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。     

MIMO-OFDM系统抗干扰信道估计算法

提出一种抗干扰信道估计(AICE)算法用于解决MIMO-OFDM系统信道估计问题。该算法在接收端通过对收到的累加信号进行分解,得到来自不同发射天线的信号,通过消除符号间干扰与子载波间干扰及采用期望值最大迭代算法进行信道估计来减小估计误差,提高信道估计的准确性。与ICE算法的性能比较证明了AICE算法在瑞利衰落信道下具有更好的信道估计均方误差及误比特率性能。     

基于部分传输序列和选择映射的ICI消除方法

OFDM(正交频分复用)是第4代移动通信系统的核心技术之一,在OFDM基本系统中,各载波间正交性的损失会导致ICI(载波间干扰)的产生。文中在介绍和比较多种传统消除ICI的方法的基础上,提出了一种新的ICI消除技术:PTS(部分传输序列)法和SLM(选择映射)法,并针对PTS算法的缺陷提出了改进优化算法。仿真结果表明PTS和SLM算法都能减小系统的ICI,对系统误码率有所改善,从而使系统的性能得到了提高。     

Emerging Immunotherapy for Acute Myeloid Leukemia

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence.     

MIMO-CDMA系统的分数间隔空频均衡接收方案

该文提出了两种适用于宽带单载波多用户MIMO-CDMA系统下行链路的分数间隔空频均衡接收方案,并进行了理论推导。第1种接收方案采用分数间隔空频均衡器对MIMO频率选择性衰落信道进行均衡,从而恢复了扩频码的正交性,减小了码间干扰和共道干扰。第2种方案在假设接收端已知各用户扩频码的前提下,将分数间隔空频均衡器与频域并行干扰消除器结合,能够进一步消除天线间干扰,提高系统性能。仿真结果表明,这两种分数间隔空频均衡接收方案都比传统的频域均衡接收方案在性能上有很大的提高,并且复杂度也比较低。     

正交频分复用系统及其关键技术研究

在无线移动通信中,要求提供高速率和高质量的通信服务,而正交频分复用（OFDM）技术因具有频带利用率高和抗多径能力强等优点,近年来正受到广泛的重视,成为第四代移动通信系统的核心技术之一。在对该技术的基本思想介绍的基础上,分别对其优缺点进行了分析,且详细地阐述了OFDM系统中的关键技术及存在的问题。     

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.     

一种针对双衰落信道OFDM的新均衡算法

在OFDM系统中，子载波间的正交性是保证OFDM性能的重要保障。针对双选择性衰落信道下的OFDM系统，该文在分析载波间干扰（ICI）的基础上，提出了一种采用频域迭代消除ICI的均衡算法。分析和仿真结果表明此方法能有效地保证载波间的正交性和改善了OFDM系统的误码率（BER）性能。     

OFDM系统中基于线性预编码技术的均衡方法

在快速移动环境中,子载波间干扰(ICI)是恶化OFDM系统性能的重要因素。为抑制OFDM系统中的ICI,采用了一种基于线性预编码技术的迫零均衡方法,并对其在无冗余情形下的误码率(BER)性能进行了理论分析,推导出了BER最优的线性预编码矩阵的选取准则。仿真结果表明,在较高信噪比条件下,所用的方法能有效抑制ICI和显著改善OFDM系统的误码率性能。