5G Mobile Communications

This book provides a comprehensive overview of the emerging technologies for next-generation 5G mobile communications, with insights into the long-term future of 5G. Written by international leading experts on the subject, this contributed volume covers a wide range of technologies, research results, and networking methods. Key enabling technologies for 5G systems include, but are not limited to, millimeter-wave communications, massive MIMO technology and non-orthogonal multiple access. 5G will herald an even greater rise in the prominence of mobile access based upon both human-centric and machine-centric networks. Compared with existing 4G communications systems, unprecedented numbers of smart and heterogeneous wireless devices will be accessing future 5G mobile systems. As a result, a new paradigm shift is required to deal with challenges on explosively growing requirements in mobile data traffic volume (1000x), number of connected devices (10–100x), typical end-user data rate (10–100x), and device/network lifetime (10x). Achieving these ambitious goals calls for revolutionary candidate technologies in future 5G mobile systems. Designed for researchers and professionals involved with networks and communication systems, 5G Mobile Communications is a straightforward, easy-to-read analysis of the possibilities of 5G systems

Immunogenetics

This open access book explores techniques for working in the field of immunogenetics, i.e. fundamental and translational research into the adaptive immune receptor repertoire. Many chapters are dedicated to lab protocols, bioinformatics, and immunoinformatics analysis of high-resolution immunome analysis, exemplified by numerous applications. Additionally, the newest technological variations on these protocols are discussed, including non-amplicon, single-cell, and cell-free strategies. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Immunogenetics: Methods and Protocols covers a broad spectrum of methodologies for applications in research and clinical diagnostics to illustrate the impact that immunogenetics has achieved and will further expand in all fields of medicine, from infection and (auto)immunity, to vaccination, to lymphoid malignancy and tumor immunity

The Complex Network of miRNA and mRNA Target Interactions in Pancreatic Cancer

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is one of the most lethal tumour types world-wide. The majority of patients present late with locally advanced or metastatic disease. Therefore, despite advances in operative techniques, perioperative management and oncological treatments, the overall 5-year survival remains <5%. Determining tumoural factors that contribute towards its aggressive nature may help in identifying novel molecular biomarkers and/or therapeutic targets. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene expression and are able to act as tumour suppressors or oncogenes. MiRNAs have been extensively profiled and implicated in the initiation and progression of PDAC. Furthermore, there is a possibility of translating miRNAs into clinically useful biomarkers. Here, I developed upon these initial observations and demonstrate that miRNAs can be used to differentiate low risk pancreatic benign cystic tumours (BCTs) from PDAC. We confirmed that these miRNAs regulate the expression of known PDAC oncogenes, and that miR-16, miR-126 and let-7d target BCL2, CRK and KRAS respectively. Next, in order to investigate the main contributors to tumourigenesis, an integrated molecular analysis (miRNA-mRNA) was performed in PDAC. By using a combination of network-based bioinformatics, miR-21, miR-23a and miR-27a were prioritised as important in PDAC progression. We demonstrated that the use of a combination of miRNA inhibitors (against miR-21, miR-23a and miR-27a) in a murine subcutaneous PDAC xenograft model was able to reduce tumour growth, better than oncomiR-21 inhibition alone. BTG2 and NEDD4L were found to be direct targets of the miRNA combination and were established as new candidate tumour suppressors in PDAC. The clinical relevance of this 3 miRNA signature was demonstrated, as high expressors of the combination have poor overall survival after surgical resection, independent of other clinicopathologic factors. Together, these studies identify specific miRNAs as important regulators of PDAC tumourigenesis and their possible use as biomarkers.Open Acces

Epigenetic gene silencing by heterochromatin primes fungal resistance

Genes embedded in H3 lysine 9 methylation (H3K9me)–dependent heterochromatin are transcriptionally silenced. In fission yeast, Schizosaccharomyces pombe, H3K9me-mediated heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent. Under certain conditions wild-type cells might utilize heterochromatin heritability to form epimutations, phenotypes mediated by unstable silencing rather than DNA changes. This study shows that resistant heterochromatin-dependent epimutants arise in threshold levels of caffeine. Unstable resistant isolates exhibit distinct heterochromatin islands, which reduce expression of underlying genes, some of which confer resistance when mutated. Targeting synthetic heterochromatin to implicated loci confirms that resistance results from heterochromatin-mediated silencing. The analyses presented here reveal that epigenetic processes promote phenotypic plasticity, allowing wild-type cells to adapt to non-favorable environments without altering their genotype. In some isolates, subsequent or co-occurring gene amplification events augment resistance. Caffeine impacts two anti silencing factors: Epe1 levels are downregulated, reducing its chromatin association; and Mst2 histone acetyltransferase expression switches to a shortened isoform. Thus, heterochromatin-dependent epimutant formation provides a bet-hedging strategy that allows cells to remain genetically wild-type but adapt transiently to external insults. Unstable caffeine-resistant isolates show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to antifungal drug resistance in plant and human pathogenic fungi

Effects of circadian rhythm phase alteration on physiological and psychological variables: Implications to pilot performance (including a partially annotated bibliography)

The effects of environmental synchronizers upon circadian rhythmic stability in man and the deleterious alterations in performance and which result from changes in this stability are points of interest in a review of selected literature published between 1972 and 1980. A total of 2,084 references relevant to pilot performance and circadian phase alteration are cited and arranged in the following categories: (1) human performance, with focus on the effects of sleep loss or disturbance and fatigue; (2) phase shift in which ground based light/dark alteration and transmeridian flight studies are discussed; (3) shiftwork; (4)internal desynchronization which includes the effect of evironmental factors on rhythmic stability, and of rhythm disturbances on sleep and psychopathology; (5) chronotherapy, the application of methods to ameliorate desynchronization symptomatology; and (6) biorythm theory, in which the birthdate based biorythm method for predicting aircraft accident susceptability is critically analyzed. Annotations are provided for most citations

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion

Computational analysis of transcriptional and post-transcriptional regulation of gene expression

The regulation of gene expression is fundamental to all life on Earth. Dynamic but precise control is vital to cell survival and function, and takes place at various tightly interwoven levels. In this thesis, we review and study the crosstalk between different types of regulators, including epigenetic regulators, transcription factors (TFs), RNA-binding proteins (RBPs) and microRNAs (miRNAs). First, we focus on the interplay between miRNAs and other types of regulators, in particular TFs and epigenetic regulators, both of which are strongly enriched among the predicted targets of miRNAs. Indeed, the direct interplay of miRNAs with other regulators that have genome-wide impact is one possible explanation for the reported importance of miRNAs to fundamental biological processes, including cell fate. We introduce a computational strategy that we apply in order to infer the transcription regulatory circuitries that act downstream of embryonic miRNAs. More precisely, we analyze genome-wide expression changes with an extended motif activity response analysis (MARA) model in order to identify transcriptional regulators that are direct targets of embryonic miRNAs and change in activity upon expression of the miRNAs. We experimentally validate our most promising predictions and integrate the extended MARA model into an automated system in order to make it available to other researchers. We demonstrate its application by modeling diverse high-throughput datasets, including paired liver biopsies of patients with chronic hepatitis C virus infections. Finally, we study alternative cleavage and polyadenylation, a process that impacts gene expression in various ways, including modulating the presence of cis-regulatory elements, such as miRNA and RBP binding sites, which tend to be located at the 3' ends of transcripts. We demonstrate that global shortening of untranslated transcript regions, which is associated with proliferative states, has a very limited effect on mRNA stability and protein output. By analyzing a large array of high-throughput 3' end sequencing data, we create comprehensive catalogs of 3' end processing sites for both human and mouse. Moreover, we identify novel cis-regulatory motifs that are involved in cleavage and polyadenylation, and point out a regulator, HNRNPC, that binds to one of the motifs, thereby globally impacting the usage of cleavage and polyadenylation sites

Large bichromatic point sets admit empty monochromatic 4-gons

We consider a variation of a problem stated by Erd˝os and Szekeres in 1935 about the existence of a number fES(k) such that any set S of at least fES(k) points in general position in the plane has a subset of k points that are the vertices of a convex k-gon. In our setting the points of S are colored, and we say that a (not necessarily convex) spanned polygon is monochromatic if all its vertices have the same color. Moreover, a polygon is called empty if it does not contain any points of S in its interior. We show that any bichromatic set of n ≥ 5044 points in R2 in general position determines at least one empty, monochromatic quadrilateral (and thus linearly many).Postprint (published version