Miracle-dz/UniFAR-FTUs huggingface dataset:
Enceladus: First Observed Primordial Soup Could Arbitrate Origin-of-Life Debate

Abstract A recent breakthrough publication has reported complex organic molecules in the plumes emanating from the subglacial water ocean of Saturn's moon Enceladus (Postberg et al., 2018, Nature 558:564–568). Based on detailed chemical scrutiny, the authors invoke primordial or endogenously synthesized carbon-rich monomers (<200 u) and polymers (up to 8000 u). This appears to represent the first reported extraterrestrial organics-rich water body, a conceivable milieu for early steps in life's origin (“prebiotic soup”). One may ask which origin-of-life scenario appears more consistent with the reported molecular configurations on Enceladus. The observed monomeric organics are carbon-rich unsaturated molecules, vastly different from present-day metabolites, amino acids, and nucleotide bases, but quite chemically akin to simple lipids. The organic polymers are proposed to resemble terrestrial insoluble kerogens and humic substances, as well as refractory organic macromolecules found in carbonaceous chondritic meteorites. The authors posit that such polymers, upon long-term hydrous interactions, might break down to micelle-forming amphiphiles. In support of this, published detailed analyses of the Murchison chondrite are dominated by an immense diversity of likely amphiphilic monomers. Our specific quantitative model for compositionally reproducing lipid micelles is amphiphile-based and benefits from a pronounced organic diversity. It thus contrasts with other origin models, which require the presence of very specific building blocks and are expected to be hindered by excess of irrelevant compounds. Thus, the Enceladus finds support the possibility of a pre-RNA Lipid World scenario for life's origin.
Imaging and manipulating pituitary function in the awake mouse.

Extensive efforts have been made to explore how the activities of multiple brain cells combine to alter physiology through imaging and cell-specific manipulation in different animal models. However, the temporal regulation of peripheral organs by the neuroendocrine factors released by the brain is poorly understood. We have established a suite of adaptable methodologies to interrogate in vivo the relationship of hypothalamic regulation with the secretory output of the pituitary gland, which has complex functional networks of multiple cell types intermingled with the vasculature. These allow imaging and optogenetic manipulation of cell activities in the pituitary gland in awake mouse models, in which both neuronal regulatory activity and hormonal output are preserved. This methodology is now readily applicable for longitudinal studies of short-lived events (e.g. calcium signals controlling hormone exocytosis) and slowly-evolving processes such as tissue remodelling in health and disease over a period of days to weeks.
Predictors of successful discontinuation of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review.

OBJECTIVE To systematically review possible predictors of successful discontinuation of biologic or targeted synthetic DMARDs (b/tsDMARDs) in RA patients in remission or low disease activity. METHODS MEDLINE database and Cochrane Library were scanned for studies that discontinued b/tsDMARDs in remission/low disease activity and searched for predictors of successful discontinuation. Additionally, EULAR and ACR meeting abstracts were hand searched. RESULTS Thirty-four studies with a total of 5724 patients were included. Predictors of successful b/tsDMARD discontinuation were (number of studies): low disease activity (n = 13), better physical function (n = 6), low or absence of rheumatoid factor (n = 5) or ACPA (n = 3), low levels of CRP (n = 3) or ESR (n = 3), shorter disease duration (n = 3), low signals of disease activity by ultrasound (n = 3). Only one study with high risk of bias was identified on tsDMARD discontinuation. CONCLUSION Several predictors of successful bDMARD discontinuation were identified. Although studies are heterogeneous, these predictors may inform clinical decision making in patients who are considered for a potential bDMARD discontinuation.
How strong is my safety net? Perceived unemployment insurance generosity and implications for job search, mental health, and reemployment.

While social science has substantially documented the individual experience of unemployment, less is known about the role of contextual variables. One contextual factor that is important for unemployed job seekers is the unemployment insurance (UI) that they receive. This study examines the relationships between job seeker perceptions of UI generosity and mental health during unemployment, reemployment speed, and reemployment quality. Drawing upon psychological construal theory, we conceptualize UI generosity as creating psychological distance from the reemployment goal, generating consequences for the job search, mental health, and reemployment. We tested our hypotheses with a four-wave survey design of job seekers looking for work in 3 different countries (United States, Germany, and the Netherlands). Perceived UI generosity was associated with slower reemployment speed, via reduced time pressure, job search priority, and job search metacognition. Perceived UI generosity was related to higher mental health, via reduced time pressure and financial strain. Finally, perceived UI generosity was related to increased reemployment quality, both directly as well as indirectly through lower time pressure and financial strain, and subsequent higher mental health. Our findings provide previously unavailable empirical insight into the mechanisms explaining the positive and negative outcomes of UI generosity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Penetration Enhancers in Ocular Drug Delivery

There are more than 100 recognized disorders of the eye. This makes the development of advanced ocular formulations an important topic in pharmaceutical science. One of the ways to improve drug delivery to the eye is the use of penetration enhancers. These are defined as compounds capable of enhancing drug permeability across ocular membranes. This review paper provides an overview of anatomical and physiological features of the eye and discusses some common ophthalmological conditions and permeability of ocular membranes. The review also presents the analysis of literature on the use of penetration-enhancing compounds (cyclodextrins, chelating agents, crown ethers, bile acids and bile salts, cell-penetrating peptides, and other amphiphilic compounds) in ocular drug delivery, describing their properties and modes of action.
Association between subclinical hypothyroidism and metabolic disorders: A retrospective chart review study in an emerging university hospital

Subclinical hypothyroidism is defined as an increase in serum levels of Thyroid Stimulating Hormone (TSH) above the normal range, without alteration of total T4 concentrations that is reported to have association with various metabolic conditions. The study aimed to investigate any association between subclinical hypothyroidism and metabolic disorders in Al Kharj city.
Clinicopathological characteristics of non‐ampullary duodenal tumors and their phenotypic classification

The tumorigenesis of non‐ampullary duodenal epithelial tumors (NADETs) might be different between the oral and anal sides of Vater's papilla. We conducted an immunohistological review to elucidate the clinicopathological features according to the tumor location and phenotypic classification. A review of an institutional database identified 121 patients with 125 superficial NADETs. NADETs were histologically evaluated and classified into the intestinal or gastric type based on immunohistochemical analysis. Clinicopathological factors were compared based on the tumor location and phenotype. Logistic regression analysis was performed to identify independent predictors for gastric‐type NADETs. According to location analysis, the mucin phenotype was significantly different (oral side, intestinal‐type 64.8%, gastric‐type 35.3%; anal side, intestinal‐type 87.3%, gastric‐type 12.7%; P < 0.01). Although the incidence of adenoma was significantly predominant in the intestinal type (75.3%), most gastric‐type NADETs were cancerous (64.3%). Notably, most gastric‐type NADETs were adenocarcinomas even when the tumor size was ≤0 mm. In multivariate analysis, tumor location on the oral side (odds ratio [OR], 4.42), villous structure (OR, 6.44), and low tumor gland density (OR, 9.49) were independent predictors of gastric‐type tumors. Gastric‐type NADETs significantly differ from intestinal‐type NADETs in terms of tumor location, morphology, and biology.
Dental Professionals’ Engagement in Tobacco, Electronic Cigarette, and Cannabis Patient Counseling

Objectives: California features low smoking prevalence, cautionary electronic cigarette (e-cigarette) public messaging, and legal recreational cannabis: a unique landscape for dental professionals to navigate tobacco cessation promotion. This cross-sectional study assessed California dental professionals’ self-reported tobacco patient counseling behaviors and the correlates of providing such assistance. Methods: Statewide surveys of dental hygienists (n = 701) and dentists (n = 725) were distributed electronically. The dentist survey was weighted for sampling and nonresponse. Prevalence of asking patients about use was compared for cigarette and noncigarette products (e.g., e-cigarettes, cannabis). Multivariable models identified independent correlates of providing cessation assistance to tobacco-using patients. Results: Respondents reported frequently (often/always) documenting patient tobacco use (hygienists: 80%; dentists: 73%) but less commonly provided forms of assistance (hygienists: 27%–49%; dentists: 10%–31%). Most respondents asked patients about cigarette smoking, but noncigarette product use (cigar, hookah, pipe, e-cigarette, or cannabis) was not commonly assessed. Greater confidence and willingness to assist were positively associated with providing assistance in multivariable models, but perceived barriers (e.g., lack of time and remuneration) were not. Results were robust to model specifications. Conclusions: California dental professionals often ask about smoking but lag in providing cessation assistance and inquiring about noncigarette products. Successful efforts to encourage dental professionals’ engagement in tobacco prevention and cessation must enhance providers’ self-efficacy and motivation and likely will require system and organizational change. Knowledge Transfer Statement: Study findings identify substantial gaps in dental professionals’ engagement in patient tobacco cessation. The results identify correlates of providing assistance and of dental professionals’ willingness and confidence to do so, which could serve to inform interventions to support and enhance engagement.
Comparative Transcriptomic and Proteomic Analysis to Deeply Investigate the Role of Hydrogen Cyanamide in Grape Bud Dormancy

Hydrogen cyanamide (HC) is an agrochemical compound that is frequently used to break bud dormancy in grapevines grown under mild winter conditions globally. The present study was carried out to provide an in-depth understanding of the molecular mechanism associated with HC releasing bud dormancy in grapevines. For this purpose, RNA-seq based transcriptomic and tandem mass tag (TMT)-based proteomic information was acquired and critically analyzed. The combined results of transcriptomic and proteomic analysis were utilized to demonstrate differential expression pattern of genes at the translational and transcriptional levels. The outcome of the proteomic analysis revealed that a total of 7135 proteins (p-value ≤ 0.05; fold change ≥ 1.5) between the treatments (HC treated versus control) were identified, out of which 6224 were quantified. Among these differentially expressed proteins (DEPs), the majority of these proteins were related to heat shock, oxidoreductase activity, and energy metabolism. Metabolic, ribosomal, and hormonal signaling pathways were found to be significantly enriched at both the transcriptional and translational levels. It was illustrated that genes associated with metabolic and oxidoreductase activity were mainly involved in the regulation of bud dormancy at the transcriptomic and proteomic levels. The current work furnishes a new track to decipher the molecular mechanism of bud dormancy after HC treatment in grapes. Functional characterization of key genes and proteins will be informative in exactly pinpointing the crosstalk between transcription and translation in the release of bud dormancy after HC application.
Liquid Biopsy for the Detection of Resistance Mechanisms in NSCLC: Comparison of Different Blood Biomarkers

The use of targeted agents and immunotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) has made it mandatory to characterize tumor tissue for patient selection. Moreover, the development of agents that are active against specific resistance mechanisms arising during treatment make it equally important to characterize the tumor tissue at progression by performing tissue re-biopsy. Given that tumor tissue is not always available for molecular characterization due to the paucity of diagnostic specimens or problems relating to the carrying out of invasive procedures, the use of liquid biopsy represents a valid approach to overcoming these difficulties. The most common material used for liquid biopsy in this setting is plasma-derived cell free DNA (cfDNA), which originates from cells undergoing apoptosis or necrosis. However, other sources of tumor material can be considered, such as extracellular vesicle (EV)-derived nucleic acids, which are actively secreted from living cells and closely correspond to tumor dynamics. In this review, we discuss the role of liquid biopsy in the therapeutic management of NSCLC with particular regard to targeted therapy and immunotherapy, and analyze the pros and cons of the different types of samples used in this context.
Plasma Vitamin C Levels: Risk Factors for Deficiency and Association with Self-Reported Functional Health in the European Prospective Investigation into Cancer-Norfolk

Background: To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health. Methods: A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin C level < 11 µmol/L indicated vitamin C deficiency. Unconditional logistic regression models assessed the association between vitamin C deficiency and potential risk factors. Associations between quartiles of vitamin C and self-reported functional health measured by the 36-item short-form questionnaire (SF-36) were assessed. Results: After adjustment, vitamin C deficiency was associated with older age, being male, lower physical activity, smoking, more socially deprived area (Townsend index) and a lower educational attainment. Compared to the highest, those in the lowest quartile of vitamin C were more likely to score in the lowest decile of physical function (adjusted odds ratio (aOR): 1.43 (95%CI: 1.21–1.70)), bodily pain (aOR: 1.29 (95% CI: 1.07–1.56)), general health (aOR: 1.4 (95%CI: 1.18–1.66)), and vitality (aOR: 1.23 (95%CI: 1.04–1.45)) SF-36 scores. Conclusions: Simple public health interventions should be aimed at populations with risk factors for vitamin C deficiency. Poor self-reported functional health was associated with lower plasma vitamin C levels, which may reflect symptoms of latent scurvy.
De novo assembly of a chromosome‐level reference genome of red‐spotted grouper (Epinephelus akaara) using nanopore sequencing and Hi‐C

The red‐spotted grouper Epinephelus akaara (E. akaara) is one of the most economically important marine fish in China, Japan and South‐East Asia and is a threatened species. The species is also considered a good model for studies of sex inversion, development, genetic diversity and immunity. Despite its importance, molecular resources for E. akaara remain limited and no reference genome has been published to date. In this study, we constructed a chromosome‐level reference genome of E. akaara by taking advantage of long‐read single‐molecule sequencing and de novo assembly by Oxford Nanopore Technology (ONT) and Hi‐C. A red‐spotted grouper genome of 1.135 Gb was assembled from a total of 106.29 Gb polished Nanopore sequence (GridION, ONT), equivalent to 96‐fold genome coverage. The assembled genome represents 96.8% completeness (BUSCO) with a contig N50 length of 5.25 Mb and a longest contig of 25.75 Mb. The contigs were clustered and ordered onto 24 pseudochromosomes covering approximately 95.55% of the genome assembly with Hi‐C data, with a scaffold N50 length of 46.03 Mb. The genome contained 43.02% repeat sequences and 5,480 noncoding RNAs. Furthermore, combined with several RNA‐seq data sets, 23,808 (99.5%) genes were functionally annotated from a total of 23,923 predicted protein‐coding sequences. The high‐quality chromosome‐level reference genome of E. akaara was assembled for the first time and will be a valuable resource for molecular breeding and functional genomics studies of red‐spotted grouper in the future.
Atmospheres on Nonsynchronized Eccentric-tilted Exoplanets. II. Thermal Light Curves

Thermal light-curve analysis is a powerful approach to probe the thermal structures of exoplanetary atmospheres, which are greatly influenced by the planetary obliquity and eccentricity. Here we investigate the thermal light curves of eccentric-tilted exoplanets across various radiative timescales, eccentricities, obliquities, and viewing geometries using results of shallow-water simulations presented in Ohno & Zhang. We also achieve an analytical theory of the thermal light curve that can explain general trends in the light curves of tilted exoplanets. For tilted planets in circular orbits, the orbital phase of the flux peak is largely controlled by either the flux from the hot spot projected onto the orbital plane or the pole heated at the summer solstice, depending on the radiative timescale τrad, planetary day Porb, and obliquity θ. We find that tilted planets potentially produce the flux peak after the secondary eclipse when obliquity is θ ≳ 90° for the hot regime τrad ≪ Prot or θ ≳ 18° for the cool regime τrad ≫ Prot. For tilted planets in eccentric orbits, the shape of the light curve is considerably influenced by the heating at the periapse. The flux peak occurring after the secondary eclipse can be used to distinguish tilted planets from nontilted planets when the periapse takes place before the secondary eclipse. Our results could help to constrain exoplanet obliquities in future observations.
Moving from Corporate Strategy to Project Strategy

Much of the management writing around strategy tends to cover the practices at the corporate and business level; there is a dearth of writing about how corporate strategy gets implemented by projects and programs and translated into program or project strategies. This paper reviews evidence from four case studies together with questionnaire data from PMI Europe members, which shows that the processes, practices, and people issues involved in moving from corporate strategy to programs and projects is done in a much more systematic way than is generally recognized. The findings point to areas that future revisions of the PMBOK® Guide should be looking at.
An example of 3-phase transformer modeling for distribution system analysis

This panel presentation summary describes a technique of developing a multiwinding, multiphase transformer model for distribution systems analysis. The model can be expressed concisely and is readily implemented in common general-purpose matrix manipulation software. One challenging example is given: the ungrounded wye/delta case from the IEEE PES 4-Bus Radial Test Feeder system. The primitive Y matrix model is developed using the Matlab program. Its use in a general distribution system analysis program is described.
GaN islanding by spontaneous rearrangement of a strained two-dimensional layer on (0001) AlN

It is shown that a two-dimensional GaN layer grown on (0001) AlN under Ga-rich conditions remains two-dimensional while annealing under a Ga flux due to a surfactant effect of Ga. In contrast, further annealing under vacuum without the Ga flux leads to evaporation of excess Ga and to spontaneous transformation of the GaN layer into islands if the initial layer is thicker than about 2.5 monolayers. The resulting morphology is studied by atomic force microscopy and transmission electron microscopy. The latter reveals that these islands sit on top of a continuous 2.5 monolayer thick wetting layer, i.e., they represent a Stranski–Krastanow structure.
Determination of stellar ages from isochrones: Bayesian estimation versus isochrone fitting

We present a new method, using Bayesian estimation, to determine stellar ages and their uncertainties from observational data and theoretical isochrones. The result for an individual star is obtained as the relative posterior probability density as function of the age ("G function"). From this can be derived the most probable age and confidence intervals. The convoluted morphology of isochrones and strong non-linearities make the age determination by any method difficult and susceptible to statistical biases, and as a result age uncertainties havee often been underestimated in the literature. From simulations we find that the G functions provide a general, robust and reliable way to quantify age information. Resulting age estimates are at least as accurate as those obtained with conventional isochrone fitting methods, and in some cases much better, especially when the observational uncertainties are large. We also find that undetected binaries, on the whole, have a surprisingly small effect on the age determinations. For a stellar sample, the individual G functions can be combined to derive the star formation history of the population; this will be developed in a forthcoming paper. For a coeval population the combination simplifies to computing the product of the individual G functions, and we apply that method to estimate the ages of the two open clusters IC 4651 and M67, using Padova isochrones and photometric data from the literature. For IC 4651 we find an estimated age of 1.56 +/- 0.03 Gyr, assuming a true distance modulus of 9.80. For M67 we find 4.05 +/- 0.05 Gyr for true distance modulus 9.48. The small formal errors of these age estimates do not include the ( much larger) uncertainties from calibration and model errors, but illustrate the statistical power of combining G functions. Our statistical approach to the age determination problem is well suited for the mass treatment of data resulting from large-scale surveys such as the Gaia mission. (Less)
Non-Hermitian acoustic metamaterials: Role of exceptional points in sound absorption

Effective non-Hermitian Hamiltonians are obtained to describe coherent perfect absorbing and lasing boundary conditions. PT -symmetry of the Hamiltonians enables to design configurations which perfectly absorb at multiple frequencies. Broadened and flat perfect absorption is predicted at the exceptional point of PT -symmetry breaking while, for a particular case, absorption is enhanced with the use of gain. The aforementioned phenomena are illustrated for acoustic scattering through Helmholtz resonators revealing how tailoring the non-Hermiticity of acoustic metamaterials leads to novel mechanisms for enhanced absorption.