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Background: VitD3 may contribute to a successful pregnancy through modulation of immune responses. Therefore, VitD3 deficiency may have a role in the immunopathogenesis of unexplained recurrent spontaneous abortion (URSA). However, the mechanisms of immunomodulatory actions of VitD3 in decreasing the risk of recurrent spontaneous abortion have not been understood well. Objective: The purpose of this research was to investigate the influence of 1,25VitD3 on regulatory T cells /Th17 axis, the gene expressions and concentrations of related cytokines including, TGF-β, IL-10, IL-6, IL-23, and IL-17A in peripheral blood mononuclear cells (PBMCs) of healthy women as a control group and women with URSA. Method: Isolation of PBMCs was performed from peripheral blood of the subjects of the studied groups (20 women with URSA as a case group, and 20 control women). The effects of 1,25VitD3 (50 nM, for 24 hours) on the studied parameters were evaluated and were compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells and Th17 cells. For gene expression measurement and cytokines assay, Realtime PCR and ELISA were carried out. Results: The proportion of regulatory T cells was markedly lower, while the proportion of Th17 cells in women with URSA was considerably higher than in the control group (P=0.01, P=0.01). The ratio of the frequency of Tregs to the baseline (1,25VitD3/Untreated) increased, while the ratio of the frequency of Th17 cells to the baseline decreased in women with URSA relative to the controls (P= 0.01, P=0.04). 1,25VitD3 increased IL-10 expressions at both the protein and mRNA levels in PBMCs in women with URSA relative to the control group (P=0.0001, P=0.04). TGF-β levels in the cultured supernatants decreased significantly in the case group in the presence of 1,25Vit- D3 relative to the controls (P=0.03). 1,25VitD3 treatment also significantly decreased gene expressions of IL-6, IL-17A, and IL-23 in PBMCs of women with URSA (P=0.01, P=0.001, P=0.0005), as well as the levels of those cytokines in cell culture supernatants (P=0.03, P=0.02, P=0.01, respectively) in women with URSA relative to the controls. Conclusion: According to the findings of this research, modulation of immune responses by 1,25VitD3 is accomplished by strengthening Tregs function and inhibiting inflammatory responses of Th17 cells, which may have a positive impact on pregnancy outcome. Thus, as an immunomodulating agent, VitD3 may be effective in reducing the risk of URSA.

Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment., Graphical abstract, circRNAs have been found to have great pre-clinical diagnostic and therapeutic values in various diseases. In this study, we characterized a novel circRNA, circRNA-DURSA, which is downregulated in URSA placental villus and exerts regulatory roles through the circRNA-DURSA/miR-760/HIST1H2BE axis in trophoblasts. These findings may provide novel mechanistic and clinical insights for future management of URSA.

Introduction Lymphocyte immunotherapy (LIT) is believed to be a viable treatment for unexplained recurrent spontaneous abortion (URSA), but its effect remains controversial. This study aims to investigate the clinical effect of LIT in patients with URSA and clarify the factors that may influence the outcome of LIT. Methods This study included a total of 704 URSA patients, of which 444 patients accepted LIT treatment. URSA patients that did not accept LIT served as control group. Clinical characteristics were collected and analyzed between LIT and control group. The blocking antibody was tested before and after LIT. The outcome of LIT treatment was recorded. Logistic regression analysis was applied to evaluate the independent predictors of LIT success. Results After LIT treatment, 77.9% (346/444) of USRA patients turned to BA positive, and the conversion rate elevated with increased LIT (p, Immunotherapy effectively induced the production of blocking antibody. Immunotherapy improved pregnancy rate and live birth rate in patients with unexplained recurrent spontaneous abortion

The economic and operational risks associated with mass transport complexes (MTCs) in deepwater hydrocarbon exploration act as a principal motivation to investigate their depositional elements using industry data. There is a lack of extensive seismic and well data coverage that limits the understanding of the processes associated with the evolution of MTCs within deepwater sedimentary basins. This study leverages a unique integrated data set to evaluate the depositional character and potential failure mechanisms of seven identified MTCs preserved in a synkinematic mid-Pleistocene MTC-dominant interval that spans the hydrocarbon-bearing Mars Ursa Basin in the northern Gulf of Mexico. Through seismic interpretation and attribute extraction methods using a 3D prestack depthmigrated seismic survey, we have determined the kinematic indicators and preserved the morphodomain geometries of the identified MTCs. The MTC-dominant interval covers an area of 631 km2, a volume of 392 km3, and a maximum thickness of 549 m in minibasin centers. The interval is penetrated by 15 boreholes that provide stratigraphic and lithologic calibration of the morphometric analyses. The lithologic composition of the MTC-rich interval is claystone/mudstone-dominant with a few interbedded, thin sandstones. The identified kinematic indicators and geometric extent of the identified MTCs are a function of the local salt tectonics extrabasinal controls. The stratigraphic framework presented in this study constrains the timing of failures to a period of high sediment deposition related to a major increase of glacial input into the Quaternary Mississippi Fan. This study offers borehole-calibrated MTC morphometrics preserved in an MTC-dominant interval whose failure is triggered by local salt inflation, but ultimately it is a consequence of loading following increased sediment supply into the basin. The results from this robust data set build upon past integrated seismic-well studies that strive to improve the understanding of MTC processes and their implications in hydrocarbon exploration across salt sedimentary basins.

While Iliad 10,251–253 has often been translated correctly, Odyssey 12,312 (≈14,483) has not fared nearly as well, although the meaning is basically the same. Whether this means that the author of Iliad 10 improved on the Odyssey or not, Odyssey 12,312 is best understood as meaning “But when it was the third part of the night and the stars had already completed a considerable part of their paths.” In the second part of this article it is argued that τeίρeα in Iliad 18,485 means not all stars or constellations, but just the most conspicuous ones, which explains why in Iliad 18,487–489 = Odyssey 5,273–275 it is asserted that only the Great Bear is barred from bathing in the ocean, a problem already debated in antiquity: the seven stars of Ursa maior forming the Big Dipper constitute the only conspicuous group of stars which was circumpolar in archaic Greece. The latter theory, an overlooked explanation of Walter Leaf, can be supported by further evidence.

Introduction. Ursa Major is the constellation most venerated by Mongolic peoples. Goals. The article seeks to examine related beliefs traced in folklore and collected field data, reveal key mythological characteristics, and cast light upon diachronous layers in the beliefs of Kalmyks and Oirats (Western Mongols). So, the work aims at analyzing basic Kalmyk and Oirat folklore plots dealing with origins of the Great Bear in comparison to those of other Mongolic cultures; and at examining the concept of Ursa Major against the background of some calendar rites and revered mythological images with due regard of contemporary ceremonies addressed to the constellation. Materials. The paper analyzes folklore and ethnographic materials. Results. Part 1 of the article identifies main variants of mythological texts about Ursa Major (Mong. Долоон бурхан, Долоон өвгөн, Kalm. Долан бурхн, Долан одн) existing in Kalmyk and Oirat discourses, comparing the latter to myths of other Mongolic populations. It shows that basically the myths narrate about seven male characters (siblings, sworn brothers, or thieves) or an ox-man, though etymology of terms may tie the constellation (its emergence) to the archaic plot of day and night alternation as a chase of shedeer, and the solar theme at large. Part 2 further analyzes Ursa Major-related beliefs and compares the latter to some calendar rites and mythological images revered in Kalmyk and Oirat culture. The paper informs that the constellation was sometimes referred to by the Oirats as ‘Seven Maral Deer’ (Oir. Долоон марал), which implies our analysis may extend to the legend of how the heavenly hunter pursued a flock of she-deer. The Oirat oral tradition believes that both the characters of Ursa Major stories and Khukhedei Mergen the Hunter (whose chase made three she-deer turn into the three stars of Orion’s Belt therefore referred to by the Mongols as ‘Three She-Deer’, Mong. Гурван марал, Kalm. Һурвн марл) can be considered masters of the two horses tied to the ‘Golden Pole’ (i.e. Pole Star) — two stars of Ursa Minor. Oirats and Kalmyks also associate Ursa Major with thawing weather, protection of children, livestock (from wolves), and increase of its numbers, remission of sins — similar functions attributed to the White Old Man (Kalm. Цаhан аав) revered by the Oirats as the Lord of the Altai, while Kalmyks tend to view him as a protector deity of the nation, one of his manifestations being that of the Lord of the Year (Kalm. Җилин эзн). The article also analyzes contemporary Buddhist rites dealing with Ursa Major among Mongolic populations.

Objective To investigate the significance of T helper type 1 (Th1)/Th2 cytokines in the pathogenesis of unexplained recurrent spontaneous abortion (URSA), and reveal the value of single cytokines and their proportions in early diagnosis. Methods A total of 44 URSA patients (URSA group), 51 patients with adverse pregnancy history (ad-pregnancy group), and 42 healthy volunteers with normal pregnancy (pregnancy group) were recruited for a cross-sectional study from July 2018 to April 2019 in the Second Xiangya Hospital. Pregnancies involving chromosomal abnormalities, infection, autoimmune diseases, and anatomical abnormalities were excluded. Flow cytometry was used to determine the level of Th1/Th2 cytokines in peripheral blood. Results The level of interleukin-6 (IL-6) in the peripheral blood of the ad-pregnancy group was significantly higher than in the other two groups. The ratio of interferon-γ (IFN-γ)/IL-4 in the URSA group was significantly higher than that of the pregnancy group. The area under the curve for IFN-γ/IL-4 was 0.821, with high diagnostic efficiency, and sensitivity as high as 84.09%. Conclusion Laboratory testing for IL-6 is not recommended for the diagnosis or monitoring of URSA. The variable IFN-γ/IL-4 can be used for the initial diagnosis of URSA to reduce the rate of missed diagnosis. This ratio was more important than the expression of a single cytokine in the Th1/Th2 immune response.

With the increasing number of users in blockchain-based cryptocurrencies, the public has raised the demand for transaction throughput, and many protocols are designed to improve the throughput following the Nakamoto consensus. Although astonishing progress has been made in the on-chain throughput improvement, high throughput makes the blockchains suffer from the increasing blockchain size, hard forks, and possible attacks. In this work, we propose a quantitative model to describe and analyze the Nakamoto consensus. We then design a robust scheme named Ursa to reduce storage requirements and to reduce the forks by automatically adjusting block size according to users’ needs.

The U.S. Gulf of Mexico (GoM) geology is well known for prolific structural hydrocarbon traps created by salt tectonics. In many areas, these structures lie below salt overhangs or thick canopies, requiring advanced seismic imaging to identify prospects and plan exploration wells. Ever-evolving geophysical technologies, such as 3D seismic, wide azimuth, multiwide azimuth, coil, and ocean-bottom node (OBN) acquisition designs, have unlocked the image for some of these structures over the past three decades. Recently, automatic velocity model building methods, particularly full-waveform inversion (FWI), introduced another step change in the subsalt image quality and refocused the acquisition methods on the need to acquire long-offset data. To make such a long-offset program affordable, a new survey geometry was set up with sparse OBN nodes and simultaneous shooting. The actual survey was acquired in 2019 and fully processed within 15 months from the end of the acquisition. Offsets up to 65 km were recorded, enabling FWI velocity updates down to 15 km depth. To provide the reader with a glimpse of the geologic insight that the new technology enabled, we report a few examples of deep geology revealed by this survey in a hydrocarbon- and seismic-data-rich area of the GoM — the Greater Mars-Ursa Basin.

Background The male factor may contribute to unexplained recurrent spontaneous abortion (URSA). The relationship between semen factors and URSA is largely unknown. The analysis of metabolomics which is broadly acknowledged as the omics closest to the phenotype is suitable for providing assistance in the semen parameters analysis. Methods We conducted a study including couples with URSA and controls which was next combined with a meta-analysis, and finally the study included 2352 subjects on semen parameters and URSA. Metabolomics analysis was conducted to detect semen metabolic factors related to URSA in total of 106 samples including seminal plasma and sperm cells. Results The URSA group had significantly lower total sperm count, sperm concentration, motility and normal morphology percentage. Meta-analysis next showed consistent findings. Metabolomics revealed that 4 metabolites and one pathway and 8 metabolites and one pathway were significantly associated with URSA in sperm and seminal plasma, respectively. The combination of ascorbic acid and guanine in seminal plasma and hexadecanedioic acid and pyroglutamic acid in sperm showed ability for URSA prediction. Conclusion We provided novel insights into semen indices in relation to URSA. Lower sperm number and quality might increase the risk of URSA, and oxidative stress and hormone metabolism in sperm as well as nucleic acid synthesis and oxidative stress in seminal plasma were related to URSA.

A decline of T regulatory cell (Treg) number and function is associated with unexplained recurrent spontaneous abortion (URSA). However, the mechanism of downregulation of Tregs in URSA patients is still unknown. This study aimed to investigate the changes of Tregs in URSA patients and the epigenetic regulation for these changes. Venous blood samples were collected from 20 patients with URSA and 20 healthy control subjects. Treg number and inhibitory capacity, and Foxp3 mRNA expression and Foxp3 TSDR methylation were compared between the 2 groups. Correlations between Treg frequency and inhibitory function and TSDR methylation status were examined by Spearman's correlation. The proportion of Tregs within the population of CD4+ T cells and the expression of Foxp3 mRNA was significantly lower in URSA patients than in healthy control subjects. Tregs from URSA patients and healthy controls both significantly inhibited the cytotoxic activity of natural killer (NK) cells toward K562 targets; however, the inhibitory ability of Tregs from URSA patients was significantly lower than that from healthy controls. The methylation level of the Treg-specific demethylated region (TSDR) in the Foxp3 gene was significantly greater in URSA patients than in the controls, and the level of methylation was inversely correlated with the proportion of Tregs and Foxp3 mRNA expression in the peripheral blood. However, the methylation level was not correlated with the inhibitory function of Tregs. A decrease of Treg number and function may be related to the pathogenesis of URSA, and Foxp3 hypermethylation may be associated with the decreased Treg number.

Unexplained recurrent spontaneous abortion (URSA) is believed to be associated with impaired immunosuppression at the maternal-fetal interface, but the detailed molecular mechanism remains unclear. The ATP-adenosine metabolic pathway regulated by CD39/CD73 has recently been recognized to be important in immunosuppression. This study aimed to investigate the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in URSA, as well as the possible regulatory mechanism of CD39/CD73 via the TGF-β-mTOR-HIF-1α pathway using clinical samples and cell models. Fewer CD39+ and CD73+ cells were found in the URSA decidual and villous tissue, respectively. Inhibition of CD39 on dNK cells transformed the cells to an activated state with increased toxicity and decreased apoptosis, and changed their cytokine secretion, leading to impaired invasion and proliferation of the co-cultured HTR8/SVneo cells. Similarly, inhibition of CD73 on HTR8/SVneo cells decreased the adenosine concentration in the cell culture media, increased the proportion of CD107a+ dNK cells, and decreased the invasion and proliferation capabilities of the HTR8/SVneo cells. In addition, transforming growth factor-β (TGF-β) triggered phosphorylation of mammalian target of rapamycin (mTOR) and Smad2/Smad3, which subsequently activated hypoxia-inducible factor-1α (HIF-1α) to induce the CD73 expression on the HTR8/SVneo cells. In summary, reduced numbers of CD39+ and CD73+ cells at the maternal-fetal interface, which may be due to downregulated TGF-β-mTOR-HIF-1α pathway, results in reduced ATP-adenosine metabolism and increased dNK cytotoxicity, and potentially contributes to URSA occurrences.

En el marco actual de gestión de servicios online lo habitual es que los usuarios, bien de forma particular o como empleados de una empresa, deban registrarse en los mismos. Como quiera que cada vez es mayor el número de servicios ofrecidos resulta difícil administrar las credenciales para todos ellos. Es un hecho que en la mayoría de los servicios online en los que se registra un usuario acaban teniendo la misma contraseña, con el grave inconveniente que esto supone ya que si la contraseña fuese descubierta quedaría comprometido el acceso a todos los servicios. Dentro de la teoría de la Web 2.0 se propone la potenciación de un modo simple de identificación en las transacciones en la red, similar al del mundo real (como por ejemplo el uso del DNI), que se ha denominado identidad 2.0 o identidad digital. Una herramienta que permite la administración de credenciales para la autenticación por múltiples factores y acceso a los distintos servicios con inicio de sesión único (mismo ID-identificador digital) es la identidad como servicio (Identity as a Service - IDaaS) en la que la gestión de identidad y acceso se presta online por un proveedor externo al servicio al que se quiere acceder, pudiendo hacerse uso de una blockchain como registro de identidades. En este trabajo se debe diseñar un sistema de autenticación IDaaS basado en blockchain para gestionar todas las transacciones relacionadas con la reserva y emisión de billetes en un marco de transporte inteligente en el que intervienen múltiples actores como los viajeros, las agencias de viaje, las compañías de transporte (aéreo, terrestre, …), entidades de pago, etc.

Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA,andITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs,IFNGmay play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.

Background & Objective: Unexplained recurrent spontaneous abortion (URSA) is defined as an unknown cause of occurrence of three or more clinically detectable pregnancy losses before 20 weeks of gestation, but it occurs presumably as a result of the immune system dysfunctions. We supposed that the disruption of semen or spermatozoa might be responsible for the dysfunction of the immune system in women with URSA. Semen and spermatozoa (as antigens) induce female reproductive tract (FRT) immunity. This stimulated immunity is necessary for pregnancy occurrence. The disruption of semen or spermatozoa can be a result of altering a variety of surface molecules on spermatozoa, especially polymorphic human leukocyte antigen (HLA) molecules or antigens. Despite the importance of HLA antigens in reproduction, to the best of our knowledge, no one has studied the relation of HLA expression between spermatozoa and URSA. Therefore, this paper aims to assess this relation. Methods: Semen samples were collected from 15 URSA couples and 20 normal couples. After purification of normal spermatozoa, the HLA class I and II expressions were evaluated by flow cytometry methods. Results: Results showed that the expression of both HLA class I and II by spermatozoa, in URSA couples, was significantly less than the control couples. Conclusion: The decreased expression of polymorphic HLA class Ⅰ and Ⅱ by spermatozoa can be related to URSA occurrence.

Unexplained recurrent spontaneous abortion (URSA) is defined as the loss of two or more consecutive pregnancies before the 20th week of gestation with normal findings on routine screening tests. Our understanding of the cellular and molecular pathogenesis of URSA is still far from complete. Noncoding RNAs (ncRNAs) play a pivotal role in transcription and expression. The functions of ncRNAs may also improve understanding of URSA pathogenesis. Because of their stability in the circulatory system and at the maternal-fetal interface, it may be possible to use ncRNAs as biomarkers for certain disease states. Here, we provide a narrative review of the current state of knowledge about ncRNAs associated with URSA. The possibility of developing a diagnostic tool using ncRNAs is discussed. The underlying mechanisms of how ncRNAs may lead to the onset of URSA are explored in this review.

OBJECTIVE To assess the efficacy of aspirin, prednisone, and multivitamin triple therapy in treating unexplained recurrent spontaneous abortion (URSA). METHODS Data were reviewed from women with early RSA attending a hospital in Beijing, China, 2013-2017. Those with no abnormal indices (e.g., endocrine, coagulation, immune, genetic) were diagnosed as having URSA, and received aspirin, prednisone, and multivitamin therapy (triple therapy group, n=106) or folic acid monotherapy (control group, n=65). Treatment efficacy was evaluated as the rate of successful treatment (12-week pregnancy with obvious embryo and embryonic heart, nuchal translucency thickness

A La Ursa é uma brincadeira carnavalesca do Nordeste do Brasil. O personagem principal é um Urso. É comum encontrar essa expressão no estado de Pernambuco. Com as diversas mudanças na sociedade, a La Ursa também se transformou, incluindo seu som e sua música. Este artigo tem como objetivo descrever e discutir a história da La Ursa em São Caitano-PE, apontando para as transformações da brincadeira durante o carnaval na sua cidade. Foram realizadas entrevistas com o presidente da Associação das La Ursas de São Caitano e com outras pessoas envolvidas com a história e com as modificações da brincadeira. As mudanças necessárias para garantir a existência da La Ursa estão ligadas, sobretudo, a fatores econômicos, políticos e culturais.

Background: The majority of unexplained recurrent spontaneous abortion (URSA) was related to immune abnormalities. Inappropriate changes of microbiota could cause immune disorders. However, the role of uterine cavity microbiota in URSA has not be elucidated and few related studies are available for reference. Methods: Using the double-lumen embryo transfer tubes to collect uterine cavity fluid samples from pregnant women in their first trimester. 16S rRNA sequencing was conducted to analysis the composition and abundance of the microbiota in samples. Findings: We enrolled 10 URSA cases and 28 induced miscarriage cases in their early pregnancy. Microbial communities were detected in all samples of URSA group (100%, n = 10) vs. none of control group (0%, n=28). Two most dominant microbes are Lactobacillus and Curvibacter. Interpretation: This study showed Lactobacillus and Curvibacter dominated colonizing in uterine cavity of URSA patients during early pregnancy and associated with URSA. Changes of dominant microbiota will lead to bad pregnancy outcome. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (grant nos. 81771660 and 81741017), the Science and Technology Planning Project of Guangdong Province (2017A020214018 and 2017A020214003), the Guangdong Natural Science Foundation (2018A030313023 and 2018A030310162), the Science and Technology Planning Project of Guangzhou City Central Universities (201704020034); the 5010 projects of Sun Yat-Sen University (2012006), and the Fundamental Research Funds for the Central Universities (Youth Program12ykpy29). Declaration of Interests: No conflicts of interest in this study. Ethics Approval Statement: Approval for our study was obtained from the Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSEC-KY-KS-2020-146) and written informed consent was obtained from all participants.

Problem Fork Head Box Protein 3 (FOXP3) is an X-linked gene, codes for a master transcription regulatory protein that controls the development and function of immunosuppressive T regulatory (Treg) cells. They are crucial mediators of maternal foetal tolerance and successful pregnancy outcome. The aim of the study is to evaluate the association of FOXP3 rs3761548 functional polymorphism and to assess the serum concentrations of full-length FOXP3 protein in Unexplained Recurrent Spontaneous Abortions (URSA) patients of Southern India. Method of study The study included blood samples from 150 URSA patients and 150 healthy, pregnant parous women. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism was done for rs3761548 FOXP3 genotyping. Serum concentrations of full-length FOXP3 protein were estimated by enzyme-linked immunosorbent assay. Results The frequencies of mutant A allele, CA and AA genotypes of rs3761548 functional polymorphism were significantly elevated in patients compared to healthy, pregnant parous women and exhibited a two, three and twofold increased risk respectively towards URSA. Serum concentrations of full-length FOXP3 protein were high in controls compared to patients (10.14 ± .30 vs. 8.84 ± 1.73 ng/ml; p Conclusion Our results advocate an association of FOXP3 rs3761548 polymorphism and reduced expression of full-length FOXP3 protein with URSA.

Author(s): Singh, Rohit; Galliers, Chris; Appleton, Mike; Hoffmann, Mike; Long, Barney; Cary-Elwes, Joanna; Fritze, Camilla; McCallum, Jamie; Parry Jones, Rob | Abstract: Global biodiversity is declining at an unprecedented rate. The majority of the protected and conserved areas (PCAs) that are the core elements of protecting the world’s biodiversity, and the ecosystem services it provides, are not under sound management. Adequate numbers of competent, well-resourced, and well-led rangers are the foundation for effective management of these PCAs. However, the majority of rangers are unrecognized, under-appreciated, and under-resourced. Rangers operate under poor and dangerous working environments with inadequate employment conditions. The International Ranger Federation (IRF), as a global representative body of rangers, has been working to connect and recognize rangers through several initiatives, including the triennial World Ranger Congress (WRC). The Chitwan Declaration of the 9th WRC, held in Nepal in 2019, strongly encourages those who manage PCAs that employ rangers to identify shortcomings, and thereafter introduce measures to improve outcomes. The Universal Ranger Support Alliance (URSA) is an alliance of seven conservation organizations to support IRF with the implementation of the Chitwan Declaration. URSA has developed a global five-year action plan to accomplish lasting transformation to create a professional, responsible, and accountable ranger workforce that is properly valued, led, and supported. URSA itself and the action plan provide a global platform for individual conservation professionals, rangers, conservation organizations, and ranger employers to work together in supporting rangers—the first responders responsible for maintaining the health of the planet.

Database platform-as-a-service (dbPaaS) is developing rapidly and a large number of databases have been migrated to run on the Clouds for the low cost and flexibility. Emerging Clouds rely on the tenants to provide the resource specification for their database workloads. However, they tend to over-estimate the resource requirement of their databases, resulting in the unnecessarily high cost and low Cloud utilization. A methodology that automatically suggests the “just-enough” resource specification that fulfills the performance requirement of every database workload is profitable. To this end, we propose URSA, a capacity planning and fair scheduling system that is comprised of an online capacity planner, a performance interference estimator, and a contention-aware scheduling engine. The capacity planner identifies the most cost-efficient resource specification for a database workload to achieve the required performance online. The interference estimator quantifies the pressure on the shared resource and the tolerance to the shared resource contention of each workload. The scheduling engine schedules the workloads across Cloud nodes carefully to eliminate unfair performance interference between the co-located workloads. Experimental results show that URSA reduces up to 25.9% of CPU usage, 53.4% of memory and reduces the performance unfairness between the co-located workloads by 47.6% usage compared to the prior works without hurting their performance.

The human implantation failure during first trimester leads to spontaneous abortions. Spontaneous abortions are consecutive and occur twice or thrice (with or without prior live births) due to factors which are either maternal or fetal. However, it also constitutes of unknown etiology; known as unexplained recurrent spontaneous abortions (URSA). In this study, the medical terminated human normal early pregnancies (NEP) of the first trimester were taken as control samples, the normal decidual sample whose molecular and epigenetic changes were compared with that of decidua of human URSA subjects. Apoptosis-related genes reported in consecutive recurrent pregnancy loss became the basis for this study. So, in this study, we evaluated the hypothesis that “p53 methylation level through methyltransferases (G9aMT and DNMT1) implicates the fate of embryo towards sustenance or cessation of pregnancy”. Further, the interaction between P53, BAX, BCL-2, CASPASE-6, G9aMT, DNMT-1, and methylated p53 expression level(s) during the first trimester of both URSA and NEP are included in this study. The degree of p53 methylation during the first trimester is found to be significant and positively correlated with that of G9aMT (p p p p-value

BACKGROUND Estrogen has an important role in unexplained recurrent spontaneous abortion (URSA). Polymorphisms of the ESR1 gene and the ESR2 gene have been identified as risk factors for URSA, but with varied associations in Chinese populations. This study aimed to compare the role of gene polymorphisms of ESR1 and ESR2 and the risk of URSA in the Chinese Hui and Chinese Han populations. MATERIAL AND METHODS Chinese Hui women (n=171) and Chinese Han women (n=234) with URSA were compared with healthy controls (n=417) matched by ethnicity and age. Genotyping was performed using direct sequencing and identified three polymorphisms of the ESR1 gene (rs9340799, rs2234693, and rs3798759) and three polymorphisms of the ESR2 gene (rs207764, rs4986938, and rs1256049). The association between ESR1 and ESR2 gene polymorphisms and the risk of URSA was evaluated statistically using the odds ratio (OR) and 95% confidence interval (CI). RESULTS No association was detected between the allelic, dominant, and recessive models of ESR1 and ESR2 gene polymorphisms and the risk of URSA in Chinese Han and Hui populations (p>0.05). The distribution of the AGT haplotype containing ESR2 gene polymorphisms rs2077647A, rs4986938G, and rs1256049T was significantly reduced in patients with URSA compared with controls in the Chinese Hui population (OR, 0.29; 95% CI, 0.14-0.62; p=0.0009; padj=0.005). CONCLUSIONS The AGT haplotype of the ESR2 gene containing the polymorphism rs2077647A, rs4986938G, and rs1256049T (ESR2 hapAGT) was a protective factor for URSA in women in the Chinese Hui population when compared with the Chinese Han population.

Monotask is a unit of work that uses only a single type of resource (e.g., CPU, network, disk I/O). While monotask was primarily introduced as a means to reason about job performance, in this paper we show that this fine-grained, resource-oriented abstraction can be leveraged by job schedulers to maximize cluster resource utilization. Although recent cluster schedulers have significantly improved resource allocation, the utilization of the allocated resources is often not high due to inaccurate resource requests. In particular, we show that existing scheduling mechanisms are ineffective for handling jobs with dynamic resource usage, which exists in common workloads, and propose a resource negotiation mechanism between job schedulers and executors that makes use of monotasks. We design a new framework, called Ursa, which enables the scheduler to capture accurate resource demands dynamically from the execution runtime and to provide timely, fine-grained resource allocation based on monotasks. Ursa also enables high utilization of the allocated resources by the execution runtime. We show by experiments that Ursa is able to improve cluster resource utilization, which effectively translates to improved makespan and average JCT.

Background Unexplained recurrent spontaneous abortion (URSA) is defined as two or more consecutive pregnancy losses, generally of unknown cause; it is related to a failure of fetal–maternal immunological tolerance. Regulatory T cells (Tregs) exert immunosuppressive effects, which are essential to maintain fetal–maternal immunological tolerance and regulate immune balance. In this study, we used the specific cell-surface phenotype of CD4+CD25highCD127low/− Tregs to investigate the number and suppressive function of Tregs isolated from the peripheral blood of patients with URSA with the aim of expanding our understanding of their role in URSA. Methods We isolated a relatively pure population of peripheral CD4+CD25highCD127low/− Tregs and CD4+CD25− responder T cells (Tresps) from the patients with URSA and normal fertile nonpregnant control women via fluorescence-activated cell sorting. We compared the frequency, suppressive capacity, and forkhead box transcription factor P3 (FOXP3) expression of Tregs in the peripheral blood between patients with URSA and normal controls. Results The frequency of CD4+CD25highCD127low/− Tregs in the peripheral blood was lower in URSA patients than in the controls (P FOXP3 mRNA expression in Tregs was also significantly lower in the URSA patients (P P P P Conclusions We observed a lower frequency of peripheral CD4+CD25highCD127low/− Tregs with lower FOXP3 expression in the peripheral blood of URSA patients. In addition, highly purified Tregs from patients with URSA exhibited impaired suppressive effects. The defect in immune regulation in URSA patients appears to be primarily related to impaired Tregs, and not to increased resistance of Tresps to suppression. Our findings reveal a potential novel therapeutic target for URSA.