Miracle-dz/UniFAR-FTUs huggingface dataset:
GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility

Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors; however, its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of cofactors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1-binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3-mediated redistribution of ESR1 binding. The GATA3-mediated redistributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1-bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen–ESR1-mediated interactions between cis-regulatory elements. Together, these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility, and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer.
Laser-mediated photodynamic therapy of actinic keratoses.

OBJECTIVE To assess the safety and efficacy of the long-pulsed pulsed dye laser (LP PDL) (595 nm) with photodynamic therapy (PDT) for treatment of actinic keratoses (AKs). DESIGN Prospective, controlled study with 10-day and 2-, 4-,6-, and 8-month follow-ups. SETTING Clinical research center. PATIENTS Volunteer sample of 41 patients (age range, 35-91 years; skin types I-III) with AKs. INTERVENTION Single treatment with application of topical 20% 5-aminolevulinic acid for 3 hours or 14 to 18 hours, followed by LP PDL irradiation at 595 nm. Controls received LP PDL irradiation alone. MAIN OUTCOME MEASURES Safety assessments, treatment and recovery times, and efficacy assessments, including patient mean percentage of lesions cleared and distribution of patients by percentage of lesions cleared for different anatomic sites. RESULTS We observed no to slight pain; slight to moderate erythema; no purpura, crusting, or scarring; treatment time of 1 lesion per second; and resolution of erythema by 7 to 14 days. The patient mean (95% confidence interval) percentage of head lesions (2620 lesions) cleared after 1 treatment was 99.47% (99.44%-99.50%) at 10 days, 98.19% (98.15%-98.23%) at 2 months, 92.94% (92.73%-93.14%) at 4 months, 91.65% (91.15%-92.15%) at 6 months, and 90.32% (78.10%-100%) at 8 months. For extremities (949 lesions), these were 83.1% (81.4%-84.9%) at 10 days, 75.5% (73.4-77.6) at 2 months, 70.9% (68.9%-72.8%) at 4 months, 92.0% (84.0%-100%) at 6 months, and 100% at 8 months. For trunk (53 lesions), these were 85% (74%-100%) at 10 days, 85% (74%-100%), and 65% (50%-80%) at 4 months. No difference in safety or efficacy was found between the 3-hour and 14- to 18-hour incubation times. In the laser-only control group, no decrease in lesions was observed. Among 31 patients with head lesions, 28 (90%) at 10 days, 19 (70%) at 2 months, 9 (47%) at 4 months, 5 (42%) at 6 months, and 5 (56%) at 8 months were completely (100%) clear following a single treatment. Skin biopsy specimens of nonresponding lesions demonstrated a high rate of squamous cell carcinoma and other non-AK neoplasms. CONCLUSIONS Treatment of AKs using LP PDL (595 nm) at nonpurpuric parameters following topical application of 5-aminolevulinic acid is safe and effective. The advantages may include minimal discomfort, rapid incubation treatment and recovery times, excellent posttreatment cosmesis, high efficacy rates with respect to head lesions, and practical applicability to large body surface areas.
Physiological Strategies to Improve the Performance of Spring Maize (Zea mays L.) Planted under Early and Optimum Sowing Conditions

Low temperature at stand establishment and high temperature at reproductive stage are involved in reduction of grain yield of spring maize. A field study was therefore conducted to evaluate different physiological strategies for improving performance of spring maize under temperature extremes. Seed priming and foliar spray with 3% moringa leaf extract (MLE) and 100 mg L-1 kinetin solution alone or in all possible combinations with each other at three growth stages (knee height, tasseling and grain filling stage) and hydropriming was compared with control. Seed priming plus foliar spray of MLE and kinetin significantly improved stand establishment especially under early sown crop as indicated by reduced mean emergence time (MET), improved emergence index (EI) and final emergence percentage (FEP). Similarly increased chlorophyll contents, crop growth rate, leaf area index, photosynthetic rate, transpiration rate, relative water content and decreased membrane permeability were recorded in both early and optimum sowing conditions in MLE priming plus foliar spray treatment. All these improvements were harvested in the form of increased yield and harvest index compared with control treatment. Overall crop sown at optimum time performed best but exogenous application of MLE through seed priming and foliar spray maximally improved the performance of early sown maize crop which is attributed more likely due to improved stand establishment, chlorophyll and phenolic contents, increased leaf area duration and grain filling period. It can be concluded that seed priming with MLE along with its foliar spray could increase production of maize under temperature extremes.
Recognizing facial actions using Gabor wavelets with neutral face average difference

This work describes a new pre-processing step to classify facial expression. Previous works suggest that Gabor wavelets applied to recognize facial expression images subtracted from neutral face from the same subject could achieve good recognition rate under controlled condition as eye and month alignment. We propose a recognition system where the Gabor kernels are applied on facial expression subtracted from an averaged neutral face. A fast pre-processing technique that generates a small dimension output data is also proposed. A correct recognition rate of 86.6% is obtained in a 7 upper face actions and 81.6% in a 7 lower face actions detection problem using a neural network based classifier. The performance is evaluated in a heterogeneous subject database with head motion and lighting variations.
Continental break-up at the Galicia margin

The Galicia margin has been at the forefront the development and testing of models on the break-up of magma-poor passive margins. However the current paradigm of continental break-up is still largely based on two dimensional observations. The data presented here from a high resolution 3D seismic reflection data reveal in unprecedented detail the complexity of continental break-up. Using the 3D geometry of the faults, analysing fault displacement at a number of different levels, and mapping syn-rift sediments it has been possible to offer a new model of break-up. This model combines elements of previous models but offers a new degree of clarity over the mechanism including fault linkage. Slip initiates at different points on the a weakened serpentinised mantle forming a slip surface that propagates up through a network of faults forming the S reflector, a detachment fault whilst also dissecting the crust, allowing further water ingress and weakening. Progressive slip and weakening rotates slip surfaces, eventually new sites of slip initiation form that propagate through the crust forming a new fault network and ceasing slip on the previous network. Continued weakening and slip eventually leads to break-up.
Phosphorylation of the RNA polymerase II C-terminal domain by TFIIH kinase is not essential for transcription of Saccharomyces cerevisiae genome

Ser-5 phosphorylation of the RNA polymerase II (Pol II) C-terminal domain by TFIIH kinase has been implicated in critical steps in mRNA synthesis, such as Pol II promoter escape and mRNA 5′-capping. However, the general requirement and precise role of TFIIH kinase in Pol II transcription still remain elusive. Here we use a chemical genetics approach to show that, for a majority of budding-yeast genes, specific inhibition of the yeast TFIIH kinase results in a dramatic reduction in both mRNA level and Ser-5 C-terminal domain phosphorylation. Surprisingly, inhibition of TFIIH kinase activity only partially affected both Pol II density and Ser-2 phosphorylation level. The discrepancy between mRNA level and Pol II density is attributed to the defective 5′-capping, which results in the destabilization of mRNAs. Therefore, contrary to the current belief, our study points strongly toward a minor role of TFIIH kinase in Pol II transcription, and a more significant role in mRNA capping in budding yeast.
Proteomic analysis of formalin-fixed paraffin-embedded glomeruli suggests depletion of glomerular filtration barrier proteins in two-kidney, one-clip hypertensive rats

Background It is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood. Methods In the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to investigate changes in the glomerular proteome in the non-clipped kidney of two-kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later prepared on tissue slides for laser microdissection. Glomeruli without severe morphological damage were isolated, and the proteomes were analysed using liquid chromatography–tandem mass spectrometry. Results 2K1C glomeruli showed reduced abundance of proteins important for slit diaphragm complex, such as nephrin, podocin and neph1. The podocyte foot process had a pattern of reduced abundance of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal proteins synaptopodin and α-actinin-4. Lower abundance of important glomerular basement membrane proteins was seen. Possible glomerular markers of damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme A thioesterase 1. Conclusions Microdissection and tandem mass spectrometry could be used to investigate the proteome of isolated glomeruli from FFPE tissue. Glomerular filtration barrier proteins had reduced abundance in the non-clipped kidney of 2K1C hypertensive rats.
Age, sex, and season affect the risk of mycoplasmal conjunctivitis in a southeastern house finch population

House finches (Carpodacus mexicanus(Muller, 1776)) in eastern North America have been affected by an- nual epidemics of an eye disease caused by the bacterium Mycoplasma gallisepticumsince 1994. To identify factors as- sociated with seasonal changes in prevalence and variation in host susceptibility, we monitored mycoplasmal conjunctivitis among wild house finches in a region of high prevalence in southeastern North America. We captured 888 birds between August 2001 and December 2003 and observed seasonal outbreaks characterized by rapid increases in prevalence from August to October each year. During periods of high prevalence, infection probability was signifi - cantly higher among juveniles than adults, and the severity of conjunctivitis among juvenile females was greater than for any other host category. We found no evidence linking moulting status to elevated infection risk among adult birds. Finally, house finches with conjunctivitis were in poorer condition than birds with no clinical signs of infection, partic - ularly among those with severe infections. Results from this study are consistent with recent reports of seasonal and re - gional variation in mycoplasmal conjunctivitis and suggest that annual changes in host reproduction, behaviour, and age structure might be important determinants of the timing and magnitude of local epidemics. Resume : Depuis 1994, les roselins familiers (Carpodacus mexicanus(Muller, 1776)) de l'est de l'Amerique du Nord
Distribution and innervation of lateral line organs in the axolotl

The lateral line system in axolotls consists of three types of receptors and the cranial nerves that innervate them. Superficial neuromasts, which are mechanoreceptors, are distributed in lines on both the head and trunk. Eight cephalic and three trunk lines can be distinguished on the basis of their innervation and differences in the orientation of the major axes of their neuromasts. A combination of histological techniques reveals that five separate pairs of cranial nerves innervate the neuromasts: anterodorsal lateral line nerves innervate cephalic supraorbital and infraorbital lines; anteroventral lateral line nerves innervate cephalic angular, oral, jugal, and preoperculomandibular lines of the cheek and lower jaw; middle and supratemporal lateral line nerves innervate the cephalic postotic lines; and posterior lateral line nerves innervate the trunk lines.
Physiology and Pharmacology of Temperature Regulation Defending body mass during food restriction in Acomys russatus : a desert rodent that does not store food

Gutman, Roee, Itzhak Choshniak, and Noga Kronfeld-Schor. Defending body mass during food restriction in Acomys russatus: a desert rodent that does not store food. Am J Physiol Regul Integr Comp Physiol 290: R881–R891, 2006. First published November 10, 2005; doi:10.1152/ajpregu.00156. 2005. —Golden spiny mice, which inhabit rocky deserts and do not store food, must therefore employ physiological means to cope with periods of food shortage. Here we studied the physiological means used by golden spiny mice for conserving energy during food restriction and refeeding and the mechanism by which food consumption may influence thermoregulatory mechanisms and metabolic rate. As comparison, we studied the response to food restriction of another rocky desert rodent, Wagner’s gerbil, which accumulates large seed caches. Ten out of 12 foodrestricted spiny mice (resistant) were able to defend their body mass after an initial decrease, as opposed to Wagner’s gerbils (n 6). Two of the spiny mice (nonresistant) kept losing weight, and their food restriction was halted. In four resistant and two nonresistant spiny mice, we measured heart rate, body temperature, and oxygen consumption during food restriction. The resistant spiny mice significantly (P 0.05) reduced energy expenditure and entered daily torpor. The nonresistant spiny mice did not reduce their energy expenditure. The gerbils’ response to food restriction was similar to that of the nonresistant spiny mice. Resistant spiny mice leptin levels dropped significantly (n 6, P 0.05) after 24 h of food restriction, and continued to decrease throughout food restriction, as did body fat. During refeeding, although the golden spiny mice gained fat, leptin levels were not correlated with body mass (r 0.014). It is possible that this low correlation allows them to continue eating and accumulate fat when food is plentiful.
A randomised clinical trial comparing the flexible fibrescope and the Pentax Airway Scope (AWS)® for awake oral tracheal intubation

We compared awake fibreoptic intubation with awake intubation using the Pentax Airway Scope® in 40 adult patients. Sedation was achieved using a target‐controlled remifentanil infusion of 1–5 ng.ml−1 and midazolam. The airway was anaesthetised with lidocaine spray and gargle. The total procedure time – a composite of sedation time, topical anaesthesia time and intubation time – was recorded. The operator's impression of the ease of the procedure and the patients' reported comfort were recorded on a 0–100 mm visual analogue scale. The median (IQR [range]) for total procedure time was 900 (739–1059 [616–1215]) s with the fibrescope and 651 (601–720 [498–900]) s with the Pentax Airway Scope (p = 0.0001). The median (IQR [range]) intubation time was 420 (283–480 [120–608]) s with the fibrescope and 183 (144–220 [107–420]) s with the Pentax Airway Scope (p = 0.0002). The median (IQR [range]) visual analogue scores for the operator's ease of intubation for the fibrescope and Pentax Airway Scope were 83.6 (72.0–98.0 [49.0–100.0]) and 86.8 (84.0–91.0 [61.0–100.0]), respectively (p = 0.3507). The median (IQR [range]) visual analogue score for patient comfort was 85.5 (81.0–97.0 [69.0–100.0]) and 79.4 (74.0–85.0 [59.0–100.0]) for the fibrescope and Pentax Airway Scope, respectively (p = 0.06). Total procedure time was significantly shorter with the Pentax Airway Scope compared with the fibrescope, with no difference in procedure difficulty or patient discomfort.
Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Isatis indigotica based on Ultra-Performance Liquid Chromatography with Photodiode Array Detector Combined with Chemometric Methods

A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.
Understanding the mechanism of action of bacterial superantigens from a decade of research

Summary: In the face of the unique diversity and plasticity of the immune system pathogenic organisms have developed multiple mechanisms in adaptation to their hosts, including the expression of a particular class of molecules called superantigens. Bacterial superantigens are the most potent stimulators of T cells. The functional consequences of the expression of superantigens by bacteria can be extended not only to T lymphocytes, but also to B lymphocytes and to cells of the myeloid compartment, including antigen‐presenting cells and phagocytes. The biological effects of bacterial superantigens as well as their molecular aspects have now been studied for a decade. Although there is still a long way to go to clearly understand the role these molecules play in the establishment of disease, recently acquired knowledge of their biochemistry now offers unique experimental opportunities in defining the molecular rules of T‐cell activation. Here, we present some of the most recent functional and molecular aspects of the interaction of bacterial superantigens with MHC class II molecules and the T‐cell receptor.
Risk-Based Prioritization among Air Pollution Control Strategies in the Yangtze River Delta, China

Background The Yangtze River Delta (YRD) in China is a densely populated region with recent dramatic increases in energy consumption and atmospheric emissions. Objectives We studied how different emission sectors influence population exposures and the corresponding health risks, to inform air pollution control strategy design. Methods We applied the Community Multiscale Air Quality (CMAQ) Modeling System to model the marginal contribution to baseline concentrations from different sectors. We focused on nitrogen oxide (NOx) control while considering other pollutants that affect fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] and ozone concentrations. We developed concentration–response (C-R) functions for PM2.5 and ozone mortality for China to evaluate the anticipated health benefits. Results In the YRD, health benefits per ton of emission reductions varied significantly across pollutants, with reductions of primary PM2.5 from the industry sector and mobile sources showing the greatest benefits of 0.1 fewer deaths per year per ton of emission reduction. Combining estimates of health benefits per ton with potential emission reductions, the greatest mortality reduction of 12,000 fewer deaths per year [95% confidence interval (CI), 1,200–24,000] was associated with controlling primary PM2.5 emissions from the industry sector and reducing sulfur dioxide (SO2) from the power sector, respectively. Benefits were lower for reducing NOx emissions given lower consequent reductions in the formation of secondary PM2.5 (compared with SO2) and increases in ozone concentrations that would result in the YRD. Conclusions Although uncertainties related to C-R functions are significant, the estimated health benefits of emission reductions in the YRD are substantial, especially for sectors and pollutants with both higher health benefits per unit emission reductions and large potential for emission reductions.
Fast Adaptive Penalized Splines

This article proposes a numerically simple method for locally adaptive smoothing. The heterogeneous regression function is modeled as a penalized spline with a varying smoothing parameter modeled as another penalized spline. This is formulated as a hierarchical mixed model, with spline coefficients following zero mean normal distribution with a smooth variance structure. The major contribution of this article is to use the Laplace approximation of the marginal likelihood for estimation. This method is numerically simple and fast. The idea is extended to spatial and non-normal response smoothing.
Analysis and Comparison in the Energy-Delay-Area Domain of Nanometer CMOS Flip-Flops: Part II—Results and Figures of Merit

In Part II of this paper, a comparison of the most representative flip-flop (FF) classes and topologies in a 65-nm CMOS technology is carried out. The comparison, which is performed on the energy-delay-area domain, exploits the strategies and methodologies for FFs analysis and design reported in Part I. In particular, the analysis accounts for the impact of leakage and layout parasitics on the optimization of the circuits. The tradeoffs between leakage, area, clock load, delay, and other interesting properties are extensively discussed. The investigation permits to derive several considerations on each FF class and to identify the best topologies for a targeted application.
Pricing and Hedging Guaranteed Annuity Options Via Static Option Replication

In this paper we derive a market value for Guaranteed Annuity Option using martingale modeling techniques. Furthermore, we show how to construct a static replicating portfolio of vanilla interest rate swaptions that replicates the Guaranteed Annuity Option. Finally, we illustrate with historical UK interest rate data from the period 1980 until 2000 that the static replicating portfolio is extremely effective as a hedge against the interest rate risk involved in the GAO, that the static replicating portfolio is considerably cheaper than up-front reserving and also that the replicating portfolio provides a much better level of protection than an up-front reserve.