Manipulator arm design for the Extravehicular Teleoperator Assist Robot (ETAR): Applications on the space station

The preliminary conceptual design of a new teleoperator robot manipulator system for space station maintenance missions has been completed. The system consists of a unique pair of arms that is part of a master-slave, force-reflecting servomanipulator. This design allows greater dexterity and greater volume coverage than that available in current designs and concepts. The teleoperator manipulator is specifically designed for space applications and is a valuable extension of the current state-of-the-art earthbound manipulators marketed today. The manipulator and its potential application on the space station are described

Paper Session I-C - Advanced Vision and Robotic Systems for Hazardous Environments

This paper describes work performed at the Rockwell Space Division, Downey, California, and at Fluor Daniel Inc. Irvine, California, related to task performance in remote hazardous environments through advanced robotic and vision systems. These environments could be in space, for example related to the Space Shuttle, Space Station and outer space and planetary environments. In addition, the environments could be on earth, for example areas contaminated by chemical or radioactive waste. In both instances, the task is most efficiently performed when the environment has been designed from the very beginning for remote task performance. While this is often not the case, much is being done in the development of two important related remote technologies: environmental characterization and inspection; and remote handling and manipulation. Important work has already taken place in developing robust systems for remote characterization, inspection and manipulation, for example, at the facilities of NASA and the Department of Energy. NASA is already integrating and testing a mobile robot system for inspection and re-waterproofing of thermal protection system tiles on the Space Shuttle. Other NASA efforts include micro-rovers, robotic devices for ground emergency responses, robots with local autonomy for ground characterization, and small, highly dexterous robots for visual inspection. In addition, the Department of Energy has many efforts to develop characterization, inspection and robotic systems for radiation areas. Notable examples include mobile systems for inspection of exterior and interior acreage sites, reactor vessels, pipes, drums, and various devices and special end-effectors for waste excavation, size reduction, manipulation, decontamination, and decommissioning. To support these activities, we have taken a systematic approach to developing some of the basic technologies necessary for remote operations in hostile environments. Our major thrust has been to develop a modular, re-configurable robotics laboratory test bed, and then to use this test bed to support advances in the following areas: simulation and engineering analysis for development and verification of remote tasks; special vision systems; and vibration isolation to stabilize and enhance remote manipulators

Acute promyelocytic Leukemia: Update on the mechanisms of leukemogenesis, resistance and on innovative treatment strategies

This review highlights new findings that have deepened our understanding of the mechanisms of leukemogenesis, therapy and resistance in acute promyelocytic leukemia (APL). Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARa) sets the cellular landscape of acute promyelocytic leukemia (APL) by repressing the transcription of RARa target genes and disrupting PML-NBs. The RAR receptors control the homeostasis of tissue growth, modeling and regeneration, and PML-NBs are involved in self-renewal of normal and cancer stem cells, DNA damage response, senescence and stress response. The additional somatic mutations in APL mainly involve FLT3, WT1, NRAS, KRAS, ARID1B and ARID1A genes. The treatment outcomes in patients with newly diagnosed APL improved dramatically since the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). ATRA activates the transcription of blocked genes and degrades PML-RAR alpha, while ATO degrades PML-RARa by promoting apoptosis and has a pro-oxidant effect. The resistance to ATRA and ATO may derive from the mutations in the RARa ligand binding domain (LBD) and in the PML-B2 domain of PML-RARa, but such mutations cannot explain the majority of resistances experienced in the clinic, globally accounting for 5-10% of cases. Several studies are ongoing to unravel clonal evolution and resistance, suggesting the therapeutic potential of new retinoid molecules and combinatorial treatments of ATRA or ATO with different drugs acting through alternative mechanisms of action, which may lead to synergistic effects on growth control or the induction of apoptosis in APL cells

Absence of FGFR3–TACC3 rearrangement in hematological malignancies with numerical chromosomal alteration

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Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML.

Acute myeloid leukemia (AML) is often characterized by the expression of fusion or mutant proteins that cause impaired differentiation and enhanced proliferation and survival. The presence of mutant proteins prone to misfolding can render the cells sensitive to endoplasmic reticulum (ER) stress and oxidative stress that could otherwise be overcome. Here, we show that the triple combination of the differentiating agent retinoic acid (RA), the ER stress-inducing drug tunicamycin (Tm), and arsenic trioxide (ATO), able to generate oxidative stress, leads to the death of AML cell lines expressing fusion proteins involving the gene MLL and the internal tandem duplication (ITD) in the FLT3 tyrosine kinase receptor. Importantly, the combination of RA, Tm, and ATO decreased the colony-forming capacity of primary leukemic blasts bearing the FLT-ITD mutation without affecting healthy hematopoietic progenitor cells. We demonstrate in cell lines that combination of these drugs generates ER and oxidative stresses and impairs maturation and causes accumulation of FLT3 protein in the ER. Our data provide a proof of concept that low amounts of drugs that generate ER and oxidative stresses combined with RA could be an effective targeted therapy to hit AML cells characterized by MLL fusion proteins and FLT3-ITD mutation

Simple, rapid and accurate molecular diagnosis of acute promyelocytic leukemia by loop mediated amplification technology

The diagnostic work-up of acute promyelocytic leukemia (APL) includes the cytogenetic demonstration of the t(15;17) translocation and/or the PML-RARA chimeric transcript by RQ-PCR or RT-PCR. This latter assays provide suitable results in 3-6 hours. We describe here two new, rapid and specific assays that detect PML-RARA transcripts, based on the RT-QLAMP (Reverse Transcription-Quenching Loop-mediated Isothermal Amplification) technology in which RNA retrotranscription and cDNA amplification are carried out in a single tube with one enzyme at one temperature, in fluorescence and real time format. A single tube triplex assay detects bcr1 and bcr3 PML-RARA transcripts along with GUS housekeeping gene. A single tube duplex assay detects bcr2 and GUSB. In 73 APL cases, these assays detected in 16 minutes bcr1, bcr2 and bcr3 transcripts. All 81 non-APL samples were negative by RT-QLAMP for chimeric transcripts whereas GUSB was detectable. In 11 APL patients in which RT-PCR yielded equivocal breakpoint type results, RT-QLAMP assays unequivocally and accurately defined the breakpoint type (as confirmed by sequencing). Furthermore, RT-QLAMP could amplify two bcr2 transcripts with particularly extended PML exon 6 deletions not amplified by RQ-PCR. RT-QLAMP reproducible sensitivity is 10(-3) for bcr1 and bcr3 and 10(-)2 for bcr2 thus making this assay particularly attractive at diagnosis and leaving RQ-PCR for the molecular monitoring of minimal residual disease during the follow up. In conclusion, PML-RARA RT-QLAMP compared to RT-PCR or RQ-PCR is a valid improvement to perform rapid, simple and accurate molecular diagnosis of APL

THE IMPROVED DIASORIN Q-LAMP ASSAY FOR THE ACCURATE AND ULTRA-FAST DETECTION OF COMMON AND RARE ISOFORMS OF THE BCR-ABL1 TRANSLOCATION

The molecular detection of BCR-ABL1 transcripts by RT-PCR is mandatory for the diagnosis of Ph+ Leukemias at onset. Recently a faster and reliable assay based on the Q-LAMP technology developed by DiaSorin has entered in laboratory routine. This assay detects in one hour BCR-ABL1 p190 (e1a2) and p210 (e13a2, e14a2) isoforms. In this study, we evaluated the new improved Q-LAMP formulation designed to detect also less frequent isoforms of the BCR-ABL1 transcripts p190 and p210 (e1a3, e13a3, e14a3). In addition, clinical studies demonstrated that the assay is capable of detecting also the rare isoform p230 (e19a2, e19a3). Methods: The new Q-LAMP technology consists in a multiplex assay for the differential detection of p190 and p210 transcripts and the amplification of the GUSB endogenous RNA. The assay has been tested on 185 clinical samples including 95 p210 positive (57 e13a2 and 28 e14a2, 8 e13a3 and 2 e14a3), 38 p190 positive (33 e1a2 and 5 e1a3) and 50 BCR-ABL1 negative samples. Additional 2 p230 rare isoforms were also included in this study. All samples were previously tested by RT-PCR, considered as the reference method. Results: The new BCR-ABL Q-LAMP assay showed 100% concordance with the RT-PCR, with an expected delayed amplification time for rare isoforms respect to the common ones. The average amplification time of p210 common isoforms were 22,24 and 25,03 min compared to the p210 and p190 rare isoforms that showed 26,54 and 36,84 min, respectively. The 2 p230 (e19a2) rare isoforms were also tested and resulted valid although, due to the very long transcript, they showed a very high average amplification time (50 and 48 min). Moreover, we observed an interesting discrimination between the e13a2 and the e14a2 isoforms in terms of amplification times (20,21 versus 26,36 min) likely associated to the different length of the two transcripts, with low coefficients of variability (0,15 and 0,11 respectively). Conclusions: The enhanced BCR-ABL Q-LAMP assay well proved to detect both common and uncommon isoforms of the BCR-ABL1 translocation. This improved performances, combined with the speed and the close tube format, allow laboratories to optimize their workflow and represent a reliable solution for molecular diagnosis of Philadelphia Positive Leukemias

Nafion-1,2,3-Triazole Blend Membranes for High Temperature PEMFCs

Nafion-1,2,3-triazole blend membranes were prepared by autoclave (AC) solution processing mixing of Nafion (R) solution (5% solution in 1- and 2-propanol and H2O) and 1,2,3-triazole. The blend membranes were very flexible, transparent, homogeneous, and stable even after boiling in water and treatment in 1M H2SO4. FTIR and NMR results suggested that 1- and 2-propanol of Nafion solution reacted with 1,2,3-triazole under the catalytic effect of the Nafion's acid side chain. IV performance of blend membranes was tested using a single membrane electrode assembly (MEA) cell. The cell performance of Nafion-5wt.% 1,2,3-triazole blend membrane was higher than that of the Nafion 112 at cell temperatures over 100 degrees C indicating that it is possible to use Nafion-1,2,3-triazole blend membrane as an electrolyte for high temperature PEMFCs

Molecular monitoring of hematologic malignancies: current and future issues

Genetic markers associated with hematologic malignancies such as acute promyelocytic leukemia (APL) can be detected with high sensitivity and specificity using the reverse-transcription polymerase chain reaction (RT-PCR). This procedure can be applied to monitor minimal residual disease. In patients with APL, RT-PCR is now being used to detect molecular relapse, and a strong association has been found between outcome and the treatment of molecular as opposed to hematologic relapse. In APL, results from PCR assays are also being used to guide therapy. Prognostic groups can be defined using molecular and clinical characteristics of the disease as well as patient characteristics. In the future, PCR monitoring strategies may be adapted to the risk of relapse of individual patients. Patients at high risk of relapse may be monitored much more rigorously than patients at low risk of relapse. Although RT-PCR is in routine use as a clinical tool, the lack of standardization of techniques in different laboratories has resulted in some difficulties in interpretation of results. There is a real need for an international consensus on standardization of PCR techniques

Neurofibromatosis type 1: Early detection program in roman scholastic institutes

Neurofibromatosis type 1 (NF1) is a multisystemic disorder and an important social pathology characterized by marked variation in clinical manifestations. In our opinion the incidence of NF1 is underestimated compared with statistical data actually estimated, so we have started an early detection program studying two groups of children six and ten year old. At the moment we have analysed 2513 children and 6 cases of NF1 have been diagnosed. According to the 95% confidence interval, the prevalence of NF1 is between 1:113 and 1:812, significantly higher than the birth incidence of 1:3000 and 1:2500 signalled in American/European and Australian statistics respectively. Moreover 197 children present only few signs (café au lait and ipochromic spots) and have been undergone to follow up. The aim of our study is to investigate, with the aid of a-cohort of medical specialists, the real incidence of NF1. © Copyright 2004, CIC Edizioni Internazionali, Roma