One of the advantages provided by fused deposition modelling (FDM) 3D printing technology is the manufacturing of product materials with infill structure, which provides advantages such as reduced production time, product weight and even the final price. In this paper, the tensile mechanical properties, tensile strength and elastic modulus, of PLA, Tough PLA and PC FDM 3D printed materials with the infill structure were analysed and compared. Also, the influence of infill pattern on tensile properties was analysed. Material testing were performed according to ISO 527-2 standard. All results are statistically analysed and results showed that infill pattern have influence on tensile mechanical properties for all three materials.
Ex-vivo expanded tumour infiltrating lymphocytes (TIL) show promise in delivering durable responses among several solid tumour indications. However, characterising, quantifying and tracking the active component of TIL therapy remains challenging as the expansion process does not distinguish between tumour reactive and bystander T-cells. Achilles Therapeutics has developed ATL001, a patient-specific TIL-based product, manufactured using the VELOS™ process that specifically targets clonal neoantigens present in all tumour cells within a patient. Two Phase I/IIa clinical trials of ATL001 are ongoing in patients with advanced Non-Small Cell Lung Cancer, CHIRON (NCT04032847), and metastatic or recurrent melanoma, THETIS (NCT03997474). Extensive product characterisation and immune-monitoring are performed through Achilles’ manufacturing and translational science programme. This enables precise quantification and characterisation of the active component of this therapy – Clonal Neoantigen T cells (cNeT) – during manufacture and following patient administration, offering unique insight into the mechanism of action of ATL001 and aiding the development of next generation processes.ATL001 was manufactured using procured tumour and matched whole blood from 8 patients enrolled in the THETIS (n=5) and CHIRON (n=3) clinical trials. Following administration of ATL001, peripheral blood samples were collected up to week 6. The active component of the product was detected via re-stimulation with clonal neoantigen peptide pools and evaluation of IFN-γ and/or TNF-α production. Deconvolution of individual reactivities was achieved via ELISPOT assays. Immune reconstitution was evaluated by flow cytometry. cNeT expansion was evaluated by restimulation of isolated PBMCs with peptide pools and individual peptide reactivities (ELISPOT).The median age was 57 (range 30 – 71) and 6/8 patients were male. The median number of previous lines of systemic anti-cancer treatment at the time of ATL001 dosing was 2.5 (range 1 – 5). Proportion of cNeT in manufactured products ranged from 0.20% - 77.43% (mean 26.78%) and unique single peptide reactivities were observed in 7 of 8 products (range 0 – 28, mean 8.6). Post-dosing, cNeTs were detected in 5/8 patients and cNeT expansion was observed in 3/5 patients.These data underscore our ability to sensitively detect, quantify and track the patient-specific cNeT component of ATL001 – during manufacture and post dosing. As the dataset matures, these metrics of detection and expansion will be correlated with product, clinical and genomic characteristics to determine variables associated with peripheral cNeT dynamics and clinical response.NCT04032847, NCT03997474The first 8 patients described have all been located within the UK and both trials (CHIRON and THETIS) have been approved by the UK MHRA (among other international bodies, e.g FDA). Additionally, these trials have been approved by local ethics boards at active sites within the UK. Patient‘s are fully informed by provided materials and investigators prior to consenting to enrol into either ATL001 trial.
Abstract Background Antimicrobial impregnated catheters (AIC) are one strategy to prevent CLABSI with existing data for central lines required for short duration, however, the strength of evidence, particularly for children, is lacking. Recent 3-year CLABSI data at our institution show 60 (51%) infections occurred in central lines within 8 weeks of insertion, suggesting an opportunity for evaluation of an intervention targeting this time frame. We implemented AIC to evaluate their effectiveness in reducing CLABSI standardized infection ratio (SIR) in patients requiring central venous access for less than 8 weeks. We also monitored for complications (malfunction, line exchange, fungal infection). Methods A stepped wedge observational design was used to implement Minocycline + Rifampin impregnated catheters in a rolling fashion across the institution. Children > 3kg were eligible if admitted to a participating unit and required central venous access through a peripherally inserted central catheter (PICC), non-tunneled catheter, or tunneled non-cuffed femoral catheter for < 8 weeks. Units, prioritized based on CLABSI SIR, were added to the intervention monthly until AIC were used throughout the institution. A multidisciplinary team (infectious diseases and infection control experts, CLABSI leaders, unit-based physicians and nurses, proceduralists, supply chain) met weekly to facilitate implementation, assess for CLABSI and monitor for complications. Figure 1. Study design. This figure describes the stepped wedge study design where units were phased into the invention on a rolling monthly basis allowing for comparison between and within units. The shaded boxes represent time periods when units were using antimicrobial impregnated catheters and the white boxes represent time periods when units were using standard non-impregnated catheters. Results AIC were systematically implemented over a 7-month period. The institution’s CLABSI SIR decreased from 0.80 to 0.59 during this timeframe. There were no NHSH defined CLABSI in patients with an AIC during the intervention. Obstacles included shortage of catheters due to supply chain disruption, adjustment of technique for line insertion and cracked/broken lines. Infections and complications were reviewed by the multidisciplinary team and compared to historical rates with non-impregnated lines. This figure shows the institution’s rolling 12-month SIR during the intervention period. Conclusion CLABSI SIR decreased at our institution during the intervention period. While many efforts likely led to this reduction (optimizing maintenance bundle, unit based CLABSI initiatives), we believe the use of AIC contributed to this improvement. There were no pediatric-specific safety events identified during implementation. Disclosures Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial stipend as Co-EiC, Clinical Therapeutics)Hologic (Consultant)Seqirus (Consultant)
Seismological constraints obtained from receiver function (RF) analysis provide important information about the crust and mantle structure. Here, we explore the utility of the free‐surface multiple of the P‐wave (PP) and the corresponding conversions in RF analysis. Using earthquake records, we demonstrate the efficacy of PPs‐RFs before illustrating how they become especially useful when limited data is available in typical planetary missions. Using a transdimensional hierarchical Bayesian deconvolution approach, we compute robust P‐to‐S (Ps)‐ and PPs‐RFs with InSight recordings of five marsquakes. Our Ps‐RF results verify the direct Ps converted phases reported by previous RF analyses with increased coherence and reveal other phases including the primary multiple reverberating within the uppermost layer of the Martian crust. Unlike the Ps‐RFs, our PPs‐RFs lack an arrival at 7.2 s lag time. Whereas Ps‐RFs on Mars could be equally well fit by a two‐ or three‐layer crust, synthetic modeling shows that the disappearance of the 7.2 s phase requires a three‐layer crust, and is highly sensitive to velocity and thickness of intra‐crustal layers. We show that a three‐layer crust is also preferred by S‐to‐P (Sp)‐RFs. While the deepest interface of the three‐layer crust represents the crust‐mantle interface beneath the InSight landing site, the other two interfaces at shallower depths could represent a sharp transition between either fractured and unfractured materials or thick basaltic flows and pre‐existing crustal materials. PPs‐RFs can provide complementary constraints and maximize the extraction of information about crustal structure in data‐constrained circumstances such as planetary missions.
The limited sensitivity of existing analysis techniques at the nanometer scale makes it challenging to systematically examine the complex interactions in redox-based resistive random access memory (ReRAM) devices. To test models of oxygen movement in ReRAM devices beyond what has previously been possible, we present a new nanoscale analysis method. Harnessing the power of secondary ion mass spectrometry, the most sensitive surface analysis technique, for the first time, we observe the movement of 16 O across electrically biased SiO x ReRAM stacks. We can therefore measure bulk concentration changes in a continuous profile with unprecedented sensitivity. This reveals the nanoscale details of the reversible field-driven exchange of oxygen across the ReRAM stack. Both the reservoir-like behavior of a Mo electrode and the injection of oxygen into the surface of SiO x from the ambient are observed within one profile. The injection of oxygen is controllable through changing the porosity of the SiO x layer. Modeling of the electric fields in the ReRAM stacks is carried out which, for the first time, uses real measurements of both the interface roughness and electrode porosity. This supports our findings helping to explain how and where oxygen from ambient moisture enters devices during operation.
In the present work, the influence of solution viscosity on growth kinetics and purification efficiency in layer melt crystallization was investigated. Melt crystallization experiments were conducted for three different types of aqueous sucrose solution as they are ideal solutions and a relatively wide viscosity range can be investigated with a moderate change of freezing points. The aqueous 10 wt%, 23 wt%, and 30 wt% sucrose solutions have a dynamic viscosity value of 2.01 mPas, 4.74 mPas, and 7.21 mPas at their respective freezing points of − 0.63 ◦ C, − 1.78 ◦ C, and − 2.64 ◦ C. The solution temperature distribution was predicted by computational fluid dynamics (CFD) simulations run in COMSOL Multiphysics 5.6 software. Experimental results showed that a higher solution viscosity caused a higher crystal layer impurity and lower crystal yields in static layer melt crystallization. The cooling process of different solutions predicted by a CFD heat transfer study showed that the supersaturation region is wider for less concentrated solutions as cooling proceeds more rapidly. Hence, the temperature gra-dients obtained follow the boundary layer theory, i.e., the thinner the boundary layer, the faster the heat transfer.
Pomological characteristics and consumer acceptability of four scab-resistant apple cultivars (‘Topaz’, ‘Florina’, ‘Goldstar’ and ‘Golden Orange’) and standard commercial cultivar ‘Golden Delicious’ were investigated. Consumer acceptability consisted of rating fruit samples on Likert scales measuring appearance, flavour, size, sweetness, acidity, crispiness, juiciness, skin texture and general impression. Consumers better evaluated the cultivar ‘Topaz’ sensory characteristics of flavour, juiciness, taste and general impression than other evaluated scab-resistant apple cultivars and the cultivar ‘Golden Delicious’. ‘Golden Delicious’ got good grades for appearance, size and sweetness. ‘Topaz’ also had the best pomological characteristic related to measured fruit firmness, contents of soluble solids and organic acids. It can be concluded that only the cultivar ‘Topaz’ among the scab-resistant apple cultivars achieved a good consumer assessment.
The Travelling Salesman Problem is categorized as NP-complete problems called combinatorial optimization problems. For the growing number of cities it is unsolvable with the use of exact methods in a reasonable time. Genetic algorithms are evolutionary techniques used for optimization purposes according to survival of the fittest idea. These methods do not ensure optimal solutions, however they give good approximation usually in time. Studies have shown that the proposed genetic algorithm can find a shorter route in real time, compared with the existing manipulator model of path selection. The genetic algorithm depends on the selection criteria, crosses, and mutation operators described in detail in this paper. Possible settings of the genetic algorithm are listed and described, as well as the influence of mutation and crossing operators on the efficiency of the genetic algorithm. The optimization results are presented graphically in the MATLAB software package for different cases, after which a comparison of the efficiency of the genetic algorithm with respect to the given parameters is performed.
UDK: 574.5(282.249 Bunica) Research into the benthic diatoms in the Bunica River was performed during the period from 5th May 2013 to 9th January 2014 on three different sites, from the headwaters to the mouth. The Bunica River is located in the south-eastern part of the Mostar valley, in the south of Bosnia and Herzegovina. The aim of this research was to test the use of benthic diatoms as indicators and the use of diatom indices as a tool for estimating water quality in an example of a small karstic river. For that purpose, diatom indices were calculated using OMNIDIA GB 5.3 software. This was the first testing of diatom indices for a small karstic river. Diatom indices showed different results and huge variations between sites on the Bunica River. According to the results, the indices in the OMNIDIA software are not applicable for karstic rivers in Bosnia and Herzegovina and they must be modified for this purpose. This paper can be the first step towards calibration indices for karstic region. Also, it can be useful for the development of biomonitoring tool for karstic rivers in Bosnia and Herzegovina.
UDK: 574:502(497.6) With the geographical position and climate conditions it has, Bosnia and Herzegovinais a countryof unique life forms and biodiversity. The flora, fauna and fungi of Bosnia and Herzegovina are among the most diverse in Europe, and the high level of endemism and relict species provide for the country’s significance at the global biodiversity level (UNCBD, 2019). Since 2002, Bosnia and Herzegovina, as a party to the United Nations Convention on Biological Diversity (UNCBD), has been following global trends of conservation and sustainable use of biodiversity. Followingthe Convention, among others, six national reports were developed, as well as the Strategy and Action Plan for Protection of Biological Diversity in Bosnia and Herzegovina (NBSAP) by 2020. These documents seek to ensure that protection and sustainable use of biodiversity become inevitable principles when relevant sectoral policies, strategies and legislation at all governmental levels of Bosnia and Herzegovina are being developed. In 2013, the Bosnian-Herzegovina Clearing House Mechanism (CHM) portal for sharing information on biodiversity was established within the global network CBD CHM. As a member country of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), Bosnia and Herzegovina actively represents and advocates for the interests of Eastern Europe. Bosnia and Herzegovina has made significant contribution to the preparation of a Regional and Sub-Regional Assessment for Biodiversity and Ecosystem Services for Europe and Central Asia, which was adopted at the Sixth Plenary Session of IPBES (Medellin, Colombia, March 2018). In the context of regional and global cooperation, Bosnia and Herzegovina significantly contributes to the organization of the workshop and the preparation of an Eastern European Action Document on Pollinators, Food Security and Rural Development, within BES-Net Trialogue. Bosnia and Herzegovina reaffirmed its commitment to the status of pollinators by accessing to the global Coalition of the Willing on Pollinators at the 6th IPBES Plenary Session.
UDK: 630*52:519.233.5]:582.475(497.6) As the result of sporadic afforestation of not-grown forest land in the past, today in B&H we have significant areas of even-aged forest plants of Scots pine of different ages. Estimate of yield capabilities of habitats/sites of these stands is one of very real issues in even-aged management planning for this tree species. In order to get the clear idea on the value of yield of even-aged stands, it is necessary to conduct long-term researches on permanent experimental plots. Considering that for the results of those researches it is necessary to wait approximately for the duration of production periods for specific tree species, to gain orientation solutions of the problem we can apply short-term researches – using temporary experimental plots set in stands of different ages. Members of the Forest Management Department of Forestry Faculty in Sarajevo in a period from 1985 to 1990 gathered data on temporary experimental plots in existing even-aged forest plantations of spruce, Scots pine and black pine in order to research their growth, structural and production characteristics. Part of those data for Scots pine is used for making of this document. Objective of this research was, based on data on measurement of 77 experimental plots positioned in even-aged not-tended plantations of Scots pine Bosnia-wide, to reach relevant information on the value of wood volume depending on their age and site quality, and to create the most favourable regression model for assessment of volume of large wood value based on known values of the stand taxation elements that could be easily and quickly determined. Besides this, in this document by comparing gained results with appropriate data from other authors we have evaluated productivity of even-aged not-tended forest plantations of Scots pine in B&H.
Recurrent Respiratory Papillomatosis (RRP) is a rare but severe manifestation of human papillomavirus (HPV). As our knowledge about HPV infections has expanded, it has become possible to understand the course of RRP disease and unravel plausible efficient methods to manage the disease. However, the surge in reports on HPV has not been accompanied by a similar increase in research about RRP specifically. In this paper, we review the clinical manifestation and typical presentation of the illness. In addition, the pathogenesis and progression of the disease are described. On the other hand, we discuss the types of treatments currently available and future treatment strategies. The role of vaccination in both the prevention and treatment of RRP will also be reviewed. We believe this review is essential to update the general knowledge on RRP with the latest information available to date to enhance our understanding of RRP and its management.
Simple Summary Fascin, an actin-binding protein, is upregulated in different types of human cancers. It is reportedly responsible for increasing the invasive and metastatic ability of cancer cells by reducing cell–cell adhesions. This review provides a brief overview of fascin and its interactions with other genes and oncoviruses to induce the onset and progression of cancer. Abstract Fascin is an actin-binding protein that is encoded by the FSCN1 gene (located on chromosome 7). It triggers membrane projections and stimulates cell motility in cancer cells. Fascin overexpression has been described in different types of human cancers in which its expression correlated with tumor growth, migration, invasion, and metastasis. Moreover, overexpression of fascin was found in oncovirus-infected cells, such as human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), disrupting the cell–cell adhesion and enhancing cancer progression. Based on these findings, several studies reported fascin as a potential biomarker and a therapeutic target in various cancers. This review provides a brief overview of the FSCN1 role in various cancers with emphasis on gynecological malignancies. We also discuss fascin interactions with other genes and oncoviruses through which it might induce cancer development and progression.
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