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Random access channel (RACH) is the first step that needs to be conducted by any devices which require data transmission in modern cellular networks. Since LTE and beyond also often used to serve IoT application due to its wide coverage and availability, conserving energy is important. This paper presents a flexible preamble allocation scheme which is applied in RACH procedure and evaluates its energy consumption. The flexible preamble allocation enables base station to fine-tune its preamble allocation, which mainly used to prioritize H2H services over IoT ones. Such access prioritization translates in more efficient signaling transmissions during RACH procedure by reducing collision. The result demonstrates that the scheme can effectively reduce energy usage compared with the standard RACH procedure with shared preamble pool.

Leveraging compromised DNA damage repair (DDR) pathways commonly found in tumor cells, a classic strategy in cancer therapy is inducing excessive DNA damage to cause cancer cell death. Small molecule poly(ADP-ribose) polymerase (PARP) inhibitors (PARP-is) have been approved for clinical use in treating breast cancer and ovarian cancer patients bearing DDR-deficient tumors with mutations in breast cancer susceptibility proteins (BRCAm). However, accumulating evidences show that both intrinsic and acquired resistances to PARP-is exist in clinic and pre-clinical animal models. Therefore, we developed panels of cells with acquired PARP-is resistance from PARP-is-sensitive triple negative breast cancer (TNBC) and estrogen receptor positive breast cancer cell lines, and used these cells to screen for common traits that can be targeted with feasible therapeutic agent combinations to overcome PARP-is resistance. Since TNBC lacks of effective targeted therapy so far, we focused on using the panel of PARP-is-resistant TNBC cells in this study. Among the molecular mechanisms known contribute to PARP-is resistance, oncogenic kinase activations, including several hyper-activated receptor tyrosine kinases (RTKs), are involved in enhancing DNA damage repair and decreasing affinity of PARP-is to PARP1. In this study, we systematically screened for activated RTKs in the PARP-is-resistant cells we developed by antibody arrays. We then identified that activations of MET, Axl and EphA2 were common traits in TNBC cells with acquired PARP-is resistance, but not in estrogen receptor positive cells. Among the three RTKs, MET has more small molecules inhibitors that can target it, and thus, we made it a priority in investigating synergism between MET inhibitor and PARP inhibitor in multiple cancer types including TNBC with intrinsic and acquired PARP-is-resistance, high-grade serous ovarian cancer (HGSOC) and liver cancer cells. Here, we demonstrated that combinations of PARP-is and MET inhibitors (MET-is) possess moderate to strong synergism in the different cancer types we studied. As we previously reported that MET translocates into cell nucleus and phosphorylates PARP1 at tyrosine (Y) 907 residue in TNBC with intrinsic PARP-is resistance, we found that this MET-mediated PARP1-Y907 phosphorylation also exist in and can serve as marker to indicate PARP-is resistance among the HGSOC, liver cancer cells and the TNBC cells with acquired PARP-is resistance. We further found that MET phosphorylation is high (immunohistological staining H-score greater than 200) in breast cancer (23 out of 31, 70%) and ovarian cancer (8 out of 23, 35%) patient-derived xenograft mouse model tissue microarrays, suggesting that the combination of MET-is and PARP-is is likely to benefit a huge population of cancer patient in multiple cancer types. Citation Format: Mei-Kuang Chen, Weiya Xia, Qiongzhu Dong, Yi Du, Hung-Ling Wang, Coya Tapia, Yongkun Wei, Ye Han, Yu-Yi Chu, Clinton Yam, Yuan Gao, Yu-Han Wang, Funda Meric-Bernstam, Jinsong Liu, Shao-Chun Wang, Dihua Yu, Mien-Chie Hung. Synergism of PARP inhibitor and MET inhibitor in multiple cancer types with intrinsic and acquired PARP inhibitor resistances [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5682.

Front line therapeutic failure happened to half of triple-negative breast cancer (TNBC) patients represent the effective treatment strategies for these patients are urgently needed. Poly (ADP-ribose) polymerase (PARP) is currently the most promising drug target for BRCA-mutated TNBC, and PARP inhibitors (PARPi), olaparib and talazoparib, were recently approved for the treatment of metastatic breast cancer (including TNBC) in patients with germline BRCA1/2 mutations. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with a PARPi is modest, suggesting the emergence of resistance. Several studies have reported that receptor tyrosine kinases (RTKs), such as c-MET (also known as hepatocyte growth factor receptor), are involved in resistance to various anti-neoplastic agents, including PARPi. However, the mechanism by which c-MET contributes to acquired resistance to PARPi in TNBC is not fully understood. In this study, we analyzed acquired PARPi resistant TNBC cells and found c-Met is hyperactivated in these cells with PARPi treatment. We further treated these cells with talazoparib and crizotinib (a multi-kinase inhibitor that inhibits c-MET) and found synergistic inhibition effects of cell proliferation. Unexpectedly, limited effects of talazoparib sensitivity showed while depleting c-MET in PARPi-resistant cells. Interestingly, we found epidermal growth factor receptor (EGFR) is also hyperactivated and interaction of EGFR/c-Met in these cells. Notably, combination of c-MET and EGFR inhibitors increased sensitivity to talazoparib in TNBC cells with acquired resistance to PARPi. Combining EGFR and PARP inhibitors also resulted in greater inhibition of proliferation in c-MET-depleted TNBC cells. Collectively, our findings suggested a potential combination therapy of inhibiting c-MET and EGFR to overcome acquired PARPi resistance in TNBC. Citation Format: Yu Yi Chu, Clinton Yam, Mei-Kuang Chen, Li-Chuan Chan, Lei Nie, Mien-Chie Hung. Reversing acquired PARPi resistance of TNBC through combined inhibition of cMet and EGFR [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4074.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PARP1 inhibitors (PARPi) are currently used in the clinic for the treatment of ovarian and breast cancers, yet their therapeutic efficacy against hepatocellular carcinoma (HCC) has been disappointing. To ensure therapeutic efficacy of PARPi against HCC, a disease often diagnosed at intermediate to advanced stages with no effective treatment options, it is critical to identify not only biomarkers to predict PARPi resistance but also rational treatments to overcome this. Here, we report that a heterodimer of EGFR and MET interacts with and phosphorylates Y907 of PARP1 in the nucleus, which contributes to PARPi resistance. Inhibition of both EGFR and MET sensitized HCC cells to PARPi, and both EGFR and MET are known to be overexpressed in HCC. This report provides an explanation for the poor efficacy of PARPi against HCC and suggests combinatorial treatment consisting of EGFR, MET, and PARP inhibitors may be an effective therapeutic strategy in HCC. Significance: Regulation of PARP by the c-MET and EGFR heterodimer suggests a potentially effective combination therapy to sensitize HCC to PARPi.

Long-term evolution (LTE)-based vehicular-to-everything (V2X) service is one of the promising technologies for supporting intelligent transportation systems (ITSs). LTE adopts a request-grant approach for allocating wireless resources. Each user follows a contention-based random access (RA) procedure to transmit its request. However, this procedure may result in unbounded delay if too many users compete for limited RA resources. Therefore, prioritized critical access in the LTE RA procedure is required to differentiate critical V2X services from noncritical ones.

This article proposes a novel separable field shaper design for electromagnetic sheet impact forming. The efficiency of the field shaper under different geometric parameters was evaluated through a combination of the Taguchi method and three-dimensional coupled simulation. The deviation in impact velocity between the experiment and the simulation was under 3%. The results indicate that the slit feature determines the performance of the field shaper. Wider slits reduce the energy loss resulting from electromagnetic repulsion. In addition, with more field shaper components, the generated magnetic pressure will be distributed more evenly. Based on the analysis result of the nonsymmetric edge effect, some guidelines for designing the field shaper are proposed.

This research to carry on the 3D model of electro-magnetic-mechanical forming analysis, its goal is lies in discusses the magnetic force which electric current produces the influence which creates to the plate, like distortion, stress and so on aspects. But before the analysis, establishes the 3D model first, in converges in ANSYS, gives the material parameter, the boundary condition and so on, then carries on the solution, subsequently obtains the analysis result. Knew by the analysis result, in approaches corner on the U shape coil dull position, its amount of deformation is the maximum value, and stress maximum value also in corner.

A circularly-polarized (CP) slot antenna comprises of a triangular wide slot, a director patch, and a metallic reflector is proposed and studied in this paper. The CP radiation of the slot antenna is excited by the proximity coupling of an L-shaped strip. To obtain an optimum peak gain and a broad CP bandwidth, the effects of varying the positions of the director and reflector on the antenna performances are respectively investigated. Several prototypes were constructed, and the measured results show that the proposed antenna can provide an average gain of 10 dBi within a CP operating bandwidth of 23% and a front-to-back ratio of over 10 dB. Simulation analyses are also carried out to validate the experimental results.

Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important targets for proliferative and immune-inflammatory disorders. Recent progress in the discovery of selective inhibitors has been significant, with selective compounds now reported for each isoform. This article summarizes the current state-of-the-art with a discussion of the most recently described selective compounds. X-ray co-crystal structures reveal the molecular reasons for the observed biochemical selectivity. A concluding analysis of JAK inhibitors in the clinic highlights increased clinical trial activity and diversity of indications. Selective JAK inhibitors, as single agents or in combination regimens, have a very promising future in the treatment of oncology, immune and inflammatory diseases.

This article presents a wide slot antenna whose polarization can be adjusted by rotating a conducting strip. To obtain an optimum gain of the slot antenna, a parasitic patch and a metallic reflector were placed at the front and rear of the wide slot, respectively. A prototype of the proposed antenna was implemented and measured. Experimental results exhibit that the prototype can provide one linear polarization and dual circular polarization operations over a 10 dB-return-loss impedance bandwidth of 21%; moreover, the antenna gain is around 10 dBi for each polarization operation. Simulation results performed by HFSS are also shown and they agree with the measured results. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 1793–1795, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23506

Latency-associated peptide (LAP) - expressing regulatory T cells (Tregs) are important for immunological self-tolerance and immune homeostasis. In order to investigate the role of LAP in human CD4⁺Foxp3⁺ Tregs, we designed a cross-sectional study that involved 42 colorectal cancer (CRC) patients. The phenotypes, cytokine-release patterns, and suppressive ability of Tregs isolated from peripheral blood and tumor tissues were analyzed. We found that the population of LAP-positive CD4⁺Foxp3⁺ Tregs significantly increased in peripheral blood and cancer tissues of CRC patients as compared to that in the peripheral blood and tissues of healthy subjects. Both LAP⁺ and LAP⁻ Tregs had a similar effector/memory phenotype. However, LAP⁺ Tregs expressed more effector molecules, including tumor necrosis factor receptor II, granzyme B, perforin, Ki67, and CCR5, than their LAP⁻ negative counterparts. The in vitro immunosuppressive activity of LAP⁺ Tregs, exerted via a transforming growth factor-β-mediated mechanism, was more potent than that of LAP⁻ Tregs. Furthermore, the enrichment of LAP⁺ Treg population in peripheral blood mononuclear cells (PBMCs) of CRC patients correlated with cancer metastases. In conclusion, we found that LAP⁺ Foxp3⁺ CD4⁺ Treg cells represented an activated subgroup of Tregs having more potent regulatory activity in CRC patients. The increased frequency of LAP⁺ Tregs in PBMCs of CRC patients suggests their potential role in controlling immune response to cancer and presents LAP as a marker of tumor-specific Tregs in CRC patients.