7,623 research outputs found
Overcoming Barriers to Efficiency
The article discusses factors that hinder the installation of high-performance heating, ventilation and air conditioning (HVAC) equipment in commercial and residential buildings in the United States. For owner-occupied buildings, the utility and capital expenses are ultimately included in one corporate budget. Thus, decision processes become a justification of any additional expense for higher performing equipment relative to the expected returns via lower energy costs. In an existing building, business management principles determine the evaluation process. Certain economic factors apply regardless of building ownership. For example, a cost is associated with the information gathering process for new technology or obtaining information relevant to current resource use. This is primarily a direct expense in the form of employee salaries or consultant fees. INSET: Sustainable HVAC for Modular Classrooms
Acetyl-L-carnitine is an anti-angiogenic agent targeting the VEGFR2 and CXCR4 pathways
Carnitines play an important role in the energy exchange in cells, involved in the transport
of fatty acids across the inner mitochondrial membrane. L-Acetylcarnitine (ALCAR) is an acetic
acid ester of carnitine that has higher bioavailability than carnitine and is considered a fat-burning
energizer supplement. We previously found that in serum samples from prostate cancer (PCa)
patients, 3 carnitine family members were significantly decreased, suggesting a potential protective
role of carnitine against PCa. Several studies support beneficial effects of carnitines on cancer, no
study has investigated the activities of carnitine on tumor angiogenesis.
We examined whether ALCAR act as an \u201cangiopreventive\u201d compound and studied the
molecular mechanisms involved. We found that ALCAR was able to limit inflammatory
angiogenesis by reducing stimulated endothelial cell and macrophage infiltration in vitro and in
vivo. Molecularly, we showed that ALCAR downregulates VEGF, VEGFR2, CXCL12, CXCR4
and FAK pathways. ALCAR blocked the activation of NF-\u3baB and ICAM-1 and reduced the
adhesion of a monocyte cell line to endothelial cells. This is the first study showing that ALCAR
has anti-angiogenesis and anti-inflammatory properties and might be attractive candidate for cancer
angiopreventionCarnitines play an important role in the energy exchange in cells, and are involved in the transport of fatty acids across the inner mitochondrial membrane. L-Acetylcarnitine (ALCAR) is an acetic acid ester of carnitine that has higher bioavailability and is considered a fat-burning energizer supplement. We previously found that in serum samples from prostate cancer (PCa) patients, 3 carnitine family members were significantly decreased, suggesting a potential protective role of carnitine against PCa. Several studies support beneficial effects of carnitines on cancer, no study has investigated the activities of carnitine on tumor angiogenesis. We examined whether ALCAR acts as an \u201cangiopreventive\u201d compound and studied the molecular mechanisms involved. We found that ALCAR was able to limit inflammatory angiogenesis by reducing stimulated endothelial cell and macrophage infiltration in vitro and in vivo. Molecularly, we show that ALCAR downregulates VEGF, VEGFR2, CXCL12, CXCR4 and FAK pathways. ALCAR blocked the activation of NF-\u3baB and ICAM-1 and reduced the adhesion of a monocyte cell line to endothelial cells. This is the first study showing that ALCAR has anti-angiogenic and anti-inflammatory properties and might be an attractive candidate for cancer angioprevention
Surface activated chemical ionization - Electrospray mass spectrometry in the analysis of urinary thiodiglycolic acid
RATIONALE
Thiodiglycolic acid (TDGA) is a urinary metabolite of the oxazaphosphorine class of chemotherapeutics, in particular of ifosfamide. Ifosfamide metabolism generates chloroacetaldehyde (CAA), a toxic compound associated with neurotoxicity, nephrotoxicity, urotoxicity and cardiotoxicity. CAA, in turn, interacts with cellular thiol groups leading to GSH depletion, cell death and generation of thiodiglycolic acid (TDGA), as a final product. TDGA is mainly excreted in the urine. The ability to accurately measure TDGA in urine, therefore, will be a useful way of monitoring the ifosfamide exposure during chemotherapy.
METHODS
TDGA in urine samples was measured with liquid chromatograpy coupled to mass spectrometry (LC-MS) by means of a novel Surface Activated Chemical Ionization - Electrospray (SACI-ESI) or a classical ESI ion source alone.
RESULTS
The SACI - ESI and ESI alone based methods for analysis of urinary TDGA were optimized and compared. A strong reduction in matrix effect together with enhanced quantification performances was obtained with the SACI \u2013 ESI when compared with the ESI. In particular, an increase in quantification precision (from 85 to 95%) and accuracy (from 59 to 90%) were observed, which allowed for optimal detection of TDGA.
CONCLUSIONS
The LC-SACI-ESI-MS approach provides a very sensitive and quantitative method for the analysis of TDGA. Thanks to sensitivity enhancement and matrix effect reduction, the SACI \u2013 ESI enables the use of a relatively low cost ion-trap mass spectrometer in the analysis of this toxicity biomarker in urine. Due to these characteristics, this approach would constitutes an invaluable tool in the clinical laboratory, for measuring TDGA and other toxicity related biomarkers of chemotherapy with proper sensitivity and accuracy
RNASET2 as a tumor antagonizing gene in a melanoma cancer model
The RNASET2 gene, mapped in 6q27, was previously found to exert control of tumorigenesis in an ovarian cancer system. We present here results indicating a similar control in a melanoma cancer model. Thus, this gene is most likely involved in a common general pathway of tumorigenesis. Moreover, its antitumorigenic activity is manifested in vivo but not in vitro, suggesting that this gene belongs to the growing category of tumor antagonizing/malignancy suppressor genes. A possible role of RNASET2 in the activation of a senescence program, whose responsible locus was mapped in the same chromosomal 6q27 region, seems to be inconsistent with our data
The Nature and Frequency of the Gas Outbursts in Comet 67P/Churyumov-Gerasimenko observed by the Alice Far-ultraviolet Spectrograph on Rosetta
Alice is a far-ultraviolet imaging spectrograph onboard Rosetta that, amongst
multiple objectives, is designed to observe emissions from various atomic and
molecular species from within the coma of comet 67P/Churyumov-Gerasimenko. The
initial observations, made following orbit insertion in August 2014, showed
emissions of atomic hydrogen and oxygen spatially localized close to the
nucleus and attributed to photoelectron impact dissociation of H2O vapor.
Weaker emissions from atomic carbon were subsequently detected and also
attributed to electron impact dissociation, of CO2, the relative H I and C I
line intensities reflecting the variation of CO2 to H2O column abundance along
the line-of-sight through the coma. Beginning in mid-April 2015, Alice
sporadically observed a number of outbursts above the sunward limb
characterized by sudden increases in the atomic emissions, particularly the
semi-forbidden O I 1356 multiplet, over a period of 10-30 minutes, without a
corresponding enhancement in long wavelength solar reflected light
characteristic of dust production. A large increase in the brightness ratio O I
1356/O I 1304 suggests O2 as the principal source of the additional gas. These
outbursts do not correlate with any of the visible images of outbursts taken
with either OSIRIS or the navigation camera. Beginning in June 2015 the nature
of the Alice spectrum changed considerably with CO Fourth Positive band
emission observed continuously, varying with pointing but otherwise fairly
constant in time. However, CO does not appear to be a major driver of any of
the observed outbursts.Comment: 6 pages, 4 figures, accepted for publication in the Astrophysical
Journal Letter
A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity
Cardiovascular toxicity remains one of the most adverse side effects in cancer patients receiving chemotherapy. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, anti-oxidant activities which could exert protective effects on heart cells. One very interesting derivative of EVOO preparation is represented by purified extracts from olive mill waste waters (OMWW) rich in polyphenols. Here, we have investigated the anti-cancer activity of a OMWW preparation, named A009, when combined with chemotherapeutics, as well as its potential cardioprotective activities. Mice bearing prostate cancer (PCa) xenografts were treated with cisplatin, alone or in combination with A009. In an in vivo model, we found synergisms of A009 and cisplatin in reduction of prostate cancer tumor weight. Hearts of mice were analyzed, and the mitochondria were studied by transmission electron microscopy. The hearts of mice co-treated with A009 extracts along with cisplatin had reduced mitochondria damage compared to the those treated with chemotherapy alone, indicating a cardioprotective role. To confirm the in vivo results, tumor cell lines and rat cardiomyocytes were treated with cisplatin in vitro, with and without A009. Another frequently used chemotherapeutic agent 5-fluorouracil (5-FU), was also tested in this assay, observing a similar effect. In vitro, the combination of A009 with cisplatin or 5-FU was effective in decreasing prostate and colon cancer cell growth, while it did not further reduce growth of rat cardiomyocytes also treated with cisplatin or 5-FU. A009 cardioprotective effects towards side effects caused by 5-FU chemotherapy were further investigated, using cardiomyocytes freshly isolated from mice pups. A009 mitigated toxicity of 5-FU on primary cultures of mouse cardiomyocytes. Our study demonstrates that the polyphenol rich purified A009 extracts enhance the effect of chemotherapy in vitro and in vivo, but mitigates chemotherpy adverse effects on heart and on isolated cardiomyocytes. Olive mill waste water extracts could therefore represent a potential candidate for cardiovascular prevention in patients undergoing cancer chemotherapy
The Effect of Agricultural Practices on a Dairy Farm on Nitrate Leaching to 1m
Dairy farms, in Ireland, carry the highest stock densities and use the highest rates of fertiliser nitrogen (N). They constitute the highest risk of nitrate leaching, especially where soils are thin or free-draining. The effect of 4 grass managements on leaching was studied on a dairy farm having free-draining soils overlying Karst limestone. This was a new, farm-comprehensive approach to nitrate leaching which had not been carried out previously
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Cytogenetic and Array-CGH Characterization of a Complex de novo Rearrangement Involving Duplication and Deletion of 9p and Clinical Findings in a 4-Month-Old Female
Approximately 15 patients with partial trisomy 9p involving de novo duplications have been previously described. Here, we present clinical, cytogenetic, FISH and aCGH findings in a patient with a de novo complex rearrangement in the short arm of chromosome 9 involving an inverted duplication at 9p24→p21.3 and a deletion at 9pter→p24.2. FISH probes generated from BACs selected from the UCSC genome browser were utilized to verify this rearrangement. It is likely that some previously described duplications of 9p may also be products of complex chromosomal aberrations. This report in which FISH and aCGH were used to more comprehensively characterize the genomic rearrangement in a patient with clinical manifestations of 9p duplication syndrome underscores the importance of further characterizing cytogenetically detected rearrangements
Response to comment on "Human-specific gain of function in a developmental enhancer"
Duret and Galtier argue that human-specific sequence divergence and gain of function in the HACNS1 enhancer result from deleterious biased gene conversion (BGC) with no contribution from positive selection. We reinforce our previous conclusion by analyzing hypothesized BGC
events genomewide and assessing the effect of recombination rates on human-accelerated conserved noncoding sequence ascertainment. We also provide evidence that AT → GC substitution bias can coexist with positive selection
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