Ageing: collagenase‐mediated collagen fragmentation as a rejuvenation target

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108666/1/bjd13267.pd

Landscape genetics reveal broad and fine‐scale population structure due to landscape features and climate history in the northern leopard frog (Rana pipiens) in North Dakota

Prehistoric climate and landscape features play large roles structuring wildlife populations. The amphibians of the northern Great Plains of North America present an opportunity to investigate how these factors affect colonization, migration, and current population genetic structure. This study used 11 microsatellite loci to genotype 1,230 northern leopard frogs (Rana pipiens) from 41 wetlands (30 samples/wetland) across North Dakota. Genetic structure of the sampled frogs was evaluated using Bayesian and multivariate clustering methods. All analyses produced concordant results, identifying a major east–west split between two R. pipiens population clusters separated by the Missouri River. Substructuring within the two major identified population clusters was also found. Spatial principal component analysis (sPCA) and variance partitioning analysis identified distance, river basins, and the Missouri River as the most important landscape factors differentiating R. pipiens populations across the state. Bayesian reconstruction of coalescence times suggested the major east– west split occurred ~13–18 kya during a period of glacial retreat in the northern Great Plains and substructuring largely occurred ~5–11 kya during a period of extreme drought cycles. A range‐wide species distribution model (SDM) for R. pipiens was developed and applied to prehistoric climate conditions during the Last Glacial Maximum (21 kya) and the mid‐Holocene (6 kya) from the CCSM4 climate model to identify potential refugia. The SDM indicated potential refugia existed in South Dakota or further south in Nebraska. The ancestral populations of R. pipiens in North Dakota may have inhabited these refugia, but more sampling outside the state is needed to reconstruct the route of colonization. Using microsatellite genotype data, this study determined that colonization from glacial refugia, drought dynamics in the northern Great Plains, and major rivers acting as barriers to gene flow were the defining forces shaping the regional population structure of R. pipiens in North Dakota

Zink rotary kiln seal: Cam followers. Revision 1

The CIF will treat hazardous and mixed low-level radioactive waste in a rotary kiln and secondary combustion chamber. A high efficiency air pollution control system follows the secondary chamber. The rotary kiln is designed with a gas seal at each end of its rotating barrel which provides a barrier between the interior of the kiln and outside air. The internal pressure of the rotary kiln will be maintained below atmospheric pressure, so exterior air passing the seals is forced into the kiln`s interior. Positive pressure may be applied in the seal labyrinth, adding a barrier to flow. Both CIF seals will be covered entirely with exhaust hoods, drawing air over the outside of the seal and into a HEPA filtered exhaust system. Cam follower misalignment on a John Zink rotary kiln seal caused damage to the seal`s rotor. The misalignment was quantified, corrected, and checked to verify straightness. The primary purpose of the correction was to allow seal testing 1 to continue, but the information is applicable to the Consolidated Incineration Facility (CIF) since two large seals of similar design will be installed there. Cam follower straightness was off as much as 3.5{degrees}, causing followers to run untrue on the rotor. High contact forces resulted, removing flakes of metal from the rotor surface. The misalignment caused weight bearing followers on one side of the seal to back out of their threaded mounts. The root cause was poor machining of the follower mounting holes. Correction was accomplished by relieving the holes and installing machined spacers and retaining nuts. Cam followers on the CIF`s Zink seals should be inspected for straightness before the seals are installed

High-precision determination of the critical exponents for the lambda-transition of 4He by improved high-temperature expansion

We determine the critical exponents for the XY universality class in three dimensions, which is expected to describe the $\lambda$-transition in ${}^4$He. They are obtained from the analysis of high-temperature series computed for a two-component $\lambda\phi^4$ model. The parameter $\lambda$ is fixed such that the leading corrections to scaling vanish. We obtain $\nu = 0.67166(55)$, $\gamma = 1.3179(11)$, $\alpha=-0.0150(17)$. These estimates improve previous theoretical determinations and agree with the more precise experimental results for liquid Helium.Comment: 8 pages, revte

25th-order high-temperature expansion results for three-dimensional Ising-like systems on the simple cubic lattice

25th-order high-temperature series are computed for a general nearest-neighbor three-dimensional Ising model with arbitrary potential on the simple cubic lattice. In particular, we consider three improved potentials characterized by suppressed leading scaling corrections. Critical exponents are extracted from high-temperature series specialized to improved potentials, obtaining $\gamma=1.2373(2)$, $\nu=0.63012(16)$, $\alpha=0.1096(5)$, $\eta=0.03639(15)$, $\beta=0.32653(10)$, $\delta=4.7893(8)$. Moreover, biased analyses of the 25th-order series of the standard Ising model provide the estimate $\Delta=0.52(3)$ for the exponent associated with the leading scaling corrections. By the same technique, we study the small-magnetization expansion of the Helmholtz free energy. The results are then applied to the construction of parametric representations of the critical equation of state, using a systematic approach based on a global stationarity condition. Accurate estimates of several universal amplitude ratios are also presented.Comment: 40 pages, 15 figure

The Electron Spectral Function in Two-Dimensional Fractionalized Phases

We study the electron spectral function of various zero-temperature spin-charge separated phases in two dimensions. In these phases, the electron is not a fundamental excitation of the system, but rather ``decays'' into a spin-1/2 chargeless fermion (the spinon) and a spinless charge e boson (the chargon). Using low-energy effective theories for the spinons (d-wave pairing plus possible N\'{e}el order), and the chargons (condensed or quantum disordered bosons), we explore three phases of possible relevance to the cuprate superconductors: 1) AF*, a fractionalized antiferromagnet where the spinons are paired into a state with long-ranged N\'{e}el order and the chargons are 1/2-filled and (Mott) insulating, 2) the nodal liquid, a fractionalized insulator where the spinons are d-wave paired and the chargons are uncondensed, and 3) the d-wave superconductor, where the chargons are condensed and the spinons retain a d-wave gap. Working within the $Z_2$ gauge theory of such fractionalized phases, our results should be valid at scales below the vison gap. However, on a phenomenological level, our results should apply to any spin-charge separated system where the excitations have these low-energy effective forms. Comparison with ARPES data in the undoped, pseudogapped, and superconducting regions is made.Comment: 10 page

Teaching in the COVID-19 era: Understanding the opportunities and barriers for teacher agency

The school closures necessitated by the COVID-19 pandemic created a rapid shift to alternative modes of educational delivery, primarily online learning and teacher-supported home-schooling. This shift has revealed deep inequities in education systems worldwide, as many children lost access to teachers and schooling. An effective response to these changes has tested teachers’ personal capacities and individual and collective agency intensely. The research lab we report on within this paper aimed to develop a better understanding of teacher agency in meeting the challenges of the pandemic and the physical and relational enablers and constraints of their environment. Drawing on case study reports from six international contexts and a series of online discussions with research lab participants, this study explores teachers’ enactment of agency in the context of various circumstances and environments. The authors argue that it is imperative that education systems support the enhancement of teachers’ personal and collective agency in the face of continued disruption to schooling and ongoing challenges to educational equity

ARQ-197, a small-molecule inhibitor of c-Met, reduces tumour burden and prevents myeloma-induced bone disease in vivo

The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit. We hypothesized that ARQ-197 (Tivantinib), a small molecule c-Met inhibitor, would reduce myeloma cell growth and prevent myeloma-associated bone disease in a murine model. In vitro we assessed the effects of ARQ-197 on myeloma cell proliferation, cytotoxicity and c-Met protein expression in human myeloma cell lines. In vivo we injected NOD/SCID-γ mice with PBS (non-tumour bearing) or JJN3 cells and treated them with either ARQ-197 or vehicle. In vitro exposure of JJN3, U266 or NCI-H929 cells to ARQ-197 resulted in a significant inhibition of cell proliferation and an induction of cell death by necrosis, probably caused by significantly reduced levels of phosphorylated c-Met. In vivo ARQ-197 treatment of JJN3 tumour-bearing mice resulted in a significant reduction in tumour burden, tumour cell proliferation, bone lesion number, trabecular bone loss and prevented significant decreases in the bone formation rate on the cortico-endosteal bone surface compared to the vehicle group. However, no significant differences on bone parameters were observed in non-tumour mice treated with ARQ-197 compared to vehicle, implying that in tumour-bearing mice the effects of ARQ-197 on bone cells was indirect. In summary, these res ults suggest that ARQ-197 could be a promising therapeutic in myeloma patients, leading to both a reduction in tumour burden and an inhibition of myeloma-induced bone disease

Landscape genetics reveal broad and fine‐scale population structure due to landscape features and climate history in the northern leopard frog (Rana pipiens) in North Dakota

Prehistoric climate and landscape features play large roles structuring wildlife populations. The amphibians of the northern Great Plains of North America present an opportunity to investigate how these factors affect colonization, migration, and current population genetic structure. This study used 11 microsatellite loci to genotype 1,230 northern leopard frogs (Rana pipiens) from 41 wetlands (30 samples/wetland) across North Dakota. Genetic structure of the sampled frogs was evaluated using Bayesian and multivariate clustering methods. All analyses produced concordant results, identifying a major east–west split between two R. pipiens population clusters separated by the Missouri River. Substructuring within the two major identified population clusters was also found. Spatial principal component analysis (sPCA) and variance partitioning analysis identified distance, river basins, and the Missouri River as the most important landscape factors differentiating R. pipiens populations across the state. Bayesian reconstruction of coalescence times suggested the major east– west split occurred ~13–18 kya during a period of glacial retreat in the northern Great Plains and substructuring largely occurred ~5–11 kya during a period of extreme drought cycles. A range‐wide species distribution model (SDM) for R. pipiens was developed and applied to prehistoric climate conditions during the Last Glacial Maximum (21 kya) and the mid‐Holocene (6 kya) from the CCSM4 climate model to identify potential refugia. The SDM indicated potential refugia existed in South Dakota or further south in Nebraska. The ancestral populations of R. pipiens in North Dakota may have inhabited these refugia, but more sampling outside the state is needed to reconstruct the route of colonization. Using microsatellite genotype data, this study determined that colonization from glacial refugia, drought dynamics in the northern Great Plains, and major rivers acting as barriers to gene flow were the defining forces shaping the regional population structure of R. pipiens in North Dakota