The effect of composition, size and number density of inclusions on the ductility of an experimental direct quenched ultra-high-strength low-alloy steel with a minimum specified tensile strength of ...1300MPa has been investigated. Two steels with impurity levels, i.e. total O+N+S contents, of 55 and 91 mass ppm have been studied. Both steels were Al-killed and Ca-treated, and had a martensitic microstructure after hot rolling and direct quenching. Ductility was characterized using tensile and Charpy V-notch testing. The number, size and composition of the inclusions were characterized using field emission scanning electron microscope with energy dispersive spectrometer (FESEM-EDS). At the higher impurity level of 91ppm, the inclusion structure consisted of titanium nitrides, spherical calcium aluminates and elongated manganese sulphides, whereas at the lower impurity level of 55ppm, the inclusion structure consisted of mainly fine spherical calcium aluminates with sulphide shells. The impurity level did not have a significant effect on the number density of inclusions, as with higher and lower impurity level the number of inclusions mm−2 was 80.5 and 73.8, respectively. However, the impurity level affected somewhat more the size distribution of the inclusions, as well as the composition of coarse inclusions with their longest length more than 8µm. The number density of coarse inclusions mm−2 rose from 0.7 to 1.2 with increasing impurity level, and with the higher impurity level of 91ppm, 72% of the coarse inclusions were titanium nitrides or manganese sulphides, whereas with the lower impurity level of 55ppm, only 14% of the coarse inclusions were titanium nitrides while no manganese sulphides were detected. Coarse titanium nitrides were especially detrimental to the impact toughness. The number density of them should be below 0.4mm−2 in order to guarantee the best possible toughness in the steel in question.
Avidin-biotin technology in targeted therapy Lesch, Hanna P; Kaikkonen, Minna U; Pikkarainen, Jere T ...
Expert opinion on drug delivery,
05/2010, Letnik:
7, Številka:
5
Journal Article
Recenzirano
The goal of drug targeting is to increase the concentration of the drug in the vicinity of the cells responsible for disease without affecting healthy cells. Many approaches in cancer treatment are ...limited because of their broad range of unwanted side effects on healthy cells. Targeting can reduce side effects and increase efficacy of drugs in the patient.
Avidin, originally isolated from chicken eggs, and its bacterial analogue, streptavidin, from Streptomyces avidinii, have extremely high affinity for biotin. This unique feature is the basis of avidin-biotin technology. This article reviews the current status of avidin-biotin systems and their use for pretargeted drug delivery and vector targeting.
The reader will gain an understanding of the following approaches using the avidin-biotin system: i) targeting antibodies and therapeutic molecules are administered separately leading to a reduction of drug dose in normal tissues compared with conventional (radio)immunotherapies; ii) introducing avidin gene into specific tissues by local gene transfer, which subsequently can sequester and concentrate considerable amounts of therapeutic ligands; and iii) enabling transductional targeting of gene therapy vectors.
Avidin and biotin technology has proved to be an extremely versatile tool with broad applications, such as pretargeting, delivering avidin gene into cells enabling targeting of biotinylated compounds and targeting of viral vectors.
The effect of as-cast structure and macrosegregation on the mechanical properties of a direct-quenched low-alloy martensitic ultrahigh-strength aluminum killed and calcium treated steel cast at ...different superheats was studied. Samples from the castings were laboratory hot rolled with two different finishing rolling temperatures to distinguish the effect of hot rolling. Using optical emission spectrometry, the steel composition was analyzed as a function of slab thickness in order to detect the variations in steel chemistry due to macrosegregation. Further, hardness profiles, prior austenite grain sizes and tensile and impact toughness were determined for the hot-rolled specimens. It was found that interdendritic segregation was more intense at the higher superheat, which led to more pronounced positive segregation in the columnar-to-equiaxed transition (CET) zone, and negative segregation between CET and the centerline. These macrosegregation patterns were inherited by the hot-rolled samples causing local variations in hardness, which followed the variations in carbon content. However, altering the superheat had a minor effect on the nominal transformed microstructures and nominal prior austenite grain sizes. This occurred because of the interdendritic segregation induced composition variations both enlarged and decreased by turns the grain sizes. The CET also reduced measured impact toughness values.
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor that regulates protection against a wide variety of toxic insults to cells, including cytotoxic cancer chemotherapeutic ...drugs. Many lung cancer cells harbor a mutation in either Nrf2 or its inhibitor Keap1 resulting in permanent activation of Nrf2 and chemoresistance. In this study, we sought to examine whether this attribute could be exploited in cancer suicide gene therapy by using a lentiviral (LV) vector expressing herpes simplex virus thymidine kinase (HSV-TK/GCV) under the regulation of antioxidant response element (ARE), a cis-acting enhancer sequence that binds Nrf2. In human lung adenocarcinoma cells in which Nrf2 is constitutively overexpressed, ARE activity was found to be high under basal conditions. In this setting, ARE-HSV-TK was more effective than a vector in which HSV-TK expression was driven by a constitutively active promoter. In a mouse xenograft model of lung cancer, suicide gene therapy with LV-ARE-TK/GCV was effective compared with LV-PGK-TK/GCV in reducing tumor size. We conclude that ARE-regulated HSV-TK/GCV therapy offers a promising approach for suicide cancer gene therapy in cells with high constitutive ARE activity, permitting a greater degree of therapeutic targeting to those cells.
Lentivirus can be engineered to be a highly potent vector for gene therapy applications. However, generation of clinical grade vectors in enough quantities for therapeutic use is still troublesome ...and limits the preclinical and clinical experiments. As a first step to solve this unmet need we recently introduced a baculovirus-based production system for lentiviral vector (LV) production using adherent cells. Herein, we have adapted and optimized the production of these vectors to a suspension cell culture system using recombinant baculoviruses delivering all elements required for a safe latest generation LV preparation. High-titer LV stocks were achieved in 293T cells grown in suspension. Produced viruses were accurately characterized and the functionality was also tested in vivo. Produced viruses were compared with viruses produced by calcium phosphate transfection method in adherent cells and polyethylenimine transfection method in suspension cells. Furthermore, a scalable and cost-effective capture purification step was developed based on a diethylaminoethyl monolithic column capable of removing most of the baculoviruses from the LV pool with 65% recovery.
Recommissioning of JYFLTRAP at the new IGISOL-4 facility Kolhinen, V.S.; Eronen, T.; Gorelov, D. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
12/2013, Letnik:
317, Številka:
Part B
Journal Article
Recenzirano
•The JYFLTRAP system has been moved to a new location and commissioned.•The line between RFQ and the Penning traps allows implementation of extra devices.•The RFQ cooler/buncher and both Penning ...traps are operational.•The buffer-gas cooling method and the excitations in the purification trap works.•TOF-ICR technique in the precision trap works. A resonance picture shown.
The JYFLTRAP double Penning-trap system was moved to a new location along with the Ion Guide Isotope Separator On-line (IGISOL) facility at the Accelerator Laboratory of the University of Jyväskylä. The move made it possible to upgrade various parts of the facility. For example, separate beam lines for JYFLTRAP and the collinear laser spectroscopy station were constructed after the radio-frequency quadrupole cooler and buncher. In this contribution we give an overview of the new JYFLTRAP facility and results from the first stable ion-beam tests.
The effect of superheat on grain sedimentation and macrosegregation has been investigated using experimental castings of a low-alloyed steel grade. With a high superheat of ∼ 40 °C, the central ...equiaxed parts of the slabs consisted of randomly oriented fine dendrites but with a low superheat of ∼ 10 °C, coarse globular structures formed. The mean carbon content measured with optical emission spectroscopy was of the order of 15% smaller with coarse globular structures than in fine equiaxed dendritic structures. Electron probe microanalysis of other alloying elements indicates that the negative segregation in the slab central zones is caused by sedimentation of globulites. With superheat in the range ∼ 20 - 40 °C, the equiaxed zone is bordered by a columnar to equiaxed transition (CET) zone. In this region a positive macrosegregation of carbon and other alloying elements was observed. These phenomena are important when considering the through-thickness properties of the slabs and final products.
School discontinuation in Finland is more common among the Finnish Roma than among the population as a whole. We lack knowledge of the perspective of those of the Roma, representing a minority inside ...a minority, who have left compulsory school without a leaving certificate. Within a study about school experiences of imprisoned early school leavers in Finland we had six participants with a Finnish Roma background, whose experiences of relatedness, and frustration of it, we examine in this paper. We conducted narrative interviews with the participants, applying a co-operative narrative interpretation to the meanings of what was told. After the field process, we interpreted the narrative accounts focusing on experiences of relatedness, and how relationships with people in the school environment affected the participants’ sense of belonging together with the people in the school environment. Frustration of relatedness was identified at three levels. Firstly, at a general, life condition level, cultural prejudice manifested itself as a sense of not being accepted and respected as an equal with other people, the situation creating a constant need to cope with outspoken prejudices. Secondly, at a contextual-specific level in the school environment, we identified experiences of being rejected by peers and their parents, as well as some of the teachers. This was linked with a sense of loneliness and detachment from other people in the school environment. Thirdly, at a situational level, the participants described both positive relationships, such as momentary friendships, and negative experiences of being excluded from the peer group. Pathways for further inquiries are discussed.
The effect of different coagulants on cake formation and hydraulic resistance in membrane filtration of strongly coloured (SUVA⩾4.8) upland surface water has been studied at bench-scale under ...constant pressure conditions. Coagulants used were aluminium sulphate, polyaluminium chloride, ferric chloride and ferric sulphate. Optimisation of coagulation parameters was carried by conventional jar testing. The
R′
c (specific cake resistance in m
−2) values were determined for all coagulants over a range of coagulant doses and slow mixing flocculation periods. Experiments indicated slight differences in cake formation trends between ferric- and aluminium-based coagulants and chloride and sulphate counterions, but that the range of measured
R′
c values was small (0.9 and 2.6×10
18
m
−2) over the range of doses studied. Greater than 99% UV
254 removal was achieved with every coagulant, whereas dissolved organic carbon (DOC) removal ranged from 78% to 88%. Optimisation of the pre-coagulation-membrane filtration process suggests ferric chloride to be slightly superior for the feedwater matrix studied on the basis of DOC removal, whereas ferric sulphate gave slightly lower filter cake specific resistance values.
Basic psychological needs and people's experiences affect the choices they make, and further shape the trajectories followed through school. The present study focuses on the perspectives of people ...who left school without graduating. Through narrative interviewing processes we collected the storied experiences of eleven imprisoned early school leavers in Finland. We triangulated data-driven themes and used as theory the concept of three basic psychological needs: autonomy, competence, and relatedness. Of these, relatedness was the most common and a shared topic brought forth by the participants. Experiencing dissatisfaction and frustration as a result of the need for relatedness played a crucial role in the participants' narratives. The dissatisfaction experienced manifested itself in a sense of detachment and alienation from school as a society of peers and adults. The conclusion of this study discusses different kinds of structure that can either support or hinder the need for satisfaction.
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