Plastic flow at the theoretical yield stress in ceramic films

Using fine-grained ceramic films based on chromium nitride, and suppressing fracture by using microcompression, it is shown that plastic flow at the theoretical yield stress can be obtained in brittle materials, with shear yield stresses of ~ G/24 at room temperature, which extrapolate to ~ G/19 at 0 K. Surprisingly, it is also found that the rate of deformation, and hence the hardness and the yield stress, are determined not by the soft, glassy grain boundary phase in the fine-grained materials, but by the harder crystal phase.This research was funded by A*STAR, Singapore and the Engineering and Physical Sciences Research Council (EPSRC) and Rolls-Royce Strategic Partnership (EP/H500375/1)

Teaching Through Collaboration: Flexibility and Diversity in Caregiver–Child Interaction Across Cultures

Supporting Information is available online at https://srcd.onlinelibrary.wiley.com/doi/10.1111/cdev.13443#support-information-section .Teaching supports the high-fidelity transmission of knowledge and skills. This study examined similarities and differences in caregiver teaching practices in the United States and Vanuatu (N = 125 caregiver and 3- to 8-year-old child pairs) during a collaborative problem-solving task. Caregivers used diverse verbal and nonverbal teaching practices and adjusted their behaviors in response to task difficulty and child age in both populations. U.S. caregivers used practices consistent with a direct active teaching style typical of formal education, including guiding children’s participation, frequent praise, and facilitation. In contrast, Ni-Vanuatu caregivers used practices associated with informal education and divided tasks with children based on difficulty. The implications of these findings for claims about the universality and diversity of caregiver teaching are discussed.Economic and Social Research Council. Grant Number: REF RES-060-25-0085; National Science Foundation. Grant Number: 173067

Ultra-stiff metallic glasses through bond energy density design

The elastic properties of crystalline metals scale with their valence electron density. Similar observations have been made for metallic glasses. However, for metallic glasses where covalent bonding predominates, such as metalloid metallic glasses, this relationship appears to break down. At present, the reasons for this are not understood. Using high energy x-ray diffraction analysis of melt spun and thin film metallic glasses combined with density functional theory based molecular dynamics simulations, we show that the physical origin of the ultrahigh stiffness in both metalloid and non-metalloid metallic glasses is best understood in terms of the bond energy density. Using the bond energy density as novel materials design criterion for ultra-stiff metallic glasses, we are able to predict a Co$_{33.0}$Ta$_{3.5}$B$_{63.5}$ short range ordered material by density functional theory based molecular dynamics simulations with a high bond energy density of 0.94 eV Å$^{-3}$ and a bulk modulus of 263 GPa, which is 17% greater than the stiffest Co-B based metallic glasses reported in literature.The authors acknowledge support by the German National Science Foundation (DFG) within the SPP-1594. Simulations were performed with computing resources granted by JARA-HPC from RWTH Aachen University under project JARA0131. Parts of this research were carried out at the light source PETRA III (beamline P02.1) at DESY, a member of the Helmholtz Association (HGF). WJC also acknowledges the support of the EPSRC/Rolls-Royce Strategic Partnership (EP/M005607/1)

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

Factors regulating Hb F synthesis in thalassemic diseases

BACKGROUND: The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo) and Hb F, between Hb F and point mutations of the gamma gene promoters. MATERIALS AND METHODS: Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. RESULTS: Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta° or severe beta(+) thal mutations are associated with evident beta thal int (88%) and almost invariably (98%) with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo) level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. CONCLUSIONS: The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

Background Osteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potentially provide early biomarkers. Methods Small RNA sequencing was performed using synovial fluid from the metacarpophalangeal joints of both control and early osteoarthritic horses. A group of differentially expressed sncRNAs was selected for further validation through qRT-PCR using an independent cohort of synovial fluid samples from control and early osteoarthritic horses. Bioinformatic analysis was performed in order to identify putative targets of the differentially expressed microRNAs and to explore potential associations with specific biological processes. Results Results revealed 22 differentially expressed sncRNAs including 13 microRNAs; miR-10a, miR-223, let7a, miR-99a, miR-23b, miR-378, miR-143 (and six novel microRNAs), four small nuclear RNAs; U2, U5, U11, U12, three small nucleolar RNAs; U13, snoR38, snord96, and one small cajal body-specific RNA; scarna3. Five sncRNAs were validated; miR-223 was significantly reduced in early osteoarthritis and miR-23b, let-7a-2, snord96A and snord13 were significantly upregulated. Significant cellular actions deduced by the differentially expressed microRNAs included apoptosis (P < 0.0003), necrosis (P < 0.0009), autophagy (P < 0.0007) and inflammation (P < 0.00001). A conservatively filtered list of 57 messenger RNA targets was obtained; the top biological processes associated were regulation of cell population proliferation (P < 0.000001), cellular response to chemical stimulus (P < 0.000001) and cell surface receptor signalling pathway (P < 0.000001). Conclusions Synovial fluid sncRNAs may be used as molecular biomarkers for early disease in equine osteoarthritic joints. The biological processes they regulate may play an important role in understanding early osteoarthritis pathogenesis. Characterising these dynamic molecular changes could provide novel insights on the process and mechanism of early osteoarthritis development and is critical for the development of new therapeutic approaches

Factors affecting the decision to investigate older adults with potential cancer symptoms: a systematic review

BACKGROUND: Older age and frailty increase the risk of morbidity and mortality from cancer surgery and intolerance of chemotherapy and radiotherapy. The effect of old age on diagnostic intervals is unknown; however, older adults need a balanced approach to the diagnosis and management of cancer symptoms, considering the benefits of early diagnosis, patient preferences, and the likely prognosis of a cancer. AIM: To examine the association between older age and diagnostic processes for cancer, and the specific factors that affect diagnosis. DESIGN AND SETTING: A systematic literature review. METHOD: Electronic databases were searched for studies of patients aged >65 years presenting with cancer symptoms to primary care considering diagnostic decisions. Studies were analysed using thematic synthesis and according to the Synthesis Without Meta-analysis guidelines. RESULTS: Data from 54 studies with 230 729 participants were included. The majority of studies suggested an association between increasing age and prolonged diagnostic interval or deferral of a decision to investigate cancer symptoms. Thematic synthesis highlighted three important factors that resulted in uncertainty in decisions involving older adults: presence of frailty, comorbidities, and cognitive impairment. Data suggested patients wished to be involved in decision making, but the presence of cognitive impairment and the need for additional time within a consultation were significant barriers. CONCLUSION: This systematic review has highlighted uncertainty in the management of older adults with cancer symptoms. Patients and their family wished to be involved in these decisions. Given the uncertainty regarding optimum management of this group of patients, a shared decision-making approach is important

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

ABSTRACTBackgroundOsteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potentially provide early biomarkers.MethodsSmall RNA sequencing was performed using synovial fluid from the metacarpophalangeal joints of both control and early osteoarthritic non-Thoroughbred horses. A group of differentially expressed sncRNAs was selected for further validation through qRT-PCR using an independent cohort of synovial fluid samples from control and early osteoarthritic horses. Bioinformatic analysis was performed in order to identify putative targets of the differentially expressed microRNAs and to explore potential associations with specific biological processes.ResultsResults revealed 22 differentially expressed sncRNAs including 13 microRNAs; miR-10a, miR-223, let7a, miR-99a, miR-23b, miR-378, miR-143 (and six novel microRNAs), four small nuclear RNAs; U2, U5, U11, U12, three small nucleolar RNAs; U13, snoR38, snord96, and one small cajal body-specific RNA; scarna3. Five sncRNAs were validated; miR-223 was significantly reduced in early OA and miR-23b, let-7a-2, snord96A and snord13 were significantly upregulated. Significant cellular functions deduced by the differentially expressed microRNAs included apoptosis (P &lt; 0.0003), necrosis (P &lt; 0.0009), autophagy (P &lt; 0.0007) and inflammation (P &lt; 0.00001). A conservatively filtered list of 57 messenger RNA targets was obtained; the top biological processes associated were regulation of cell population proliferation (P &lt; 0.000001), cellular response to chemical stimulus (P &lt; 0.000001) and cell surface receptor signalling pathway (P &lt; 0.000001).ConclusionsSynovial fluid sncRNAs can be used as molecular biomarkers for early disease in equine osteoarthritic joints. The biological processes they regulate may play an important role in understanding early osteoarthritis pathogenesis. Characterising these dynamic molecular changes could provide novel insights on the process and mechanism of early osteoarthritis development and is critical for the development of new therapeutic approaches.</jats:sec