95 research outputs found
Advanced sequencing technologies applied to human cytomegalovirus
The betaherpesvirus human cytomegalovirus (HCMV) is a ubiquitous viral pathogen. It is the most common cause of congenital infection in infants and of opportunistic infections in immunocompromised patients worldwide. The large double-stranded DNA genome of HCMV (236 kb) contains several genes that exhibit a high degree of variation among strains within an otherwise highly conserved sequence. These hypervariable genes encode immune escape, tropism or regulatory factors that may affect virulence. Variation arising from these genes and from an evolutionary history of recombination between strains has been hypothesised to be linked to disease severity. To investigate this, the HCMV genome has been scrutinised in detail over the years using a variety of molecular techniques, most looking only at one or a few of these genes at a time. The advent of high-throughput sequencing (HTS) technology 20 years ago then started to enable more in-depth whole-genome analyses. My study extends this field by using both HTS and the more recently developed long-read nanopore technology to determine HCMV genome sequences directly from clinical samples. Firstly, I used an Illumina HTS pipeline to sequence HCMV strains directly from formalin-fixed, paraffin-embedded (FFPE) tissues. FFPE samples are a valuable repository for the study of relatively rare diseases, such as congenital HCMV (cCMV). However, formalin fixation induces DNA fragmentation and cross-linking, making this a challenging sample type for DNA sequencing. I successfully sequenced five whole HCMV genomes from FFPE tissues. Next, I developed a pipeline utilising the single-molecule, long-read sequencer from Oxford Nanopore Technologies (ONT) to sequence HCMV initially from high-titre cellcultured laboratory strains and then from clinical samples with high HCMV loads. Finally, I utilised a direct RNA sequencing protocol with the ONT sequencer to characterise novel HCMV transcripts produced during infection in cell culture, demonstrating the existence of transcript isoforms with multiple splice sites. Overall, my findings demonstrate how advanced sequencing technologies can be used to characterise the genome and transcriptome of a large DNA virus, and will facilitate future studies on HCMV prognostic factors, novel antiviral targets and vaccine development
Reconstruction of graph colourings
A -deck of a (coloured) graph is a multiset of its induced -vertex
subgraphs. Given a graph , when is it possible to reconstruct with high
probability a uniformly random colouring of its vertices in colours from
its -deck? In this paper, we study this question for grids and random
graphs. Reconstruction of random colourings of -dimensional -grids from
the deck of their -subgrids is one of the most studied colour reconstruction
questions. The 1-dimensional case is motivated by the problem of reconstructing
DNA sequences from their `shotgunned' stretches. It was comprehensively studied
and the above reconstruction question was completely answered in the '90s. In
this paper, we get a very precise answer for higher . For every
and every , we present an almost linear algorithm that reconstructs
with high probability a random -colouring of vertices of a -dimensional
-grid from the deck of all its -subgrids for every and prove that the random -colouring is not
reconstructible with high probability if .
This answers the question of Narayanan and Yap (that was asked for )
on "two-point concentration" of the minimum so that -subgrids determine
the entire colouring. Next, we prove that with high probability a uniformly
random -colouring of vertices of a uniformly random graph is
reconstructible from its full -deck if and is not
reconstructible with high probability if . We further
show that the colour reconstruction algorithm for random graphs can be modified
and used for graph reconstruction: we prove that with high probability
is reconstructible from its full -deck if
while it is not reconstructible with high probability if
An Algorithm to Recover Shredded Random Matrices
Given some binary matrix , suppose we are presented with the collection of
its rows and columns in independent arbitrary orderings. From this information,
are we able to recover the unique original orderings and matrix? We present an
algorithm that identifies whether there is a unique ordering associated with a
set of rows and columns, and outputs either the unique correct orderings for
the rows and columns or the full collection of all valid orderings and valid
matrices. We show that there is a constant such that the algorithm
terminates in time with high probability and in expectation for random
binary matrices with i.i.d.\ Bernoulli entries
such that
Shotgun assembly of random graphs
In the graph shotgun assembly problem, we are given the balls of radius
around each vertex of a graph and asked to reconstruct the graph. We study the
shotgun assembly of the Erd\H{o}s-R\'enyi random graph from a
wide range of values of . We determine the threshold for reconstructibility
for each , extending and improving substantially on results of Mossel
and Ross for . For , we give upper and lower bounds that improve on
results of Gaudio and Mossel by polynomial factors. We also give a sharpening
of a result of Huang and Tikhomirov for .Comment: 36 pages, 3 figure
Play Among Books
How does coding change the way we think about architecture? Miro Roman and his AI Alice_ch3n81 develop a playful scenario in which they propose coding as the new literacy of information. They convey knowledge in the form of a project model that links the fields of architecture and information through two interwoven narrative strands in an “infinite flow” of real books
Assuming Data Integrity and Empirical Evidence to The Contrary
Background: Not all respondents to surveys apply their minds or understand
the posed questions, and as such provide answers which lack coherence, and
this threatens the integrity of the research. Casual inspection and limited
research of the 10-item Big Five Inventory (BFI-10), included in the dataset of
the World Values Survey (WVS), suggested that random responses may be
common.
Objective: To specify the percentage of cases in the BRI-10 which include
incoherent or contradictory responses and to test the extent to which the
removal of these cases will improve the quality of the dataset.
Method: The WVS data on the BFI-10, measuring the Big Five Personality (B5P), in South Africa (N=3 531), was used. Incoherent or contradictory responses were removed. Then the cases from the cleaned-up dataset were analysed for their theoretical validity.
Results: Only 1 612 (45.7%) cases were identified as not including incoherent
or contradictory responses. The cleaned-up data did not mirror the B5P- structure, as was envisaged. The test for common method bias was negative. Conclusion: In most cases the responses were incoherent. Cleaning up the data did not improve the psychometric properties of the BFI-10. This raises concerns about the quality of the WVS data, the BFI-10, and the universality of B5P-theory. Given these results, it would be unwise to use the BFI-10 in South Africa. Researchers are alerted to do a proper assessment of the
psychometric properties of instruments before they use it, particularly in a
cross-cultural setting
Leading Towards Voice and Innovation: The Role of Psychological Contract
Background: Empirical evidence generally suggests that psychological
contract breach (PCB) leads to negative outcomes. However, some literature
argues that, occasionally, PCB leads to positive outcomes.
Aim: To empirically determine when these positive outcomes occur, focusing
on the role of psychological contract (PC) and leadership style (LS), and
outcomes such as employ voice (EV) and innovative work behaviour (IWB).
Method: A cross-sectional survey design was adopted, using reputable
questionnaires on PC, PCB, EV, IWB, and leadership styles. Correlation
analyses were used to test direct links within the model, while regression
analyses were used to test for the moderation effects.
Results: Data with acceptable psychometric properties were collected from 11
organisations (N=620). The results revealed that PCB does not lead to
substantial changes in IWB. PCB correlated positively with prohibitive EV, but did not influence promotive EV, which was a significant driver of IWB. Leadership styles were weak predictors of EV and IWB, and LS only partially moderated the PCB-EV relationship. Conclusion: PCB did not lead to positive outcomes. Neither did LS influencing the relationships between PCB and EV or IWB. Further, LS only partially influenced the relationships between variables, and not in a manner which positively influence IWB
The Deep End: A Journey of Faith
This paper is an expansion of papers written in my MFA program’s creative non-fiction writing class and workshop. In English 600: Editing, Layout, and Publishing, the class wrote a paper to document our faith journey and our approach to understanding ourselves and our worldview based on our religious indoctrination. This paper was 10-15 pages long and had a title page, a table of contents, an acknowledgment page, and a dedication page. After writing this paper, I began to consider the possibility of writing a longer work that would dig deeper into the real essence of my faith walk. It would take a lot more than 10-15 pages for me to provide a more detailed story. Therefore, this thesis is a longer version of that paper. Though it may cover some of the same issues, there is more depth and clarity. It is both a literary work and a testimony of my faith
Hardware / Software System for Portable and Low-Cost Genome Assembly
“The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political belief, economic or social condition” [56]. Genomics (the study of the entire DNA) provides such a standard of health for people with rare diseases and helps control the spread of pandemics. Still, millions of human beings are unable to access genomics due to its cost, and portability.
In genomics, DNA sequencers digitise DNA information, and computers analyse the digitised information. We have desktop and thumb-sized DNA sequencers, that digitise the DNA data rapidly. But computations necessary for the analysis of this data are inevitably performed on high-performance computers (HPCs) and cloud computers. These computations not only require powerful computers but also necessitate high-speed networks since the data generated are in the hundreds of gigabytes.
Relying on HPCs and high-speed networks, deny the benefits that can be reaped by genomics for the masses who live in remote areas and in poorer nations. Developing a low-cost and portable genomics computation platform would provide personalised treatment based on an individual’s DNA and identify the source of the fast-spreading epidemics in remote areas and areas without HPC or network infrastructure. But developing a low-cost and portable genome analysing computing platform is a challenging task. This thesis develops novel computer architecture solutions to assemble the whole human DNA and COVID-19 virus RNA on a low-cost and portable platform.
The first phase of the solution describes a ring-pipelined processor architecture for a key genome assembly algorithm. The human genome is partitioned to fit into the small memory footprint of embedded processors. These techniques allow an entire human genome to be assembled using highly portable and low-cost embedded processor cores. These processor cores can be housed within a single chip. Each processor was only 0.08 mm 2 and consumed just 37.5 mW. It has only 2 GB memory, 32-bit instruction width, and a clock with a 1 GHz frequency.
The second phase of the solution describes how application-specific instruction-set processors can be sped up to execute a key genome assembly algorithm. A fully automated design system is presented, which improves the performance of large applications (such as genome assembly algorithm) and generates application-specific instructions for a commercial processor design tool (Xtensa). The tool enhances the base processor, which was used in the ring pipeline processor architecture. Thus, the alignment algorithms execute 2.1 times faster with only 11% additional hardware. The energy-delay product was reduced by 7.3× compared to the base processor. This tool is the only one of its type which can handle applications which are large. The third phase of the solution designs a portable low-cost genome assembly computer (PGA). PGA enhances the ring pipeline architecture with the customised processor found in phase two and with improved inter-processor communication. The results show that the COVID-19 virus RNA can be assembled in under 10 minutes and the whole human genome can be assembled in 11 days on a portable platform (HPC take around two days) for 30× coverage.
PGA has an area footprint of just 5.68 mm 2 in a 28 nm technology node and is far smaller than a high-performance computer processor chip. The PGA consumes only 4W of power, which is lower than the power requirement of a high-performance processor chip. The manufacturing cost of the PGA also would be much cheaper than the high-performance system cost, when produced in volume.
The developed solution can be powered by a USB port of a laptop. This thesis is the first of its type to show the design of a single-chip solution to be able to process a complex genomic problem.
This thesis contributes to attaining one of the fundamental rights of every human being wherever they may live
Men in David Malouf’s Fiction
[eng] The aim of this thesis is to assess David Malouf’s contribution to the field of gender and men studies in his fiction books. In order to do so, I have proceeded by offering a close reading of each of his novels so as to emphasise those parts of the plot where gender and masculinities are more relevant, and from here engaging in a series of theoretical discourses as I saw convenient in the course of my analysis. We read his largely autobiographical novel Johnno in the tradition of the Bildungsroman. In this tradition, the main characters fulfil themselves when they meet the roles that society expects of them. Therefore, becoming a man or a woman means meeting these expectations. In Johnno, Malouf offers an alternative form of successful socialisation that redeems the main character, Dante as an artist but is also built on personal tragedy. We use Judith Butler’s studies on the performativity of gender, Hélène Cixous and Julia Kristeva’s ècriture feminine and their distinction between symbolic and semiotic language, Eve K. Sedgwick and René Girard’s studies on homosocial desire and triangulation, and Simone the Beauvoir and Pierre Bourdieu’s ethnographic research on women and Kabyle society, respectively, to read An Imaginary Life and Harland’s Half Acre. In An Imaginary Life, Malouf fictionalises the life of the poet Ovid in exile. In Rome, Ovid defies patriarchy and the Emperor writing a poetry that is uncivil and gay. In his exile in Tomis, Ovid decides to raise a feral Child against the advice of the women in the village, who end up using their power, based on folklore and superstition, to get rid of them. In Harland’s Half Acre, Malouf creates a male household where women are mostly absent, and a female one where the women are the main actors and men play a secondary role. When the main character of the novel, Frank Harland, finally recovers the family estate for his family’s only descendant, his nephew Gerald, the latter commits suicide. One of Malouf’s main concerns in his writings, the outcome of the novels privilege a spiritual sort of possession over one based on the values of patriarchy, that is, bloodline succession by right of the first-born male child, hierarchical power relations and ownership: Ovid survives in his poems thanks to the human need for magic and superstition, and so does Frank in his art. Michael S. Kimmel and R. W. Connell’s studies on men and masculinities, and historical research on Australian identity as it was forged during the colonial period and the World Wars help us read Fly Away Peter, The Great World, Remembering Babylon and The Conversations at Curlow Creek. In Australia, national identity and definitions of manhood are closely tied to frontier and war masculinities. In these novels, Malouf portrays the Australian legend: sceptical of authority, easy-going, egalitarian, larrikin, resourceful, etc. Unfortunately, the legend had a destructive effect on women and the feminine, and that is the reason why we recover from oblivion the important role that women played in the construction of Australia. Edward Said’s research in Culture and Imperialism, Homi Bhabha’s notions of hybridity and mimicry, and Joseph Conrad’s Heart of Darkness provide us valuable tools to analyse class and ethnic issues when we ask ourselves what it means to be a man in Remembering Babylon. Margaret M. Gullette’s studies on the representation of age bias in literature and Ashton Applewhite’s research against ageism provide the theoretical framework for Ransom, where Malouf tells the story of Priam’s ransom of his son Hector, urging us to wonder what kind of heroism is left to a man in his old age. Finally, we offer a close reading of the outcome of the novels, where the agents of transformation are always male or involve male characters: Dante and Johnno, the eponymous hero of the novel; the Child in An Imaginary Life; Digger and Vic in The Great World; Gemmy in Remembering Babylon or Priam and Achilles in Ransom. In this way, we hope to better understand and more clearly render the world of men that Malouf portrays in his novels.[cat] L’objectiu de la tesi és valorar la contribució de les obres de ficció de David Malouf als estudis de gènere i de masculinitats. Per tal d’aconseguir-ho, hem dut a terme una lectura fidel de les seves novel·les tot emfasitzant aquells elements de la història on el gènere i les masculinitats són més rellevants, i a partir d’aquí hem emprat una sèrie de teories que consideràvem adients en la nostra anàlisi. Hem llegit la seva novel·la àmpliament autobiogràfica, Johnno en la tradició de la Bildungsroman. En aquesta tradició, els personatges principals es realitzen quan compleixen les expectatives que la societat espera d’ells. Així doncs, fer-se un home o una dona vol dir complir aquestes expectatives. A Johnno, Malouf ens dóna una forma alternativa de socialització exitosa que redimeix al personatge principal, Dante, però que també s’erigeix sobre una tragèdia personal. Emprem la recerca de Judith Butler sobre la “performativitat” del gènere, l’ècriture feminine d’Hélène Cixous i Julia Kristeva i la distinció que fan entre llenguatge semiòtic i simbòlic, els estudis de Eve K. Sedgwick i René Girard sobre desig homosocial i el triangle amorós, i la recerca etnogràfica de Simone the Beauvoir i Pierre Bourdieu sobre la dona I la societat Kabyle, respectivament, en la nostra anàlisi d’An Imaginary Life i Harland’s Half Acre. A An Imaginary Life, Malouf narra la vida del poeta Ovidi a l’exili. A Roma, Ovidi desafia el patriarcat escrivint una poesia que és impertinent i divertida. Al seu exili a Tomis, Ovidi decideix criar un nen salvatge, contradient el consell de les dones del poble, que acaben utilitzant el seu poder, basat en les tradicions populars i la superstició, per lliurar-se’n. A Harland’s Half Acre, Malouf crea una llar principalment masculina on les dones hi són absents, i una de femenina on les dones porten les rendes de la casa i els homes hi tenen un paper secundari. Quan el personatge principal de la novel·la, Frank Harland, finalment recupera l’herència de la seva família i la vol entregar a l’únic descendent que queda de la família, el seu nebot Gerald, aquest es suïcida. Un dels temes més recurrents a les novel·les de David Malouf, el desenllaç de les novel·les privilegien una possessió de tipus espiritual per damunt d’una possessió basada en els valors del patriarcat, és a dir, la descendència basada en els fills legítims o de sang i els privilegis del fill primogènit, relacions jeràrquiques de poder i la propietat. Emprem els estudis sobre homes i masculinitats de Michael S. Kimmel i R. W. Connell, la recerca històrica de la identitat Australiana tal com es va forjar durant el període colonial i les dues Guerres Mundials en la nostra anàlisi de Fly Away Peter, The Great World, Remembering Babylon i The Conversations at Curlow Creek. A Austràlia, la identitat nacional i les definicions de masculinitat estan estretament lligades a les masculinitats de fronteres i de guerra. En aquestes novel·les, Malouf representa la llegenda del típic Australià: escèptic de l’autoritat, relaxat, igualitari, malparlat, informal, amb recursos, etc. Malauradament, la llegenda va tenir un efecte molt destructiu en les dones i els valors femenins, i per això recuperem de l’oblit l’important paper que van jugar les dones en la construcció d’Austràlia. La recerca d’Edward Said a Culture and Imperialism, les nocions d’hibridització i mimetisme d’Homi Bhabha, i la novel·la Heart of Darkness, de Joseph Conrad, ens proporcionen eines valuoses per la nostra anàlisi de qüestions ètniques i de classe quan ens preguntem què vol dir ser home a Remembering Babylon. Els estudis de Margaret M. Gullette sobre els prejudicis de la representació de l’edat a la literatura, i la recerca d’Ashton Applewhite contra els prejudicis de l’edat, ens proporcionen el marc teòric de la nostra lectura de Ransom, on Malouf explica la història de Priam, que rescata el cos del seu fill Hèctor de les mans d’Aquil·les, tot preguntant-nos quin tipus d’heroisme li queda a un home quan es fa vell. Finalment, oferim una lectura atenta de la resolució de les novel·les, on els agents del canvi són sempre masculins o impliquen personatges masculins. Per exemple, Dante i Johnno, l’heori epònim de la novel·la; el nen salvatge a An Imaginary Life; Digger i Vic a The Great World; Gemmy a Remembering Babylon o Priam i Achilles a Ransom. D’aquesta manera, esperem entendre millor i transmetre més clarament el món dels homes que Malouf ens representa a les seves novel·les
- …