Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to Restrain Mitotic Progression following DNA Damage

Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA

Anchorage of High-Strength Reinforcing Bars with Standard Hooks - Initial Tests

The effects of embedment length, side cover, quantity of confining transverse reinforcement, location of hook (inside or outside the column core), concrete compressive strength, hooked bar size, and hook bend angle on anchorage capacity are investigated using the results of 329 tests of standard hooks loaded in tension. No. 5, 8, and 11 hooks were tested in beam-column joints with concrete compressive strengths ranging from 4,300 to 13,700 psi. The results of the tests are compared with the provisions in ACI 318-11, and equations to describe the anchorage strength of 90° hooks for hooks not confined by transverse reinforcement, hooks confined by two No. 3 ties, and hooks confined by No. 3 ties spaced at 3db are developed. Hooks cast inside the column core have greater ultimate anchorage force than those cast outside the column core, hook bend angle has a negligible effect on ultimate anchorage force, and ultimate anchorage force increases as the quantity of confining transverse reinforcement increases. For hooks not confined by transverse reinforcement, the anchorage capacity increases more rapidly than embedment length. For hooks confined by transverse reinforcement, small embedment lengths develop significant anchorage forces; increases in embedment length result in additional capacity, but anchorage capacity is less than proportional to embedment length. Comparisons to the provisions in ACI 318-11 show that the ultimate anchorage force of larger hooked bars and the effect of concrete compressive strength are overpredicted by the current design requirements. Analysis of 90° hooks cast inside the column core show that there is an increase in ultimate anchorage force with an increase in bar diameter; this effect increases as the quantity of confining transverse reinforcement increases within the range of values evaluated in this study. Ultimate anchorage force also increases with an increase in cover to the center of the bar for bars not confined by transverse reinforcement; this effect decreases as the quantity of transverse reinforcement increases and has no effect for bars confined by No. 3 ties spaced at 3db

Aboriginal and Torres Strait Islander Peoples' perceptions of foot and lower limb health : a systematic review

Background: Ongoing colonisation produces inequity in healthcare delivery and inequality in healthcare outcomes for Aboriginal and Torres Strait Islander Peoples. As a consequence, within the domain of lower limb health, foot disease has severe impacts for First Nations Peoples. Central to developing culturally safe healthcare and driving positive foot health change for First Nations Peoples, is the need for health professionals to develop understanding of First Nations perspectives of foot health. The aim of this systematic review was to evaluate studies investigating Aboriginal and Torres Strait Islander Peoples’ perceptions of foot and lower limb health. Methods: PubMeD, Ovid (Embase, Emcare, Medline), CINAHL, Informit Indigenous collection, and grey literature sources were searched to 23rd July 2021. We included any published reports or studies that examined Aboriginal and Torres Strait Islander Peoples’ perceptions of foot and lower limb health, or meanings of, or attitudes to, foot and lower limb health. Results: Four studies with a total of 1515 participants were included. Studies found that Aboriginal and Torres Strait Islander people self-assessed foot health with a demonstrated ability to perceive their feet as healthy relative to Western clinical measures of peripheral blood supply and neurological function. Footwear, including ill-fitting or lack of footwear was considered a contributing factor to reduced foot and lower limb health. Foot pain affected up to 60% of participants with up to 70% of foot pain untreated. Lack of access to culturally safe health care delivered by culturally capable health professionals was perceived to contribute to worse foot and lower limb health outcomes. Conclusions: Aboriginal and Torres Strait Islander Peoples’ perceptions of foot and lower limb health are influenced by multiple complex interrelated factors. The limited number of studies in this area indicates ongoing failings to consult First Nations Peoples regarding their own lower limb and foot health. It is therefore essential that healthcare service and cultural capability implementation is led by Aboriginal and Torres Strait Islander Peoples in co-design. Urgent need for further research that exemplifies design and delivery of culturally safe care is required

Graduate Teaching Communities of Practice: Fostering a Sense of Belonging and Professional Development for Graduate Students, by Graduate Students

Communities of Practice provide explicit formal recognition for teaching work and serve as a network of pedagogical resources. Communities of Practice create a safe space and a strengthened sense of community. Communities of Practice can be formed anywhere to meet any set of needs but always thrive with members’ agency and institutional support

The temporal evolution of subduction initiation in the Samail ophiolite: high-precision U–Pb zircon petrochronology of the metamorphic sole

High-precision dating of the metamorphic sole of ophiolites can provide insight into the tectonic evolution of ophiolites and subduction zone processes. To understand subduction initiation beneath a young, well-preserved and well-characterized ophiolite, we performed coupled zircon laser-ablation inductively coupled mass spectrometry trace element analyses and high-precision isotope dilution-thermal ionization mass spectrometry U–Pb dating on 25 samples from the metamorphic sole of the Samail ophiolite (Oman-United Arab Emirates). Zircon grains from amphibolite- to granulite-facies (0.8–1.3 GPa, ~700–900°C), garnet- and clinopyroxene-bearing amphibolite samples (n = 18) show systematic trends of decreasing heavy rare earth element slope (HREE; Yb/Dy) with decreasing Yb concentration, reflecting progressive depletion of the HREE during prograde garnet growth. For half of the garnet-clinopyroxene amphibolite samples, Ti-in-zircon temperatures increase, and U–Pb dates young with decreasing HREE slope, consistent with coupled zircon and garnet growth during prograde metamorphism. In the remaining samples, there is no apparent variation in Ti-in-zircon temperature with decreasing HREE slope, and the combined U–Pb and geochemical data suggest zircon crystallization along either the prograde to peak or prograde to initial retrograde portions of the metamorphic P–T–t path. The new data bracket the timing of prograde garnet and zircon growth in the highest grade rocks of the metamorphic sole between 96.698 ± 0.094 and 95.161 ± 0.064 Ma, in contrast with previously published geochronology suggesting prograde metamorphism at ~104 Ma. Garnet-free amphibolites and leucocratic pods from lower grade (but still upper amphibolite facies) portions of the sole are uniformly HREE enriched (Yb/Dy > 5) and are ~0.5–1.3 Myr younger than the higher grade rocks from the same localities, constraining the temporal offset between the metamorphism and juxtaposition of the higher and lower grade units. Positive zircon εHf (+6.5 to +14.6) for all but one of the dated amphibolites are consistent with an oceanic basalt protolith for the sole. Our new data indicate that prograde sole metamorphism (96.7–95.2 Ma) immediately predated and overlapped growth of the overlying ophiolite crust (96.1–95.2 Ma). The ~600 ky offset between the onset of sole metamorphism in the northern portion of the ophiolite versus the start of ophiolite magmatism is an order of magnitude shorter than previously proposed (~8 Ma) and is consistent with either spontaneous subduction initiation or an abbreviated period of initial thrusting during induced subduction initiation. Taken together, the sole and ophiolite crust preserve a record of the first ~1.5 Myr of subduction. A gradient in the initiation of high-grade metamorphism from the northwest (96.7 Ma) to southeast (96.0–95.7 Ma) may record propagation of the nascent subduction zone and/or variations in subduction rate along the length of the ophiolite

Extending gravitational wave burst searches with pulsar timing arrays

Pulsar timing arrays (PTAs) are being used to search for very low frequency gravitational waves. A gravitational wave signal appears in pulsar timing residuals through two components: one independent of and one dependent on the pulsar's distance, called the 'Earth term' (ET) and 'pulsar term' (PT), respectively. The signal of a burst (or transient) gravitational wave source in pulsars' residuals will in general have the Earth and pulsar terms separated by times of the order of the time of flight from the pulsar to the Earth. Therefore, both terms are not observable over a realistic observation span, but the ETs observed in many pulsars should be correlated. We show that pairs (or more) of pulsars can be aligned in such a way that the PTs caused by a source at certain sky locations can arrive at Earth within a time window short enough to be captured during a realistic observation span. We find that for the pulsars within the International Pulsar Timing Array (IPTA) ~67 per cent of the sky produces such alignments for pulsars terms separated by less than 10 years. We compare estimates of the source event rate that would be required to observe one signal in the IPTA if searching for the correlated ETs, or in searching via the PTs, and find that event rates would need to be about two orders of magnitude higher to observe an event with the PTs than the ETs. We also find that an array of hundreds of thousands of pulsars would be required to achieve similar numbers of observable events in PT or ET searches. This disfavours PTs being used for all-sky searches, but they could potentially be used target specific sources and be complementary to ET only searches.Comment: version accepted for MNRA

Conventional and High-Strength Hooked Bars—Part 1: Anchorage Tests

This paper presents the results of an experimental study on the anchorage strength of conventional and high-strength steel hooked bars. Three hundred and thirty-seven exterior beam-column joint specimens were tested with compressive strengths ranging from 4300 to 16,500 psi (30 to 114 MPa). Parameters investigated included the number of hooked bars per specimen, bar diameter, side cover, amount of confining reinforcement, hooked bar spacing, hook bend angle, hook placement, and embedment length. Bar stresses at failure ranged from 22,800 to 144,100 psi (157 and 994 MPa). The majority of the hooked bars failed by a combination of front and side failure, with front failure being the dominant failure mode. Test results show that development lengths of hooked bars calculated based on ACI 318-14 are very conservative for No. 5 (No. 16) bars and become progressively less conservative with increasing bar size and concrete compressive strength

Anchorage of High-Strength Reinforcing Bars with Standard Hooks

Hooked bars are used to anchor reinforcing steel where member dimensions prevent straight bars from developing their full yield strength. Prior to the current study, the quantity of data has been limited with regards to the capacity of hooked bars–particularly when high-strength steel or concrete is used. As a result, current design provisions in ACI 318-14 limit yield strength and concrete compressive strength to 80,000 psi and 10,000 psi, respectively, for the purpose of determining the development length of hooked bars. The purpose of this study was to determine the critical factors that affect the anchorage strength of hooked bars in concrete and to develop new design guidelines for development length allowing for the use of high-strength reinforcing steel and concrete. In this study, a total of 337 beam-column joint specimens were tested. Parameters included number of hooks (2, 3, or 4), concrete compressive strength (4,300 to 16,510 psi), bar diameter (No. 5, No. 8, and No. 11), concrete side cover (1.5 to 4 in.), amount of transverse reinforcement in the joint region, hooked bar spacing (3db to 11db center-to-center), hook bend angle (90° or 180°), placement of the hook (inside or outside the column core, and inside or outside of the column compressive region), and embedment length. The results of this study show that current ACI 318-14 code provisions are unconservative for larger hooked bars and higher compressive strength concrete. The effect of concrete compressive strength on the anchorage capacity of hooked bars is less than represented by the 0.5 power currently used in ACI provisions; the 0.25 power provides a more realistic estimate of capacity. The addition of confining transverse reinforcement in the hook region increases the anchorage capacity of hooked bars–the value of the increase depends on the quantity of confining reinforcement per hooked bar. Hooked bars with 90° and 180° bend angles exhibit similar capacities, and no increase in capacity was observed when increasing side cover from 2.5 to 3.5 in. Anchoring a hooked bar outside the column core or outside the compressive region of a column provides less capacity than anchoring the hooks at the far side of a beam-column joint or in a wall with a high side cover. Hooked bars also exhibit a reduction in capacity if the center-to-center spacing is less than seven bar diameters. These observations are used to develop a new design equation that allows for the conservative design of hooked bars

On the Interstellar Medium and Star Formation Demographics of Galaxies in the Local Universe

We present a demographic analysis of integrated star formation and gas properties for a sample of galaxies representative of the overall population at z~0. This research was undertaken in order to characterise the nature of star formation and interstellar medium behaviour in the local universe, and test the extent to which global star formation rates can be seen as dependent on the interstellar gas content. Archival 21 cm derived HI data are compiled from the literature, and are combined with CO (J=1-0) derived H_2 masses to calculate and characterise the total gas content for a large sample of local galaxies. The distribution in stellar mass-normalised HI content is found to exhibit the noted characteristic transition at stellar masses of ~3x10^10 M_sun, turning off towards low values, but no such transition is observed in the equivalent distribution of molecular gas. H-alpha based star formation rates and specific star formation rates are also compiled for a large (1110) sample of local galaxies. We confirm two transitions as found in previous work: a turnover towards low SFRs at high luminosities, indicative of the quenching of SF characteristic of the red sequence; and a broadening of the SF distribution in low-luminosity dwarf galaxies, again to extremely low SFRs of < 0.001 M_sun/yr. However, a new finding is that while the upper luminosity transition is mirrored by the turn over in HI content, suggesting that the low SFRs of the red sequence result from a lack of available gas supply, the transition towards a large spread of SFRs in the least luminous dwarf galaxies is not matched by a prominent increase in scatter in gas content. Possible mass-dependent quenching mechanisms are discussed, along with speculations that in low mass galaxies, the H-alpha luminosity may not faithfully trace the SFR.Comment: 15 pages, 12 figures; accepted for publication in MNRA