Vascular adhesion protein 1 (VAP-1) mediates lymphocyte subtype-specific, selectin-independent recognition of vascular endothelium in human lymph nodes

Interactions between lymphocyte surface receptors and their ligands on vascular endothelial cells regulate the exit of lymphocytes from the circulation. Distinct subsets of mononuclear cells bind to high endothelial venules (HEVs) in different lymphoid organs to a different extent, but the molecular mechanisms behind this selectivity have remained poorly characterized. Here we show that vascular adhesion protein-1 (VAP-1) mediates subtype-specific binding of CD8-positive T cells and natural killer cells to human endothelium. VAP-1-dependent, oligosaccharide-dependent peripheral lymph node (PLN) HEV adhesion under shear was independent of L-selectin, P-selectin glycoprotein ligand 1, and alpha4 integrins, the known lymphocyte receptors involved in the initial recognition of endothelial cells. PLN HEV adhesion was also critically dependent on peripheral lymph node vascular addressins (PNAds), but lymphocyte L-selectin was absolutely required for PNAd binding. Most lymphocytes relied on both PNAd and VAP-1 in HEV binding. The overlapping function of L-selectin ligands and VAP-1 in PLN introduces a new control point into the lymphocyte extravasation process. Finally, intravital microscopy revealed that VAP-1 is involved in initial interactions between human lymphocytes and endothelial cells in inflamed rabbit mesenterial venules in vivo. In conclusion, VAP-1 is a novel contact-initiating ligand that discriminates between different subpopulations of mononuclear cells and is an appealing target for selective modulation of adhesion of CD8- and CD16-positive effector cells.     

Work conditions, mastery and psychological distress: are housework and paid work contexts conceptually similar?

This research examined how the conditions of paid work and unpaid housework were related to women's sense of mastery, depressed mood and anxiety. The data for these analyses were taken from the American Changing Lives (ACL) survey (House, 1986). This research draws from a subsample of 992 black and non-Hispanic white women aged 24 to 59. The conditions of work on the job and in the home are not consistently related to women's psychological functioning. Among employed women, decision latitude on the job is related to depressed mood indirectly through their sense of mastery; the physical demands of work are directly related to depressed mood, but the effect is stronger among employed women than employed homemakers. In contrast, decision latitude at home is directly related to depressed mood among homemakers; the physical demands of housework are related to depressed mood only indirectly through women's sense of mastery. This pattern is repeated in the relationship between anxiety and decision latitude both at home and on the job, and in the relationship between anxiety and physical demands of work on the job. Both unpaid housework and paid work are forms of productive activity, but these findings suggest they are not a ubiquitous entity with similar effects for all women. Rather the context of work shapes the effect of work conditions for women's psychological functioning.     

Optimal corrective actions for power systems using multi-objective genetic algorithms

In this paper, optimal corrective control actions are presented to restore the secure operation of power system for different operating conditions. Genetic algorithm (GA) is one of the modern optimization techniques, which has been successfully applied in various areas in power systems. Most of the corrective control actions involve simultaneous optimization of several objective functions, which are competing and conflicting each other. The multi-objective genetic algorithm (MOGA) is used to optimize the corrective control actions. Three different procedures based on GA and MOGA are proposed to alleviate the violations of the overloaded lines and minimize the transmission line losses for different operation conditions. The first procedure is based on corrective switching of the transmission lines and generation re-dispatch. The second procedure is carried out to determine the optimal siting and sizing of distributed generation (DG). While, the third procedure is concerned into solving the generation-load imbalance problem using load shedding. Numerical simulations are carried out on two test systems in order to examine the validity of the proposed procedures.     

Multiplexed immunohistochemical detection of tumor markers in breast cancer tissue using laser ablation inductively coupled plasma mass spectrometry

We optimized multiplexed immunohistochemistry (IHC) on breast cancer tissue. Up to 20 tumor markers are routinely evaluated for one patient, and thus, a common analysis results in a series of time consuming staining procedures. As an alternative, we used lanthanides for labeling of primary antibodies, which are applied in IHC. Laser ablation (LA) ICPMS was elaborated as a detection tool for multiplexed IHC of tissue sections. In this study, we optimized sample preparation steps and LA ICPMS parameters to achieve a sufficient signal-to-background ratio. The results prove the high selectivity of applied antibodies, which was sustained after labeling. Up to three tumor markers (Her 2, CK 7, and MUC 1) were detected simultaneously in a single multiplex analysis of a 5 μm thin breast cancer tissue at a laser spot size of 200 μm. Furthermore, the LA ICPMS results indicate a significantly higher expression level of MUC 1 compared to Her 2 and CK 7, which was not obvious from the conventionally stained tissue sections.     

Mineralogical and industrial characterization of the Batn El-Ghoul clay deposits, southern Jordan

The non-calcareous and thinly laminated Batn El-Ghoul clay deposit is a part of the Clayey Shale Unit of Lower Silurian age in Jordan. Its thickness is of about 50 m and it overlies a bituminous clayey deposit. 128 samples were selected from three boreholes and afterwards were subjected to detailed petrological, mineralogical and chemical analyses. The clay deposit is essentially composed of kaolinite as predominant mineral, with subsidiary mica-illite, vermiculite, smectite, chlorite, and mixed-layer mica-smectite. The non-clay minerals are quartz, feldspars, goethite and, occasionally, secondary gypsum. The Fe₂O₃ content is relatively high (7%) and is a detrital mineral. Palynomorph assemblages suggested a marine environment although authigenic micas are common. The clay deposits originated from highly weathered surfaces related to the basement. Industrial tests have proved the suitability of the clay deposit for ceramic industry.     

Enalapril prevents imminent and reduces manifest cerebral edema in stroke-prone hypertensive rats

BACKGROUND AND PURPOSE: Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake, show severe hypertension, organ damage, and early death. Preventive treatment with an angiotensin-converting enzyme (ACE) inhibitor is known to reduce mortality. Previously we found that proteinuria always precedes cerebral edema in SHRSP. Hence, in this study ACE inhibition was started later, ie, directly after manifestation of either proteinuria or cerebral edema. METHODS: SHRSP were subjected to 1% NaCl intake. Group 1 served as a control. In group 2 early-onset treatment with the ACE inhibitor enalapril was initiated after proteinuria was >40 mg/d. In group 3 late-onset ACE inhibition was started after the first observation of cerebral edema with T2-weighted MRI. Cerebral edema was expressed as the percentage of pixels with an intensity above a defined threshold. RESULTS: In controls median survival was 54 days (range, 32 to 80 days) after start of salt loading. The terminal level of cerebral edema was 19.0+/-3.0%. Under early-onset enalapril, median survival increased to 320 days (range, 134 to 368 days; P<0.01 versus group 1). Cerebral edema was prevented in all but 1 rat. Systolic blood pressure was slightly and transiently reduced at day 14. Proteinuria was markedly reduced (52+/-7 versus 190+/-46 mg/d in group 1 at day 7; P<0.05). Under late-onset enalapril, median survival was 264 days (range, 154 to 319 days; P<0.01 versus group 1). Cerebral edema decreased to baseline levels (9.6+/-2.9 at day 0 to 3.4+/-0.5% at day 3; (P<0.05). Ultimately cerebral edema reoccurred in 6 of the 8 rats. SBP decreased slightly at day 7 only. Proteinuria decreased from 283+/-27 at day 0 to 116+/-22 mg/d at day 7 (P<0.05). Complete remission of the original locus of cerebral edema was confirmed histologically. CONCLUSIONS: In SHRSP with proteinuria, treatment with an ACE inhibitor both prevented the development of cerebral edema and reduced manifest cerebral edema and proteinuria. Survival was markedly prolonged. These findings support the use of ACE inhibition for treatment in hypertensive encephalopathy.     

Evaluation of the developmental toxicity of caffeine and caffeine metabolites using the frog embryo teratogenesis assay--Xenopus (FETAX)

The developmental toxicities of caffeine and 13 metabolites, including theophylline, and paraxanthine and a synthetic methylxanthine analogue 3-isobutyl-methylxanthine (IBMX) were evaluated using the Frog Embryo Teratogenesis Assay Xenopus (FETAX). Young X. laevis embryos were exposed to these compounds in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS). Results obtained from these studies indicated that relative teratogenic potencies of caffeine and each of its di- and monomethylxanthine metabolites were similar. Representatives of both the substituted uric and uracil metabolites were less developmentally toxic on an equimolar basis than the methylxanthines, suggesting that they may have represented detoxification metabolites. IBMX, a phosphodiesterase inhibitor also known to be an adenosine receptor antagonist, was the most potent developmental toxicant of the materials evaluated. In conclusion, none of the caffeine metabolites tested was found to be significantly more potent than caffeine itself in the FETAX assay.