Intended as a companion to the Fundamentals of Forensic DNA Typing volume published in 2009, Advanced Topics in Forensic DNA Typing: Methodology contains 18 chapters with 4 appendices providing ...up-to-date coverage of essential topics in this important field and citation to more than 2800 articles and internet resources. The book builds upon the previous two editions of John Butler's internationally acclaimed Forensic DNA Typing textbook with forensic DNA analysts as its primary audience. This book provides the most detailed information written to-date on DNA databases, low-level DNA, validation, and numerous other topics including a new chapter on legal aspects of DNA testing to prepare scientists for expert witness testimony. Over half of the content is new compared to previous editions. A forthcoming companion volume will cover interpretation issues.
Contains the latest information - hot-topics and new technologiesWell edited, attractively laid out, and makes productive use of its four-color formatAuthor John Butler is ranked as the number one "high-impact author in legal medicine and forensic science, 2001 to 2011" by ScienceWatch.com
Multi-component, high-entropy alloys (HEAs) are being investigated as potential alternatives for high temperature structural materials due to their reported high symmetry crystal structures, ...favorable mechanical properties, high temperature phase stabilities, and resistances to degradation in oxidizing/corrosive environments. However, their high temperature oxidation behaviors are poorly understood. In this work, the as-cast microstructures and 1050 °C oxidation behaviors of a series of arc-melted Alx(NiCoCrFe)100-x HEAs where x = 8, 10, 12, 15, 20, and 30 (at.%) were investigated. The dominant structure of the low Al concentration HEAs was determined to be FCC, while the high Al concentration HEAs were BCC dominant. A structural transition point at ∼15 at. % Al exists where a large fraction of both FCC and BCC are present. Each HEA exhibited initial transient oxidation followed by various degrees of parabolic oxide growth. All of the HEAs formed a combination of Al2O3 and AlN beneath an external Cr2O3 scale. Increased Al content improved the continuity and internal position of the Al2O3 scale, resulting in enhanced oxidation resistances. These results are discussed relative to chemically similar conventional alloys and existing Ni–Cr–Al oxide formation models. The resulting phase equilibria has been compared to thermodynamic predictions made using the CALPHAD method.
•The as-cast HEAs formed FCC, BCC, and/or B2 (i.e. ordered BCC) crystal structures.•Thermodynamic CALPHAD based models were fairly consistent with experimental results.•All of the HEAs selectively oxidized to form predominantly Al2O3 and Cr2O3 scales.•The HEAs exhibited some parabolic oxide growth comparable to model NiCrAl alloys.•The oxidation performance was heavily influenced by the relative Al concentrations.
Endothelial cells that line capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establishes specialized vascular niches that deploy sets of growth factors, ...known as angiocrine factors. These cues participate actively in the induction, specification, patterning and guidance of organ regeneration, as well as in the maintainance of homeostasis and metabolism. When upregulated following injury, they orchestrate self-renewal and differentiation of tissue-specific resident stem and progenitor cells into functional organs. Uncovering the mechanisms by which organotypic endothelium distributes physiological levels of angiocrine factors both spatially and temporally will lay the foundation for clinical trials that promote organ repair without scarring.
Genome editing using sequence-specific nucleases (SSNs) offers an alternative approach to conventional genetic engineering and an opportunity to extend the benefits of genetic engineering in ...agriculture. Currently available SSN platforms, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas (clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems (Cas)) have been used in a range of plant species for targeted mutagenesis via non-homologous end joining (NHEJ) are just beginning to be explored in crops such as potato (Solanum tuberosum Group Tuberosum L.). In this study, CRISPR/Cas reagents expressing one of two single-guide RNA (sgRNA) targeting the potato ACETOLACTATE SYNTHASE1 (StALS1) gene were tested for inducing targeted mutations in callus and stable events of diploid and tetraploid potato using Agrobacterium-mediated transformation with either a conventional T-DNA or a modified geminivirus T-DNA. The percentage of primary events with targeted mutations ranged from 3-60% per transformation and from 0-29% above an expected threshold based on the number of ALS alleles. Primary events with targeted mutation frequencies above the expected threshold were used for mutation cloning and inheritance studies using clonal propagation and crosses or selfing. Four of the nine primary events used for mutation cloning had more than one mutation type, and eight primary events contained targeted mutations that were maintained across clonal generations. Somatic mutations were most evident in the diploid background with three of the four primary events having more than two mutation types at a single ALS locus. Conversely, in the tetraploid background, four of the five candidates carried only one mutation type. Single targeted mutations were inherited through the germline of both diploid and tetraploid primary events with transmission percentages ranging from 87-100%. This demonstration of CRISPR/Cas in potato extends the range of plant species modified using CRISPR/Cas and provides a framework for future studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Regulatory initiatives obligate maritime operators to reduce emission via retrofitting propulsion and exhaust treatment systems or by using alternative fuels. Although these initiatives facilitate ...the emergence of LNG as a marine fuel, the proliferation of LNG technology is dependent on the relationship that defines the competitiveness of conventionally fueled and LNG-fueled ships.
This article proposes a methodology to evaluate the commercial incentives that are required to promote LNG as a marine fuel, which can be used to assess policy initiatives that encourage the use of alternative technologies and estimate their market impact. To develop the context and support this methodology, the following areas are discussed: (1) international regulatory frameworks and regional initiatives supporting the use of LNG as a marine fuel; (2) commercial and operational attributes that determine the competitiveness of LNG-fueled ships; and (3) challenges preventing the adoption of LNG as a marine fuel, including the uncertainties and less-quantifiable concerns expressed by the maritime operators.
•Regulatory requirements and drivers promoting LNG-fueled ships.•Presentation of the cost of energy based on a statistical analysis that determines the benefits of using LNG.•Estimation of the potential economic benefit for operators; an illustrative example given available technology is provided.•Derivation of a condition that assesses the competitiveness of LNG-fueled ships given the accepted cost-structure of commercial ships.•Recommendation of regional policy initiatives that promote LNG fueled ships towards achieving ‘clean air’ goals.•Introduction of the term 'regulatory acupuncture' indicating local action that assists global relief.
With the advent of effective tools to study lipids, including mass spectrometry-based lipidomics, lipids are emerging as central players in cancer biology. Lipids function as essential building ...blocks for membranes, serve as fuel to drive energy-demanding processes and play a key role as signaling molecules and as regulators of numerous cellular functions. Not unexpectedly, cancer cells, as well as other cell types in the tumor microenvironment, exploit various ways to acquire lipids and extensively rewire their metabolism as part of a plastic and context-dependent metabolic reprogramming that is driven by both oncogenic and environmental cues. The resulting changes in the fate and composition of lipids help cancer cells to thrive in a changing microenvironment by supporting key oncogenic functions and cancer hallmarks, including cellular energetics, promoting feedforward oncogenic signaling, resisting oxidative and other stresses, regulating intercellular communication and immune responses. Supported by the close connection between altered lipid metabolism and the pathogenic process, specific lipid profiles are emerging as unique disease biomarkers, with diagnostic, prognostic and predictive potential. Multiple preclinical studies illustrate the translational promise of exploiting lipid metabolism in cancer, and critically, have shown context dependent actionable vulnerabilities that can be rationally targeted, particularly in combinatorial approaches. Moreover, lipids themselves can be used as membrane disrupting agents or as key components of nanocarriers of various therapeutics. With a number of preclinical compounds and strategies that are approaching clinical trials, we are at the doorstep of exploiting a hitherto underappreciated hallmark of cancer and promising target in the oncologist's strategy to combat cancer.
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Background
The 15q11.2 BP1–BP2 microdeletion (Burnside–Butler susceptibility locus) is an emerging condition with over 200 individuals reported in the literature. TUBGCP5, CFYIP1, NIPA1 and NIPA2 ...genes are located in this chromosome 15 region and when disturbed individually are known to cause neurological, cognitive or behavioural problems as well as playing a role in both Prader–Willi and Angelman syndromes. These syndromes were the first examples in humans of genomic imprinting and typically caused by a deletion but involving the distal chromosome 15q11–q13 breakpoint BP3 and proximally placed breakpoints BP1 or BP2 of different parental origin. The typical 15q11–q13 deletion involves BP1 and BP3 and the typical type II deletion at BP2 and BP3. Several studies have shown that individuals with the larger type I deletion found in both Prader–Willi and Angelman syndromes are reported with more severe neurodevelopmental symptoms compared to those individuals with the smaller type II deletion.
Methods
The literature was reviewed and clinical and cytogenetic findings summarised in 200 individuals with this microdeletion along with the role of deleted genes in diagnosis, medical care and counseling of those affected and their family members.
Results
Reported findings in this condition include developmental delays (73% of cases) and language impairment (67%) followed by motor delay (42%), attention deficit disorder/attention deficit hyperactivity disorder (35%) and autism spectrum disorder (27%). The de novo deletion frequency has been estimated at 5 to 22% with low penetrance possibly related to subclinical manifestation or incomplete clinical information on family members. A prevalence of 0.6 to 1.3% has been identified in one study for patients with neurological or behavioural problems presenting for genetic services and chromosomal microarray analysis.
Conclusions
The summarised results indicate that chromosome 15q11.2 BP1–BP2 microdeletion is emerging as one of the most common cytogenetic abnormalities seen in individuals with intellectual impairment, autism spectrum disorder and other related behavioural or clinical findings, but more research is needed.
Advanced Topics in Forensic DNA Typing: Interpretation builds upon the previous two editions of John Butler's internationally acclaimed Forensic DNA Typing textbook with forensic DNA analysts as its ...primary audience. Intended as a third-edition companion to the Fundamentals of Forensic DNA Typing volume published in 2010 and Advanced Topics in Forensic DNA Typing: Methodology published in 2012, this book contains 16 chapters with 4 appendices providing up-to-date coverage of essential topics in this important field. Over 80 % of the content of this book is new compared to previous editions. * Provides forensic DNA analysts coverage of the crucial topic of DNA mixture interpretation and statistical analysis of DNA evidence * Worked mixture examples illustrate the impact of different statistical approaches for reporting results * Includes allele frequencies for 24 commonly used autosomal STR loci, the revised Quality Assurance Standards which went into effect September 2011
Abstract
The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases ...(https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative analysis environment that provides users with access to over 250 000 uniformly annotated and publicly available genomes with curated metadata. PATRIC offers web-based visualization and comparative analysis tools, a private workspace in which users can analyze their own data in the context of the public collections, services that streamline complex bioinformatic workflows and command-line tools for bulk data analysis. Over the past several years, as genomic and other omics-related experiments have become more cost-effective and widespread, we have observed considerable growth in the usage of and demand for easy-to-use, publicly available bioinformatic tools and services. Here we report the recent updates to the PATRIC resource, including new web-based comparative analysis tools, eight new services and the release of a command-line interface to access, query and analyze data.