Miracle-dz/UniFAR-FTUs huggingface dataset:
B Cell Depletion Eliminates FVIII Memory B Cells and Enhances AAV8-coF8 Immune Tolerance Induction When Combined With Rapamycin

Hemophilia A is an inherited coagulation disorder resulting in the loss of functional clotting factor VIII (FVIII). Presently, the most effective treatment is prophylactic protein replacement therapy. However, this requires frequent life-long intravenous infusions of plasma derived or recombinant clotting factors and is not a cure. A major complication is the development of inhibitory antibodies that nullify the replacement factor. Immune tolerance induction (ITI) therapy to reverse inhibitors can last from months to years, requires daily or every other day infusions of supraphysiological levels of FVIII and is effective in only up to 70% of hemophilia A patients. Preclinical and recent clinical studies have shown that gene replacement therapy with AAV vectors can effectively cure hemophilia A patients. However, it is unclear how hemophilia patients with high risk inhibitor F8 mutations or with established inhibitors will respond to gene therapy, as these patients have been excluded from ongoing clinical trials. AAV8-coF8 gene transfer in naïve BALB/c-F8e16−/Y mice (BALB/c-HA) results in anti-FVIII IgG1 inhibitors following gene transfer, which can be prevented by transient immune modulation with anti-mCD20 (18B12) and oral rapamycin. We investigated if we could improve ITI in inhibitor positive mice by combining anti-mCD20 and rapamycin with AAV8-coF8 gene therapy. Our hypothesis was that continuous expression of FVIII protein from gene transfer compared to transient FVIII from weekly protein therapy, would enhance regulatory T cell induction and promote deletion of FVIII reactive B cells, following reconstitution. Mice that received anti-CD20 had a sharp decline in inhibitors, which corresponded to FVIII memory B (Bmem) cell deletion. Importantly, only mice receiving both anti-mCD20 and rapamycin failed to increase inhibitors following rechallenge with intravenous FVIII protein therapy. Our data show that B and T cell immune modulation complements AAV8-coF8 gene therapy in naïve and inhibitor positive hemophilia A mice and suggest that such protocols should be considered for AAV gene therapy in high risk or inhibitor positive hemophilia patients.
A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition

Background: Breast cancer (BC) represents a heterogeneous disease with distinct subtypes and high tumor metastatic potentials. Recent researchers identify the implication of circular RNAs (circRNAs) in the initiation of BC. Herein, we uncover a novel circRNA hsa_circRPPH1_015 as a tumor promoter in BC. Methods: A total of 86 paired cancerous and non-cancerous tissues were surgically resected and collected from BC patients. Cell proliferation, colony formation, and cell invasion were examined by Edu staining, clone formation assays, propidium iodide (PI)-labeled flow cytometry, and Transwell invasion assays. PCNA, Ki67, MMP-2, MMP-9, Cyclin D1, and CDK4 expression was assayed using Western blot analysis. RNA pull-down, dual-luciferase reporter gene assay, and RNA binding protein immunoprecipitation (RIP) assay were performed to investigate the relationships among hsa_circRPPH1_015, microRNA-326 (miR-326), and ELK1. The tumor growth of human BC MCF-7 cells in vivo was evaluated in nude mice by subcutaneous xenografts of MCF-7 cells. Results: hsa_circRPPH1_015 expression was upregulated in BC tissues. Knockdown of hsa_circRPPH1_015 restrained the aggressive behavior of MCF-7. hsa_circRPPH1_015 could bind to miRNA-326 that negatively regulates ELK1. Elevation of miRNA-326 expression resulted in inhibition of cell proliferation, colony formation, and cell invasion of MCF-7. Disturbance of miRNA-326 or overexpression of ELK1 restored the proliferation and aggressiveness in hsa_circRPPH1_015-depleted MCF-7 cells. Tumor growth of MCF-7 cells in vivo was reduced in nude mice lack of endogenous hsa_circRPPH1_015 expression. Conclusion: Overall, the present study demonstrates that hsa_circRPPH1_015 was an oncogene and unfavorable prognostic factor in BC, providing an exquisite therapeutic target for BC.
Response of non–glufosinate-resistant cotton to reduced rates of glufosinate

Abstract Field research was conducted for 2 yr to determine the effect of reduced rates of glufosinate on growth and yield of non–glufosinate-resistant cotton. Rates of 3.4, 6.7, 13, 26.5, 52.5, and 105 g ha−1, representing 0.008, 0.016, 0.031, 0.063, 0.125, and 0.25 of an effective use rate (420 g ha−1), were applied to cotton at the two-, five-, or nine-node growth stage. Based on analysis of visual injury, cotton response decreased as application timing was delayed in one of the three experiments. Injury response was increased slightly with application at the five- compared with the two-node growth stage and was not significant for the latest application timing (nine-node stage) in two of three experiments. In two of the three experiments, plant height reduction response was lowest at the five-node stage and greatest at the nine-node stage. Regardless of application timing, plant dry weight was negatively affected only with the highest rate of glufosinate. Glufosinate application, based on node above white flower number and percent open boll, did not result in a delay in maturity. Final plant population was reduced in all experiments at the two-node application and in one of the three experiments at the five-node stage. Glufosinate application did not adversely affect final plant population when applied to nine-node cotton. Negative effects on cotton growth were not manifested in seedcotton yield reduction after glufosinate application. Nomenclature: Glufosinate; cotton, Gossypium hirsutum L. ‘Stoneville 474’, ‘DP33B’.
Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity

Despite the identification of molecular mechanisms associated with pain persistence, no significant therapeutic improvements have been made. Advances in the understanding of the molecular mechanisms that induce pain hypersensitivity will allow the development of novel, effective, and safe therapies for chronic pain. Various pro-inflammatory cytokines are known to be increased during chronic pain, leading to sustained inflammation in the peripheral and central nervous systems. The pro-inflammatory environment activates additional metabolic routes, including the kynurenine (KYN) and tetrahydrobiopterin (BH4) pathways, which generate bioactive soluble metabolites with the potential to modulate neuropathic and inflammatory pain sensitivity. Inflammation-induced upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) and guanosine triphosphate cyclohydrolase I (GTPCH), both rate-limiting enzymes of KYN and BH4 biosynthesis, respectively, have been identified in experimental chronic pain models as well in biological samples from patients affected by chronic pain. Inflammatory inducible KYN and BH4 pathways upregulation is characterized by increase in pronociceptive compounds, such as quinolinic acid (QUIN) and BH4, in addition to inflammatory mediators such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). As expected, the pharmacologic and genetic experimental manipulation of both pathways confers analgesia. Many metabolic intermediates of these two pathways such as BH4, are known to sustain pain, while others, like xanthurenic acid (XA; a KYN pathway metabolite) have been recently shown to be an inhibitor of BH4 synthesis, opening a new avenue to treat chronic pain. This review will focus on the KYN/BH4 crosstalk in chronic pain and the potential modulation of these metabolic pathways that could induce analgesia without dependence or abuse liability.
Oil Content and Fatty Acid Characteristics in Mediterranean Sesame Core Collection

The Mediterranean sesame core collection is a valuable genetic resource for the development of seed quality and quantity. To better characterize and exploit the core collection, this study investigated the oil and fatty acid composition of seeds in the collection. Oil content, determined by a Soxhlet apparatus, varied from 32.3 to 57.3%, with a mean of 46.6%. Oil yield varied greatly among the accessions, with the highest oil yield being 891.1 kg ha⁻¹. Gas chromatography–mass spectrometry (GC-MS) determination of fatty acid composition within the core collection showed significant differences among genotypes. Oleic acid contents ranged from 38.2 to 47.3% and linoleic acid contents from 31.0 to 40.9%. Up to 80% of fatty acids were unsaturated, indicating their importance for human dietary needs. Palmitic and stearic acids were present in small amounts in all accessions, ranging from 8.85 to 12.0% and from 6.3 to 8.9%, respectively. These results indicated that oil profiles varied widely among seeds in the Mediterranean sesame core collection, providing information that may enable the development of new varieties with high oil contents. A cluster analysis of fatty acid data based on continent affiliation yielded results highly similar to those of a cluster analysis based on agromorphological data. To our knowledge, this is the first report indicating that agromorphological and oil composition data were compatible with geographical patterns.
Sonochemically synthetized ZnO-Graphene nanohybrids and its characterization

Abstract The paper presents the morphological, structural and compositional properties of the sonochemically prepared ZnO-1.4wt% Graphene (Z-G) nanocomposites as a function of pH value of suspension varying from 8.5 to 14 and thermal annealing at 450°C in nitrogen or air ambient. The SEM analysis of the Z-G hybrids dried at 150°C in air has shown a nano-flower like nanostructure for a pH value of 14. The XRD analysis of dried Z-G hybrids revealed a crystallite size increase from 3.5 nm to 18.4 nm with pH increase, and this result was explained in terms of colloids zeta potential evolution with pH value. The Raman and EDS spectroscopy have shown a split of the G band (1575 cm−1) of graphene into two bands (1575 cm−1 and 1605 cm−1), an increased height of D (1323 cm−1) band, and an additional amount of carbon due to CO2 absorption from the air, respectively. The carbon incorporation increased with the decrease of pH, and was associated with a hydrozincite phase, Zn5(CO3)2(OH)6. The formation of dried Z-G nanocomposite was clearly demonstrated only at a pH value equal to 14, where two ZnO Raman active bands at 314.9 cm−1 and 428.2 cm−1 appeared. This result may indicate the sensitivity of the Raman spectroscopy to the nanoflower-like nanostructure of dried Z-G hybrids prepared at pH=14. The thermal treatment of Z-G hybrids in N2at 450°C has increased the number of ZnO Raman bands as a function of pH value, it has decreased the amount of additional carbon by conversion of hydrozincite to ZnO and preserved the graphene profile. The thermal treatment in air at 450°C has increased the crystalline symmetry and stoichiometry of the ZnO as revealed by high and narrow Raman band from 99 cm−1 specific to Zn optical phonons, but it has severely affected the graphene profile in the Z-G hybrid, due to combustion of graphene in oxygen from the ambient.
Comparison of the Effect of Vix Fear Index on Stock Exchange Indices of Developed and Developing Countries: the G20 Case

Abstract This study aims to examine the potential causal relationship between the VIX and the indicator stock exchange index returns of G20 (9 developed and 10 developing) countries. Nineteen countries of the sample are G20 countries with available data. In this respect, the frequency domain Granger causality test of Breitung and Candelon (2006) is employed for the daily data between March 2011 and December 2017. The results obtained from the study indicate that there is no causal relationship between the VIX and the returns of the NASDAQ 100 index in developed countries. Similarly, no causal relationship is detected which runs from the VIX to the BIST100, BOVESPA, MERVAL, S&P/BMV IPC and TADAWUL stock index returns in developing countries. As a result, the causal relationship is more tend to be found in developed countries in comparison to developing countries.
The Importance of Human Emotions for Wildlife Conservation

Animals have always been important for human life due to the ecological, cultural, and economic functions that they represent. This has allowed building several kinds of relationships that have promoted different emotions in human societies. The objective of this review was to identify the main emotions that humans show toward wildlife species and the impact of such emotions on animal population management. We reviewed academic databases to identify previous studies on this topic worldwide. An analysis of the emotions on wildlife and factors causing them is described in this study. We identified a controversy about these emotions. Large predators such as wolves, coyotes, bears, big felids, and reptiles, such as snakes and geckos, promote mainly anger, fear, and disgust. This is likely due to the perceptions, beliefs, and experiences that societies have historically built around them. However, in some social groups these animals have promoted emotions such as happiness due to their values for people. Likewise, sadness is an emotion expressed for the threatening situations that animals are currently facing. Furthermore, we associated the conservation status of wildlife species identified in the study with human emotions to discuss their relevance for emerging conservation strategies, particularly focused on endangered species promoting ambiguous emotions in different social groups.
Demography and foraging ecology of Chelonia mydas on tropical shallow reefs in Bahia, Brazil

Long-term tagging studies, particularly those that target life stages away from nesting beaches can provide important insights in key life history traits, which are essential for the effective management of endangered species. The coast of Bahia hosts important green turtle foraging areas, but information on demography, spatial use and foraging ecology in this region is lacking. Here, we (1) examined the size-class structure of green turtles in Bahia, (2) compared the size distribution from Bahia to other foraging aggregations in Brazil, and (3) studied the somatic growth dynamics. Additionally, we investigated the (4) diet, (5) habitat use and (6) activity patterns of green turtles along shallow reefs in Bahia. From 2009 to 2013, 322 green turtles were captured and 44 were recaptured between 7 and 1218 days after initial tagging. Curved carapace length varied from 32.9 to 122.5 cm. Mean annual growth rate was 3.03 ± 1.18 cm year−1. The diet of the turtles was mainly composed of red algae of the family Gelidiaceae, Gelidiellaceae and Cystocloniaceae. There was a positive relationship between the abundance of red algae and the number of turtle sightings, with a significant increase in foraging activity during late afternoon. This study highlights the importance of this area as a mixed foraging aggregation of juvenile and adult green turtles, and reveals that foraging grounds for this species in Brazil exhibit southern immature-dominated assemblages and northern mixed aggregations. Areas with high aggregation of green turtles comprising individuals from different life stages must be targeted for conservation management.
Factors influencing incidence of red spider mite of tea, Oligonychus coffeae (Nietner) in Assam.

relative humidity, total rainfall and bright sunshine hours were collected for the entire period of study from the Department of Agrometeorology, AAU, Jorhat.The incidence of red spider mite, Oligonychus coffeae on tea leaves was maximum during month of April to May-June and September-October (2011). The minimum number of mites was recorded from JulyAugust and November (2011) to February (2012). The data taken from 1 week of April, 2011 to last week of March 2012. In case of eggs population, there was a gradual increasing trend in egg number to reach the peak population in the month of April. From April to June overall higher population of eggs/leaf was noticed. Afterwards sharp decline in number of eggs was noticed during July and August. Again population of eggs was increased during September and October. Very minimum population of eggs was observed from November to January. Population of eggs was started increasing again from 1 week of February to March. Results of the present studies showed that the buildup of the red spider mite, O. coffeae population, as well as the number of eggs had a significantly positive correlation with the maximum temperature(r=0.320 and r=0.286 for the mites and eggs, respectively) and minimum temperature (r=0.268 and r=0.279 for mites and eggs, respectively). Whereas the motile stage of red spider mite, O. coffeae and eggs had a negative and significant correlation with average relative humidity (r = -0.357 and r = -0.282 for mites and eggs, respectively).
Altered Effective Connectivity of Bilateral Hippocampus in Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (T2DM) experience cognitive deficits but the underlying pathophysiologic mechanisms are not known. We therefore applied Granger causality analysis of resting-state functional magnetic resonance imaging to study the effective connectivity (EC) of the hippocampus in patients with T2DM. Eighty six patients with T2DM and 84 matched healthy controls (HC) were recruited. The directional EC between anatomically defined seeds in left hippocampus (LHIP) and right hippocampus (RHIP) and other brain regions was compared between T2DM and HC and Pearson correlation analysis was performed to determine whether alterations in EC were related to clinical characteristics of diabetes. Compared with HC, patients with T2DM had altered EC between LHIP and RHIP and the default mode network (DMN), occipital cortex and cerebellum. In addition, for LHIP only duration of diabetes positively correlated with decreased inflow from right postcentral gyrus and right parietal lobe, glycosylated hemoglobin (HbA1c) negatively correlated with decreased inflow from right thalamus (r = −0.255, p = 0.018) and Montreal Cognitive Assessment (MoCA) negatively correlated with decreased inflow from left inferior parietal lobe (r = −0.206, p = 0.05). The altered EC between hippocampus and DMN is interpreted to be related to cognitive deficits in patients with T2DM particularly affecting memory and learning.
Task-specific Disruptions in Theta Oscillations during Working Memory for Temporal Order in People with Schizophrenia

Abstract Prior studies demonstrated that neural oscillations are enhanced during working memory (WM) maintenance and that this activity can predict behavioral performance in healthy individuals. However, it is unclear whether the relationship holds for people with WM deficits. People with schizophrenia have marked WM deficits, and such deficits are most prominent when patients are required to process relationships between items, such as temporal order. Here, we used EEG to compare the relationship between oscillatory activity and WM performance in patients and controls. EEG was recorded as participants performed tasks requiring maintenance of complex objects (“Item”) or the temporal order of objects (“Order”). In addition to testing for group differences, we examined individual differences in EEG power and WM performance across groups. Behavioral results demonstrated that patients showed impaired performance on both Item and Order trials. EEG analyses revealed that patients showed an overall reduction in alpha power, but the relationship between alpha activity and performance was preserved. In contrast, patients showed a reduction in theta power specific to Order trials, and theta power could predict performance on Order trials in controls, but not in patients. These findings demonstrate that WM impairments in patients may reflect two different processes: a general deficit in alpha oscillations and a specific deficit in theta oscillations when temporal order information must be maintained. At a broader level, the results highlight the value of characterizing brain–behavior relationships, by demonstrating that the relationship between neural oscillations and WM performance can be fundamentally disrupted in those with WM deficits.
Emotion Display Rules, Emotion Regulation, and Teacher Burnout

Cognitive appraisal theories of emotions suggest that emotions are elicited by evaluations of events and situations and that our beliefs influence the ways we appraise or judge situations that we encounter. Gross and John (2003) theorized cognitive reappraisal and expressive suppression as two general forms to regulate emotions. Although teacher emotion has been studied more extensively in the recent decade, Chang (2009b) has argued that there is a need for research into the ways that teachers' implicit beliefs and cognitive processes influence their emotional reactions to the sources of burnout. Particularly, how emotional display rules serve as underlying principles that guide teachers to make decisions either consciously or unconsciously to express or not to express emotions. This study aims to examine the relationships among teachers' beliefs about emotional display rules in the classroom, and the approaches in emotion regulation, and the subsequent feelings of burnout. Survey data was collected from 561 full-time teachers and subjected to hypothesis testing using structural equation modeling. The model provides evidence supporting a pathway between emotion display rules and expressive suppression. These display rules are particularly influential to expressive suppression which also leads to all three dimensions of burnout: emotional exhaustion, depersonalization, and reduced personal accomplishment. Further, uses of cognitive reappraisals are found negatively associated with teacher burnout in all three dimensions. Results of the study indicated that teacher education or profession development should be designed to help teachers to detect and reframe their beliefs about display rules and to engage in cognitive reappraisal so that they may effectively manage their day-to-day emotions in the classroom.
Evaluating German Transformer Language Models with Syntactic Agreement Tests

Pre-trained transformer language models (TLMs) have recently refashioned natural language processing (NLP): Most state-of-the-art NLP models now operate on top of TLMs to benefit from contextualization and knowledge induction. To explain their success, the scientific community conducted numerous analyses. Besides other methods, syntactic agreement tests were utilized to analyse TLMs. Most of the studies were conducted for the English language, however. In this work, we analyse German TLMs. To this end, we design numerous agreement tasks, some of which consider peculiarities of the German language. Our experimental results show that state-of-the-art German TLMs generally perform well on agreement tasks, but we also identify and discuss syntactic structures that push them to their limits.