Concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in soil, moss and reindeer dung collected at Ny-Ålesund of the Arctic were measured to investigate their accumulation trends and ...distribution in the three compartments. Compared with the other regions, the proportions of 2 + 3 ring PAHs to the total PAHs were higher, whereas the proportions of 5 + 6 ring PAHs were lower in the three compartments at Ny-Ålesund. Significant log/log-linear relationship was observed between the sub-cooled liquid vapor pressure
(
p
L
°
)
and the soil/moss quotient (
Q
SM). The relation was similar to the relationship between the gas/particle partition coefficient (
K
P) and
p
L
°
of PAHs, implying
Q
SM would be a “mirror image” of
K
P. Excellent log/log-linear relationships were observed between
Q
SM and
K
OA as well as between the moss/dung quotient (
Q
MD) and
K
OW. The results presented here indicate the physicochemical properties are suitable for characterizing the distribution of PAHs in soil, moss and reindeer dung.
The physicochemical properties of PAHs are suitable for characterizing their distribution in soil, moss and reindeer dung.
To optimize the flattening filter-free (FFF) beam selection in stereotactic body radiotherapy (SBRT) treatment for Stage I lung cancer in different fraction schemes.
Treatment plans from 12 patients ...suffering from Stage I lung cancer were designed using the 6XFFF and 10XFFF beams in different fraction schemes of 4 × 12, 3 × 18 and 1 × 34 Gy. Plans were evaluated mainly in terms of organs at risk (OARs) sparing, normal tissue complication probability (NTCP) estimation and treatment efficiency.
Compared with the 10XFFF beam, 6XFFF beam showed statistically significant lower dose to all the OARs investigated. The percentage of NTCP reduction for both lung and chest wall was about 10% in the fraction schemes of 4 × 12 and 3 × 18 Gy, whereas only 7.4% and 2.6% was obtained in the 1 × 34 Gy scheme. For oesophagus, heart and spinal cord, the reduction was greater with the 6XFFF beam, but their absolute estimates were <10(-6)%. The mean beam-on time for 6XFFF and 10XFFF beams at 4 × 12, 3 × 18 and 1 × 34 Gy schemes were 2.2 ± 0.2 vs 1.5 ± 0.1, 3.3 ± 0.9 vs 2.0 ± 0.5 and 6.3 ± 0.9 vs 3.5 ± 0.4 min, respectively.
The 6XFFF beam obtains better OARs sparing and lower incidence of NTCP in SBRT treatment of Stage I lung cancer, whereas the 10XFFF beam improves the treatment efficiency. To balance the OARs sparing and intrafractional variation owing to the prolonged treatment time, the authors recommend using the 6XFFF beam in the 4 × 12 and 3 × 18 Gy schemes but the 10XFFF beam in the 1 × 34 Gy scheme.
This study optimizes the FFF beam selection in different fraction schemes in SBRT treatment of Stage I lung cancer.
Bioluminescence imaging (BLI) using luciferase reporters is an indispensable method for the noninvasive visualization of cell populations and biochemical events in living animals. BLI is widely ...performed with preclinical rodent models to understand disease processes and evaluate potential cell- or gene-based therapies. However, in vivo BLI remains constrained by low photon production and tissue attenuation, limiting the sensitivity of reporting from small numbers of cells in deep locations and hindering its application to larger animal models. This Review highlights recent advances in the development of luciferase systems that improve the sensitivity of in vivo BLI and discusses the expanding array of biological applications.
We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that ...FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM).
Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay.
R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1β induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1β mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery.
R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.
Platinum resistance is a major obstacle in the treatment of epithelial ovarian cancer (EOC). Activation of the AKT pathway promotes platinum resistance while inhibition of AKT sensitizes ...chemoresistant cells. Patients with BRCA mutant EOC, and thus a defect in the homologous recombination (HR) repair pathway, demonstrate greater clinical response to platinum and olaparib therapy than patients with BRCA wild-type EOC. MK-2206, an allosteric inhibitor of AKT phosphorylation, sensitizes a variety of cell types to various anticancer agents and is currently undergoing phase II trials as monotherapy for platinum-resistant ovarian, fallopian tube, and peritoneal cancer. This study examines the differential effects of AKT inhibition with cisplatin and olaparib therapy in BRCA1/2-deficient versus wild-type EOC.
PEO1, a chemosensitive BRCA2-mutant serous ovarian adenocarcinoma, and PEO4, a reverted BRCA2-proficient line from the same patient after the development of chemotherapeutic resistance, were primarily used for the study. In PEO1, MK-2206 demonstrated moderate to strong synergism with cisplatin and olaparib at all doses, while demonstrating antagonism at all doses in PEO4.
Baseline phospho-AKT activity in untreated cells was upregulated in both BRCA1- and 2-deficient cell lines. MK-2206 prevented cisplatin- and olaparib-induced AKT activation in the BRCA2-deficient PEO1 cells. We propose that BRCA-deficient EOC cells upregulate baseline AKT activity to enhance survival in the absence of HR. Higher AKT activity is also required to withstand cytotoxic agent-induced DNA damage, leading to strong synergism between MK-2206 and cisplatin or olaparib therapy in BRCA-deficient cells.
MK-2206 shows promise as a chemosensitization agent in BRCA-deficient EOC and merits clinical investigation in this patient population.
The aims were to investigate the effects of gastric electrical stimulation (GES) on autonomic function, gastric distention and tone, and central control mechanisms in gastroparetic patients. Ten ...gastroparetic patients refractory to standard medical therapy participated in this study and data were collected at baseline, within two weeks before surgery for implantation of GES system, and at follow‐up sessions between 6 and 12 weeks after GES therapy was initiated. In each session, electrocardiogram, electrogastrogram (EGG) and gastric barostat measurements were conducted before and after a caloric liquid meal. Positron Emission Tomography (PET) brain scans were performed on a separate day. During GES therapy there was a significant increase in the discomfort threshold for mean pressure from 21 mmHg at baseline to 25 mmHg at follow‐up, and for mean volume from 561 mL to 713 mL. A significant increase in the postprandial EGG power (amplitude) was observed between baseline and follow up. The sympathovagal balance was significantly decreased after GES therapy, indicating a significant increase in vagal activity. The cumulative PET data showed an increase in quantitative radioactive counts relative to the standardized data base in both the thalamic and caudate nuclei after chronic GES therapy. We conclude that our data suggest that the symptomatic improvement achieved by GES in gastroparesis is best explained by activation of vagal afferent pathways to influence CNS control mechanisms for nausea and vomiting accompanied by enhanced vagal efferent autonomic function and decreased gastric sensitivity to volume distention which enhances postprandial gastric accommodation.
Summary
Background
Oxidative stress and low antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Pemphigus vulgaris (PV) is an extremely severe autoimmune ...bullous dermatosis characterized by intraepithelial bullae on the skin and mucosa, and its antioxidant status is not fully understood.
Aim
To assess correlations between PV and serum antioxidant levels of bilirubin, uric acid (UA) and albumin.
Methods
We enrolled 116 patients newly diagnosed with PV who were admitted to the First Affiliated Hospital of Guangxi Medical University (Guangxi, China), and 108 healthy controls (HCs). Clinical characteristics and laboratory parameters of patients were retrospectively analysed.
Results
Our survey shows that compared with the HC groups, serum levels of bilirubin total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil), UA and albumin were significantly lower in patients with PV, regardless of sex. In all groups, serum Tbil, Dbil, Ibil, UA and albumin levels were lower for women than for men. Severity of pemphigus was slightly negatively associated with Tbil, Dbil and Ibil, but was not associated with UA or albumin. Moreover, when the data were adjusted for the covariances of age and sex separately, Tbil, Dbil, Ibil, UA and albumin were all relevant to PV.
Conclusions
Our findings demonstrate that serum levels of bilirubin (Tbil, Dbil and Ibil), UA and albumin are reduced in patients with PV supporting the hypothesis that oxidative stress and antioxidant status are important in the pathogenic mechanism of PV.
We present a data‐driven method for automatically cropping photographs to be well‐composed and aesthetically pleasing. Our method matches the composition of an amateur's photograph to an expert's ...using point correspondences. The correspondences are based on a novel high‐level local descriptor we term the ‘Object Context’. Object Context is an extension of Shape Context: it is a descriptor encoding which objects and scene elements surround a given point. By searching a database of expertly composed images, we can find a crop window which makes an amateur's photograph closely match the composition of a database exemplar. We cull irrelevant matches in the database efficiently using a global descriptor which encodes the objects in the scene. For images with similar content in the database, we efficiently search the space of possible crops using generalized Hough voting. When comparing the result of our algorithm to expert crops, our crop windows overlap the expert crops by 83.6%. We also perform a user study which shows that our crops compare favourably to an expert humans' crops.
We present a data‐driven method for automatically cropping photographs to be well‐composed and aesthetically pleasing. Our method matches the composition of an amateur's photograph to an expert's using point correspondences. The correspondences are based on a novel high‐level local descriptor we term the ‘Object Context’. Object Context is an extension of Shape Context: it is a descriptor encoding which objects and scene elements surround a given point. By searching a database of expertly composed images, we can find a crop window which makes an amateur's photograph closely match the composition of a database exemplar. We cull irrelevant matches in the database efficiently using a global descriptor which encodes the objects in the scene.