Finite element analysis of single-storey unreinforced alternative masonry walls

The most commonly cited obstacles to the uptake of alternative masonry units on a meaningful scale, despite significant research investment, are a lack of standards and understanding of their structural behaviour. This paper contributes to the body of knowledge on finite element analysis of alternative masonry structures, towards improved understanding of their structural behaviour. Two critical masonry wall configurations, in the context of South African low-income, government-subsidised housing, are analysed using the simplified micro-modelling approach, under ultimate limit state wind and seismic actions. Three alternative masonry materials are characterised and employed in the numerical analyses, geopolymer, compressed-stabilised earth and adobe blocks, as well as conventional concrete blocks as benchmark. Despite the wide spectrum in masonry materials analysed, the chosen modelling approach captured the major failure mechanisms well. The four materials performed as expected relative to one another, but most wall/material configurations failed to resist the required design load, including the conventional concrete masonry material.http://ase.sagepub.comhj2022Civil Engineerin

Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis

A new technique based on diffusion tensor imaging and computational neuroanatomy was developed to efficiently and quantitatively characterize the three- dimensional morphology of the developing brains. The technique was used to analyze the phenotype of conditional Bcl-x knock-out mice, in which the bcl-x gene was deleted specifically in neurons of the cerebral cortex and hippocampus beginning at embryonic day 13.5 as cells became postmitotic. Affected brain regions and associated axonal tracts showed severe atrophy in adult Bcl-x-deficient mice. Longitudinal studies revealed that these phenotypes are established by regressive processes that occur primarily during the first postnatal week, whereas neurogenesis and migration showed no obvious abnormality during embryonic stages. Specific families of white matter tracts that once formed normally during the embryonic stages underwent dramatic degeneration postnatally. Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial manifestation of morphological phenotype

Expanding contraceptive options for PMTCT clients: a mixed methods implementation study in Cape Town, South Africa

Abstract Background Clients of prevention of mother-to-child transmission (PMTCT) services in South Africa who use contraception following childbirth rely primarily on short-acting methods like condoms, pills, and injectables, even when they desire no future pregnancies. Evidence is needed on strategies for expanding contraceptive options for postpartum PMTCT clients to include long-acting and permanent methods. Methods We examined the process of expanding contraceptive options in five health centers in Cape Town providing services to HIV-positive women. Maternal/child health service providers received training and coaching to strengthen contraceptive counseling for postpartum women, including PMTCT clients. Training and supplies were introduced to strengthen intrauterine device (IUD) services, and referral mechanisms for female sterilization were reinforced. We conducted interviews with separate samples of postpartum PMTCT clients (265 pre-intervention and 266 post-intervention) to assess knowledge and behaviors regarding postpartum contraception. The process of implementing the intervention was evaluated through systematic documentation and interpretation using an intervention tracking tool. In-depth interviews with providers who participated in study-sponsored training were conducted to assess their attitudes toward and experiences with promoting voluntary contraceptive services to HIV-positive clients. Results Following the intervention, 6% of interviewed PMTCT clients had the desired knowledge about the IUD and 23% had the desired knowledge about female sterilization. At both pre- and post-intervention, 7% of clients were sterilized and IUD use was negligible; by comparison, 75% of clients used injectables. Intervention tracking and in-depth interviews with providers revealed intervention shortcomings and health system constraints explaining the failure to produce intended effects. Conclusions The intervention failed to improve PMTCT clients’ knowledge about the IUD and sterilization or to increase use of those methods. To address the family planning needs of postpartum PMTCT clients in a way that is consistent with their fertility desires, services must expand the range of contraceptive options to include long-acting and permanent methods. In turn, to ensure consistent access to high quality family planning services that are effectively linked to HIV services, attention must also be focused on resolving underlying health system constraints weakening health service delivery more generally

Increased cerebral blood volume in small arterial vessels is a correlate of amyloid-β-related cognitive decline

The protracted accumulation of amyloid-β (Aβ) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]. After 2 years, inflow-based vascular space occupancy at ultra-high field strength of 7-Tesla was administered for measuring CBVa, and neuropsychological testing for cognitive decline. Crushing gradients were incorporated during MR-imaging to suppress signals from fast-flowing blood in large arteries, and thereby sensitize inflow-based vascular space occupancy to CBVa in pial arteries and arterioles. CBVa was significantly elevated in MCI compared to cognitively normal controls and regional CBVa related to local Aβ deposition. For both MCI and controls, Aβ burden and follow-up CBVa in several brain regions synergistically predicted cognitive decline over 2 years. Orbitofrontal CBVa was positively associated with apolipoprotein E e4 carrier status. Increased CBVa may reflect long-term effects of region-specific pathology associated with Aβ deposition. Additional studies are needed to clarify the role of the arteriolar system and the potential of CBVa as a biomarker for Aβ-related vascular downstream pathology

Pretubulysin: From Hypothetical Biosynthetic Intermediate to Potential Lead in Tumor Therapy

Pretubulysin is a natural product that is found in strains of myxobacteria in only minute amounts. It represents the first enzyme-free intermediate in the biosynthesis of tubulysins and undergoes post-assembly acylation and oxidation reactions. Pretubulysin inhibits the growth of cultured mammalian cells, as do tubulysins, which are already in advanced preclinical development as anticancer and antiangiogenic agents. The mechanism of action of this highly potent compound class involves the depolymerization of microtubules, thereby inducing mitotic arrest. Supply issues with naturally occurring derivatives can now be circumvented by the total synthesis of pretubulysin, which, in contrast to tubulysin, is synthetically accessible in gram-scale quantities. We show that the simplified precursor is nearly equally potent to the parent compound. Pretubulysin induces apoptosis and inhibits cancer cell migration and tubulin assembly in vitro. Consequently, pretubulysin appears to be an ideal candidate for future development in preclinical trials and is a very promising early lead structure in cancer therapy

Evidence of Distinct Tumour-Propagating Cell Populations with Different Properties in Primary Human Hepatocellular Carcinoma

Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC).After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice.The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features.Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie