Two Dimensional Dislocation Sources in Fiber Composite Laminates

The method which is frequently adopted in order to determine the response of an elastic body to internal impulsive dislocations is to make use of the representation theorem due to Burridge and Knopoff (see for example Vasudevan and Mal [1]). In this approach, the problem of evaluating the transient response at a specified location due to a point dislocation source is replaced by the problem of evaluating the stress state at the source due to an impulsive point load placed at the measuring location. This technique is particularly useful in the acoustic emission problem where the interest lies in the response measured at the surface of the body, arising from some internal source. In particular, if attention is restricted to evaluating the normal component of displacement at the surface, the response to dislocation sources at any internal point is determined from the solution of the transient response of the body to an impulsive normal load acting at the surface. The representation theorem approach has been applied by Vasudevan and Mal [1] and by Suzuki et.al. [2] in order to evaluate the response of isotropic plates to dislocation sources

Surface Response of an Anisotropic Laminate to Acoustic Emission Sources

In earlier papers, Green [1–4], results have been presented which show the surface response of a cross-ply fiber composite plate due to buried impulsive sources. The sources considered were line loads and line double forces. The present paper extends these results for sources which are line couples and line double couples without moment. The impetus for carrying out this extensive study is the need for a thorough understanding of the nature of the stress waves generated as a result of internal impulsive events. This in turn is a prerequisite for the application of acoustic emission techniques which are now standard methods used for the detection of faults in engineering structures. This technique has the potential for not only locating the source of the emission but also for determining the nature of the source. The pulses arising from events such as crack formation, crack growth or the relative slip of crack surfaces are completely different in character and give rise to different signals at the receivers. By recording the time history of these signals it should be possible to determine the nature of the initiating event. This has particular relevance to the monitoring of laminated composites where there exists a wide variety of possible defects such as fiber breakage, matrix cracking, fiber/matrix debonding and ply delamination, in addition to the crack related events mentioned above. The surface response due to a number of different internal point sources in a plate of isotropic elastic material has been calculated by Ceranoglu and Pao [5] and by Vasudevan and Mal [6]. An analytical methodology for predicting the acoustic emission associated with crack propagation and arrest in an isotropic material has been developed by Jacobs et. al [7] and they have compared their theoretical predictions with experimental results. For fiber composite plates and laminates, Lih and Mal [8] have calculated the response of a unidirectional laminate to surface point loads and line loads, and the same authors [9] consider distributed surface loading on both cross-ply and quasi-isotropic plates. An experimental study of the relation between the received signals and the initiating events has been carried out by Ono and Huang [10]

Transient Response of a Four-Ply Fiber Composite Laminate to an Internal Line Source

The detection of internal processes such as delamination and crack propagation by surface monitoring is of prime concern in QNDE. The derivation of the corresponding theoretical results is important in that they can serve to validate NDE techniques. This is the motivation behind our interest here in the general problem of the response of a laminated plate to an internal impulsive line load

The Effect of Rise Times on the Response of Fiber Composite Laminates to Dislocation Sources

The stress states which arise in fiber composite laminates under in-service conditions can give rise to a wide variety of local defects and microfractures whilst the laminate still preserves its structural integrity. In any attempt to assess the remaining life of the structure it is necessary to determine the nature and location of these damage events and to monitor the subsequent growth of the defects. Both the onset and the growth of the defects lead to the release of elastic stored energy which gives rise to acoustic emission signals. These signals can be recorded as transient disturbances on the surface of the structure and the nature of these disturbances depends on the location of the source, the character of the damage event and the time history of the energy release, as well as on the mode of propagation of elastic waves through the laminate. The inverse problem of locating and classifying the nature of the source event from the recorded surface disturbance is a formidable task, which requires a detailed knowledge of the propagation of stress waves through the laminate due to a range of sources with known characteristics, located at a specified internal position

Acoustic Emission in a Fiber Composite Plate

Acoustic emission techniques are being widely used for the detection of faults in engineering structures. These techniques allow the possibility of real time monitoring of large areas of in-service structures, with a high probability of crack detection (see e.g. Granata et. al. [1], Jacobs et. al. [2]). A prerequisite for this application is a thorough understanding of the nature of the stress waves generated as a result of internal impulsive events. A number of authors have examined the problem both theoretically and experimentally and the reader is referred to [2] for a list of references. Amongst these in particular, Ceranoglu and Pao [3] have made a comprehensive theoretical and numerical study of the transient response of an isotropic plate to a variety of dynamic nuclei of strain They show plots of the time histories of both the normal and tangential surface displacements at the epicenter and at radial distances of two, four and six plate thicknesses from the source location. Results are presented for surface sources and buried sources located at the mid-plane of the plate. The surface sources consist of normal, tangential and oblique step function point loads, whilst the buried forces include also double forces, couples, centers of explosion, centers of rotation and double couples without moment.</p

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

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Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead