[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Salt and drought stress signal transduction consists of ionic and osmotic homeostasis signaling pathways, detoxification (i.e., damage control and repair) response pathways, and pathways for growth regulation. The ionic aspect of salt stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2 protein kinase complex controls the expression and activity of ion transporters such as SOS1. Osmotic stress activates several protein kinases including mitogen-activated kinases, which may mediate osmotic homeostasis and/or detoxification responses. A number of phospholipid systems are activated by osmotic stress, generating a diverse array of messenger molecules, some of which may function upstream of the osmotic stress-activated protein kinases. Abscisic acid biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent and -independent osmotic stress signaling first modify constitutively expressed transcription factors, leading to the expression of early response transcriptional activators, which then activate downstream stress tolerance effector genes.

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Salt and drought stress signal transduction in plants

Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.

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Macrophage plasticity and polarization: in vivo veritas

▪ Abstract Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to t...

Plant cellular and molecular responses to high salinity.

Additive manufacturing of metallic components – Process, structure and properties

e20600 Background: Recent studies show that the use of circulating tumor DNA (ctDNA) has potential to guide precision medicine and transform the management of early-stage lung cancers. We aim to investigate whether plasma is suitable for detecting tumor‐derived DNA in patients with stage I single-lesion lung cancer and multifocal lung cancer which has rarely been investigated. Methods: Matched tumor tissues (n = 114) and plasma samples (n = 95) from Chinese patients with stage I lung cancer (n = 95), including 80 patients with single-lesion and 15 patients with multiple primary lung cancer (MPLC) diagnosed by American College of Chest Physicians (ACCP) guidelines, were analyzed by Acornmed panel with 808 cancer-related genes. Results: Using tumor tissue-based results as the gold standard, we performed variant-level assessment of the ctDNA tests. In patients with single-lesion, sequencing detected alterations in 98.8% (79/80) ctDNA and 9.3% (74/797) of variants in ctDNA were detected by corresponding tDNA. Among them, 31.3% (25/80) patients had at least one overlapping variant called by tDNA and ctDNA, and 5% (4/80) patients shared EGFR in both tDNA and ctDNA. Meanwhile, we identified 2 mutated EGFR in ctDNA that were not detected in tissues. As for multiple primary lung cancers, 86.7% (13/15) of MPLC patients had ≥1 alteration in ctDNA. In addition, 7.4% (9/122) of variants in ctDNA were detected by corresponding tDNA in MPLC. The overall concordance for all variants detected in both ctDNA and any tDNA of patients was 53.3% (8/15) in MPLC, with EGFR and KRAS as the most two frequent mutations. Furthermore, mutations consistent with ctDNA were detected in 29.4% (10/34) of the lesions in MPLC. Conclusions: Our analysis showed that plasma with high mutation detection rate and considerable concordance rate with tDNA maybe a powerful complement to tissues for molecular testing in lung cancer. Furthermore, ctDNA detection not only may be able to overcome the heterogeneity of tumors but also more comprehensively reflect the disease state of patients with multifocal lung cancer.

Somatic aberrations detected in tumor tissue and plasma in Chinese patients with stage I single-lesion and multi-lesions lung cancer.

Rapid simplification of 3D geometry model of mechanisms in the digital twins-driven manufacturing system design


 Background: Despite recent FDA approval of immune checkpoint inhibitor pembrolizumab and drug-antibody conjugate in the treatment of mTNBC, the overall survival benefit of these patients remains modest. We conducted a phase 2 study to assess the efficacy and safety of anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in mTNBC patients (pts) regardless of PD-L1 status. Preliminary results have been delivered in 2021 AACR[1], here we reported the final results of the progression-free survival (PFS) and overall survival (OS) analysis. Methods: This study enrolled pts with treatment-naïve locally advanced inoperable or metastatic TNBC. Eligible pts received nab-paclitaxel plus KN046 at two dose levels (DL1: KN046 3 mg/kg Q2W or DL2: KN046 5 mg/kg Q2W). Tumor response was evaluated Q8W per RECIST 1.1. The primary endpoint included objective response (ORR) and duration of response (DoR), secondary included disease control rate (DCR), clinical benefit rate (CBR), PFS, 1-year/2-year OS rate and safety/tolerability. Results: As of May 9, 2022 (cut-off date), 27 pts were enrolled into DL1 (n=16) and DL2 (n=11). Median patient age in the study was 50 years (range, 33-70 years). At baseline, 52% and 48% of patients had ECOG PS of 0 and 1, respectively. By the cut-off date, there are 1 pts under treatment and 16pts alive. The median study follow-up time was 26.3 months (95% CI, 20.7 - 29.8). Based on the intent-to-treatment (ITT) population, the confirmed ORR was 33.3% (95% CI, 16.5% - 54.0%), DCR was 88.9% (95% CI, 70.8% - 97.7%), and CBR was 48.1% (95% CI, 28.7% - 68.1%), which remained stable compared with last reported in 2021 [1]. The DoR was 11.9 (95% CI, 5.6 - NR) months. The median PFS was 7.3 (95% CI, 3.7 - 13.7) months. The median OS is immature, the preliminary result is 27.7 (95% CI, 14.8 - NR) months, and the 2-year OS rate was 60.1% (95%CI, 37.2% - 76.9%). Among the 11 pts with PD-L1 positive (≥1% IC), confirmed ORR was 45.5% (95%CI, 16.7% - 76.6%) and mPFS was 8.61 (95%CI, 1.6 - 13.8) months. Both PD-L1 positive and negative pts derived OS benefit from the combination treatment, with the 2-year OS rate of 57.14% (95%CI, 25.4% - 79.6%) and 62.5% (95%CI, 22.9% - 86.1%) respectively. Patients tolerated well to combination therapy in this trial. The most common reported treatment related adverse event (TRAEs) were ALT elevation (13 pts, 48%), AST elevation (12 pts, 44%), pyrexia (9 pts, 33%), neutropenia (8 pts, 30%), and anemia (7 pts, 26%). Grade ≥3 TRAEs (≥10%) were neutropenia (7 pts, 26%), leukopenia (6 pts, 22%) and AST elevation (5 pts, 15%). 13 pts (48%) experienced immune related adverse events (irAEs), and only 3 irAEs (11%) were grade 3. The incidence of SAE was 33%, with no TRAE leading to death. Conclusions: The combination therapy of KN046 plus nab-paclitaxel has shown favorable clinical efficacy in mTNBC, especially in PD-L1 positive patients. By the cut-off date, the mOS is not mature and there is still more than half of pts alive, which demonstrated an encouraging 2-year OS rate. Pts in this trial tolerated well to the combination therapy and safety profile was manageable. Clinical trial information: NCT03872791 Reference 1. Cancer Res (2021) 81 (13_Supplement): 1660.
 Citation Format: Qiao Li, Qingyuan Zhang, Yue Zhang, Quchang Ouyang, Qiang Liu, Tao Sun, Feng Ye, Baochun Zhang, Ting Xu, Summer Xia, Karl Zhang, Bangyong Zhang, Binghe Xu. PD11-10 Efficacy, Safety, and Tolerability of KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in combination with Nab-paclitaxel in Metastatic Triple-negative Breast Cancer (mTNBC):Final results of the Phase II trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-10.

Abstract PD11-10: PD11-10 Efficacy, Safety, and Tolerability of KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in combination with Nab-paclitaxel in Metastatic Triple-negative Breast Cancer (mTNBC):Final results of the Phase II trial

The astigmatic mode converter is exploited as an intracavity element to establish a structured-light laser scheme, realizing free control of two-dimensional indices of laser modes and large-range tunability of radial- and orbital-angular-momenta (p-to-4ℏ and l-to-±15ℏ).

Intracavity-Mode-Conversion Structured-Light Laser

When evaluating the detection probability of a pulsed Gm-APD laser ranging system with a propagation path close to the ground, the detection probability limitation caused by the atmospheric turbulence cannot be ignored. Based on modulated Poisson model, the detection probability limitation due to the turbulence effects is investigated, and a cumulative pulses detection method is proposed to restrain the turbulence effects. The results show that the influence of the turbulence effects is equivalent to adding a new noise source to the echo intensity, the detection probability results in a worse situation with stronger turbulence effects, when the turbulence degree is 1.5 and the echo intensity is 10, the target detection probability decrease by 0.17, and the false alarm probability increases by 0.03. By utilizing the cumulative pulses detection technique, the target detection probability and false alarm probability improve by 0.3 and 0.07, respectively.

Qiang Liu

Papers

Somatic aberrations detected in tumor tissue and plasma in Chinese patients with stage I single-lesion and multi-lesions lung cancer.

Rapid simplification of 3D geometry model of mechanisms in the digital twins-driven manufacturing system design

Abstract PD11-10: PD11-10 Efficacy, Safety, and Tolerability of KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in combination with Nab-paclitaxel in Metastatic Triple-negative Breast Cancer (mTNBC):Final results of the Phase II trial

Intracavity-Mode-Conversion Structured-Light Laser

Detection probability limitation of a pulsed Gm-APD laser ranging system with turbulence effects