Nano-optical studies of superconducting nanowire single-photon detectors

uperconducting single-photon detectors based on superconducting nanowires offer broadband single-photon sensitivity, from visible to mid-infrared wavelengths. They have attracted particular attention due to their promising performance at telecommunications wavelengths. The additional benefits of superconducting nanowire single-photon detectors (SNSPDs) include low dark count rates (Hz) and low timing jitter (sub 100 ps). SNSPDs have been employed in practical photon-counting applications such as quantum key distribution (QKD), operation of quantum waveguide circuits and quantum emitter characterisation. Major challenges in the development of SNSPDs are the improvement of device uniformity and achieving efficient optical coupling. Nano-optical techniques such as confocal microscopy can be used to image localised areas of SNSPDs providing a direct measurement of the device uniformity. The work in this thesis describes both initial nano-optical testing at visible wavelengths in liquid helium and the construction of a fibre based miniature confocal microscope configuration operating at telecommunications wavelengths for use in a closed cycle refrigerator. In both cases localised areas of SNSPDs can be studied whilst maintaining efficient optical coupling. The miniature confocal microscope configuration has sub-nanometre position resolution over a 30 μm x 30 μm area by way of a piezoelectric X-Y scanner. A full width at half maximum (FWHM) optical resolution of 1305 nm at a wavelength of 1550 nm is achieved. SNSPDs based upon niobium nitride (NbN) nanowires fabricated on magnesium oxide (MgO) have been studied. The microscope system has allowed us to map the temporal response (timing jitter and output pulse timing delay) of constricted (non-uniform) SNSPDs. By fitting to a theoretical model, the variations in output pulse timing delay have been shown to be caused by variations in hotspot resistances across the device. This observation has provided insights into the underlying physics of SNSPDs and especially the origins of timing jitter in SNSPDs. This provides a pathway to exploitation of this effect in next-generation device designs for applications such as imaging

Applying digital content management to support localisation

The retrieval and presentation of digital content such as that on the World Wide Web (WWW) is a substantial area of research. While recent years have seen huge expansion in the size of web-based archives that can be searched efficiently by commercial search engines, the presentation of potentially relevant content is still limited to ranked document lists represented by simple text snippets or image keyframe surrogates. There is expanding interest in techniques to personalise the presentation of content to improve the richness and effectiveness of the user experience. One of the most significant challenges to achieving this is the increasingly multilingual nature of this data, and the need to provide suitably localised responses to users based on this content. The Digital Content Management (DCM) track of the Centre for Next Generation Localisation (CNGL) is seeking to develop technologies to support advanced personalised access and presentation of information by combining elements from the existing research areas of Adaptive Hypermedia and Information Retrieval. The combination of these technologies is intended to produce significant improvements in the way users access information. We review key features of these technologies and introduce early ideas for how these technologies can support localisation and localised content before concluding with some impressions of future directions in DCM

Multilingual adaptive search for digital libraries

This paper describes a framework for Adaptive Multilingual Information Retrieval (AMIR) which allows multilingual resource discovery and delivery using on-the-fly machine translation of documents and queries. Result documents are presented to the user in a contextualised manner. Challenges and affordances of both Adaptive and Multilingual IR, with a particular focus on Digital Libraries, are detailed. The framework components are motivated by a series of results from experiments on query logs and documents from The European Library. We conclude that factoring adaptivity and multilinguality aspects into the search process can enhance the user’s experience with online Digital Libraries

Disambiguating past events: accurate source memory for time and context depends on different retrieval processes

Participant payment was provided by the School of Psychology and Neuroscience ResPay scheme.Current animal models of episodic memory are usually based on demonstrating integrated memory for what happened, where it happened, and when an event took place. These models aim to capture the testable features of the definition of human episodic memory which stresses the temporal component of the memory as a unique piece of source information that allows us to disambiguate one memory from another. Recently though, it has been suggested that a more accurate model of human episodic memory would include contextual rather than temporal source information, as humans’ memory for time is relatively poor. Here, two experiments were carried out investigating human memory for temporal and contextual source information, along with the underlying dual process retrieval processes, using an immersive virtual environment paired with a ‘Remember-Know’ memory task. Experiment 1 (n = 28) showed that contextual information could only be retrieved accurately using recollection, while temporal information could be retrieved using either recollection or familiarity. Experiment 2 (n = 24), which used a more difficult task, resulting in reduced item recognition rates and therefore less potential for contamination by ceiling effects, replicated the pattern of results from Experiment 1. Dual process theory predicts that it should only be possible to retrieve source context from an event using recollection, and our results are consistent with this prediction. That temporal information can be retrieved using familiarity alone suggests that it may be incorrect to view temporal context as analogous to other typically used source contexts. This latter finding supports the alternative proposal that time since presentation may simply be reflected in the strength of memory trace at retrieval – a measure ideally suited to trace strength interrogation using familiarity, as is typically conceptualised within the dual process framework.PostprintPeer reviewe

Strategies for the production of long-acting therapeutics and efficient drug delivery for cancer treatment

Protein therapeutics play a significant role in treating many diseases. They, however, suffer from patient's proteases degradation and antibody neutralization which lead to short plasma half-lives. One of the ways to overcome these pitfalls is the frequent injection of the drug albeit at the cost of patient compliance which affects the quality of life of patients. There are several techniques available to extend the half-life of therapeutics. Two of the most common protocols are PEGylation and fusion with human serum albumin. These two techniques improve stability, reduce immunogenicity, and increase drug resistance to proteases. These factors lead to the reduction of injection frequency which increases patient compliance and improve quality of life. Both techniques have already been used in many FDA approved drugs. This review describes many technologies to produce long-acting drugs with the attention of PEGylation and the genetic fusion with human serum albumin. The report also discusses the latest modified therapeutics in the field and their application in cancer therapy. We compare the modification methods and discuss the pitfalls of these modified drugs

HIVBrainSeqDB: a database of annotated HIV envelope sequences from brain and other anatomical sites

<p>Abstract</p> <p>Background</p> <p>The population of HIV replicating within a host consists of independently evolving and interacting sub-populations that can be genetically distinct within anatomical compartments. HIV replicating within the brain causes neurocognitive disorders in up to 20-30% of infected individuals and is a viral sanctuary site for the development of drug resistance. The primary determinant of HIV neurotropism is macrophage tropism, which is primarily determined by the viral envelope (<it>env</it>) gene. However, studies of genetic aspects of HIV replicating in the brain are hindered because existing repositories of HIV sequences are not focused on neurotropic virus nor annotated with neurocognitive and neuropathological status. To address this need, we constructed the HIV Brain Sequence Database.</p> <p>Results</p> <p>The HIV Brain Sequence Database is a public database of HIV envelope sequences, directly sequenced from brain and other tissues from the same patients. Sequences are annotated with clinical data including viral load, CD4 count, antiretroviral status, neurocognitive impairment, and neuropathological diagnosis, all curated from the original publication. Tissue source is coded using an anatomical ontology, the Foundational Model of Anatomy, to capture the maximum level of detail available, while maintaining ontological relationships between tissues and their subparts. 44 tissue types are represented within the database, grouped into 4 categories: (i) brain, brainstem, and spinal cord; (ii) meninges, choroid plexus, and CSF; (iii) blood and lymphoid; and (iv) other (bone marrow, colon, lung, liver, etc). Patient coding is correlated across studies, allowing sequences from the same patient to be grouped to increase statistical power. Using Cytoscape, we visualized relationships between studies, patients and sequences, illustrating interconnections between studies and the varying depth of sequencing, patient number, and tissue representation across studies. Currently, the database contains 2517 envelope sequences from 90 patients, obtained from 22 published studies. 1272 sequences are from brain; the remaining 1245 are from blood, lymph node, spleen, bone marrow, colon, lung and other non-brain tissues. The database interface utilizes a faceted interface, allowing real-time combination of multiple search parameters to assemble a meta-dataset, which can be downloaded for further analysis.</p> <p>Conclusions</p> <p>This online resource, which is publicly available at <url>http://www.HIVBrainSeqDB.org</url>, will greatly facilitate analysis of the genetic aspects of HIV macrophage tropism, HIV compartmentalization and evolution within the brain and other tissue reservoirs, and the relationship of these findings to HIV-associated neurological disorders and other clinical consequences of HIV infection.</p

Stereoselective Lewis Acid Mediated (3+2) Cycloadditions of N-H- and N-Sulfonylaziridines with Heterocumulenes

Alkyl and aryl isothiocyanates and carbodiimides are effective substrates in (3+2) cycloadditions with N-sulfonyl-2-substituted aziridines and 2-phenylaziridine for the synthesis of iminothiazolidines and iminoimidazolidines. Additionally, the stereoselective (3+2) cycloaddition of N-H- and N-sulfonylaziridines with isothiocyanates can be accomplished, allowing for the synthesis of highly enantioenriched iminothiazolidines. Evidence for an intimate ion-pair mechanism is presented herein in the context of these chemo-, regio-, and diastereoselective transformations. The demonstrated ability to remove the sulfonyl group from the heterocyclic products displays the utility of these compounds for further derivatization and application