Features, Applications Description The HA-A1370 Series of quartz crystal oscillators provide enable/disable 3-state CMOS compatible signals for bus connected systems. Supplying Pin 1 of the HA-A1370 units with a logic '0' enables the output on Pin 5. Alternately, supplying pin 1 of the HA-A1380 units with a logic '1' enables its Pin 5 output.
Gami installer v181. In the disabled mode, Pin 5 presents a high impedance to the load. All units are resistance welded in an all metal package, offering RFI shielding, and are designed to survive standard wave soldering operations without damage. Insulated standoffs to enhance board cleaning are standard.
7 UC1842/3/4/5 UC2842/3/4/5 UC3842/3/4/5 OFFLINE FLYBACK REGULATOR SLOPE COMPENSATION A fraction of the oscillator ramp can be resistively summed with the current sense signal to provide. Jul 10, 2012 Como fazer para atualizar o tablet genesis 7205 para o Android 4.0 disponivel pelo fabricante em http://www.everteksa.com/drive/GT7205.
In 1988, the gene responsible for the autosomal recessive disease ataxia- telangiectasia (A-T) was localized to 11q22.3-23.1. It was eventually cloned in 1995. Many independent laboratories have since demonstrated that in replicating cells, ataxia telangiectasia mutated (ATM) is predominantly a nuclear protein that is involved in the early recognition and response to double-stranded DNA breaks.
ATM is a high-molecular-weight PI3K-family kinase. ATM also plays many important cytoplasmic roles where it phosphorylates hundreds of protein substrates that activate and coordinate cell-signaling pathways involved in cell-cycle checkpoints, nuclear localization, gene transcription and expression, the response to oxidative stress, apoptosis, nonsense-mediated decay, and others. Appreciating these roles helps to provide new insights into the diverse clinical phenotypes exhibited by A-T patients—children and adults alike—which include neurodegeneration, high cancer risk, adverse reactions to radiation and chemotherapy, pulmonary failure, immunodeficiency, glucose transporter aberrations, insulin-resistant diabetogenic responses, and distinct chromosomal and chromatin changes. An exciting recent development is the ATM-dependent pathology encountered in mitochondria, leading to inefficient respiration and energy metabolism and the excessive generation of free radicals that themselves create life-threatening DNA lesions that must be repaired within minutes to minimize individual cell losses.
Introduction Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by a broad spectrum of disease phenotypes that can be viewed from many perspectives, much like the Indian parable of the blind men probing different parts of an elephant while not seeing the entirety of the animal, because each relies on only 1 methodology—his touch. The A-T phenotype is similarly complex and includes progressive neuronal degeneration, ocular telangiectasias, variable immunodeficiency, and cancer susceptibility, - whereas the overall functions of the ataxia telangiectasia mutated (ATM) protein suggest a much broader pathology. Indeed, the extended phenotype can include growth retardation, premature aging, insulin resistance, manifestations of mitochondrial dysfunction, inadequate responses to oxidative stress, and adverse reactions to the DNA-damaging agents commonly used to treat cancer. Cells derived from A-T patients exhibit cytoskeletal abnormalities, requirements for serum growth factors and clastogenic factors,,, chromosomal instabilities, - chromatin changes, hypersensitivity to ionizing radiation,, and aberrant checkpoint controls. The gene responsible for A-T was first localized to chromosome 11q22.3-23.1 by Gatti et al using mathematical analysis of cosegregation (linkage) data. During the next 7 years, the region was “fine mapped” by an international consortium, - and then identified as the ATM gene by Savitsky et al.
ATM is a high-molecular-weight (350 kDa) protein kinase, and it is a member of the large phosphoinositidyl 3-kinase-related protein kinase (PIKK) family; other family members include the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), A-T and Rad3-related protein (ATR), mammalian target of rapamycin (mTOR)/FKBP-rapamycin-associated protein (mTOR/FRAP), and ATX/SMG.,, Much of the structural similarity of these proteins lies in their domains for (1) kinase activity; (2) FRAP-ATM-TRRAP (FAT); and (3) C-terminal FAT (FATC) and binding sites for p53, BLM, and other ATM-binding proteins. In steady-state cells, ATM appears to exist as an inactive dimer/tetramer that can be rapidly activated and recruited to sites of double-strand breaks (DSBs) by the Mre11-Rad50-NBS1 (MRN complex) proteins via its interaction with the C-terminal domain of NBS1.
ATM responses to oxidative stress The DNA of eukaryotic cells is continuously exposed to reactive oxygen species (ROS) generated either by exposure to physical sources (UV light and ionizing radiation), or via the physiological functions of numerous intracellular enzymes, including NADPH oxidases, xanthine oxidase, cyclooxygenases, cytochrome P450, lipoxygenases, and those of immune cells., However, the vast majority of intracellular ROS is produced by the respiratory chain in the mitochondria. ROS are an important class of toxicants that are capable of causing damage to lipids and proteins and are able to generate a plethora of DNA lesions, including oxidized DNA bases, apurinic/apyrimidinic (AP) sites, and single- and double-strand breaks., When the damage caused by ROS exceeds the cells’ capacity for repair, a general self-perpetuating state of oxidative stress is produced. Conversely, reducing the oxidation of ATM should (1) improve the efficiency of DNA repair by increasing ATM kinase activity; and (2) reduce cancer risk.