Loss of function of the maternally inherited allele for the UBE3A ubiquitin ligase gene causes Angelman syndrome (AS), which is characterized by severe neurological impairment and motor dysfunction. ...In addition, UBE3A lies within chromosome 15q11–q13 region, where maternal, but not paternal, duplications cause autism. The UBE3A gene product, E6-AP, has been shown to function both as an E3 ligase in the ubiquitin proteasome pathway and as a transcriptional coactivator. However, the specific role of E6-AP in the brain, or how loss of function of E6-AP results in AS, is unclear. Herein, we show, using a recombinant transgenic mouse expressing a Ube3aYFP fusion gene, that the maternal Ube3aYFP allele is upregulated and preferentially expressed in neurons, and that the fusion protein, E6-AP:YFP, is enriched in the nucleus and dendrites in vivo. We also show that E6-AP:YFP localizes to the nucleus and to presynaptic and postsynaptic compartments in cultured hippocampal neurons. Furthermore, we show that cerebellar Purkinje cell number and dendritic branching are not affected in Ube3a maternal-deficient mice, but that dendritic spine development, including spine morphology, number and length, is affected on cerebellar Purkinje cells and on pyramidal neurons in the hippocampus and cortex. Collectively, these data suggest that the neurological deficits observed in AS patients and in AS mice may result from specific abnormalities in synaptic development and/or plasticity.
In addition to chloride induced corrosion, the other commonly occurring type of rebar corrosion in reinforced concrete structures is that induced by the ingress of atmospheric carbon dioxide into ...concrete, commonly referred to as ‘carbonation induced corrosion’. This paper presents a new approach for detecting the onset and quantifying the level of carbonation induced rebar corrosion. The approach is based on the changes in the mechanical impedance parameters acquired using the electro-mechanical coupling of a piezoelectric lead zirconate titanate (PZT) ceramic patch bonded to the surface of the rebar. The approach is non-destructive and is demonstrated though accelerated tests on reinforced concrete specimens subjected to controlled carbon dioxide exposure for a period spanning over 230days. The equivalent stiffness parameter, extracted from the frequency response of the admittance signatures of the PZT patch, is found to increase with penetration of carbon dioxide inside the surface and the consequent carbonation, an observation that is correlated with phenolphthalein staining. After the onset of rebar corrosion, the equivalent stiffness parameter exhibited a reduction in magnitude over time, providing a clear indication of the occurrence of corrosion and the results are correlated with scanning electron microscope images and Raman spectroscopy measurements. The average rate of corrosion is determined using the equivalent mass parameter. The use of PZT ceramic transducers, therefore, provides an alternate and effective technique for diagnosis of carbonation induced rebar corrosion initiation and progression in reinforced concrete structures non-destructively.
The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain ...largely unknown. In this study, we showed that probiotic
DSM 17938 (
) ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by T
17 and T
1 cells. We discovered that
treatment reduced T
1/T
17 cells and their associated cytokines IFN-γ/IL-17 in EAE mice. We also showed that the loss of diversity of gut microbiota induced by EAE was largely restored by
treatment. Taxonomy-based analysis of gut microbiota showed that three "beneficial" genera
, and
were negatively correlated with EAE clinical severity, whereas the genera
, and
were positively correlated with disease severity. Notably,
treatment coordinately altered the relative abundance of these EAE-associated taxa. In conclusion, probiotic
changed gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.
The presence of chloride ions in reinforced concrete (RC) plays a major role in reinforcement corrosion and hence for the durability and service life of RC structures. With growing concern towards ...the deterioration of reinforced concrete structures, the use of electrochemical techniques for their performance evaluation has become an important topic of durability study. This paper illustrates the findings of an experimental investigation carried out on large number of specimens for evaluating the performance of different types of rebar in chloride contaminated concrete made with different types of cement through different corrosion rate techniques. The specimens were prepared with three types of cement and three types of steel. From the results of corrosion rate, it was observed that the values of corrosion rate obtained by linear polarization resistance (LPR) technique with guard ring arrangement were in close agreement with those obtained by gravimetric method. On the other hand the corrosion rate values obtained by AC impedance spectroscopy were slightly lower than those obtained by LPR measurement. Further, correlations between different corrosion rate techniques were also obtained. From the results of analysis of variance (ANOVA), it was observed that chloride content has the strongest effect on corrosion rate as compared to other factors.
Rebar corrosion in chloride environment Pradhan, Bulu; Bhattacharjee, B.
Construction & building materials,
05/2011, Letnik:
25, Številka:
5
Journal Article
Recenzirano
► Corrosion performance of cement and steel in internal and external chloride exposure. ► Comparison of corrosion parameters obtained from different corrosion tests. ► Corrosion current in internal ...chloride varies much from that in external chloride. ► A methodology in proposed to rank performance of different cement-steel combination.
Chloride induced reinforcement corrosion in concrete is a serious durability problem. Different sources of chloride, i.e. chloride introduced at the fresh stage of concrete (i.e. internal chloride) and chloride entered during the hardened state (i.e. external chloride) may affect the performance of concrete in different ways. For the performance evaluation of reinforced concrete in chloride environment (i.e. both internal and external chloride), there is a need for performing different electrochemical tests to obtain various corrosion parameters that will specify the possibility and the magnitude of corrosion in concrete. In the present study, the results of an experimental investigation that includes different corrosion tests namely potential measurement, corrosion rate measurement and potentiodynamic polarization test have been presented and analyzed to evaluate the performance of concrete both in internal chloride and external chloride exposure conditions. In addition an attempt is made to correlate the corrosion parameters obtained from internal and external chloride exposure conditions. From the results it was observed that, dropped half-cell potential value obtained from external chloride exposure mostly lie in the active zone obtained from internal chloride exposure. In addition it was observed that there was significant difference in corrosion current values obtained from both internal and external chloride exposure conditions. Further on the basis of overall ranking obtained from the results of critical parameters from different exposure conditions, the performance of different cement–steel combinations against chloride induced rebar corrosion has been evaluated.
In this study, in situ strength of concrete was determined through compression test of cores drilled out from laboratory cast beams. The apparent porosity and pore size distribution of the same ...concrete were determined through mercury intrusion porosimetry, performed on small-drilled cores. The normal-strength concrete mixes used in the experimental investigation were designed to exhibit a wide variation in their strengths. To ensure further variation in porosity, pore size distribution and strength, two modes of compaction, two varieties of coarse aggregates, different levels of age, curing period and exposure condition of concrete were also introduced in experimental scheme. With the data so generated, an appraisal of the most frequently referred relationships involving strength, porosity and pore size of cement-based materials was carried out. Finally, a new empirical model relating the in situ strength of concrete with porosity, pore size characteristics, cement content, aggregate type, exposure conditions, etc., is presented.
Amyloid plaques in Alzheimer's disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (Aβ) pathogenesis; however, the ...mechanisms are still not well understood. We hypothesize that the gut bears the Aβ burden prior to brain, highlighting gut-brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular Aβ deposition in the IEB occur before cerebral Aβ aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral Aβ pathology. Lastly, we report Aβ deposition in the intestinal autopsy from AD patients with confirmed cerebral Aβ pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut dysfunction occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve the early manipulation of gut physiology and its microbiota.
Effects of rate of pressure application and forms and type of sample on porosity and pore size distribution of concrete estimated through mercury intrusion porosimetry (MIP) are presented in this ...experimental work. Two different forms of concrete sample, namely, crushed chunks of concrete and small core drilled out from the concrete beam specimens, were used for this study. The results exhibit that the rate of pressure application in mercury porosimetry has little effect on porosity and pore size distribution of concrete. It is also demonstrated that small cores drilled out from large concrete specimens are preferable as samples for performing porosimetry test on concrete.
Clinical studies treating pediatric and adult solid tumors, such as glioblastoma (GBM), with a triple-drug regimen of temozolomide (TMZ), bevacizumab (BEV), and irinotecan (IRI) TBI have demonstrated ...various efficacies, but with no unexpected toxicities. The TBI regimen has never been studied in recurrent GBM (rGBM) patients. In this retrospective study, we investigated the outcomes and side effects of rGBM patients who had received the TBI regimen. We identified 48 adult rGBM patients with a median age of 56 years (range: 26-76), who received Tumor Treating Fields (TTFields) treatment for 30 days or longer, and concurrent salvage chemotherapies. The patients were classified into two groups based on chemotherapies received: TBI with TTFields (TBI+T,
= 18) vs. bevacizumab (BEV)-based chemotherapies with TTFields (BBC+T,
= 30). BBC regimens were either BEV monotherapy, BEV+IRI or BEV+CCNU. Patients in TBI+T group received on average 19 cycles of TMZ, 26 and 21 times infusions with BEV and IRI, respectively. Median overall survival (OS) and progression-free survival (PFS) for rGBM (OS-R and PFS-R) patients who received TBI+T were 18.9 and 10.7 months, respectively. In comparison, patients who received BBC+T treatment had OS-R and PFS-R of 11.8 (
> 0.05) and 4.7 (
< 0.05) months, respectively. Although the median PFS results were significantly different by 1.5 months (6.6 vs. 5.1) between TBI+T and BBC+T groups, the median OS difference of 14.7 months (32.5 vs. 17.8) was more pronounced,
< 0.05. Patients tolerated TBI+T or BBC+T treatments well and there were no unexpected toxicities. The most common side effects from TBI+T treatment included grade III hypertension (38.9%) and leukopenia (22.2%). In conclusion, the TBI regimen might play a role in the improvement of PFS-R and OS-R among rGBM patients. Prospective studies with a larger sample size are warranted to study the efficacy and toxicity of TBI+T regimen for rGBM.
The results of an experimental study conducted on specimens similar to ASTM G109 made with different types of cement and steel, and varying water/cement (w/c) ratios are reported in this paper. A ...portion of the top surface of the specimens was subjected to an exposure to 3% sodium chloride solution followed by an exposure to air, in cycles, for a large number of repetitions. Half-cell potential measurements were carried out periodically at the beginning of every exposure to chloride solution and also just prior to exposure to air, until a sudden drop in the potential was noticed. The average half-cell potential value of top steel bar, after sudden drop, is observed to be nearly the same, irrespective of steel, cement, and w/c ratio. However, corresponding free and total chloride concentrations, just after the preceding sudden drop, varied with experimental factors. The aforementioned sudden drop is also accompanied by reversal in the direction of current between top and bottom steel bars, indicated by a sign change in the potential difference. Thus, it is demonstrated that half-cell potential is a stable indicator of rebar corrosion initiation.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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