Spectral Line-by-Line Pulse Shaping of an On-Chip Microresonator Frequency Comb

We report, for the first time to the best of our knowledge, spectral phase characterization and line-by-line pulse shaping of an optical frequency comb generated by nonlinear wave mixing in a microring resonator. Through programmable pulse shaping the comb is compressed into a train of near-transform-limited pulses of \approx 300 fs duration (intensity full width half maximum) at 595 GHz repetition rate. An additional, simple example of optical arbitrary waveform generation is presented. The ability to characterize and then stably compress the frequency comb provides new data on the stability of the spectral phase and suggests that random relative frequency shifts due to uncorrelated variations of frequency dependent phase are at or below the 100 microHertz level.Comment: 18 pages, 4 figure

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Parental attributions of control for child behaviour and their relation to discipline practices in parents of children with and without developmental delays

Children with developmental delays (DD) are at risk for developing behavior problems. Research suggests that parents’ causal attributions for child behavior are related to parenting. This study investigated this association in parents of children with DD compared to parents of typically developing (TD) children. It specifically focused on attributions of child control by separating these from attributions of responsibility, blame and intent, and from attributions of parent control and responsibility. Fifty-one parents of children with DD and 69 parents of TD children completed two questionnaires. The Written Analogue Questionnaire measured causal attributions. The Parenting Scale measured dysfunctional discipline practices. Parents of children with DD viewed the child’s role in problematic behavior more positively while also viewing misbehavior as more fixed than parents of TD children. Parents of TD children who viewed their child as more in control over misbehavior used less dysfunctional discipline, but this association was not found for parents of children with DD. The results advance understanding of how parents perceive behavior problems in children with DD and the important role these perceptions play in parental behavior management strategies. More importantly, these perceptions relate to discipline practices differently for parents of children with DD compared to parents of TD children, highlighting that parent interventions should be adapted to the specific needs of parents of children with DD

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Ethnic Variation in Inflammatory Profile in Tuberculosis

PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

QGP Theory: Status and Perspectives

The current status of Quark-Gluon-Plasma Theory is reviewed. Special emphasis is placed on QGP signatures, the interpretation of current data and what to expect from RHIC in the near future.Comment: 20 pages, invited overview talk at the 4th International Conference on the Physcis and Astrophysics of the Quark-Gluon-Plasma, November 2001, Jaipur, India, to appear in Praman

Inferring Carbon Sources from Gene Expression Profiles Using Metabolic Flux Models

Background: Bacteria have evolved the ability to efficiently and resourcefully adapt to changing environments. A key means by which they optimize their use of available nutrients is through adjustments in gene expression with consequent changes in enzyme activity. We report a new method for drawing environmental inferences from gene expression data. Our method prioritizes a list of candidate carbon sources for their compatibility with a gene expression profile using the framework of flux balance analysis to model the organism’s metabolic network. Principal Findings: For each of six gene expression profiles for Escherichia coli grown under differing nutrient conditions, we applied our method to prioritize a set of eighteen different candidate carbon sources. Our method ranked the correct carbon source as one of the top three candidates for five of the six expression sets when used with a genome-scale model. The correct candidate ranked fifth in the remaining case. Additional analyses show that these rankings are robust with respect to biological and measurement variation, and depend on specific gene expression, rather than general expression level. The gene expression profiles are highly adaptive: simulated production of biomass averaged 94.84% of maximum when the in silico carbon source matched the in vitro source of the expression profile, and 65.97% when it did not. Conclusions: Inferences about a microorganism’s nutrient environment can be made by integrating gene expression data into a metabolic framework. This work demonstrates that reaction flux limits for a model can be computed which are realistic in the sense that they affect in silico growth in a manner analogous to that in which a microorganism’s alteration of gene expression is adaptive to its nutrient environment.National Institute of Allergy and Infectious Diseases (U.S.) (grant HHSN 2722008000059C)National Institute of Allergy and Infectious Diseases (U.S.) (grant HHSN 26620040000IC)Bill & Melinda Gates Foundation (grant 18651010-37352-A

An efficient algorithm for systematic analysis of nucleotide strings suitable for siRNA design

<p>Abstract</p> <p>Background</p> <p>The "off-target" silencing effect hinders the development of siRNA-based therapeutic and research applications. Existing solutions for finding possible locations of siRNA seats within a large database of genes are either too slow, miss a portion of the targets, or are simply not designed to handle a very large number of queries. We propose a new approach that reduces the computational time as compared to existing techniques.</p> <p>Findings</p> <p>The proposed method employs tree-based storage in a form of a modified truncated suffix tree to sort all possible short string substrings within given set of strings (i.e. transcriptome). Using the new algorithm, we pre-computed a list of the best siRNA locations within each human gene ("siRNA seats"). siRNAs designed to reside within siRNA seats are less likely to hybridize off-target. These siRNA seats could be used as an input for the traditional "set-of-rules" type of siRNA designing software. The list of siRNA seats is available through a publicly available database located at <url>http://web.cos.gmu.edu/~gmanyam/siRNA_db/search.php</url></p> <p>Conclusions</p> <p>In attempt to perform top-down prediction of the human siRNA with minimized off-target hybridization, we developed an efficient algorithm that employs suffix tree based storage of the substrings. Applications of this approach are not limited to optimal siRNA design, but can also be useful for other tasks involving selection of the characteristic strings specific to individual genes. These strings could then be used as siRNA seats, as specific probes for gene expression studies by oligonucleotide-based microarrays, for the design of molecular beacon probes for Real-Time PCR and, generally, any type of PCR primers.</p