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"Johnson, Daniel"
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Blacksmithing : a guide to practical metalworking, tools and techniques
\"Skilled artisans at the heart of human civilization since the Iron Age, blacksmiths gained the respect of their communities through the utility of their creations, whether these were weapons, armour, farming tools, wagon axles or household items. Industrialization and mass production may have led to the disappearance of the blacksmith from everyday life, but the art of metalworking is alive and well. Today, blacksmithing is still practised throughout the world and is experiencing a revival. Blacksmithing provides a photographic introduction to blacksmith practices today from an expert teacher, offering the novice and enthusiast an insight into this ancient trade. Learn how blacksmiths heat the metal using a variety of methods, including electric induction and traditional coal-fired forges; see the huge range of items that a metalworker can produce, including wrenches, shovels, door plates, bicycle stands and railings; see craftspeople practicing specialist metalworking techniques, such as upsetting, collaring, twisting, fullering and swaging; and understand how blacksmiths respect the environment by using old iron ore and scrap iron. Illustrated with 350 photographs -- many of them of the author at work, with step-by-step guides -- that will instruct and inspire, Blacksmithing is a dazzling pictorial celebration of a craft as old as civilization itself.\"--Publisher website.
BOOK
Population-Based Disparities in U.S. Urban Heat Exposure from 2003 to 2018
Previous studies have shown, in the United States (U.S.), that communities of color are exposed to significantly higher temperatures in urban environments than complementary White populations. Studies highlighting this disparity have generally been cross-sectional and are therefore “snapshots” in time. Using surface urban heat island (SUHI) intensity data, U.S. Census 2020 population counts, and a measure of residential segregation, this study performs a comparative analysis between census tracts identified as prevalent for White, Black, Hispanic and Asian populations and their thermal exposure from 2003 to 2018. The analysis concentrates on the top 200 most populous U.S. cities. SUHI intensity is shown to be increasing on average through time for the examined tracts. However, based on raw observations the increase is only statistically significant for White and Black prevalent census tracts. There is a 1.25 K to ~2.00 K higher degree of thermal exposure on average for communities of color relative to White prevalent areas. When examined on an inter-city basis, White and Black prevalent tracts had the largest disparity, as measured by SUHI intensity, in New Orleans, LA, by <6.00 K. Hispanic (>7.00 K) and Asian (<6.75 K) prevalent tracts were greatest in intensity in San Jose, CA. To further explore temporal patterns, two models were developed using a Bayesian hierarchical spatial temporal framework. One models the effect of varying the percentages of each population group relative to SUHI intensity within all examined tracts. Increases in percentages of Black, Hispanic, and Asian populations contributed to statistically significant increases in SUHI intensity. White increases in population percentage witnessed a lowering of SUHI intensity. Throughout all modeled tracts, there is a statistically significant 0.01 K per year average increase in SUHI intensity. A second model tests the effect of residential segregation on thermal inequity across all examined cities. Residential segregation, indeed, has a statistically significant positive association with SUHI intensity based on this portion of the analysis. Similarly, there is a statistically significant 0.01 K increase in average SUHI intensity per year for all cities. Results from this study can be used to guide and prioritize intervention strategies and further urgency related to social, climatic, and environmental justice concerns.
Journal Article
Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization
The molecular basis of serpin polymerization
The serpins are a family of proteins that can multimerize via β-sheet linkages. Accumulation of such multimers can give rise to diseases such as thrombosis, cirrhosis and dementia. While the structures of many serpins are known, the structure of the linkage between monomers was unclear. In this work, Huntington and colleagues have solved the crystal structure of an antithrombin dimer. They find that the high stability of the serpin polymer is due to a large domain swap between beta sheets of the neighbouring monomers. In addition, the structure explains the how certain pathogenic mutations stabilize a polymerogenic folding intermediate.
Repeating intermolecular protein association by means of β-sheet expansion is the mechanism underlying a multitude of diseases including Alzheimer’s, Huntington’s and Parkinson’s and the prion encephalopathies
1
. A family of proteins, known as the serpins, also forms large stable multimers by ordered β-sheet linkages leading to intracellular accretion and disease
2
. These ‘serpinopathies’ include early-onset dementia caused by mutations in neuroserpin, liver cirrhosis and emphysema caused by mutations in α
1
-antitrypsin (α
1
AT), and thrombosis caused by mutations in antithrombin
3
. Serpin structure and function are quite well understood, and the family has therefore become a model system for understanding the β-sheet expansion disorders collectively known as the conformational diseases
4
. To develop strategies to prevent and reverse these disorders, it is necessary to determine the structural basis of the intermolecular linkage and of the pathogenic monomeric state. Here we report the crystallographic structure of a stable serpin dimer which reveals a domain swap of more than 50 residues, including two long antiparallel β-strands inserting in the centre of the principal β-sheet of the neighbouring monomer. This structure explains the extreme stability of serpin polymers, the molecular basis of their rapid propagation, and provides critical new insights into the structural changes which initiate irreversible β-sheet expansion.
Journal Article
Green farming
\"This STEM-based set of True Books introduces students to the engineering innovations that can help us reach more environmentally friendly goals\"-- Provided by publisher.
CHILDBOOK
Targeting the IL-6/JAK/STAT3 signalling axis in cancer
The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response. Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity. Agents targeting IL-6, the IL-6 receptor, or JAKs have already received FDA approval for the treatment of inflammatory conditions or myeloproliferative neoplasms and for the management of certain adverse effects of chimeric antigen receptor T cells, and are being further evaluated in patients with haematopoietic malignancies and in those with solid tumours. Novel inhibitors of the IL-6/JAK/STAT3 pathway, including STAT3-selective inhibitors, are currently in development. Herein, we review the role of IL-6/JAK/STAT3 signalling in the tumour microenvironment and the status of preclinical and clinical investigations of agents targeting this pathway. We also discuss the potential of combining IL-6/JAK/STAT3 inhibitors with currently approved therapeutic agents directed against immune-checkpoint inhibitors.
Journal Article
Holistic musical thinking : a pedagogical model for hands-on and heart-felt musical engagement
\"Holistic Musical Thinking presents a comprehensive view of how people engage with music from a hands-on and heart-felt perspective. This approach embraces the teaching and learning processes as a multi-dimensional amalgamation of knowing, doing, and feeling through musical experiences. The result is a five-dimensional model that synthesizes cognitive, affective, and psychomotor learning with curricular integration. With pedagogical applications, Holistic Musical Thinking offers a multi-faceted perspective that benefits both music teachers and their students. This innovative approach uses established research for a new model of musical thinking and taxonomy of musical engagement. Complete with classroom vignettes and pedagogical strategies, this book reframes musical thinking as a new direction in music education. Written for music teachers, teacher-educators, and their students, this book provides practical applications of the multi-dimensional Model of Holistic Musical Thinking for K-12 music education, and beyond\"-- Provided by publisher.
BOOK
Efficient Antibacterial Membrane based on Two-Dimensional Ti3C2Tx (MXene) Nanosheets
Advanced membranes that enable ultrafast water flux while demonstrating anti-biofouling characteristics can facilitate sustainable water/wastewater treatment processes. MXenes, two-dimensional (2D) metal carbides and nitrides, have attracted attention for applications in water/wastewater treatment. In this work, we reported the antibacterial properties of micrometer-thick titanium carbide (Ti
3
C
2
T
x
) MXene membranes prepared by filtration on a polyvinylidene fluoride (PVDF) support. The bactericidal properties of Ti
3
C
2
T
x
modified membranes were tested against
Escherichia coli
(
E
.
coli
) and
Bacillus subtilis
(
B
.
subtilis
) by bacterial growth on the membrane surface and its exposure to bacterial suspensions. The antibacterial rate of fresh Ti
3
C
2
T
x
MXene membranes reaches more than 73% against
B
.
subtilis
and 67% against
E
.
coli
as compared with that of control PVDF, while aged Ti
3
C
2
T
x
membrane showed over 99% growth inhibition of both bacteria under same conditions. Flow cytometry showed about 70% population of dead and compromised cells after 24 h of exposure of both bacterial strains. The damage of the cell surfaces was also revealed by scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis, respectively. The demonstrated antibacterial activity of MXene coated membranes against common waterborne bacteria, promotes their potential application as anti-biofouling membrane in water and wastewater treatment processes.
Journal Article
EGFR-targeted therapies in the post-genomic era
Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials. The humanized monoclonal antibody nimotuzumab is also approved for head and neck cancers in Cuba, Argentina, Colombia, Peru, India, Ukraine, Ivory Coast, and Gabon in addition to nasopharyngeal cancers in China. Few other EGFR-targeted therapeutics for head and neck cancers have led to as significant responses as seen in lung carcinomas, for instance. Recent genome sequencing of head and neck tumors has helped identify patient subgroups with improved response to EGFR inhibitors, for example, cetuximab in patients with the KRAS-variant and the tyrosine kinase inhibitor erlotinib for tumors harboring MAPK1
E322K
mutations. Genome sequencing has furthermore broadened our understanding of dysregulated pathways, holding the potential to enhance the benefit derived from therapies targeting EGFR.
Journal Article