Fatigue damage initiation life prediction for heterogeneous metals

In particle-strengthened metallic alloys, fatigue damage incubates at inclusion particles near the surface or at the change of geometries. Micromechanical simulation of inclusions such that the fatigue damage incubation mechanisms can be categorized. As micro-plasticity gradient field around different inclusions is different, a novel concept for nonlocal evaluation of micro-plasticity intensity is introduced. The effects of void aspects ration and spatial distributions are quantified for fatigue incubation life in the high-cycle fatigue regime. At last, these effects are integrated based on the statistical facts of inclusions to predict the fatigue life of structural components.

Writing the Barbaric Recent Past : Holocaust Fiction for Young Adults

Horror and redemption in Holocaust writing for young adults: Marcus Zusak’s The Book Thief, John Boyne’s The Boy in the Striped Pyjamas. While it has long been thought that the Holocaust is not an appropriate subject matter for young audiences, from The Diary of Anne Frank onwards it has always been part of their reading matter. Never, however, has there been so much interest as in the recent best-selling publications by Zusak and Boyne (the latter of which has been made into a film). This chapter examines the politics of crafting stories for young people about the unspeakable events of the recent past, about who has the right to ‘speak for’ the victims, and whether some genres (for example, fairy stories or fabulism) work best, given the horrific nature of the subject matter.

Review : "The Culture of Curating and the Curating of Culture(s)", Paul O’Neill (2012)

Paul O'Neill's book, 'The Culture of Curating and the Curating of Culture(s)provides a concise overview of how curating has changed art and how art has changed curating. The book is divided into three sections, each dealing with a key transitional development: (1) the historical development of curatorial discourse; (2) the influence of the Biennial phenomenon and, finally, (3) how art and curating have converged since the 1990s. This review discusses the publication as a significant contribution to the development of a curatorial history and discourse.

Oral immunization with a novel lipid-based adjuvant protects against genital Chlamydia infection

Oral immunization is attractive as a delivery route because it is needle-free and useful for rapid mass vaccination programs to target pandemics or bioterrorism. This potential has not been realized for human vaccination, due to the requirement of large antigen doses and toxic (to humans) adjuvants to overcome the induction of oral tolerance and potential degradation of antigens in the stomach. To date, only oral vaccines based on live attenuated organisms have been approved for human use. In this study we describe the use of a lipid-based delivery system/adjuvant, Lipid C, for oral immunization to protect mice against genital tract chlamydial infection. Lipid C is formulated from food-grade purified and fractionated triglycerides. Bacterial shedding following vaginal challenge with Chlamydia muridarum was reduced by 50% in female mice orally immunized with the chlamydial major outer membrane protein (MOMP) formulated in Lipid C, protection equivalent to that seen in animals immunized with MOMP admixed with both cholera toxin (CT) and CpG oligodeoxynucleotides (CpG-ODN). Protection was further enhanced when MOMP, CT and CpG were all combined in the Lipid C matrix. Protection correlated with production of gamma interferon (IFN) by splenic T cells, a serum MOMP-specific IgG response and low but detectable levels of MOMP-specific IgA in vaginal lavage.

Transcutaneous immunization with a novel lipid-based adjuvant protects against Chlamydia genital and respiratory infections

Mucosal adjuvants are important to overcome the state of immune tolerance normally associated with mucosal delivery and to enhance adaptive immunity to often-weakly immunogenic subunit vaccine antigens. Unfortunately, adverse side effects of many experimental adjuvants limit the number of adjuvants approved for vaccination. Lipid C is a novel, non-toxic, lipid oral vaccine-delivery formulation, developed originally for oral delivery of the live Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine. In the present study, murine models of chlamydial respiratory and genital tract infections were used to determine whether transcutaneous immunization (TCI) with Lipid C-incorporated protein antigens could elicit protective immunity at the genital and respiratory mucosae. BALB/c mice were immunized transcutaneously with Lipid C containing the chlamydial major outer membrane protein (MOMP), with and without addition of cholera toxin and CpG-ODN 1826 (CT/CpG). Both vaccine combinations induced mixed cell-mediated and mucosal antibody immune responses. Immunization with Lipid C-incorporated MOMP (Lipid C/MOMP), either alone or with CT/CpG resulted in partial protection following live challenge with Chlamydia muridarum as evidenced by a significant reduction in recoverable Chlamydia from both the genital secretions and lung tissue. Protection induced by immunization with Lipid C/MOMP alone was not further enhanced by the addition of CT/CpG. These results highlight the potential of Lipid C as a novel mucosal adjuvant capable of targeting multiple mucosal surfaces following TCI. Protection at both the respiratory and genital mucosae was achieved without the requirement for potentially toxic adjuvants, suggesting that Lipid C may provide a safe effective mucosal adjuvant for human vaccination.

Role of Human Topoisomerase I in DNA Repair and Apoptosis

Human topoisomerase I (htopoI) is an enzyme that up to now was believed to function mainly in the removal of torsional stress generated during transcription and replication. In 1998, it was found that htopoI might play another important role in the cellular response to DNA damage -- the so-called htopoI damage response. Since this initial discovery, many studies have suggested that the htopoI damage response is involved in DNA repair as well as in apoptosis. Here we discuss the earliest as well as the latest results in this field. Combining all of the published and as yet unpublished results, we suggest and discuss a model of how htopoI may function during DNA repair and apoptosis. Furthermore, numerous results show that the htopoI damage response is not a spontaneous event, but is strictly regulated by cellular signalling pathways. We discuss which pathways may be involved and how the htopoI damage response is activated. Although the htopoI damage response was discovered several years ago, research in this area is just beginning. The future will surely bring more clarity regarding the precise mechanism behind the involvement of htopoI in DNA repair and apoptosis, as well as its implications for a broader understanding of how the human organism ensures genomic stability.

The human topoisomerase I damage response plays a role in apoptosis

Previous studies have shown that human topoisomerase I cleavage complexes form as a response to various DNA damages in vivo, the so called human topoisomerase I “damage response”. It was suggested that this damage response may play a role in DNA repair as well as in apoptosis, but only very few investigations have been done and the significance of the damage response still remains unclear. Here we demonstrate that human topoisomerase I cleavage complexes induced by high doses of UV irradiation are highly stable for up to 48 h. Furthermore, we show that human topoisomerase I cleavage complexes correlate with apoptosis. However, at low UV doses the cleavage complex level was very low and the complexes were repaired. Surprisingly, we found that high levels of stable cleavage complexes were not only found in UV-irradiated cells but also in untreated cells that underwent apoptosis. A possible role of human topoisomerase I in apoptosis is discussed.

The double risk of primitivism

This essay examines the possibilities for practices that appeal to the primitive in the contemporary cultural context. The idea of the primitive is driven by a desire to challenge the limitations of Western culture, while at the same time attracting the charge of promoting Eurocentrism. This essay investigates this double risk and how artists have sought to evade it, confound it, or accentuate it.

Dispelling ageing myths in technology design

We present a review of literature from the fields of gerontology, gerontechnology, HCI and government policy that deals with social and technical solutions for the ageing population. We highlight common assumptions about ageing people, which we argue are still embedded in much of the research related to the domain of ageing. This paper challenges six common assumptions across four broad themes that we identified in the literature. It aims to provide a reminder and resource for designers to eschew assumptions during designing technology for 'older' users.

A randomized controlled trial of a correspondence-based intervention for carers of relatives with psychosis

Background Family members play a crucial role in supporting the recovery of loved ones with psychosis. The journey of recovery is not only traversed by the person experiencing the mental illness but also by their family. Interventions to support these families have traditionally either focused on psychoeducation or addressed problematic interactions or expressed emotion. Family programmes have far less frequently emphasized supporting family members' adjustment to the challenges posed by their relative's disorder or their recovery from associated distress. The study compared a control condition that received only a psychoeducational booklet (Information) and a condition also receiving a correspondence-based interactive recovery-oriented intervention (Connections). The Connections group was expected to show greater improvements in recovery knowledge, well-being, experiences of caregiving, hopefulness and distress. Method A randomized controlled trial was conducted to evaluate the effectiveness of two correspondence-based family interventions delivered to 81 carers of relatives with psychosis. Results Intent-to-treat analyses showed no differential outcomes between conditions, but an analysis of participants who substantially completed their allocated treatment showed that carers receiving Connections had significantly more improvements in well-being, positive experiences of caregiving and distress. Conclusions Correspondence interventions that support carer's recovery may result in more positive mental health for those who complete key elements of the programme compared with information alone. However, many carers do not complete a correspondence programme and this may limit its impact.

2. Contact lens care and ocular surface homeostasis

Moderator Opening The early focus of contact lens wear and ocular health was on oxygen delivery. However, as we learn more about how the eye works, and investigate how the contact lens interacts with the cornea, the role of the tear film has risen in prominence. A healthy tear film is critical for normal ocular homeostasis, and abnormalities of the tear film are the primary cause of dry eye. In order to improve patient eye health and comfort during lens wear, we need to further elucidate the relationship among contact lenses, contact lens solutions, the tear film, and the corneal epithelium, and find ways to maintain homeostasis of the ocular surface. In this section, we review the latest data and opinions on this complex relationship between contact lenses and lens care solutions

The science behind the “stain”

It has been almost fi ve years since I fi rst published the article entitled “Much Ado About Staining” in Review of Optometry, which explored what we really knew in 2006 about the relationship between “corneal staining” and contact lens multipurpose solutions (MPS). This was published just prior to the controversial “staining grid.” While the Grid showed MPS-associated hyperfl uorescence under the slitlamp at two hours, it did not explain the “what” or “why” behind it; even so, many proponents of the Grid continue to suggest that it shows us which solution/lens combinations are “biocompatible” and which are not. New evidence suggests that the preservative-associated transient hyperfl uorescence (or PATH) observed at two hours after lens insertion is a benign phenomenon due to an interaction between fl uorescein, MPS preservatives, and corneal cell membranes. The misinterpretation of PATH as “real” corneal staining, like that observed in pathological conditions, may be due in part to the fact that there is not a lot of teaching regarding the true properties of fl uorescein and what is actually occurring when we see either PATH or corneal staining. To discuss the science of fl uorescein, corneal staining, and PATH, I have asked some of the preeminent research experts in the study of fl uorescence spectroscopy and corneal staining from around the world to share their new research and personal opinions on these topics...

Perspectives on research in project management : the nine schools

This paper demonstrates that project management is a developing field of academic study in management, of considerable diversity and richness, which can make a valuable contribution to the development of management knowledge, as well as being of considerable economic importance. The paper reviews the substantial progress and trends of research in the subject, which has been grouped into nine major schools of thought: optimization, modelling, governance, behaviour, success, decision, process, contingency, and marketing. The paper addresses interactions between the different schools and with other related management fields, and provides insights into current and potential research in each and across these schools.

Habituated interaction and social objects

In this position paper we draw from critical approaches to the concept of habit from cultural theory to argue that considering the sociality of everyday objects might be productive for understanding and designing for habituated interaction within the emerging Internet of Things.

The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior

Recently, we defined a new syndromic form of X-linked mental retardation in a 4-generation family with a unique clinical phenotype characterized by mild mental retardation, choreoathetosis, and abnormal behavior (MRXS10). Linkage analysis in this family revealed a candidate region of 13.4 Mb between markers DXS1201 and DXS991 on Xp11; therefore, mutation analysis was performed by direct sequencing in most of the 135 annotated genes located in the region. The gene (HADH2) encoding L-3-hydroxyacyl-CoA dehydrogenase II displayed a sequence alteration (c.574 C-->A; p.R192R) in all patients and carrier females that was absent in unaffected male family members and could not be found in 2,500 control X chromosomes, including in those of 500 healthy males. The silent C-->A substitution is located in exon 5 and was shown by western blot to reduce the amount of HADH2 protein by 60%-70% in the patient. Quantitative in vivo and in vitro expression studies revealed a ratio of splicing transcript amounts different from those normally seen in controls. Apparently, the reduced expression of the wild-type fragment, which results in the decreased protein expression, rather than the increased amount of aberrant splicing fragments of the HADH2 gene, is pathogenic. Our data therefore strongly suggest that reduced expression of the HADH2 protein causes MRXS10, a phenotype different from that caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency, which is a neurodegenerative disorder caused by missense mutations in this multifunctional protein.