1,138 research outputs found
Microfibre-Functionalised Silk Hydrogels
No full textSilk hydrogels have shown potential for tissue engineering applications, but several gaps and challenges, such as a restricted ability to form hydrogels with tuned mechanics and structural features, still limit their utilisation. Here, Bombyx mori and Antheraea mylitta (Tasar) silk microfibres were embedded within self-assembling B. mori silk hydrogels to modify the bulk hydrogel mechanical properties. This approach is particularly attractive because it creates structured silk hydrogels. First, B. mori and Tasar microfibres were prepared with lengths between 250 and 500 μm. Secondary structure analyses showed high beta-sheet contents of 61% and 63% for B. mori and Tasar microfibres, respectively. Mixing either microfibre type, at either 2% or 10% (w/v) concentrations, into 3% (w/v) silk solutions during the solution–gel transition increased the initial stiffness of the resulting silk hydrogels, with the 10% (w/v) addition giving a greater increase. Microfibre addition also altered hydrogel stress relaxation, with the fastest stress relaxation observed with a rank order of 2% (w/v) > 10% (w/v) > unmodified hydrogels for either fibre type, although B. mori fibres showed a greater effect. The resulting data sets are interesting because they suggest that the presence of microfibres provided potential ‘flow points’ within these hydrogels. Assessment of the biological responses by monitoring cell attachment onto these two-dimensional hydrogel substrates revealed greater numbers of human induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) attached to the hydrogels containing 10% (w/v) B. mori microfibres as well as 2% (w/v) and 10% (w/v) Tasar microfibres at 24 h after seeding. Cytoskeleton staining revealed a more elongated and stretched morphology for the cells growing on hydrogels containing Tasar microfibres. Overall, these findings illustrate that hydrogel stiffness, stress relaxation and the iPSC-MSC responses towards silk hydrogels can be tuned using microfibres
James Bond: international man of gastronomy
No full textThis article is concerned with the representation of food and drink in Ian Fleming’s James Bond novels. In particular, it examines how the author uses Bond’s culinary knowledge and habits of consumption as an important constituent of his hero’s character. Similarly, the food choices of other characters, notably villains, are shown to be linked, by Fleming, to core aspects of their identity − principally their ethnicity. Bond’s impulse to observe and classify, very much in evidence in the novels’ food sequences, is examined in terms of the texts’ construction of Bond as a skilled identifier of signs
Selective anticancer activity of a hexapeptide with sequence homology to a non-kinase domain of Cyclin Dependent Kinase 4
No full textBackground: cyclin-dependent kinases 2, 4 and 6 (Cdk2, Cdk4, Cdk6) are closely structurally homologous proteins which are classically understood to control the transition from the G1 to the S-phases of the cell cycle by combining with their appropriate cyclin D or cyclin E partners to form kinase-active holoenzymes. Deregulation of Cdk4 is widespread in human cancer, CDK4 gene knockout is highly protective against chemical and oncogene-mediated epithelial carcinogenesis, despite the continued presence of CDK2 and CDK6; and overexpresssion of Cdk4 promotes skin carcinogenesis. Surprisingly, however, Cdk4 kinase inhibitors have not yet fulfilled their expectation as 'blockbuster' anticancer agents. Resistance to inhibition of Cdk4 kinase in some cases could potentially be due to a non-kinase activity, as recently reported with epidermal growth factor receptor. Results: a search for a potential functional site of non-kinase activity present in Cdk4 but not Cdk2 or Cdk6 revealed a previously-unidentified loop on the outside of the C'-terminal non-kinase domain of Cdk4, containing a central amino-acid sequence, Pro-Arg-Gly-Pro-Arg-Pro (PRGPRP). An isolated hexapeptide with this sequence and its cyclic amphiphilic congeners are selectively lethal at high doses to a wide range of human cancer cell lines whilst sparing normal diploid keratinocytes and fibroblasts. Treated cancer cells do not exhibit the wide variability of dose response typically seen with other anticancer agents. Cancer cell killing by PRGPRP, in a cyclic amphiphilic cassette, requires cells to be in cycle but does not perturb cell cycle distribution and is accompanied by altered relative Cdk4/Cdk1 expression and selective decrease in ATP levels. Morphological features of apoptosis are absent and cancer cell death does not appear to involve autophagy. Conclusion: these findings suggest a potential new paradigm for the development of broad-spectrum cancer specific therapeutics with a companion diagnostic biomarker and a putative functional site for kinase-unrelated activities of Cdk4
Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers
No full textBackgroundThe MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.MethodsGenomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus.ResultsThe polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80).ConclusionWe found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1
Relations that unite and divide : a study of Freedom of Information legislation and transparency in Scotland
No full textThis research (the first long-term ethnographic study of FOI in Britain) investigates concepts at the heart of FOI - transparency, trust, secrecy, truth, private, public, power and agency. Eighteen months participant observation fieldwork, alongside policy-makers, practitioners, and end-users facilitated in depth, study of the radical subject-object transformations that FOI requires, and the aesthetics that underpin it.
The introduction of FOI entailed a 'culture change' - from a culture of secrecy to one of disclosure - driven, in Scotland, by the Scottish Information Commissioner through conferences. These were an opportunity for practitioners to come into new knowledge about the Act, their shared knowledge dissolving the divisions between them. But new divisions then opened between practitioners and colleagues; culture change being in the replication of a form of a relationship that previously lay between government and citizens.
In their replicated form, individual practitioners disappeared - were made 'transparent' - only to reappear on being differentiated, leaving them acutely aware of the personal relations this fissure disclosed, and throwing into sharp question a theory of people's division as indicative of their 'secrecy'. Transparency, here, depended on whether people were divided or combined - acting in their own capacity, or that of the organization.
While making personal relations absent from new disclosures was necessary for FOI compliance, this concealment hid a complex network of relations, and turned knowledge into 'information'. Yet the division between information and knowledge was not crisp: end-users continued to read practitioners' personal relations in disclosed information, thus relations were both absent from and implied in the information released.
Whether information was public (and accessible) depended on the undifferentiated status of those who created, handled, or were the subjects of, information. As people came into new knowledge, invoking their divided or common footing, they alternated between appearing 'private' or 'public' - person or thing - a division between individuals reflecting a division within each of them
Expanding the synthesis of distributed memory implementations
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (page 63).In this thesis, I expanded the programming model implemented by the Sketch language to supplement its distributed memory parallelism with shared memory parallelism that uses the popular fork-join model. The primary contribution of this thesis is the means by which the code is assured to be free of race conditions. Sketch uses constraint satisfaction analysis to ensure it synthesizes code the functions properly for all inputs, and I demonstrate how assertions can be generated and inserted into the analysis to guarantee freedom from race conditions. This expanded programming model is then evaluated using test cases to ensure correct operation and benchmarks to examine overall performance.by Jeremy Edward Sharpe.M. Eng
An interpreter for a novice-oriented programming language with runtime macros
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 77-78).In this thesis, we present the design and implementation of a new novice-oriented programming language with automatically hygienic runtime macros, as well as an interpreter framework for creating such languages. The language is intended to be used as a pedagogical tool for introducing basic programming concepts to introductory programming students. We designed it to have a simple notional machine and to be similar to other modern languages in order to ease a student's transition into other programming languages.by Jeremy Daniel Kaplan.M. Eng
A low power display driver with simultaneous image transformation
No full textThesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (leaves 70-73).In this thesis, I designed, implemented, and evaluated the energy consumption of a system that uses a liquid crystal display to perform a one-dimensional transform. The RMS response of the liquid crystal elements themselves were exploited to perform a matrix multiplication (image transformation) over a single frame period. This image transformation was used as the last step of the decompression process in an image processing system. The system was implemented first in Matlab, then as a printed circuit board, and finally as an integrated circuit. While the initial Matlab and printed circuit board implementations looked promising, a number of practical considerations arose during the integrated circuit design that ultimately resulted in moderate performance: 14.3% energy savings.by Jeremy Zaks Walker.M.Eng
Interactive debugger with reversible state
No full textThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: M. Eng. in Computer Science and Engineering, Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2019Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (page 43).This thesis describes PSI (Python Semantic Investigator), a program designed to help students explore their code by allowing them to see the state of their program at any step along its execution. PSI enables them to move forwards or backwards freely along the timeline of their program. It also enables them to designate variable names or object IDs and jump back to the last time such a variable or object was modified. Doing so is intended to help novice students learn to debug more effectively.by Jeremy Theard Wright.M. Eng. in Computer Science and EngineeringM.Eng.inComputerScienceandEngineering Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Scienc
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