Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2

Significance The molecular clock provides an anticipatory mechanism, allowing organisms to prepare and respond to daily changes in the external environment. The response of the innate immune system to pathogenic threats is dependent on time of day; however, the molecular mechanisms underlying this have yet to be fully uncovered. We observe that the core molecular clock component, BMAL1, is crucial in promoting an antioxidant response in myeloid cells. Deletion of Bmal1 in macrophages disrupts NRF2 activity, facilitating accumulation of reactive oxygen species and the proinflammatory cytokine, IL-1β. Thus the molecular clock directly controls NRF2 transcriptional activity and antioxidant capacity to regulate IL-1β in myeloid cells. A variety of innate immune responses and functions are dependent on time of day, and many inflammatory conditions are associated with dysfunctional molecular clocks within immune cells. However, the functional importance of these innate immune clocks has yet to be fully characterized. NRF2 plays a critical role in the innate immune system, limiting inflammation via reactive oxygen species (ROS) suppression and direct repression of the proinflammatory cytokines, IL-1β and IL-6. Here we reveal that the core molecular clock protein, BMAL1, controls the mRNA expression of Nrf2 via direct E-box binding to its promoter to regulate its activity. Deletion of Bmal1 decreased the response of NRF2 to LPS challenge, resulting in a blunted antioxidant response and reduced synthesis of glutathione. ROS accumulation was increased in Bmal1−/− macrophages, facilitating accumulation of the hypoxic response protein, HIF-1α. Increased ROS and HIF-1α levels, as well as decreased activity of NRF2 in cells lacking BMAL1, resulted in increased production of the proinflammatory cytokine, IL-1β. The excessive prooxidant and proinflammatory phenotype of Bmal1−/− macrophages was rescued by genetic and pharmacological activation of NRF2, or through addition of antioxidants. Our findings uncover a clear role for the molecular clock in regulating NRF2 in innate immune cells to control the inflammatory response. These findings provide insights into the pathology of inflammatory conditions, in which the molecular clock, oxidative stress, and IL-1β are known to play a role.
Altered Auditory Processing, Filtering, and Reactivity in the Cntnap2 Knock-Out Rat Model for Neurodevelopmental Disorders

Sensory processing, and auditory processing in particular, is altered in individuals with neurodevelopmental disorders such as autism spectrum disorders (ASDs). The typical maturation of the auditory system is perturbed in these individuals during early development, which may underlie altered auditory reactivity that persists in later life. Of the many genes that regulate the auditory system development, loss-of-function mutations in the CNTNAP2 gene are strongly associated with language processing deficits and ASD. Therefore, using a novel Cntnap2 knock-out rat model, we tested the impact of Cntnap2 loss on auditory processing, filtering, and reactivity throughout development and young adulthood in male and female animals. Although hearing thresholds were not altered in Cntnap2 knock-out animals, we found a reduction in response amplitudes and a delay in response latency of the auditory brainstem response (ABR) in juvenile Cntnap2 knock-out rats compared with age-matched controls. Amplitudes and latency of the ABR largely normalized by adulthood, indicating a delayed maturation of auditory processing pathways in Cntnap2 knock-out rats. Despite the reduced ABR amplitudes, adolescent Cntnap2 knock-out animals displayed increased startle reactivity accompanied by disruptions in sensory filtering and sensorimotor gating across various conditions, most of which persisted in adulthood. All of these observations show striking parallels to disruptions reported in ASD. Our results also imply that developmental disruptions of sensory signal processing are associated with persistent changes in neural circuitries responsible for implicit auditory evoked behavior, emphasizing the need for interventions that target sensory processing disruptions early during development in ASD. SIGNIFICANCE STATEMENT This is the first study of brainstem auditory processing in a novel knock-out rat model with very high construct and face validity for autism spectrum disorders. Electrophysiological and behavioral measures of implicit auditory-evoked responses were systematically taken across developmental stages. Auditory processing, filtering, and reactivity disruptions show striking similarities to observations in autism. We also show for the first time that, whereas auditory brainstem responses normalize by adulthood, disruptions in brainstem-mediated auditory-evoked behavior persist. This indicates that early developmental perturbations in sensory processing can cause permanent maladaptive changes in circuitries responsible for auditory reactivity, underlining the importance for interventions early during development aiming at normalizing sensory processing.
How selfish is a thirsty man? A pilot study on comparing sharing behavior with primary and secondary rewards

Human social interactions in daily life involve sharing various types of rewards. Previous research evolving around issues of selfish versus altruistic behavior indicates that when individuals share rewards like money with powerless others, some are purely selfish while a substantial number shares evenly. It is, however, mostly unknown how they share primary rewards like water, compared to secondary rewards like money. We adopt the widely studied Dictator Game for comparing water to be divided among study participants with a monetary reward. We show that thirsty participants share water more often equally with powerless, anonymous others than they do money. This is the case even when they earned both types of rewards in a preceding task. Results indicate that altruistic behavior is more likely to occur when it comes to sharing primary rewards. The ecologically more valid scenario employed in this study provides initial evidence that the concept of a self-interested homo economicus might not apply to everyday social interactions involving rewards other than money.
Application of quasi-emulsification and modified double emulsification techniques for formulation of tacrolimus microsponges

Background The present study was to develop a stable and sustained-release delivery system of tacrolimus (TCM). TCM is a macrolide antibiotic used as an immunosuppressant. It is formulated as a microsponge, which is a safe and effective delivery system with reduced side effects. Materials and methods The method used to prepare ethyl cellulose (EC) and xanthan gum (XG)-facilitated EC-based microsponges employed emulsification and modified double emulsification techniques. TCM-containing microsponges were prepared using varying concentrations followed by evaluation of micromeritics, compatibility of drug and excipients, production yield, drug content and entrapment efficiency, zeta potential, size distribution and drug release. Results The results showed excellent flow properties with adequate entrapment efficiency of the system and satisfactory release of active pharmaceutical ingredient. In vitro dissolution studies, which were conducted to determine the amount of drug released, illustrated a pronounced sustained effect up to 8 h. Zeta size and zeta potential analysis of microsponges confirmed the existence of micro-sized (1.99–3.09 µm) and stable particles (−15.33 to −3.38 mV), respectively. Conclusion Conclusively, the applied technique and selected combination of ingredients were found suitable for the preparation of TCM-containing sustained-release microsponges.
SentencePiece: A simple and language independent subword tokenizer and detokenizer for Neural Text Processing

This paper describes SentencePiece, a language-independent subword tokenizer and detokenizer designed for Neural-based text processing, including Neural Machine Translation. It provides open-source C++ and Python implementations for subword units. While existing subword segmentation tools assume that the input is pre-tokenized into word sequences, SentencePiece can train subword models directly from raw sentences, which allows us to make a purely end-to-end and language independent system. We perform a validation experiment of NMT on English-Japanese machine translation, and find that it is possible to achieve comparable accuracy to direct subword training from raw sentences. We also compare the performance of subword training and segmentation with various configurations. SentencePiece is available under the Apache 2 license at https://github.com/google/sentencepiece.
Antibiotic resistance pattern and molecular characterization of extended-spectrum β-lactamase producing enteroaggregative Escherichia coli isolates in children from southwest Iran

Introduction Enteroaggregative Escherichia coli (EAEC) has been implicated as an emerging cause of traveler’s diarrhea, persistent diarrhea among children, and immunocompromised patients. The present study aimed to investigate the prevalence of antibiotic resistance, extendedspectrum β-lactamase (ESBL) production, and virulence factors of EAEC isolates obtained from Iranian children suffered from diarrhea. Materials and methods In this cross-sectional study, from March 2015 to February 2016, 32 EAEC isolates were collected from fecal samples of children aged <12 years with diarrhea in southwest of Iran. All EAEC isolates identified using phenotypic and molecular methods and the cell line adhesion assay. Antimicrobial susceptibility testing was determined using disk diffusion method. The presence of virulence factors and ESBL resistance genes were determined by polymerase chain reaction. Results Overall, 28.1% (9/32) of the isolates were positive for at least one of virulence genes. The most frequent gene was aap with a frequency of 96.9%. Neither aafA nor aggA gene was detected among all of the EAEC isolates. Antimicrobial susceptibility testing revealed the highest resistance rate to ampicillin (100%) and co-trimoxazole (100%), followed by ceftriaxone (81.3%). Further analysis revealed that the rate of ESBLs-producing isolates was 71.9% (23/32). Polymerase chain reaction screening revealed that 87.5% and 65.5% of EAEC isolates were positive for blaTEM and blaCTX-M genes, respectively, and 17 (53.1%) of isolates contained both blaTEM and blaCTX-M genes. Conclusion The high detection rate of ESBL-producing EAEC isolates accompanied with virulence genes highlights a need to restrict infection control policies in order to prevent further dissemination of the resistant and virulent EAEC strains.
Total Ionizing Dose Response and Annealing Behavior of Bulk nFinFETs With ON-State Bias Irradiation

The total ionizing dose response of bulk nFinFETs with multiple gate lengths and multiple fins is investigated for on-state bias condition. Experiments and Technology Computer Aided Design simulations were performed to analyze the effect of the trapped charges in the gate oxide and shallow trench isolation (STI) oxide on the threshold voltage and transconductance of the devices. The increases in the threshold voltage and transconductance are observed after X-ray irradiation. The positive shift of the threshold voltage is caused by the net negative charges trapped in the gate oxide. The simulation results show that the trapped holes in the STI oxide reduce the electric field and increase the electron mobility in channel near the fin bottom, which is the major contribution to the increased transconductance. An interesting phenomenon was also observed that the threshold voltage continues to increase during the annealing process, whereas the transconductance decreases. These results suggest that there may also be a small amount of trapped holes in gate oxide during irradiation, and those trapped holes are compensated by electrons transporting from the silicon during the anneal, leading to further positive shift of the threshold voltage. Moreover, the decrease in transconductance is mainly introduced by the neutralization of the trapped holes at STI/silicon interface.
Internal transcribed spacer 2 (ITS2) barcodes: A useful tool for identifying Chinese Zanthoxylum

Premise of the Study The genus Zanthoxylum in the Rutaceae family of trees and shrubs has a long history of domestication and cultivation in Asia for both economic and medicinal purposes. However, many Zanthoxylum species are morphologically similar and are easily confused. This often leads to false authentication of source materials and confusion in herbal markets, hindering their safe utilization and genetic resource conservation. DNA barcoding is a promising tool for identifying plant taxa. Methods We used three candidate DNA barcoding regions (ITS2, ETS, and trnH‐psbA) to identify 69 accessions representing 13 Chinese Zanthoxylum species. The discriminatory capabilities of these regions were evaluated in terms of PCR amplification success, intra‐ and interspecific divergence, DNA barcoding gaps, and identification efficiency using the BLAST and tree‐building methods. Results ITS2 proved the most useful for discriminating Chinese Zanthoxylum species, with a correct identification rate of 100%, and this region also exhibited significantly higher intra‐ and interspecific divergence. Discussion Phylogenetic analysis confirmed that ITS2 has a powerful discriminatory ability both at and below the species level. We confirmed that ITS2 is a powerful barcoding region for identifying Chinese Zanthoxylum species, and will be useful for analyzing and managing Chinese Zanthoxylum germplasm collections.
Temperature Quenching of Radio- and Photoluminescence of Y3(Ga,Al)5O12:Ce3+ and Gd3(Ga,Al)5O12:Ce3+ Garnet Ceramics

Cerium-doped mixed oxide garnets are promising luminescent materials to use as LED phosphors or scintillators for radiation detectors. In this paper, temperature-dependent characteristics of Ce-doped multicomponent garnets ceramics have been studied under photo and X-ray excitation. Ceramic samples of Y<sub>3</sub>Ga<sub>x</sub>Al<sub>5−x</sub>O<sub>12</sub>:Ce<sub>0.006</sub> (<inline-formula> <tex-math notation="LaTeX">$x = 1$ </tex-math></inline-formula>, 2, 3, and 4) and of Gd<sub>3</sub>Ga<sub>x</sub>Al<sub>5−x</sub>O<sub>12</sub>:Ce<sub>0.006</sub> (<inline-formula> <tex-math notation="LaTeX">$x = 1$ </tex-math></inline-formula>, 2, and 3) have been used. At high temperature, all samples showed decrease in the Ce<sup>3+</sup> luminescence intensity, luminescence decay, and luminescence lifetime due to thermal ionization of Ce<sup>3+</sup> excited 5d states. Values of activation energies of the thermal ionization process have been determined from photoluminescence lifetime measurements and shown in comparison with literature data. At low temperature, Gd-containing samples showed significant decrease in light output. In the same temperature range, large thermoluminescence peaks have been observed, indicating that the reduction of Ce<sup>3+</sup> emission at low temperatures can be attributed to the localization of charge carriers on traps.
The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR

Background The antiparasitic agent niclosamide has been demonstrated to inhibit the arthropod-borne Zika virus. Here, we investigated the antiviral capacity of niclosamide against dengue virus (DENV) serotype 2 infection in vitro and in vivo. Principle finding Niclosamide effectively retarded DENV-induced infection in vitro in human adenocarcinoma cells (A549), mouse neuroblastoma cells (Neuro-2a), and baby hamster kidney fibroblasts (BHK-21). Treatment with niclosamide did not retard the endocytosis of DENV while niclosamide was unable to enhance the antiviral type I interferon response. Furthermore, niclosamide did not cause a direct effect on viral replicon-based expression. Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. Similar to the vacuolar-type H+-ATPase inhibitor bafilomycin A1, both niclosamide and other protonophores, such as CCCP (carbonyl cyanide m-chlorophenyl hydrazone), and FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone), effectively reduced endosomal acidification and viral dsRNA replication. Co-administration of a single dose of niclosamide partially decreased viral replication, viral encephalitis, and mortality in DENV-infected ICR suckling mice. Significance These results demonstrate that niclosamide diminishes viral infection by hindering endosomal acidification.
Variations of external load variables between medium- and large-sided soccer games in professional players

ABSTRACT This study compared the relative physical demands of official matches and sided games (medium and large) in professional soccer players by means of a global positioning system. Twenty-three professional male soccer players (24.632.84 years old; 180.946.49 cm; 77.196.46 kg; 52.995.01 VO2max) participated in the study. Total distance, running distance, sprinting distance, number of sprints, and acceleration sum were quantified per minute to compare the different games. Running distance in full match was greater than in 5vs5+GK (d = 2.303, moderate effect), 6vs6+GK (d = 1.719, moderate effect) and 9vs9+GK (d = 1.084, minimum effect) sided games. Greater values for sprinting distance were found in the full match compared to 5vs5+GK (d = 3.673, strong effect), 6vs6+GK (d = 2.606, moderate effect) and 9vs9+GK (d = 1.903, moderate effect) sided games. However, the load was greater in the 5vs5+GK game compared to the 6vs6+GK (d = 1.323, moderate effect) and 9vs9+GK (d = 1.030, minimum effect) games and the full match (d = 1.478, moderate effect). This study revealed that medium-sided games are not appropriate for simulating the sprinting conditions of official full matches. However, medium-sided games are more intense than full matches in that accelerations are made more often in medium-sided games.
Embracing Uncertainty to Enable Transformation: The Process of Engaging in Trialogue for Mental Health Communities in Ireland

Introduction: Community-based participatory approaches are valuable methods for improving outcomes and effectively integrating care among mental health communities. Trialogue is one such approach which uses Open Dialogue methods with groups of three or more people from different backgrounds who deal with mental health systems. Theory and Method: The current study employed a participatory action research design, which prospectively documented the processes and challenges of participating in Trialogue Meetings. Individuals from participating communities took part in interviews, focus groups or Open Dialogue discussions across three cycles of research. Results: Three prospective themes were identified from participants’ dialogue across the three cycles of research relating to the experience of participating in Trialogue, the development of Open Dialogue skills and the growth of individual Trialogue communities. Conclusions and Discussion: The findings demonstrate that, where desirable conditions are present, Trialogue Meetings are worthwhile and sustainable community-based participatory approaches which encourage disclosure and dialogue surrounding mental health, and may assist in improved integration of care between mental health stakeholders. In particular, Trialogue Meetings stimulate the development of Open Dialogue skills, provide a platform for “vital” and “transformative” self-expression with the potential for positive mental health outcomes and may facilitate the growth of communities surrounding mental health.
Biological parameters of the triatomine, Meccus phyllosomus pallidipennis, fed on two bloodmeal sources under laboratory conditions

Chagas disease is one of the most important vector‐borne diseases in Latin America, including Mexico. Meccus phyllosomus pallidipennis (Stål), 1872 (Hemiptera: Reduviidae) is a Mexican triatomine vector that is commonly associated with hens and rabbits. The biological parameters of two cohorts fed on hens (H) and on rabbits (R) were evaluated. The median lifecycles of the two cohorts were 198 days (H) and 180 days (R). Moreover, mortality was around 30% in both cohorts. Time lapse for beginning of feeding was 0.5–1.9 (H) and 1.1–2.4 min (R). Feeding times of each instar in both cohorts were over 10 min. Most specimens fed on hens defecated immediately after feeding, whereas those that fed on rabbits defecated within 1–5 min post‐feeding. Similar numbers of males and females (50%) were obtained in both cohorts. An average of 2.1–2.3 eggs per female per day was noted in both cohorts, with eclosion rates of 95.4 (H) and 88.8% (R). Thus, it can be concluded that M. phyllosomus pallidipennis may take advantage of feeding in hens, as in rabbits, which could imply a higher risk of Trypanosoma cruzi transmission to humans and animals in its distribution area.
Comparison of Quality of Life before and after pancreaticoduodenectomy: a prospective study

Background Pancreatic cancer is an aggressive malignancy, and surgical resection is the only therapeutic option with pancreaticoduodenectomy being considered the standard of care. It is essential to take into account the patients’ Quality of Life after the resection, in order to make more informed decisions about treatment options. Objective The aim of the study was to determine perceived Quality of Life levels among patients who undergo pancreaticoduodenectomy, in a period of six months after surgery. Methods This prospective study was conducted on all patients (n=40) who underwent pancreaticoduodenectomy in Attikon University General Hospital in Athens, Greece, from January 2013 to June 2015. The Quality of Life was assessed by use of EORTC QLQ-C30 and EORTC QOL-PAN26 questionnaires at four phases: First, after admission at the hospital preoperatively, and then one month, three months, and six months postoperatively. Repeated measurements analysis of variance (ANOVA) was used in order to evaluate changes in Quality of Life measures during the follow-up (postoperative) period. Data analysis was conducted using SPSS version 19. A p-value of less than or equal to 0.05 was set as the level of significance. Results The study revealed a mixed image. Except for the nausea and vomiting scale, where indeed a symptom increase is initially reported and then gradually decreases below preoperative levels by 6 months, scoring in many symptom scales worsens postoperatively. From first to fourth assessment, fatigue (Mean from 23.61 to 38.72, p=0.005) and financial difficulties scoring (Mean from 5.98 to 42.42, p<0.001) consistently worsen. Functionality scales scoring also tends to get worse between first and fourth assessment, with statistically significant changes for physical (p<0.001), role (p<0.001) and social functioning (p<0.001). However, a slight improvement can be noted in many scales from third to fourth assessment, as in diarrhea (Mean from 32.38 to 29.29), pancreatic pain (Mean from 17.71 to 2.34), global health status (Mean from 50.48 to 52.53) and social functioning (Mean from 43.81 to 48.48) scales. Conclusions Quality of Life levels among patients who undergo pancreaticoduodenectomy are getting worse following surgery. However, the longitudinal study of these changes may improve patients’ postoperative life by formulating evidence-based interventions concerning symptoms treatment and psychological and social support.