40,041 research outputs found
Novel 2-amino-5-benzylidenethiazol-4-one derivatives with SHP-2 inhibitory action. Potent drugs for the treatment patients with Noonan Syndrome and high tendency for leukemia.
No full textHeterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
2-THIAZOLYLIMINO/ HETEROARYLIMINO-5-ARYLIDENE-4-THIAZOLIDINONES AS NEW AGENTS WITH SHP-2 INHIBITORY ACTION
No full textSHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway. Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients. Moreover, SHP-2 mutations leading to continuously active enzyme were found in more than 50% of Noonan syndrome patients and are considered to be responsible for the high tendency of these patients to juvenile leukemias and other cancer types. Recently SHP-2 became a new drug target, but till now little has been done in this field. In the present study, 17 2-thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones divided into three series of derivatives bearing thiazole-, benzo[d]thiazole-, and benzo[d]isothizole rings were tested for SHP-2 inhibitory activity. Most of the compounds were good SHP-2 inhibitors. Benzo[d]thiazole derivatives exhibited the best inhibitory action. Docking studies revealed that hydrophobic interactions and hydrogen bond formation stabilize enzyme-inhibitor complex
Novel benzo[d]thiazolimino-5-aryliden-4-thiazolidinones as cycloxygenase/lipoxygenase inhibitors. Estimation of structure-activity relationship.
No full textWave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
Efficient Pipelined Execution of CNNs Based on In-Memory Computing and Graph Homomorphism Verification
No full textIn-memory computing is an emerging computing paradigm enabling deep-learning inference at significantly higher energy-efficiency and reduced latency. The essential idea is mapping the synaptic weights of each layer to one or more in-memory computing (IMC) cores. During inference, these cores perform the associated matrix-vector multiplications in place with O(1) time complexity, obviating the need to move the synaptic weights to additional processing units. Moreover, this architecture enables the execution of these networks in a highly pipelined fashion. However, a key challenge is designing an efficient communication fabric for the IMC cores. In this work, we present one such communication fabric based on a graph topology that is well-suited for the widely successful convolutional neural networks (CNNs). We show that this communication fabric facilitates the pipelined execution of all state-of-the-art CNNs by proving the existence of a homomorphism between the graph representations of these networks and that corresponding to the proposed communication fabric. We then present a quantitative comparison with established communication topologies and show that our proposed topology achieves the lowest bandwidth requirements per communication channel. Finally, we present one hardware implementation and show a concrete example of mapping ResNet-32 onto an IMC core array interconnected via the proposed communication fabric
E-book : Industrial Transformation In The Developing World (author: Michael T. Rock & David P. Angel)
No full textArsip Kuliah Online 2010: E-book : Industrial Transformation In The Developing World (author: Michael T. Rock & David P. Angel
Letter from Carl Hayden to P. J Moran
No full textLetter from Carl T. Hayden to P. J. Moran concerning the alignment of the road to Bright Angel Trail
E-book : "industrial Transformations In The Developing World (author: Michael T. Rock & David. P Angel)
No full textArsip Kuliah Online 2010: E-book : "industrial Transformations In The Developing World (author: Michael T. Rock & David. P Angel
Letter from P. J. Moran to Carl Hayden
No full textLetter from P. J. Moran to Carl T. Hayden inquiring when construction will begin on the approach road to Bright Angel Trai
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