353 research outputs found
Maryland\u27s Family Divisions Are a Model for Change
In fiscal year 2014, 43 percent of all cases filed in Maryland’s trial court of general jurisdiction (the circuit court) were family law cases (Court Operations Department, 2014: CC-5). Historically, Maryland courts, like many states’ family justice systems, lacked a uniform structure to consolidate family law issues for an individual family. As a result, families often faced multiple hearings before different judges in different courtrooms to address a variety of issues, such as divorce, domestic violence, delinquency, and child abuse/neglect. This system created tremendous hardship for families (particularly low-income families, many of whom were self-represented litigants) and resulted in fragmented service delivery and inconsistent decision making. Through the leadership and dedication of former Chief Judge Robert M. Bell, in 1998 the judges of the Maryland Court of Appeals signed Maryland Rule 16-204 (see Babb, 2013: 1126). This rule created family divisions in the circuit courts of Maryland’s five largest jurisdictions and transformed how Maryland courts handle family law cases
Maryland\u27s Family Divisions Are a Model for Change
In fiscal year 2014, 43 percent of all cases filed in Maryland’s trial court of general jurisdiction (the circuit court) were family law cases (Court Operations Department, 2014: CC-5). Historically, Maryland courts, like many states’ family justice systems, lacked a uniform structure to consolidate family law issues for an individual family. As a result, families often faced multiple hearings before different judges in different courtrooms to address a variety of issues, such as divorce, domestic violence, delinquency, and child abuse/neglect. This system created tremendous hardship for families (particularly low-income families, many of whom were self-represented litigants) and resulted in fragmented service delivery and inconsistent decision making. Through the leadership and dedication of former Chief Judge Robert M. Bell, in 1998 the judges of the Maryland Court of Appeals signed Maryland Rule 16-204 (see Babb, 2013: 1126). This rule created family divisions in the circuit courts of Maryland’s five largest jurisdictions and transformed how Maryland courts handle family law cases
Better Environment, Better Staff
The article discusses result of a survey addressing the quality of work life among audit personnel in the U.S. The result shows that dissatisfaction in the work environment affects staff\u27s performance. Creating customer value is one of the issues in business establishment. As stated, clients are demanding the expertise that comes with experiences. The quality of work environment may persuade outstanding staff members to pursue other career options. Financial rewards of public accounting are not the basis for changes in the rating of staff
The Causal Structure of Emotions in Aristotle: Hylomorphism, Causal Interaction between Mind and Body, and Intentionality
Recently, a strong hylomorphic reading of Aristotelian emotions has been put forward, one that allegedly eliminates the problem of causal interaction between soul and body. Taking the presentation of emotions in de An. I 1 as a starting point and basic thread, but relying also on the discussion of Rh. II, I will argue that this reading only takes into account two of the four causes of emotions, and that, if all four of them
are included into the picture, then a causal interaction of mind and body remains within Aristotelian emotions, independent of how strongly their hylomorphism is understood. Beyond the discussion with this recent reading, the analysis proposed of the fourfold causal structure of emotions is also intended as a hermeneutical starting point for a comprehensive analysis of particular emotions in Aristotle. Through the different causes Aristotle seems to account for many aspects of the complex phenomenon of emotion, including its physiological causes, its mental causes, and its intentional object
Does Vesta Have Moons?
Previous searches for moons around Vesta have found nothing to an upper limit of 22.5 magnitude, that corresponds to 44 +/- 4 m diameter assuming the same albedo as Vesta. The Dawn mission's approach phase has dedicated satellite search observations consisting of two mosaic sequences bracketing the first observations of a complete rotation of Vesta scheduled for early July, 2011. In addition, we use the approach optical navigation image sequences for initial satellite searches. We will report any findings from these observations, and upper limits of magnitude and size
Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.
BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC.
METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months.
RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019).
CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies
Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells
The forkhead-box protein P3 (Foxp3) is a key transcription factor for the development and suppressive activity of regulatory T cells (Tregs), a T cell subset critically involved in the maintenance of self-tolerance and prevention of over-shooting immune responses. However, the transcriptional regulation of Foxp3 expression remains incompletely understood. We have previously shown that epigenetic modifications in the CpG-rich Treg-specific demethylated region (TSDR) in the Foxp3 locus are associated with stable Foxp3 expression. We now demonstrate that the methylation state of the CpG motifs within the TSDR controls its transcriptional activity rather than a Treg-specific transcription factor network. By systematically mutating every CpG motif within the TSDR, we could identify four CpG motifs, which are critically determining the transcriptional activity of the TSDR and which serve as binding sites for essential transcription factors, such as CREB/ATF and NF-κB, which have previously been shown to bind to this element. The transcription factor Ets-1 was here identified as an additional molecular player that specifically binds to the TSDR in a demethylation-dependent manner in vitro. Disruption of the Ets-1 binding sites within the TSDR drastically reduced its transcriptional enhancer activity. In addition, we found Ets-1 bound to the demethylated TSDR in ex vivo isolated Tregs, but not to the methylated TSDR in conventional CD4+ T cells. We therefore propose that Ets-1 is part of a larger protein complex, which binds to the TSDR only in its demethylated state, thereby restricting stable Foxp3 expression to the Treg lineage
Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development
SummaryThe impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating TÂ cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators
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