FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model

Background: Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. Methods: Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)-a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo. Results: We show that FTY720 significantly suppressed MM cell viability and anchorage-independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity. Conclusions: Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment

Analysis of Drug Molecules in Living Cells

Cells are the fundamental units of life, comprising a highly concentrated and complex assembly of biomolecules that interact dynamic ally across spatial and temporal scales. Living cells are constantly undergoing dynamic processes, therefore, to understand the interactions between drug molecules and living cells is of paramount importance in the biomedical sciences and pharmaceutical development. Compared with traditional end-point assays and fixed cell analysis, analysis of drug molecules in living cells can provide more insight into the effects of drugs on cells in real-time and allowing for a better understanding of drug mechanisms and effects, which will contribute to the development of drug developing and testing and personalize medicine. However, the high demands of living cell analysis, including high costs, technical complexity, and throughput limitations, hinder the widespread application of this technology. In recent years, the rapid development of analytical methods such as Raman spectroscopy and fluorescence has made the in situ and real-time detection possible, allowing the analysis of single cell or cell populations at various conditions. In this review, we summarize the advanced analytical methods and technologies from last few years for drug detection in living cells

Studi Potensi Jumlah Penumpang Bus Pemadu Moda Rute Malang – Bandar Udara Juanda Pp

Bandar Udara Malang yang belum melayani banyak tujuan penerbangan membuat pengguna moda pesawat memilih Bandar Udara Juanda. Disisi lain angkutan yang melayani rute Malang-Juanda PP hanya angkutan travel. Untuk itu dibutuhkan moda lain yang lebih ekonomis dan memiliki kapasitas lebih banyak dibandingkan angkutan travel. Bus pemadu moda adalah moda alternatif yang dapat memenuhi kebutuhan tersebut.Pengumpulan data dilakukan dengan penyebaran kuisioner karakteristik sosial-ekonomi, karakteristik perjalanan serta kuisioner dengan teknik penyusunan stated preference. Stated preference memiliki atribut biaya perjalanan, waktu tempuh dan frekuensi keberangkatan. Sedangkan untuk prediksi tarif bus pemadu moda yang direncanakan diperoleh dari perhitungan BOK. Tarif yang telah diperoleh dari perhitungan BOK dibandingkan dengan nilai ATP dan WTP yang diperoleh dari kuisioner yang telah disebarkan. Sehingga didapatkan tarif ideal yang akan diberlakukan apabila bus pemadu moda tersebut direalisasikan.Setelah melakukan perhitungan tarif berdasarkan BOK diperoleh tarif sebesar Rp 23.374,- serta berdasarkan ATP dan WTP diperoleh tarif sebesar Rp 43.675,-. Dengan demikian perkiraan awal tarif bus pemadu moda sebesar Rp 40.000,- dapat diberlakukan. Hasil dari pemodelan pemilihan moda dengan metode stated preference untuk selisih biaya perjalanan Malang-Juanda: dan Juanda-Malang : , untuk selisih waktu tempuh perjalanan () rute Malang-Juanda : dan rute Juanda-Malang : , sedangkan untuk selisih Frekuensi Keberangkatan () rute Malang-Juanda : dan rute Juanda-Malang : .Potensi perpindahan pengguna travel ke bus pemadu moda rute Malang-Juanda sebanyak 705 orang per hari (83,97%). Sedangkan untuk rute Juanda-Malang sebanyak 1516 orang per hari (90,24%)

Influences of Coil Radius on Effective Transfer Distance in WPT System

The improvement of effective transfer distance is significant for wireless power transfer (WPT) via coupled magnetic resonances, with coil radius being the most important influencing factor. To study the relationship between effective transfer distance and coil radius, a model of WPT is established at first. Based on analyses of circuit and magnetic field, the influencing factors for effective transfer distance are obtained. Second, the models of WPT are constructed using software COMSOL, and the influences of Tx and Rx coil radius on the effective transfer distance are studied in detail. In addition, they are not proportional and the coil impedance is the most important factor. On this basis, a coil design method is proposed. Finally, an experiment device was built, and experimental results were well consistent with the theoretical analysis, showing the rationality and effectiveness of the proposed method

Identification of Blue Horizontal-Branch Stars From LAMOST DR5

We construct a new catalog of the blue horizontal-branch (BHB) stars from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) DR5 dataset, which contains 5355+81 BHB stars at high Galactic latitude (($|Glat|>20^{\circ}$). We combine the spectral line indices with a set of Balmer line profile selection criteria to identify the BHB stars. During the selection process, we use the line index of \ion{Ca}{2}\,K to exclude the metal-rich A-type dwarfs. We obtain their atmospheric parameters by cross-matching our BHB stars with the catalog provided by \citet{Xiang2022}. The results show that our sample is consistent with the theoretical $T_{\rm eff}$-log\,$g$ evolutionary tracks of the BHB stars, indicating that our method is robust for identifying BHB stars from the LAMOST spectra. Their spatial distribution indicates that most of our BHB stars are located in the inner halo or the disk of the Milky Way. Combined with other BHB samples from the literature, the BHB stars can cover a large Galactic volume, which makes it a better probe for studying the kinematics, dynamics, and structural characteristics of the Milky Way.Comment: accepted by ApJS.15 pages, 18 figure

OpenNDD: Open Set Recognition for Neurodevelopmental Disorders Detection

Neurodevelopmental disorders (NDDs) are a highly prevalent group of disorders and represent strong clinical behavioral similarities, and that make it very challenging for accurate identification of different NDDs such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Moreover, there is no reliable physiological markers for NDDs diagnosis and it solely relies on psychological evaluation criteria. However, it is crucial to prevent misdiagnosis and underdiagnosis by intelligent assisted diagnosis, which is closely related to the follow-up corresponding treatment. In order to relieve these issues, we propose a novel open set recognition framework for NDDs screening and detection, which is the first application of open set recognition in this field. It combines auto encoder and adversarial reciprocal points open set recognition to accurately identify known classes as well as recognize classes never encountered. And considering the strong similarities between different subjects, we present a joint scaling method called MMS to distinguish unknown disorders. To validate the feasibility of our presented method, we design a reciprocal opposition experiment protocol on the hybrid datasets from Autism Brain Imaging Data Exchange I (ABIDE I) and THE ADHD-200 SAMPLE (ADHD-200) with 791 samples from four sites and the results demonstrate the superiority on various metrics. Our OpenNDD has achieved promising performance, where the accuracy is 77.38%, AUROC is 75.53% and the open set classification rate is as high as 59.43%.Comment: 10 pages, 2 figure

The Characteristics of Sleep Apnea in Tibetans and Han Long-Term High Altitude Residents

Purpose: Obstructive sleep apnea (OSA) is common both at low and high altitude. Since adaptations to high altitude and respiratory control may differ among Tibetans and Hans, we compared characteristics of sleep-disordered breathing in the two ethnic groups at high altitude. Materials and methods: This was a prospective observational study including 86 Tibetan and Han long-term (>5 years) high altitude residents with chief complaints of snoring and/or witnessed apnea underwent clinical evaluation and polysomnography at 3200 meters in Shangri-La, China. Results: In 42 Tibetans, 38 men, median (quartiles) age was 50.0 (41.0; 56.0)y, total apnea/hypopnea index (AHI) 53.9 (32.0; 77.5)/h, obstructive AHI 51.0 (28.0; 72.2)/h and central AHI 1.5 (0.2; 3.1)/h. In 44 Hans, 32 men, median (quartiles) age was 47.0 (43.5; 51.0)y, total AHI 22.2 (12.8; 39.2)/h, obstructive AHI 17.7 (12.0; 33.0)/h and central AHI 2.4 (0.5; 3.4)/h (p < 0.001 total and obstructive AHI vs Tibetans). In Tibetans, mean nocturnal oxygen saturation was lower [median 85.0 (83.0; 88.0)% vs 88.5 (87.0; 90.0)%] and obstructive apnea and hypopnea duration was longer [22.0 (19.6; 24.8) sec vs 18.3 (16.7; 20.6) sec] than in Hans (all p < 0.001). In regression analysis, Tibetan ethnicity, neck circumference and high-altitude living duration were the predictors of total AHI. We also found that with every 10/h increase in total AHI, there were an approximately 0.9 beat/min and 0.8 beat/min increase in mean heart rate during rapid eye movement (REM) and non-REM sleep and 1.9 mmHg and 2.0 mmHg increase in evening and morning systolic blood pressure. Conclusion: Our data suggest that Tibetans presented more severe obstructive sleep apnea, hypoxemia and longer apnea duration compared to Hans at 3200 meters, which was correlated with higher heart rate and blood pressure suggesting a greater cardiovascular risk. Keywords: Tibetan; high altitude; long-term Han resident; obstructive sleep apnea