bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase noise analysis of voltage controlled oscillator used in cesium atomic clock
Authors: Zhi Menghui , Tang Liang , Qiao Donghai 
Published: March 2017

Coherent population trapping (CPT) cesium frequency standard plays a significant role in precision guidance of missile and global positioning system (GPS). Low noise 4.596 GHz voltage controlled oscillator (VCO) is an indispensable part of microwave signal source in cesium frequency standard. Low-phase noise is also the most important and difficult performance indicator of VCO. Starting from phase noise analysis method proposed by Leeson, the formulas about the relationship between phase noise of output signal of oscillator feedback model and phase fluctuation spectrum of amplifier, phase noise of oscillator are derived in this paper. Finally, the asymptote model of microwave oscillator is proposed based on the formula derivation. The experiment shows that when the reverse bias voltage of variode is 1.8 V, the designed oscillation frequency of VCO is 4.596 GHz, the power is −1 dBm and the DC power consumption is 19.6 mW. The tendency of phase noise simulation curve and actual test curve conform to asymptote model. The phase noise in 1 and 10 kHz is, respectively, −60.86 and −86.58 dBc/Hz. The significance of the paper lies in determining the main factors influencing oscillator phase noise and providing guiding direction for the design of low-phase noise VCO.
Scavenging energy from the motion of human lower limbs via a piezoelectric energy harvester
Authors: Fan Kangqi , Yu Bo , Zhu Yingmin , Liu Zhaohui , Wang Liansong 
Published: March 2017

Scavenging energy from human motion through piezoelectric transduction has been considered as a feasible alternative to batteries for powering portable devices and realizing self-sustained devices. To date, most piezoelectric energy harvesters (PEHs) developed can only collect energy from the uni-directional mechanical vibration. This deficiency severely limits their applicability to human motion energy harvesting because the human motion involves diverse mechanical motions. In this paper, a novel PEH is proposed to harvest energy from the motion of human lower limbs. This PEH is composed of two piezoelectric cantilever beams, a sleeve and a ferromagnetic ball. The two beams are designed to sense the vibration along the tibial axis and conduct piezoelectric conversion. The ball senses the leg swing and actuates the two beams to vibrate via magnetic coupling. Theoretical and experimental studies indicate that the proposed PEH can scavenge energy from both the vibration and the swing. During each stride, the PEH can produce multiple peaks in voltage output, which is attributed to the superposition of different excitations. Moreover, the root-mean-square (RMS) voltage output of the PEH increases when the walking speed ranges from 2 to 8 km/h. In addition, the ultra-low frequencies of human motion are also up-converted by the proposed design.
The earliest geological observations in Lithuania: a historical viewpoint
Authors: Grigelis A. 
Published: March 2017

Abstract
Our earliest knowledge of Lithuania's geology derives from historical data on the use of natural mineral resources in the daily life of its population, such as building stones, clay, chalk, amber and salt-bearing mineral waters. The first scientific data on geognosy appeared at the beginning of the eighteenth century in the works of educated monks. From the middle of the eighteenth century natural philosophy was taught at the Vilnius Academy. The last quarter of the eighteenth century is notable for the completion of the first geological maps compiled from field observations. The Department of Mineralogy was established in the secularized Vilnius University in 1803. Studies of mineralogy flourished there until the university's closure in 1832. Geological surveying was carried out under the auspices of the Russian Mines Department, which paid particular attention to the exploration of sources of salt, iron ores and coal. A number of localities of likely useful minerals were investigated, but they were not of sufficient quality to be economically viable. By the mid-nineteenth century, the geological survey in Lithuania had resulted in the recognition of Devonian, Jurassic, Cretaceous and Tertiary sedimentary rocks. Quaternary sediments were reported in hilly areas and sandy soils and notable occurrences of boulders were recorded in low-lying areas.
HDAC Inhibitor Panobinostat Engages Host Innate Immune Defenses to Promote the Tumoricidal Effects of Trastuzumab in HER2+ Tumors
Authors: Medon Mikolaj , Vidacs Eva , Vervoort Stephin J , Li Jason , Jenkins Misty R. , Ramsbottom Kelly M. , Trapani Joseph A. , Smyth Mark J. , Darcy Phillip K. , Atadja Peter W. , Henderson Michael A. , Johnstone Ricky W. , Haynes Nicole M. 
Published: March 2017

AbstractHistone deacetylase inhibitors (HDACi) may engage host immunity as one basis for their antitumor effects. Herein, we demonstrate an application of this concept using the HDACi panobinostat to augment the antitumor efficacy of trastuzumab (anti-HER2) therapy, through both tumor cell autonomous and nonautonomous mechanisms. In HER2+ tumors that are inherently sensitive to the cytostatic effects of trastuzumab, cotreatment with panobinostat abrogated AKT signaling and triggered tumor regression in mice that lacked innate and/or adaptive immune effector cells. However, the cooperative ability of panobinostat and trastuzumab to harness host anticancer immune defenses was essential for their curative activity in trastuzumab-refractory HER2+ tumors. In trastuzumab-resistant HER2+ AU565pv xenografts and BT474 tumors expressing constitutively active AKT, panobinostat enhanced the antibody-dependent cell-mediated cytotoxicity function of trastuzumab. IFNγ–mediated, CXCR3-dependent increases in tumor-associated NK cells underpinned the combined curative activity of panobinostat and trastuzumab in these tumors. These data highlight the immune-enhancing effects of panobinostat and provide compelling evidence that this HDACi can license trastuzumab to evoke NK-cell–mediated responses capable of eradicating trastuzumab-refractory HER2+ tumors. Cancer Res; 77(10); 2594–606. ©2017 AACR.
Acquired Resistance with Epigenetic Alterations Under Long-Term Antiangiogenic Therapy for Hepatocellular Carcinoma
Authors: Ohata Yoshiteru , Shimada Shu , Akiyama Yoshimitsu , Mogushi Kaoru , Nakao Keisuke , Matsumura Satoshi , Aihara Arihiro , Mitsunori Yusuke , Ban Daisuke , Ochiai Takanori , Kudo Atsushi , Arii Shigeki , Tanabe Minoru , Tanaka Shinji 
Published: March 2017

Abstract
Antiangiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma; however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human hepatocellular carcinoma cells by long-term treatment with VEGF receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones. Highlighting epigenetic alterations involved in drug resistance, we revealed that Tβ4 could be aberrantly expressed following demethylation of DNA and active modification of histone H3 at the promoter region. Ectopic overexpression of Tβ4 in hepatocellular carcinoma cells could significantly enhance sphere-forming capacities and infiltrating phenotypes in vitro, and promote growth of tumors refractory to the VEGFR multikinase inhibitor sorafenib in vivo. Clinically, sorafenib failed to improve the progression-free survival in patients with Tβ4-high hepatocellular carcinoma, indicating that Tβ4 expression could be available as a surrogate marker of susceptibility to this drug. This study suggests that Tβ4 expression triggered by epigenetic alterations could contribute to the development of resistance to antiangiogenic therapy by the acquisition of stemness, and that epigenetic control might be one of the key targets to regulate the resistance in hepatocellular carcinoma. Mol Cancer Ther; 16(6); 1155–65. ©2017 AACR.
Abstract A31: Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis
Authors: Liu Chun , Bronson Roderick T. , Wang Xiang-Dong 
Published: March 2017

Abstract
Ulcerative colitis is a risk factor for colon cancer. Dietary lutein, a nutrient rich in kale, is inversely associated with the risk of developing colon cancer in human observational epidemiologic studies. Besides lutein, kale also contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects on colonic inflammation and neoplasia than lutein alone. Additionally, it is unclear if lutein prevents colon neoplasia via the inhibition of colonic inflammation. Using a dextran sulfate sodium (DSS)-induced colitis and neoplasia mouse model, we evaluated the effects of dietary lutein supplementation and kale on the DSS-induced colorectal inflammation, ulceration, hyperplasia, dysplasia and cancer. Two hundred sixty four 8-week old Swiss-Webster (CFW) mice were assigned to one of ten groups (n = 26 to 27 in each group [13 males and 13 to 14 females]) for 21 weeks as follows: 1) 0.0005% of lutein plus DSS; 2) 0.001% of lutein plus DSS; 3) 0.002% of lutein plus DSS; 4) 0.005% of lutein plus DSS; 5) kale equivalent to 0.0005% of lutein plus DSS; 6) kale equivalent to 0.001% of lutein plus DSS; 7) kale equivalent to 0.002% of lutein plus DSS; 8) kale equivalent to 0.005% of lutein plus DSS; 9) DSS only; and 10) control with no treatment. During the 21-week experimental period, mouse body weights were recorded weekly. At week 7, the mice in groups 1-9 were given DSS for 4 cycles (1 cycle = 1 week 3% of DSS in drinking water followed by 2-week water) to induce colitis and colorectal neoplasia. This report described the findings on the presence of clinical signs of colitis (hemoccult and loose stools, which were evaluated at the end of each week throughout the experiments), and the findings from histopathological evaluations (inflammation, ulceration, hyperplasia, dysplasia, and neoplasia). Dietary lutein and kale, particularly two higher doses (0.002% and 0.005%), reduced the DSS-induced hemoccult and loose stools, as well as the DSS-induced inflammation, ulceration, hyperplasia, dysplasia, and neoplasia. These data suggest that dietary lutein and kale may prevent the DSS-induced colorectal inflammation and associated preneoplastic and neoplastic lesions.
Grant Funding Sources: This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2014-67017-21754 from the USDA National Institute of Food and Agriculture and by USDA/ARS grant 1950-51000-074S.
Citation Format: Chun Liu, Roderick T. Bronson, Xiang-Dong Wang. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A31.
Abstract A59: Glycosylation dynamically tunes the biophysical properties of the cancer cell glycocalyx
Authors: Shurer Carolyn , Paszek Matthew 
Published: March 2017

Abstract
Muc1 is a large, heavily O-glycosylated membrane protein that is overexpressed in the majority of cancers and constitutes the major structural element of the cancer cell glycocalyx. While the biophysical properties of the glycocalyx directly regulate cell-ECM adhesion, cell-cell interactions, and receptor spatial organization, how these properties change dynamically during acquisition of a metastatic phenotype is largely unknown. To dissect the relationship among glycan biosynthesis, mucin rigidity, and the bulk properties of the cancer-specific glycocalyx, we isolated sub-populations of Muc1-expressing breast epithelial cells that present with distinct mucin glycophenotypes. Remarkably, alterations in glycosylation were associated with profound differences in glycocalyx structure, even in isogenic cell lines. In one stable glycophenotype, cellular mucins were highly rigid and mechanically disrupted integrin adhesion, resulting in complete dissociation of cells from the substrate. On the other extreme, we isolated a stable population of cells that expresses high levels of Muc1, but these mucins were apparently flexible and had no observable effect on cell adhesion or motility. Based on lectin profiling, we identified specific patterns of Muc1 O-glycosylation associated with the two extremes in glycocalyx structures. Of notable significance, we discovered that metabolic reprogramming by the H-Ras oncogene could induce a glycophenotype consistent with mechanically rigid mucins. Future studies will identify the specific glycosylation machinery associated with the different glycophenotypes, with the hope of identifying new avenues of therapeutic intervention based on normalizing the mechano-phenotype of the cancer cell glycocalyx.
Citation Format: Carolyn Shurer, Matthew Paszek. Glycosylation dynamically tunes the biophysical properties of the cancer cell glycocalyx. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A59.
Abstract P1-05-18: Genomic copy number alterations (CNA) associated with pCR in HER2-positive (HER2+) early-stage breast cancer (BrCa) patients receiving neoadjuvant trastuzumab (T)
Authors: Walsh N , Gullo G , Maguire A , O'Donovan N , Quinn C , Crown J 
Published: March 2017

Abstract
Introduction: Genetic alterations such as amplifications and deletions frequently contribute to tumorigenesis. These alterations can change gene expression which alters the normal cell growth and survival regulatory mechanisms. Characterisation of DNA copy number alterations (CNA) is important to understand cancer progression and response to therapy. The aim of this study is to determine patterns of CNAs in HER2+ early-stage BrCa patients achieving pathological complete response (pCR) to neoadjuvant T therapy.
Methods: Retrospective analysis of our database of 95 HER2+ BrCa (stages I-III) who received T neoadjuvantly revealed 46 % (44/95) achieved pCR compared with 53 % (51/95) who did not respond (NR). DNA from pre-treatment tumour biopsy specimens from neoadjuvant T therapy patients was extracted, and array-based comparative genomic hybridization (aCGH, n = 8; 6 pCR:2 NR) was used to identify CNAs, which correlated with pCR. Pathway analysis was then used to identify functionally relevant genes in aberrant regions.
Results: aCGH analysis of DNA from pCR and NR identified distinct patterns of CNAs. HER2 amplicon was confirmed by IHC and aCGH in all samples. Although there was no significant difference in the average CNAs between groups (20±17 vs 17±2), there was greater variation in the range of CNAs in pCR (8-56 CNA) compared to NR (15-19 CNA). More gains and amplifications were observed in pCR patients with more deletions in the NR group. The most common chromosomal amplification region included chr8q12.1-q24 with 87.5% of all cases displaying gains. Of the 6 patients who achieved pCR, 50% displayed a deletion in chr9 spanning p24.3-p21.3, consistent with a deletion of tumour suppressor CDKN2A. No aberrations in chr9 were observed in NR cohort. The deleted genomic region contained 65 common protein-coding genes, with the interferon biological pathway as the most significant (p=1.03E-36).
Conclusions: Distinct genomic CNAs were observed between patients achieving pCR compared to NR. However, of the 8 pts characterised here, none have relapsed. Follow-up data revealed a relapse rate of 6.8 % (3/44) vs 11.8 % (6/51) in the pCR and NR groups, respectively. To further elucidate the immunological response, we will present CNA data patterns on relapse and response and compare the impact of CNAs, immune-related proteins and pCR as surrogate predictors for outcome.
Citation Format: Walsh N, Gullo G, Maguire A, O'Donovan N, Quinn C, Crown J. Genomic copy number alterations (CNA) associated with pCR in HER2-positive (HER2+) early-stage breast cancer (BrCa) patients receiving neoadjuvant trastuzumab (T) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-18.
Abstract P3-05-07: Flutamide reduced tumor progression and altered steroid hormone secretion in human and canine inflammatory breast cancer cell lines
Authors: Caceres S , Pena L , Silvan G , Illera MJ , Monsalve B , Woodward WA , Reuben J , Illera JC 
Published: March 2017

Abstract
Background: Inflammatory breast carcinoma (IBC) is a special type of breast cancer with a poor survival rate and accounts for 6% of diagnosed breast cancers. The role of androgens on breast cancer is on rise in research, trying to propose anti-androgen therapeutic strategies. The aim of this study was to determine the effects in vivo and in vitro of flutamide (anti-androgen drug) on cell proliferation, tumor progression and steroid production in two cancer IBC triple negative cell lines (SUM-149 and IPC-366, human and canine, respectively). Material and Methods: IPC-366 was cultured in Dulbecco's modified Eagle medium nutrient mixture F-12 Ham (DMEM/F12) and SUM149 was maintained in Ham's F-12 media. Flutamide concentrations added to the culture media were: 5 µm, 10 µm, and 15 µm for 72 hours. Additionally, IPC-366 and SUM149 xenotrasplanted mice were used for in vivo assays with the same flutamide concentrations administrated subcutaneously. Steroid hormones determination in culture media and tumor homogenates (pregnenolone (P5), progesterone (P4), dihydroepiandrostenedione (DHEA), androstenedione (A4), testosterone (T), dihydritestosterone (DHT), 17β-estradiol (E2) and estrone sulphate (SO4E1)) were assayed by EIA previously validated. Immunohistochemical (IHC) analysis of the steroidogenic enzymes CYP11A1, 3β-HSD, CYP19A1, 17β-HSD and 5α-reductase were assayed. Results: Percentage of cell proliferation showed a decrease in all treatments in IPC-366 and SUM149. In vivo tumor progression was reduced in around 65% in IPC-366 and SUM149 xenotrasplanted mice. Regarding hormonal secretion assayed in pellets and homogenates. in treated groups there was an increased in steroid secretion as showed the high levels found in P5, P4 and A4. T and DHT concentrations were higher in treated groups, in contrast to E2 levels that decreased. 17β-HSD and 5α-reductase by IHC showed a high expression in treated groups. Conclusion: IPC-366 and SUM149 treated with flutamide reduced the proliferation of neoplastic cells, reduced tumor progression in xenotrasplanted mice and altered steroid hormone secretion by increasing T production and decreasing in E2 levels. These results open a future approach for IBC and triple negative breast cancer.
Citation Format: Caceres S, Pena L, Silvan G, Illera MJ, Monsalve B, Woodward WA, Reuben J, Illera JC. Flutamide reduced tumor progression and altered steroid hormone secretion in human and canine inflammatory breast cancer cell lines [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-05-07.
Abstract P4-05-02: Conditional inactivation of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) in the mouse mammary epithelium alters mammary gland development
Authors: Sheng L , Turner AG , Tarulli GA , Barratt K , Kremer R , Morris HA , Callen DF , Anderson PH 
Published: March 2017

Abstract
The biologically active form of vitamin D (1,25(OH)2D) regulates proliferation, differentiation, and apoptosis in diverse cell types. We have previously identified anti-proliferative activities of 1,25(OH)2D in human breast tissue, as well as 1,25(OH)2D target gene expression consistent with reports that elevated vitamin D levels may protect against cancer. In mouse studies, vitamin D signaling modulates normal mammary gland development, including ductal outgrowth and branching, and protects against tumorigenesis. Degradation of 1,25(OH)2D is initiated by the enzyme Cyp24a1 in target tissues, providing critical local control of 1,25(OH)2D bioactivity. In vitro, blockade of Cyp24a1 activity potentiates the anti-proliferative effects of 1,25(OH)2D. However, the extent to which endogenous Cyp24a1 activity within the mammary epithelium regulates local 1,25(OH)2D levels to modulate normal mammary gland development, with possible implications for cancer, has not been investigated. We generated a novel mouse model with conditional knockout of the Cyp24a1 gene specifically in the mammary epithelium (MMTV-Cre x Cyp24a1lox/lox). Ablation of Cyp24a1 activity in the mammary epithelium does not alter either gland or body weight at 4, 6 or 10 weeks of age. Preliminary analyses of mammary gland whole mounts indicate that virgin knockout mice form fewer terminal end buds compared to glands from wild-type littermates at 4 and 6 weeks of age (P&lt;0.05). Moreover, the width of the ducts proximal to the central lymph node of knockout mice was less than that of wild-type mice at 4 and 10 weeks of age (P&lt;0.05 and P&lt;0.01, respectively). In addition, the number of secondary and tertiary branching points is reduced in mammary glands from knockout mice at 6 weeks of age (P&lt;0.05 and P&lt;0.01, respectively). In summary, our findings suggest that Cyp24a1 activity within epithelial cells plays a crucial role to modulate postnatal mammary gland development, presumably by limiting the local accumulation of 1,25(OH)2D.

Citation Format: Sheng L, Turner AG, Tarulli GA, Barratt K, Kremer R, Morris HA, Callen DF, Anderson PH. Conditional inactivation of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) in the mouse mammary epithelium alters mammary gland development [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-05-02.