Pure phase-encoded MRI and classification of solids

Here, the authors combine a pure phase-encoded magnetic resonance imaging (MRI) method with a new tissue-classification technique to make geometric models of a human tooth. They demonstrate the feasibility of three-dimensional imaging of solids using a conventional 11.7-T NMR spectrometer. In solid-state imaging, confounding line-broadening effects are typically eliminated using coherent averaging methods. Instead, the authors circumvent them by detecting the proton signal at a fixed phase-encode time following the radio-frequency excitation. By a judicious choice of the phase-encode time in the MRI protocol, the authors differentiate enamel and dentine sufficiently to successfully apply a new classification algorithm. This tissue-classification algorithm identifies the distribution of different material types, such as enamel and dentine, in volumetric data. In this algorithm, the authors treat a voxel as a volume, not as a single point, and assume that each voxel may contain more than one material. They use the distribution of MR image intensities within each voxel-sized volume to estimate the relative proportion of each material using a probabilistic approach. This combined approach, involving MRI and data classification, is directly applicable to bone imaging and hard-tissue contrast-based modeling of biological solids

PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells

Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity

From Dose to Response: In Vivo Nanoparticle Processing and Potential Toxicity

Adverse human health impacts due to occupational and environmental exposures to manufactured nanoparticles are of concern and pose a potential threat to the continued industrial use and integration of nanomaterials into commercial products. This chapter addresses the inter-relationship between dose and response and will elucidate on how the dynamic chemical and physical transformation and breakdown of the nanoparticles at the cellular and subcellular levels can lead to the in vivo formation of new reaction products. The dose-response relationship is complicated by the continuous physicochemical transformations in the nanoparticles induced by the dynamics of the biological system, where dose, bio-processing, and response are related in a non-linear manner. Nanoscale alterations are monitored using high-resolution imaging combined with in situ elemental analysis and emphasis is placed on the importance of the precision of characterization. The result is an in-depth understanding of the starting particles, the particle transformation in a biological environment, and the physiological response

The Prevalence and Clinical Implications of Comorbid Back Pain in Shoulder Instability: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.

Background:Understanding predictors of pain is critical, as recent literature shows that comorbid back pain is an independent risk factor for worse functional and patient-reported outcomes (PROs) as well as increased opioid dependence after total joint arthroplasty. Purpose/Hypothesis:The purpose of this study was to evaluate whether comorbid back pain would be predictive of pain or self-reported instability symptoms at the time of stabilization surgery. We hypothesized that comorbid back pain will correlate with increased pain at the time of surgery as well as with worse scores on shoulder-related PRO measures. Study Design:Cross-sectional study; Level of evidence, 3. Methods:As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients consented to participate in pre- and intraoperative data collection. Demographic characteristics, injury history, preoperative PRO scores, and radiologic and intraoperative findings were recorded for patients undergoing surgical shoulder stabilization. Patients were also asked, whether they had any back pain. Results:The study cohort consisted of 1001 patients (81% male; mean age, 24.1 years). Patients with comorbid back pain (158 patients; 15.8%) were significantly older (28.1 vs 23.4 years; P < .001) and were more likely to be female (25.3% vs 17.4%; P = .02) but did not differ in terms of either preoperative imaging or intraoperative findings. Patients with self-reported back pain had significantly worse preoperative pain and shoulder-related PRO scores (American Shoulder and Elbow Surgeons score, Western Ontario Shoulder Instability Index) (P < .001), more frequent depression (22.2% vs 8.3%; P < .001), poorer mental health status (worse scores for the RAND 36-Item Health Survey Mental Component Score, Iowa Quick Screen, and Personality Assessment Screener) (P < .01), and worse preoperative expectations (P < .01). Conclusion:Despite having similar physical findings, patients with comorbid back pain had more severe preoperative pain and self-reported symptoms of instability as well as more frequent depression and lower mental health scores. The combination of disproportionate shoulder pain, comorbid back pain and mental health conditions, and inferior preoperative expectations may affect not only the patient's preoperative state but also postoperative pain control and/or postoperative outcomes

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

The effect of phase fluctuations on the single-particle properties of the underdoped cuprates

We study the effect of order parameter phase fluctuations on the single-particle properties of fermions in the underdoped cuprate superconductors using a phenomenological low-energy theory. We identify the fermion-phase field coupling as the Doppler-shift of the quasiparticle spectrum induced by the fluctuating superfluid velocity and we calculate the effect of these fluctuations on the fermion self-energy. We show that the vortex pair unbinding near the superconducting transition causes a significant broadening in the fermion spectral function, producing a pseudogap-like feature. We also discuss the specific heat and show that the phase fluctuation effect is visible due to the short coherence length.Comment: RevTex 11 pages; 11 epsf figures included. Added and updated reference

What caused extinction of the pleistocene megafauna of sahul?

2016 The Author(s) Published by the Royal Society. All rights reserved. During the Pleistocene, Australia and New Guinea supported a rich assemblage of large vertebrates. Why these animals disappeared has been debated for more than a century and remains controversial. Previous synthetic reviews of this problem have typically focused heavily on particular types of evidence, such as the dating of extinction and human arrival, and have frequently ignored uncertainties and biases that can lead to misinterpretation of this evidence. Here, we review diverse evidence bearing on this issue and conclude that, although many knowledge gaps remain, multiple independent lines of evidence point to direct human impact as the most likely cause of extinction

A comprehensive database of quality-rated fossil ages for Sahul\u27s Quaternary vertebrates

The study of palaeo-chronologies using fossil data provides evidence for past ecological and evolutionary processes, and is therefore useful for predicting patterns and impacts of future environmental change. However, the robustness of inferences made from fossil ages relies heavily on both the quantity and quality of available data. We compiled Quaternary non-human vertebrate fossil ages from Sahul published up to 2013. This, the FosSahul database, includes 9,302 fossil records from 363 deposits, for a total of 478 species within 215 genera, of which 27 are from extinct and extant megafaunal species (2,559 records). We also provide a rating of reliability of individual absolute age based on the dating protocols and association between the dated materials and the fossil remains. Our proposed rating system identified 2,422 records with high-quality ages (i.e., a reduction of 74%). There are many applications of the database, including disentangling the confounding influences of hypothetical extinction drivers, better spatial distribution estimates of species relative to palaeo-climates, and potentially identifying new areas for fossil discovery

Equilibrium and nonequilibrium properties associated with the chiral phase transition at finite density in the Gross-Neveu Model

We study the dynamics of the chiral phase transition at finite density in the Gross-Neveu (GN) model in the leading order in large-N approximation. The phase structure of the GN model in this approximation has the property that there is a tricritical point at a fixed temperature and chemical potential separating regions where the chiral transition is first order from that where it is second order. We consider evolutions starting in local thermal and chemical equilibrium in the massless unbroken phase for conditions pertaining to traversing a first or second order phase transition. We assume boost invariant kinematics and determine the evolution of the order parameter $\sigma$, the energy density and pressure as well as the effective temperature, chemical potential and interpolating number densities as a function of the proper time $\tau$. We find that before the phase transition, the system behaves as if it were an ideal fluid in local thermal equilibrium with equation of state $p=\epsilon$. After the phase transition, the system quickly reaches its true broken symmetry vacuum value for the fermion mass and for the energy density. The single particle distribution functions for Fermions and anti-Fermions go far out of equilibrium as soon as the plasma traverses the chiral phase transition. We have also determined the spatial dependence of the "pion" Green's function $<\bar{\psi}(x) \gamma_5 \psi(x) \bar{\psi}(0) \gamma_5 \psi(0)>$ as a function of the proper time.Comment: 39 pages, 23 figure