79 research outputs found
Infusion Micro-Pump Development Using MEMS Technology
International audienceDiabetes is a chronic condition that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. People having type 1 diabetes require insulin (10% of all diabetics). People with type 2 diabetes can be treated with oral medication, but may also require insulin; 10% of all type 2 diabetics require insulin. Among the actual different methods to administer insulin (syringes, pens and conventional infusion pumps) a possibility to increase infuser performances is offered by the utilization of silicon based MEMS pumps (Micro- Electro Mechanical Systems). The main two pump families are classified as mechanical and non-mechanical pumps. The former contains check-valve, peristaltic, rectification without valves and rotary ones (“Displacement Pumps”) or Ultrasonic and Centrifugal (“Dynamic Pumps”); the latter consists in Pressure, Concentration, Electrical Potential gradients and Magnetic Potential micro-pumps. The micro-pump described here is an electro-mechanical device actuated with a piezoelectric-element and based on MEMS technology, able to minimize size and costs, offering a high precision pharmacological dispense. Three slices are bonded to reach the final results: top and bottom caps and an intermediate SOI. In case of anodic bonding, top and bottom caps are constituted of micromachined borophosphosilicate wafers, whereas in case of metallic bonding three silicon slices are used. The paper deals with the fabrication evolution of the device according to the different items that had to be faced during development: design, fluidic, mechanical and electrical simulations and characterization, safety requirements and final testing. Built-in reliability is ensured by two inner sensors able to detect any occlusion or malfunctioning and informing so the patient. The result is a compact, core pump chip that can deliver from 0.02 Units of insulin up to 3.6 Units per minute with accuracy better than 5%
Infectious Complications After Laser Vaporization of Urinary Stones During Retrograde Intrarenal Surgery Are Not Associated with Spreading of Bacteria into Irrigation Fluid but with Previous Use of Fluoroquinolones
Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation
Background: Breast cancer risk increases drastically in individuals carrying a germline BRCA1 mutation. The exposure to ionizing radiation for diagnostic or therapeutic purposes of BRCA1 mutation carriers is counterintuitive, since BRCA1 is active in the DNA damage response pathway. The aim of this study was to investigate whether healthy BRCA1 mutations carriers demonstrate an increased radiosensitivity compared with healthy individuals.
Methods: We defined a novel radiosensitivity indicator (RIND) based on two endpoints measured by the G2 micronucleus assay, reflecting defects in DNA repair and G2 arrest capacity after exposure to doses of 2 or 4 Gy. We investigated if a correlation between the RIND score and nonsense-mediated decay (NMD) could be established.
Results: We found significantly increased radiosensitivity in the cohort of healthy BRCA1 mutation carriers compared with healthy controls. In addition, our analysis showed a significantly different distribution over the RIND scores (p = 0.034, Fisher’s exact test) for healthy BRCA1 mutation carriers compared with non-carriers: 72 % of mutation carriers showed a radiosensitive phenotype (RIND score 1–4), whereas 72 % of the healthy volunteers showed no radiosensitivity (RIND score 0). Furthermore, 28 % of BRCA1 mutation carriers had a RIND score of 3 or 4 (not observed in control subjects). The radiosensitive phenotype was similar for relatives within several families, but not for unrelated individuals carrying the same mutation. The median RIND score was higher in patients with a mutation leading to a premature termination codon (PTC) located in the central part of the gene than in patients with a germline mutation in the 5′ end of the gene.
Conclusions: We show that BRCA1 mutations are associated with a radiosensitive phenotype related to a compromised DNA repair and G2 arrest capacity after exposure to either 2 or 4 Gy. Our study confirms that haploinsufficiency is the mechanism involved in radiosensitivity in patients with a PTC allele, but it suggests that further research is needed to evaluate alternative mechanisms for mutations not subjected to NMD
Tumor Suppression by RNA from C/EBPβ 3′UTR through the Inhibition of Protein Kinase Cε Activity
BACKGROUND: Since the end of last century, RNAs from the 3'untranslated region (3'UTR) of several eukaryotic mRNAs have been found to exert tumor suppression activity when introduced into malignant cells independent of their whole mRNAs. In this study, we sought to determine the molecular mechanism of the tumor suppression activity of a short RNA from 3'UTR of C/EBPβ mRΝΑ (C/EBPβ 3'UTR RNA) in human hepatocarcinoma cells SMMC-7721. METHODOLOGY/PRINCIPAL FINDINGS: By using Western blotting, immunocytochemistry, molecular beacon, confocal microscopy, protein kinase inhibitors and in vitro kinase assays, we found that, in the C/EBPβ 3'UTR-transfectant cells of SMMC-7721, the overexpressed C/EBPβ 3'UTR RNA induced reorganization of keratin 18 by binding to this keratin; that the C/EBPβ 3'UTR RNA also reduced phosphorylation and expression of keratin 18; and that the enzyme responsible for phosphorylating keratin 18 is protein kinase Cε. We then found that the C/EBPβ 3'UTR RNA directly inhibited the phosphorylating activity of protein kinase Cε; and that C/EBPβ 3'UTR RNA specifically bound with the protein kinase Cε-keratin 18 conjugate. CONCLUSION/SIGNIFICANCE: Together, these facts suggest that the tumor suppression in SMMC-7721 by C/EBPβ 3'UTR RNA is due to the inhibition of protein kinase Cε activity through direct physical interaction between C/EBPβ 3'UTR RNA and protein kinase Cε. These facts indicate that the 3'UTR of some eukaryotic mRNAs may function as regulators for genes other than their own
Channel Assignment with Separation for Interference Avoidance in Wireless Networks
Given an integer , a vector of nonnegative integers, and an undirected graph , an -coloring of is a function from the vertex set to a set of nonnegative integers such that , if where is the distance (i.e. the minimum number of edges) between the vertices and . An optimal -coloring for is one using the smallest range of integers over all such colorings. This problem has relevant application in channel assignment for interference avoidance in wireless networks, where channels (i.e. colors) assigned to interfering stations (i.e. vertices) at distance must be at least apart, while the same channel can be reused in vertices whose distance is at least . In particular, two versions of the coloring problem -- , and -- are considered. Since these versions of the problem are -hard for general graphs, efficient algorithms for finding optimal colorings are provided for specific graphs modeling realistic wireless networks including rings, bidimensional grids, and cellular grids
Non-Small Cell Lung Carcinoma Cell Motility, Rac Activation and Metastatic Dissemination Are Mediated by Protein Kinase C Epsilon
Background: Protein kinase C (PKC) e, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCe in lung cancer metastasis has not yet been established. Principal Findings: Here we show that RNAi-mediated knockdown of PKCe in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCe depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCe with eV1-2, a specific PKCe inhibitor. PKCe was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCe-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. Conclusions: Our results implicate PKCe as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target
Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation
CARDIOTOXICITY INDUCED BY DOXORUBICIN INVIVO - PROTECTIVE ACTIVITY OF THE SPIN TRAP ALPHA-PHENYL-TERT-BUTYL NITRONE
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