External Domain Research Articles

Influence of the external ear tissue domains on the sound attenuation of an earplug predicted by a finite element model

Earplugs are a widespread solution to prevent the problem of hearing loss in the workplace environment, but they do not always perform as desired. Using a model of the ear canal occluded by an earplug could be helpful to perform sensitivity analyses (geometry and materials of the earplug) and to better understand the role of the earplug. The human external ear is a complex system made up of different tissues with a 3D geometry. In practice, it is reduced to a 2D cylindrical geometry for the acoustical tests fixtures. The purpose of this study is to compare the insertion loss predicted by a 3D complex finite element model of the ear canal surrounded by different tissue domains (skin, soft tissue, and bone) and occluded by a silicon earplug versus a 2D axisymmetric model of the same system. In both models, some investigations are made in order to verify if the models could be simplified by replacing the tissue domains by mechanical impedances. These investigations are made to reduce the complexity of the models and to discuss the relevance of whether or not including external ear tissue domains in a sound attenuation model of an earplug.

LMP1 signaling in vivo downregulates DUSP1 and exacerbates inflammatory responses (P5204)

Abstract The EBV oncogenic protein LMP1 is implicated in pathogenesis of B cell malignancies and exacerbation of autoimmune disease. We previously produced mice that express, in B and myeloid cells, a transgene with the external domain of CD40 and signaling domain of LMP1. CD40-LMP1 substitutes for CD40 to induce a humoral response in CD40-/- mice, but they display elevated autoantibodies, enlarged lymphoid organs, and elevated inflammatory cytokines. Co-expression of CD40 and CD40-LMP1 partially ameliorates this inflammatory/autoreactive phenotype. The phosphatase DUSP1 is downregulated in B cells from CD40-LMP1tg mice, and upon induced expression of Wt LMP1 in a B cell line. DUSP1 is implicated in the control of inflammatory signaling pathways, and DUSP1 deficiency has been shown to increase susceptibility of mice to LPS induced sepsis. We hypothesized that inhibition of DUSP1 expression caused by LMP1 signaling contributes to the association of LMP1 with inflammation. We tested the impact of LMP1 expression on in vivo responses to LPS in mice expressing CD40-LMP1, CD40, or both. Two hrs after challenge with a low dose of LPS, serum TNFa and IL1b were increased to a markedly greater degree in mice expressing CD40-LMP1, and this was alleviated by co-expression of CD40. Additionally, >50% of CD40-LMP1 Tg mice, but none of the mice expressing Wt CD40, developed sepsis. These findings suggest a potential mechanism by which LMP1 promotes exacerbation of chronic inflammatory disease.

Soil-High-Rise Building Group Dynamic Interaction Considering Site Effect

This article reports a sub-domain method to analyze the dynamic interaction of soil-high-rise building group considering sit effect, which is the extension of the domain reduction method proposed by Bielak and his coworkers in the framework of the finite-element method, originally for building–soil–foundation interaction problems. The whole domain with high-rise building group is divided into two interrelated sub-domains, the external domain and the internal one. And the method contains two steps. In addition, the effect of the external domain to the internal domain is expressed by the equivalent forces which are put on the nodes of the interface between the two sub-domains in the second step. The formation of the equivalent force is attained according to the equation of motion. In the first step the free-field ground motion is calculated under the bedrock wave excitation, and all the nodal displacements are stored. Then the equivalent forces are calculated according the data in the first step, using the formulation of the equivalent force. In the second step a finite element analysis model of the sub-domain containing the internal domain and the high-rise building group is established, and the equivalent forces are put on the nodes of the interface. Later the seismic response of soil-high-rise building group can be calculated.

Diversity patterns of Early Jurassic brachiopod assemblages from the westernmost Tethys (Eastern Subbetic)

A detailed faunal succession based upon 6400 brachiopods from the Early Jurassic in the Eastern External Subbetic palaeogeographical domain (Betic Range, Spain) is characterized and analyzed. This study allows recognition of five assemblages with original biostratigraphical data in sediments where biostratigraphical markers were very scarce. It also enables a sound diversity dynamics pattern to be established among the brachiopod assemblages recorded. This pattern shows progressive diversification from the Sinemurian to the Late Pliensbachian, although with significant episodes. During the Sinemurian–Pliensbachian transition, the first initial pulses of the disintegration of the South Iberian palaeomargin played an important role in the brachiopod assemblages, as a notable faunal renewal event is detected (Assemblage 1 to Assemblage 2). Maximum biodiversity and abundance were reached in the Pliensbachian–Toarcian transition, due to the partial contemporaneity of Assemblages 2 and 3 and the settlement of taxa from nearby palaeogeographical basins. A decrease related to the Early Toarcian Anoxic Event (ETOAE) global effect is suggested, after which a slight recovery began, with colonization by opportunistic taxa (Soaresirhynchia bouchardi) but pre-ETOAE diversity and abundance were subsequently never again reached.A palaeogeographical analysis has been carried out to compare taxonomic diversity dynamics in the Eastern Subbetic with other representative Tethyan basins. This study also enables palaeobiogeographical affinities to be established for the Eastern Subbetic domain, showing Mediterranean palaeobioprovince influences until the Late Pliensbachian–Early Toarcian, a period when replacement occurred that shows faunal unification. Free connection between the Sub-boreal and Mediterranean provinces may be inferred from the Late Pliensbachian–Early Toarcian onwards.

Abstract 4696: Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy.

Abstract Background: PSMA is nearly universally expressed by prostate cancer and is upregulated with castration-resistance. Recently, non-invasive measurement of PSMA expression has been demonstrated to be a novel biomarker of androgen receptor activity in animal models. J591 is a monoclonal antibody which selectively and efficiently binds the external domain of PSMA with no direct effect on PSA expression or secretion. Four therapeutic phase I and II trials of radiolabeled (RL)-J591 using (177Lu-J591 and 90Y-J591) have been performed in men with metastatic castration-resistant prostate cancer (CRPC). In addition to therapeutic infusion with RL-J591, planar gamma camera imaging was performed. Methods: Following IRB approval, a combined analysis of 4 prospective studies of RL-J591 for metastatic CRPC was performed. RL-J591 images were semi-quantitatively scored using 2 methods by 2 independent radiologists blinded to outcome. A 5-point visual score (VS) of 0 - 4+ was assigned. In addition, a semi-quantitative Tissue Targeting Index (TTI) was calculated for the most prominent lesions in each subject using the ratio of lesion count density (corrected for background) to whole body count density, with maximum and mean scores recorded. PSMA expression as measured by imaging was correlated with efficacy measures in long-term follow up of all studies. Results: 130 patients (pts) with metastatic CRPC received RL- J591 with semi-quantitative imaging. 86.2% had bone metastases, 51.5% lymph node, 16.9% lung, 9.2% liver. 87.7% had accurate targeting of known sites of disease by planar imaging. Only 8.0% of pts with no evidence of PSMA expression via J591 imaging (VS=0) experienced treatment response versus 40.6% of those with the highest strongest expression as measured by VS (p=0.01). In addition to PSA declines, for the subset of 17 pts with baseline and follow up circulating tumor cell (CTC) counts, those with higher VS tended to have more CTC decreases (p=0.12). Those with the lowest level of PSMA expression as measured by TTI tended to have fewer PSA declines (p=0.12). PSA response was associated with superior overall survival compared to those without >30% PSA decline (p=0.02). Conclusions: Non-invasive measurement of PSMA expression may be semi-quantitatively measured with planar gamma-camera imaging following infusion with RL-J591. Level of PSMA expression is associated with response to radiolabeled anti-PSMA radioimmunotherapy. Improvements in quantitative molecular imaging techniques such as PSMA PET/CT with 89Zr-J591 may prove to be a valuable predictive biomarker for PSMA-based therapeutics. Citation Format: Naveed H. Akhtar, Joseph Osborne, David M. Nanus, Shankar Vallabhajosula, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa. Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4696. doi:10.1158/1538-7445.AM2013-4696

Abstract 3045: Glycosylation dependence in MUC16/CA125 expression in ovarian cancer..

Abstract CA125 antigen is an established characteristic of human ovarian cancer. Yet its function remains largely unknown. The cloning of MUC16, encoding the CA125 antigen, has opened the door to additional functional exploration. MUC16 has a molecular size of over 14,000 amino acids and consists of a 31 amino acid cytoplasmic domain, a 25 amino acid transmembrane region, a 58 amino acid ectodomain (proximal to the putative cleavage site) and an external domain of up to 60 tandem repeats. As previously reported, as little as 114 AA of MUC16 from the carboxyterminus will traffic to the membrane and induce an altered, more aggressive phenotype, and longer elements from the carboxyterminus with multiple CA125 antigenic tandem repeats were not substantially different. When A2780, SKOV3 or 3T3 cell lines expressed these short elements (both the c114 and the c344) of the MUC16 gene carboxyterminus, they had substantial increases in soft agar colony formation, matrigel invasion and increased phosphorylation of AKT and ERK signaling. Associated with these alterations in signal transduction are changes in gene expression including upregulation of fibronectin, IL-1β, MMP7, and MMP9. While expression of these MUC16 fragments does not change in vitro growth, when placed in nu/nu mice, the transformed tumors were more aggressive with a more disseminated phenotype and statistically significant more rapid tumor growth. Examination the c114 fragment for functional areas has been undertaken. Deletion of the ectodomain (c80) completely blocks these effects and is similar to the vector only controls for invasion, soft agar colony formation and xenograft growth. In contrast, loss of the intracellular domain (c86) has no effect and is similar to the c114 transformants. However, coprecipitation experiments did not yield specific partners. We hypothesized that the ectodomain function was related to glycosylation. Cell surface MUC16 interacts with key growth factor receptors via lectins like Galectin 3 to alter cell surface expression, receptor recycling, and phosphorylation to promote growth and invasion. Using our paired isogenic, MUC16+/- cell lines (3T3 and SKOV3), N-glycosylation site mutant were created and these mutants inhibited the matrigel invasion, lowered activation of AKT and ERK and also inhibited tumor growth in nude mice. We explored this phenomena and created shRNA knock down of MGAT5 (the first enzyme in protein glycosylation) or Galectin 3 (amplified in many high grade serous cancers) and expressed in SKOV3 and 3T3 cell lines. These lines completely reversed the effect of MUC16 expression of matrigel invasion, soft agar growth, ERK /AKT activation, EGFr phosphorylation, and xenograft growth, confirming that intact glycosylation is required for MUC16 effects on oncogene activation, matrigel invasion and in vivo growth. Mucins expression in malignant cells are associated with an enhanced tumor aggressiveness through N-glycosylation. Citation Format: Dharmarao Thapi, Xiu Jun Yan, Nestor Rosales, David R. Spriggs. Glycosylation dependence in MUC16/CA125 expression in ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3045. doi:10.1158/1538-7445.AM2013-3045

Abstract 4992: A novel role of soluble E-selectin as a chemoatractant to human leukocytes through the PI3kinase signaling pathway in breast cancer.

Abstract Solid tumors are multicellular complexes where the tumor stroma that is comprised of endothelial cells, pericytes, fibroblasts and immune cells, all of which orchestrate to assist in cancer cell growth, angiogenesis and invasion. The tissue infiltration of immune cells is mediated by a multistep adhesion cascade and involves the selectin family of calcium-dependent cell surface glycoproteins Among this family, E-selectin (CD62E, ELAM-1 or LECAM-2) is exclusively expressed on the surface of endothelial cells in a highly inducible manner in response to inflammatory cytokines, and consequently an elevated E-selectin expression has been reported in many types of diseases including cancer. Endothelial E-selectin (eE-sel) assists in the initial adhesion of circulatory leukocytes to the surface of vascular endothelium by interacting with its ligands (sLeX, sLeA and CD44). The external domain of E-selectin can be cleaved off and shed into the circulation as soluble E-selectin (sE-sel). sE-sel is present in the serum of cancer patients and is associated with occurrence of metastases and poor survival in breast and colorectal cancers. However, the biological relevance of sE-sel is not clearly understood. In this study, we aim to identify the biological role of sE-sel in breast cancer growth. We have demonstrated that sE-sel enhances the adhesion and tissue migration of leukocytes into breast tumor both in vitro through the activation of PI3 kinase and its downstream signaling cascade. We have also demonstrated that 7 times more peripheral blood mononuclear cells (PBMC) migrate into breast tumor when pre-incubated with sE-sel as compared to untreated condition. Therefore, we conclude that sE-sel serves as a chemoattractant that enhances the tissue migration of leukocytes, which lead to the development of solid tumor stroma that enhances the growth of breast tumor and invasion. Citation Format: Celine A. Blache, Nafis Hasan, Jeehna Park, Stephen Suh, David G. Gorenstein, Hallgeir Rui, Takemi Tanaka. A novel role of soluble E-selectin as a chemoatractant to human leukocytes through the PI3kinase signaling pathway in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4992. doi:10.1158/1538-7445.AM2013-4992

Secretion of truncated recombinant rabies virus glycoprotein with preserved antigenic properties using a co-expression system in Hansenula polymorpha

Rabies virus infection remains a serious public health threat in the developing world, where cost-concerns make wide-scale public health interventions impractical. The development of novel and inexpensive ELISA diagnostic antigens is critical in early detection and prevention of complications. The transmembrane glycoprotein (G) of rabies virus (RV) contains an external domain capable of inducing the synthesis of anti-rabies, virus-neutralizing antibodies, in infected or immunized hosts. In our study, the external G domain was synthesized and fused in-frame with a polyhistidine-tag coding sequence present in the expression plasmid. Soluble truncated recombinant G was secreted in Hansenula polymorpha (H. polymorpha) using H. polymorpha-derived calnexin (HpCNE1) overproduction and found to be correctly N-glycosylated. The truncated recombinant G was purified from cell culture supernatant by Ni-agarose affinity chromatography and when compared with the full-length glycoprotein, found to be similarly immunogenic in vaccinated rabbits. These results subsequently led us to explore the potential of truncated recombinant G as a diagnostic antigen in ELISA. Our results show that the truncated recombinant G can detect antibodies directed to both whole virion and native glycoprotein. More sophisticated applications of truncated recombinant G would profit from the correctly N-glycosylated and soluble monomer.

Biological and biochemical characterization of HIV‐1 Gag/dgp41 virus‐like particles expressed in Nicotiana benthamiana

The transmembrane HIV-1 envelope protein gp41 has been shown to play critical roles in the viral mucosal transmission and infection of CD4+ cells. Gag is a structural protein configuring the enveloped viral particles and has been suggested to constitute a target of the cellular immunity that may control viral load. We hypothesized that HIV enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the membrane proximal external, transmembrane and cytoplasmic domains (dgp41) could be expressed in plants. To this end, plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a Tobamovirus-based expression system or a combination of both. Our results of biophysical, biochemical and electron microscopy characterization demonstrates that plant cells could support not only the formation of enveloped HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These findings provide further impetus for the journey towards a broadly efficacious and inexpensive subunit vaccine against HIV-1.

Use of G-Protein-Coupled and -Uncoupled CCR5 Receptors by CCR5 Inhibitor-Resistant and -Sensitive Human Immunodeficiency Virus Type 1 Variants

Small-molecule CCR5 inhibitors such as vicriviroc (VVC) and maraviroc (MVC) are allosteric modulators that impair HIV-1 entry by stabilizing a CCR5 conformation that the virus recognizes inefficiently. Viruses resistant to these compounds are able to bind the inhibitor-CCR5 complex while also interacting with the free coreceptor. CCR5 also interacts intracellularly with G proteins, as part of its signal transduction functions, and this process alters its conformation. Here we investigated whether the action of VVC against inhibitor-sensitive and -resistant viruses is affected by whether or not CCR5 is coupled to G proteins such as Gαi. Treating CD4(+) T cells with pertussis toxin to uncouple the Gαi subunit from CCR5 increased the potency of VVC against the sensitive viruses and revealed that VVC-resistant viruses use the inhibitor-bound form of Gαi-coupled CCR5 more efficiently than they use uncoupled CCR5. Supportive evidence was obtained by expressing a signaling-deficient CCR5 mutant with an impaired ability to bind to G proteins, as well as two constitutively active mutants that activate G proteins in the absence of external stimuli. The implication of these various studies is that the association of intracellular domains of CCR5 with the signaling machinery affects the conformation of the external and transmembrane domains and how they interact with small-molecule inhibitors of HIV-1 entry.

Developing Integrated Arts Curriculum in Hong Kong: Chaos Theory at Work?

This article reports the development of integrated arts curriculum in two Hong Kong secondary schools over a 9‐year period. Initial findings display a range of individual responses to educational change that are both non‐predictable and non‐linear. Chaos theory is used to explain these varied responses in terms of bifurcations. The findings of this study are presented as a narrative that posits a developmental model comprising personal and external domains being informed by contextual feedback. Personal domains refer to the teachers’ education, their teaching experience and their motivational energies to improve their professional status quo. External domains refer to such contextual influences as educational policies, students, colleagues and school administration. Bifurcation explains why integrated arts curriculums impact different schools and individuals in different ways. Four factors are identified to have contributed to the failure or success of integrated arts curriculum: (1) school management support, (2) individual teachers’ specialized knowledge, (3) feedback that regenerates and redefines curriculum design, and (4) teacher autonomy and professional growth. A conclusion is drawn that questions the final form of Hong Kong integrated arts curriculum which retains the non‐integrated features of subject specialisation and individual teaching rather than co‐teaching.

A 247 µW 800 Mb/s/pin DLL-Based Data Self-Aligner for Through Silicon via (TSV) Interface

Among the stacked dies using through silicon via (TSV), data conflictions occur due to process mismatches, which decrease the data valid window and consume unwanted power due to the short circuit current. This paper presents the DLL-based data self-aligner (DBDA), which reduces data conflictions among stacked dies. The stacked dies employing the proposed DBDAs automatically align their data output timings without relying on any control signals from the master die or an extra signal among the stacked die. The DBDA reduces the data confliction time (tDC) due to process, voltage and temperature (PVT) variations from 500 ps to 50 ps and thereby reduces the short current from 3.62 mA to 0.41 mA. The proposed DBDA has two operation modes: the synchronous self-align mode (SSAM), in which the data is aligned in the external clock domain and the asynchronous self-align mode (ASAM). The lock time of DBDA is less than 20 cycles in SSAM. Additionally, the lock detector (LD) and proposed re-calibrator help the DBDA to find the optimal calibration period under temperature variation. They also reduce the calibration current of DBDA by 45.5%. A prototype DBDA implemented in 130 nm CMOS technology dissipates 247 μW for 800 Mb/s/pin. For reduction of the leakage current during the power down mode or the self-refresh mode, this paper proposes a leakage current controller, which reduces the leakage power by 90.5%.

Three dimensional non-axisymmetric transient acoustic radiation from an eccentric hollow cylinder

Theoretical analysis and detailed numerical simulations are presented for three-dimensional non-stationary vibroacoustic response of a doubly fluid-loaded infinitely long eccentric hollow elastic circular cylinder of arbitrary wall thickness, under arbitrary non-axisymmetric time-dependent on-surface mechanical drives. The formulation is based on the Navier equations of linear elasticity for the solid material, the wave equation for the internal and external fluid domains, the classical method of separation of variables, and the translational addition theorem for cylindrical wave functions. Laplace transform with respect to the time coordinate, Fourier transform with respect to the axial coordinate, and Fourier series expansion in the circumferential direction, are employed to obtain the transformed solutions in the form of partial-wave expansions of transcendental functions. A set of equally spaced virtual sources are assumed along the axial direction, and semi-analytical solutions are obtained in the Laplace domain as discrete summations of simple two dimensional solutions with different axial wave numbers. Time domain solutions are subsequently calculated by using Durbin’s numerical inverse Laplace transform scheme. The analytical results are illustrated with numerical examples in which air- or water-filled concentric and eccentric steel cylinders, submerged in water, are driven by a pair of equal and opposite external radial point loads of finite duration described by a Ricker pulse. Some interesting features of the transient fluid–solid interaction problem such as the generation of shell-induced circumnavigating waves, appearance of multiple high/low amplitude pressure spots in the internal fluid, and formation of non-propagating evanescent waves in the external fluid are noted using appropriate 2D images of the three dimensional sound fields. Limiting cases are considered and the validity of results is established with the aid of a commercial finite element package as well as by comparison with the data in the existing literature.

Full-Vectorial Meshfree Spectral Method for Optical-Waveguide Analysis

A full-vectorial multidomain spectral method (MDSM) for optical modal analysis is developed and presented. The formulation is based on considering the coupling between the transverse magnetic (TM) field components as the other electromagnetic components can be calculated directly from them. The method is meshfree where Chebyshev polynomials are used to expand the components in the internal domains and tempered exponential sets are used for the external domains. Practically, the presented method is applicable to 3-D optical-waveguide structures that are invariant in one direction. The field profiles are expanded by 1-D preselected basis functions with variable expansion coefficients. The presented method is used to study different waveguide structures and exhibits superior performance in time and accuracy and highly agrees with the published results obtained by various methods. The presented method computations are very fast when compared with the conventional mesh-based methods. To have the same accuracy, the required number of unknowns in MDSM is orders of magnitude less than those needed by finite-difference and finite-element methods.

Health-related Quality of Life in Psoriasis: Important Role of Personal Resources

Many patients with psoriasis demonstrate psychological disturbances, including decreased health-related quality of life (HRQoL). The aim of this study was to evaluate selected personal resources and HRQoL in 168 in-patients with psoriasis vulgaris. The following questionnaires were used: Skindex-29, General Health Questionnaire, Coping with Skin Disease Scale, Acceptance of Illness Scale, Life Orientation Test, Multidimensional Health Locus of Control Scale and General Self-Efficacy Scale. It was demonstrated that younger patients experienced fewer problems in psychosocial functioning, and that they showed a correlation between worse HRQoL and both external powerful others and external chance domains in locus of health control. Subjective self-evaluation of health correlated with HRQoL irrespective of patient's age. Coping with stress strategies hopelessness/helplessness and distraction/catastrophization correlated with worse overall HRQoL, whereas fighting spirit strategy correlated with better overall HRQoL. Hopelessness/helplessness coping strategy, somatic symptoms, disease acceptance, psoriasis severity and patient's age explained 61% of overall HRQoL variance. Psychomedical interventions designed for psoriatic patients should take into account the above variables.

Plasmamembrane Organization in Signaling

The composition of the plasma membrane has long been modeled as a fluid mosaic. (Singer and Nicolson, 1972) Studies in the last few years have identified microdomains like lipid rafts and caveolae that constrain membrane proteins within a small region of the cellular plasma membrane. These domains facilitate anchoring of different signaling proteins, like H-Ras, that has been shown to co-localize with nano domains upon activation (Lommerse et al. 2005, Rotblat et al. 2004). It is believed that these nanodomains function as important platforms for a multitude of signaling cascades that are initiated at the plasma membrane. Given that many of the transmembrane signals will need a coordinated domain organization, it is of importance to investigate properties like size, shape, stability and their mutual interaction.Here we transfected 3T3-cells to express the membrane anchor of H-Ras linked to Dendra2 or mEos2. Photo Activated Localization Microscopy (PALM) and Stimulated Emission Depletion Microscopy (STED) were used to make high resolution images of H-Ras distribution on the membrane as a probe for inner membrane domains. The GPI-anchored protein CD59 is used as a probe for the outer membrane domains to investigate colocalization of internal and external membrane domains. Using a SNAP-tag we covalently link Alexa647n to CD59 and image with direct stochastic optical microscopy (dSTORM).

Toward a universal influenza vaccine: from the perspective of protective efficacy

Toward a universal influenza vaccine: from the perspective of protective efficacy

HIV/AIDS in Physiotherapy Education – Mainstreaming Using UN Principles

HIV /AID S remains at epidemic levels in South Africa with onein ten people affected by the HI virus. The United Nations program for AID S(UNAID S) has defined five principles that can be used to mainstream HIV .The five key principles are: the development of a clearly defined entry point;use of existing policies, structures and frameworks; advocacy sensitizationand capacity building; distinguishing between the external (institutionalinterventions) and internal (staff risks and vulnerability) domain; and developingstrategic partnerships. A proposed HIV curriculum for physiotherapists wasbeen developed from a series of studies undertaken to understand the issues related to HIV using the principles ofmainstreaming.The purpose of this paper is to explore how each principle of mainstreaming can be applied in physiotherapyeducation and curricula.Each mainstreaming principle was considered and ways in which it could be mainstreamed into physiotherapytraining and practice, using data from the patients’, academics’ and clinicians’ experience were proposed.The five principles can be used in South African settings. In principle one the aetiology, approaches to treatment,management of conditions and symptoms are used to identify entry points for introducing HIV teaching. Relevantexamples of conditions associated with HIV include pain, stroke, specific muscle weakness patterns, fatigue andcardiopulmonary system problems (e.g. breathlessness). The role of physiotherapy in HIV management is also a goodentry point.For principle two, policies were considered. Pertinent areas such as antiretroviral use, frameworks such as theInternational Classification of Function (ICF), Worthington’s rehabilitation framework and CBR can also be integratedwith HIV physiotherapy curriculum and practice. Sensitised and aware staff as promoted in principle three,can advocate for affected patients and role model appropriate practice and attitudes in HIV management thuscontributing to reducing stigma and burnout. Integrating policies with the need to avoid risks and correct inappropriateattitudes of staff is promoted and promoting strategic partnerships and collaborative work will help provideappropriate services.Using the mainstreaming principles allows for the inclusion of HIV content in physiotherapy education and practice.Both physiotherapy curriculum and continuous professional development may use this information to respondappropriately.

Camel Heavy Chain Antibodies Against Prostate-Specific Membrane Antigen

Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.

Geodynamic implications derived from Numidian‐like distal turbidites deposited along the Internal–External Domain Boundary of the Betic Cordillera (S Spain)

Terra Nova, 00, 1–12, 2012AbstractNew data reveal Early Burdigalian ‘Numidian‐like lithofacies’ in successions of the internal (southernmost) part of the South Iberian Margin (SIM) and the south‐western margin of the Mesomediterranean Microplate (MM). The well‐known Numidian Formation was deposited in the external (Massylian) sub‐domain of the Maghrebian Flysch Basin (a south‐western branch of the Tethys Ocean). The anomalous occurrence of ‘Numidian‐like lithofacies’ is induced by the particular Early Miocene palaeogeographical and geodynamic complexity of the sector. This consisted of a ‘triple point’ with a dextral transform fault between the SIM and the MM‐Maghrebian Flysch Basin system. In this framework, the ageing of Iberian reliefs and the MM collapse, coupled with an African Margin upbulging, and a shortening of the Maghrebian Flysch Basin (both related to the subduction), could have resulted in the arrival of the Numidian depositional system from so far away.