Suppose (X,Ω,g) is a compact Spin(7)-manifold, e.g. a Riemannian 8-manifold with holonomy Spin(7), or a Calabi–Yau 4-fold. Let G be U(m) or SU(m), and P→X be a principal G-bundle. We show that the ...infinite-dimensional moduli space BP of all connections on P modulo gauge is orientable, in a certain sense. We deduce that the moduli space MPSpin(7)⊂BP of irreducible Spin(7)-instanton connections on P modulo gauge, as a manifold or derived manifold, is orientable. This improves theorems of Cao and Leung 9 and Muñoz and Shahbazi 42.
If X is a Calabi–Yau 4-fold, the derived moduli stack M of (complexes of) coherent sheaves on X is a −2-shifted symplectic derived stack (M,ω) by Pantev–Toën–Vaquié-Vezzosi 46, and so has a notion of orientation by Borisov–Joyce 7. We prove that (M,ω) is orientable, by relating algebro-geometric orientations on (M,ω) to differential-geometric orientations on BP for U(m)-bundles P→X, and using orientability of BP.
This has applications to defining Donaldson–Thomas type invariants counting semistable coherent sheaves on a Calabi–Yau 4-fold, as in Donaldson and Thomas 15, Cao and Leung 8, and Borisov and Joyce 7.
During routine genome duplication, many potential replication origins remain inactive or 'dormant'. Such origin dormancy is achieved, in part, by an interaction with the metabolic sensor SIRT1 ...deacetylase. We report here that dormant origins are a group of consistent, pre-determined genomic sequences that are distinguished from baseline (i.e. ordinarily active) origins by their preferential association with two phospho-isoforms of the helicase component MCM2. During normal unperturbed cell growth, baseline origins, but not dormant origins, associate with a form of MCM2 that is phosphorylated by DBF4-dependent kinase (DDK) on serine 139 (pS139-MCM2). This association facilitates the initiation of DNA replication from baseline origins. Concomitantly, SIRT1 inhibits Ataxia Telangiectasia and Rad3-related (ATR)-kinase-mediated phosphorylation of MCM2 on serine 108 (pS108-MCM2) by deacetylating the ATR-interacting protein DNA topoisomerase II binding protein 1 (TOPBP1), thereby preventing ATR recruitment to chromatin. In cells devoid of SIRT1 activity, or challenged by replication stress, this inhibition is circumvented, enabling ATR-mediated S108-MCM2 phosphorylation. In turn, pS108-MCM2 enables DDK-mediated phosphorylation on S139-MCM2 and facilitates replication initiation at dormant origins. These observations suggest that replication origin dormancy and activation are regulated by distinct post-translational MCM modifications that reflect a balance between SIRT1 activity and ATR signaling.
Students with a foster care background experience significant disparity in enrollment and postsecondary completion when compared to their peers without foster care experience. A number of barriers ...exist that may impact college persistence and completion. Finances and inadequate financial aid are often identified as a primary concern for students with a foster care background who are attending college. Using a national sample, this study examined the relationship between receipt of financial aid and the likelihood of completing a postsecondary credential among students with a foster care background. Findings indicate that financial aid has a positive relationship with earning a postsecondary credential, however, other sources of financial support and services were not always indicative of positive outcomes. Study findings reinforce the importance of social support, postsecondary education support services, academic support services, and employment as postsecondary education promoters. Several policy and practice implications are discussed that are relevant in postsecondary education settings, and child welfare settings.
•Developing a comprehensive procedure for repairing concrete structures.•The procedure can aid civil engineers in modeling and selecting suitable repair materials according to a set of predefined ...criteria.•The procedure is able to cover almost all criteria and technical requirements for concrete repair.•Using VIKOR method to handle the target base criteria in the procedure.
The premature failure of repaired concrete structures has become a big concern for civil engineers in recent years. While premature failure can be greatly reduced through the selection of an appropriate repair material, civil engineers must take into account a large number of conflicting criteria for candidate repair materials to make the final decision. In this paper, a procedure coupled with the VIKOR method is proposed to obtain the best repair material for concrete structures. This procedure can aid civil engineers in modeling and selecting suitable repair materials according to a set of predefined criteria. A case study is included to validate the accuracy of the outcomes of the proposed procedure. Since weights play a significant role in the ranking of results for the repair materials, sensitivity analysis is conducted using three different methods for assigning weights to find more reliable results.
Safeguards against excess DNA replication are often dysregulated in cancer, and driving cancer cells towards over-replication is a promising therapeutic strategy. We determined DNA synthesis patterns ...in cancer cells undergoing partial genome re-replication due to perturbed regulatory interactions (re-replicating cells). These cells exhibited slow replication, increased frequency of replication initiation events, and a skewed initiation pattern that preferentially reactivated early-replicating origins. Unlike in cells exposed to replication stress, which activated a novel group of hitherto unutilized (dormant) replication origins, the preferred re-replicating origins arose from the same pool of potential origins as those activated during normal growth. Mechanistically, the skewed initiation pattern reflected a disproportionate distribution of pre-replication complexes on distinct regions of licensed chromatin prior to replication. This distinct pattern suggests that circumventing the strong inhibitory interactions that normally prevent excess DNA synthesis can occur via at least two pathways, each activating a distinct set of replication origins.
In 2004, Colorado introduced the nation's first voucher model for financing public higher education. With state appropriations now allocated to students, rather than institutions, state officials ...expect this model to create cost efficiencies while also expanding college access. Using difference-in-difference regression analysis, we find limited evidence that these outcomes occurred within the 4-year sector; however, the policy increased cost efficiencies among community college and reduced college access for some underrepresented groups. The paper discusses the challenges of applying market-based reforms to public higher education.
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