Miracle-dz/UniFAR-FTUs huggingface dataset:
Linear Superposition and Prediction of Bacterial Promoter Activity Dynamics in Complex Conditions

Bacteria often face complex environments. We asked how gene expression in complex conditions relates to expression in simpler conditions. To address this, we obtained accurate promoter activity dynamical measurements on 94 genes in E. coli in environments made up of all possible combinations of four nutrients and stresses. We find that the dynamics across conditions is well described by two principal component curves specific to each promoter. As a result, the promoter activity dynamics in a combination of conditions is a weighted average of the dynamics in each condition alone. The weights tend to sum up to approximately one. This weighted-average property, called linear superposition, allows predicting the promoter activity dynamics in a combination of conditions based on measurements of pairs of conditions. If these findings apply more generally, they can vastly reduce the number of experiments needed to understand how E. coli responds to the combinatorially huge space of possible environments.
Topography and timing of activity in right inferior frontal cortex and anterior insula for stopping movement

Stopping incipient action activates both the right inferior frontal cortex (rIFC) and the anterior insula (rAI). Controversy has arisen as to whether these comprise a unitary cortical cluster—the rIFC/rAI—or whether rIFC is the primary stopping locus. To address this, we recorded directly from these structures while taking advantage of the high spatiotemporal resolution of closely spaced stereo‐electro‐encephalographic (SEEG) electrodes. We studied 12 patients performing a stop‐signal task. On each trial they initiated a motor response (Go) and tried to stop to an occasional stop signal. Both the rIFC and rAI exhibited an increase in broadband gamma activity (BGA) after the stop signal and within the time of stopping (stop signal reaction time, SSRT), regardless of the success of stopping. The proportion of electrodes with this response was significantly greater in the rIFC than the rAI. Also, the rIFC response preceded that in the rAI. Last, while the BGA increase in rIFC occurred mainly prior to SSRT, the rAI showed a sustained increase in the beta and low gamma bands after the SSRT. In summary, the rIFC was activated soon after the stop signal, prior to and more robustly than the rAI, which on the other hand, showed a more prolonged response after the onset of stopping. Our results are most compatible with the notion that the rIFC is involved in triggering outright stopping in concert with a wider network, while the rAI is likely engaged by other processes, such as arousal, saliency, or behavioral adjustments. Hum Brain Mapp 39:189–203, 2018. © 2017 Wiley Periodicals, Inc.
Droplet size, concentration, and temperature mapping in sprays using SLIPI-based techniques

Structured laser illumination planar imaging (SLIPI) is a technique capable of suppressing multiple light scattering effects in optically dense sprays, resulting in spray images without blurs and with enhanced contrast. The novelty of the work presented in this thesis concerns the applications of a variety of SLIPI-based techniques for the measurement of droplet size, droplet concentration, and liquid temperature in atomizing sprays. Two types of spray systems are investigated here: 1) Steady hollow-cone water sprays using temporally averaged imaging. 2) Transient Direct-Injection spark ignition (DISI) biofuel sprays using instantaneous imaging. The temporally averaged measurements are performed using three-phase SLIPI (3p-SLIPI) with liquid injection pressures in the range of 20–50 bar and at ambient conditions. Droplet sizing is obtained by combining SLIPI with the laser-induced fluorescence (LIF)/Mie ratio approach, where the droplet Sauter mean diameter is deduced after calibration with phase Doppler anemometry measurements. The droplet concentration and liquid volume fraction are obtained by combining the SLIPI-LIF/Mie method with light transmission measurements. This is performed using a laser sheet scanning approach, which provides three-dimensional quantitative reconstructions. Finally, the spray temperature is obtained by combining SLIPI with two-color LIF ratio thermometry for a liquid temperature ranging from 25–55°C. It is found that multiple light scattering induces measurement errors even for sprays having singly scattered photons in majority. This finding, therefore, strongly supports the application of SLIPI for quantitative spray measurements, even for optically dilute sprays. The 3p-SLIPI approach is based on recording a minimum of three modulated sub-images successively, each having a different spatial phase; therefore, it has been primarily used for temporally averaged imaging. To circumvent this limitation, two novel instantaneous imaging approaches, 2p-SLIPI and 1p-SLIPI (corresponding to two-phase and one-phase, respectively), have been developed. In the 2p-SLIPI optical setup, the “lines structure” is optically shifted by exploiting the birefringence property of a calcite crystal. This novel optical approach is used to image spray dynamics in ethanol and butanol DISI sprays at liquid fuel injection pressures of 80 and 160 bar, where the spray chamber is operated at 2-bar air pressure. Finally, the results from instantaneous 2p-SLIPI and 1p-SLIPI imaging have been compared, showing promising applications for the study of spray dynamics.
Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database

Researchers in a recent multicenter study developed and validated a novel prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates α‐fetoprotein (AFP) at liver transplantation (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet Milan criteria by imaging and underwent LT between 2012 and ‐2014. On explantation (n = 3276), 13% had microvascular invasion, 30% had no viable tumor, and 15% exceeded Milan criteria. Post‐LT survival at 3 years decreased with increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for a score ≥5 (P < .001). Post‐LT HCC recurrence probability within 3 years increased from 1.6% with RETREAT score of 0% to 29% for a score ≥5 (P < .001). Increasing RETREAT score was also associated with a shorter time to HCC recurrence. RETREAT was superior to Milan criteria (explant) in predicting HCC recurrence by the net reclassification index (P < .001). This study validates the prognostic power of RETREAT, which may help standardize post‐LT surveillance, provide a framework for tumor staging and risk stratification, and select candidates for adjuvant therapies.
Spectrum Effect Relationship and Component Knock-Out in Angelica Dahurica Radix by High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer

Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We applied spectrum-effect relationship and component knock-out methods to make it clear. HPLC was used to obtain the specific chromatograms. The effects on tyrosinase activity were examined by measuring the oxidation rate of levodopa in vitro. Partial least squares method was used to examine the spectrum-effect relationships. The knocked-out samples were prepared by HPLC method, and the identification of knocked-out compounds was conducted by the high performance liquid chromatography-four stage rod-electrostatic field orbit trap high resolution mass spectrometry. Results showed that S6, S14, S18, S21, S35, S36, S37, S40, and S41 were positively correlated to inhibitory activity of Angelica dahuricae on tyrosinase whereas S9, S11, S8, S12, S22, and S30 were negatively correlated. When the concentration of each sample was 1 g·mL−1, equal to the amount of raw medicinal herbs, oxypeucedanin hydrate, imperatorin, cnidilin, and isoimperatorin had inhibitory effects on tyrosinase activity whereas byakangelicin and bergapten had activating effects.
Treatment of Children With Congenital Severe Blepharoptosis by Frontalis Aponeurosis Flap Advancement Under General Anesthesia in a Single Incision

Purpose: This study aimed to investigate the effect of frontalis aponeurosis flap advancement in children with congenital severe blepharoptosis. Methods: A total of 23 cases (25 eyes) of children who had congenital severe blepharoptosis and poor levator function (⩽4 mm) and received frontalis aponeurosis flap advancement treatment in the Plastic Surgery Department of the Children's Hospital of Fudan University from January 1, 2013, to January 1, 2015, were retrospectively analyzed to evaluate the postoperative effects. Results: All patients (age range, 6–27 months) were followed up for an average duration of 15.3 months. Twenty eyes (80%) had excellent effects, 2 eyes (8%) had good effects, and 3 eyes (12%) had poor effects. The average preoperative marginal reflex distance was 0.2 mm (–2 to 2 mm), and the postoperative average marginal reflex distance was 3.1 mm (1–4 mm). None of the patients showed hematoma, infection, keratohelcosis, symblepharon separation, ectropion, trichiasis, or other postoperative complications. Conclusion: Frontalis aponeurosis flap advancement could be used to treat congenital severe blepharoptosis with good short-term effects.
Relationship between Tobacco Craving and Quality of Life among French Students: Results of a Cross-Sectional Study

ABSTRACT Background: Understanding the factors leading to smoking cessation is of primary importance in reducing the death burden. Recently introduced in the DSM-5, craving is a potentially promising mechanism involved in relapse, but its articulation with quality of life and deprivation on tobacco student's consumers has never been investigated. Objectives: Our study explores the relationship between tobacco craving and sub-dimensions of quality of life when controlling effect of deprivation on a youth population with tobacco consumption. Method: Comparison between deprived and non-deprived students were conducted with online questionnaires on demographic data, level of dependency, perceived quality of life, deprivation and craving. Multivariate linear regression with backward procedure was conducted to assess the predictive validity of these variables on craving. Finally, Bayesian analysis was conducted to evaluate the model proposed by the regression. Results: One hundred and seventy-four participants were included. Craving was significantly correlated with all the other variables and increases when the level of deprivation rises, while it decreases when physical health improves. These results are confirmed by Bayesian linear regression. Conclusions/Importance: Environmental and social factors are usually overlooked when it comes to understanding individuals, deeply rooted biological mechanisms such as craving. Working on physical health is of interest to diminished craving and improves the quality of life during smoking cessation and thereby to support success on the student population. Consequences for the triadic neurocognitive model of addiction are discussed.
Population Pharmacokinetic Model Linking Plasma and Peripheral Blood Mononuclear Cell Concentrations of Efavirenz and Its Metabolite, 8-Hydroxy-Efavirenz, in HIV Patients

ABSTRACT The objectives of this study were to characterize the population pharmacokinetics (PK) of efavirenz (EFV) and 8-hydroxy-efavirenz (8OHEFV) in plasma and peripheral blood mononuclear cells (PBMCs) and to explore covariates affecting the PK parameters. Fifty-one patients had steady-state 0-to-24-h concentrations of EFV and 8OHEFV in plasma with corresponding concentrations in PBMCs, while 261 patients had one or two sparse concentrations at 16 ± 1 h postdose at weeks 4 and/or 16. The pharmacogenetic markers CYP2B6*6, CYP3A5*3, CYP3A5*6, UGT2B7*2, ABCB1 (3435C→T, 3842A→G), OATP1B1*1B, and OATP1B1*5, the presence of a rifampin-based antituberculosis (anti-TB) regimen, baseline body weight and organ function values, and demographic factors were explored as covariates. EFV concentration data were well described by a two-compartment model with first-order absorption (Ka) and absorption lag time (Alag) (Ka = 0.2 h−1; Alag = 0.83 h; central compartment clearance [CLc/F] for CYP2B6*1/*1 = 18 liters/h, for CYP2B6*1/*6 = 14 liters/h, and for CYP2B6*6/*6 = 8.6 liters/h) and PBMCs as a peripheral compartment. EFV transfer from plasma to PBMCs was first order (CLp/F = 32 liters/h), followed by capacity-limited return (Vmax = 4,400 ng/ml/h; Km = 710 ng/ml). Similarly, 8OHEFV displayed a first-order elimination and distribution to PBMCs, with a capacity-limited return to plasma. No covariate relationships resulted in a significant explanation of interindividual variability (IIV) on the estimated PK parameters of EFV and 8OHEFV, except for CYP2B6*6 genotypes, which were consistent with prior evidence. Both EFV and 8OHEFV accumulated to higher concentrations in PBMCs than in plasma and were well described by first-order input and Michaelis-Menten kinetics removal from PBMCs. CYP2B6*6 genotype polymorphisms were associated with decreased EFV and 8OHEFV clearance.
Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases

The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA) encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD). This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders.
Prevalence of Invasive Infections Due to Carbapenem-Resistant Enterobacteriaceae among Adult Patients in U.S. Hospitals

ABSTRACT This large-scale retrospective analysis (n = 60,551) of the Premier inpatient database (1 January 2011 to 31 December 2014) found an overall prevalence of carbapenem-resistant Enterobacteriaceae strains of 2.3% (range, 0.9% to 5.8% by geographic region) among patients with infections due to Enterobacteriaceae. Ongoing monitoring and development of decision support tools/algorithms are needed for identification of high-risk patients.
Proteomics reveals novel protein associations with early endosomes in an epidermal growth factor–dependent manner

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. EGFRs on the cell surface become activated upon EGF binding and have an increased rate of endocytosis. Once in the cytoplasm, the EGF·EGFR complex is trafficked to the lysosome for degradation, and signaling is terminated. During trafficking, the EGFR kinase domain remains active, and the internalized EGFR can continue signaling to downstream effectors. Although effector activity varies based on the EGFR's endocytic location, it is not clear how this occurs. In an effort to identify proteins that uniquely associate with the internalized, liganded EGFR in the early endosome, we developed an early endosome isolation strategy to analyze their protein composition. Post-nuclear supernatant from HeLa cells stimulated with and without EGF were separated on an isotonic 17% Percoll gradient. The gradient was fractionated, and early endosomal fractions were pooled and immunoisolated with an EEA1 mAb. The isolated endosomes were validated by immunoblot using antibodies against organelle-specific marker proteins and transmission EM. These early endosomes were also subjected to LC–MS/MS for proteomic analysis. Five proteins were detected in endosomes in a ligand-dependent manner: EGFR, RUFY1, STOML2, PTPN23, and CCDC51. Knockdown of RUFY1 or PTPN23 by RNAi indicated that both proteins play a role in EGFR trafficking. These experiments indicate that endocytic trafficking of activated EGFR changes the protein composition, membrane trafficking, and signaling potential of the early endosome.
Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 Receptors and their Role in the Modulation of Pain Response in the Central Nervous System

Background: The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physio-logical, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional expe-rience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. Serotonin [5-HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1–5-HT7) and approximately 15 receptor subtypes. Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS). Method: In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain. Conclusion We concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration in order to inhibit, excite, or even maintain the nociceptive response.
Daily-level Associations between Negative Mood, Perceived Stress, and College Drinking: Do Associations Differ by Sex and Fraternity/Sorority Affiliation?

ABSTRACT Background: Individuals experiencing elevated negative mood and stress may drink to self-medicate, yet daily-level evidence for these associations is mixed. Objective: To clarify daily associations between negative mood and perceived stress with alcohol use among high-risk college students and test whether these associations may vary by same-day versus next-day drinking, sex, and fraternity/sorority affiliation. Methods: Frequently drinking college students (n = 347) participated in a daily diary study, which included daily morning and evening assessments that occurred for two weeks in four consecutive academic quarters. Multilevel zero-inflated Poisson regressions were conducted to examine the effects of daily negative mood and perceived stress on same-day and next-day drinking. Results: Students with higher average negative mood and perceived stress across the sampled days reported a lower likelihood of drinking. Examination of daily-level associations showed that on days students experienced elevated negative mood and perceived stress, they were less likely to drink any alcohol the same day. However, days with elevated negative mood were associated with greater alcohol use the next day. Tests of cross-level interactions indicated that four daily-level associations between higher negative mood or perceived stress and reductions in drinking were found to be significant among females and students unaffiliated with fraternity/sorority only. Conclusions/Importance: Among high-risk college drinkers, negative mood and perceived stress were associated with decreased risk of drinking, particularly among females and students unaffiliated with fraternity/sorority. Daily elevations in negative mood may lead to drinking on a subsequent day and the reason for this lagged effect warrants future research.
Mice lacking ARV1 have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

Metabolic syndrome (MetS) is a term used to characterize individuals having at least three of the following diseases: obesity, dyslipidemia, hyperglycemia, insulin resistance, hypertension, and nonalcoholic fatty liver disease (NAFLD). It is widespread, and the number of individuals with MetS is increasing. However, the events leading to the manifestation of MetS are not well-understood. Here, we show that loss of murine ARV1 (mARV1) results in resistance to acquiring diseases associated with MetS. Arv1−/− animals fed a high-fat diet were resistant to diet-induced obesity, had lower blood cholesterol and triglyceride levels, and retained glucose tolerance and insulin sensitivity. Livers showed no gross morphological changes, contained lower levels of cholesterol, triglycerides, and fatty acids, and showed fewer signs of NAFLD. Knockout animals had elevated levels of liver farnesol X receptor (FXR) protein and its target, small heterodimer protein (SHP). They also had decreased levels of CYP7α1, CYP8β1, and mature SREBP1 protein, evidence suggesting that liver FXR signaling was activated. Strengthening this hypothesis was the fact that peroxisome proliferator-activating receptor α (PPARα) protein was elevated, along with its target, fibroblast growth factor 21 (FGF21). Arv1−/− animals excreted more fecal cholesterol, free fatty acids, and bile acids. Their small intestines had 1) changes in bile acid composition, 2) an increase in the level of the intestinal FXR antagonist, tauromuricholic acid, and 3) showed signs of attenuated FXR signaling. Overall, we believe that ARV1 function is deleterious when consuming a high-fat diet. We further hypothesize that ARV1 is critical for initiating events required for the progression of diseases associated with MetS and NAFLD.