Physical-layer key generation (PKG) in multi-user massive MIMO networks faces great challenges due to the large length of pilots and the high dimension of channel matrix. To tackle these problems, we ...propose a novel massive MIMO key generation scheme with pilot reuse based on the beam domain channel model and derive close-form expression of secret key rate. Specifically, we present two algorithms, i.e., beam-domain based channel probing (BCP) algorithm and interference neutralization based multi-user beam allocation (IMBA) algorithm for the purpose of channel dimension reduction and multi-user pilot reuse, respectively. Numerical results verify that the proposed PKG scheme can achieve the secret key rate that approximates the perfect case, and significantly reduce the dimension of the channel estimation and pilot overhead.
The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications ...and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.
Newcastle disease virus (NDV) encodes a highly phosphorylated P protein; however, the phosphorylation sites have not been identified, and the relationship between phosphorylation and protein function ...is still unclear. In this study, we bioinformatically predicted 26 amino acid residues in the P protein as potential phosphorylation sites. Furthermore, we treated infected cells with kinase inhibitors to investigate NDV propagation and found that protein kinase C (PKC) is involved in the NDV life cycle and that PKC-activated phosphorylation functions in NDV replication. Using an NDV minigenome assay, we found that expression of a reporter protein decreased when the minigenome system contained P mutants lacking T44, S48, T271, S373 and especially T111. The phosphorylation status of S48, T111, S125 and T271 was determined by Phos-tag SDS-PAGE analysis. Coimmunoprecipitation assays showed that the binding activity of NP and the P-T111A mutant was stronger than that of NP and the wild-type P, suggesting that P-T111 is involved in NP-P interaction. This study sheds light on the mechanism by which P protein phosphorylation affects NDV replication and transcription.
Contrast-induced nephropathy (CIN) is an iatrogenic acute renal failure occurring following the intravascular injection of iodinated radiographic contrast medium. However, the regulatory mechanisms ...for CIN remain to be fully elucidated. The present study aimed to investigate whether atorvastatin protects against CIN via anti‑apoptotic effects by the upregulation of Hsp27 in vivo and in vitro. To determine whether atorvastatin attenuated CIN, the inflammatory response and apoptosis in vivo and in vitro, a rat model of iopamidol‑induced CIN was used, and human embryonic proximal tubule (HK2) cell damage was assessed. The rats were assigned into four groups (n=10 per group), as follows: Control rats; rats+atorvastatin; rats + iopamidol; rats+iopamidol+atorvastatin. In vitro, the HK2 cells were treated with iopamidol in the presence or absence of atorvastatin, heat shock protein (Hsp)27 small interfering (si)RNA or pcDNA3.1‑Hsp27. The renal tissues were examined histopathologically and collected for western blot analysis. The results showed that atorvastatin ameliorated the apoptosis and deterioration of renal function (P<0.05). Furthermore, atorvastatin reduced the iopamidol‑induced activity of B cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax)/caspase‑3 and increased the expression of Bcl‑2 in vivo and in vitro. Notably, following treatment with Hsp27 siRNA or pcDNA3.1‑Hsp27, it was found that iopamidol enhanced or weakened the upregulation of Bax/caspase‑3 and downregulation of Bcl‑2 in the HK2 cells, respectively. The results of the present study suggested that atorvastatin protected against contrast‑induced renal tubular cell apoptosis through the upregulation of Hsp27 in vivo and in vitro.
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A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. ...Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases.
Introduction: Spleen Tyrosine Kinase (SYK), a non-receptor type of tyrosine kinase, is a member of Syk/ZAP70 tyrosine kinase family. It plays a pivotal role in the regulation of B-cell receptor (BCR) ...signal pathway, which regulates proliferation, differentiation and survival of B lymphocytes. The abnormal activation of BCR singling is closely related to transformation and development of B cell lymphoma. Targeting BCR downstream molecules, such as Bruton’ tyrosine kinase (BTK) and phosphoinositide-3-kinase δ (PI3Kδ) has emerged as new therapeutic approaches and inhibitors of BTK and PI3Kδ were approved recently by FDA for treatment of some subtypes of B-cell malignancies. Currently, a couple small molecular inhibitors against SYK, another BCR downstream molecule, are under the early clinical development and showed initial efficacy in B cell lymphomas.
HMPL-523, discovered and currently being developed in Phase I clinical trial by Hutchison MediPharma, is a novel, highly potent and selective SYK inhibitor (IC50: 0.025 μM). The anti-tumor activity of HMPL-523 was evaluated in this study.
Methods: Inhibitory effects of HMPL-523 on cell viability were investigated in a panel of B cell lymphoma cell lines with SYK/BCR dysregulation by CellTiter-Glo luminescent or CCK-8 assay. The effect of HMPL-523 on SYK signaling pathway was detected by western blot. Annexin-V- positive and PI-negative population was recognized as apoptotic cells by FACS. Nude mice bearing B cell lymphoma xenograft tumors with SYK/BCR dysregulation were used to determine anti-tumor activity of HMPL-523 in vivo.
Result: HMPL-523 blocked phosphorylation of BLNK, downstream protein of Syk, in human mantle cell line REC-1 and human plasma cell line ARH-7777 with IC50 of 0.105 µM and 0.173 μM, respectively. HMPL-523 also inhibited cell viability of Ba/F3 Tel-Syk with IC50 of 0.033 μM. Furthermore, inhibitory effects of HMPL-523 on cell viability were evaluated in a panel of B -cell lymphoma cell lines with SYK/BCR deregulation. Results showed that HMPL- 523 potently inhibited cell survival with IC50s from 0.4 to 2 μM. Consistent with the effect on cell viability, HMPL-523 increased the apoptotic rate of REC-1 cells. Moreover, HMPL-523 showed the synergistic activities on killing human diffused large B cell lymphoma (DLBCL) in combination with other drugs such as BTK inhibitor, PI3Kδ inhibitors and Bcl2 family inhibitor. The detailed mechanisms underlying the synergism are still under investigation. Anti-tumor activity of HMPL-523 was determined in Syk dependent xenograft models. Daily oral administration of 100 mg/kg HMPL-523 showed potent anti-tumor activity in B cell lymphoma REC-1 (TGI: 59%).
Conclusion:HMPL-523 is a highly potent SYK inhibitor with good activity against B-cell lymphoma in pre-clinical in vitro and in vivo models, supporting further clinical research for HMPL-523 as either single agent or combination drug with other agents to treat B-cell malignancies e.g. DLBCL
Yang:Hutchison MediPharma Ltd: Employment, Research Funding. Deng:Hutchison MediPharma Ltd: Employment, Research Funding. Sun:Hutchison MediPharma Ltd: Employment, Research Funding. Liang:Hutchison MediPharma Ltd: Employment, Research Funding. Wang:Hutchison MediPharma Ltd: Employment, Research Funding. Fan:Hutchison MediPharma Ltd: Employment, Research Funding. Tang:Hutchison MediPharma Ltd: Employment, Research Funding. Yu:Hutchison MediPharma Ltd: Employment, Research Funding. Sun:Hutchison MediPharma Ltd: Employment, Equity Ownership. Zhou:Hutchison MediPharma Ltd: Employment, Research Funding. Dai:Hutchison MediPharma Ltd: Employment, Research Funding. Qing:Hutchison MediPharma Ltd: Employment, Research Funding. Su:Hutchison MediPharma Ltd: Employment, Research Funding. Ren:Hutchison MediPharma Ltd: Employment, Research Funding.
MicroRNAs (miRNAs) are known to regulate most biological processes including contrast-induced acute kidney injury (CI-AKI). Few studies have investigated microRNA (miRNAs) expressions in a novel rat ...model of CI-AKI using nonionic low-osmolar iodic contrast medium Ultravist, and performed gene ontology (GO) categories analysis.
In this study, kidney tissues were collected from Sprague-Dawley rats at 24 h after contrast-exposure (CI-AKI) and saline-administration (control). MiRNAs microarray assays were used to detect miRNAs in the kidney tissue by next-generation sequencing. Real-time PCR was performed to verify the microarray assays results. All significant differently expressed miRNAs were analyzed by GO categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
Of the 173 detected miRNAs, 22 were down-regulated (miR-328a-5p, miR-31a-5p, miR-377-3p,
) and 19 were up-regulated (miR-3558-5p, miR-34c-3p, miR-384-5p,
) in the kidneys of CI-AKI rats according to log2 (fold change, control) >1, P<0.001 as significant differently expressed miRNAs, which included new differently expressed miRNAs, such as miRNA-1949 and miR-3558. The results showed that a large set of genes involved in essential biological processes were targeted by these miRNAs, such as dysfunction metabolic process, apoptotic process, and endoplasmic reticulum stress, in addition to genes implicated in signaling pathways involved in inflammation and dysfunctional metabolism, including AGE-RAGE signaling pathway and glycerophospholipid metabolism.
The 41 miRNAs identified were differentially expressed in the kidneys of a novel rat model of CI-AKI, and thus possess the potential to serve as novel biological markers and new molecular targets for CI-AKI.
In situ electron-beam irradiation was performed in a transmission electron microscope to fabricate nanocrystals of IV−VI semiconducting lead chalcogenides PbE (E = S, Se, and Te) and ...low-melting-point metals (Zn, Ga, Sn, and Cd). The source powders consisting particles of 300−1000 nm in diameter were supported on a thin carbon (C) film. A convergent electron beam was focused on an individual particle, which caused partial melting and evaporation of the particle and subsequent nucleation and growth of new nanoparticles on the C film. These nanocrystals are structurally uniform and free of any linear and planar defect and do not have any other impurity contamination. The method is easy to set up and is low in cost and is very fast (several seconds to several minutes) in process. It is believed that this new method can also be employed to synthesize many other material nanocrystals and one-dimensional nanostructures, beyond semiconductors and (low melting point) metals, such as oxides and even sulfides and nitrides.
A multicolor photodetector based on the heterojunction of n-Si(111)/TiO sub(2) nanorod arrays responding to both ultraviolet (UV) and visible light is developed by utilizing interface engineering. ...The photodetector is fabricated via a consecutive process including chemical etching, magnetron sputtering, hydrothermal growth, and assembling. Under a small reverse bias (from 0 to approximately -2 V), only the photogenerated electrons in TiO sub(2) are possible to tunnel through the low barrier of Delta E sub(C), and the device only responses to UV light; as the reverse bias increases, the photogenerated holes in Si also begin to tunnel through the high barrier of Delta E sub(V). As a result, the device is demonstrated to have the capacity to detect both UV and visible lights, which is useful in the fields of rapid detection and multicolor imaging. It has been also observed that the crystal orientation of Si affects the characteristics of bias-controlled spectral response of the n-Si/TiO sub(2) heterojunctions. A multicolor photodetector based on a n-Si(111)/TiO sub(2) nanorod array heterojunction is developed by utilizing interface engineering, responding to both ultraviolet and visible light by changing the applied bias.
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