Showing papers by "Dublin City University published in 2011"

Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

Abstract: Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)–dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor–bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8 + T-cell–dependent manner. These data provide a rationale for targeting macrophage recruitment/response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. Significance: These findings reveal that response to chemotherapy is in part regulated by the tumor immune microenvironment and that common cytotoxic drugs induce neoplastic cells to produce monocyte/macrophage recruitment factors, which in turn enhance macrophage infiltration into mammary adenocarcinomas. Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8 + T-cell–dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy. Cancer Discovery; 1(1); 54–67. ©2011 AACR . This article is highlighted in the In This Issue feature, p. 4

The place of the literature review in grounded theory research

Abstract: TSRM_A_494930.sg m For those employing grounded theory as a research methodology, the issue of how and when to engage with existing literature is often problematic, especially for PhD students. With this in mind, the current article seeks to offer some clarity on the topic and provide novice grounded theory researchers in particular with advice on how to approach the issue of the literature review in grounded theory. This is done by reviewing the origins of grounded theory, exploring the original stance taken by the founders of the methodology with regard to the literature review, tracking how this position has changed over time, outlining the rationale associated with specific positions and discussing ideas for reconciling opposing perspectives. Coupled with this, the author draws on his own experience of using grounded theory for his PhD research to explain how extant literature may be used and discusses how the nature of engagement with existing literature may impact upon the overall written presentation of a grounded theory study.

How many steps/day are enough? for children and adolescents

Abstract: Worldwide, public health physical activity guidelines include special emphasis on populations of children (typically 6-11 years) and adolescents (typically 12-19 years). Existing guidelines are commonly expressed in terms of frequency, time, and intensity of behaviour. However, the simple step output from both accelerometers and pedometers is gaining increased credibility in research and practice as a reasonable approximation of daily ambulatory physical activity volume. Therefore, the purpose of this article is to review existing child and adolescent objectively monitored step-defined physical activity literature to provide researchers, practitioners, and lay people who use accelerometers and pedometers with evidence-based translations of these public health guidelines in terms of steps/day. In terms of normative data (i.e., expected values), the updated international literature indicates that we can expect 1) among children, boys to average 12,000 to 16,000 steps/day and girls to average 10,000 to 13,000 steps/day; and, 2) adolescents to steadily decrease steps/day until approximately 8,000-9,000 steps/day are observed in 18-year olds. Controlled studies of cadence show that continuous MVPA walking produces 3,300-3,500 steps in 30 minutes or 6,600-7,000 steps in 60 minutes in 10-15 year olds. Limited evidence suggests that a total daily physical activity volume of 10,000-14,000 steps/day is associated with 60-100 minutes of MVPA in preschool children (approximately 4-6 years of age). Across studies, 60 minutes of MVPA in primary/elementary school children appears to be achieved, on average, within a total volume of 13,000 to 15,000 steps/day in boys and 11,000 to 12,000 steps/day in girls. For adolescents (both boys and girls), 10,000 to 11,700 may be associated with 60 minutes of MVPA. Translations of time- and intensity-based guidelines may be higher than existing normative data (e.g., in adolescents) and therefore will be more difficult to achieve (but not impossible nor contraindicated). Recommendations are preliminary and further research is needed to confirm and extend values for measured cadences, associated speeds, and MET values in young people; continue to accumulate normative data (expected values) for both steps/day and MVPA across ages and populations; and, conduct longitudinal and intervention studies in children and adolescents required to inform the shape of step-defined physical activity dose-response curves associated with various health parameters.

Viral subversion of the host protein synthesis machinery.

Abstract: Viruses are fully reliant on the translation machinery of their host cells to produce the polypeptides that are essential for viral replication. Consequently, viruses recruit host ribosomes to translate viral mRNAs, typically using virally encoded functions to seize control of cellular translation factors and the host signalling pathways that regulate their activity. This not only ensures that viral proteins will be produced, but also stifles innate host defences that are aimed at inhibiting the capacity of infected cells for protein synthesis. Remarkably, nearly every step of the translation process can be targeted by virally encoded functions. This Review discusses the diverse strategies that viruses use to subvert host protein synthesis functions and regulate mRNA translation in infected cells.

On Using Twitter to Monitor Political Sentiment and Predict Election Results

Abstract: The body of content available on Twitter undoubtedly contains a diverse range of political insight and commentary. But, to what extent is this representative of an electorate? Can we model political sentiment effectively enough to capture the voting intentions of a nation during an election capaign? We use the recent Irish General Election as a case study for investigating the potential to model political sentiment through mining of social media. Our approach combines sentiment analysis using supervised learning and volume-based measures. We evaluate against the conventional election polls and the final election result. We find that social analytics using both volume-based measures and sentiment analysis are predictive and wemake a number of observations related to the task of monitoring public sentiment during an election campaign, including examining a variety of sample sizes, time periods as well as methods for qualitatively exploring the underlying content.

Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS)

Abstract: We present a self-powered integrated microfluidic blood analysis system (SIMBAS) that does not require any external connections, tethers, or tubing to deliver and analyze a raw whole-blood sample. SIMBAS only requires the user to place a 5 μL droplet of whole-blood at the inlet port of the device, whereupon the stand-alone SIMBAS performs on-chip removal of red and white cells, without external valving or pumping mechanisms, followed by analyte detection in platelet-containing plasma. Five complete biotin–streptavidin sample-to-answer assays are performed in 10 min; the limit of detection is 1.5 pM. Red and white blood cells are removed by trapping them in an integral trench structure. Simulations and experimental data show 99.9% to 100% blood cell retention in the passive structure. Powered by pre-evacuation of its PDMS substrate, SIMBAS' guiding design principle is the integration of the minimal number of components without sacrificing effectiveness in performing rapid complete bioassays, a critical step towards point-of-care molecular diagnostics.

Nurse forecasting in Europe (RN4CAST): Rationale, design and methodology

Abstract: Background: Current human resources planning models in nursing are unreliable and ineffective as they consider volumes, but ignore effects on quality in patient care. The project RN4CAST aims innovative forecasting methods by addressing not only volumes, but quality of nursing staff as well as quality of patient care. Methods/Design: A multi-country, multilevel cross-sectional design is used to obtain important unmeasured factors in forecasting models including how features of hospital work environments impact on nurse recruitment, retention and patient outcomes. In each of the 12 participating European countries, at least 30 general acute hospitals were sampled. Data are gathered via four data sources (nurse, patient and organizational surveys and via routinely collected hospital discharge data). All staff nurses of a random selection of medical and surgical units (at least 2 per hospital) were surveyed. The nurse survey has the purpose to measure the experiences of nurses on their job (e.g. job satisfaction, burnout) as well as to allow the creation of aggregated hospital level measures of staffing and working conditions. The patient survey is organized in a sub-sample of countries and hospitals using a one-day census approach to measure the patient experiences with medical and nursing care. In addition to conducting a patient survey, hospital discharge abstract datasets will be used to calculate additional patient outcomes like in-hospital mortality and failure-to-rescue. Via the organizational survey, information about the organizational profile (e.g. bed size, types of technology available, teaching status) is collected to control the analyses for institutional differences. This information will be linked via common identifiers and the relationships between different aspects of the nursing work environment and patient and nurse outcomes will be studied by using multilevel regression type analyses. These results will be used to simulate the impact of changing different aspects of the nursing work environment on quality of care and satisfaction of the nursing workforce.

Discourse representation theory

Abstract: Discourse Representation Theory, or DRT, is one of a number of theories of dynamic semantics, which have come upon the scene in the course of the past twenty years. The central concern of these theories is to account for the context dependence of meaning. It is a ubiquitous feature of natural languages that utterances are interpretable only when the interpreter takes account of the contexts in which they are made – utterance meaning depends on context. Moreover, the interaction between context and utterance is reciprocal.

Treatment options for wastewater effluents from pharmaceutical companies

Abstract: In recent years, concerns about the occurrence and fate of active pharmaceutical ingredients, solvents, intermediates and raw materials that could be present in water and wastewater including pharmaceutical industry wastewater has gained increasing attention. Traditional wastewater treatment methods, such as activated sludge, are not sufficient for the complete removal of active pharmaceutical ingredients and other wastewater constituents from these waters. As a result, complementary treatment methods such as membrane filtration, reverse osmosis and activated carbon are often used in conjunction with the traditional methods for treatment of industrial wastewater. Most of the literature published to date has been on the treatment of municipal wastewater. However, there is a growing body of research that looks at the presence of active pharmaceutical ingredients in industrial wastewater, the treatment of these wastewaters and the removal rates. This article, reviews these treatment methods and includes both traditional methods and advanced oxidation processes. The paper concludes by showing that the problem of pharmaceuticals in wastewaters cannot be solved merely by adopting end of pipe measures. At source measures, such as replacement of critical chemicals, reduction in raw material consumption should continue to be pursued as the top priority.

"I'm eating a sandwich in Glasgow": modeling locations with tweets

Abstract: Social media such as Twitter generate large quantities of data about what a person is thinking and doing in a particular location. We leverage this data to build models of locations to improve our understanding of a user's geographic context. Understanding the user's geographic context can in turn enable a variety of services that allow us to present information, recommend businesses and services, and place advertisements that are relevant at a hyper-local level.In this paper we create language models of locations using coordinates extracted from geotagged Twitter data. We model locations at varying levels of granularity, from the zip code to the country level. We measure the accuracy of these models by the degree to which we can predict the location of an individual tweet, and further by the accuracy with which we can predict the location of a user. We find that we can meet the performance of the industry standard tool for predicting both the tweet and the user at the country, state and city levels, and far exceed its performance at the hyper-local level, achieving a three- to ten-fold increase in accuracy at the zip code level.

Water-soluble superparamagnetic magnetite nanoparticles with biocompatible coating for enhanced magnetic resonance imaging.

Abstract: Ultrasmall superparamagnetic Fe3O4 nanoparticles (USIRONs) were synthesized by a novel, easily scalable chemical reduction of colloidal iron hydroxide under hydrothermal conditions. The average crystallite size (5.1 ± 0.5 nm) and good crystallinity of the samples were supported by HR-TEM analysis and the saturation magnetization value (47 emu g–1). Vitamin C, used as a chemical reducing agent, also served as a capping agent in the oxidized form (dehydroascorbic acid, DHAA) to impart nanoparticles with exceptional solubility and stability in water, PBS buffer, and cell culture medium. Detailed physicochemical analysis of the USIRON suspensions provided insight into the magnetic ordering phenomena within the colloid, arising from the formation of uniform clusters displaying a hydrodynamic size of 41 nm. Phantom experiments on the contrast agent (clinical 3 T MRI scanner) revealed an enhanced r2/r1 ratio of 36.4 (r1= 5 s–1 mM–1 and r2= 182 s–1 mM–1) when compared to the clinically approved agents. The potent...

The Trouble with Transparency: A Critical Review of Openness in e-Government

Abstract: Transparency in public administration is generally held to be desirable, something to be fostered and enabled. This long standing idea has gained considerable further momentum with the emergence of e-government and the affordances of computing in general and the Internet in particular. This paper examines the argument that transparency may, in certain and not uncommon circumstances, be inimical to good government and good governance and suggests that the importance of understanding why this is so has increased as information and communications technology permeates government and society. It suggests that in an electronic age, the scope and nature of transparency needs to be carefully managed, and that expectations of the benefits of ICT enabled transparency may be too high.

Production of cellulose nanocrystals using hydrobromic acid and click reactions on their surface

Abstract: Cellulose nanocrystals (CNCs) were prepared by acidic hydrolysis of cotton fibers (Whatman #1 filter paper). In our efforts to select conditions in which the hydrolysis media does not install labile protons on the cellulose crystals, a mineral acid other than sulfuric acid (H2SO4) was used. Furthermore, in our attempts to increase the yields of nanocrystals ultrasonic energy was applied during the hydrolysis reaction. The primary objective was to develop hydrolysis reaction conditions for the optimum and reproducible CNC production. As such, the use of hydrobromic acid (HBr) with the application of sonication as a function of concentration (1.5–4.0 M), temperature (80–100 °C), and time (1–4 h) was examined. Applying sonic energy during the reaction was found to have significant positive effects as far as reproducible high yields are concerned. Overall, the combination of 2.5 M HBr, 100 °C, and 3 h associated with the sonication during the reaction generated the highest nanocrystal yields. In addition to the optimization study three types of surface modifications including TEMPO-mediated oxidation, alkynation, and azidation were used to prepare surface-activated, reactive CNCs. Subsequently, click chemistry was employed for bringing together the modified nanocrystalline materials in a unique regularly packed arrangement demonstrating a degree of molecular control for creating these structures at the nano level.

Intracellular and Extracellular MicroRNAs in Breast Cancer

Abstract: BACKGROUND: Successful treatment of breast cancer is enhanced by early detection and, if possible, subsequent patient-tailored therapy. Toward this goal, it is essential to identify and understand the most relevant panels of biomarkers, some of which may also have relevance as therapeutic targets. METHODS: We critically reviewed published literature on microRNAs (miRNAs) as relevant to breast cancer. SUMMARY: Since the initial recognition of the association of miRNAs with breast cancer in 2005, studies involving cell lines, in vivo models, and clinical specimens have implicated several functions for miRNAs, including suppressing oncogenesis and tumors, promoting or inhibiting metastasis, and increasing sensitivity or resistance to chemotherapy and targeted agents in breast cancer. For example, miR-21 is overexpressed in both male and female breast tumors compared with normal breast tissue and has been associated with advanced stage, lymph node positivity, and reduced survival time. miR-21 knock-down in cell-line models has been associated with increased sensitivity to topotecan and taxol in vitro and the limitation of lung metastasis in vivo. Furthermore, the discovery of extracellular miRNAs (including miR-21), existing either freely or in exosomes in the systemic circulation, has led to the possibility that such molecules may serve as biomarkers for ongoing patient monitoring. Although additional investigations are necessary to fully exploit the use of miRNAs in breast cancer, there is increasing evidence that miRNAs have potential not only to facilitate the determination of diagnosis and prognosis and the prediction of response to treatment, but also to act as therapeutic targets and replacement therapies.

Extreme-ultraviolet pump–probe studies of one-femtosecond-scale electron dynamics

Abstract: Pump–probe measurements are now an essential tool for investigating ultrafast dynamics in atoms and molecules. A lack of sources producing high-intensity attosecond pulses of extreme-ultraviolet (EUV) light has, however, hindered progress. Now, a technique that induces nonlinear processes with EUV light is demonstrated that could circumvent this problem.

Evaluating a dancer's performance using kinect-based skeleton tracking

Abstract: In this work, we describe a novel system that automatically evaluates dance performances against a gold-standard performance and provides visual feedback to the performer in a 3D virtual environment. The system acquires the motion of a performer via Kinect-based human skeleton tracking, making the approach viable for a large range of users, including home enthusiasts. Unlike traditional gaming scenarios, when the motion of a user must by kept in synch with a pre-recorded avatar that is displayed on screen, the technique described in this paper targets online interactive scenarios where dance choreographies can be set, altered, practiced and refined by users. In this work, we have addressed some areas of this application scenario. In particular, a set of appropriate signal processing and soft computing methodologies is proposed for temporally aligning dance movements from two different users and quantitatively evaluating one performance against another.

The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?

Abstract: The ADAMs are transmembrane proteins implicated in proteolysis and cell adhesion. Forty gene members of the family have been identified, of which 21 are believed to be functional in humans. As proteases, their main substrates are the ectodomains of other transmembrane proteins. These substrates include precursor forms of growth factors, cytokines, growth factor receptors, cytokine receptors and several different types of adhesion molecules. Although altered expression of specific ADAMs has been implicated in different diseases, their best-documented role is in cancer formation and progression. ADAMs shown to play a role in cancer include ADAM9, ADAM10, ADAM12, ADAM15 and ADAM17. Two of the ADAMs, i.e., ADAM10 and 17 appear to promote cancer progression by releasing HER/EGFR ligands. The released ligands activate HER/EGFR signalling that culminates in increased cell proliferation, migration and survival. Consistent with a causative role in cancer, several ADAMs are emerging as potential cancer biomarkers for aiding cancer diagnosis and predicting patient outcome. Furthermore, a number of selective ADAM inhibitors, especially against ADAM10 and ADAM17, have been shown to have anti-cancer effects. At least one of these inhibitors is now undergoing clinical trials in patients with breast cancer.

Characterisation and manipulation of docetaxel resistant prostate cancer cell lines

Abstract: There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.

Improvised internationalization in new ventures: The role of prior knowledge and networks

Abstract: How do entrepreneurs identify foreign market opportunities and how do they identify foreign market(s) and customers? We draw on the concepts of effectuation, improvisation, prior knowledge and networks to study the early internationalization of new ventures operating in the Irish Shellfish sector. We argue that the internationalization process was strongly influenced by two ‘resources to hand’: the entrepreneurs’ idiosyncratic prior knowledge and their prior social and business ties. We observe an effectuation logic and extensive improvisation in the internationalization process of these new ventures.

A role for TLR4 in clostridium difficile infection and the recognition of surface layer proteins

Abstract: Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4−/− and Myd88−/−, but not TRIF−/− mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system.

Hospital nurse‐staffing models and patient‐ and staff‐related outcomes

Abstract: Michelle Butler, Rita Collins, Jonathan Drennan, Phil Halligan, Donal P O'Mathuna, Timothy J Schultz, Ann Sheridan, Eileen Vilis

Microencapsulation using vibrating technology

Abstract: For over a half a century now, microencapsulation has played a very important role in many industries and in the recent decades, this versatile technology has been applied to numerous biotechnology and medical processes. However, successful application in these areas requires a methodology which has the capability to produce mono-dispersed, homogenous-shaped capsules, with a narrow size distribution, using a short production time. The manufacture of capsules using vibrating technology has gained significant interest mainly due to its simplistic approach to produce homogenous microcapsules with the desired characteristics for biotechnological and medical processes. However, certain limitations still exist for this methodology, which include the inability to manufacture microcapsules at large quantities and/or using highly viscous polymers. In this review, a detailed description of the theoretical and practical aspects behind the production of different types of alginate-based microcapsules, for application in biotechnological and medical processes, using vibrating technology, is given.

Modification of the deoxy-myoglobin/carbonmonoxy-myoglobin UV-vis assay for reliable determination of CO-release rates from organometallic carbonyl complexes

Abstract: The deoxy-myoglobin (deoxy-Mb)/carbonmonoxy-myoglobin (Mb-CO) UV-vis assay is the principal method used for quantifying the rates of CO release from CO-releasing molecules (CO-RMs) that might possess therapeutic benefits. Some issues emerge when the Mb-CO assay is utilized for testing CO-RMs with novel structures, which are comprehensively discussed here for the first time. Two methods for processing raw UV-vis spectroscopic data generated from the assay are presented in this paper.

Effect of antibody immobilization strategies on the analytical performance of a surface plasmon resonance-based immunoassay.

Abstract: Antibody immobilization strategies (random, covalent, orientated and combinations of each) were examined to determine their performance in a surface plasmon resonance-based immunoassay using human fetuin A (HFA) as the model antigen system. The random antibody immobilization strategy selected was based on passive adsorption of anti-HFA antibody on 3-aminopropyltriethoxysilane (APTES)-functionalized gold (Au) chips. The covalent strategy employed covalent crosslinking of anti-HFA antibody on APTES-functionalized chips using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC) and sulfo-N-hydroxysuccinimide (SNHS). The orientation strategy used passive adsorption of protein A (PrA) on Au chips, with subsequent binding of the anti-HFA antibody in an orientated fashion via its fragment crystallisable (Fc) region. In the covalent-orientated strategy, PrA was first bound covalently, to the surface, which in turn, then binds the anti-HFA antibody in an orientated manner. Finally, in the most widely used strategy, covalent binding of anti-HFA antibody to carboxymethyldextran (CM5-dextran) was employed. This immobilization strategy gave the highest anti-HFA antibody immobilization density, whereas the highest HFA response was obtained with the covalent-orientated immobilization strategy. Therefore, the covalent-orientated strategy was the best for SPR-based HFA immunoassay and can detect 0.6–20.0 ng/mL of HFA in less than 10 min.

Generation of Coherent Multicarrier Signals by Gain Switching of Discrete Mode Lasers

Abstract: The authors demonstrate the generation of a highly coherent multicarrier signal that consists of eight clearly resolved 10.7-GHz coherent sidebands generated within 3 dB of the spectral envelope peak and with an extinction ratio in excess of 45 dB by gain switching a discrete mode (DM) laser. The generated spectral comb displays a corresponding picosecond pulse train at a repetition rate of 10.7 GHz with a pulse duration of 24 ps and a temporal jitter of ~450 fs. The optical spectra and associated pulses of the gain-switched DM laser are subsequently compared with a gain-switched distributed feedback (DFB) laser that generates a spectrum with no discernible sidebands and corresponding pulses with ~3 ps of temporal jitter. By means of external injection, the temporal jitter of the gain-switched DFB laser is then reduced to <; 1 ps, resulting in visible tones on the output spectrum. Finally, a nonlinear scheme is employed and initially tailored to compress the optical pulses, after which, the setup is slightly altered to expand the original frequency comb from the gain-switched DM laser.