325 research outputs found
Real time detection of in vitro tumor cell apoptosis induced by CD8+ T cells to study immune suppressive functions of tumor-infiltrating myeloid cells
Obliquity of an Earth-like planet from frequency modulation of its direct imaged lightcurve: mock analysis from general circulation model simulation
Direct-imaging techniques of exoplanets have made significant progress
recently, and will eventually enable to monitor photometric and spectroscopic
signals of earth-like habitable planets in the future. The presence of clouds,
however, would remain as one of the most uncertain components in deciphering
such direct-imaged signals of planets. We attempt to examine how the planetary
obliquity produce different cloud patterns by performing a series of GCM
(General Circulation Model) simulation runs using a set of parameters relevant
for our Earth. Then we use the simulated photometric lightcurves to compute
their frequency modulation due to the planetary spin-orbit coupling over an
entire orbital period, and attempt to see to what extent one can estimate the
obliquity of an Earth-twin. We find that it is possible to estimate the
obliquity of an Earth-twin within the uncertainty of several degrees with a
dedicated 4 m space telescope at 10 pc away from the system if the stellar flux
is completely blocked. While our conclusion is based on several idealized
assumptions, a frequency modulation of a directly-imaged earth-like planet
offers a unique methodology to determine its obliquity.Comment: 29 pages, 18 figures, accepted for publication in Ap
Adenoid cystic carcinoma of the peripheral lung: a case report
Adenoid cystic carcinoma of the peripheral lung is a rare entity. We recently encountered a patient with adenoid cystic carcinoma. A 75-year-old woman showed a nodular lesion with 10 mm in diameter in the right upper lung field on chest radiography. The diagnosis was unclear, but lung cancer could not be ruled out. Thoracoscopic biopsy was performed, and intraoperative pathological diagnosis revealed the carcinoma of the lung. We enforced upper lobectomy and mediastinal lymph node dissection to the patient. Histopathological examination revealed adenoid cystic carcinoma with a characteristic cribriform structure. Immunohistochemical examination revealed that the tumor cells were positive for thyroid transcription factor 1 (TTF-1), this tumor was diagnosed primary ACC of the lung
DirectLiNGAM: A Direct Method for Learning a Linear Non-Gaussian Structural Equation Model
Structural equation models and Bayesian networks have been widely used to analyze causal relations between continuous variables. In such frameworks, linear acyclic models are typically used to model the data-generating process of variables. Recently, it was shown that use of non-Gaussianity identifies the full structure of a linear acyclic model, i.e., a causal ordering of variables and their connection strengths, without using any prior knowledge on the network structure, which is not the case with conventional methods. However, existing estimation methods are based on iterative search algorithms and may not converge to a correct solution in a finite number of steps. In this paper, we propose a new direct method to estimate a causal ordering and connection strengths based on non-Gaussianity. In contrast to the previous methods, our algorithm requires no algorithmic parameters and is guaranteed to converge to the right solution within a small fixed number of steps if the data strictly follows the model
A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies
Immunotherapy promotes the attack of cancer cells by the immune system; however, it is difficult to detect early responses before changes in tumor size occur. Here, we report the rational design of a fluorogenic peptide able to detect picomolar concentrations of active granzyme B as a biomarker of immune-mediated anticancer action. Through a series of chemical iterations and molecular dynamics simulations, we synthesize a library of FRET peptides and identify probe H5 with an optimal fit into granzyme B. We demonstrate that probe H5 enables the real-time detection of T cell-mediated anticancer activity in mouse tumors and in tumors from lung cancer patients. Furthermore, we show image-based phenotypic screens, which reveal that the AKT kinase inhibitor AZD5363 shows immune-mediated anticancer activity. The reactivity of probe H5 may enable the monitoring of early responses to anticancer treatments using tissue biopsies
Structure and Engineering of Francisella novicida Cas9
Summary The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 Å resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5′-NGG-3′ PAM, and used the structural information to create a variant that can recognize the more relaxed 5′-YG-3′ PAM. Furthermore, we demonstrated that the FnCas9-ribonucleoprotein complex can be microinjected into mouse zygotes to edit endogenous sites with the 5′-YG-3′ PAM, thus expanding the target space of the CRISPR-Cas9 toolbox
The Obesity and Fatty Liver Are Reduced by Plant-Derived Pediococcus pentosaceus LP28 in High Fat Diet-Induced Obese Mice
We evaluated the effect of an oral administration of a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), on metabolic syndrome by using high fat diet-induced obese mice. The obese mice were divided into 2 groups and fed either a high fat or regular diet for 8 weeks. Each group was further divided into 3 groups, which took LP28, another plant-derived Lactobacillus plantarum SN13T (SN13T) or no lactic acid bacteria (LAB). The lean control mice were fed a regular diet without inducing obesity prior to the experiment. LP28 reduced body weight gain and liver lipid contents (triglyceride and cholesterol), in mice fed a high fat diet for 8 weeks (40%, 54%, and 70% less than those of the control group without LAB, and P = 0.018, P<0.001, and P = 0.021, respectively), whereas SN13T and the heat treated LP28 at 121°C for 15 min were ineffective. Abdominal visceral fat in the high fat diet mice fed with LP28 was also lower than that without LAB by 44%, although it was not significant but borderline (P = 0.076). The sizes of the adipocytes and the lipid droplets in the livers were obviously decreased. A real-time PCR analyses showed that lipid metabolism-related genes, such as CD36 (P = 0.013), SCD1 encoding stearoyl-CoA desaturase 1 (not significant but borderline, P = 0.066), and PPARγ encoding peroxisome proliferator-activated receptor gamma (P = 0.039), were down-regulated by taking LP28 continuously, when compared with those of the control group. In conclusion, LP28 may be a useful LAB strain for the prevention and reduction of the metabolic syndrome
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