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1.
Non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) mutations has notoriously challenged oncologists and researchers for three notable reasons: (1) the historical assumption that KRAS is “undruggable”, (2) the disease heterogeneity and (3) the shaping of the tumor microenvironment by KRAS downstream effector functions. Better insights into KRAS structural biochemistry allowed researchers to develop direct KRAS(G12C) inhibitors, which have shown early signs of clinical activity in NSCLC patients and have recently led to an FDA breakthrough designation for AMG-510. Following the approval of immune checkpoint inhibitors for PDL1-positive NSCLC, this could fuel yet another major paradigm shift in the treatment of advanced lung cancer. Here, we review advances in our understanding of the biology of direct KRAS inhibition and project future opportunities and challenges of dual KRAS and immune checkpoint inhibition. This strategy is supported by preclinical models which show that KRAS(G12C) inhibitors can turn some immunologically “cold” tumors into “hot” ones and therefore could benefit patients whose tumors harbor subtype-defining STK11/LKB1 co-mutations. Forty years after the discovery of KRAS as a transforming oncogene, we are on the verge of approval of the first KRAS-targeted drug combinations, thus therapeutically unifying Paul Ehrlich’s century-old “magic bullet” vision with Rudolf Virchow’s cancer inflammation theory. 相似文献
2.
In clustering algorithm, one of the main challenges is to solve the global allocation of the clusters instead of just local tuning of the partition borders. Despite this, all external cluster validity indexes calculate only point-level differences of two partitions without any direct information about how similar their cluster-level structures are. In this paper, we introduce a cluster level index called centroid index. The measure is intuitive, simple to implement, fast to compute and applicable in case of model mismatch as well. To a certain extent, we expect it to generalize other clustering models beyond the centroid-based k-means as well. 相似文献
3.
Traditional approach to clustering is to fit a model (partition or prototypes) for the given data. We propose a completely opposite approach by fitting the data into a given clustering model that is optimal for similar pathological data of equal size and dimensions. We then perform inverse transform from this pathological data back to the original data while refining the optimal clustering structure during the process. The key idea is that we do not need to find optimal global allocation of the prototypes. Instead, we only need to perform local fine-tuning of the clustering prototypes during the transformation in order to preserve the already optimal clustering structure. 相似文献
4.
Thomas Canhao XuAuthor Vitae Alexander Wei YinAuthor Vitae Pasi LiljebergAuthor Vitae Hannu TenhunenAuthor Vitae 《Microprocessors and Microsystems》2011,35(7):603-612
In this paper, we implement, analyze and compare different Network-on-Chip (NoC) architectures aiming at higher efficiencies for MPEG-4/H.264 coding. Two-dimensional (2D) and three-dimensional (3D) NoCs based on Non-Uniform Cache Access (NUCA) are analyzed. We present results using a full system simulator with realistic workloads. Experiments show the average network latencies in two 3D NoCs are reduced by 28% and 34% respectively, comparing with 2D design. It is also shown that heat dissipation is a trade-off in improving performance of 3D chips. Our analysis and experiment results provide a guideline to design efficient 3D NoCs for data parallel H.264 coding applications. 相似文献
5.
Jyrki Kimmel Tapani Levola Pasi Laakkonen 《Journal of the Society for Information Display》2008,16(8):863-870
Abstract— The display backlight unit (BLU) is the most power‐consuming subunit in mobile liquid‐crystal displays. The state‐of‐the‐art BLUs utilize scattering, refractive, and reflective microstructures to generate a uniform distribution of white light through the display. More effective means of transmitting light through the display color filters could be obtained by using diffraction, but previously proposed diffractive backlights do not fully utilize all the possibilities to design gratings effectively for optimal color separation and outcoupling. This paper presents a new pixelated diffractive backlight grating array as an approach for overcoming these obstacles in BLU design. A model array was fabricated to couple out red, green, and blue primary colors from the respective subpixel locations. The results show that it is possible to manufacture such an array and that the light couples out as intended, giving a starting point to design mobile‐display modules with low light‐transmission losses. 相似文献
6.
Heikki Ailisto Lauri Pohjanheimo Pasi Välkkynen Esko Strömmer Timo Tuomisto Ilkka Korhonen 《Personal and Ubiquitous Computing》2006,10(6):333-344
The prevalent visions of ambient intelligence emphasise natural interaction between user and functions and services embedded in the environment or available through mobile devices. In these scenarios the physical and virtual worlds seamlessly gear into each other, making crossing the border between these worlds natural or even invisible to the user. The bottleneck in reaching these scenarios appear in the natural mapping between the physical objects and their virtual counterparts. The emergence of local connectivity in mobile devices opens possibilities for implementing novel user interface paradigms to enhance this mapping. We present physical selection paradigm for implementing an intuitive human technology interaction for mobile devices. In order to demonstrate the feasibility of the paradigm we implemented two experimental set-ups using commercially available smart phones with IrDA connectivity. The experiments involved selecting a website by physically pointing at its symbol and making a phone call by pointing at an icon representing the person to be called. In tentative user experiments the physical selection method was more time-efficient and it was perceived more positively by the users than a conventional method.
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Heikki AilistoEmail: |
7.
Jouni Isoaho Vesa Köppä Jarkko Oksala Pasi OjalaAuthor vitae 《Microprocessors and Microsystems》1997,20(10):2330-615
The BOAR emulation system is targeted to hardware/software (HW/SW) codevelopment of advanced embedded DSP and telecom systems. The challenge of the BOAR system is efficient customization of programmable hardware, and dedicated partitioning routine to target applications and structures, which allows quite high overall system performance. The system allows multiple configurations for communication between processors and field programmable gate arrays (FPGAs) making the BOAR system an efficient tool for real-time HW/SW coverification. The reprogrammable hardware of the emulation tool is based on four Xilinx 4000-series devices, two Texas TMS320C50 signal processors and one Motorola MC68302 microcontroller. With current devices the BOAR hardware provides approximately 40–70 kgates of logic capacity in DSP applications. The emulation capacity can be expanded by connecting several similar boards in chain. The system has also a versatile internal reprogrammable test environment for test bench development, performance evaluations and design debugging. The logic development environment is based on the Synopsys synthesis tools and an automatic design management software, which performs resource mapping and performance-driven design partitioning between FPGAs. The emulation hardware is currently connected to logic and software development environments via an RS-232C bus. The BOAR emulation system has been found a very efficient platform for real-life prototyping of different types of DSP algorithms and systems, and validating correct functionality of a VHDL macro library. 相似文献
8.
The crystallography of martensite formed in 0.2C-2.0Mn-1.5Si-0.6Cr steel was studied using the electron backscattered diffraction(EBSD) technique.The results showed that the observed orientation relationship(OR) was closer to that of Nishiyama-Wassermann(N-W) than Kurdjumov-Sachs.The martensite consisted of parallel laths forming morphological packets.Typically,there were three different lath orientations in a morphological packet consisting of three specific N-W OR variants sharing the same {111} austenite plane.A packet of martensite laths with a common {111} austenite plane was termed a crystallographic packet.Generally,the crystallographic packet size corresponded to the morphological packet size,but occasionally the morphological packet was found to consist of two or more crystallographic packets.Therefore,the crystallographic packet size appeared to be finer than the morphological packet size.The relative orientation between the variants in crystallographic packets was found to be near 60 /<110>,which explains the strong peak observed near 60 in the grain boundary misorientation distribution.Martensite also contained a high fraction of boundaries with a misorientation in the range 2.5-8.Typically these boundaries were found to be located inside the martensite laths forming sub-laths. 相似文献
9.
Antti Juhani Kaijalainen Pasi Suikkanen L. Pentti Karjalainen John J. Jonas 《Metallurgical and Materials Transactions A》2014,45(3):1273-1283
The effect of austenite pancaking in the non-recrystallization regime on microstructure and texture evolution and thereby on bendability was investigated in an ultrahigh-strength strip steel with a martensitic-bainitic microstructure. The results indicate that an increase in rolling reduction (R tot) below the non-recrystallization temperature, which improves the strength and toughness properties, increases the intensities of the ~{554}〈225〉 α and ~{112}〈110〉 α texture components along the strip centerline and of the ~{112}〈111〉 α component at the surface region. Even with the highest R tot of 79 pct, the bendability along the rolling direction was good, but the preferred alignment of rod-shaped MA constituents along the rolling direction led to a dramatic decrease in the bendability transverse to the rolling direction, with severe cracking occurring even at small bending angles. The early cracking is attributed to localization of the strain in narrow shear bands. It is concluded that the Rtot value has to be limited to guarantee successful bendability. 相似文献
10.
Journal of Intelligent Manufacturing - Principles of typical motion planning algorithms are investigated and analyzed in this paper. These algorithms include traditional planning algorithms,... 相似文献