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131.
Thalamic neurons exhibit subthreshold resonance when stimulated with small sine wave signals of varying frequency and stochastic
resonance when noise is added to these signals. We study a stochastic Hindmarsh-Rose model using Monte-Carlo simulations to
investigate how noise, in conjunction with subthreshold resonance, leads to a preferred frequency in the firing pattern. The
resulting stochastic resonance (SR) exhibits a preferred firing frequency that is approximately exponential in its dependence
on the noise amplitude. In similar experiments, frequency dependent SR is found in the reliability of detection of alpha-function
inputs under noise, which are more realistic inputs for neurons. A mathematical analysis of the equations reveals that the
frequency preference arises from the dynamics of the slow variable. Noise can then transfer the resonance over the firing
threshold because of the proximity of the fast subsystem to a Hopf bifurcation point. Our results may have implications for
the behavior of thalamic neurons in a network, with noise switching the membrane potential between different resonance modes. 相似文献
132.
Computational discovery of gene modules and regulatory networks 总被引:23,自引:0,他引:23
Bar-Joseph Z Gerber GK Lee TI Rinaldi NJ Yoo JY Robert F Gordon DB Fraenkel E Jaakkola TS Young RA Gifford DK 《Nature biotechnology》2003,21(11):1337-1342
133.
Elimrani I Lahjouji K Seidman E Roy MJ Mitchell GA Qureshi I 《American journal of physiology. Gastrointestinal and liver physiology》2003,284(5):G863-G871
l-Carnitine is derived both from dietary sources and biosynthesis. Dietary carnitine is absorbed in the small intestine and then distributed to other organs. Previous studies using Caco-2 cells demonstrated that the transport of l-carnitine in the intestine involves a carrier-mediated system. The purpose of this study was to determine whether the uptake of l-carnitine in Caco-2 cells is mediated by the recently identified organic cation/carnitine transporter (OCTN2). Kinetics of l-[(3)H]carnitine uptake were investigated with or without specific inhibitors. l-Carnitine uptake in mature cells was sodium dependent and linear with time. K(m) and V(max) values for saturable uptake were 14.07 +/- 1.70 micro M and 26.3 +/- 0.80 pmol. mg protein(-1). 6 min(-1), respectively. l-carnitine uptake was inhibited (P < 0.05-0.01) by valproate and other organic cations. Anti-OCTN2 antibodies recognized a protein in the brush-border membrane (BBM) of Caco-2 cells with an apparent molecular mass of 60 kDa. The OCTN2 expression was confirmed by double immunostaining. Our results demonstrate that l-carnitine uptake in differentiated Caco-2 cells is primarily mediated by OCTN2, located on the BBM. 相似文献
134.
Adeno-Associated Virus Vector-Mediated Transgene Integration into Neurons and Other Nondividing Cell Targets 总被引:3,自引:2,他引:1 下载免费PDF全文
The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors. 相似文献
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138.
Daniel Ajona Cristina Razquin Maria Dolores Pastor Maria Jose Pajares Javier Garcia Felipe Cardenal Michael Fleischhacker Maria Dolores Lozano Javier J. Zulueta Bernd Schmidt Ernest Nadal Luis Paz-Ares Luis M. Montuenga Ruben Pio 《PloS one》2015,10(3)
Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71–0.94) and 0.67 (95%CI = 0.58–0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56–0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease. 相似文献
139.
Yohanna Kamabi Avong Petros Isaakidis Sven Gudmund Hinderaker Rafael Van den Bergh Engy Ali Bolajoko Oladunni Obembe Ernest Ekong Clement Adebamowo Nicaise Ndembi James Okuma Adeline Osakwe Olanrewaju Oladimeji Gabriel Akang Joshua Olusegun Obasanya Osman Eltayeb Aderonke Vivian Agbaje Alash’le Abimiku Charles Olalekan Mensah Patrick Sunday Dakum 《PloS one》2015,10(3)
Background
Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria.Method
This was a retrospective, observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria. Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed.Results
Four hundred and sixty patients were included in the analysis: 62% were male; median age was 33 years [Interquartile Range (IQR):28–42] and median weight was 51 kg (IQR: 45–59). Two hundred and three (44%) patients experienced AEs; four died of conditions associated with SLD AEs. Gastro-intestinal (n = 100), neurological (n = 75), ototoxic (n = 72) and psychiatric (n = 60) AEs were the most commonly reported, whereas ototoxic and psychiatric AEs were the most debilitating. Majority of AEs developed after 1–2 months of therapy, and resolved in less than a month after treatment. Some treatment centers were twice as likely to report AEs compared with others, highlighting significant inconsistencies in reporting at different treatment centers. Patients with a higher body weight had an increased risk of experiencing AEs. No differences were observed in risk of AEs between HIV-infected and uninfected patients. Similarly, age was not significantly associated with AEs.Conclusion
Patients in the Nigerian MDR-TB cohort experienced a wide range of AEs, some of which were disabling and fatal. Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed. Safer regimens for drug-resistant TB with the shortest duration are advocated. 相似文献140.
Marsh K?nigs Wouter D. Weeda L. W. Ernest van Heurn R. Jeroen Vermeulen J. Carel Goslings Jan S. K. Luitse Bwee Tien Poll-Thé Anita Beelen Marleen van der Wees Rachèl J. J. K. Kemps Coriene E. Catsman-Berrevoets Jaap Oosterlaan 《PloS one》2015,10(12)