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991.
The proliferation of human melanoma cell line A375-6 is inhibited by several cytokines, including interleukin-1 (IL-1) and interleukin-6 (IL-6). However, during a long period of culture, the cells progressively acquire resistance to IL-1 irrespective of functional IL-1 receptor expression. These cells constitutively produce IL-1alpha and IL-6, and also acquire resistance to IL-6. In order to investigate the mechanism of the acquired resistance to these cytokines, we performed somatic cell hybridization experiments. Parental cells for the construction of hybrid cells were rendered G418- or hygromycin B-resistant by transfection with expression vectors containing drug-resistant genes. Hybridization was conducted using IL-1-resistant subclones A375-R8 and R19 and an IL-1 highly sensitive clone C2-1, which was originally resistant but became sensitive to IL-1 upon transfection with a human type I IL-1 receptor (IL-1R) expression plasmid. Cells produced by hybridization of resistant cells and C2-1 cells appeared to be sensitive to IL-1 and IL-6. In contrast, production of IL-1 was augmented in the hybrid cells. These results suggest that resistance to IL-1 and IL-6 is a recessive phenotype, while production of IL-1 is dominant in melanoma cells.  相似文献   
992.
Fatal crash rates of passenger cars and vans were compared for the last model year before four-wheel antilock brakes were introduced and the first model year for which antilock brakes were standard equipment. Vehicles selected for analysis had no other significant design changes between the model years being compared, and the model years with and without antilocks were no more than two years apart. The overall fatal crash rates were similar for the two model years. However, the vehicles with antilocks were significantly more likely to be involved in crashes fatal to their own occupants, particularly single-vehicle crashes. Conversely, antilock vehicles were less likely to be involved in crashes fatal to occupants of other vehicles or nonoccupants (pedestrians, bicyclists). Overall, antilock brakes appear to have had little effect on fatal crash involvement. Further study is needed to better understand why fatality risk has increased for occupants of antilock vehicles.  相似文献   
993.
Posttraumatic stress disorder (PTSD) typically follows an acute to chronic course. However, some trauma victims do not report significant symptoms until a period of time has elapsed after the event. Although originally dismissed as an artifact of retrospective methodologies, recent prospective studies document apparent instances of delayed-onset PTSD. Little is known currently about factors associated with the delayed onset of PTSD. This study was designed to examine the course of PTSD in a sample of 1,040 U.S. military peacekeepers who served in Somalia. A small but nontrivial subset of participants endorsed clinically significant levels of PTSD after a period of minimal distress, the magnitude of which cannot be ascribed to minor waxing and waning of symptoms. War-zone exposure and perceived meaningfulness of the mission, as rated by soldiers after returning to the United States, predicted symptom course over the next 18 months. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
994.
The effect of nitrapyrin [2-chloro-6-(trichloromethyl)pyridine] application on nitrapyrin residues and nitrate content in red beet (Beta vulgaris L. var. conditiva) roots and in soil fertilised with urea was studied during the 1977 growing season. The nitrapyrin residues in roots were on 15 August between 0.00–1.19 μg g?1 and on 1 October between 0.00–0.45 μg g?1 (dry weight basis) correlating significantly r = 0.99, P<0.01) to the rates of nitrapyrin applied on 8 June (0–34 kg ha?1). The content of nitrapyrin in roots decreased in autumn having in August-September a ‘biological half-life’ of 3 weeks. In soil the same parameter was in July-September more than 4 months. The ratio of nitrapyrin to its main breakdown product varied in soil between 3.5–24.8 and in red beets between 0.6–1.4. Neither of these compounds were found in processed canned red beets. Nitrapyrin treatment decreased the nitrate content in both soil and beets. The inhibitor application of 18 kg ha?1 caused the highest reduction of the NO3-nitrogen content in beets, the average values on dry weight basis being 0.51–0.34 mg g?1 for 0–18 kg ha?1 nitrapyrin application, respectively. The reduction of NO3-nitrogen in beets from its level of 15 August to its September level was 44%. After 5 September the reduction of the nitrate level in beets was not significant.  相似文献   
995.
We consider in this paper the class M k n of generalized Motzkin paths of length n, that is, lattice paths using steps (1,1), (1,−1), (k,0), where k is a fixed positive integer, starting at the origin (0,0), running above the x-axis, and ending at (n,0). The area is the region bounded by the path and the x-axis. We first establish a bijection between the area of paths in M k n and some lattice paths of length n+1. Then, by using a rejection technique, we obtain a linear algorithm with an average time complexity (k mod 2 +1)(n+1).With the support of NSERC (Canada), G.N.C.S. – Istituto Nazionale di Alta Matematica (Italia), MIUR Project: Linguaggi Formalie Automi: Teoriae Applicazioni  相似文献   
996.
Push-based systems for distributing information through Internet are today becoming more and more popular and widely used. The widespread use of such systems raises non trivial security concerns. In particular, confidentiality, integrity and authenticity of the distributed data must be ensured. To cope with such issues, we describe here a system for securing push distribution of XML documents, which adopts digital signature and encryption techniques to ensure the above mentioned properties and allows the specification of both signature and access control policies. We also describe the implementation of the proposed system and present an extensive performance evaluation of its main components.  相似文献   
997.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Gemcitabine (GEM) is used as the gold standard drug in PDAC treatment. However, due to its poor efficacy, it remains urgent to identify novel strategies to overcome resistance issues. In this context, an intense stroma reaction and the presence of cancer stem cells (CSCs) have been shown to influence PDAC aggressiveness, metastatic potential, and chemoresistance. Methods: We used three-dimensional (3D) organotypic cultures grown on an extracellular matrix composed of Matrigel or collagen I to test the effect of the new potential therapeutic prodrug 4-(N)-stearoyl-GEM, called C18GEM. We analyzed C18GEM cytotoxic activity, intracellular uptake, apoptosis, necrosis, and autophagy induction in both Panc1 cell line (P) and their derived CSCs. Results: PDAC CSCs show higher sensitivity to C18GEM treatment when cultured in both two-dimensional (2D) and 3D conditions, especially on collagen I, in comparison to GEM. The intracellular uptake mechanisms of C18GEM are mainly due to membrane nucleoside transporters’ expression and fatty acid translocase CD36 in Panc1 P cells and to clathrin-mediated endocytosis and CD36 in Panc1 CSCs. Furthermore, C18GEM induces an increase in cell death compared to GEM in both cell lines grown on 2D and 3D cultures. Finally, C18GEM stimulated protective autophagy in Panc1 P and CSCs cultured on 3D conditions. Conclusion: We propose C18GEM together with autophagy inhibitors as a valid alternative therapeutic approach in PDAC treatment.  相似文献   
998.
Mutations in the CNGA3 gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the Cnga3 knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in Cnga3 KO mice. Virus-mediated knockdown or genetic ablation of Prkg2 in Cnga3 KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in Cnga3 KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.  相似文献   
999.
Phosphatidylserines are known to sustain skeletal muscle activity during intense activity or hypoxic conditions, as well as preserve neurocognitive function in older patients. Our previous studies pointed out a potential cardioprotective role of phosphatidylserine in heart ischemia. Therefore, we investigated the effects of phosphatidylserine oral supplementation in a mouse model of acute myocardial infarction (AMI). We found out that phosphatidylserine increases, significantly, the cardiomyocyte survival by 50% in an acute model of myocardial ischemia-reperfusion. Similar, phosphatidylserine reduced significantly the infarcted size by 30% and improved heart function by 25% in a chronic model of AMI. The main responsible mechanism seems to be up-regulation of protein kinase C epsilon (PKC-ε), the main player of cardio-protection during pre-conditioning. Interestingly, if the phosphatidylserine supplementation is started before induction of AMI, but not after, it selectively inhibits neutrophil’s activation, such as Interleukin 1 beta (IL-1β) expression, without affecting the healing and fibrosis. Thus, phosphatidylserine supplementation may represent a simple way to activate a pre-conditioning mechanism and may be a promising novel strategy to reduce infarct size following AMI and to prevent myocardial injury during myocardial infarction or cardiac surgery. Due to the minimal adverse effects, further investigation in large animals or in human are soon possible to establish the exact role of phosphatidylserine in cardiac diseases.  相似文献   
1000.
Doping of semiconductors enables fine control over the excess charge carriers, and thus the overall electronic properties, crucial to many technologies. Controlled doping in lead‐halide perovskite semiconductors has thus far proven to be difficult. However, lower dimensional perovskites such as nanocrystals, with their high surface‐area‐to‐volume ratio, are particularly well‐suited for doping via ground‐state molecular charge transfer. Here, the tunability of the electronic properties of perovskite nanocrystal arrays is detailed using physically adsorbed molecular dopants. Incorporation of the dopant molecules into electronically coupled CsPbI3 nanocrystal arrays is confirmed via infrared and photoelectron spectroscopies. Untreated CsPbI3 nanocrystal films are found to be slightly p‐type with increasing conductivity achieved by incorporating the electron‐accepting dopant 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F4TCNQ) and decreasing conductivity for the electron‐donating dopant benzyl viologen. Time‐resolved spectroscopic measurements reveal the time scales of Auger‐mediated recombination in the presence of excess electrons or holes. Microwave conductance and field‐effect transistor measurements demonstrate that both the local and long‐range hole mobility are improved by F4TCNQ doping of the nanocrystal arrays. The improved hole mobility in photoexcited p‐type arrays leads to a pronounced enhancement in phototransistors.  相似文献   
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