Miracle-dz/UniFAR-FTUs huggingface dataset:
Stabilizing a different cyclooctatetraene stereoisomer

Significance Cyclooctatetraene (COT) is a poster child for nonaromatic molecules. An isomer of tub-shaped COT, with one of the ring double bonds changed from the usual cis form to a trans one, lies some 23 kcal/mol higher in energy. Devising a substitution strategy for turning the tables, making the trans isomer the stable point of the system, is the challenge. Simple bonding ideas, of the bulk of substituents, of clamping and turning aromaticity on and off, of pushing electrons in and out of the system, guide us in devising several realistic candidates. Along the way, a set of molecules that might easily split hydrogen reversibly emerges. An unconventional cis-cis-cis-trans or (Z,Z,Z,E) structure B of cyclooctatetraene (COT) is calculated to lie only 23 kcal/mol above the well-known tub-shaped (Z,Z,Z,Z) isomer A; one example of this type of structure is known. The barrier for B returning to A is small, 3 kcal/mol. However, by suitable choice of substituents, the (Z,Z,Z,E) isomer can be made to lie in energy below the tub-shaped structure. Steric, clamping, and electronic strategies are proposed for achieving this. In the steric strategy, the C8H4(CH3)2(C(tBu)3)2 structure B is predicted to lie 21 kcal/mol below structure A, which is separated from form B only by a small barrier. A simple clamping strategy, effective for COT planarization, does not influence the A/B isomerization much. But, if the clamping group is aromatic (a fused benzene, pyrrole, thiophene, furan), the subtle interplay of potential aromaticity with clamping can be used to confer persistence if not stability on the (Z,Z,Z,E) isomer. An electronic strategy of a different kind, push–pull substitution on the COT ring, was not very effective in stabilizing the B form. However, it led us to vicinal amine–borane-substituted normal COTs that proved to be quite good at activating H2 in a frustrated Lewis pair scenario.
MeCP2 regulates Tet1-catalyzed demethylation, CTCF binding, and learning-dependent alternative splicing of the BDNF gene in Turtle

MECP2 mutations underlying Rett syndrome cause widespread misregulation of gene expression. Functions for MeCP2 other than transcriptional are not well understood. In an ex vivo brain preparation from the pond turtle Trachemys scripta elegans, an intraexonic splicing event in the brain-derived neurotrophic factor (BDNF) gene generates a truncated mRNA transcript in naïve brain that is suppressed upon classical conditioning. MeCP2 and its partners, splicing factor Y-box binding protein 1 (YB-1) and methylcytosine dioxygenase 1 (Tet1), bind to BDNF chromatin in naïve but dissociate during conditioning; the dissociation correlating with decreased DNA methylation. Surprisingly, conditioning results in new occupancy of BDNF chromatin by DNA insulator protein CCCTC-binding factor (CTCF), which is associated with suppression of splicing in conditioning. Knockdown of MeCP2 shows it is instrumental for splicing and inhibits Tet1 and CTCF binding thereby negatively impacting DNA methylation and conditioning-dependent splicing regulation. Thus, mutations in MECP2 can have secondary effects on DNA methylation and alternative splicing. DOI: http://dx.doi. org/10.7554/eLife.25384. 001
On the seasonal variability of eddy kinetic energy in the Gulf Stream region

In the Gulf Stream region, eddy kinetic energy (EKE) peaks in summer while, as measured by the baroclinic eddy growth time scale, the ocean is most baroclinically unstable in late winter. We argue that the seasonally‐varying Ekman pumping is unlikely to be responsible for the seasonal variation in growth time, and that the summer peak in EKE results from a reduction in dissipation in summer compared to winter.
Species characteristics and intraspecific variation in growth and photosynthesis of Cryptomeria japonica under elevated O3 and CO2

In order to predict the effects of future atmospheric conditions on forest productivity, it is necessary to clarify the physiological responses of major forest tree species to high concentrations of ozone (O3) and carbon dioxide (CO2). Furthermore, intraspecific variation of these responses should also be examined in order to predict productivity gains through tree improvements in the future. We investigated intraspecific variation in growth and photosynthesis of Cryptomeria japonica D. Don, a major silviculture species in Japan, in response to elevated concentrations of O3 (eO3) and CO2 (eCO2), separately and in combination. Cuttings of C. japonica were grown and exposed to two levels of O3 (ambient and twice-ambient levels) in combination with two levels of CO2 (ambient and 550 µmol mol-1 in the daytime) for two growing seasons in a free-air CO2 enrichment experiment. There was no obvious negative effect of eO3 on growth or photosynthetic traits of the C. japonica clones, but a positive effect was observed for annual height increments in the first growing season. Dry mass production and the photosynthetic rate increased under eCO2 conditions, while the maximum carboxylation rate decreased. Significant interaction effects of eO3 and eCO2 on growth and photosynthetic traits were not observed. Clonal effects on growth and photosynthetic traits were significant, but the interactions between clones and O3 and/or CO2 treatments were not. Spearman's rank correlation coefficients between growth traits under ambient conditions and for each treatment were significantly positive, implying that clonal ranking in growth abilities might not be affected by either eO3 or eCO2. The knowledge obtained from this study will be helpful for species selection in afforestation programs, to continue and to improve current programs involving this species, and to accurately predict the CO2 fixation capacity of Japanese forests.
Whose Trades Convey Information? Evidence from a Cross-Section of Traders

This paper contributes empirically to our understanding of informed traders. It analyzes traders' characteristics in a foreign exchange electronic limit order market via anonymous trader identities. We use six indicators of informed trading in a cross-sectional multivariate approach to identify traders with high price impact. More information is conveyed by those traders' trades which--simultaneously--use medium-sized orders (practice stealth trading), have large trading volume, are located in a financial center, trade early in the trading session, at times of wide spreads and when the order book is thin.
Litter Size Variation in Hypothalamic Gene Expression Determines Adult Metabolic Phenotype in Brandt's Voles (Lasiopodomys brandtii)

Background Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10–12) and small (3–4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China. Methodology/Principal Findings Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters. Conclusions/Significance These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.
Haemodynamically stimulated and in vivo generated axially vascularized soft‐tissue free flaps for closure of complex defects: Evaluation in a small animal model

The arteriovenous (AV) loop model permits the creation of significant volumes of axially vascularized tissue that represents an alternative to conventional free flaps, circumventing their common limitations. However, such AV loop‐based flaps have never before been examined in standardized animal models with respect to their suitability for reconstruction of critical bone‐exposing defects. In the course of our preliminary studies, we implemented a novel defect model in rats that provides standardized and critical wound conditions and evaluated whether AV loop‐generated flaps are suitable for free microsurgical transfer and closure of composite defects. We compared three groups of rodents with similar scapular defects: one received the AV flap, whereas controls were left to heal by secondary intention or with supplementary acellular matrix alone. To create the flaps, AV loops were placed into subcutaneous Teflon chambers filled with acellular matrix and transferred to the thigh region. Flap maturation was evaluated by histological analysis of angiogenesis and cell migration at days 14 and 28 after loop creation. Flap transfer to the scapular region and microsurgical anastomoses were performed after 14 days. Postoperative defect closure and perfusion were continually compared between groups. Within the AV flap chamber, the mean vessel number, cell count and the proportion of proliferating cells increased significantly over time. The novel defect model revealed that stable wound coverage with homogeneous vascular integration was achieved by AV loop‐vascularized soft‐tissue free flaps compared with controls. In summary, our study indicates for the first time that complex composite defects in rats can successfully be treated with AV loop‐based free flaps.
A randomized, double‐blind, placebo‐controlled trial to determine the efficacy and safety of lactoferrin with vitamin E and zinc as an oral therapy for mild to moderate acne vulgaris

Lactoferrin is an iron‐binding milk‐derived protein that has shown antibacterial and anti‐inflammatory effects in vitro and in vivo. The objective of this study was to determine the efficacy and safety of lactoferrin, combined with vitamin E and zinc, for mild to moderate acne vulgaris. In this randomized, double‐blind, placebo‐controlled trial, 168 subjects aged 13–40 years old were randomly assigned to take either a capsule formulation containing lactoferrin with vitamin E and zinc or placebo twice a day for 3 months. The primary outcome measure was a reduction in the number of acne lesions compared to placebo. A total of 164 subjects completed the study per protocol. The lactoferrin group (n = 82) showed a significant median percent reduction in total lesions as early as 2 weeks (14.5%, P = 0.0120), with the maximum reduction occurring at week 10 (28.5%, P < 0.0001) compared to placebo group (n = 82). Maximum reduction in comedones (32.5%, P < 0.0001) and inflammatory lesions (44%, P < 0.0001) was also seen at week 10 compared to placebo. Sebum scores were improved by week 12. No adverse events were observed during the trial. A twice daily regimen of lactoferrin with vitamin E and zinc significantly reduced acne lesions in people with mild to moderate acne vulgaris.
Biocontrol of Fusarium graminearum sensu stricto, Reduction of Deoxynivalenol Accumulation and Phytohormone Induction by Two Selected Antagonists

Fusarium head blight (FHB) is a devastating disease that causes extensive yield and quality losses to wheat and other small cereal grains worldwide. Species within the Fusarium graminearum complex are the main pathogens associated with the disease, F. graminearum sensu stricto being the main pathogen in Argentina. Biocontrol can be used as part of an integrated pest management strategy. Phytohormones play a key role in the plant defense system and their production can be induced by antagonistic microorganisms. The aims of this study were to evaluate the effect of the inoculation of Bacillus velezensis RC 218, F. graminearum and their co-inoculation on the production of salicylic acid (SA) and jasmonic acid (JA) in wheat spikes at different periods of time under greenhouse conditions, and to evaluate the effect of B. velezensis RC 218 and Streptomyces albidoflavus RC 87B on FHB disease incidence, severity and deoxynivalenol accumulation on Triticum turgidum L. var. durum under field conditions. Under greenhouse conditions the production of JA was induced after F. graminearum inoculation at 48 and 72 h, but JA levels were reduced in the co-inoculated treatments. No differences in JA or SA levels were observed between the B. velezensis treatment and the water control. In the spikes inoculated with F. graminearum, SA production was induced early (12 h), as it was shown for initial FHB basal resistance, while JA was induced at a later stage (48 h), revealing different defense strategies at different stages of infection by the hemibiotrophic pathogen F. graminearum. Both B. velezensis RC 218 and S. albidoflavus RC 87B effectively reduced FHB incidence (up to 30%), severity (up to 25%) and deoxynivalenol accumulation (up to 51%) on durum wheat under field conditions.
School Victimization, Immigration, Dropping Out, and Gender Disparities

The children of immigrants face a number of educational hurdles, such as disparate rates of victimization and increased risk of dropping out of high school. Few studies have explored how school victimization can explain the relationship between immigrant generation status and the likelihood of dropping out. The current study explores if, and how, the associations between school victimization, feeling unsafe at school, and dropping out vary across immigration generations andgender. Data are drawn from the Educational Longitudinal Study of 2002. The sample for this study consists of 9,870 first (N = 1,170, 12%), second (N = 1,540, 16%), and third-plus (N = 7,160, 73%) generation, female (N = 5,050; 51%), and male (4,820; 49%) students in 580 public schools. Results indicate partial support for segmented assimilation and highlight important nuances related to immigrant generation status.in relation to key variables. For both males and females, generational status, victimization, and feeling unsafe at school significantly influence the likelihood (positively and negatively) of dropping out. In regard to school victimization, first generation females are less likely to drop out than third-plus generation females. For males, victimization at school generally decreases their likelihood of dropping out, except for second generation males who have an increased likelihood of dropping out. Females who feel unsafe are generally more likely to drop out, with no significant differences across generations. For males, feeling unsafe at school generally increases the likelihood of dropping out, except for second generation males who have a decreased likelihood of dropping out.
Early Experience with a Short, Tapered Titanium Porous Plasma Sprayed Stem with Updated Design.

INTRODUCTION Short stem femoral components in primary total hip arthroplasty (THA) have increased in popularity since the advent of minimally invasive surgical techniques. The concept of a short stem is particularly compatible with tapered designs where the goal is to offload forces proximally in the femur. The purpose of this retrospective review was to review our early experience with a short, tapered titanium femoral component with updated design features. MATERIALS AND METHODS Beginning in November 2011 through February 2012, 92 consented patients (93 hips), at a single center, were treated with primary cementless THA using a short stem, tapered femoral component (Taperloc® Complete Microplasty; Zimmer Biomet, Warsaw, Indiana) and were available for review with a minimum two-year follow-up. Mean patient age at surgery was 63.2 years and body mass index (BMI) was 30.8 kg/m2. Mean stem length used was 110.3mm (range, 95-125). RESULTS Mean follow-up was 4.5 years (2-6). Harris hip scores improved from 52.5 preoperatively to 84.7 at most recent. One stem was revised the same day for periprosthetic fracture. One patient with early infection was treated with single-stage exchange followed by recurrence that was treated successfully with two-stage exchange. A non-healing wound in one patient was treated with incision and debridement. Radiographic assessment demonstrated no evidence of loosening, osteolysis, distal hypertrophy, or pedestal formation in any hip, and all components appeared well fixed and in appropriate alignment. CONCLUSION In this series of patients treated with primary THA using a short, tapered titanium porous plasma-sprayed femoral component with updated design features, good results were achieved with a low incidence of complications and revision. No aseptic loosening or osteolysis has occurred. Radiographic assessment was excellent for all patients.
Potent Phototoxicity of Marine Bunker Oil to Translucent Herring Embryos after Prolonged Weathering

Pacific herring embryos (Clupea pallasi) spawned three months following the Cosco Busan bunker oil spill in San Francisco Bay showed high rates of late embryonic mortality in the intertidal zone at oiled sites. Dead embryos developed to the hatching stage (e.g. fully pigmented eyes) before suffering extensive tissue deterioration. In contrast, embryos incubated subtidally at oiled sites showed evidence of sublethal oil exposure (petroleum-induced cardiac toxicity) with very low rates of mortality. These field findings suggested an enhancement of oil toxicity through an interaction between oil and another environmental stressor in the intertidal zone, such as higher levels of sunlight-derived ultraviolet (UV) radiation. We tested this hypothesis by exposing herring embryos to both trace levels of weathered Cosco Busan bunker oil and sunlight, with and without protection from UV radiation. Cosco Busan oil and UV co-exposure were both necessary and sufficient to induce an acutely lethal necrotic syndrome in hatching stage embryos that closely mimicked the condition of dead embryos sampled from oiled sites. Tissue levels of known phototoxic polycyclic aromatic compounds were too low to explain the observed degree of phototoxicity, indicating the presence of other unidentified or unmeasured phototoxic compounds derived from bunker oil. These findings provide a parsimonious explanation for the unexpectedly high losses of intertidal herring spawn following the Cosco Busan spill. The chemical composition and associated toxicity of bunker oils should be more thoroughly evaluated to better understand and anticipate the ecological impacts of vessel-derived spills associated with an expanding global transportation network.
Anticipated Tax Reforms and Temporary Tax Cuts: A General Equilibrium Analysis

Macroeconomic studies of tax policy in dynamic general equilibrium usually assume that reforms hit the economy unexpectedly and last forever. Here, we explore how previous results change when we allow policy changes to be pre-announced and of finite duration and when these facts are anticipated by households and firms. Quantitatively we demonstrate a headstart advantage from pre-announcement that is never caught up by a surprising reform. The welfare gain stemming from a 5-year announcement phase of a corporate tax cut, for example, is estimated to be around 10 percent of the total gain from the reform. We show that impulse responses of important variables like firm value, dividends, and investment differ qualitatively depending on whether the reform comes expected or not. We are also able to demonstrate a genuine welfare gain from temporary tax cuts. Impulse responses generated by our numerical method can be retraced by phase diagram analysis, which facilitates explanation and interpretation of the produced results.
A model of reward-modulated motor learning with parallelcortical and basal ganglia pathways

Many recent studies of the motor system are divided into two distinct approaches: Those that investigate how motor responses are encoded in cortical neurons' firing rate dynamics and those that study the learning rules by which mammals and songbirds develop reliable motor responses. Computationally, the first approach is encapsulated by reservoir computing models, which can learn intricate motor tasks and produce internal dynamics strikingly similar to those of motor cortical neurons, but rely on biologically unrealistic learning rules. The more realistic learning rules developed by the second approach are often derived for simplified, discrete tasks in contrast to the intricate dynamics that characterize real motor responses. We bridge these two approaches to develop a biologically realistic learning rule for reservoir computing. Our algorithm learns simulated motor tasks on which previous reservoir computing algorithms fail, and reproduces experimental findings including those that relate motor learning to Parkinson's disease and its treatment.
British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding

Laura Green, Paula Bolton-Maggs, Craig Beattie, Rebecca Cardigan, Yiannis Kallis, Simon J Stanworth, Jecko Thachil and Sharon Zahra NHS Blood and Transplant, Barts Health NHS Trust, Blizard Institute, Queen Mary University of London, London, Serious Hazards of Transfusion Office, Manchester Blood Centre, Manchester, Dept of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, NHS Blood and Transplant/Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, Department of Hepatology, Barts Health NHS Trust, London, Oxford University Hospitals NHS Trust/NHS Blood and Transplant, University of Oxford, Oxford, Haematology Department, Manchester Royal Infirmary, Manchester, and Scottish National Blood Transfusion Service, Edinburgh, UK