Miracle-dz/UniFAR-FTUs huggingface dataset:
The adaptive potential of early life-stage Fucus vesiculosus under multifactorial environmental change

Multiple global and local stressors threaten populations of the bladderwrack Fucus vesiculosus (Phaeophyceae). Baltic F. vesiculosus populations presumably have a lower genetic diversity compared to other populations. I investigated the adaptive potential under multifactorial environmental change in F. vesiculosus germlings. Effects of warming and acidification were crossed during one year at the two levels “present” and “future” (according to the year 2110) at the “Kiel Outdoor Benthocosms” by applying delta-treatments. Effects of warming varied with season while acidification showed generally weak effects. The two factors “ocean acidification and warming” (OAW) and nutrients were crossed showing that nutrient enrichment mitigated heat stress. Germlings previously treated under the OAW x nutrient experiment were subsequently exposed to a simulated hypoxic upwelling. Sensitivity to hypoxia was enhanced by the previous OAW conditions. Difference in the performance of genetically different sibling groups and diversity level were observed indicating an increased adaptive potential at higher genetic diversity. Different sibling groups were analysed under multiple factors to test correlations of genotypic sensitivities. Sensitivity towards warming, acidification and nutrient enrichment correlated positively while sensitivities towards OAW and hypoxia showed a negative correlation demonstrating that genotypes previously selected under OAW are sensitive to hypoxic upwelling. In a literature review, responses of marine organisms to climate change were analysed through different levels of biological organisation showing that climate change has different effects on each single level of biological organisation. This study highlights that global change research requires an upscaling approach with regard to multiple factors, seasons, natural fluctuations, different developmental stages and levels of biological organisation in the light of the adaptive potential.
Effects of Unprocessed Versus Vinegar-Processed Schisandra chinensison the Activity of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 andCYP2D6 Enzymes in Rats

Schisandra chinensis (SC) is a well-known traditional Chinese herbal medicine that has been used in clinical practices for thousands of years. However, the differences between the effects of unprocessed and vinegarprocessed Schisandra chinensis (VSC) on cytochrome P450 (CYP450) activities are poorly understood. To evaluate the differences between processed and unprocessed SC on the metabolism of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2D6 substrates in rats using a cocktail method based on a developed and validated high performance liquid chromatography-mass spectrometry (HPLC-MS) method. Six probe substrates (coumarin (CYP2A6), bupropion (CYP2B6), paclitaxel (CYP2C8), tolbutamide (CY2C9), omeprazole (CYP2C19) and metoprolol (CYP2D6)) were delivered simultaneously into rats treated with single or multiple doses of processed or crude SC extract. The plasma concentrations of the six probes were profiled by HPLC-MS, and their corresponding pharmacokinetic parameters were calculated. Treatment with single or multiple doses of either extract of SC or VSC induced CYP2A6, CYP2B6 and CYP2C9 enzyme activity and inhibited CYP2D6, CYP2C19 and CYP2C8 enzyme activity in rats. Furthermore, the inhibitory or induced effect of multiple doses of SC was more potent after vinegar processing than without vinegar processing. CYP2A6, 2B6 and 2C9 enzyme activity were induced significantly after treatment with multiple doses but not after a single dose. CYP2C19 enzyme activity were inhibited significantly after treatment with multiple doses but not after a single dose. These results provide useful scientific data for the safe clinical application of either extract of SC in combination with other drugs, which should lack the side effects induced by other herb-drug interactions.
Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

ABSTRACT Although DNA vaccines have shown a good antitumor effect in animal models, they are often not effective in clinical trials. This requires researchers to find an effective way to significantly improve the immunogenicity of vaccines. Here, we developed a new DNA vaccine based on MAGE-A3, which has been suggested as a potential target for lung cancer therapy. We enhanced the potency of this DNA vaccine by overcoming tumour-induced immunosuppressive environment through blockade of the PD-1/PD-L pathway using a soluble PD-1 (sPD1). A series of DNA plasmids encoding MAGE-A3, the extracellular domain of murine PD-1 (sPD1) and their conjugates were constructed and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were evaluated by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the therapeutic efficacy of the plasmids, a mouse model with a MAGE-A3-expressing tumour was designed. Mice vaccinated with the fusion expression plasmid generated the strongest MAGE-A3-specific immune responses. Furthermore, these vaccinations inhibited the growth of MAGE-A3-expressing tumours and prolonged mouse survival. These findings suggest that the combination of DNA vaccines with PD-1 pathway inhibitors may be a promising approach in clinical trials. This approach may be viable for vaccines targeting cancer, as anti-tumour vaccines have demonstrated clinical benefit but PD-1 pathway inhibitors alone have demonstrated poor efficacy so far.
The Application of Electric Fields in Biology and Medicine

We discuss a wide range of applications of electric fields in biology and medicine. For example, physiological strength (<500 V/m) fields are used to improve the healing of wounds, the stimulation of neurons, and the positioning and activation of cells on scaf - folds for tissue engineering purposes. The brief, strong pulses used in electroporation are used to improve the insertion of drugs into tumors and DNA into cell nuclei. The refer - ences direct readers to detailed reviews of these applications. The mechanism by which cells detect physiological strength fields is not well understood. We also describe a field- transduction mechanism that shares features common to the detection of fluid shear by cells. We then provide some experimental evidence that supports our model.
Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues

Clinical features of idiosyncratic drug induced liver injury (DILI) are well described in cases that have been assessed for causality using the Roussel Uclaf Causality Assessment Method (RUCAM), but our understanding of the mechanistic steps leading to injury is fragmentary. The difficulties describing mechanistic events can be traced back to the lack of an animal model of experimental idiosyncratic DILI that can mimic the genetic requirements of human idiosyncratic DILI. However, immune tolerance plays a dominant role in the immune response of the liver, and impairment of immune tolerance with immune checkpoint inhibitors increases DILI in both humans and animals. This may provide one method to study the individual steps involved. In general. the human DILI liver is a secret keeper providing little insight into what occurs in the diseased organ. Sufficient evidence exists that most idiosyncratic cases are mediated by the adaptive immune system, which depends on stimulation of the innate immune system, but the triggering factors are unknown. It is attractive to hypothesize that the gut microbiome plays a role; however, it is very difficult to study. Similarly, exosomes are likely to play an important role in communication between hepatic cells and the immune system, but there is a lack of data on blood exosomes in affected patients. Reactive metabolites are likely to play an important role. This is supported by the current analysis, which revealed an association between metabolism by cytochrome P450 and drugs most commonly involved in causing idiosyncratic DILI with causality verified by RUCAM. Circumstantial evidence suggests that reactive oxygen species (ROS) generated by cytochrome P450 could be responsible for the initial steps of injury, but details are unknown. In conclusion, most of the mechanistic steps leading to idiosyncratic DILI remain unclear.
Communicative Pathways Predicting Adherence in Type II Diabetic Patients: A Mediation Analysis

ABSTRACT Type II diabetes is a chronic health condition and its successful management requires effective patient-provider communication. Responding to a call to model pathways between provider communication and patient health outcomes, this study tested four models of type II diabetic patient adherence with four mediators. Given the complex nature of type II diabetic care, patient adherence was conceptualized as wellness, screening, medication, and treatment adherence. Mediators included patient understanding, agreement, trust, and motivation. A sample of U.S. patients with type II diabetes patients who were both under the care of a medical provider and taking medication for their type II diabetes completed online surveys (n = 793). Findings indicated that the relationships between patient-centered communication and adherence outcomes were mediated by proximal outcomes. The results contribute to the understanding of patient-centered communication, adherence behaviors, and proximal outcomes of patient understanding, agreement, trust, and motivation. Findings indicate that relationships between patient-centered communication and wellness adherence is mediated by patient motivation, patient-centered communication and screening adherence is mediated by patient agreement, trust, and motivation, and patient-centered communication and treatment adherence is mediated by patient agreement, trust, and motivation. The discussion addresses theoretical and practical implications and directions for future research.
An Electromagnetic–Thermal Coupling Numerical Study of the Synchronous Generator with Second-Generation High-Temperature Superconducting Armatures

Generators with high-temperature superconducting armatures have an advantage in the fact that they can carry high currents. However, the AC loss of high-temperature superconducting (HTS) armatures is difficult to calculate precisely because HTS coils exist in a complex and time-varying electromagnetic environment. In addition, when the HTS coil is carrying a short circuit fault overcurrent, an electromagnetic–thermal simulation study of this process is required to ensure that the HTS coil is not damaged. In this paper, first, a fully coupled T-A formulation model is used to calculate the AC loss of HTS armatures. Then, the current and temperature distributions are simulated, considering the intrinsic characteristic of superconducting coated conductors, when the generator suffers the worst short circuit fault accidently. It is found that the turn with the lowest critical current quenches after 0.01 s, but the temperature rise cannot damage the coil if the circuit breaker can clear the fault quickly. The effects of the copper stabilizer thickness on the thermal stability of the HTS coil during the worst short circuit fault are also investigated. A thicker copper stabilizer improves the thermal stability of the HTS coil in the event of a short circuit fault, but the use of a simulation model is needed to make trade-offs between the engineering current density and the thermal stability of the HTS tapes. The work in this paper is necessary and can provide an important reference for manufacturing superconducting generators.
The Educational Implications of Populism, Emotions and Digital Hate Speech: A Dialogue with Scholars from Canada, Chile, Spain, the UK, and the US

The recent rise of authoritarian populism, fueled by the spread of digital hate speech and the preeminence of emotions in the political arena, has not aroused much interest among educational researchers. In response to this gap in the literature, the authors of the present article aim to provide an overview of the educational implications of the recent wave of authoritarian populism by interviewing a group of experts on democratic citizenship education from various countries and backgrounds. The dialogue resulting from their responses helps to move forward the educational debate on how schools can deal with the emotions and hate speech that motivate support for authoritarian populisms.
Do the school adaptation levels of preschoolers vary according to their relationship with their teachers?

In this study, the differentiation status of preschool children's adaptation to school according to their relationship with teachers was examined. The study participants consisted of 326 children aged 60-72 months and 21 preschool teachers in different preschool educational institutions affiliated to the Provincial Directorate of National Education in Konya, Turkey. The School Adaptation Teacher Assessment Scale and Teacher-Student Relationship Scale were utilized to collect the research data. In the evaluation of the research data, firstly, teacher-child relationship scores were divided into groups for cluster analysis: conflictual/non-conflictual, dependent/ independent, and close/distant teacher-child relationship. The data gathered were analyzed using the independent-samples t-test. The results of the study revealed that the level of school adaptation of the children who had close, non-conflictual, and independent relationships with their teachers differed significantly from that of children who had distant, conflictual, and dependent relationships with their teachers. Positive teacher-child relationships reflected positively on the level of the child's school adaptation level. Teachers should establish close relationships with children in order to facilitate their adaptation to the school in the preschool period.
A combination of pain indices based on momentary assessments can predict placebo response in patients with fibromyalgia syndrome.

Many factors are known to affect assay sensitivity; however, limited attention has been devoted to understanding whether characteristics of patients' baseline pain impact assay sensitivity. In this study, we tested whether a combination of three baseline pain indices based on ecological momentary assessments (EMA) could detect patients with enhanced responses to placebo. The analysis was conducted with secondary data from two clinical trials in fibromyalgia patients (N=2084). For each patient, pain intensity, pain variability (individual standard deviation), and pain consistency (first-order autocorrelation) were computed from baseline EMA. A latent profile analysis (LPA) identified three subgroups of patients based on these indices. Group 1 (n=857, 41.3%) showed the lowest pain intensity levels, coupled with the highest consistency and greatest variability of pain. Group 3 (n=110, 5.3%) showed the opposite pattern, and group 2 (n=1109, 53.4%) showed intermediate levels on all pain indices. It was then tested whether the subgroups moderated treatment effects (changes in pain for active treatment versus placebo) using repeated-measures ANOVA. Treatment effects varied significantly between subgroups. Patients in group 3 demonstrated greater reduction in pain in response to placebo then those in groups 1 and 2. Further analysis showed that the removal of patients in class 3 would significantly enhance the observed treatment effect by 8-15%. In conclusion, profiles of pain characteristics derived from baseline EMA may be useful for detecting patient subgroups with enhanced placebo responses that can diminish assay sensitivity in pain clinical trials.
Four Earing’s Prediction in Deep Drawing of AISI 1008 Steel Sheet Conical Product

Earing is a phenomenon that appears in deep drawing of parts produced using this process because of the anisotropic material properties. Most of, recent theories didn’t fully employ the mechanical materials properties, and ears number achieved depends on the FE simulation approaches. To anticipate the ears form issue in conical parts of AISI 1008 steel sheet deep drawing, in this work a new method is used to predict the earing formation during deep drawing. This method proposed combines the yielding limits and anisotropy r-values of the material to determine Hill48 yield criterion variables using several conical angles with several punch velocities. Equation for the value of yielding and anisotropy index for different orientation is used. AISI 1008 steel sheet is used as a case in this work, the zone of deformation or blank is partitioned radially to equal parts according to the anisotropic behavior. Hill48 yield function constants solved based on the material yielding point and anisotropy index together for the parallel deformed regions. A simulation using FE software for the process on the base of this method is executed to compare it results of lab work. and it noticed that Increasing speed may contribute slightly in decreasing the severity of anisotropy effect and this can be explained the process propagate the material need time to flow and if the speed increase this lead to increasing in strain hardening of the material[m]. Increasing die angle shows that the different between the highest point to lowest point in the cup edge may increase. This work produces a conductive and dependable way to anticipate the forms of earing during cup drawing, which will have positive effective in manufacturing implementations and numerical outcomes and shows high agreement with lab work.
High-quality-factor Optical Microresonators Fabricated on Lithium Niobite Thin Film with an Electro-optical Tuning Range Spanning Over One Free Spectral Range

We demonstrate high quality (intrinsic Q factor ~2.8×106) racetrack microresonators fabricated on lithium niobate (LN) thin film with a free spectral range (FSR) of ~86.38 pm. By integrating microelectrodes alongside the two straight arms of the racetrack resonator, the resonance wavelength around the 1550 nm can be red shifted by 92 pm when the electric voltage is raised from -100 V to 100 V. The microresonators of the tuning range spanning over a full FSR is fabricated using photolithography assisted chemo-mechanical etching (photolithography assisted chemo-mechanical etching, PLACE).
Estimating densities for sympatric kit foxes (Vulpes macrotis) and coyotes (Canis latrans) using noninvasive genetic sampling

Kit fox (Vulpes macrotis Merriam, 1888) populations in the Great Basin Desert have declined and are of increasing concern for managers. Increasing coyote (Canis latrans Say, 1823) abundance and subsequent intraguild interactions may be one cause for this decline. Concurrent monitoring of carnivores is challenging and therefore rarely conducted. One possible solution for monitoring elusive carnivores is using noninvasive genetic sampling. We used noninvasive genetic sampling to collect fecal DNA from kit foxes and coyotes and estimate their densities from 2013–2014 in Utah, USA. We identified individuals based on microsatellite genotypes and estimated density with multisession spatially explicit capture–recapture models. Mean kit fox density was 0.02 foxes·km−2, while coyote densities were up to four times greater (0.07–0.08 coyotes·km−2). Kit fox densities were significantly lower than densities in the 1950s but were comparable with estimates from the late 1990s, suggesting that populations may be stabilizing after a precipitous decline. Our kit fox density estimates were among the lowest documented for the species. Our coyote density estimate was the first reported in our region and revealed that despite seemingly high abundance, densities are low compared with other regions. Our results suggested that kit foxes may be able to coexist with coyotes.
Determination of 2-chloroethylphosphonic acid and its intermediate vinylphosphonic acid from artificially ripened sapota fruit by modified dispersive solid-phase extraction cleanup and gas chromatography/mass spectrometry analysis.

RATIONALE Fruit is generally ripened after harvesting using artificial ripeners such as ethylene, calcium carbide, and ethephon (2-chloroethylphosphonic acid), which can release some residues into the fruits. These residues must be within the maximum levels described in various international standards. The presence of the residues of artificial ripeners must be verified using sensitive and selective detection methods. METHODS The residues of ethephon and vinylphosphonic acid (VPA) were extracted from the pulp of sapota fruit using acetone, and the extract was treated with MgSO4 to remove residual water. The extract was subjected to dispersive solid-phase extraction cleanup using DSC-6S sorbent and graphitized carbon black mix, and the cleaned sample was evaporated to dryness and reconstituted in ether containing diazomethane. The analytes were quantitatively identified using gas chromatography/mass spectrometry. RESULTS The developed method was observed to be linear in the concentration range of 1-5000 ng/g, and the limits of detection and quantification of the method were 1 and 2 ng/g, respectively, for both ethephon and VPA residues. The inter-day and intra-day precision was below 15%. The developed method was used for the quantification of ethephon residues from sapota fruit ripened with 100, 200, 500, 1000, 5000, and 10 000 mg/L solutions of ethephon, and ethephon residues were detected in the pulp samples up to a concentration of 5 ng/g. VPA residues were not detected in the fruit pulp; however, the washing solution of fruit ripened with a 10 000 mg/L ethephon solution showed VPA residues. CONCLUSIONS The validated method exhibited high sensitivity for the analytes with a limit of quantification of 2 ng/g, which is lower than the described maximum residue level of 0-5 μg/g. The ethephon residues were below the maximum residue limits in the pulp of sapota fruit ripened with ethephon solutions up to 10 000 mg/L concentration.