The miR-15/16 family targets a large network of genes in T cells to restrict their cell cycle, memory formation, and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid ...expansion of differentiated effector T cells to mediate a sustained response. Here, we used conditional deletion of miR-15/16 in regulatory T cells (Tregs) to identify immune functions of the miR-15/16 family in T cells. miR-15/16 are indispensable to maintain peripheral tolerance by securing efficient suppression by a limited number of Tregs. miR-15/16 deficiency alters expression of critical Treg proteins and results in accumulation of functionally impaired FOXP3loCD25loCD127hi Tregs. Excessive proliferation in the absence of miR-15/16 shifts Treg fate and produces an effector Treg phenotype. These Tregs fail to control immune activation, leading to spontaneous multi-organ inflammation and increased allergic inflammation in a mouse model of asthma. Together, our results demonstrate that miR-15/16 expression in Tregs is essential to maintain immune tolerance.
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•Treg-specific miR-15/16 expression is essential to prevent systemic tissue inflammation•miR-15/16 restrict Treg proliferation and regulate expression of key functional molecules•miR-15/16 limit formation of effector Tregs and are necessary for high suppressive capacity
Tregs are essential suppressors of autoimmunity and allergy. Johansson et al. demonstrate that the miR-15/16 family of microRNAs control core Treg function by limiting their proliferation and expression of the key functional molecules FOXP3, IL-2Rα, CTLA4, PD-1, and IL-7Rα.
► Two new corrugated duplex grades have been studied as cheaper alternatives to 304. ► 2304 is more corrosion-resistant than the austenitic 304, but less than duplex 2205. ► 2001 has similar ...corrosion performance than the much more expensive 304. ► In 2304, ferrite preferentially corrodes in all studied aggressive pore solutions. ► In 2001 duplex, austenite shows lower corrosion resistance than ferrite.
This work studies the corrosion behaviour of two corrugated lean duplex stainless steels (SAF 2001 and 2304 grades) in eight alkaline solutions (carbonated and non-carbonated, saturated Ca(OH)
2 solutions with different chloride contents). 2001 stainless steel is a new grade in market because of its composition. 2304 is a grade previously studied under different conditions. However, its use as reinforcement in concrete is new. Studies are carried out by polarization curves following scanning electronic microscopy (SEM) and optical observations. Results are compared to those of carbon steel and austenitic AISI 304 and duplex SAF 2205 under similar conditions. After corrosion tests in alkaline media with chloride, ferrite tends to corrode selectively in 2304 duplex, while austenite corrodes selectively in 2001 under the same conditions. The influence of the duplex microstructure on attack development and morphology is analyzed. The electrochemical parameters obtained from the polarization curves suggest 2001 could replace 304 keeping the structure its corrosion performance (and with clear economical advantages). 2304 shows better corrosion behaviour than the more expensive 304, but somewhat lower than the excellent behaviour shown by 2205.
Over 60 years ago, stone tools and remains of megafauna were discovered on the Southeast Asian islands of Flores, Sulawesi and Luzon, and a Middle Pleistocene colonization by Homo erectus was ...initially proposed to have occurred on these islands
. However, until the discovery of Homo floresiensis in 2003, claims of the presence of archaic hominins on Wallacean islands were hypothetical owing to the absence of in situ fossils and/or stone artefacts that were excavated from well-documented stratigraphic contexts, or because secure numerical dating methods of these sites were lacking. As a consequence, these claims were generally treated with scepticism
. Here we describe the results of recent excavations at Kalinga in the Cagayan Valley of northern Luzon in the Philippines that have yielded 57 stone tools associated with an almost-complete disarticulated skeleton of Rhinoceros philippinensis, which shows clear signs of butchery, together with other fossil fauna remains attributed to stegodon, Philippine brown deer, freshwater turtle and monitor lizard. All finds originate from a clay-rich bone bed that was dated to between 777 and 631 thousand years ago using electron-spin resonance methods that were applied to tooth enamel and fluvial quartz. This evidence pushes back the proven period of colonization
of the Philippines by hundreds of thousands of years, and furthermore suggests that early overseas dispersal in Island South East Asia by premodern hominins took place several times during the Early and Middle Pleistocene stages
. The Philippines therefore may have had a central role in southward movements into Wallacea, not only of Pleistocene megafauna
, but also of archaic hominins.
Medical managements are becoming personalized while diseases are being understood at the molecular level. Nuclear medicine is one of the fields actively contributing to this development. In ...particular, theranostics, a combinatorial term for therapy and diagnostics, enables accurate imaging and subsequent targeted radionuclide treatment. Due to its high impact in healthcare, many countries have begun to offer Ga-68 PET/CT scans and Lu-177 therapies. The Philippines has followed suit through the initiative of this author and able support of the administration and staff of St. Luke’s Medical Center. The Ga-68 DOTATATE and PSMA PET/CT scans became officially available in January 2018 while the first peptide receptor radionuclide therapy for neuroendocrine tumor and first PSMA radioligand therapy for prostate cancer occurred in May and June 2018, respectively. Amidst past, present, and future challenges, theranostics has emerged in the Philippines, offering hope to cancer patients in the country.
A new class of conformal invariants for a given spacetime M is introduced exploiting the conformal geometry of any light ray
Γ
. Each congruence of light rays passing through a given point p defines ...the sky S(p) of such point. The new conformal invariants are defined on the bundle of skies of the spacetime M, being called sky invariants accordingly. The natural conformal covariant derivative defined on a light ray and its associated covariant calculus allows us to show the existence of a natural conformal invariant differential of arc that, together with the restriction of the curvature of the conformal covariant derivative, can be used to construct a sky invariant that will be called the sky curvature. An algorithm, that can be implemented on any symbolic manipulation software system, to compute the sky curvature will be discussed and the main ideas and the explicit computation of the sky curvature are illustrated in Schwarzschild spacetime.
The cathodic delamination and wear resistance of epoxy powder coatings were evaluated after adding 3 % (by wt.) of calcium ion exchanged micropigments from amorphous synthetic silica. The materials ...were manufactured through the innovative and economical hot mixing method, and three different coatings were considered: commercial epoxy, epoxy without micropigments submitted to the hot mixing treatment, and epoxy with micropigments. The curing kinetics of the powder coatings was studied in order to evaluate the possible effects of the micropigments on the epoxy, using differential scanning calorimetry (DSC). In addition, mechanical properties of coatings (hardness and scratch resistance) and their wear resistance (reciprocal tribometer tests) were assessed. After provoking a controlled mechanical failure in the coatings, their delamination resistance was analyzed by scanning Kelvin probe (SKP). The delamination front was calculated after adding a drop of 3.5 % NaCl solution and taking measurements for 26 days. The results show that the corrosion attack progresses through a cathodic delamination mechanism. The addition of corrosion inhibitors in epoxy powder coatings has not only allowed a considerable improvement in delamination resistance, but has also led to greater mechanical and wear resistance. At the same time, it has simultaneously reduced the chances for mechanical failure of the coating and decreased the progression rate of damage, if it occurs. The study has also been completed with electrochemical impedance spectroscopy and polarization measured of fully-immersed defective coatings in 3.5 % NaCl.
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•Calcium ion exchanged micropigments from silica are hot-mixed to epoxy powders.•The cathodic delamination is studied with SKP for organic coated carbon steel.•3 % micropigments in the coating delay the progress of delamination damage from a defect.•Microparticles addition also improve mechanical and wear properties.
The study investigates the influence of Advertising Creativity (AC) on Ad effectiveness in the context of Interactive Digital Media (IDM). The inquiry seeks to bridge a somewhat limited regard for AC ...in the context of IDM and provide insight into AC's place in audience communication processes as opposed to generally outcome-based perspectives. The study extends the process of AC effects towards the stages of the Hierarchy of Effects (HOE) by the inclusion of conditional media effects and media response states, which are major components of the Differential Susceptibility to Media Effects Model (DSMM), to elucidate dynamic audience processes especially in the context of interactive media. This study was limited to Filipino Millennials (born between 1980 and 1994) residing in the National Capital Region (NCR), Philippines. Data was collected from 326 respondents through a questionnaire survey, with PLS-SEM utilized for the analysis. The results show that AC effects occur through engaging immediate responses as manifested by the media response states at the time of exposure to ad stimuli rather than moderating relationships between conditional and response media effects, positively influencing all HOE stages. However, the strengths of these effects vary, with stages related to experiential responses such as Awareness, Learning/Memory, and Brand Liking reflecting more practical implications compared to more rationally involved HOE stages of accepting or rejecting ad claims and brand intentions. By its very nature, advertising is designed to disrupt original motivations and activities. Furthermore, media response is immediate upon introducing AC stimuli despite conditional dispositions. These results provide potential practical use in campaign development and conceptualization related to consumer demographics, as customized ad outputs addressing different audience traits or motivations can equate to higher production costs. Awareness, memory, and brand liking are posited to benefit the most from AC, allowing for better allocation of resources when developing outputs throughout campaigns. The study provides a practical view of AC's benefits to specific HOE stages enabling advertisers to develop strategies given the value and limitations of AC within integrated marketing campaigns keeping us abreast with the dynamic consumer processing of ad communications constantly developing in line with emerging media technology.
With its multifaceted health benefits, ginger is one of the commonly consumed dietary condiments with continued demand worldwide leading to more importation into countries such as the U.S. The ...rhizome of ginger, the seed-piece but also the edible portion, is highly vulnerable to pathogen infections causing seed-piece and soil-borne diseases (SSDs). Laboratory and high tunnel (HT) studies were conducted between 2018 and 2020 to evaluate the effect of soil and transplant drenches of selected biocontrol agents (BCAs) and chemicals. In vitro dual-culture tests revealed that the Trichoderma harzianum strain T-22 (Th-22) grew significantly faster than Fusarium oxysporum f.sp. zingiberi (Foz), the fungus causing yellows and rhizome rot in ginger. Th-22 grew more than three times faster than Foz within 3 days and engulfed the pathogen within 7 days when incubated at 30 °C. The bioproducts (RootShield® Plus, LifeGard®), an insecticide/nematicide (Vydate®) and disinfectant (10% Clorox) tested against Foz and any pre-existing pathogens in a HT significantly reduced severity of yellowing and rhizome rot when compared with the non-treated control. Yield was significantly higher for RootShield® Plus compared to the control in one of the trials. Spatially, declining ginger growth but an increased incidence of SSDs were observed as one walked from the door towards the back of the HT. Phospho-lipid fatty acid analysis showed better microbial activity on soils that received drenches of BCAs than on soils sampled pre-treatment.
The stained colors of the tissue components are popularly used as features for image analysis. However, variations in the staining condition of the histology slides prompt variations to the color ...distribution of the stained tissue samples which could impact the accuracy of the analysis. In this paper, we present a method to correct the staining condition of a histology image. In the method, a look-up table (LUT) based on the dye amounts absorbed by the sample is built. The LUT can be built when either (i) the source and reference staining conditions are specified or (ii) when the user simply wants to recreate his/her preferred staining condition without specifying any reference slide. The effectiveness of the present method was evaluated in two aspects: (i) CIELAB color difference of nuclei, cytoplasm, and red blood cells, between the ten different slides of liver tissue, and (ii) classification of the different tissue components. Application of the present staining correction method reduced the color difference between the slides by an average factor of 9.8 and the classification performance of a linear discriminant classifier improved by 16.5 % on the average. Results of the paired
t
test statistical analysis further showed that the reduction in the CIELAB color difference between the slides and the improvement in the classifier’s performance when staining correction was implemented is significant at
p
< 0.001.