A New Hand-Held Microsystem Architecture for Biological Analysis

This paper presents a hand-held microsystem based on new fully integrated magnetoresistive biochips for biomolecular recognition (DNA hybridization, antibody antigen interaction, etc.). Magnetoresistive chip surfaces are chemically treated, enabling the immobilization of probe biomolecules such as DNA or antibodies. Fluid handling is also integrated in the biochip. The proposed microsystem not only integrates the biochip, which is an array of 16times16 magnetoresistive sensors, but it also provides all the electronic circuitry for addressing and reading out each transducer. The proposed architecture and circuits were specifically designed for achieving a compact, programmable and portable microsystem. The microsystem also integrates a hand-held analyzer connected through a wireless channel. A prototype of the system was already developed and detection of magnetic nanoparticles was obtained. This indicates that the system may be used for magnetic label based bioassays     

Granular Reasoning Using Zooming In & Out: Part 2. Aristotle's Categorical Syllogism

The concept of granular computing is applied to Aristotle's categorical syllogism. Such kind of reasoning is called granular reasoning in this paper. For the purpose, two operations called zooming in & out are introduced to reconstruct granules of possible worlds.     

Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats

PURPOSE: Retrospective studies suggest that adult patients with intractable epilepsy may have a history of febrile seizures in childhood. Risk factors for a febrile seizure may include the rate of increase in the core temperature (T-core), its peak (Tmax), the duration of the temperature increase, or an underlying brain pathology. Recently, neuronal migration disorders (NMD) have been diagnosed with increasing frequency in patients with epilepsy, but the link between NMD, febrile seizures, and epilepsy is unclear. We studied rat pups rendered hyperthermic to ascertain the incidence of seizures, mortality, and extent of hippocampal cell loss in each group. METHODS: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature > 42 degrees C). RESULTS: The incidence of hyperthermia-induced behavioral seizures and mortality rate were significantly higher in rats with NMD than in controls (p < 0.05). The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0.05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage correlated positively with the duration of hyperthermia. In control rats, occasional neuronal loss and astrocytosis occurred only after prolonged hyperthermia. CONCLUSIONS: In immature rats, NMD lower the threshold to hyperthermia-induced behavioral seizures and hyperthermia in the presence of NMD may cause irreversible hippocampal neuronal damage.     

An investigation of methods of pileup rejection for 2-D array detectors employed in high resolution PET

Two methods of rejecting pileup events in 2-D array detectors used in positron emission tomography (PET) are investigated. Since the methods are based on different physical properties, they were investigated separately and in combination. Method one is based on the fact that valid events in the 2-D array detector occur only in a limited pulseheight range for each detector element, and by rejecting events outside these energy ranges, many of the pileup events can be rejected. Method two is based on the fact that most pileup event pairs have a time differential, which will cause a difference in the shape of the signal which increases the rise time of an integrated signal or the crossover time of a bipolar signal from a shaping amplifier. Method two proved to be somewhat better than method one. However, the ideal system would most likely use both methods simultaneously.     

Deleting files in the Celeste peer-to-peer storage system

Celeste is a robust peer-to-peer object store built on top of a distributed hash table (DHT). Celeste is a working system, developed by Sun Microsystems Laboratories. During the development of Celeste, we faced the challenge of complete object deletion, and moreover, of deleting “files” composed of several different objects. This important problem is not solved by merely deleting meta-data, as there are scenarios in which all file contents must be deleted, e.g., due to a court order. Complete file deletion in a realistic peer-to-peer storage system has not been previously dealt with due to the intricacy of the problem — the system may experience high churn rates, nodes may crash or have intermittent connectivity, and the overlay network may become partitioned at times. We present an algorithm that eventually deletes all file contents, data and meta-data, in the aforementioned complex scenarios. The algorithm is fully functional and has been successfully integrated into Celeste.     

Mechanisms of Sensitivity and Resistance of Primary Effusion Lymphoma to Dimethyl Fumarate (DMF)

PEL is a rare B cell lymphoma associated with KSHV that mainly arises in immune-deficient individuals. The search for new drugs to treat this cancer is still ongoing given its aggressiveness and the poor response to chemotherapies. In this study, we found that DMF, a drug known for its anti-inflammatory properties which is registered for the treatment of psoriasis and relapsing–remitting MS, could be a promising therapeutic strategy against PEL. Indeed, although some mechanisms of resistance were induced, DMF activated NRF2, reduced ROS and inhibited the phosphorylation of STAT3 and the release of the pro-inflammatory and immune suppressive cytokines IL-6 and IL-10, which are known to sustain PEL survival. Interestingly, we observed that DMF displayed a stronger cytotoxic effect against fresh PEL cells in comparison to PEL cell lines, due to the activation of ERK1/2 and autophagy in the latter cells. This finding further encourages the possibility of using DMF for the treatment of PEL.     

Modeling Lung Carcinoids with Zebrafish Tumor Xenograft

Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)^y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.     

The ECHORD project proposals analysis – Research profiles,collaboration patterns and research topic trends

This paper investigates the research profiles, collaboration patterns and research topic trends which can be identified in the proposals submitted to the ECHORD (European Clearing House for Open Robotics Development) FP7 project. On a country level, clusters were identified and characterized by patterns of proposal production per inhabitant, score and international cooperation. Belgium and Sweden constitute a cluster characterized by high proposal production, with very high scores and extensive international collaboration. Belgium also excels from another cluster analysis, being as the only country where 100% of proposals involve industry–academia cooperation and obtain scores above 10. Other findings show that single partner proposals have significantly lower quality than multi-partner proposals but, on the other hand, the number of countries involved shows no influence on the quality of the proposals. Despite the high number of industrial participants present on the proposals, it is observed that they play secondary roles in the proposals, with a very low number projects leaded by companies. Also, it is observed that partnerships between research institutions (non-universities) are the most successful. Concerning topics of the proposals, the technology human–robot interface and the product vision robot for small-scale manufacturing are the most significant. Finally, the paper shows clusters of institutions extracted from the giant network of relations obtained from the ECHORD set of proposals.     

Physical properties of spray dried acerola pomace extract as affected by temperature and drying aids

The objective of this study was to assess the impact of some processing parameters on moisture content, flowability, hygroscopicity and water solubility of spray dried acerola pomace extract using maltodextrin and cashew tree gum as drying aids. The experiment was conducted according to Response Surface Methodology, with the independent variables being: inlet temperature (170-200 °C), drying aid/acerola ratio (2:1-5:1), and percent replacement of maltodextrin by cashew tree gum (0-100%). Higher inlet temperatures favored the desired physical properties of the powders, decreasing their moisture contents and hygroscopicity, and increasing flowability. The drying aids decreased the powder hygroscopicity, especially cashew tree gum (CTG), which also enhanced the powder flowability. The best processing conditions to obtain a free-flowing and least hygroscopic acerola pomace extract powder by spray drying were: inlet temperature above 194 °C; drying aid/acerola solid ratio, 4:1; percent replacement of maltodextrin by CTG, at least 80%.     

Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)^y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.