Grain refinement of stainless steel in ultrasound-assisted additive manufacturing

Metals and alloys fabricated by fusion-based additive manufacturing (AM), or 3D printing, undergo complex dynamics of melting and solidification, presenting challenges to the effective control of grain structure. Herein, we report on the use of high-intensity ultrasound that controls the process of solidification during AM of 316L stainless steel. We find that the use of ultrasound favours the columnar-to-equiaxed transition, promoting the formation of fine equiaxed grains with random crystallographic texture. Moreover, the use of ultrasound increases the number density of grains from 305 mm−2 to 2748 mm−2 despite an associated decrease in cooling rate and temperature gradient in the melt pool during AM. Our assessment of the relationship between grain size and cooling rate indicates that the formation of crystallites during AM is enhanced by ultrasound. Furthermore, the use of ultrasound increases the amount of constitutional supercooling during solidification by lowering the temperature gradient in the bulk of the melt pool, thus creating an environment that favours nucleation, growth, and survival of grains. This new understanding provides opportunities to better exploit ultrasound to control grain structure in AM-fabricated metal products

Laser powder bed fusion of high-strength and corrosion-resistant Inconel alloy 725

The development of additive manufacturing, or three-dimensional (3D) printing, technologies has produced breakthroughs in the design and manufacturing of products by enhancing design freedom and minimising manufacturing steps. In addition, the complex, unique microstructures imparted by the additive processes offer prospects of unprecedented advances to produce high-performance metal alloys for high-temperature and corrosive environments. Here, we present the first additive manufacturing of Inconel alloy 725, an advanced nickel-base superalloy that is the widely accepted gold standard material of choice for oil and gas, chemical, and marine applications. We explore the printability of Inconel alloy 725 and identify a wide processing space to build material with a crack- and near-pore-free microstructure. The conventionally heat-treated Inconel alloy 725 has an equiaxed, near-fully recrystallised microstructure containing copious twin boundaries and nano-precipitates. It also displays promising tensile properties and corrosion resistance compared to its wrought counterpart. Our work opens the door toward additive manufacturing of Inconel alloy 725 components with optimised microstructure and topology geometry for applications in harsh environments

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

The burden of disease profile of residents of Nairobi's slums: Results from a Demographic Surveillance System

BACKGROUND: With increasing urbanization in sub-Saharan Africa and poor economic performance, the growth of slums is unavoidable. About 71% of urban residents in Kenya live in slums. Slums are characteristically unplanned, underserved by social services, and their residents are largely underemployed and poor. Recent research shows that the urban poor fare worse than their rural counterparts on most health indicators, yet much about the health of the urban poor remains unknown. This study aims to quantify the burden of mortality of the residents in two Nairobi slums, using a Burden of Disease approach and data generated from a Demographic Surveillance System. METHODS: Data from the Nairobi Urban Health and Demographic Surveillance System (NUHDSS) collected between January 2003 and December 2005 were analysed. Core demographic events in the NUHDSS including deaths are updated three times a year; cause of death is ascertained by verbal autopsy and cause of death is assigned according to the ICD 10 classification. Years of Life Lost due to premature mortality (YLL) were calculated by multiplying deaths in each subcategory of sex, age group and cause of death, by the Global Burden of Disease standard life expectancy at that age. RESULTS: The overall mortality burden per capita was 205 YLL/1,000 person years. Children under the age of five years had more than four times the mortality burden of the rest of the population, mostly due to pneumonia and diarrhoeal diseases. Among the population aged five years and above, HIV/AIDS and tuberculosis accounted for about 50% of the mortality burden. CONCLUSION: Slum residents in Nairobi have a high mortality burden from preventable and treatable conditions. It is necessary to focus on these vulnerable populations since their health outcomes are comparable to or even worse than the health outcomes of rural dwellers who are often the focus of most interventions

ALDH Activity Selectively Defines an Enhanced Tumor-Initiating Cell Population Relative to CD133 Expression in Human Pancreatic Adenocarcinoma

Multiple studies in recent years have identified highly tumorigenic populations of cells that drive tumor formation. These cancer stem cells (CSCs), or tumor-initiating cells (TICs), exhibit properties of normal stem cells and are associated with resistance to current therapies. As pancreatic adenocarcinoma is among the most resistant human cancers to chemo-radiation therapy, we sought to evaluate the presence of cell populations with tumor-initiating capacities in human pancreatic tumors. Understanding which pancreatic cancer cell populations possess tumor-initiating capabilities is critical to characterizing and understanding the biology of pancreatic CSCs towards therapeutic ends. cell populations were further examined for co-expression of CD44 and/or CD24. We demonstrate that unlike cell populations demonstrating low ALDH activity, as few as 100 cells enriched for high ALDH activity were capable of tumor formation, irrespective of CD133 expression. In direct xenograft tumors, the proportions of total tumor cells expressing ALDH and/or CD133 in xenograft tumors were unchanged through a minimum of two passages. We further demonstrate that ALDH expression among patients with pancreatic adenocarcinoma is heterogeneous, but the expression is constant in serial generations of individual direct xenograft tumors established from bulk human pancreatic tumors in NOD/SCID mice. phenotypes do not appear to significantly contribute to tumor formation at low numbers of inoculated tumor cells. ALDH expression broadly varies among patients with pancreatic adenocarcinoma and the apparent expression is recapitulated in serial generations of direct xenograft tumors in NOD/SCID. We have thus identified a distinct population of TICs that should lead to identification of novel targets for pancreatic cancer therapy

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer

BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients

An approach to the control of disease transmission in pig-to-human xenotransplantation.

Abstract: Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering