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Readout electronics for a High-Rate CSC detector
A readout system for a high-rate muon Cathode Strip Chamber (CSC) is described. The system, planned for use in the forward region of the ATLAS muon spectrometer, uses two custom CMOS integrated circuits to achieve good position resolution at a flux of up to 2,500 tracks/cm{sup 2}/s
Auditory Cortex Responses to Clicks and Sensory Modulation Difficulties in Children with Autism Spectrum Disorders (ASD)
Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD
Smoking-related DNA adducts as potential diagnostic markers of lung cancer: new perspectives
In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers)
ĐОНокŃĐťŃŃĐ˝ŃĐľ ĐžŃОйоннОŃŃи пОŃĐľŃнО-кНоŃĐžŃнОгО Ńака: ŃаннŃŃ Đ´Đ¸Đ°ĐłĐ˝ĐžŃŃика и поŃŃпокŃĐ¸Đ˛Ń ŃĐľŃапии
Kidney cancer (renal cell carcinoma) is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task.Đ Đ°Đş пОŃки пО ĐżŃĐ°Đ˛Ń ŃŃиŃĐ°ĐľŃŃŃ ĐžĐ´Đ˝ĐžĐš иС ĐžŃнОвнŃŃ
ĐżŃОйНоП ŃОвŃоПоннОК ОнкОŃŃОНОгии. Đ ŃŃŃŃĐşŃŃŃĐľ ОнкОНОгиŃĐľŃкОК СайОНоваоПОŃŃи в Đ ĐžŃŃии Đ´ĐžĐťŃ ĐˇĐťĐžĐşĐ°ŃĐľŃŃвоннŃŃ
нОвООйŃаСОваниК пОŃки ŃĐžŃŃавНŃĐľŃ 4,3 %. РпОŃНоднио ĐłĐžĐ´Ń ĐžŃПоŃĐ°ĐľŃŃŃ ŃондонŃĐ¸Ń Đş ŃвоНиŃĐľĐ˝Đ¸Ń Đ°ĐąŃОНŃŃнОгО ŃиŃНа даннОК каŃогОŃии йОНŃĐ˝ŃŃ
. РОйŃоК ŃŃŃŃĐşŃŃŃĐľ СайОНоваоПОŃŃи СНОкаŃĐľŃŃвоннŃĐľ нОвООйŃĐ°ĐˇĐžĐ˛Đ°Đ˝Đ¸Ń ĐżĐžŃки ŃĐžŃŃавНŃŃŃ 3,6 %, ŃŃĐž ŃООŃвоŃŃŃвŃĐľŃ 10âĐźŃ ŃĐ°Đ˝ĐłĐžĐ˛ĐžĐźŃ ĐźĐľŃŃŃ. ĐĐťŃ Đ˝ĐľĐşĐžŃĐžŃŃŃ
нОвООйŃаСОваниК, напŃĐ¸ĐźĐľŃ ĐžĐżŃŃ
ОНоК ĐżŃĐžŃŃĐ°ŃŃ и ŃиŃникОв, ŃŃŃĐľŃŃвŃŃŃ Đ´Đ¸Đ°ĐłĐ˝ĐžŃŃиŃĐľŃкио ПаŃкоŃŃ, ŃŃĐž пОСвОНиНО в пОŃНоднио ĐłĐžĐ´Ń Đ˛ŃŃвНŃŃŃ Đ´Đ°Đ˝Đ˝ŃĐľ ĐˇĐ°ĐąĐžĐťĐľĐ˛Đ°Đ˝Đ¸Ń Đ˝Đ° СнаŃиŃоНŃнО йОНоо ŃанниŃ
ŃŃадиŃŃ
, ноМоНи ŃĐ°Đ˝ŃŃĐľ. Đ Đ°Đş пОŃки пОâĐżŃĐľĐśĐ˝ĐľĐźŃ ĐžŃŃĐ°ĐľŃŃŃ Đ´ĐžŃŃĐ°ŃĐžŃнО ŃНОМнŃĐź в диагнОŃŃиŃĐľŃкОП и ŃĐľŃаповŃиŃĐľŃкОП пНано СайОНованиоП, кОŃĐžŃОо ŃиПпŃОПаŃиŃĐľŃки ĐżŃĐžŃвНŃĐľŃ ŃĐľĐąŃ ŃМо на пОСдниŃ
ŃŃадиŃŃ
. Đ Đ ĐžŃŃии на ĐźĐžĐźĐľĐ˝Ń ŃŃŃĐ°Đ˝ĐžĐ˛ĐťĐľĐ˝Đ¸Ń Đ´Đ¸Đ°ĐłĐ˝ĐžĐˇĐ° НОкаНиСОваннŃĐš и ПоŃŃнО-ŃĐ°ŃĐżŃĐžŃŃŃаноннŃĐš ŃĐ°Đş пОŃки вŃŃвНŃĐľŃŃŃ Ń 75,4 % СайОНовŃиŃ
. ĐĐľŃПОŃŃŃ Đ˝Đ° наНиŃио на ŃĐ°ŃПаŃовŃиŃĐľŃкОП ŃŃнко ŃаСНиŃĐ˝ŃŃ
ŃĐ°ŃгоŃĐ˝ŃŃ
ĐżŃопаŃĐ°ŃОв, напŃавНоннŃŃ
на НоŃонио даннОгО СайОНованиŃ, ŃĐľŃĐ°ĐżĐ¸Ń ĐżĐžŃĐľŃнО-кНоŃĐžŃнОгО Ńака на даннŃĐš ĐźĐžĐźĐľĐ˝Ń Đ˝Đľ Đ´ĐžŃŃигНа СнаŃиŃоНŃĐ˝ŃŃ
ŃŃпоŃ
Ов. ĐОНŃŃинŃŃвО ŃОвŃоПоннŃŃ
ŃĐ°ŃгоŃĐ˝ŃŃ
ŃĐľŃаповŃиŃĐľŃкиŃ
 агонŃОв, напŃавНоннŃŃ
на НоŃонио Ńака пОŃки, вкНŃŃĐ°ĐľŃ Đ˛ ŃĐľĐąŃ Đ¸Đ˝ĐłĐ¸ĐąĐ¸ŃĐžŃŃ ŃаСНиŃĐ˝ŃŃ
кОПпОнонŃОв ОднОгО ŃигнаНŃнОгО ĐżŃŃи, йоŃŃŃогО ŃвОо наŃаНО ĐžŃ ĐžĐżŃŃ
ОНовОгО ŃŃĐżŃĐľŃŃĐžŃĐ° VHL1, пОŃĐľŃŃ ŃĐşŃĐżŃĐľŃŃии кОŃĐžŃОгО найНŃĐ´Đ°ĐľŃŃŃ Đ˛ йОНŃŃинŃŃво ŃĐťŃŃаов пОŃĐľŃнО-кНоŃĐžŃĐ˝ŃŃ
каŃŃинОП. ĐŃовиднО, ŃŃĐž ŃŃŃĐľŃŃвŃŃŃио на ŃĐ°ŃПаŃовŃиŃĐľŃкОП ŃŃнко ĐżŃопаŃĐ°ŃŃ Đ˝Đľ ОйНадаŃŃ Đ´ĐžŃŃĐ°ŃĐžŃнОК ŃĐľŃаповŃиŃĐľŃкОК ŃŃŃокŃивнОŃŃŃŃ. ĐПоннО пОŃŃĐžĐźŃ Đ˛ĐžĐˇĐ˝Đ¸ĐşĐ°ĐľŃ Đ˝ĐľĐžĐąŃ
ОдиПОŃŃŃ ĐżĐžĐ¸Ńка нОвŃŃ
ŃигнаНŃĐ˝ŃŃ
ĐżŃŃоК, ŃогŃНиŃŃŃŃиŃ
ваМноКŃио кНоŃĐžŃĐ˝ŃĐľ ĐżŃĐžŃĐľŃŃŃ, Ńакио как ĐżŃОНиŃĐľŃĐ°ŃиŃ, ПигŃĐ°ŃĐ¸Ń Đ¸ апОпŃОС. ĐĄŃŃĐľŃŃвŃŃŃио на ŃогОднŃŃниК Đ´ĐľĐ˝Ń ĐźĐ°ŃкоŃŃ пŃОгнОСа и ПиŃони ŃĐľŃапии пОŃĐľŃнО-кНоŃĐžŃнОгО Ńака ПаНОŃиŃĐťĐľĐ˝Đ˝Ń Đ¸ ниСкОŃпоŃиŃиŃĐ˝Ń. Đ ŃвŃСи Ń ŃŃиП пОиŃĐş и ваНидаŃĐ¸Ń Đ˝ĐžĐ˛ŃŃ
 ПаŃкоŃОв, Đ° в ĐžŃОйоннОŃŃи нОвŃŃ
ŃпоŃиŃиŃĐľŃкиŃ
ПиŃоноК Đ´ĐťŃ ĐťĐľŃĐľĐ˝Đ¸Ń ĐžĐ˝ĐşĐžĐżĐ°ŃОНОгиК пОŃки ĐżŃодŃŃавНŃŃŃŃŃ ŃŃоСвŃŃаКнО Đ°ĐşŃŃĐ°ĐťŃĐ˝ŃПи
Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis
Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. Recently, we have identified the top 10 master regulators that were involved in the accumulation of cholesterol in cultured macrophages induced by the incubation with modified LDL. It was found that most of the identified master regulators were related to the regulation of the inflammatory immune response, but not to lipid metabolism. A possible explanation for this unexpected result is a stimulation of the phagocytic activity of macrophages by modified LDL particle associates that have a relatively large size. In the current study, we investigated gene regulation in macrophages using transcriptome analysis to test the hypothesis that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. We identified genes that were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads (inert phagocytosis stimulators). Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. The obtained results indicated that pro-inflammatory response to phagocytosis stimulation precedes the accumulation of intracellular lipids and possibly contributes to the formation of foam cells. In this way, the currently recognized hypothesis that the accumulation of lipids triggers the pro-inflammatory response was not confirmed. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. Additionally, the knock-down effect of five master regulators, such as IL15, EIF2AK3, F2RL1, TSPYL2, and ANXA1, on intracellular lipid accumulation was tested. We knocked down these genes in primary macrophages derived from human monocytes. The addition of atherogenic naturally occurring LDL caused a significant accumulation of cholesterol in the control cells. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages. The knock-down of the ANXA1 gene caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. The results obtained allowed us to explain in which way the inflammatory response and the accumulation of cholesterol are related confirming our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response
Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC
The uncertainty on the calorimeter energy response to jets of particles is
derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the
calorimeter response to single isolated charged hadrons is measured and
compared to the Monte Carlo simulation using proton-proton collisions at
centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009
and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter
response to specific types of particles (positively and negatively charged
pions, protons, and anti-protons) is measured and compared to the Monte Carlo
predictions. Finally, the jet energy scale uncertainty is determined by
propagating the response uncertainty for single charged and neutral particles
to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3%
for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table,
submitted to European Physical Journal
Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC
Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H âÎł Îł, H â Z Zâ â4l and H âW Wâ âlνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of âs = 7 TeV and âs = 8 TeV, corresponding to an integrated luminosity of about 25 fbâ1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined ďŹts probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson
Standalone vertex ďŹnding in the ATLAS muon spectrometer
A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at âs = 7 TeV collected with the ATLAS detector at the LHC during 2011
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