A Normalization Model for Analyzing Multi-Tier Millimeter Wave Cellular Networks

Based on the distinguishing features of multi-tier millimeter wave (mmWave) networks such as different transmit powers, different directivity gains from directional beamforming alignment and path loss laws for line-of-sight (LOS) and non-line-of-sight (NLOS) links, we introduce a normalization model to simplify the analysis of multi-tier mmWave cellular networks. The highlight of the model is that we convert a multi-tier mmWave cellular network into a single-tier mmWave network, where all the base stations (BSs) have the same normalized transmit power 1 and the densities of BSs scaled by LOS or NLOS scaling factors respectively follow piecewise constant function which has multiple demarcation points. On this basis, expressions for computing the coverage probability are obtained in general case with beamforming alignment errors and the special case with perfect beamforming alignment in the communication. According to corresponding numerical exploration, we conclude that the normalization model for multi-tier mmWave cellular networks fully meets requirements of network performance analysis, and it is simpler and clearer than the untransformed model. Besides, an unexpected but sensible finding is that there is an optimal beam width that maximizes coverage probability in the case with beamforming alignment errors.Comment: 7 pages, 4 figure

Germline PTPRD mutations in Ewing sarcoma: biologic and clinical implications.

Ewing sarcoma occurs in children, adolescents and young adults. High STAT3 levels have been reported in approximately 50% of patients with Ewing sarcoma, and may be important in tumorigenesis. Protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor that inhibits STAT3 activation. To date, while somatic mutations in PTPRD have been reported in diverse tumors, germline mutations of PTPRD have not been investigated in Ewing sarcoma or other cancers. We identified a novel germline mutation in the PTPRD gene in three of eight patients (37.5%) with metastatic Ewing sarcoma. Although the functional impact in two of the patients is unclear, in one of them the aberration was annotated as a W775stop germline mutation, and would be expected to lead to gene truncation and, hence, loss of the STAT3 dephosphorylation function of PTPRD. Since STAT3 is phosphorylated after being recruited to the insulin growth factor receptor (IGF-1R), suppression of IGF-1R could attenuate the enhanced STAT3 activation expected in the presence of PTPRD mutations. Of interest, two of three patients with germline PTPRD mutations achieved durable complete responses following treatment with IGF-1R monoclonal antibody-based therapies. Our pilot data suggest that PTPRD germline mutations may play a role in the development of Ewing sarcoma, a disease of young people, and their presence may have implications for therapy

Dual EGFR inhibition in combination with anti-VEGF treatment: a phase I clinical trial in non-small cell lung cancer.

BackgroundPreclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models.MethodsWe conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response.ResultsThirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD) ≥6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD≥6 months or uPR. Correlation between grade of rash and rate of SD≥6 months/PR was observed (p less than 0.01).ConclusionThe combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC

The plasma level changes of VEGF and soluble VEGF receptor-1 are associated with high-altitude pulmonary edema

Hypoxia-induced plasma levels of VEGF and sFlt-1 are responsible for increased vascular permeability occurred in both brain and pulmonary edema. Currently, it remains unclear the exact roles of VEGF and sFlt-1 in High Altitude Pulmonary Edema (HAPE) pathogenesis. In this study, plasma levels of VEGF and sFlt-1 from 10 HAPE and 10 non-HAPE subjects were measured and compared. The results showed that plasma levels of both VEGF and sFlt-1 in HAPE patients were significantly increased as compared to the non-HAPE group. Interestingly, increased plasma levels of these two protein factors were markedly reduced after treatments. As compared to VEGF, sFlt-1 was much more affected by hypoxia and treatments, suggesting this factor was a key factor contributed to HAPE pathogenesis. Importantly, the ratio of sFlt-1 and VEGF in group of either non-HAPE or HAPE after recovery was significantly lower than the ratio in HAPE patients prior to treatments. Our findings suggested that sFlt-1 was a key factor that involved in HAPE pathogenesis and the sFlt-1/VEGF ratio could be used as a sensitive diagnostic marker for HAPE

Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells

We recently discovered that dectin-1-activated dendritic cells (DCs) drive potent T helper (Th) 9 cell responses and antitumor immunity. However, the underlying mechanisms need to be further defined. The cytokine microenvironment is critical for Th cell differentiation. Here, we show that dectin-1 activation enhances interleukin (IL)-33 expression in DCs. We found that blocking IL-33/ST2 inhibits dectin-1-activated DC-induced Th9 cell differentiation. More importantly, the addition of IL-33 further promotes Th9 cell priming and antitumor efficacy induced by dectin-1-activated DCs. Mechanistically, in addition to the promotion of Th9 and Th1 cells, dectin-1-activated DCs combined with IL-33 abolish the activity of IL-33 in the induction of regulatory T cells. Furthermore, the combined treatment of dectin-1-activated DCs and IL-33 increases the frequencies of CD4+ T cells by fostering their proliferation and inhibiting their exhaustive differentiation. Thus, our results demonstrate the important role of IL-33 in dectin-1-activated DC-induced Th9 cell differentiation and antitumor efficacy, and suggest that the combination of dectin-1-activated DCs and IL-33 may present a new effective modality of DC-based vaccines in tumor immunotherapy

Cyclin E overexpression sensitizes triple negative breast cancer to Wee1 kinase Inhibition

Purpose: Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression of cyclin E and phosphorylated-CDK2 are correlated with poor survival in TNBC patients, and the absence of CDK2 desensitizes cells to inhibition of Wee1 kinase, a key cell cycle regulator. We hypothesize that cyclin E expression can predict response to therapies, which include the Wee1 kinase inhibitor, AZD1775. Experimental Design: Mono and combination therapies with AZD1775 were evaluated in TNBC cell lines and multiple patient derived xenograft (PDX) models with different cyclin E expression profiles. The mechanism(s) of cyclin E-mediated replicative stress were investigated following cyclin E induction or CRISPR/Cas9 knockout by a number of assays in multiple cells lines. Results: Cyclin E overexpression (1) is enriched in TNBCs with high recurrence rates, (2) sensitizes TNBC cell lines and PDX models to AZD1775, (3) leads to CDK2-dependent activation of DNA replication stress pathways and (4) increases Wee1 kinase activity. Moreover, treatment of cells with either CDK2 inhibitors or carboplatin leads to transient transcriptional induction of cyclin E (in cyclin E-low tumors) and result in DNA replicative stress. Such drug mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy. Conclusions: Cyclin E is a potential biomarker of response (1) for AZD1775 as monotherapy in cyclin E high TNBC tumors and (2) for sequential combination therapy with CDK2 inhibitor or carboplatin followed by AZD1775 in cyclin E low TNBC tumors

Direct Synthesis of α-Silicon Nitride Nanowires from Silicon Monoxide on Alumina

Silicon nitride nanowires were synthesized using silicon monoxide as raw materials and an alumina plate as substrate at 1500°C. The obtained nanowires were characterized by X-ray diffraction, Fourier transform infrared spectrosco‐ py, scanning electron microscopy, high-resolution trans‐ mission electron microscopy and thermogravimetric- differential scanning calorimetry. The results revealed that silicon nitride nanowires possess a diameter of about 200 nm and a length of several hundred micrometres. The preferred growth direction of the nanowires was [100]. The chemical and structural composition of the silicon nitride nanowires were also studied and were shown to have a composition of primarily α-Si3N4. The temperature for fierce oxidation in air was above 1135°C. The formation mecha‐ nism of silicon nitride nanowires was assumed to be a vapour-solid (VS) process

(Effect of hydrophilicity of dust particles on their removal efficiency in a gas cyclone with atomized water vapor)

In this paper, the effect of hydrophilicity of dust particles on their removal efficiency in a gas cyclone with atomized water vapor was studied by experiments. The water vapor was generated by electro-acoustic transducing ultrasonic atomization technique. Several kinds of industrial dust with different hydrophilicities were injected in the cyclone and their removal efficiencies were measured and compared. The results showed generally the removal efficiency will increase with water vapor added to the cyclone. Such increase will be more significant for more hydrophilic dust particles. The removal efficiency of the talcum powder increased from 76.9% to 90.1% by 13.2% when 4 g•m-3 vapor was added. However, for the S-zorb desulfurization catalyst with poorer hydrophilicity, the increase was only 8.0% with the same amount of vapor. The effect of hydrophilicity was especially manifested in fine particles with diameter about 2.5 μm. The highest increase of the removal efficiency of the talcum powder appeared at particle size 2 μm, which was from 31.5% to 72.8% with 4 g•m-3 vapor added,while the highest increase of that of the S-zorb desulfurization catalyst was only from 43.9% to 61.6% at particle size 2.3 μm. Moreover, the dust particles before and after the cyclonewere examined by scanning electron microscopy (SEM) images, and the results confirmed the hydrophilicity has a significant impact on the agglomeration and growth of particles, which should be responsible for the difference in the removal efficiency of different particles. These studies could help optimize and improve the cloud-air-purifying (CAP) technology that combines gas cyclone with atomized water vapor technologies, and extend its versatility to industrial applications for decreasing the emission of PM2.5

Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model

Breakthrough cancer pain (BTcP) is a high-intensity, short-duration, unpredictable and uncontrollable pain. Recent studies have shown that activation of gap junction (GJ) in spinal cord plays an important role in the pathogenesis of BTcP. We examined the expressions of Glial fibrillary acidic protein (GFAP), connexin (Cx) 43 protein and phosphorylation of Cx43 (p-Cx43) in the spinal cord of mice. In addition, we investigated the effects of Gap26, a selective GJ blocker, on the expressions of GFAP, Cx43 and p-Cx43 in BTcP mice. We found that the expressions of GFAP and Cx43 proteins were significantly upregulated while p-Cx43 was down-regulated in the spinal cord in a mouse model of BTcP. The overexpression of Cx43 protein in the spinal cord increased GJ formation and enhanced BTcP. The variation of the ratio of p-Cx43/T-Cx43 (total Cx43) affected the function of GJ to induce BTcP. Furthermore, BTcP was alleviated by Gap26 via reducing pain hypersensitivity. The inhibition of Cx43 and p-Cx43 by Gap26 attenuated BTcP but the p/T ratio of Cx43 remained unchanged in BTcP mice. We reveal that the expression and phosphorylation of Cx43 affected BTcP and GJ activation facilitated BTcP via a Cx43-mediated signaling in the spinal cord. The finding may provide a scientific rationale for discovery and development of novel therapeutic targets for the treatment of BTcP clinically