (10 ns) molecular dynamics (MD) simulations. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy calculations were performed for 89 ligands and tightly bound 17 ligands based on average MM/GBSA scores were selected for long (100 ns) MD simulations. The same protocol was also applied for the known 4 AChE inhibitors. Selected hits were also docked to the binding pocket of butyrylcholinesterase (BChE). Finally, based on MM/GBSA scores, as well as their corresponding docking scores and metabolite production profiles, 7 compounds were selected and their in vitro tests were performed. Out of 7 compounds, 6 of them showed μM-level inhibition for both AChE and BChE targets. Communicated by Ramaswamy H. Sarma
Synthesis and mode of action studies of novel {2‐(3‐R‐1H‐1,2,4‐triazol‐5‐yl)phenyl}amines to combat pathogenic fungi

Due to their high specificity and efficacy, triazoles have become versatile antifungals to treat fungal infections in human healthcare and to control phytopathogenic fungi in agriculture. However, azole resistance is an emerging problem affecting human health as well as food security. Here we describe the synthesis of 10 novel {2‐(3‐R‐1H‐1,2,4‐triazol‐5‐yl)phenyl}amines. Their structure was ascertained by liquid chromatography–mass spectrometry, 1H and 13C NMR, and elemental analysis data. Applying an in vitro growth assay, these triazoles show moderate to significant antifungal activity against the opportunistic pathogen Aspergillus niger, 12 fungi (Fusarium oxysporum, Fusarium fujikuroi, Colletotrichum higginsianum, Gaeumannomyces graminis, Colletotrichum coccodes, Claviceps purpurea, Alternaria alternata, Mucor indicus, Fusarium graminearum, Verticillium lecanii, Botrytis cinerea, Penicillium digitatum) and three oomycetes (Phytophtora infestans GL‐1, P. infestans 4/91; R+ and 4/91; R−) in the concentration range from 1 to 50 µg/ml (0.003–2.1 μM). Frontier molecular orbital energies were determined to predict their genotoxic potential. Molecular docking calculations taking into account six common fungal enzymes point to 14α‐demethylase (CYP51) and N‐myristoyltransferase as the most probable fungal targets. With respect to effectiveness, structure–activity calculations revealed the strong enhancing impact of adamantyl residues. The shown nonmutagenicity in the Salmonella reverse‐mutagenicity assay and no violations of drug‐likeness parameters suggest the good bioavailability and attractive ecotoxicological profile of the studied triazoles.
Pulmonary Function Testing in Dentists versus Controls: A Pilot Study Exploring the Potential Respiratory-Related Occupational Hazards of Dentistry.

OBJECTIVE Minimal research exists evaluating respiratory-related occupational hazards associated with dentistry in the United States. The purpose of this study was to evaluate the pulmonary function of dentists as compared with controls. METHODS This is a case-control study evaluating pulmonary function in dentists versus controls. Outcomes included measurements of FEV1%, FVC%, and FEV1/FVC. RESULTS Our findings indicate that dentists had a statistically significant lower percent predicted FEV1% (p < 0.05) and FVC% (p < 0.05) compared to controls. The prevalence of abnormal FVC% and FEV1% was greater among dentists, but only the increase in abnormal FEV1% approached significance. CONCLUSIONS Dentists had lower percent predicted values for FVC% and FEV1% versus controls. More research is required to further investigate the association between the dental profession and pulmonary function in dentists.
Frizzled3 and Frizzled6 Cooperate with Vangl2 to Direct Cochlear Innervation by Type II Spiral Ganglion Neurons

Type II spiral ganglion neurons provide afferent innervation to outer hair cells of the cochlea and are proposed to have nociceptive functions important for auditory function and homeostasis. These neurons are anatomically distinct from other classes of spiral ganglion neurons because they extend a peripheral axon beyond the inner hair cells that subsequently makes a distinct 90 degree turn toward the cochlear base. As a result, patterns of outer hair cell innervation are coordinated with the tonotopic organization of the cochlea. Previously, it was shown that peripheral axon turning is directed by a nonautonomous function of the core planar cell polarity (PCP) protein VANGL2. We demonstrate using mice of either sex that Fzd3 and Fzd6 similarly regulate axon turning, are functionally redundant with each other, and that Fzd3 genetically interacts with Vangl2 to guide this process. FZD3 and FZD6 proteins are asymmetrically distributed along the basolateral wall of cochlear-supporting cells, and are required to promote or maintain the asymmetric distribution of VANGL2 and CELSR1. These data indicate that intact PCP complexes formed between cochlear-supporting cells are required for the nonautonomous regulation of axon pathfinding. Consistent with this, in the absence of PCP signaling, peripheral axons turn randomly and often project toward the cochlear apex. Additional analyses of Porcn mutants in which WNT secretion is reduced suggest that noncanonical WNT signaling establishes or maintains PCP signaling in this context. A deeper understanding of these mechanisms is necessary for repairing auditory circuits following acoustic trauma or promoting cochlear reinnervation during regeneration-based deafness therapies. SIGNIFICANCE STATEMENT Planar cell polarity (PCP) signaling has emerged as a complementary mechanism to classical axon guidance in regulating axon track formation, axon outgrowth, and neuronal polarization. The core PCP proteins are also required for auditory circuit assembly, and coordinate hair cell innervation with the tonotopic organization of the cochlea. This is a non–cell-autonomous mechanism that requires the formation of PCP protein complexes between cochlear-supporting cells located along the trajectory of growth cone navigation. These findings are significant because they demonstrate how the fidelity of auditory circuit formation is ensured during development, and provide a mechanism by which PCP proteins may regulate axon outgrowth and guidance in the CNS.
Auditory Space Perception in the Blind: Horizontal Sound Localization in Acoustically Simple and Complex Situations

Even though it is widely believed that cross-modal neuroplasticity in blindness results in enhanced auditory spatial abilities, a growing number of studies also indicate disadvantages of blind persons for specific, more demanding audiospatial tasks. Here, the effects of blindness on horizontal sound localization were compared for simple localization of target sounds presented in isolation and target localization in an acoustically complex (cocktail-party) situation with multiple distractor sounds. While performances of blind and sighted subjects were similar in the cocktail-party setting, a significant disadvantage of blind subjects was found for simple localization of sound sources presented in the center of the frontal space, with the mean absolute error being more than twice that of controls for targets in the median plane. The latter result could be due to the lack of visual calibration of auditory space, which may, in sighted persons, be most effective in the region of maximum visual acuity. On the other hand, the normal performance of blind persons in cocktail-party localization could be explained by the fact that this task, in addition to genuine spatial analysis, critically involved spectrotemporal analysis of the auditory scene to separate different sources for which superior performance is known from previous research.
The Impact of an Ice Slurry-Induced Gastrointestinal Heat Sink on Gastrointestinal and Rectal Temperatures Following Exercise

Gastrointestinal temperature (Tgint) measurement with a telemetric pill (TP) is increasingly used in exercise science. Contact of cool water with a TP invalidates Tgint assessment. However, what effect a heat sink created in the proximity of a TP may have on the assessment of Tgint remains unknown. We examined the impact of an ice slurry-induced heat sink on Tgint and rectal temperature (Trec) following exercise. After 20 min of seating (20–22 °C, 25–40% relative humidity (RH)), 11 men completed two intersperse exercise periods (31–32 °C, 35% RH) at 75–80% of estimated maximal heart rate until a Trec increase of 1 °C above baseline level. Following the first exercise period, participants were seated for 45 min and ingested 7.5 g·kg−1 of thermoneutral water, whereas, following the second period, they ingested 7.5 g·kg−1 of ice slurry. Both Tgint and Trec were measured continuously. The TPs were swallowed 10 h prior to the experiments. A bias ≤0.27 °C was taken as an indication that Tgint and Trec provided similar core temperature indices. Mean biases and 95% limits of agreement during passive sitting, first exercise, water ingestion, second exercise, and ice slurry ingestion periods were 0.16 ± 0.53, 0.13 ± 0.41, 0.21 ± 0.70, 0.17 ± 0.50, and 0.18 ± 0.66 °C, respectively. The rates of decrease in Tgint and Trec did not differ between the water and ice slurry ingestion periods. Our results indicate that ice slurry ingestion following exercise does not impact TP-derived assessment of Tgint compared with Trec.