The Protection of Life During Pregnancy Act 2013: Suicide, dignity and the Irish discourse on abortion

Accepted Version

Oscillations by minimal bacterial suicide circuits reveal hidden facets of host-circuit physiology.

Synthetic biology seeks to enable programmed control of cellular behavior though engineered biological systems. These systems typically consist of synthetic circuits that function inside, and interact with, complex host cells possessing pre-existing metabolic and regulatory networks. Nevertheless, while designing systems, a simple well-defined interface between the synthetic gene circuit and the host is frequently assumed. We describe the generation of robust but unexpected oscillations in the densities of bacterium Escherichia coli populations by simple synthetic suicide circuits containing quorum components and a lysis gene. Contrary to design expectations, oscillations required neither the quorum sensing genes (luxR and luxI) nor known regulatory elements in the P(luxI) promoter. Instead, oscillations were likely due to density-dependent plasmid amplification that established a population-level negative feedback. A mathematical model based on this mechanism captures the key characteristics of oscillations, and model predictions regarding perturbations to plasmid amplification were experimentally validated. Our results underscore the importance of plasmid copy number and potential impact of "hidden interactions" on the behavior of engineered gene circuits - a major challenge for standardizing biological parts. As synthetic biology grows as a discipline, increasing value may be derived from tools that enable the assessment of parts in their final context.

ROLE OF ICAM-1-MEDIATED ENDOCYTOSIS IN ENDOTHELIAL FUNCTION AND IMPLICATIONS FOR CARRIER-ASSISTED DRUG DELIVERY

Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein found on the surface of vascular endothelial cells (ECs). Its expression is upregulated at inflammatory sites, allowing for targeted delivery of therapeutics using ICAM-1-binding drug carriers. Engagement of multiple copies of ICAM-1 by these drug carriers induces cell adhesion molecule (CAM)-mediated endocytosis, which results in trafficking of carriers to lysosomes and across ECs. Knowledge about the regulation behind CAM-mediated endocytosis can help improve drug delivery, but questions remain about these regulatory mechanisms. Furthermore, little is known about the natural function of this endocytic pathway. To address these gaps in knowledge, we focused on two natural binding partners of ICAM-1 that potentially elicit CAM-mediated endocytosis: leukocytes (which bind ICAM-1 via β₂ integrins) and fibrin polymers (a main component of blood clots which binds ICAM-1 via the γ3 sequence). First, inspired by properties of these natural binding partners, we varied the size and targeting moiety of model drug carriers to determine how these parameters affect CAM-mediated endocytosis. Increasing ICAM-1-targeted carrier size slowed carrier uptake kinetics, reduced carrier trafficking to lysosomes, and increased carrier transport across ECs. Changing targeting moieties from antibodies to peptides decreased particle binding and uptake, lowered trafficking to lysosomes, and increased transport across ECs. Second, using cell culture models of leukocyte/EC interactions, inhibiting regulatory elements of the CAM-mediated pathway disrupted leukocyte sampling, a process crucial to leukocyte crossing of endothelial layers (transmigration). This inhibition also decreased leukocyte transmigration across ECs, specifically through the transcellular route, which occurs through a single EC without disassembly of cell-cell junctions. Third, fibrin meshes, which mimic blood clot fragments/remnants, bound to ECs at ICAM-1-enriched sites and were internalized by the endothelium. Inhibiting the CAM-mediated pathway disrupted this uptake. Following endocytosis, fibrin meshes trafficked to lysosomes where they were degraded. In mouse models, CAM-mediated endocytosis of fibrin meshes appeared to remove fibrin remnants at the endothelial surface, preventing re-initiation of the coagulation cascade. Overall, these results support a link between CAM-mediated endocytosis and leukocyte transmigration as well as uptake of fibrin materials by ECs. Furthermore, these results will guide the future design of ICAM-1-targeted carrier-assisted therapies.

A framework for e-learning: a blended solution?: current developments in technology-assisted education

This paper describes a Framework for e-Learning and presents the findings of a study investigating whether the use of Blended Learning can fulfill or at least accommodate some of the human requirements presently neglected by current e-Learning systems. This study evaluates the in-house system: Teachmat, and discusses how the use of Blended Learning has become increasingly prevalent as a result of its enhancement and expansion, its relationship to the human and pedagogical issues, and both the positive and negative implications of this reality. [From the Authors]

A psychodynamic approach to suicide

This paper begins by critically exploring Freudian and post-Freudian understandings of suicide while drawing several examples from clinical practice. The paper then reconsiders psychodynamic approaches to suicidal clients from a Levinasian ethical position. Suggests that suicide may be a logical part of what it is to be human, rather than an indication of mental illness.

Genome- and transcriptome-assisted development of nuclear insertion/deletion markers for Calanus species (Copepoda: Calanoida) identification

Copepods of the genus Calanus are key zooplankton species in temperate to arctic marine ecosystems. Despite their ecological importance, species identification remains challenging. Furthermore, the recent report of hybrids among Calanus species highlights the need for diagnostic nuclear markers to efficiently identify parental species and hybrids. Using next-generation sequencing analysis of both the genome and transcriptome from two sibling species, Calanus finmarchicus and Calanus glacialis, we developed a panel of 12 nuclear insertion/deletion markers. All the markers showed species-specific amplicon length. Furthermore, most of the markers were successfully amplified in other Calanus species, allowing the molecular identification of Calanus helgolandicus, Calanus hyperboreus and Calanus marshallae.

The Role of Tool/Sheet Contact in Plug-Assisted Thermoforming.

Plug-assisted thermoforming produces a wide range of polymer products through a combination of deformation by air pressure and contact with tool surfaces. In this paper the role of tool/sheet contact in determining the process output is investigated. A combination of thermoforming, friction and heat transfer tests were carried out on common tool and sheet materials. The results show that the typical friction coefficients for the material combinations are within the range 0.1 to 0.3, but the values rise sharply on approaching thermoforming temperatures. Thermal imaging tests demonstrate that all of the plug materials significantly cool the heated sheet on contact, even over very short periods of time. The temperature of the plug is very important. At low plug temperatures heat transfer effects predominate, whereas at high plug temperatures friction effects predominate. A plug temperature of approximately 100oC balances these effects and creates the most effective material distribution.

Flavian laws, the railway, the newspaper and Loring’s breads

It is abound the research on the formation, rise and failure of the financial and industrial network undertaken by the Loring-Heredia-Larios triangle, bourgeois families who introduced the Industrial Revolution in the south of Andalusia. On the contrary, there are almost nonexistent studies from the perspective of the mentality that sustained their business, social and ethical model in the algid decades of their action (1850-1860). In this paper we propose some hypotheses about the ideological structures of bourgeois group and point out some keys, clues and signs for a future reconstruction of this kind, which so far has not been incardinated that early and failed malaguenan industrial revolution in streams thinking of that time.

An algorithm to predict pregnancy in assisted conception

BACKGROUND: Male fertility potential cannot be measured by conventional parameters for assisted reproduction by intracytoplasmic sperm injection. This study determines the relationship between testicular and ejaculated sperm mitochondrial (mt) DNA deletions, nuclear (n) DNA fragmentation and fertilisation and pregnancy rates in ICSI. METHODS: Ejaculated sperm were obtained from 77 men and testicular sperm from 28 men with obstructive azoospermia undergoing ICSI. Testicular sperm were retrieved using a Trucut needle. MtDNA analysed using a long polymerase chain reaction. The alkaline Comet assay determined nDNA fragmentation. RESULTS: Of subjects who achieved a pregnancy (50%) using testicular sperm, only 26% had partners�??�?�¢?? sperm with wild type (WT) mtDNA. Of pregnant subjects (38%) using ejaculated sperm, only 8% had partner sperm with WT mtDNA.. In each, the successful group had less mtDNA deletions and less nDNA fragmentation. There were inverse relationships between pregnancy and mtDNA deletion numbers, size and nDNA fragmentation for both testicular and ejaculated sperm. No relationships were observed with fertilisation rates. An algorithm for the prediction of pregnancy is presented based on the quality of sperm nDNA and mtDNA. CONCLUSION: In both testicular and ejaculated sperm, mtDNA deletions and nDNA fragmentation are closely associated with pregnancy in ICSI.