MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer.

Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-587 modulates drug resistance through downregulation of expression of PPP2R1B, a regulatory subunit of the PP2A complex, which negatively regulates AKT activation. Knockdown of PPP2R1B expression increases AKT phosphorylation, which leads to elevated XIAP expression and enhanced 5-FU resistance; whereas rescue of PPP2R1B expression in miR-587-expressing cells decreases AKT phosphorylation/XIAP expression, re-sensitizing colon cancer cells to 5-FU-induced apoptosis. Moreover, a specific and potent AKT inhibitor, MK2206, reverses miR-587-conferred 5-FU resistance. Importantly, studies of colorectal cancer specimens indicate that the expression of miR-587 and PPP2R1B positively and inversely correlates with chemoresistance, respectively, in colorectal cancer. These findings indicate that the miR-587/PPP2R1B/pAKT/XIAP signaling axis has an important role in mediating response to chemotherapy in colorectal cancer. A major implication of our study is that inhibition of miR-587 or restoration of PPP2R1B expression may have significant therapeutic potential to overcome drug resistance in colorectal cancer patients and that the combined use of an AKT inhibitor with 5-FU may increase efficacy in colorectal cancer treatment

Ultrathin MgB2 films fabricated on Al2O3 substrate by hybrid physical-chemical vapor deposition with high Tc and Jc

Ultrathin MgB2 superconducting films with a thickness down to 7.5 nm are epitaxially grown on (0001) Al2O3 substrate by hybrid physical-chemical vapor deposition method. The films are phase-pure, oxidation-free and continuous. The 7.5 nm thin film shows a Tc(0) of 34 K, which is so far the highest Tc(0) reported in MgB2 with the same thickness. The critical current density of ultrathin MgB2 films below 10 nm is demonstrated for the first time as Jc ~ 10^6 A cm^{-2} for the above 7.5 nm sample at 16 K. Our results reveal the excellent superconducting properties of ultrathin MgB2 films with thicknesses between 7.5 and 40 nm on Al2O3 substrate.Comment: 7 pages, 4 figures, 2 table

Rethinking Knowledge Graph Propagation for Zero-Shot Learning

Graph convolutional neural networks have recently shown great potential for the task of zero-shot learning. These models are highly sample efficient as related concepts in the graph structure share statistical strength allowing generalization to new classes when faced with a lack of data. However, multi-layer architectures, which are required to propagate knowledge to distant nodes in the graph, dilute the knowledge by performing extensive Laplacian smoothing at each layer and thereby consequently decrease performance. In order to still enjoy the benefit brought by the graph structure while preventing dilution of knowledge from distant nodes, we propose a Dense Graph Propagation (DGP) module with carefully designed direct links among distant nodes. DGP allows us to exploit the hierarchical graph structure of the knowledge graph through additional connections. These connections are added based on a node's relationship to its ancestors and descendants. A weighting scheme is further used to weigh their contribution depending on the distance to the node to improve information propagation in the graph. Combined with finetuning of the representations in a two-stage training approach our method outperforms state-of-the-art zero-shot learning approaches.Comment: The first two authors contributed equally. Code at https://github.com/cyvius96/adgpm. To appear in CVPR 201

End-to-End Modeling Hierarchical Time Series Using Autoregressive Transformer and Conditional Normalizing Flow based Reconciliation

Multivariate time series forecasting with hierarchical structure is pervasive in real-world applications, demanding not only predicting each level of the hierarchy, but also reconciling all forecasts to ensure coherency, i.e., the forecasts should satisfy the hierarchical aggregation constraints. Moreover, the disparities of statistical characteristics between levels can be huge, worsened by non-Gaussian distributions and non-linear correlations. To this extent, we propose a novel end-to-end hierarchical time series forecasting model, based on conditioned normalizing flow-based autoregressive transformer reconciliation, to represent complex data distribution while simultaneously reconciling the forecasts to ensure coherency. Unlike other state-of-the-art methods, we achieve the forecasting and reconciliation simultaneously without requiring any explicit post-processing step. In addition, by harnessing the power of deep model, we do not rely on any assumption such as unbiased estimates or Gaussian distribution. Our evaluation experiments are conducted on four real-world hierarchical datasets from different industrial domains (three public ones and a dataset from the application servers of Alipay's data center) and the preliminary results demonstrate efficacy of our proposed method

Development of an incoherent broad-band cavity-enhanced aerosol extinction spectrometer and its application to measurement of aerosol optical hygroscopicity

We report on the development of a blue light-emitting-diode-based incoherent broad-band cavity-enhanced absorption spectroscopy (IBBCEAS) instrument for the measurement of the aerosol extinction coefficient at \u1d706=461  nm. With an effective absorption path length of 2.8 km, an optimum detection limit of 0.05  Mm−1 (5×10−10  cm−1) was achieved with an averaging time of 84 s. The baseline drift of the developed spectrometer was about ±0.3  Mm−1 over 2.5 h (1\u1d70e standard deviation). The performance of the system was evaluated with laboratory-generated monodispersed polystyrene latex (PSL) spheres. The retrieved complex refractive index of PSL agreed well with previously reported values. The relative humidity (RH) dependence of the aerosol extinction coefficient was measured using IBBCEAS. The measured extinction enhancement factor values for 200 nm dry ammonium sulphate particles at different RH were in good agreement with the modeled values. Field performance of the aerosol extinction spectrometer was demonstrated at the Hefei Radiation Observatory site

Research progress and development tendency of polymer drilling fluid technology for unconventional gas drilling

Unconventional gas includes tight sandstone gas, shale gas, coalbed methane, and natural gas hydrate. With huge reserves, unconventional gas has become the most important natural gas resource successor after the end of the “Easy Oil era.” The drilling fluid is an indispensable wellbore working fluid for unconventional gas drilling with multiple functions. The polymer drilling fluid (PDF) is the most common, longest developed, and most diverse drilling fluid type. With advantages of easily controlled rheology, convenient on-site performance maintenance, and specifically low cost and weak environment pollution, the PDF is gradually replacing the oil-based drilling fluid as the first choice for unconventional gas drilling. The invention of the non-disperse low-solid-content PDF in the 1960s shows that PDF technology has entered the stage of scientific development, and until now, its development has generally experienced five stages: beginning, developing, improving, re-developing, and re-improving. Dozens of polymer additives and PDF systems have been invented and applied, which have solved severe drilling problems, greatly improved drilling efficiency, and promoted exploration and development in difficult oil and gas resources. This paper first reviews the research progress of PDF technology according to the timeline by introducing the composition, feature, advantages, and disadvantages of some representative polymer additives and PDF systems, emphatically the function and mechanism of stabilizing wellbores, lubricating drilling tools, and protecting reservoirs of the biomimetic wellbore-strengthening PDF and amphiphobic high-efficiency PDF in unconventional gas drilling. Then, combining future global demands, especially China’s strategic needs of oil and gas exploration and development, the development tendency of PDF technology is critically illustrated by introducing several potential research directions including intelligent PDF, ecological PDF, and PDF for natural gas hydrate and deep layer gas resources

Konferencija Što činimo po pitanju transparentnosti

Additional file 2: Figure S2. PCR and phenotypic analysis of the Δcre1 strain T. reesei SDC11. a PCR analysis of T. reesei SDC11 with SP4 as control. 1 and 2 represent the fragment (upstream region and open reading frame of gene cre1) amplificated by the prime pair cre1-2426UF/cre1-1069R in T. reesei SDC11 and SP4, respectively; 3 and 4 represent the internal fragment of gene cre1 amplificated by the prime pair cre1-497F/cre1-1069R in T. reesei SDC11 and SP4, respectively. 5 and 6 represent the fragment of gene pyrG amplificated by the prime pair pyrG-UF1/pyrG-2426DR in T. reesei SDC11 and SCP11, respectively. b Southern blot analysis of the genomic DNA isolated from SP4 and SCP11, which were digested with EcoRI/HindIII. A 5.5-kb fragment is present in the parental strain SP4, and a 7.0-kb band is shown in Δcre1 + pyrG strain SCP11. c Growth of T. reesei SN1, Δcre1 + pyrG strain SCP11 and Δcre1 strain SDC11 on MM plate. d Growth of T. reesei SP4, Δcre1 + pyrG strain SCP11 and Δcre1 strain SDC11 on the MM plate containing uracil (0.1%)

Gastrodin Rescues Autistic-Like Phenotypes in Valproic Acid-Induced Animal Model

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized by impaired social interaction, restricted/repetitive behavior, and anxiety. GABAergic dysfunction has been postulated to underlie these autistic symptoms. Gastrodin is widely used clinically in the treatment of neurological disorders and showed to modulate GABAergic signaling in the animal brain. The present study aimed to determine whether treatment with gastrodin can rescue valproic acid (VPA) induced autistic-like phenotypes, and to determine its possible mechanism of action. Our results showed that administration of gastrodin effectively alleviated the autistic-associated behavioral abnormalities as reflected by an increase in social interaction and decrement in repetitive/stereotyped behavior and anxiety in mice as compared to those in untreated animals. Remarkably, the amelioration in autistic-like phenotypes was accompanied by the restoration of inhibitory synaptic transmission, α5 GABAA receptor, and type 1 GABA transporter (GAT1) expression in the basolateral amygdala (BLA) of VPA-treated mice. These findings indicate that gastrodin may alleviate the autistic symptoms caused by VPA through regulating GABAergic synaptic transmission, suggesting that gastrodin may be a potential therapeutic target in autism