The evolution, modifications and interactions of proteins and RNAs

Proteins and RNAs are two of the most versatile macromolecules that carry out almost all functions within living organisms. In this thesis I have explored evolutionary and regulatory aspects of proteins and RNAs by studying their structures, modifications and interactions. In the first chapter of my thesis I investigate domain atrophy, a term I coined to describe large-scale deletions of core structural elements within protein domains. By looking into truncated domain boundaries across several domain families using Pfam, I was able to identify rare cases of domains that showed atrophy. Given that even point mutations can be deleterious, it is surprising that proteins can tolerate such large-scale deletions. Some of the structures of atrophied domains show novel protein-protein interaction interfaces that appear to compensate and stabilise their folds. Protein-protein interactions are largely influenced by the surface and charge complementarity, while RNA-RNA interactions are governed by base-pair complementarity; both interaction types are inherently different and these differences might be observed in their interaction networks. Based on this hypothesis I have explored the protein-protein, RNA-protein and the RNA-RNA interaction networks of yeast in the second chapter. By analysing the three networks I found no major differences in their network properties, which indicates an underlying uniformity in their interactomes despite their individual differences. In the third chapter I focus on RNA-protein interactions by investigating post-translational modifications (PTMs) in RNA-binding proteins (RBPs). By comparing occurrences of PTMs, I observe that RBPs significantly undergo more PTMs than non-RBPs. I also found that within RBPs, PTMs are more frequently targeted at regions that directly interact with RNA compared to regions that do not. Moreover disorderedness and amino acid composition were not observed to significantly influence the differential PTMs observed between RBPs and nonRBPs. The results point to a direct regulatory role of PTMs in RNA-protein interactions of RBPs. In the last chapter, I explore regulatory RNA-RNA interactions. Using differential expression data of mRNAs and lncRNAs from mouse models of hereditary hemochromatosis, I investigated competing regulatory interactions between mRNA, lncRNA and miRNA. A mutual interaction network was created from the predicted miRNA interaction sites on mRNAs and lncRNAs to identify regulatory RNAs in the disease. I also observed interesting relations between the sense-antisense mRNA-lncRNA pairs that indicate mutual regulation of expression levels through a yet unknown mechanism

Processing of ultrafine-size particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Metallurgical & Materials Transactions A 40A(3) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Lack of efficient mixing technology to achieve a uniform distribution of fine-size reinforcement within the matrix and the high cost of producing components have hindered the widespread adaptation of particulate metal matrix composites (PMMCs) for engineering applications. A new rheo-processing method, the melt-conditioning high-pressure die-cast (MC-HPDC) process, has been developed for manufacturing near-net-shape components of high integrity. The MC-HPDC process adapts the well-established high shear dispersive mixing action of a twin-screw mechanism to the task of overcoming the cohesive force of the agglomerates under a high shear rate and high intensity of turbulence. This is followed by direct shaping of the slurry into near-net-shape components using an existing cold-chamber die-casting process. The results indicate that the MC-HPDC samples have a uniform distribution of ultrafine-sized SiC particles throughout the entire sample in the as-cast condition. Compared to those produced by conventional high-pressure die casting (HPDC), MC-HPDC samples have a much improved tensile strength and ductility.EP-SR

Liquid Biopsy: Novel Progressions and Comparisons

Liquid biopsy technology has evolved into a promising, minimally invasive clinical tool for cancer diagnosis and oncology research. Liquid biopsy is a broad term referring to the testing of bodily fluids: spinal fluid, sweat, urine, and most commonly blood as it is materially dense; it is an analysis technique that detects various biomarkers, including common biomarkers such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. There is particular interest in how effective early cancer diagnosis with liquid biopsies are, and its accuracy in early diagnosis prior to other prominent cancer testing/screenings. After studying a bibliometric review, we identified hot spot topics to focus on and wrote this non-systematic review article regarding new details about common biomarkers (ctDNA, exosomes, and CTC), novel technology, and recent tissue vs. liquid biopsy comparisons (non-small cell lung cancer and glioblastoma). More specifically, our study focuses on particular cancers and associated novel progressions in clinical studies that utilize liquid biopsies. This literature review covers updated findings from other reviews and clinical studies centered on recent advances in standardization, development, and application of novel high-throughput technology. This study also compares tissue biopsies—a standard cancer diagnostic technique—and its complementary role in early cancer detection with liquid biopsies. Additionally, this paper explores topical challenges in liquid biopsy specificity, efficacy, and cost-efficiency in regards to personalized cancer diagnosis and treatment

Graphene Oxide and Graphene Nanosheet Reinforced Aluminium Matrix Composites: powder synthesis and prepared composite characteristics

The preparation and properties of reduced graphene oxide (rGO) and graphene nanosheets (GNSs) reinforcement of aluminium matrix nanocomposites (AMCs) are reported. For the rGO-AMCs, commercial colloidal GO was coated onto aluminium powder particles and then reduced via thermal annealing. For the GNS-AMCs, graphene exfoliated from graphite through ultrasonication and centrifugation was coated onto aluminium particle surfaces via dispersion mixing, filtering and drying. Pure aluminium and aluminium composites with various reinforcement concentrations of rGO and GNS were cold compacted into disc-shaped specimens and sintered in inert atmosphere. The mechanical properties and microstructure were studied and characterised via Vickers hardness, X-ray diffraction, density measurement, and scanning electron microscopy. The reinforcements were uniformly distributed onto the aluminium particle surfaces before and after consolidation within the composites. The relevant factors for the powder metallurgy process (compaction pressure, density, and sintering conditions) were optimised. Increased levels of increased hardness were recorded, over baseline compacted and sintered pure aluminium samples, prepared under identical experimental conditions, of 32% and 43% respectively for the 0.3 wt.% rGO-Al and 0.15 wt.% GNSs-Al composites. The process developed and presented herein provides encouraging results for realising rGO-AMC and GNS–AMC nanocomposites via low cost cold powder compaction and sintering metallurgy techniques

Solidification Processing of Magnesium Based In-Situ Metal Matrix Composites by Precursor Approach

In-situ magnesium based metal matrix composites (MMCs) belong to the category of advanced light weight metallic composites by which ceramic dispersoids are produced by a chemical reaction within the metal matrix itself. In-situ MMCs comprised uniform distribution of thermodynamically stable ceramic dispersoids, clean and unoxidized ceramic-metal interfaces having high interfacial strength. In last two decades, investigators have been collaborating to explore the possibility of enhancing the high temperature creep resistance performance in polymer-derived metal matrix composites (P-MMCs) by utilizing polymer precursor approach. A unique feature of the P-MMC process is that since all constituents of the ceramic phase are built into the polymer molecules itself, there is no need for a separate chemical reaction between the host metal and polymer precursor in order to form in-situ ceramic particles within the molten metal. Among the different polymer precursors commercially available in the market, the silicon-based polymers convert into the ceramic phase in the temperature range of 800–1000°C. Therefore, these Si-based polymers can be infused into molten Mg or Mg-alloys easily by simple stir-casting method. This chapter mainly focuses on understanding the structure–property correlation in both the Mg-based and Mg-alloy based in-situ P-MMCs fabricated by solidification processing via polymer precursor approach

Study of the Efficiency and Temperature Loss Caused by Degassing and Filtration of AlSi9Cu3 Alloy

This paper presents a research on the ability of the techniques of degassing and filtration to improve the properties of the AlSi9Cu3 alloy. The study includes four types of samples: (1) nontreated, (2) filtered, (3) degassed, and (4) filtered and subsequently degassed samples. Degassing was carried out using nitrogen gas, whereas a 20-pores-per-inch (ppi) alumina filter was used for filtering the samples. The analysis was focused on three aspects: First, the influence of these processes on the porosity was determined by means of software to analyze micrographs. Second, the distribution of phases and the presence of inclusions were obtained by combining optical and scanning electron microscopy. Finally, the temperature loss as a result of each of the treatments received by the material was measured. This information is particularly relevant in view of the subsequent use of the molten material to manufacture parts through highpressure die casting.This investigation was developed within a research project sponsored by the Society for the Regional Development of Cantabria (SODERCAN)

Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study

Background The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear. Objective This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive surgery, and such delay had an impact on cancer outcomes. Study Design This was a multicenter, international, prospective cohort study. Consecutive patients with gynecologic cancers who were initially planned for nonpalliative surgery, were recruited from the date of first COVID-19-related admission in each participating center for 3 months. The follow-up period was 3 months from the time of the multidisciplinary tumor board decision to operate. The primary outcome of this analysis is the incidence of pandemic-related changes in care. The secondary outcomes included 30-day perioperative mortality and morbidity and a composite outcome of unresectable disease or disease progression, emergency surgery, and death. Results We included 3973 patients (3784 operated and 189 nonoperated) from 227 centers in 52 countries and 7 world regions who were initially planned to have cancer surgery. In 20.7% (823/3973) of the patients, the standard of care was adjusted. A significant delay (>8 weeks) was observed in 11.2% (424/3784) of patients, particularly in those with ovarian cancer (213/1355; 15.7%; P<.0001). This delay was associated with a composite of adverse outcomes, including disease progression and death (95/424; 22.4% vs 601/3360; 17.9%; P=.024) compared with those who had operations within 8 weeks of tumor board decisions. One in 13 (189/2430; 7.9%) did not receive their planned operations, in whom 1 in 20 (5/189; 2.7%) died and 1 in 5 (34/189; 18%) experienced disease progression or death within 3 months of multidisciplinary team board decision for surgery. Only 22 of the 3778 surgical patients (0.6%) acquired perioperative SARS-CoV-2 infections; they had a longer postoperative stay (median 8.5 vs 4 days; P<.0001), higher predefined surgical morbidity (14/22; 63.6% vs 717/3762; 19.1%; P<.0001) and mortality (4/22; 18.2% vs 26/3762; 0.7%; P<.0001) rates than the uninfected cohort. Conclusion One in 5 surgical patients with gynecologic cancer worldwide experienced management modifications during the COVID-19 pandemic. Significant adverse outcomes were observed in those with delayed or cancelled operations, and coordinated mitigating strategies are urgently needed