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The article focuses on the Beyceğiz Tumulus, located 11.5 km east of Gordion, which was subjected to multiple looting attempts, leading to a salvage excavation conducted between 2013 and 2017. It reveals that the tumulus, identified as a cenotaph, contained no burial or ritual deposits but rather a stone platform at its center, surrounded by guide walls, highlighting the architectural and planning expertise involved in its construction.

This study aimed to examine changes in emergency department (ED) visits for ambulatory care sensitive conditions (ACSCs) among uninsured or Medicaid-covered Black, Hispanic, and White adults aged 26–64 in the first 5 years of the Affordable Care Act Medicaid expansion. Using 2010–2018 inpatient and ED discharge data from nine expansion and five nonexpansion states, an event study difference-in-differences regression model was used to estimate changes in number of annual ACSC ED visits per 100 adults ("ACSC ED rate") associated with the 2014 Medicaid expansion, overall and by race/ethnicity. A secondary outcome was the proportion of ACSC ED visits out of all ED visits ("ACSC ED share"). Analyses were conducted in 2022–2023. Medicaid expansion was associated with no change in ACSC ED rates among all, Black, Hispanic, or White adults. When excluding California, where most counties expanded Medicaid before 2014, expansion was associated with a decrease in ACSC ED rate among all, Black, Hispanic, and White adults. Expansion was also associated with a decrease in ACSC ED share among all, Black, and White adults. White adults experienced the largest reductions in ACSC ED rate and share. Medicaid expansion was associated with reductions in ACSC ED rates in some expansion states and reductions in ACSC ED share in all expansion states combined, with some heterogeneity by race/ethnicity. Expansion should be coupled with policy efforts to better link newly insured Black and Hispanic patients to non-ED outpatient care, alongside targeted outreach and expanded primary care capacity, which may reduce disparities in ACSC ED visits. [ABSTRACT FROM AUTHOR]

Objective: To estimate changes in the emergency department (ED) visit rate, hospitalization share of ED visits, and ED visit volumes associated with Medicaid expansion among Hispanic, Black, and White adults. Data Collection/Extraction Methods: For the population of adults aged 26–64 with no insurance or Medicaid coverage, we obtained census population and ED visit counts during 2010–2018 in nine expansion and five nonexpansion states. Main Outcomes and Measures: The primary outcome was the annual number of ED visits per 100 adults ("ED rate"). The secondary outcomes were the share of ED visits leading to hospitalization, total number ("volumes") of all ED visits, ED visits leading to discharge ("treat‐and‐release") and ED visits leading to hospitalization ("transfer‐to‐inpatient"), and the share of the study population with Medicaid ("Medicaid share"). Study Design: An event‐study difference in differences design that contrasts pre‐ versus post‐expansion changes in outcomes in Medicaid expansion and nonexpansion states. Principal Findings: In 2013, the ED rate was 92.6, 34.4, and 59.2 ED visits among Black, Hispanic, and White adults, respectively. The expansion was associated with no change in ED rate in all three groups in each of the five post‐expansion years. We found that expansion was associated with no change in the hospitalization share of ED visits and the volume of all ED visits, treat‐and‐release ED visits, and transfer‐to‐inpatient ED visits. The expansion was associated with an 11.7% annual increase (95% CI, 2.7%–21.2%) in the Medicaid share of Hispanic adults, but no significant change among Black adults (3.8%; 95% CI, −0.04% to 7.7%). Conclusion: ACA Medicaid expansion was associated with no changes in the rate of ED visits among Black, Hispanic, and White adults. Expanding Medicaid eligibility may not change ED use, including among Black and Hispanic subgroups. [ABSTRACT FROM AUTHOR]

This paper considers copper production in the Niari Basin, Republic of the Congo, during a period dated to the mid-fifteenth–mid-seventeenth centuries CE. Using a combination of pXRF, OM, SEM–EDS, and FTIR, it assesses the microstructure and composition of slags and technical ceramics from sites associated with two different regional pottery traditions: Moubiri-type at the site of Kingoyi near Mindouli and Kindangakanzi-type at Kindangakanzi near Boko-Songho. Both sites are characterised by the use of refractory domestic pottery as crucibles for copper smelting. Moubiri-type pottery is alumina-rich, while Kindangakanzi-type pottery is formed from a magnesia-rich clay, a crucible type unique in sub-Saharan Africa. Similarities in chaînes opératoires at Kingoyi and Kindangakanzi suggest sharing of knowledge at mining and smelting sites, interactions we reconstruct as a metallurgical constellation of practice comprised of the distinct potting communities of practice (see Supplementary information for abstract in Lingala and French). [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) are important in regulating cell cycle transitions, particularly in coordinating DNA replication. Although the role of CDK2 activity on the replication apparatus has been extensively studied, the role of CDK4/6 in DNA replication control is less understood. Through targeted inhibition of CDK4/6 activity, we demonstrate that CDK4/6 kinase activity promotes cdc6 and cdt1 expression, and pre-replication complex (pre-RC) assembly in cycling cells. Conversely, CDK2 inhibition had no effect on the pre-RC assembly. The inhibition of pre-RC assembly is dependent on a functional retinoblastoma (RB) protein, which mediates downstream effects. As such, CDK4/6 inhibition has minimal effect on the replication apparatus in the absence of RB. The requirement of CDK4/6 was further interrogated using cells lacking D-type cyclins, in which replication complexes form normally, and correspondingly CDK4/6 inhibition had no effect on cell cycle or replication control. However, in the absence of D-type cyclins, CDK2 inhibition resulted in the attenuation of cdc6 and cdt1 levels, suggesting overlapping roles for CDK4/6 and CDK2 in regulating replication protein activity. Finally, CDK4/6 inhibition prevented the accumulation of cdc6 and cdt1 as cells progressed from mitosis through the subsequent G1. Combined, these studies indicate that CDK4/6 activity is important in regulating the expression of these critical mediators of DNA replication.Oncogene (2008) 27, 7083–7093; doi:10.1038/onc.2008.319; published online 8 September 2008 [ABSTRACT FROM AUTHOR]

Organisms growing aerobically generate reactive oxygen-containing molecules, such as hydrogen peroxide (H2O2). These reactive oxygen molecules damage enzymes and DNA and may even cause cell death. In response, Bacillus subtilis produces at least nine potential peroxide-scavenging enzymes, two of which appear to be the primary enzymes responsible for detoxifying peroxides during vegetative growth: a catalase (encoded by katA) and an alkylhydroperoxide reductase (Ahp, encoded by ahpC). AhpC uses two redox-active cysteine residues to reduce peroxides to nontoxic molecules. A specialized thioredoxin-like protein, AhpF, is then required to restore oxidized AhpC back to its reduced state. Curiously, B. subtilis has two genes encoding Ahp: ahpC and ahpA. Although AhpC is well characterized, very little is known about AhpA. In fact, numerous bacterial species have multiple ahp genes; however, these additional Ahp proteins are generally uncharacterized. We seek to understand the role of AhpA in the bacterium's defense against toxic peroxide molecules in relation to the roles previously assigned to AhpC and catalase. Our results demonstrate that AhpA has catalytic activity similar to that of the primary enzyme, AhpC. Furthermore, our results suggest that a unique thioredoxin redox protein, AhpT, may reduce AhpA upon its oxidation by peroxides. However, unlike AhpC, which is expressed well during vegetative growth, our results suggest that AhpA is expressed primarily during postexponential growth. [ABSTRACT FROM AUTHOR]

Functional inactivation of the retinoblastoma tumor suppressor gene product (RB) is a common event in human cancers. Classically, RB functions to constrain cellular proliferation, and loss of RB is proposed to facilitate the hyperplastic proliferation associated with tumorigenesis. To understand the repertoire of regulatory processes governed by RB, two models of RB loss were utilized to perform microarray analysis. In murine embryonic fibroblasts harboring germline loss of RB, there was a striking deregulation of gene expression, wherein distinct biological pathways were altered. Specifically, genes involved in cell cycle control and classically associated with E2F-dependent gene regulation were upregulated via RB loss. In contrast, a program of gene expression associated with immune function and response to pathogens was significantly downregulated with the loss of RB. To determine the specific influence of RB loss during a defined period and without the possibility of developmental compensation as occurs in embryonic fibroblasts, a second system was employed wherein Rb was acutely knocked out in adult fibroblasts. This model confirmed the distinct regulation of cell cycle and immune modulatory genes through RB loss. Analyses of cis-elements supported the hypothesis that the majority of those genes upregulated with RB loss are regulated via the E2F family of transcription factors. In contrast, those genes whose expression was reduced with the loss of RB harbored different promoter elements. Consistent with these analyses, we found that disruption of E2F-binding function of RB was associated with the upregulation of gene expression. In contrast, cells harboring an RB mutant protein (RB-750F) that retains E2F-binding activity, but is specifically deficient in the association with LXCXE-containing proteins, failed to upregulate these same target genes. However, downregulation of genes involved in immune function was readily observed with disruption of the LXCXE-binding function of RB. Thus, these studies demonstrate that RB plays a significant role in both the positive and negative regulations of transcriptional programs and indicate that loss of RB has distinct biological effects related to both cell cycle control and immune function.Oncogene (2007) 26, 6307–6318; doi:10.1038/sj.onc.1210450; published online 23 April 2007 [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Biomechanical human cadaveric study. OBJECTIVE: We hypothesized that increasing compressive preload will reduce the segmental instability after nucleotomy, posterior ligament resection, and decompressive surgery. SUMMARY OF BACKGROUND DATA: The human spine experiences significant compressive preloads in vivo due to spinal musculature and gravity. Although the effect of destabilization procedures on spinal motion has been studied, the effect of compressive preload on the motion response of destabilized, multisegment lumbar spines has not been reported. METHODS: Eight human cadaveric spines (L1-sacrum, 51.4 ± 14.1 yr) were tested intact, after L4-L5 nucleotomy, after interspinous and supraspinous ligaments transection, and after midline decompression (bilateral laminotomy, partial medial facetectomy, and foraminotomy). Specimens were loaded in flexion (8 Nm) and extension (6 Nm) under 0-N, 200-N, and 400-N compressive follower preload. L4-L5 range of motion (ROM) and flexion stiffness in the high-flexibility zone were analyzed using repeated-measures analysis of variance and multiple comparisons with the Bonferroni correction. RESULTS: With a fixed set of loading conditions, a progressive increase in segmental ROM along with expansion of the high-flexibility zone (decrease of flexion stiffness) was noted with serial destabilizations. Application of increasing compressive preload did not substantially change segmental ROM, but did significantly increase the segmental stiffness in the high-flexibility zone. In the most destabilized condition, 400-N preload did not return the segmental stiffness to intact levels. CONCLUSION: Anatomical alterations representing degenerative and iatrogenic instabilities are associated with significant increases in segmental ROM and decreased segmental stiffness. Although application of compressive preload, mimicking the effect of increased axial muscular activity, significantly increased the segmental stiffness, it was not restored to intact levels; thereby suggesting that core strengthening alone may not compensate for the loss of structural stability associated with midline surgical decompression. This suggests that there may be a role for surgical implants or interventions that specifically increase flexion stiffness and limit flexion ROM to counteract the iatrogenic instability resulting from surgical decompression.Level of Evidence: N/A. [ABSTRACT FROM AUTHOR]