Manufacturing of 42SiCr-pipes for quenching and partitioning by longitudinal HFI-Welding

In the pipe manufacturing and pipe processing industry, the demand for cost-effective pipes with high strength and good ductility is increasing. In the present study, the inductive longitudinal welding process was combined with a Quenching and Partitioning (Q&P) treatment to manufacture pipes with enhanced mechanical properties. The aim of the Q&P process is to establish a martensitic structure with increased retained austenite content. This allows for the beneficial use of both phases: the strength of martensite as well as the ductility of retained austenite. A 42SiCr steel, developed for Q&P processes, was joined at the longitudinal seam by a high-frequency induction (HFI) welding process and was subsequently heat-treated. The applied heat treatments included normalizing, austenitizing, quenching, and two Q&P strategies (Q&P-A/Q&P-B) with distinct quenching (Tq = 200/150◦ C) and partitioning temperatures (Tp = 300/250◦ C). Investigations of the microstructures revealed that Q&P tubes exhibit increased amounts of retained austenite in the martensitic matrix. Differences between the weld junction and the base material occurred, especially regarding the morphology of the martensite; the martensite found in the weld junction is finer and corresponds more to the lath-type morphology, compared to the base material in the circumference. In all zones of the welded tube circumference, retained austenite has been found in similar distributions. The mechanical testing of the individual tubes demonstrated that the Q&P treatments offer increased strength compared to all other states and significantly improved ductility compared to the quenched condition. Therefore, the approach of Q&P treatment of HFI-welded tubes represents a route for the mass production of high-strength tubular products with improved ductility

Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia

Investigation of the activity of a family of fusion proteins that cause aggressive leukemia suggests transcriptional elongation as a new mechanism for oncogenic transformation

ggstThe role of tendon microcirculation in Achilles and patellar tendinopathy

Tendinopathy is of distinct interest as it describes a painful tendon disease with local tenderness, swelling and pain associated with sonographic features such as hypoechogenic texture and diameter enlargement. Recent research elucidated microcirculatory changes in tendinopathy using laser Doppler flowmetry and spectrophotometry such as at the Achilles tendon, the patellar tendon as well as at the elbow and the wrist level. Tendon capillary blood flow is increased at the point of pain. Tendon oxygen saturation as well as tendon postcapillary venous filling pressures, determined non-invasively using combined Laser Doppler flowmetry and spectrophotometry, can quantify, in real-time, how tendon microcirculation changes over with pathology or in response to a given therapy. Tendon oxygen saturation can be increased by repetitive, intermittent short-term ice applications in Achilles tendons; this corresponds to 'ischemic preconditioning', a method used to train tissue to sustain ischemic damage. On the other hand, decreasing tendon oxygenation may reflect local acidosis and deteriorating tendon metabolism. Painful eccentric training, a common therapy for Achilles, patellar, supraspinatus and wrist tendinopathy decreases abnormal capillary tendon flow without compromising local tendon oxygenation. Combining an Achilles pneumatic wrap with eccentric training changes tendon microcirculation in a different way than does eccentric training alone; both approaches reduce pain in Achilles tendinopathy. The microcirculatory effects of measures such as extracorporeal shock wave therapy as well as topical nitroglycerine application are to be studied in tendinopathy as well as the critical question of dosage and maintenance. Interestingly it seems that injection therapy using color Doppler for targeting the area of neovascularisation yields to good clinical results with polidocanol sclerosing therapy, but also with a combination of epinephrine and lidocaine

ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia

Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of \u3e50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX

Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation

International audienceThe process of metastasis formation in cancer is not completely understood and is the main reason cancer therapies fail. Previously, we showed that dual liposomes simultaneously containing the hemostatic inhibitor, dipyridamole and the anticancer drug, perifosine potently inhibited metastasis, causing a 90% reduction in the number of lung metastases in a murine experimental metastasis model. To gain deeper insight into the mechanisms leading to the inhibition of metastasis by these dual liposomes, in the present study, the development of metastases by MT3 breast cancer cells in a mouse xenograft model was analyzed in more detail with regard to tumor cell settlement and metastatic growth. We found that the development of lung metastases by MT3 tumor cells is essentially dependent on the formation of fibrin clots as a precondition for the pulmonary arrest of tumor cells and the subsequent intravascular expansion of micrometastases before their invasion into the surrounding tissue

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies

Transposon activation mutagenesis as a screening tool for identifying resistance to cancer therapeutics

Background: The development of resistance to chemotherapies represents a significant barrier to successful cancer treatment. Resistance mechanisms are complex, can involve diverse and often unexpected cellular processes, and can vary with both the underlying genetic lesion and the origin or type of tumor. For these reasons developing experimental strategies that could be used to understand, identify and predict mechanisms of resistance in different malignant cells would be a major advance. Methods: Here we describe a gain-of-function forward genetic approach for identifying mechanisms of resistance. This approach uses a modified piggyBac transposon to generate libraries of mutagenized cells, each containing transposon insertions that randomly activate nearby gene expression. Genes of interest are identified using next-gen high-throughput sequencing and barcode multiplexing is used to reduce experimental cost. Results: Using this approach we successfully identify genes involved in paclitaxel resistance in a variety of cancer cell lines, including the multidrug transporter ABCB1, a previously identified major paclitaxel resistance gene. Analysis of co-occurring transposons integration sites in single cell clone allows for the identification of genes that might act cooperatively to produce drug resistance a level of information not accessible using RNAi or ORF expression screening approaches. Conclusion: We have developed a powerful pipeline to systematically discover drug resistance in mammalian cells in vitro. This cost-effective approach can be readily applied to different cell lines, to identify canonical or context specific resistance mechanisms. Its ability to probe complex genetic context and non-coding genomic elements as well as cooperative resistance events makes it a good complement to RNAi or ORF expression based screens

Acute and chronic response of the right ventricle to surgically induced pressure and volume overload: An analysis of pressure-volume relations

We aimed to determine the response of the right ventricle (RV) to surgically induced pressure and volume overload in both acute and chronic settings. Four-month-old sheep were operated via left anterior thoracotomy. Pressure overload of the RV was established by banding of the pulmonary trunk. Volume overload was induced by the implantation of a transannular patch to the right ventricular outflow tract. Right ventricular function was obtained with conductance catheters before and after surgery as well as three months postoperatively. Acute pressure overload resulted in an increase of end-systolic volume (ESV) (P=0.002) and end-diastolic volume (EDV) (P=0.004), increments in contractile indexes [maximal slope of systolic pressure increment (dP/dt(max)), P=0.002; slope of end-systolic pressure volume relation (Ees), P=0.002; preload recruitable stroke work (PRSW), P=0.002] and an acceleration of early diastole [relaxation time (tau), P=0.012; maximal slope of diastolic pressure decrement (dP/dt(min)), P=0.002]. Acute volume overload revealed better contractility and more prominent increases in preload (ESV, EDV; both P=0.008). Three months postoperatively, pressure overloaded hearts demonstrated superior systolic (Ees, P=0.022; PRSW, P=0.013) and diastolic reserves (dP/dt(min), P=0.013; slope of end-diastolic pressure volume relation (Eed), P=0.005; P(20), P=0.003) than volume overloaded hearts. Acute pressure overload leads to enhanced contractility of the RV as a result of the Anrep effect and the Frank-Starling mechanism whereas volume overload institutes only the latter. The chronically pressure overloaded RV exposes more contractile and elastic reserves than the chronically volume overloaded RV under stress conditions