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We performed a high resolution study of ${0}^{+}$ states in $^{134}\mathrm{Ba}$ using the $^{136}\mathrm{Ba}(p,t)$ two-neutron transfer reaction. Our experiment shows a significant portion of the $L=0$ pair-transfer strength concentrated at excited ${0}^{+}$ levels in $^{134}\mathrm{Ba}$. Potential implications in the context of $^{136}\mathrm{Xe}\phantom{\rule{4pt}{0ex}}\ensuremath{\rightarrow}\phantom{\rule{4pt}{0ex}}^{136}\mathrm{Ba}$ neutrinoless double beta decay matrix element calculations are briefly discussed.

AimsPatients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality.Method and resultsWe used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existent heart disease and in-hospital mortality. 16,511 patients with COVID-19 were included (21.1% aged 66 – 75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male and often had other comorbid conditions when compared to those without. Mortality was higher in patients with cardiac disease (29.7%; n=1545 versus 15.9%; n=1797). However, following multivariable adjustment this difference was not significant (adjusted risk ratio (aRR) 1.08 [95% CI 1.02 – 1.15; p-value 0.12 (corrected for multiple testing)]). Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure aRR (1.19 [1.10 – 1.30]; p-value ConclusionConsiderable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare.

Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression., DNA methylation profiles from 26 bat species accurately predicts chronological age, while longevity-related methylation patterns across the genome suggest that bat longevity results from augmented immune response and cancer suppression.

The $\beta$-decay of neutron-rich $^{129}$In into $^{129}$Sn was studied using the GRIFFIN spectrometer at the ISAC facility at TRIUMF. The study observed the half-lives of the ground state and each of the $\beta$-decaying isomers. The level scheme of $^{129}$Sn has been expanded with thirty-one new $\gamma$-ray transitions and nine new excited levels, leading to a re-evaluation of the $\beta$-branching ratios and level spin assignments. The observation of the $\beta$-decay of the (29/2$^{+}$) 1911-keV isomeric state in $^{129}$In is reported for the first time, with a branching ratio of 2.0(5)$\%$.

This chapter explores working Paulistanos’ access to good jobs and the limits to mobility in the 1920s. By the end of the Old Republic, laborers and liberal professionals comprised São Paulo’s middle class, and a segmented labor market existed with good jobs in commerce, transportation, and the mechanical sector and bad jobs in the textile sector. Interview transcripts and worker profiles show workers valued a high salary, opportunities for training and advancement, and family employment. Established residents and new residents, who were internal migrants, Eastern Europeans, or immigrants from other Southern Cone ports, vied for these good jobs. Despite tightening immigration regulations and increasing cost of living, the city doubled in size. Not everyone had equal access to these positions: a good appearance and the right connections facilitated entry, placing individuals coming directly from the lavoura, who could not afford the city’s overpriced clothing, women, and Afro-Brazilians increasingly at a disadvantage. The search for housing compounded disadvantages, and the working class increasingly built outward, expanding São Paulo’s footprint into the city’s floodplains. The Great Flood of 1929 demonstrated the precariousness of success and limits of opportunity as flood victims sought refuge in the Hospedaria.

This chapter explores working-class residents’ daily lives, standards of living, and challenges in São Paulo between 1891 and 1918. Examining this understudied period underscores the dramatic changes World War I wrought in the city. Wartime shortages disrupted the natural ebb and flow of migration, job opportunities, and urbanization, making a difficult reality more challenging for much of the city’s working class. Some scholars have argued that the war incentivized textile production and encouraged growth, but evidence from immigrant letters and prices demonstrates increased costs for low-quality textiles. The war also cut short job opportunities and educational advancements, saw a slowdown in most standard-of-living measures, and institutionalized the family wage and informality. While city officials founded weekly food markets to assist with rising food costs, these efforts were insufficient. By 1917, the situation had deteriorated enough to provide the necessary conditions for workers, both women and men, to mobilize a general strike.

This chapter explores the textile industry’s response to wartime shortages, postwar overstocks, and sectoral crises in the mid-1920s. In the prewar era, industrialists became accustomed to government intervention and continuous labor supply. The war fundamentally changed the Paulistano labor composition and the state’s relative protection of the textile sector, but industrialists continued to manipulate labor costs by employing children and women. Budget constraints often prevented the implementation of new machinery, but in contrast to other sectors that adopted rationalization, training, and innovation, textile industrialists lobbied for extreme protection, actively dismissed labor laws, and were at the forefront of labor repression. The Centro dos Industriais de Fiação e Tecelagem de São Paulo formed after the 1917 General Strike demonstrates this preference for repressive labor tactics that included blacklists and even disappearing problematic workers. A case study of the Jafet textile factory highlights how these choices negatively impacted workers’ lives. Jafet increasingly employed women for shorter tenures, awarded minimal wage increases to combat the rising cost of living, and relied on blacklists and police intervention. As the company failed to provide schools, training, childcare, and adequate housing, these choices disproportionately impacted women and intensified labor inequities.

This chapter analyzes why São Paulo’s labor organization was weak prior to World War I. It breaks with traditional explorations into organizers, focusing instead on how industrialist interests and state interventions intersected with the motivations and experiences of rank-and-file and non-striking workers. Prior to the 1917 General Strike, industrialists relied on the state’s increasing willingness to provide police intervention and intimidation to guarantee the “freedom to work.” When these measures proved insufficient and strikes persisted, employers could and did look to the Hospedaria to provide replacement workers. Industrialist interests and the state’s willingness to intervene on industrialists’ behalf certainly limited organization success when compared to other Southern Cone immigration centers, but so too did São Paulo’s distinctive nuclear family–centered immigration and workers’ unwillingness to strike. Newspaper accounts reveal rank-and-file divisions, and Hospedaria records explain the phenomenon by demonstrating the large number of nuclear families arriving and living in the city. For those immigrants and Paulistanos with minimal social connections and opportunities, family goals and survival trumped labor organization and camaraderie. These divisions existed across gender and national lines, but evidence suggests that Portuguese and Afro-Brazilians were more likely to be non-striking workers than other groups.

This chapter demystifies how São Paulo’s population expanded from around 65,000 inhabitants in 1890 to roughly one million by 1930. It demonstrates São Paulo distinguished itself as a node of family immigration among immigrant receiving nations in the late nineteenth and early twentieth centuries. Immigrant registrations from the Hospedaria de Imigrantes and calls to immigrate, chamadas, demystify how the state’s immigration program built to support coffee agriculture dramatically impacted the city's growth and allow for distinctions between immigrant groups. There were complex and diverse migration streams to the city. Early Italian migration was followed by unskilled, Portuguese migration between 1903 and 1913, and a skilled German migration in the postwar period. This change signals that World War I marked a turning point in the city from labor-intensive toward capital-intensive growth. The records also suggest the war marked an increase in northeastern migration to São Paulo. In contrast to most regional assumptions, migrants from northeastern Brazil were more literate than many immigrant groups and Brazilians from other regions. Despite their literacy, they were much less likely to be contracted in the city than their European counterparts.

This chapter evaluates the degree of gender, racial, and national discrimination facing Paulistanos using firm-level employment records and complementary education and job evidence. By distinguishing between national groups, standard linear regressions and logit analyses demonstrate three groups faced substantial formal labor market discrimination, albeit to differing degrees and through different mechanisms. Portuguese workers were disproportionately hired into unskilled positions, Afro-Brazilians faced substantial hiring discrimination, and women faced both hiring and wage discrimination. Employers expected Portuguese workers to be unskilled and women to leave the labor market upon marriage, but Afro-Brazilians faced substantial prejudice. Hiring discrimination was consistent across the textile, commercial, railroad, and the urban transportation sectors. Prior to the war, periods of rapid growth and scarce labor supply could lessen racial prejudice and help explain the language of hope drawing Afro-Brazilians to São Paulo, but the postwar period brought a substantial contraction, making Afro-Brazilian women the most consistently excluded. Lifetime consequences of labor market discrimination were substantial, but the period saw minimal organization in opposition. One probable hypothesis explaining why more substantial mobilization did not occur was the class wage discrepancies that paled gendered, racial, and national differences.

The level structure of $^{25}\mathrm{Na}$ and $^{22}\mathrm{Ne}$ in the high excitation energy/high spin regime was studied using $\ensuremath{\gamma}$-ray spectroscopy and Doppler shift lifetime measurements following $^{12}\mathrm{C}(^{18}\mathrm{O},\ensuremath{\alpha}p)^{25}\mathrm{Na}$ and $^{12}\mathrm{C}(^{18}\mathrm{O},2\ensuremath{\alpha})^{22}\mathrm{Ne}$ reactions. Multiple new levels and transitions were identified in both nuclides based on $\ensuremath{\gamma}\text{\ensuremath{-}}\ensuremath{\gamma}$ coincidence data. In $^{25}\mathrm{Na}$, evidence was found for higher-spin negative-parity states up to ${I}^{\ensuremath{\pi}}=13/{2}^{\ensuremath{-}}$ resulting from neutron excitation into the $pf$ shell, in good agreement with shell model calculations using the SDPF-MU and FSU interactions. Candidates for the yrast ${7}^{+}$ and ${8}^{+}$ levels in $^{22}\mathrm{Ne}$, consistent with calculations using the USDB interaction, were also identified.

This book examines the experiences of São Paulo’s diverse working class as they encountered rapid urbanization and industrialization brought on by the coffee boom during Brazil’s Old Republic (1891–1930). It places the rank-and-file at the center of its analysis to understand how macroeconomic trends connected to daily life and individual and family responses to labor market discrimination, inflation, and fluctuating (im)migration. The study emphasizes the family-centered nature of immigration to São Paulo in comparison to other immigrant cities like Buenos Aires and New York City. It shows how World War I exacerbated existing working-class hierarchies and cut short important standard-of-living advancements. The study demonstrates how despite its intended purpose to funnel agricultural laborers into the coffee interior, the city’s immigrant receiving station also played a decisive role in shaping the city of São Paulo, serving both as a safety net for residents and labor supplier for employers. Methodologically, this book embraces both social and economic history, deconstructing the population along racial, ethnic, national, and gender lines. Combining statistical analysis alongside close readings of immigrant letters provides a nuanced analysis of recently arrived Paulistanos from Italy, Portugal, Germany, Lebanon, and Japan and from northeastern Brazil. The research demonstrates how Portuguese, women, and Afro-Brazilians all faced significant labor market discrimination, impacting individual and family decisions about where to work and live and whether to join labor movements. The approach provides a powerful tool to address archival silences, recover embedded narratives, and understand historic underdevelopment.

A high-precision branching ratio measurement for the superallowed Fermi $\beta^{+}$ emitter $^{62}$Ga was performed with the Gamma-Ray Infrastructure for Fundamental Investigations of Nuclei (GRIFFIN) spectrometer at the Isotope Separator and Accelerator (ISAC) radioactive ion beam facility at TRIUMF. The high efficiency of the GRIFFIN spectrometer allowed 63 $\gamma$-ray transitions, with intensities down to $\approx$1 part per million (ppm) per $^{62}$Ga $\beta^{+}$ decay, to be placed in the level scheme of the daughter nucleus $^{62}$Zn, establishing the superallowed $\beta$ branching ratio for $^{62}$Ga decay to be 99.8577$^{+0.0023}_{-0.0029}\%$, a factor of 4 more precise than the previous world average. For several cascades, $\gamma-\gamma$ angular correlation measurements were performed to assign spins and/or determine the mixing ratios of transitions. In particular, the spin of the 2.342 MeV excited state in the daughter nucleus $^{62}$Zn was definitively assigned as $J = 0$. This assignment resolves a discrepancy between previous measurements and has important implications for the isospin symmetry breaking correction, $\delta_{C1}$, in $^{62}$Ga superallowed Fermi $\beta$ decay.

The $\beta^-$ decay of $^{47}$K to $^{47}$Ca is an appropriate mechanism for benchmarking interactions spanning the $sd$ and $pf$ shells, but current knowledge of the $\beta^-$-decay scheme is limited. We have performed a high-resolution, high-efficiency study of the $\beta^-$-decay of $^{47}$K with the GRIFFIN spectrometer at TRIUMF-ISAC. The study revealed 48 new transitions, a more precise value for the $^{47}$K half-life (17.38(3)~s), and new spin and parity assignments for eight excited states. Levels placed for the first time here raise the highest state observed in $\beta^-$ decay to within 568(3) keV of the $Q$-value and confirm the previously measured large $\beta^-$-decay branching ratios to the low-lying states. Previously unobserved $\beta^-$-feeding to 3/2$^+$ states between 4.5 and 6.1~MeV excitation energy was identified with a total $\beta^-$-feeding intensity of 1.29(2)\%. The sum of the $B(GT)$ values for these states indicates that the $1s_{1/2}$ proton hole strength near this excitation energy is comparable to the previously known $1s_{1/2}$ proton and neutron hole strengths near 2.6 MeV.

Severe obesity is increasingly common in youth and young adults, but outcomes following bariatric surgery remain largely unknown. The purpose of this study was to examine the trends, clinical characteristics, and postoperative outcomes of youth who underwent bariatric surgery.This retrospective cohort study was conducted using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data registry from 2015 to 2018 inclusive. All youth and young adults aged 15-24 who underwent elective sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) were included. Bivariate analysis of trends, clinical characteristics, and postoperative outcomes was performed using Chi-squared tests for categorical variables and independent two sample t test for continuous variables. Multivariable logistic regression modeling was used to determine patient and operative factors predictive of serious complications.A total of 21,592 youth and young adults underwent bariatric surgery during the study time frame, representing 3.7% of total cases (n = 583,567) within the MBSAQIP. The cohort had a mean age of 21.5 ± 2.0 years and a mean BMI of 47.2 ± 8.0 kg/mBariatric surgery in youth is safe but comprised only 3.7% of total MBSAQIP cases from 2015 to 2018. These data should serve as a call to government and healthcare agencies to develop policies and strategies that prioritize bariatric surgery for young people living with severe obesity.

The Ge80 structure was investigated in a high-statistics β-decay experiment of Ga80 using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, β-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 02+ 639-keV level suggested as evidence for low-energy shape coexistence in Ge80. Large-scale shell model calculations performed in Ge78,80,82 place the 02+ level in Ge80 at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in Ge80.

Bats hold considerable potential for understanding exceptional longevity because some species can live eight times longer than other mammals of similar size [1]. Estimating their age or longevity is difficult because they show few signs of aging. DNA methylation (DNAm) provides a potential solution given its utility for estimating age [2-4] and lifespan [5-7] in humans. Here, we profile DNAm from wing biopsies of nearly 700 individuals representing 26 bat species and demonstrate that DNAm can predict chronological age accurately. Furthermore, the rate DNAm changes at age-informative sites is negatively related to longevity. To identify longevity-informative sites, we compared DNAm rates between three long-lived and two short-lived species. Hypermethylated age and longevity sites are enriched for histone and chromatin features associated with transcriptional regulation and preferentially located in the promoter regions of helix-turn-helix transcription factors (TFs). Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results, in part, from augmented immune response and cancer suppression.

Spectroscopy of doubly magic $^{132}_{50}$Sn$_{82}$ has been performed with the GRIFFIN spectrometer at TRIUMF-ISAC following the $\beta$ decay of $^{132}_{49}$In$_{83}$. The analysis has allowed for the placement of a total of 70 transitions and 29 excited states in $^{132}$Sn. Detailed spectroscopy has also been performed on $^{131}$Sb, resulting from the $\beta$ decay of $^{131}$Sn, produced from the $\beta$-delayed neutron decay of $^{132}$In. Measurement of $\gamma$-rays in both $^{131}$Sn and $^{131}$Sb has led to the determination of the $\beta$-delayed neutron emission probability, $P_{n}$, from $^{132}$In. This is the first time the $P_{n}$ has been measured for this nucleus using $\gamma$ spectroscopy, and the new value of 12.3(4)% is consistent with the most recent $\beta-n$ counting experiment. Additionally, $\gamma$-$\gamma$ angular correlations have been performed in $^{132}$Sn, supporting the spin assignments of several excited states. Novel ab initio calculations are presented which describe several of the excited states, and these are compared to the experimental spectrum.

Cold acclimation by sustained downregulation of PSII was studied in intact leaves of an Australian mistletoe Amyema miquelii (Lehm. ex Miq.) Tiegh. and its host Eucalyptus. The trends were followed from autumn to spring on leaves that had developed in summer and were exposed to different microclimates with progress of the seasons. In sun leaves of mistletoe, efficiency of excitation energy transfer from light-harvesting pigments to Chl a molecules in PSII core complexes was markedly reduced in winter. Concomitantly, a band in 77K fluorescence emission spectra emerged at 715 nm, in the same way as the cold-hard band found in overwintering snow gum seedlings (Gilmore and Ball 2000, Proceedings of the National Academy of Sciences USA 97, 11 098–11 101). Further, a distinct band, which presumably involves Chl-b-containing antennae complexes, appeared at 705 nm in –2°C fluorescence emission spectra with decreasing intensity of the PSII band. Much shorter PSII fluorescence lifetimes measured in sun leaves of mistletoe that were exhibiting sustained downregulation of PSII indicated enhanced thermal dissipation of excitation energy. Winter acclimation symptoms of the photosynthetic apparatus were more striking in mistletoe sun leaves compared with eucalypt sun leaves. Because the light and temperature environments of sun leaves are similar for the parasite and host, we primarily attribute the enhanced light-acclimation symptoms to the limited photosynthetic capacity of A. miquelii in winter.

Infrared video thermography was used to study space and time dependence of freezing in intact, attached leaves of snow gum (Eucalyptus pauciflora Sieb. ex Spreng.) seedlings. Freezing initiated in the midvein and spread through the apoplast at 10 mm s–1. Freezing of apoplastic water was detected by a local, rapid increase in temperature, and was followed by a slower increase in leaf temperature to the equilibrium freezing temperature as symplastic water moved from cells to extracellular sites of ice formation. The duration of freezing varied with position, leaf thickness and water content. Most of the cellular water in the leaf tip and margins froze quickly, while freezing was slower near the petiole and midvein. Regions that had frozen more rapidly then began to cool more rapidly, producing steep gradients in leaf temperatures and hence also freeze-induced dehydration. Thus, spatial variation in physical properties of leaves could affect the distribution of minimum leaf temperatures, and hence, the distribution and extent of damage due to freeze-induced dehydration. These results are consistent with patterns of freezing damage in autumn when the duration of freezing may be insufficient for the whole leaf to freeze before sunrise, and may explain the general observation of increased leaf water content and thickness with altitude.

Freeze-induced damage to leaf tissues was studied at different states of acclimation to low temperatures in snow gum, Eucalyptus pauciflora Sieber ex Sprengel. Intact, attached leaves of plants grown under glasshouse or field conditions were frozen at natural rates (frost-freezing) and thawed under laboratory conditions. Leaves were cryo-fixed unfrozen, during frost-freezing or after thawing for observation in a cryo-scanning electron microscope. Frost-freezing in unacclimated tissues caused irreversible tissue damage consistent with tissue death. Intracellular ice formed in the cambium and phloem, killing the cells and leaving persistent gaps between xylem and phloem. Many other cells were damaged by frost-freeze-induced dehydration and failed to resorb water from thawed extracellular ice, leaving substantial amounts of liquid water in intercellular spaces. In contrast, acclimated leaves showed reversible tissue displacements consistent with leaf survival. In these leaves during freezing, massive extracellular ice formed in specific expansion zones within the midvein. On thawing, water was resorbed by living cells, restoring the original tissue shapes. Possible evolutionary significance of these expansion zones is discussed. Acclimated leaves showed no evidence of intracellular freezing, nor tissue lesions caused by extracellular ice. While the observations accord with current views of freeze-sensitivity and tolerance, cryo-microscopy revealed diverse responses in different tissue types.

From detailed spectroscopy of Cd-110 and Cd-112 following the beta(+)/EC decay of In-110,In-112 and the beta(-) decay of Ag-112, the presence of very weak decay branches from nonyrast states is revealed. In Cd-112, 2(5)(+) -> 0(4)(+) and 4(6)(+) -> 2(5)(+) transitions are observed that yield B(E2; 2(5)(+) -> 0(4)(+)) = 34 +/- 15 W.u. and B(E2; 4(6)(+) -> 2(5)(+)) = 77 +/- 30 W.u., respectively, clearly indicating a collective structure. In 110Cd, a weak decay branch from the 4(6)(+) level to the 2(5)(+) level is observed, and from a lifetime measurement following the (n, n gamma' reaction, B(E2; 4(6)(+) -> 2(5)(+)) = 55 +/- 14 W.u. is determined. A new branch is also observed for the decay of the 6(4)(+) level to the 4(6)(+) state, indicating that the sequence 2(5)(+), 4(6)(+), and 6(4)(+) forms part of a collective structure. The presence of 3(3)(+) and 5(2)(+) levels spaced between the previous sequence is highly suggestive of a gamma band built on the 0(2)(+) shape-coexisting intruder state. The 0(4)(+) levels in Cd-110,Cd-112,Cd-114 have preferred decays to the lowest 2(+) members of the intruder bands, and for 114Cd a previous measurement had established an enhanced B(E2; 0(4)(+) -> 2(3)(+)). The energy systematics of the 0(2)(+), 0(3)(+), and 0(4)(+) levels all display the characteristic parabolic-shaped pattern, suggesting that they are built on multiparticle-multihole proton excitations. The results are compared with beyond-mean-field calculations that reproduce qualitatively the observed levels and their decays and suggest that the 0(1)(+), 0(2)(+), 0(3)(+), and 0(4)(+) levels and the excited states built on them possess different deformations.

Summary Objective Lysosomes are the major catabolic organelle of the cell and regulate the macromolecular and organelle turnover and programmed cell death. Here, we investigated the lysosome dysfunction in cartilage and its role in chondrocytes apoptosis and the associated mechanism. Design Lysosomal acidification in Osteoarthritis (OA) and aged cartilage was determined by LysoSensor staining. Lysosomal function in chondrocytes was blocked by siRNA mediated depletion of Lysosomal Associated Membrane Protein 2 (LAMP2) or with lysosome inhibitors. Chondrocyte apoptosis was determined by LDH release, Caspase-3/7 activation, TUNEL and PI uptake assays. Loss of mitochondrial membrane potential (MMP/ΔΨM) and mitochondrial superoxide level was determined by JC-1 and MitoSOX staining, respectively. Colocalization of mitochondria with BCL2 associated X (BAX) and Cytochrome c was determined by immunostaining. Destabilization of medial meniscus (DMM) was performed to induce OA in mice. Results Lysosomal acidification was found to be significantly decreased in aged mouse and human and mouse OA cartilage which also showed increased chondrocyte apoptosis. Inhibition of lysosomal function resulted in increased oxidative stress, accumulation of dysfunctional mitochondria and apoptosis in chondrocytes in monolayer and in cartilage explant cultures. Depletion of LAMP2 expression or treatment of chondrocytes with lysosomal function inhibitors increased the expression and mitochondrial translocation of BAX leading to Cytochrome c release. Lysosomal dysfunction-induced apoptosis in chondrocytes was not blocked by antioxidants MitoTempo or Diphenyleneiodonium (DPI) but was abrogated by inhibiting BAX. Conclusion Lysosomal dysfunction induce apoptosis in chondrocytes through BAX-mediated mitochondrial damage and release of Cytochrome c. Our data points to lysosomal function restoration and/or BAX inhibition in chondrocytes as a therapeutic approach for OA.

We employ a combined density functional theory (DFT) and experimental approach to screen different elements (M) and Pt3M alloys (M = Sc, Y, V, Nb, Ta, Ti, Zr, Hf, Cr, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Cu, Ag, Au and Al) for oxygen reduction reaction (ORR) activity and stability. The results of the calculations are validated using a series of carbon supported alloy nanoparticles measured within membrane electrode assembly (MEA) environments. We assess the reliability of descriptors such as surface d-band centre and O adsorption energy as computed from DFT calculations. We also assess the stability of the alloy surfaces under different adsorbate environments as encountered under ORR conditions. Our calculations predict that under an oxygen atmosphere segregation of M to the surface is likely to occur. The calculated segregation energies correlate reasonably well with the amount of base metal leached in the carbon-supported catalysts and good correlation of computed O adsorption energies with ORR activity is also shown.

We used a high-resolution magnetic spectrograph to study neutron pair-correlated 0 + states in 136Ba, produced via the Ba 138 ( p , t ) reaction. In conjunction with state-of-the-art shell model calculations, these data benchmark part of the dominant Gamow-Teller component of the nuclear matrix element (NME) for 136Xe neutrinoless double beta ( 0 ν β β ) decay. We demonstrate for the first time an evaluation of part of a 0 ν β β decay NME by use of an experimental observable, presenting a new avenue of approach for more accurate calculations of 0 ν β β decay matrix elements.

PURPOSE: Transposable elements are known to remodel gene structure and provide a known source of genetic variation. Retrotransposon gag-like-3 (RTL3) is a mammalian retrotransposon-derived transcript (MART) whose function in the skeletal tissue is unknown. This study aimed to elucidate the biological significance of RTL3 in chondrogenesis and type-II collagen (COL2A1) gene expression in chondrocytes. MATERIALS AND METHODS: Expression of RTL3, SOX-9 and COL2A1 mRNAs was determined by TaqMan assays and the protein expression by immunoblotting. RTL3 and Sox-9 depletion in human chondrocytes was achieved using validated siRNAs. An RTL3 mutant (ΔRTL3) lacking the zinc finger domain was created using in vitro mutagenesis. Forced expression of RTL3, ΔRTL3 and SOX-9 was achieved using CMV promoter containing expression plasmids. CRISPR-Cas9 was utilized to delete Rtl3 and create a stable ATDC5(Rlt3−/−) cell line. Matrix deposition and Col2a1 quantification during chondrogenesis was determined by Alcian blue staining and Sircol™ Soluble Collagen Assay, respectively. RESULTS: RTL3 is not ubiquitously expressed but showed strong expression in cartilage, chondrocytes and synoviocytes but not in muscle, brain or other tissues analyzed. Loss-of-function and gain-of-function studies demonstrated a critical role of RTL3 in the regulation of SOX-9 and COL2A1 expression and matrix synthesis during chondrogenesis. Both RTL3 and SOX-9 displayed co-regulated expression in chondrocytes. Gene regulatory activity of RTL3 requires the c-terminal CCHC zinc-finger binding domain. CONCLUSIONS: Our results identify a novel regulatory mechanism of COL2A1 expression in chondrocytes that may help to further understand the skeletal development and the pathogenesis of diseases with altered COL2A1 expression.

With the EV market set to grow rapidly over the coming years, the industry faces a challenging ramp-up of volume and material performance demands. From the current trend towards high-energy high-nickel cathode materials, driven in-part by consumer range anxiety, to the emergence of solid-state and beyond lithium ion technologies, herein we review the changing requirements for active materials in automotive lithium ion battery applications, and how science and industry is set to respond.

We report on high-statistics data from the $\beta^-$ decay of the $^{46}$K $J^{\pi}$ = 2$^-$ ground state taken with the GRIFFIN spectrometer located at the TRIUMF-ISAC facility. In total, 199 $\gamma$ rays and 42 excited states were placed in the level scheme, and from the observed $\beta$ feeding and angular correlations of pairs of cascading $\gamma$ rays, it was possible to assign spins and parities to excited states and determine mixing ratios for selected $\gamma$ rays. The level structure of $^{46}$Ca is compared to theoretical predictions from a microscopic valence-space Hamiltonian derived from two- (NN) and three-nucleon (3N) forces. These calculations are in reasonable agreement with the experimental data and indicate that the protons in this region are not as inert as would be expected for semi-magic nuclei.

Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-β or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/β-catenin pathway—a cellular signaling cascade linked to both bone loss and neuropathology. We showed that low BMD persisted in male htau mice aged from 6 to 14 months, remaining significantly lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female and male htau mice was markedly reduced from controls, indicating impaired bone remodeling. In both the bone and brain, htau mice showed alterations in Wnt/β-catenin signaling genes suggestive of increased inhibition of this pathway. These findings implicate dysfunctional Wnt signaling as a potential target for addressing bone loss in AD.

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the β^{+}/electron-capture decay of ^{110,112}In and the β^{-} decay of ^{112}Ag, very weak decay branches from nonyrast states are observed. The transition rates determined from the measured branching ratios and level lifetimes obtained with the Doppler-shift attenuation method following inelastic neutron scattering reveal collective enhancements that are suggestive of a series of rotational bands. In ^{110}Cd, a γ band built on the shape-coexisting intruder configuration is suggested. For ^{112}Cd, the 2^{+} and 3^{+} intruder γ-band members are suggested, the 0_{3}^{+} band is extended to spin 4^{+}, and the 0_{4}^{+} band is identified. The results are interpreted using beyond-mean-field calculations employing the symmetry conserving configuration mixing method with the Gogny D1S energy density functional and with the suggestion that the Cd isotopes exhibit multiple shape coexistence.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

The TIGRESS Integrated Plunger device (TIP) has been developed for recoil distance method (RDM) lifetime measurements using the TIGRESS array of HPGe γ -ray detectors at TRIUMF’s ISAC-II facility. A commissioning experiment was conducted utilizing a 250 MeV 84Kr beam at ≈ 2 × 1 0 8 particles per second. The 84Kr beam was Coulomb excited to the 2 1 + state on a movable 27Al target. A thin Cu foil fixed downstream from the target was used as a degrader. Excited nuclei emerged from the target and decayed by γ -ray emission at a distance determined by their velocity and the lifetime of the 2 1 + state. The ratio of decays which occur between the target and degrader to those occurring after traversing the degrader changes as a function of the target–degrader separation distance. Gamma-ray spectra at 13 target–degrader separation distances were measured and compared to simulated lineshapes to extract the lifetime. The result of τ = 5 . 541 ± 0 . 013 (stat.) ± 0 . 063 (sys.) ps is shorter than the literature value of 5 . 84 ± 0 . 18 ps with a reduction in uncertainty by a factor of approximately two. The TIP plunger device, experimental technique, analysis tools, and result are discussed.

Disease risk modeling is a key first step to understand the spatio-temporal dynamics of wildlife disease and to direct cost-effective surveillance and management. In Alberta, active surveillance for chronic wasting disease (CWD) in wild cervids began in 1998 with the first case detected in free-ranging cervids in 2005. Following the detection, a herd reduction program was implemented during 2005-2008 and in 2006 the ongoing hunter-based CWD Surveillance Program became mandatory in high-risk Wildlife Management Units (WMU). We used data collected during the CWD surveillance program to 1) document growth in sex-specific CWD prevalence (proportion of deer in sample that is CWD-positive) in hunter-harvest deer in 6 WMUs consistently monitored from 2006 to 2018, 2) document landscape features associated with where CWD-positive compared to CWD-negative deer were removed during hunter harvest and herd reduction in an early (2005-2012) and in a late period (2013-2017), and 3) to map the spatial risk of harvesting a deer infected with CWD in the prairie parklands of Alberta. In the 6 continuously monitored WMUs, risk of a harvested deer being CWD positive increased from 2006 to 2018 with CWD prevalence remaining highest in male mule deer whereas overall growth rate in CWD prevalence was greater in female mule deer, but similar to male white-tailed deer. We found no evidence that the 3-year herd reduction program conducted immediately after CWD was first detected affected the rate at which CWD grew over the course of the invasion. Risk of deer being CWD-positive was the highest in animals taken near small stream drainages and on soils with low organic carbon content in the early period, whereas risk became highest in areas of agriculture especially when far from large river drainages where deer often concentrate in isolated woody patches. The change in the influence of proximity to known CWD-positive cases suggested the disease was initially patchy but became more spatially homogeneous over time. Our results indicate that a targeted-removal program will remove more CWD positive animals compared to hunter harvest. However, the discontinuation of targeted removals during our research program, restricted our ability to assess its long term impact on CWD prevalence.

Background: Ventriculoperitoneal (VP) shunt failures in adult patients are common and subject patients to multiple surgeries and a decreased quality of life. A prospective cohort Shunt Outcomes Quality Improvement (ShOut-QI) initiative was implemented to reduce shunt failure incidence through neuronavigation-assisted proximal catheter insertion and laparoscopy-guided distal catheter anchoring over the liver dome to drain CSF away from the omentum. Methods: “Pre-ShOut” and “Post-ShOut” groups of patients included those with and without neuronavigation/laparoscopy, respectively for insertion of a new VP shunt. The primary outcome was shunt failure which was defined as any return to surgery for shunt revision as determined with a standardized clinical and radiology follow-up protocol. Results: 244 patients (97 Pre-ShOut, 147 Post-ShOut), mean age 73 years, were enrolled over a 7-year interval and observed for a mean duration of 4 years after shunt insertion. Neuronavigation improved proximal catheter placement accuracy by 20% (pConclusions: Adult shunt failure incidence may be significantly reduced by improving the accuracy of proximal catheter placement with neuronavigation and reducing the risk of distal catheter failure with laparoscopic-guided placement.

Fuels in modern diesel engine fuel systems are exposed to highly oxidizing conditions, thus it is important to understand their degradation mechanisms. A range of chemical and physical properties was monitored during the oxidation and polymerization of soybean methyl ester biodiesel (B100), a diesel fuel (B0), and their blends (B10, B30) at 90 °C with aeration. The initial rapid oxidation of polyunsaturated fatty acid methyl esters (FAMEs) provided a transient pool of peroxides that led to the formation of aldehydes, ketones, and acids as secondary products. Monounsaturated and saturated FAMEs were oxidized concurrently with polyunsaturated FAMEs in B10, B30, and B100, but only B100 showed significant oxidation reactions continuing after the polyunsaturated FAMEs were depleted. New esters were a major oxidation product, eventually comprising 40–60% of the incorporated oxygen. Carboxylic acids and alcohols react to form esters and water, with vaporization of water driving the equilibrium toward ester forma...

Globally soil quality and food security continue to decrease indicating that agriculture and the food system need to adapt. Improving connection to the soil by knowledge exchange can help achieve this. We propose a framework of three types of connections that allow the targeting of appropriate messages to different groups of people. Direct connection by, for example, handling soil develops soil awareness for management that can be fostered by farmers joining groups on soil-focused farming such as organic farming or no-till. Indirect connections between soil, food and ecosystem services can inform food choices and environmental awareness in the public and can be promoted by, for example, gardening, education and art. Temporal connection revealed from past usage of soil helps to bring awareness to policy workers of the need for the long-term preservation of soil quality for environmental conservation. The understanding of indirect and temporal connections can be helped by comparing them with the operations of the networks of soil organisms and porosity that sustain soil fertility and soil functions.

Visual soil evaluation techniques have gained popularity and are increasingly used in agriculture and soil science for research, consultancy and teaching purposes. We describe recent applications, developments, opportunities and limitations, mainly of the Visual Evaluation of Soil Structure (for topsoil (VESS) and for subsoil (SubVESS)), and of the Visual Soil Assessment (VSA). Data are taken from experiments on compaction and from assessments made in farmer’s fields in the UK, Brazil and New Zealand. The methods are widely used to detect compaction and are well-suited for monitoring changes in compaction status, particularly in relation to weather extremes. VESS proved useful in distinguishing grazing vs wheel compaction in the UK and Brazil by permitting detection of layers at different depths within the topsoil zone. The depths of compact layers are important for scoring management decisions for soil improvement. However the use of scores as limiting thresholds in different soil types needs the support of further soil measurements and/or additional visual assessments of soil and crop. VSA and VESS were also used to estimate the risk of significant soil emissions of nitrous oxide where compaction damage was present and rates of mineral N fertiliser were high. Visual assessments also have the potential to assess the risk of surface water runoff and nutrient loss. The potential role of soil colour was shown for the further development of visual evaluation techniques for a soil carbon storage index. Visual soil evaluation techniques also provide a useful visual aid for improving soil awareness in groups of stakeholders, helping the exchange of knowledge and ideas for innovation in agriculture.

The Visual Evaluation of Soil Structure (VESS) is a straightforward and practical method for characterising and scoring soil structural and physical quality, ideally suited to evaluate and monitor soil degradation in remote and undeveloped areas. The research presented here tested for the first time the feasibility of using VESS in the Amazon basin, under the specific land uses and soils (Oxisol and “Terra Preta de Indio”) of the region, and its relation with quantitative soil properties commonly used as indicators of soil physical quality. The evaluated areas, which had never been subjected to mechanisation, chemical fertilisation nor tillage, were “Terra Preta de Indio”/Anthropogenic Dark Earth; Regenerating Forest; Slash and Burn; Pasture; and Pristine Forest. The results showed that the quantitative properties were less sensitive at revealing signs of degradation than VESS and that VESS brought to light evidence of historic land use change and limitations to crop productivity. VESS was significantly correlated with soil resistance to penetration. However, VESS had difficulty capturing surface sealing, but the hands on approach to VESS allowed the user to identify these problems, despite not being listed in the reference chart. Overall, VESS was a more integrated soil quality indicator, providing more information about different soil functions than the quantitative properties, it was also a more practical method to perform making it ideal for tracking soil degradation and structural quality in similarly challenging situations. However, more research is required to fully enable VESS to capture structural quality in ‘sandified’ soils, caused by the slash and burn method widely used in the Amazon region.

Potentiostatic and potentiodynamic Pt and Co dissolution were investigated for three Pt3Co/C catalysts with particle sizes of 4.9, 8.1, and 14.8 nm in aqueous electrolyte at potentials encountered by the PEMFC cathode. For all three Pt3Co/C catalysts under prolonged potentiostatic dissolution, the dissolved Pt steady state concentration increases from 0.85 V to reach a maximum at 1.1−1.15 V and decreases at higher potentials. The dependence of the dissolved Pt steady state concentration on particle size reveals that catalyst stability decreases with decreasing mean particle size, whereas the stability under potential cycling conditions is non-monotonic with particle size. Preferential dissolution of Co from all three Pt3Co catalysts was observed at all potentials, which increases at >1.1 V, the region over which Pt dissolution decreases, reflecting the opposing effects of Pt oxide formation on Pt and Co dissolution. Comparison of Pt3Co/C and Pt/C with similar mean particle sizes (4.9 vs 5.0 nm) and particle size distributions reveals that the Pt3Co/C has a higher potentiostatic dissolution rate (4–5 times), a higher steady state concentration of dissolved Pt (∼2 times), and a larger change in electrochemically-active surface area (ECA) (18 times) after prolonged cycling, indicating that Pt3Co has inferior stability. The higher rates of Pt dissolution for Pt3Co vs Pt have been attributed to higher extents of surface Pt oxidation, as determined using voltammetric oxide reduction charges and the white line intensities in Pt L3 X-ray absorption spectra.