If Virchow and Ehrlich Had Dreamt Together: What the Future Holds for KRAS-Mutant Lung Cancer

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.     

Kalman滤波预测的多小区子载波分配方法

小区间干扰协调是3G演进系统中抑制小区间干扰的重要策略, 并且在各类小区间干扰协调方案包含着不同的频率复用方法。为了在抑制干扰的同时提高频谱利用率,提出了可用频率集合的概念。如何分配可用频率集合中不同频点的子载波直接关系到小区间干扰的强弱程度,而现有的子载波分配方法往往基于当前信道状况, 导致在分配过程中因时间的滞后性而带来较大的干扰。针对这种情况,提出了一种基于Kalman滤波预测的自适应子载波分配方法。该方法通过检测获取不同子载波对用户的信道增益干扰比(GIR), 进而采用Kalman滤波估计得到下一时刻的GIR预测值大小,并以该预测值作为子载波分配的依据。仿真结果表明,与固定子载波分配方法和基于当前GIR的子载波分配方法相比,该方法能有效降低不同频率复用方法下的小区间干扰,改善小区和用户的性能,具体表现在提高了小区吞吐量,降低了用户的阻塞率,以及改善了小区边缘用户的比特丢失率。     

一种新的适应于OFDM系统的载波间干扰抑制方案

针对高速移动环境下多普勒效应引起的载波间干扰严重影响了正交频分复用系统的性能问题,提出了新的基于时域干扰自消除的载波间干扰抑制算法．该算法基于符号重复的正交频分复用系统,在接收端进行一系列的信号处理后,得到大量具有不同附加延时的重构正交频分复用符号; 之后,利用信道的统计特性对这些重构的正交频分复用符号进行合并接收,从而抑制载波间干扰．仿真与分析表明,时域干扰自消除能有效地抑制载波间干扰,提高系统性能,为高速移动环境中应用正交频分复用提供了一种有效的解决方案．     

OFDM系统中的频偏估计和符号定时算法

为克服正交频分复用( OFDM)系统中同步偏差带来的符号间干扰和载波间干扰,提出了一种基于相关矩阵的频偏估计和符号定时算法.该算法通过求解相关矩阵的非对角元素的极值确定小数倍频偏;通过分析相关矩阵对角线上元素的大小可确定整数倍频偏;通过平移FFT窗口,满足定义函数最大可实现符号定时同步.仿真结果表明该算法具有较好的估计...     

数字电视多媒体广播系统的相位噪声抑制

为提高数字电视多媒体广播(DTMB)系统抗相位噪声的能力,提出了利用DTMB系统保护间隔内所填充的PN序列的时域公共相位误差校正方案,以及利用传输参数信令(TPS)的判决辅助子载波间干扰抑制方案.计算机仿真结果表明,该方法可有效地抑制接收机本振相位噪声引起的相位旋转和子载波间干扰,降低系统误符号率.而且时域公共相位误差校正方案具有抗噪声、抗干扰能力强的优点.     

Kernel density estimation with adaptive varying window size

A new method of kernel density estimation with a varying adaptive window size is proposed. It is based on the so-called intersection of confidence intervals (ICI) rule. Several examples of the proposed method are given for different types of densities and the quality of the adaptive density estimate is assessed by means of numerical simulations.     

Performance Analysis of OFDM with Frequency Offset and Correction Model

1　IntroductionIntheOrthogonalFrequencyDivisionMulti plexing (OFDM ) ,datasymbolsaretransmittedinparallel,andthewholetransmissionbandwidthisdividedintomanynarrowsubchannels.Moreover,OFDMcanalmosteliminateInterSymbolInterfer ence (ISI)forhighratedatatransmissionovertimedispersivechannelsifasuitableguardintervalischo sen[1 ] .Comparedtothetraditionalsinglecarriertransmission,thestructureofOFDMissimple,bandwidthefficiencyofOFDMishigher,andOFDMisrobusttotimedispersionfadingandim pulsen…     

OFDM系统中基于时域干扰自消除的载波间干扰抑制技术

为了降低信道时变造成的载波间干扰(ICI)对正交频分复用(OFDM)系统性能的影响,提出了基于时域干扰自消除(TDISC)的ICI抑制方案和基于导频辅助估计的次优合并TDISC算法。仿真与分析表明,该算法能有效对抗信道中的时变衰落,提高OFDM在高速移动环境中的系统性能。     

正交频分复用系统中的判决反馈干扰消除方法

针对正交频分复用系统中Hadamard载波干扰矩阵估计方法估计效果差,提出了基于判决反馈的载波干扰矩阵估计方法.该方法根据载波干扰矩阵可用傅里叶变换矩阵对角化的特性,通过离散傅里叶变换的输出来估计载波干扰系数,再根据符号判决结果更新载波干扰矩阵,可较快地跟踪信道的快速衰落.实验仿真表明,该方法与Hadamard载波干扰矩阵估计方法相比,结合比特交织编码调制技术可进一步提高系统的载波干扰消除能力.     

Imaging Memory T-Cells Stratifies Response to Adjuvant Metformin Combined with αPD-1 Therapy

The low response rates associated with immune checkpoint inhibitor (ICI) use has led to a surge in research investigating adjuvant combination strategies in an attempt to enhance efficacy. Repurposing existing drugs as adjuvants accelerates the pace of cancer immune therapy research; however, many combinations exacerbate the immunogenic response elicited by ICIs and can lead to adverse immune-related events. Metformin, a widely used type 2 diabetes drug is an ideal candidate to repurpose as it has a good safety profile and studies suggest that metformin can modulate the tumour microenvironment, promoting a favourable environment for T cell activation but has no direct action on T cell activation on its own. In the current study we used PET imaging with [¹⁸F]AlF-NOTA-KCNA3P, a radiopharmaceutical specifically targeting K_V1.3 the potassium channel over-expressed on active effector memory T-cells, to determine whether combining PD1 with metformin leads to an enhanced immunological memory response in a preclinical colorectal cancer model. Flow cytometry was used to assess which immune cell populations infiltrate the tumours in response to the treatment combination. Imaging with [¹⁸F]AlF-NOTA-KCNA3P demonstrated that adjuvant metformin significantly improved anti-PD1 efficacy and led to a robust anti-tumour immunological memory response in a syngeneic colon cancer model through changes in tumour infiltrating effector memory T-cells.