Science.gov

Sample records for regional nodal failure

  1. The Association Between Biological Subtype and Isolated Regional Nodal Failure After Breast-Conserving Therapy

    SciTech Connect

    Wo, Jennifer Y.; Taghian, Alphonse G.; Nguyen, Paul L.; Raad, Rita Abi; Sreedhara, Meera B.A.; Bellon, Jennifer R.; Wong, Julia S.; Gadd, Michele A.; Smith, Barbara L.; Harris, Jay R.

    2010-05-01

    Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status-, progesterone receptor status-, and HER-2-status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients.

  2. Impact of Incidental Irradiation on Clinically Uninvolved Nodal Regions in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Involved-Field Radiation Therapy: Does Incidental Irradiation Contribute to the Low Incidence of Elective Nodal Failure?

    SciTech Connect

    Kimura, Tomoki; Togami, Taro; Nishiyama, Yoshihiro; Ohkawa, Motoomi; Takashima, Hitoshi

    2010-06-01

    Purpose: To evaluate the incidental irradiation dose to elective nodal regions in the treatment of advanced non-small-cell lung cancer with involved-field radiation therapy (IF-RT) and the pattern of elective nodal failure (ENF). Methods and Materials: Fifty patients with advanced non-small-cell lung cancer, who received IF-RT at Kagawa University were enrolled. To evaluate the dose of incidental irradiation, we delineated nodal regions with a Japanese map and the American Thoracic Society map (levels 1-11) in each patient retrospectively and calculated the dose parameters such as mean dose, D95, and V95 (40 Gy as the prescribed dose of elective nodal irradiation). Results: Using the Japanese map, the median mean dose was more than 40 Gy in most of the nodal regions, except at levels 1, 3, and 7. In particular, each dosimetric parameter of level 1 was significantly lower than those at other levels, and each dosimetric parameter of levels 10 to 11 ipsilateral (11I) was significantly higher than those in other nodal regions. Using the American Thoracic Society map, basically, the results were similar to those of the Japanese map. ENF was observed in 4 patients (8%), five nodal regions, and no mean dose to the nodal region exceeded 40 Gy. On the Japanese map, each parameter of these five nodal region was significantly lower than those of the other nodal regions. Conclusions: These results show that a high dose of incidental irradiation may contribute to the low incidence of ENF in patients who have received IF-RT.

  3. Does Lymphovascular Invasion Predict Regional Nodal Failure in Breast Cancer Patients With Zero to Three Positive Lymph Nodes Treated With Conserving Surgery and Radiotherapy? Implications for Regional Radiation

    SciTech Connect

    Boutrus, Rimoun; Abi-Raad, Rita; Niemierko, Andrzej; Brachtel, Elena F.; Rizk, Levi; Kelada, Alexandra; Taghian, Alphonse G.

    2010-11-01

    Purpose: To examine the relationship between lymphovascular invasion (LVI) and regional nodal failure (RNF) in breast cancer patients with zero to three positive nodes treated with breast-conservation therapy (BCT). Methods and Materials: The records of 1,257 breast cancer patients with zero to three positive lymph nodes were reviewed. All patients were treated with BCT at Massachusetts General Hospital from 1980 to December 2003. Lymphovascular invasion was diagnosed by hematoxylin and eosin-stained sections and in some cases supported by immunohistochemical stains. Regional nodal failure was defined as recurrence in the ipsilateral supraclavicular, axillary, or internal mammary lymph nodes. Regional nodal failure was diagnosed by clinical and/or radiologic examination. Results: The median follow-up was 8 years (range, 0.1-21 years). Lymphovascular invasion was present in 211 patients (17%). In univariate analysis, patients with LVI had a higher rate of RNF (3.32% vs. 1.15%; p = 0.02). In multivariate analysis, only tumor size, grade, and local failure were significant predictors of RNF (p = 0.049, 0.013, and 0.0001, respectively), whereas LVI did not show a significant relationship with RNF (hazard ratio = 2.07; 95% CI, 0.8-5.5; p = 0.143). The presence of LVI in the T2/3 population did not increase the risk of RNF over that for those with no LVI (p = 0.15). In addition, patients with Grade 3 tumors and positive LVI did not have a higher risk of RNF than those without LVI (p = 0.96). Conclusion: These results suggest that LVI can not be used as a sole indicator for regional nodal irradiation in breast cancer patients with zero to three positive lymph nodes treated with BCT.

  4. Regional Nodal Involvement and Patterns of Spread Along In-Transit Pathways in Children With Rhabdomyosarcoma of the Extremity: A Report From the Children's Oncology Group;Rhabdomyosarcoma; Regional failure; In-transit nodes; Radiotherapy; Extremity

    SciTech Connect

    La, Trang H.; Wolden, Suzanne L.; Rodeberg, David A.; Hawkins, Douglas S.; Anderson, James R.; Donaldson, Sarah S.

    2011-07-15

    Purpose: To evaluate the incidence and prognostic factors for regional failure, with attention to the in-transit pathways of spread, in children with nonmetastatic rhabdomyosarcoma of the extremity. Methods and Materials: The Intergroup rhabdomyosarcoma studies III, IV-Pilot, and IV enrolled 226 children with rhabdomyosarcoma of the extremity. Failure at the in-transit (epitrochlear/brachial and popliteal) and proximal (axillary/infraclavicular and inguinal/femoral) lymph nodes was evaluated. The median follow-up for the surviving patients was 10.4 years. Results: Of the 226 children, 55 (24%) had clinical or pathologic evidence of either in-transit and/or proximal lymph node involvement at diagnosis. The actuarial 5-year risk of regional failure was 12%. The prognostic factors for poor regional control were female gender and lymph node involvement at diagnosis. In the 116 patients with a distal extremity primary tumor, 5% had in-transit lymph node involvement at diagnosis. The estimated 5-year incidences of in-transit and proximal nodal failure was 12% and 8%, respectively. The in-transit failure rate was 0% for patients who underwent radiotherapy and/or underwent lymph node sampling of the in-transit nodal site but was 15% for those who did not (p = .07). However, the 5-year event-free survival rate did not differ between these two groups (64% vs. 55%, respectively, p = .47). Conclusion: The high incidence of regional involvement necessitates aggressive identification and treatment of regional lymph nodes in patients with rhabdomyosarcoma of the extremity. In patients with distal extremity tumors, in-transit failures were as common as failures in more proximal regional sites. Patients who underwent complete lymph node staging with appropriate radiotherapy to the in-transit nodal site, if indicated, were at a slightly lower risk of in-transit failure.

  5. Nodal failure index approach to groundwater remediation design

    USGS Publications Warehouse

    Lee, J.; Reeves, H.W.; Dowding, C.H.

    2008-01-01

    Computer simulations often are used to design and to optimize groundwater remediation systems. We present a new computationally efficient approach that calculates the reliability of remedial design at every location in a model domain with a single simulation. The estimated reliability and other model information are used to select a best remedial option for given site conditions, conceptual model, and available data. To evaluate design performance, we introduce the nodal failure index (NFI) to determine the number of nodal locations at which the probability of success is below the design requirement. The strength of the NFI approach is that selected areas of interest can be specified for analysis and the best remedial design determined for this target region. An example application of the NFI approach using a hypothetical model shows how the spatial distribution of reliability can be used for a decision support system in groundwater remediation design. ?? 2008 ASCE.

  6. Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

    PubMed Central

    Seol, Ki Ho

    2016-01-01

    Purpose To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Materials and Methods Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4–72 Gy (39.6–45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. Results The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. Conclusion No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC. PMID:27104162

  7. Combined-modality therapy for patients with regional nodal metastases from melanoma

    SciTech Connect

    Ballo, Matthew T. . E-mail: mballo@mdanderson.org; Ross, Merrick I.; Cormier, Janice N.; Myers, Jeffrey N.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Hwu, Patrick; Zagars, Gunar K.

    2006-01-01

    Purpose: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Methods and Materials: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. Results: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed.

  8. Intra and Interfraction Mediastinal Nodal Region Motion: Implications for Internal Target Volume Expansions

    SciTech Connect

    Thomas, Jonathan G.; Kashani, Rojano; Balter, James M.; Tatro, Daniel; Kong, F.-M.; Pan, Charlie C.

    2009-07-01

    The purpose of this study was to determine the intra and interfraction motion of mediastinal lymph node regions. Ten patients with nonsmall-cell lung cancer underwent controlled inhale and exhale computed tomography (CT) scans during two sessions (40 total datasets) and mediastinal nodal stations 1-8 were outlined. Corresponding CT scans from different sessions were registered to remove setup error and, in this reference frame, the centroid of each nodal station was compared for right-left (RL), anterior-posterior (AP), and superior-inferior (SI) displacement. In addition, an anisotropic volume expansion encompassing the change of the nodal region margins in all directions was used. Intrafraction displacement was determined by comparing same session inhale-exhale scans. Interfraction reproducibility of nodal regions was determined by comparing the same respiratory phase scans between two sessions. Intrafraction displacement of centroid varied between nodal stations. All nodal regions moved posteriorly and superiorly with exhalation, and inferior nodal stations showed the most motion. Based on anisotropic expansion, nodal regions expanded mostly in the RL direction from inhale to exhale. The interpatient variations in intrafraction displacement were large compared with the displacements themselves. Moreover, there was substantial interfractional displacement ({approx}5 mm). Mediastinal lymph node regions clearly move during breathing. In addition, deformation of nodal regions between inhale and exhale occurs. The degree of motion and deformation varies by station and by individual. This study indicates the potential advantage of characterizing individualized nodal region motion to safely maximize conformality of mediastinal nodal targets.

  9. Typical nodal calcifications in the maxillofacial region: a case report

    PubMed Central

    Wu, Guomin; Sun, Xiumei; Ni, Shilei; Zhang, Zhimin

    2014-01-01

    Multiple nodal calcifications in the maxillofacial region are very rare. This case report described a 49-year-old female patient diagnosed with calcified lymph nodes due to chronic inflammation of the lymphatic nodes, including the parotid lymphatic nodes, the posterior auricular lymphatic nodes and submandibular lymphatic nodes in the right maxillofacial region. In clinical practice, we conducted ultrasonography, three-dimensional reconstruction of CT and sialography make a preliminary diagnosis. Then we took surgery, while removing the calcified blocks within the lymphatic node and cleaning the wound cavity. After surgery, we used anti-inflammatory therapy for one week. Six months follow-up indicated no evidence of other calcified lymph nodes infection. PMID:25356188

  10. Comparison between submucosal (extra-nodal) and nodal non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region.

    PubMed

    Shindoh, M; Takami, T; Arisue, M; Yamashita, T; Saito, T; Kohgo, T; Notani, K; Totsuka, Y; Amemiya, A

    1997-07-01

    Fifty-two cases of non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region, comprising 31 submucosal (extra-nodal) and 21 cervical node NHLs, were investigated. The patients' ages ranged from 5 to 86 years, with a bimodal age distribution among young people below 12 years of age (average 8 years) and in those aged 30 years or older (average 60.3 years). The male-to-female gender difference ratio was 1.3:1. Patients presented with swelling as the major symptom. Histologically, diffuse, large cell malignant lymphoma was the most frequent type and 67.9% of lymphomas were of intermediate malignancy as defined by the Working Formulation for Clinical Usage. All submucosal lymphomas showed diffuse proliferation patterns, although follicular proliferation was identified in 5 of the 21 nodal lymphomas. Immunohistochemistry showed that the B-cell type was predominant, especially in nodal lymphomas. PMID:9234189

  11. Xenopus tropicalis nodal-related gene 3 regulates BMP signaling: an essential role for the pro-region.

    PubMed

    Haramoto, Yoshikazu; Tanegashima, Kousuke; Onuma, Yasuko; Takahashi, Shuji; Sekizaki, Hiroyuki; Asashima, Makoto

    2004-01-01

    In vertebrates, nodal-related genes are crucial for specifying mesendodermal cell fates. Six nodal-related genes have been identified in Xenopus, but only one, nodal, has been identified in the mouse. The Xenopus nodal-related gene 3 (Xnr3), however, lacks the mesoderm-inducing activity of the other five nodal-related genes in Xenopus, and can directly induce neural tissue in animal caps by antagonizing BMP signals. In this study, we isolated three clones of the Xenopus (Silurana) tropicalis nodal-related gene 3 (Xtnr3) and analyzed their function. The Xtnr3 genes show high homology to Xnr3 and have the same activity. Southern blot and genomic PCR analyses indicate that the X. tropicalis genome has duplications in the Xtnr3 gene sequences and our three clones represent separate gene loci. We also found a partial clone of Xtnr3 that coded for the N-terminal part of its pro-region. Surprisingly, this sequence also induced neural tissue by antagonizing BMP signals, and its coded protein physically associated with BMP4 mature protein. Furthermore, we showed that the pro-region of Xnr5 has the same activity. Together, these findings indicate that the pro-region of nodal-related genes acts antagonistically towards BMP signals, which identifies a novel mechanism for the inhibition of BMP signaling. PMID:14697360

  12. Salvage therapy of small volume prostate cancer nodal failures: a review of the literature.

    PubMed

    De Bari, Berardino; Alongi, Filippo; Buglione, Michela; Campostrini, Franco; Briganti, Alberto; Berardi, Genoveffa; Petralia, Giuseppe; Bellomi, Massimo; Chiti, Arturo; Fodor, Andrei; Suardi, Nazareno; Cozzarini, Cesare; Nadia, Di Muzio; Scorsetti, Marta; Orecchia, Roberto; Montorsi, Francesco; Bertoni, Filippo; Magrini, Stefano Maria; Jereczek-Fossa, Barbara Alicja

    2014-04-01

    New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients. PMID:24315428

  13. Role of Ultrasonography of Regional Nodal Basins in Staging Triple-Negative Breast Cancer and Implications For Local-Regional Treatment

    SciTech Connect

    Shaitelman, Simona F.; Tereffe, Welela; Dogan, Basak E.; Hess, Kenneth R.; Caudle, Abigail S.; Valero, Vicente; Stauder, Michael C.; Krishnamurthy, Savitri; Candelaria, Rosalind P.; Strom, Eric A.; Woodward, Wendy A.; Hunt, Kelly K.; Buchholz, Thomas A.; Whitman, Gary J.

    2015-09-01

    Purpose: We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. Methods and Materials: We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients' disease with and without ultrasonography of the regional nodal basins were compared using the Pearson χ{sup 2} test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. Results: A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P<.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P<.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P<.0001). Conclusions: Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning.

  14. An essential role for maternal control of Nodal signaling

    PubMed Central

    Kumari, Pooja; Gilligan, Patrick C; Lim, Shimin; Tran, Long Duc; Winkler, Sylke; Philp, Robin; Sampath, Karuna

    2013-01-01

    Growth factor signaling is essential for pattern formation, growth, differentiation, and maintenance of stem cell pluripotency. Nodal-related signaling factors are required for axis formation and germ layer specification from sea urchins to mammals. Maternal transcripts of the zebrafish Nodal factor, Squint (Sqt), are localized to future embryonic dorsal. The mechanisms by which maternal sqt/nodal RNA is localized and regulated have been unclear. Here, we show that maternal control of Nodal signaling via the conserved Y box-binding protein 1 (Ybx1) is essential. We identified Ybx1 via a proteomic screen. Ybx1 recognizes the 3’ untranslated region (UTR) of sqt RNA and prevents premature translation and Sqt/Nodal signaling. Maternal-effect mutations in zebrafish ybx1 lead to deregulated Nodal signaling, gastrulation failure, and embryonic lethality. Implanted Nodal-coated beads phenocopy ybx1 mutant defects. Thus, Ybx1 prevents ectopic Nodal activity, revealing a new paradigm in the regulation of Nodal signaling, which is likely to be conserved. DOI: http://dx.doi.org/10.7554/eLife.00683.001 PMID:24040511

  15. Patterns of Failure for Rhabdomyosarcoma of the Perineal and Perianal Region

    SciTech Connect

    Casey, Dana L.; Wexler, Leonard H.; LaQuaglia, Michael P.; Meyers, Paul A.; Wolden, Suzanne L.

    2014-05-01

    Purpose: To analyze prognostic factors and patterns of failure for rhabdomyosarcoma of the perineal and perianal region (PRMS), with an emphasis on radiation therapy for locoregional control. Methods and Materials: Detailed records of all 14 patients treated for PRMS at Memorial Sloan-Kettering Cancer Center between 1998 and 2012 were reviewed. The Kaplan-Meier method was used to assess the event-free survival (EFS) and overall survival (OS), and a competing-risks analysis was used to assess the cumulative incidence of local, regional, and distant failures. Results: Median age was 15.8 years (range, 1.1-31.9 years). High-risk features were identified: 9 of 14 patients (64%) had group 3 disease and 3 of 14 (21%) had group 4; 11 of 14 tumors (78%) were alveolar; 12 of 14 tumors (86%) were ≥5 cm; and 9 of 14 patients (64%) had involved lymph nodes (N1). Of those aged ≥10 years at diagnosis, 9 of 10 (90%) had alveolar histology, all had tumors ≥5 cm, and 8 of 10 (80%) presented with N1 disease. The rates of local, regional, and distant failure at 5 years were 17%, 31%, and 52%, respectively. Although 3 of the 4 patients with regional failure received nodal irradiation, only one of the nodal failures occurred in the radiation therapy field. The 5-year EFS was 33%, and OS was 39%. Age ≥10 years was associated with poor outcomes: EFS was 13% in patients aged ≥10 years, compared with 75% in those aged <10 years (P=.04); the OS was 13% in patients aged ≥10 years, compared with 100% in those aged <10 years (P=.04). Conclusions: Patients with PRMS, especially those aged ≥10 years, present with poor prognostic features and continue to have poor outcomes. Given the high incidence of regional node recurrence, we recommend prophylactic ilioinguinal lymph node irradiation for all patients aged ≥10 years. For children aged <10 years, nodal evaluation is essential to determine the role for lymph node irradiation.

  16. Implant failure: regional versus cumulative evaluation.

    PubMed

    Lauc, T; Krnić, D; Katanec, D

    2000-07-01

    In this paper the success rate of implant therapy in various bone regions is discussed. The objective is to determine whether differences existed in success rates of cylinder implants placed in different areas in the both maxilla and mandible. Forty four patients have been treated and reviewed five years after the placement of the fixed prosthetic restoration. The patients were provided with a total of 92 implants. Results from this study show very low survival rate for implants placed in anterior region of maxilla (55.6%) after five years. It is concluded that simple cumulative follow up studies do not entirely correspond to actual situations, positioning the implants has an important role in the planning of the implant therapy and that important factor for force compensation is not only the surrounding bone density, but also the region of the jaw where the implants are placed. PMID:10946471

  17. High sex determining region Y-box 2 (SOX2) expression correlates with absence of nodal metastasis in esophageal squamous cell carcinoma

    PubMed Central

    Chuang, Wen-Yu; Chang, Yu-Sun; Chao, Yin-Kai; Yeh, Chi-Ju; Liu, Yun-Hen; Tseng, Chen-Kan; Chang, Hsien-Kun; Wan, Yung-Liang; Hsueh, Chuen

    2015-01-01

    Sex determining region Y-box 2 (SOX2) is a transcription factor involved in self-renewal and pluripotency. Dysregulation of SOX2 expression has been found in squamous cell carcinoma (SCC), including esophageal SCC. Recently, high SOX2 expression was found to be a negative predictor of occult lymph node metastasis in early oral SCC, but the clinical significance of SOX2 expression in esophageal SCC remains controversial. Here we investigated SOX2 expression by immunohistochemistry in 75 cases of surgically resected esophageal SCC. Similar to oral SCC, we found for the first time that high SOX2 expression correlates with absence of clinical nodal metastasis (P = 0.011). Podoplanin is a glycoprotein which is variably expressed by esophageal SCC. Since we previously found that podoplanin expression correlates with nodal metastasis in esophageal SCC, we also assessed podoplanin expression in these cases. Interestingly, SOX2 expression correlates negatively with podoplanin expression (P = 0.018). It is in contrast with a recent finding that SOX2 can up-regulate podoplanin expression in SCC of the skin. Our result suggests that SOX2 might suppress nodal metastasis through down-regulation of podoplanin in esophageal SCC. Further studies are needed to clarify the exact mechanism of regulation. PMID:26464673

  18. Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: What is the role of elective neck irradiation?

    SciTech Connect

    Chen, Allen M. . E-mail: allenmchen@yahoo.com; Garcia, Joaquin; Lee, Nancy Y.; Bucci, M. Kara; Eisele, David W.

    2007-03-15

    Purpose: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). Methods and Materials: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinoma (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3-267 months). Results: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. Conclusion: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.

  19. Radiotherapy for Esthesioneuroblastoma: Is Elective Nodal Irradiation Warranted in the Multimodality Treatment Approach?

    SciTech Connect

    Noh, O Kyu; Lee, Sang-wook; Yoon, Sang Min; Kim, Sung Bae; Kim, Sang Yoon; Kim, Chang Jin; Jo, Kyung Ja; Choi, Eun Kyung; Song, Si Yeol; Kim, Jong Hoon; Ahn, Seung Do

    2011-02-01

    Purpose: The role of elective nodal irradiation (ENI) in radiotherapy for esthesioneuroblastoma (ENB) has not been clearly defined. We analyzed treatment outcomes of patients with ENB and the frequency of cervical nodal failure in the absence of ENI. Methods and Materials: Between August 1996 and December 2007, we consulted with 19 patients with ENB regarding radiotherapy. Initial treatment consisted of surgery alone in 2 patients; surgery and postoperative radiotherapy in 4; surgery and adjuvant chemotherapy in 1; surgery, postoperative radiotherapy, and chemotherapy in 3; and chemotherapy followed by radiotherapy or concurrent chemoradiotherapy in 5. Five patients did not receive planned radiotherapy because of disease progression. Including 2 patients who received salvage radiotherapy, 14 patients were treated with radiotherapy. Elective nodal irradiation was performed in 4 patients with high-risk factors, including 3 with cervical lymph node metastasis at presentation. Results: Fourteen patients were analyzable, with a median follow-up of 27 months (range, 7-64 months). The overall 3-year survival rate was 73.4%. Local failure occurred in 3 patients (21.4%), regional cervical failure in 3 (21.4%), and distant failure in 2 (14.3%). No cervical nodal failure occurred in patients treated with combined systemic chemotherapy regardless of ENI. Three cervical failures occurred in the 4 patients treated with ENI or neck dissection (75%), none of whom received systemic chemotherapy. Conclusions: ENI during radiotherapy for ENB seems to play a limited role in preventing cervical nodal failure. Omitting ENI may be an option if patients are treated with a combination of radiotherapy and chemotherapy.

  20. Selective Nodal Irradiation on Basis of {sup 18}FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

    SciTech Connect

    Loon, Judith van; De Ruysscher, Dirk; Wanders, Rinus; Boersma, Liesbeth; Simons, Jean; Oellers, Michel; Dingemans, Anne-Marie C.; Hochstenbag, Monique; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Teule, Jaap; Rhami, Ali; Thimister, Willy; Snoep, Gabriel; Dehing-Oberije, Cary; Lambin, Philippe

    2010-06-01

    Purpose: To evaluate the results of selective nodal irradiation on basis of {sup 18}F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. Methods and Materials: A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. Results: A difference was seen in the involved nodal stations between the pretreatment {sup 18}F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. Conclusion: PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

  1. Risk Factors for Regional Nodal Relapse in Breast Cancer Patients With One to Three Positive Axillary Nodes

    SciTech Connect

    Yates, Lucy; Kirby, Anna; Crichton, Siobhan; Gillett, Cheryl; Cane, Paul; Fentiman, Ian; Sawyer, Elinor

    2012-04-01

    Purpose: In many centers, supraclavicular fossa radiotherapy (SCF RT) is not routinely offered to breast cancer patients with one to three positive lymph nodes. We aimed to identify a subgroup of these patients who are at high risk of supra or infraclavicular fossa relapse (SCFR) such that they can be offered SCFRT at the time of diagnosis to improve long term locoregional control. Methods and Materials: We performed a retrospective analysis of the pathological features of 1,065 cases of invasive breast cancer with one to three positive axillary lymph nodes. Patients underwent radical breast conserving surgery or mastectomy. A total of 45% of patients received adjuvant chest wall/breast RT. No patients received adjuvant SCFRT. The primary outcome was SCFR. Secondary outcomes were chest wall/breast recurrence, distant metastasis, all death, and breast-cancer specific death. Kaplan-Meier estimates were used to calculate actuarial event rates and survival functions compared using log-rank tests. Multivariate analyses (MVA) of factors associated with outcome were conducted using Cox proportional hazards models. Results: Median follow-up was 9.7 years. SCFR rate was 9.2%. Median time from primary diagnosis to SCFR was 3.4 years (range, 0.7-14.4 years). SCFR was associated with significantly lower 10-year survival (18% vs. 65%; p < 0.001). Higher grade and number of positive lymph nodes were the most significant predictors of SCFR on MVA (p < 0.001). 10 year SCFR rates were less than 1% in all patients with Grade 1 cancers compared with 30% in those having Grade 3 cancers with three positive lymph nodes. Additional factors associated with SCFR on univariate analysis but not on MVA included larger nodal deposits (p = 0.002) and proportion of positive nodes (p = 0.003). Conclusions: Breast cancer patients with one to three positive lymph nodes have a heterogenous risk of SCFR. Patients with two to three positive axillary nodes and/or high-grade disease may warrant

  2. Three-Dimensional Conformal Radiation Therapy for Esophageal Squamous Cell Carcinoma: Is Elective Nodal Irradiation Necessary?

    SciTech Connect

    Zhao Kuaile; Ma Jinbo; Liu Guang; Wu Kailiang; Shi Xuehui; Jiang Guoliang

    2010-02-01

    Purpose: To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. Methods and Materials: A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. Results: All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. Conclusions: In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems.

  3. Human Cerberus Prevents Nodal-Receptor Binding, Inhibits Nodal Signaling, and Suppresses Nodal-Mediated Phenotypes

    PubMed Central

    Aykul, Senem; Ni, Wendi; Mutatu, Washington; Martinez-Hackert, Erik

    2015-01-01

    The Transforming Growth Factor-ß (TGFß) family ligand Nodal is an essential embryonic morphogen that is associated with progression of breast and other cancers. It has therefore been suggested that Nodal inhibitors could be used to treat breast cancers where Nodal plays a defined role. As secreted antagonists, such as Cerberus, tightly regulate Nodal signaling during embryonic development, we undertook to produce human Cerberus, characterize its biochemical activities, and determine its effect on human breast cancer cells. Using quantitative methods, we investigated the mechanism of Nodal signaling, we evaluated binding of human Cerberus to Nodal and other TGFß family ligands, and we characterized the mechanism of Nodal inhibition by Cerberus. Using cancer cell assays, we examined the ability of Cerberus to suppress aggressive breast cancer cell phenotypes. We found that human Cerberus binds Nodal with high affinity and specificity, blocks binding of Nodal to its signaling partners, and inhibits Nodal signaling. Moreover, we showed that Cerberus profoundly suppresses migration, invasion, and colony forming ability of Nodal expressing and Nodal supplemented breast cancer cells. Taken together, our studies provide mechanistic insights into Nodal signaling and Nodal inhibition with Cerberus and highlight the potential value of Cerberus as anti-Nodal therapeutic. PMID:25603319

  4. Zero-energy bound states in a nodal topological lattice

    NASA Astrophysics Data System (ADS)

    Lee, Soo-Yong; Han, Jung Hoon

    2015-06-01

    A nodal topological lattice is a form of magnetic crystal with topologically nontrivial spin texture, which further exhibits a periodic array of nodes with vanishing magnetization. An electronic structure for conduction electrons strongly Hund coupled to such a nodal topological lattice is examined. Our analysis shows that each node attracts two localized states which form narrow bands through internode hybridization within the mid-gap region. Nodal bands carry a Chern number under suitable perturbations, suggesting their potential role in the topological Hall effect. Enhancement of the density of states near zero energy observable in a tunneling experiment will provide a signature of the formation of a nodal topological lattice.

  5. Temporal Nodal Regression and Regional Control After Primary Radiation Therapy for N2-N3 Head-and-Neck Cancer Stratified by HPV Status

    SciTech Connect

    Huang, Shao Hui; O'Sullivan, Brian; Ringash, Jolie; Hope, Andrew; Gilbert, Ralph; Irish, Jonathan; Perez-Ordonez, Bayardo; Weinreb, Ilan; Waldron, John

    2013-12-01

    Purpose: To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related [HPV(+)] versus human papillomavirus-unrelated [HPV(−)] head-and-neck cancer (HNC). Methods and Materials: All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV(−). Initial radiologic complete nodal response (CR) (≤1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV(−) HNC. Multivariate analysis identified outcome predictors. Results: A total of 257 HPV(+) and 236 HPV(−) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(−) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(−) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(−) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(−) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(−) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(−) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 [95% confidence interval, 1.1-1.7]; P<.01) and RC (hazard ratio, 0.3 [95% confidence interval 0.2-0.6]; P<.01). Conclusions: HPV(+) LNs involute more quickly than HPV(−) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to 12

  6. Study on Flexible Pavement Failures in Soft Soil Tropical Regions

    NASA Astrophysics Data System (ADS)

    Jayakumar, M.; Chee Soon, Lee

    2015-04-01

    Road network system experienced rapid upgrowth since ages ago and it started developing in Malaysia during the colonization of British due to its significant impacts in transportation field. Flexible pavement, the major road network in Malaysia, has been deteriorating by various types of distresses which cause descending serviceability of the pavement structure. This paper discusses the pavement condition assessment carried out in Sarawak and Sabah, Malaysia to have design solutions for flexible pavement failures. Field tests were conducted to examine the subgrade strength of existing roads in Sarawak at various failure locations, to assess the impact of subgrade strength on pavement failures. Research outcomes from field condition assessment and subgrade testing showed that the critical causes of pavement failures are inadequate design and maintenance of drainage system and shoulder cross fall, along with inadequate pavement thickness provided by may be assuming the conservative value of soil strength at optimum moisture content, whereas the exiting and expected subgrade strengths at equilibrium moisture content are far below. Our further research shows that stabilized existing recycled asphalt and base materials to use as a sub-base along with bitumen stabilized open graded base in the pavement composition may be a viable solution for pavement failures.

  7. Nodal Promotes Glioblastoma Cell Growth

    PubMed Central

    De Silva, Tanya; Ye, Gang; Liang, Yao-Yun; Fu, Guodong; Xu, Guoxiong; Peng, Chun

    2012-01-01

    Nodal is a member of the transforming growth factor-β (TGF-β) superfamily that plays critical roles during embryogenesis. Recent studies in ovarian, breast, prostate, and skin cancer cells suggest that Nodal also regulates cell proliferation, apoptosis, and invasion in cancer cells. However, it appears to exert both tumor-suppressing and tumor-promoting effects, depending on the cell type. To further understand the role of Nodal in tumorigenesis, we examined the effect of Nodal in glioblastoma cell growth and spheroid formation using U87 cell line. Treatment of U87 with recombinant Nodal significantly increased U87 cell growth. In U87 cells stably transfected with the plasmid encoding Nodal, Smad2 phosphorylation was strongly induced and cell growth was significantly enhanced. Overexpression of Nodal also resulted in tight spheroid formation. On the other hand, the cells stably transfected with Nodal siRNA formed loose spheroids. Nodal is known to signal through activin receptor-like kinase 4 (ALK4) and ALK7 and the Smad2/3 pathway. To determine which receptor and Smad mediate the growth promoting effect of Nodal, we transfected siRNAs targeting ALK4, ALK7, Smad2, or Smad3 into Nodal-overexpressing cells and observed that cell growth was significantly inhibited by ALK4, ALK7, and Smad3 siRNAs. Taken together, these findings suggest that Nodal may have tumor-promoting effects on glioblastoma cells and these effects are mediated by ALK4, ALK7, and Smad3. PMID:22645523

  8. The structural robustness of geographical networks against regional failure and their pre-optimization

    NASA Astrophysics Data System (ADS)

    Li, Yixiao; Zhang, Lin; Huang, Chaogeng; Shen, Bin

    2016-06-01

    Failures of real-world infrastructure networks due to natural disasters often originate in a certain region, but this feature has seldom been considered in theoretical models. In this article, we introduce a possible failure pattern of geographical networks-"regional failure"-by which nodes and edges within a region malfunction. Based on a previous spatial network model (Louf et al., 2013), we study the robustness of geographical networks against regional failure, which is measured by the fraction of nodes that remain in the largest connected component, via simulations. A small-area failure results in a large reduction of their robustness measure. Furthermore, we investigate two pre-deployed mechanisms to enhance their robustness: One is to extend the cost-benefit growth mechanism of the original network model by adding more than one link in a growth step, and the other is to strengthen the interconnection of hubs in generated networks. We measure the robustness-enhancing effects of both mechanisms on the basis of their costs, i.e., the amount of excessive links and the induced geographical length. The latter mechanism is better than the former one if a normal level of costs is considered. When costs exceed a certain level, the former has an advantage. Because the costs of excessive links affect the investment decision of real-world infrastructure networks, it is practical to enhance their robustness by adding more links between hubs. These results might help design robust geographical networks economically.

  9. Topological semimetals and nodal superconductors

    NASA Astrophysics Data System (ADS)

    Chang, Po-Yao

    Besides topological band insulators, which have a full bulk gap, there are also gapless phases of matter that belong to the broad class of topological materials, such as topological semimetals and nodal superconductors. We systematically study these gapless topological phases described by the Bloch and Bogoliubov-de Gennes Hamiltonians. We discuss a generalized bulk-boundary correspondence, which relates the topological properties in the bulk of gapless topological phases and the protected zero-energy states at the boundary. We study examples of gapless topological phases, focusing in particular on nodal superconductors, such as nodal noncentrosymmetric superconductors (NCSs). We compute the surface density of states of nodal NCSs and interpret experimental measurements of surface states. In addition, we investigate Majorana vortex-bound states in both nodal and fully gapped NCSs using numerical and analytical methods. We show that different topological properties of the bulk Bogoliubov-quasiparticle wave functions reflect themselves in different types of zero-energy vortex-bound states. In particular, in the case of NCSs with tetragonal point-group symmetry, we find that the stability of these Majorana zero modes is guaranteed by a combination of reflection, time-reversal, and particle-hole symmetries. Finally, by using K-theory arguments and a dimensional reduction procedure from higher-dimensional topological insulators and superconductors, we derive a classification of topologically stable Fermi surfaces in semimetals and nodal lines in superconductors.

  10. Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Hsu, Feng-Ming; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh; Lee, Yung-Chie; Chia-Hsien Cheng, Jason

    2011-11-15

    Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal

  11. Wnt/Axin1/β-Catenin Signaling Regulates Asymmetric Nodal Activation, Elaboration, and Concordance of CNS Asymmetries

    PubMed Central

    Carl, Matthias; Bianco, Isaac H.; Bajoghli, Baubak; Aghaallaei, Narges; Czerny, Thomas; Wilson, Stephen W.

    2007-01-01

    Summary Nodal activity in the left lateral plate mesoderm (LPM) is required to activate left-sided Nodal signaling in the epithalamic region of the zebrafish forebrain. Epithalamic Nodal signaling subsequently determines the laterality of neuroanatomical asymmetries. We show that overactivation of Wnt/Axin1/β-catenin signaling during late gastrulation leads to bilateral epithalamic expression of Nodal pathway genes independently of LPM Nodal signaling. This is consistent with a model whereby epithalamic Nodal signaling is normally bilaterally repressed, with Nodal signaling from the LPM unilaterally alleviating repression. We suggest that Wnt signaling regulates the establishment of the bilateral repression. We identify a second role for the Wnt pathway in the left/right regulation of LPM Nodal pathway gene expression, and finally, we show that at later stages Axin1 is required for the elaboration of concordant neuroanatomical asymmetries. PMID:17678853

  12. Regional sensitivity analysis of aleatory and epistemic uncertainties on failure probability

    NASA Astrophysics Data System (ADS)

    Li, Guijie; Lu, Zhenzhou; Lu, Zhaoyan; Xu, Jia

    2014-06-01

    To analyze the effects of specific regions of the aleatory and epistemic uncertain variables on the failure probability, a regional sensitivity analysis (RSA) technique called contribution to failure probability (CFP) plot is developed in this paper. This RSA technique can detect the important aleatory and epistemic uncertain variables, and also measure the contribution of specific regions of these important input variables to failure probability. When computing the proposed CFP, the aleatory and epistemic uncertain variables are modeled by random and interval variables, respectively. Then based on the hybrid probabilistic and interval model (HPIM) and the basic probability assignments in evidence theory, the failure probability of the structure with aleatory and epistemic uncertainties can be obtained through a successive construction of the second-level limit state function and the corresponding reliability analysis. Kriging method is used to establish the surrogate model of the second-level limit state function to improve the computational efficiency. Two practical examples are employed to test the effectiveness of the proposed RSA technique, and the efficiency and accuracy of the established kriging-based solution.

  13. Evaluation of the use of nodal methods for MTR neutronic analysis

    SciTech Connect

    Reitsma, F.; Mueller, E.Z.

    1997-08-01

    Although modern nodal methods are used extensively in the nuclear power industry, their use for research reactor analysis has been very limited. The suitability of nodal methods for material testing reactor analysis is investigated with the emphasis on the modelling of the core region (fuel assemblies). The nodal approach`s performance is compared with that of the traditional finite-difference fine mesh approach. The advantages of using nodal methods coupled with integrated cross section generation systems are highlighted, especially with respect to data preparation, simplicity of use and the possibility of performing a great variety of reactor calculations subject to strict time limitations such as are required for the RERTR program.

  14. Molecular cytogenetic analysis of Xq critical regions in premature ovarian failure

    PubMed Central

    2013-01-01

    Background One of the frequent reasons for unsuccessful conception is premature ovarian failure/primary ovarian insufficiency (POF/POI) that is defined as the loss of functional follicles below the age of 40 years. Among the genetic causes the most common one involves the X chromosome, as in Turner syndrome, partial X deletion and X-autosome translocations. Here we report a case of a 27-year-old female patient referred to genetic counselling because of premature ovarian failure. The aim of this case study to perform molecular genetic and cytogenetic analyses in order to identify the exact genetic background of the pathogenic phenotype. Results For premature ovarian failure disease diagnostics we performed the Fragile mental retardation 1 gene analysis using Southern blot technique and Repeat Primed PCR in order to identify the relationship between the Fragile mental retardation 1 gene premutation status and the premature ovarion failure disease. At this early onset, the premature ovarian failure affected patient we detected one normal allele of Fragile mental retardation 1 gene and we couldn’t verify the methylated allele, therefore we performed the cytogenetic analyses using G-banding and fluorescent in situ hybridization methods and a high resolution molecular cytogenetic method, the array comparative genomic hybridization technique. For this patient applying the G-banding, we identified a large deletion on the X chromosome at the critical region (ChrX q21.31-q28) which is associated with the premature ovarian failure phenotype. In order to detect the exact breakpoints, we used a special cytogenetic array ISCA plus CGH array and we verified a 67.355 Mb size loss at the critical region which include total 795 genes. Conclusions We conclude for this case study that the karyotyping is definitely helpful in the evaluation of premature ovarian failure patients, to identify the non submicroscopic chromosomal rearrangement, and using the array CGH technique we can

  15. Less may be more: nodal treatment in neck positive head neck cancer patients.

    PubMed

    Studer, Gabriela; Huber, Gerhard F; Holz, Edna; Glanzmann, Christoph

    2016-06-01

    Ongoing debates about the need and extent of planned neck dissection (PND), and required nodal radiation doses volumes lead to this evaluation. Aim was to assess nodal control after definitive intensity modulated radiation therapy (IMRT ± systemic therapy) followed by PND in our head neck cancer cohort with advanced nodal disease. Between 01/2005 and 12/2013, 99 squamous cell cancer HNC patients with pre-therapeutic nodal metastasis ≥3 cm were treated with definitive IMRT followed by PND. In addition, outcome in 103 patients with nodal relapse after IMRT and observation only (no-PND cohort) were analyzed. Prior to PND, PET-CT, fine needle aspirations, ultrasound and palpation were assessed regarding its predictive value. Patterns of nodal relapse were assessed in patients with isolated neck failure after definitive IMRT alone. 70/99 (70 %) PND specimens showed histopathological complete response (hCR), which translated into statistically significantly superior survival compared with partial response (hPR) with 4-year overall survival, disease specific survival and nodal control rates of 90/83/96 vs 67/60/78 % (p = 0.002/0.001/0.003). 1/99 patient developed isolated subsequent nodal disease. 64/2147 removed nodes contained viable tumor (3 %). Predictive information of the performed diagnostic investigations was not reliable. 17/70 hCR patients showed true negative findings in available three to four investigations (0/29 hPR). 27/103 no-PND patients developed isolated neck disease (26 %) with successful salvage in 21/24 [88 %, or 21/27 (78 %)]. Nearly all failures occurred in the prior nodal gross tumor volume area. A more restrictive approach regarding PND and/or nodal IMRT dose-volumes may be justified. PMID:25920604

  16. CRRT Regional Anticoagulation Using Citrate in the Liver Failure and Liver Transplant Population.

    PubMed

    Wonnacott, Rob; Josephs, Brandi; Jamieson, Jill

    2016-01-01

    Regional citrate for continuous renal replacement therapy (CRRT) use in patients with liver failure or post-liver transplant has been considered a contraindication because of the risk of citrate toxicity development. Regional citrate has the benefit of decreased bleeding risks over systemic anticoagulation; therefore, it is of great benefit to the coagulopathic and surgical populations. This article analyzes current empiric data and compares with a case study specifically related to liver failure, liver transplant, and CRRT use. We found that the use of a total serum to ionized calcium ratio was much more reliable in measuring liver function than liver enzyme figures. This when paired with a citrate-reduction guideline based on serum to ionized calcium ratios provided effective, early management of citrate toxicity. Using new measurements to calculate liver metabolism of citrate and using a new citrate-reducing guideline allow the bedside practitioner to use regional citrate anticoagulation in patients with liver failure and liver transplant who require CRRT. PMID:27254640

  17. Synchronous Gastric Carcinoma and Nodal Malignant Lymphoma: A Rare Case Report and Literature Review.

    PubMed

    Xue, Li-Jun; Yang, Ji-Hong; Su, Quan-Sheng; Wang, Hai; Liu, Chang

    2010-01-01

    Synchronous double malignancies of gastric carcinoma (GC) and malignant lymphoma (ML) are rare and very difficult to treat. We report a case of synchronous GC and nodal ML, regarding which clinical and pathological features and treatment are discussed. A 68-year-old woman with a history of inguinal hernia was admitted for abdominal pain and high fever and subsequently underwent herniorrhaphy, but the fever remained. Computerized tomography showed a stomach mass and multiple enlarged lymph nodes in the abdominal cavity and inguinal regions. Gastric adenocarcinoma coexistent with advanced in situ follicular lymphoma was confirmed by endoscopy, biopsy of inguinal lymph nodes and bone marrow examination. Two chemotherapy regimens, R-CHOP (rituximab, cyclophosphamide, perarubicin, vincristine and prednisone) and systemic therapy (5-fluorouracil and calcium folinate) combined with regional perfusion (oxaliplatin and etoposide) through the left gastric artery were performed at intervals against ML and GC, respectively. Partial remission in both tumors was achieved after 4 courses of treatment, but the patient finally died of heart failure. Scrupulous biopsy of non-draining lymph nodes in patients with gastrointestinal carcinomas is supposed to improve the diagnostic rate of simultaneous nodal ML. The interval chemotherapy strategy with two independent regimens is beneficial for such patients, especially for those unable to tolerate major surgery. PMID:20740201

  18. Time-Dependent Regional Myocardial Strains in Patients with Heart Failure with a Preserved Ejection Fraction

    PubMed Central

    Smith, Shane P.; Secomb, Timothy W.; Hong, Brian D.; Moulton, Michael J.

    2016-01-01

    Objectives. To better understand the etiology of HFpEF in a controlled human population, regional time-varying strains were computed using echocardiography speckle tracking in patients with heart failure with a preserved ejection fraction and normal subjects. Methods. Eleven normal volunteers and ten patients with echo-graded diastolic dysfunction and symptoms of heart failure were imaged with echocardiography and longitudinal, circumferential, and rotational strains were determined using speckle-tracking. Diastolic strain rate was also determined. Patient demographics and echo-derived flows, volumes, and pressures were recorded. Results. Peak longitudinal and circumferential strain was globally reduced in patients (p < 0.001), when compared to controls. The patients attained peak longitudinal and circumferential strain at a consistently later point in systole than controls. Rotational strains were not different in most LV regions. Early diastolic strain rate was significantly reduced in the patients (p < 0.001). LV mass and wall thickness were significantly increased in the patients; however ejection fraction was preserved and stroke volume was diminished (p < 0.001). Conclusions. This study shows that patients with HFpEF have reduced early diastolic strain rate and reduced peak strain that is regionally homogeneous and that they also utilize a longer fraction of systole to achieve peak axial strains. PMID:27042673

  19. Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

    SciTech Connect

    Hodges, Joseph C.; Das, Prajnan; Eng, Cathy; Reish, Andrew G.; Beddar, A. Sam; Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H.

    2009-11-01

    Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions were treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.

  20. Freedom From Local and Regional Failure of Contralateral Neck With Ipsilateral Neck Radiotherapy for Node-Positive Tonsil Cancer: Results of a Prospective Management Approach

    SciTech Connect

    Rusthoven, Kyle E. Raben, David; Schneider, Charles; Witt, Robert; Sammons, Sarah; Raben, Adam

    2009-08-01

    Purpose: To review the outcomes of a prospective management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion. Methods and Materials: Between August 2003 and June 2007, 20 patients who presented with squamous cell carcinoma of the tonsil, without involvement of the base of the tongue or midline soft palate, and with Stage N1-N2b disease were prospectively treated with radiotherapy to the primary site and ipsilateral neck. In addition, 18 patients received concurrent chemotherapy. The actuarial freedom from contralateral nodal and in-field progression was determined. Acute and late toxicity were prospectively evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, and Radiation Therapy Oncology Group criteria. Results: The nodal disease was Stage N1 in 4 patients, N2a in 3 patients, and N2b in 13 patients. At a median follow-up 19 months (range, 12-40), no in-field or contralateral nodal recurrences had been observed. The 2-year freedom from distant metastasis rate was 87.4%. The actuarial 2-year disease-free and overall survival rates were both 79.5%. Late Radiation Therapy Oncology Group grade 2 xerostomia occurred in 1 patient (5%). No late Grade 3 or greater toxicity was observed. No patient was feeding tube dependent at their last follow-up visit. Conclusion: In carefully selected patients with node-positive, lateralized tonsillar cancer, treatment of the ipsilateral neck and primary site does not appear to increase the risk of contralateral nodal failure and reduces late morbidity compared with historical controls. Although the outcomes with ipsilateral radiotherapy in the present series were promising, these findings require longer follow-up and validation in a larger patient cohort.

  1. Occult Nodal Disease Prevalence and Distribution in Recurrent Laryngeal Cancer Requiring Salvage Laryngectomy

    PubMed Central

    Birkeland, Andrew C.; Rosko, Andrew J.; Issa, Mohamad R.; Shuman, Andrew G.; Prince, Mark E.; Wolf, Gregory T.; Bradford, Carol R.; McHugh, Jonathan B.; Brenner, J. Chad; Spector, Matthew E.

    2016-01-01

    Objectives The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort. Study Design Case series with planned data collection. Setting Tertiary academic center. Subjects Patients with persistent or recurrent laryngeal squamous cell carcinoma after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection. Methods We analyzed a single-institution retrospective case series of patients between 1997–2014 and identified those who had clinically N0 necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution were collected, and statistical analyses were performed. Results Overall, cN0 necks had histologically positive occult nodes in 17% (n=35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs. 12% non-T4; p=0.0003), and supraglottic subsite (28% supraglottic vs. 10% non-supraglottic; p=0.0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral level II and III (17% and 16%). Positive nodes for glottic SCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%). Conclusion Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based upon tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic SCCs, the most frequent sites of occult nodal disease are the paratracheal nodal basins. PMID:26884365

  2. Regional circulatory response to converting-enzyme inhibition in congestive heart failure

    PubMed Central

    Faxon, D. P.; Creager, M. A.; Halperin, J. L.

    1982-01-01

    1 To determine the distribution of flow, the regional haemodynamic response to 100 mg of captopril was determined in 36 patients with refractory cardiac heart failure. Measurements included forearm blood flow by venous occlusion plethysmography (eight patients), splanchnic blood flow by indocyanine green clearance (10 patients), and coronary blood flow by thermodilution (12 patients). 2 Cardiac index significantly rose in one hour (1.9 ± 0.1 to 2.2 ± 0.1 l/m/m2, p < 0.01) while forearm blood flow rose slightly (2.9 ± 0.8 to 3.2 ± 0.3 ml/100 ml/min). Renal blood flow rose significantly by 30% (344 ± 48 to 533 ± 82 ml/min, p < 0.02). Despite a fall in rate pressure product (8.8 ± 0.7 to 7.1 ± 0.5 mm Hg bt × 103, p < 0.02), coronary blood flow did not significantly change (160 ± 20 to 133 ± 12 ml/min), indicating an improved supply-demand relationship. 3 External myocardial efficiency improved (19 ± 3 to 26 ± 6%, p < 0.05). Coronary blood flow is unaffected and converting-enzyme inhibitor improves myocardial efficiency. This strategic reduction in vascular impedence distinguishes converting-enzyme inhibitors as a unique class of vasodilators in the treatment of coronary heart failure. PMID:6753899

  3. Performances and failure of field-aged PV modules operating in Saharan region of Algeria

    NASA Astrophysics Data System (ADS)

    Sadok, M.; Benyoucef, B.; Othmani, M.; Mehdaoui, A.

    2016-07-01

    This article deals with behaviour of PV modules, of different technologies and manufacturers, exposed for long periods in Saharan region of Algeria. These modules are exposed in Adrar in the south-western part of Algeria. The study uses experimental I-V curves of PV modules for determining their performances. The datasheet information of modules will be useful in determination of degradation rates of the modules. Three types of modules have been tested: Photowatt (PWX 500), UDTS-50 and Isofoton (I-75 and I-100 serials). Results showed that Isofoton I-100 modules present the highest degradation rate while the lowest degradation rate was reached with I-75 serial. However, these rates tallies with other studies. The visual inspection of the modules has revealed various kinds of failures and defects responsible of performances drop (EVA browning, delamination, burn marks,…).

  4. A New Stabilized Nodal Integration Approach

    SciTech Connect

    Puso, M; Zywicz, E; Chen, J S

    2006-02-08

    A new stabilized nodal integration scheme is proposed and implemented. In this work, focus is on the natural neighbor meshless interpolation schemes. The approach is a modification of the stabilized conforming nodal integration (SCNI) scheme and is shown to perform well in several benchmark problems.

  5. Heterogeneous treatment in the variational nodal method

    SciTech Connect

    Fanning, T.H.; Palmiotti, G.

    1995-06-01

    The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations.

  6. Recurrence in Region of Spared Parotid Gland After Definitive Intensity-Modulated Radiotherapy for Head and Neck Cancer

    SciTech Connect

    Cannon, Donald M.; Lee, Nancy Y.

    2008-03-01

    Purpose: To discuss the implications of three examples of periparotid recurrence after definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). Methods and Materials: We present 3 patients with HNC who underwent definitive IMRT with concurrent chemotherapy and later had treatment failure in or near a spared parotid gland. Two patients had bilateral multilevel nodal disease, and all had Level II nodal disease ipsilateral to the site of recurrence. The patients were treated using dose-painting IMRT with a dose of 70 Gy to the gross tumor volume and 59.4 Gy or 54 Gy to the high-risk or low-risk clinical tumor volume, respectively. The parotid glands were spared bilaterally. The patients had not undergone any surgical treatment for HNC before radiotherapy. Results: All patients had treatment failure in the region of a spared parotid gland. Failure in the 2 patients with bilateral multilevel nodal involvement occurred in the periparotid lymph nodes. The third patient developed a dermal metastasis near the tail of a spared parotid gland. On pretreatment imaging, the 2 patients with nodal failure had small nonspecific periparotid nodules that showed no hypermetabolic activity on positron emission tomography. Conclusion: For HNC patients receiving definitive IMRT, nonspecific positron emission tomography-negative periparotid nodules on pretreatment imaging should raise the index of suspicion for subclinical disease in the presence of multilevel or Level II nodal metastases. Additional evaluation of such nodules might be indicated before sparing the ipsilateral parotid gland.

  7. The Upside of Failure: How Regional Student Groups Learn from Their Mistakes

    PubMed Central

    Mishra, Tarun; Parra, R. Gonzalo; Abeel, Thomas

    2014-01-01

    Success is the result of planning, hard work, determination, foresight, and a little bit of luck. Unfortunately, nobody has thought to pave the road to success. Although failure can be discouraging and time-consuming, it presents incredible learning opportunities—the biggest difference between those who succeed and those who abandon their projects lies in their response to adversity. This article reviews events undertaken by the Regional Student Groups (RSGs) in India and Argentina, the problems they encountered, and what can be learned from them. RSG-India attempted to organize an online scientific meeting (also known as a virtual conference) with geographically dispersed stakeholders, a totally new concept for them. RSG-Argentina tackled the challenge of organizing a two-day symposium, their first event ever. Some of the complications they faced were easy to fix, others led to the cancellation of activities, and all of them resulted in valuable lessons. The main goal of this article is to highlight, through their experiences, the universal importance of a healthy panel of contingency plans. PMID:25101799

  8. The upside of failure: how regional student groups learn from their mistakes.

    PubMed

    Mishra, Tarun; Parra, R Gonzalo; Abeel, Thomas

    2014-08-01

    Success is the result of planning, hard work, determination, foresight, and a little bit of luck. Unfortunately, nobody has thought to pave the road to success. Although failure can be discouraging and time-consuming, it presents incredible learning opportunities-the biggest difference between those who succeed and those who abandon their projects lies in their response to adversity. This article reviews events undertaken by the Regional Student Groups (RSGs) in India and Argentina, the problems they encountered, and what can be learned from them. RSG-India attempted to organize an online scientific meeting (also known as a virtual conference) with geographically dispersed stakeholders, a totally new concept for them. RSG-Argentina tackled the challenge of organizing a two-day symposium, their first event ever. Some of the complications they faced were easy to fix, others led to the cancellation of activities, and all of them resulted in valuable lessons. The main goal of this article is to highlight, through their experiences, the universal importance of a healthy panel of contingency plans. PMID:25101799

  9. Chronic heart failure selectively induces regional heterogeneity of insulin-responsive glucose transporters

    PubMed Central

    Ware, Bruce; Bevier, Marie; Nishijima, Yoshinori; Rogers, Suzanne; Carnes, Cynthia A.

    2011-01-01

    Glucose uptake across the sarcolemma is regulated by a family of membrane proteins called glucose transporters (GLUTs), which includes GLUT4 (the major cardiac isoform) and GLUT12 (a novel, second insulin-sensitive isoform). Potential regional patterns in glucose transport across the cardiac chambers have not been examined; thus, we hypothesized that insulin-responsive GLUT4 and -12 protein and gene expression would be chamber specific in healthy subjects and during chronic heart failure (HF). Using a canine model of tachypacing-induced, progressive, chronic HF, total GLUT protein and messenger RNA in both ventricles and atria (free wall and appendage) were investigated by immunoblotting and real-time PCR. In controls, GLUT4, but not GLUT12, protein content was significantly higher in the atria compared with the ventricles, with the highest content in the right atrium (RA; P < 0.001). GLUT4 and GLUT12 mRNA levels were similar across the cardiac chambers. During chronic HF, GLUT4 and GLUT12 protein content was highest in the left ventricle (LV; by 2.5- and 4.2-fold, respectively, P < 0.01), with a concomitant increase in GLUT4 and GLUT12 mRNA (P < 0.001). GLUT4, but not GLUT12, protein content was decreased in RA during chronic HF (P = 0.001). In conclusion, GLUT4 protein was differentially expressed across the chambers in the healthy heart, and this regional pattern was reversed during HF. Our data suggest that LV was the primary site dependent on both GLUT4 and GLUT12 during chronic HF. In addition, the paradoxical decrease in GLUT4 content in RA may induce perturbations in atrial energy production during chronic HF. PMID:21849635

  10. Global and Regional Brain Mean Diffusivity Changes in Patients with Heart Failure

    PubMed Central

    Woo, Mary A.; Palomares, Jose A.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

    2014-01-01

    Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes, and can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age, 55.1±7.8 years; 12 male) and 26 controls (49.7±10.8 years; 17 male), using a 3.0-Tesla MRI scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared using analysis of covariance (covariates: age, gender). Global brain MD (HF vs. controls; Unit ×10−6 mm2/s; 1103.8±76.6 vs. 1035.9±69.4, p=0.038) and regional autonomic and motor site values (left insula, 1085.4±95.7 vs. 975.7±65.4, p=0.001; right insula, 1050.2±100.6 vs. 965.7±58.4, p=0.004; left hypothalamus, 1419.6±165.2 vs. 1234.9±136.3, p=0.002; right hypothalamus, 1446.5±178.8 vs. 1273.3±136.9, p=0.004; left cerebellar cortex, 889.1±81.9 vs. 796.6±46.8, p<0.001; right cerebellar cortex, 797.8±50.8 vs. 750.3±27.5, p=0.001; cerebellar deep nuclei, 1236.1±193.8 vs. 1071.7±107.1; p=0.002) were significantly higher in HF over controls, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient functions in HF. The chronic tissue changes likely result from processes which develop over a prolonged time-period. PMID:25502071

  11. Optical conductivity of nodal metals

    NASA Astrophysics Data System (ADS)

    Homes, C. C.; Gu, G. D.; Tu, J. J.; Li, J.; Akrap, A.

    2014-03-01

    Fermi liquid theory is remarkably successful in describing the transport and optical properties of metals; at frequencies higher than the scattering rate, the optical conductivity adopts the well-known power law behavior σ1(ω) ~ω-2 . We have observed an unusual non-Fermi liquid response σ1(ω) ~ω - 1 +/- 0 . 2 in the ground states of several quasi two-dimensional cuprate (optimally doped Bi2Sr2CaCu2O8+δ, optimally and underdoped YBa2Cu3O7-δ) and iron-based materials (AFe2As2, A = Ba, Ca) which undergo electronic or magnetic phase transitions resulting in dramatically reduced or nodal Fermi surfaces. The identification of an inverse (or fractional) power-law behavior in the residual optical conductivity now permits the removal of this contribution, revealing the direct transitions across the gap and allowing the nature of the electron-boson coupling to be probed. The non-Fermi liquid behavior in these systems may be the result of a common Fermi surface topology of Dirac cone-like features in the electronic dispersion. Supported by the DOE under Contract No. DE-AC02-98CH10886.

  12. Optical conductivity of nodal metals

    PubMed Central

    Homes, C. C.; Tu, J. J.; Li, J.; Gu, G. D.; Akrap, A.

    2013-01-01

    Fermi liquid theory is remarkably successful in describing the transport and optical properties of metals; at frequencies higher than the scattering rate, the optical conductivity adopts the well-known power law behavior σ1(ω) ∝ ω−2. We have observed an unusual non-Fermi liquid response σ1(ω) ∝ ω−1±0.2 in the ground states of several cuprate and iron-based materials which undergo electronic or magnetic phase transitions resulting in dramatically reduced or nodal Fermi surfaces. The identification of an inverse (or fractional) power-law behavior in the residual optical conductivity now permits the removal of this contribution, revealing the direct transitions across the gap and allowing the nature of the electron-boson coupling to be probed. The non-Fermi liquid behavior in these systems may be the result of a common Fermi surface topology of Dirac cone-like features in the electronic dispersion. PMID:24336241

  13. Risk Factors Associated with Loco-Regional Failure after Surgical Resection in Patients with Resectable Pancreatic Cancer

    PubMed Central

    Kim, Hyun Ju; Lee, Woo Jung; Kang, Chang Moo; Hwang, Ho Kyoung; Bang, Seung Min; Song, Si Young; Seong, Jinsil

    2016-01-01

    Purpose To evaluate the risk factors associated with loco-regional failure after surgical resection and to identify the subgroup that can obtain benefits from adjuvant radiotherapy (RT). Materials and Methods We identified patients treated with surgical resection for resectable pancreatic cancer at Severance hospital between January 1993 and December 2014. Patients who received any neoadjuvant or adjuvant RT were excluded. A total of 175 patients were included. Adjuvant chemotherapy was performed in 107 patients with either a gemcitabine-based regimen (65.4%) or 5-FU based one (34.9%). Results The median loco-regional failure-free survival (LRFFS) and overall survival (OS) were 23.9 and 33.6 months, respectively. A recurrence developed in 108 of 175 patients (61.7%). The predominant pattern of the first failure was distant (42.4%) and 47 patients (26.9%) developed local failure as the first site of recurrence. Multivariate analysis identified initial CA 19–9 ≥ 200 U/mL, N1 stage, perineural invasion (PNI), and resection margin as significant independent risk factors for LRFFS. Patients were divided into four groups according to the number of risk factors, including initial CA 19–9, N stage, and PNI. Patients exhibiting two risk factors had 3.2-fold higher loco-regional failure (P < 0.001) and patients with all risk factors showed a 6.5-fold increase (P < 0.001) compared with those with no risk factors. In the analysis for OS, patients with more than two risk factors also had 3.3- to 6-fold higher risk of death with statistical significance. Conclusion The results suggest that patients who exhibit more than two risk factors have a higher risk of locoregional failure and death. This subgroup could be benefited by the effective local adjuvant treatment. PMID:27332708

  14. Nodal network generator for CAVE3

    NASA Technical Reports Server (NTRS)

    Palmieri, J. V.; Rathjen, K. A.

    1982-01-01

    A new extension of CAVE3 code was developed that automates the creation of a finite difference math model in digital form ready for input to the CAVE3 code. The new software, Nodal Network Generator, is broken into two segments. One segment generates the model geometry using a Tektronix Tablet Digitizer and the other generates the actual finite difference model and allows for graphic verification using Tektronix 4014 Graphic Scope. Use of the Nodal Network Generator is described.

  15. Nodal signalling determines biradial asymmetry in Hydra.

    PubMed

    Watanabe, Hiroshi; Schmidt, Heiko A; Kuhn, Anne; Höger, Stefanie K; Kocagöz, Yigit; Laumann-Lipp, Nico; Ozbek, Suat; Holstein, Thomas W

    2014-11-01

    In bilaterians, three orthogonal body axes define the animal form, with distinct anterior-posterior, dorsal-ventral and left-right asymmetries. The key signalling factors are Wnt family proteins for the anterior-posterior axis, Bmp family proteins for the dorsal-ventral axis and Nodal for the left-right axis. Cnidarians, the sister group to bilaterians, are characterized by one oral-aboral body axis, which exhibits a distinct biradiality of unknown molecular nature. Here we analysed the biradial growth pattern in the radially symmetrical cnidarian polyp Hydra, and we report evidence of Nodal in a pre-bilaterian clade. We identified a Nodal-related gene (Ndr) in Hydra magnipapillata, and this gene is essential for setting up an axial asymmetry along the main body axis. This asymmetry defines a lateral signalling centre, inducing a new body axis of a budding polyp orthogonal to the mother polyp's axis. Ndr is expressed exclusively in the lateral bud anlage and induces Pitx, which encodes an evolutionarily conserved transcription factor that functions downstream of Nodal. Reminiscent of its function in vertebrates, Nodal acts downstream of β-Catenin signalling. Our data support an evolutionary scenario in which a 'core-signalling cassette' consisting of β-Catenin, Nodal and Pitx pre-dated the cnidarian-bilaterian split. We presume that this cassette was co-opted for various modes of axial patterning: for example, for lateral branching in cnidarians and left-right patterning in bilaterians. PMID:25156256

  16. Topological Phase Transitions in Line-nodal Superconductors

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Han, Sangeun; Moon, Eun-Gook

    Fathoming interplay between symmetry and topology of many-electron wave-functions deepens our understanding in quantum nature of many particle systems. Topology often protects zero-energy excitation, and in a certain class, symmetry is intrinsically tied to the topological protection. Namely, unless symmetry is broken, topological nature is intact. We study one specific case of such class, symmetry-protected line-nodal superconductors in three spatial dimensions (3d). Mismatch between phase spaces of order parameter fluctuation and line-nodal fermion excitation induces an exotic universality class in a drastic contrast to one of the conventional ϕ4 theory in 3d. Hyper-scaling violation and relativistic dynamic scaling with unusually large quantum critical region are main characteristics, and their implication in experiments is discussed. For example, continuous phase transition out of line-nodal superconductors has a linear phase boundary in a temperature-tuning parameter phase-diagram. This work was supported by the Brain Korea 21 PLUS Project of Korea Government and KAIST start-up funding.

  17. Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis.

    PubMed

    Coman, I; Aigrot, M S; Seilhean, D; Reynolds, R; Girault, J A; Zalc, B; Lubetzki, C

    2006-12-01

    Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Na(v)) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na(v) channels), paranodal (paranodin/Caspr) and juxtaparanodal (K(v) channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Na(v) channels is heterogeneous, with a diffuse immunoreactivity but also few broad Na(v) channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na(v) channels, paranodin/Caspr, K(v) channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Na(v) channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Na(v) channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells. PMID:16766541

  18. Nodal equivalence theory for hexagonal geometry, thermal reactor analysis

    SciTech Connect

    Zika, M.; Downar, T. )

    1992-01-01

    An important aspect of advanced nodal methods is the determination of equivalent few-group parameters for the relatively large homogenized regions used in the nodal flux solution. The theoretical foundation for light water reactor (LWR) assembly homogenization methods has been clearly established, and during the last several years, its successes have secured its position in the stable of dependable LWR analysis methods. Groupwise discontinuity factors that correct for assembly homogenization errors are routinely generated along with the group constants during lattice physics analysis. During the last several years, there has been interest in applying equivalence theory to other reactor types and other geometries. A notable effort has been the work at Argonne National Laboratory to incorporate nodal equivalence theory (NET) for hexagonal lattices into the nodal diffusion option of the DIF3D code. This work was originally intended to improve the neutronics methods used for the analysis of the Experimental Breeder Reactor II (EBR-II), and Ref. 4 discusses the success of that application. More recently, however, attempts were made to apply NET to advanced, thermal reactor designs such as the modular high-temperature gas reactor (MHTGR) and the new production heavy water reactor (NPR/HWR). The same methods that were successful for EBR-II have encountered problems for these reactors. Our preliminary analysis indicates that the sharp global flux gradients in these cores requires large discontinuity factors (greater than 4 or 5) to reproduce the reference solution. This disrupts the convergence of the iterative methods used to solve for the node-wise flux moments and partial currents. Several attempts to remedy the problem have been made over the last few years, including bounding the discontinuity factors and providing improved initial guesses for the flux solution, but nothing has been satisfactory.

  19. Global and regional brain mean diffusivity changes in patients with heart failure.

    PubMed

    Woo, Mary A; Palomares, Jose A; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

    2015-04-01

    Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P < 0.001; right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue

  20. Nodal signaling in Xenopus gastrulae is cell-autonomous and patterned by beta-catenin.

    PubMed

    Hashimoto-Partyka, Minako K; Yuge, Masahiro; Cho, Ken W Y

    2003-01-01

    The classical three-signal model of amphibian mesoderm induction and more recent modifications together propose that an activin-like signaling activity is uniformly distributed across the vegetal half of the Xenopus blastula and that this activity contributes to mesoderm induction. In support of this, we have previously shown that the activin-response element (DE) of the goosecoid promoter is uniformly activated across the vegetal half of midgastrula-stage embryos. Here, we further examine the nature of this activity by measuring DE activation by endogenous signals over time. We find that the spatiotemporal pattern of DE activation is much more dynamic than was previously appreciated and also conclude that DE(6X)Luc activity reflects endogenous nodal signaling in the embryo. Using both the DE(6X)Luc construct and endogenous Xbra and Xgsc expression as read-outs for nodal activity, and the cleavage-mutant version of Xnr2 (CmXnr2) to regionally suppress endogenous nodal activity, we demonstrate that nodal signals act cell-autonomously in Xenopus gastrulae. Nodal-expressing cells are unable to rescue either reporter gene activation or target gene expression in distant nodal-deficient cells, suggesting that nodals function at short range in this context. Finally, we show that DE activation by endogenous signals occurs in the absence of dorsal beta-catenin-mediated signaling, but that the timing of dorsal initiation is altered. We conclude that nodal signals in Xenopus gastrulae function cell autonomously at short ranges and that the spatiotemporal pattern of this signaling along the dorsoventral axis is regulated by maternal Wnt-like signaling. PMID:12490202

  1. Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto

    PubMed Central

    Harms, Paul W.; Chang, Chenbei

    2003-01-01

    Transforming growth factor β (TGF-β) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin in early Xenopus embryos. Here we report that TMEFF1 binds to the nodal coreceptor Cripto, but does not associate with either nodal or the type I ALK (activin receptor-like kinase) 4 receptor in coimmunoprecipitation assays. The inhibition of the nodal signaling by TMEFF1 in Xenopus ectodermal explants is rescued with wild-type but not mutant forms of Cripto. Furthermore, we show that the Cripto-FRL1-Cryptic (CFC) domain in Cripto, which is essential for its binding to ALK4, is also important for its interaction with TMEFF1. Our results demonstrate for the first time that nodal signaling can be regulated by a novel mechanism of blocking the Cripto coreceptor. PMID:14563676

  2. Keeping a lid on nodal: transcriptional and translational repression of nodal signalling

    PubMed Central

    Robertson, Elizabeth J.

    2016-01-01

    Nodal is an evolutionarily conserved member of the transforming growth factor-β (TGF-β) superfamily of secreted signalling factors. Nodal factors are known to play key roles in embryonic development and asymmetry in a variety of organisms ranging from hydra and sea urchins to fish, mice and humans. In addition to embryonic patterning, Nodal signalling is required for maintenance of human embryonic stem cell pluripotency and mis-regulated Nodal signalling has been found associated with tumour metastases. Therefore, precise and timely regulation of this pathway is essential. Here, we discuss recent evidence from sea urchins, frogs, fish, mice and humans that show a role for transcriptional and translational repression of Nodal signalling during early development. PMID:26791244

  3. Nodal Quasiparticle in Pseudogapped Colossal Magnetoresistive Manganites

    SciTech Connect

    Mannella, N.

    2010-06-02

    A characteristic feature of the copper oxide high-temperature superconductors is the dichotomy between the electronic excitations along the nodal (diagonal) and antinodal (parallel to the Cu-O bonds) directions in momentum space, generally assumed to be linked to the d-wave symmetry of the superconducting state. Angle-resolved photoemission measurements in the superconducting state have revealed a quasiparticle spectrum with a d-wave gap structure that exhibits a maximum along the antinodal direction and vanishes along the nodal direction. Subsequent measurements have shown that, at low doping levels, this gap structure persists even in the high-temperature metallic state, although the nodal points of the superconducting state spread out in finite Fermi arcs. This is the so-called pseudogap phase, and it has been assumed that it is closely linked to the superconducting state, either by assigning it to fluctuating superconductivity or by invoking orders which are natural competitors of d-wave superconductors. Here we report experimental evidence that a very similar pseudogap state with a nodal-antinodal dichotomous character exists in a system that is markedly different from a superconductor: the ferromagnetic metallic groundstate of the colossal magnetoresistive bilayer manganite La{sub 1.2}Sr{sub 1.8}Mn{sub 2}O{sub 7}. Our findings therefore cast doubt on the assumption that the pseudogap state in the copper oxides and the nodal-antinodal dichotomy are hallmarks of the superconductivity state.

  4. Nodal analysis of two-phase instabilities

    SciTech Connect

    Lahey, R.T. Jr.; Garea, V.P.

    1995-10-01

    Nodal models having moving nodal boundaries have been developed for the analysis of two-phase flow instabilities in a boiling channel. The first model, which was based on a Galerkin method for the discretization, has been found to be accurate in the prediction of the onset of instabilities as well as the frequency of oscillations. This model however, had some problems with the prediction of chaotic phenomena and did not allow for flow reversal in the channel. A second nodal model, based on a finite difference approach, has been found to perform better for the prediction of non-linear response and it also allows for flow reversal. Both models are numerically more efficient than the existing fixed grid models for instabilities analysis.

  5. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    SciTech Connect

    Varlotto, John M.; Yao, Aaron N.; DeCamp, Malcolm M.; Ramakrishna, Satvik; Recht, Abe; Flickinger, John; Andrei, Adin; Reed, Michael F.; Toth, Jennifer W.; Fizgerald, Thomas J.; Higgins, Kristin; Zheng, Xiao; Shelkey, Julie; and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  6. A lymph nodal capillary-cavernous hemangioma.

    PubMed

    Dellachà, A; Fulcheri, E; Campisi, C

    1999-09-01

    A capillary-cavernous hemangioma in an obturator lymph node was found incidentally in a 64 year-old woman who had undergone unilateral salpingo-oophorectomy and lymphadenectomy for an ovarian neoplasm. Vascular tumors of lymph nodes are briefly reviewed including eight previously described nodal capillary-cavernous hemangiomas. The association with other splanchnic hemangiomas is pointed out and the likelihood that the lesion is a hamartoma rather than a true neoplasm is addressed. Despite its rarity, this entity needs to be recognized by lymphologists who image lymph nodes by lymphangiography as well as by lymph nodal pathologists. PMID:10494525

  7. The role of nodal and internodal responses in gravitropism and autotropism in Galium aparine L

    NASA Technical Reports Server (NTRS)

    Heathcote, D. G.; Brown, A. H. (Principal Investigator)

    1987-01-01

    This time course and location of gravitropically induced curvatures in stems of goosegrass (Gallium aparine L.), a member of the Rubiaceae, have been investigated. In the early stages of the response (0-5 h), curvature develops throughout the growing region, and is followed by an autotropic straightening which affects the internodes only, leading to the production of essentially straight internodes some 15 h after the onset of gravistimulation. Curvatures developing in the nodal regions, however, continue to increase over this period, and are not subject to reversal by autotropism. The nodal curvatures are not entirely dependent on the presence of any other part of the plant, since marked curvatures can be induced in isolated nodal segments. This pattern of response leads ultimately to correction of the growth direction of the plant by means of curvature responses confined exclusively to the nodes, despite the initial participation of both nodes and internodes in the gravitropic reaction.

  8. Nodal·Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

    PubMed Central

    Fuerer, Christophe; Nostro, M. Cristina; Constam, Daniel B.

    2014-01-01

    The TGFβ family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on the shared co-receptor Cryptic to specify visceral left-right axis asymmetry. We therefore asked whether the functionality of Nodal can be augmented by Gdf1. Because Nodal and Gdf1 coimmunoprecipitate each other, they were predicted to form heterodimers, possibly to facilitate diffusion or to increase the affinity for signaling receptors. Here, we report that Gdf1 suppresses an unexpected dependence of Nodal on serum proteins and that it is critically required for non-autonomous signaling in cells expressing Cryptic. Nodal, Gdf1, and their cleaved propeptides copurified as a heterodimeric low molecular weight complex that stimulated Activin receptor (Acvr) signaling far more potently than Nodal alone. Although heterodimerization with Gdf1 did not increase binding of Nodal to Fc fusions of co-receptors or Acvr extracellular domains, it was essential for soluble Acvr2 to inhibit Nodal signaling. This implies that Gdf1 potentiates Nodal activity by stabilizing a low molecular weight fraction that is susceptible to neutralization by soluble Acvr2. Finally, in differentiating human ES cells, endodermal markers were more efficiently induced by Nodal·Gdf1 than by Nodal, suggesting that Nodal·Gdf1 is an attractive new reagent to direct stem cell differentiation. PMID:24798330

  9. Network and Nodal Accessibility Teaching Exercise.

    ERIC Educational Resources Information Center

    Wheeler, James O.

    1988-01-01

    Presents an exercise, for use in college-level economic geography courses, which teaches the concept of nodal and network accessibility with an application to manufacturing locations. Intended to guide students to think spatially and to generalize from numeric data, this out-of-class activity teaches students to discover results, to do simple…

  10. First Case of Automatic His Potential Detection With a Novel Ultra High-density Electroanatomical Mapping System for AV Nodal Ablation

    PubMed Central

    Hilbert, Sebastian; Kosiuk, Jedrzej; John, Silke; Hindricks, Gerhard; Bollmann, Andreas

    2016-01-01

    A 74-year old was considered for atrioventricular (AV) nodal ablation in view of atrial fibrillation (AF) with poorly controlled ventricular rate despite being on amiodarone. Targeted AV nodal ablation was successfully performed after identifying the target site for ablation by reviewing an ultra high-density map of the His region produced by automatic electrogram annotation. PMID:25852249

  11. Exploratory Investigation of Failure Mechanisms in Transition Regions between Solid Laminates and X-cor(registered tm) Truss Sandwich

    NASA Technical Reports Server (NTRS)

    OBrien, T. Kevin; Paris, Isabelle L.

    2004-01-01

    Small sub-component specimens consisting of solid laminates at the ends that transition to X-cor(R) truss sandwich in the center, were tested in a combination of three point bending, uni-axial tension, and combined tension and bending. The failure process in the transition region was documented for each loading using digital video and high-resolution cameras. For the 3-point bending tests, most of the deformation occurred in the solid laminate regions on either end of the specimen. Some pin debonding from the skin of the X-cor(R) truss sandwich was observed in the transition region and was accompanied by audible "pings" throughout the loading. Tension loaded specimens failed in the sandwich skin in the middle of the gage length, accompanied by separation of the sandwich core from the back skin and by delamination between the top skin and bottom skin at the transition region. The pinging associated with pin debonding occurred as the load was increased. However, the frequency of the pinging exceeded any visual observations of pin debonding in the video of the transition region. For specimens tested in combined tension and bending, the greatest amount of pinging occurred during initial application of the axial load. High-resolution images in the transition region indicated that the pinging corresponded to pins debonding and buckling due to the through-thickness Poisson contraction of the specimen. This buckling continued to a much smaller extent as the transverse load was applied.

  12. Nodal Diffusion Burnable Poison Treatment for Prismatic Reactor Cores

    SciTech Connect

    A. M. Ougouag; R. M. Ferrer

    2010-10-01

    The prismatic block version of the High Temperature Reactor (HTR) considered as a candidate Very High Temperature Reactor (VHTR)design may use burnable poison pins in locations at some corners of the fuel blocks (i.e., assembly equivalent structures). The presence of any highly absorbing materials, such as these burnable poisons, within fuel blocks for hexagonal geometry, graphite-moderated High Temperature Reactors (HTRs) causes a local inter-block flux depression that most nodal diffusion-based method have failed to properly model or otherwise represent. The location of these burnable poisons near vertices results in an asymmetry in the morphology of the assemblies (or blocks). Hence the resulting inadequacy of traditional homogenization methods, as these “spread” the actually local effect of the burnable poisons throughout the assembly. Furthermore, the actual effect of the burnable poison is primarily local with influence in its immediate vicinity, which happens to include a small region within the same assembly as well as similar regions in the adjacent assemblies. Traditional homogenization methods miss this artifact entirely. This paper presents a novel method for treating the local effect of the burnable poison explicitly in the context of a modern nodal method.

  13. Auxin controls local cytokinin biosynthesis in the nodal stem in apical dominance.

    PubMed

    Tanaka, Mina; Takei, Kentaro; Kojima, Mikiko; Sakakibara, Hitoshi; Mori, Hitoshi

    2006-03-01

    In intact plants, the shoot apex grows predominantly and inhibits outgrowth of axillary buds. After decapitation of the shoot apex, outgrowth of axillary buds begins. This phenomenon is called an apical dominance. Although the involvement of auxin, which represses outgrowth of axillary buds, and cytokinin (CK), which promotes outgrowth of axillary buds, has been proposed, little is known about the underlying molecular mechanisms. In the present study, we demonstrated that auxin negatively regulates local CK biosynthesis in the nodal stem by controlling the expression level of the pea (Pisum sativum L.) gene adenosine phosphate-isopentenyltransferase (PsIPT), which encodes a key enzyme in CK biosynthesis. Before decapitation, PsIPT1 and PsIPT2 transcripts were undetectable; after decapitation, they were markedly induced in the nodal stem along with accumulation of CK. Expression of PsIPT was repressed by the application of indole-3-acetic acid (IAA). In excised nodal stem, PsIPT expression and CK levels also increased under IAA-free conditions. Furthermore, beta-glucuronidase expression, under the control of the PsIPT2 promoter region in transgenic Arabidopsis, was repressed by an IAA. Our results indicate that in apical dominance one role of auxin is to repress local biosynthesis of CK in the nodal stem and that, after decapitation, CKs, which are thought to be derived from the roots, are locally biosynthesized in the nodal stem rather than in the roots. PMID:16507092

  14. Nodal and Lefty signaling regulates the growth of pancreatic cells

    PubMed Central

    Zhang, You-Qing; Sterling, Lori; Stotland, Aleksandr; Hua, Hong; Kritzik, Marcie; Sarvetnick, Nora

    2014-01-01

    Nodal and its antagonist, Lefty, are important mediators specifying the laterality of the organs during embryogenesis. Nodal signals through activin receptors in the presence of its co-receptor, Cripto. In the present study, we investigated the possible roles of Nodal and Lefty signaling during islet development and regeneration. We found that both Nodal and Lefty are expressed in the pancreas during embryogenesis and islet regeneration. In vitro studies demonstrated that Nodal inhibits, whereas Lefty enhances, the proliferation of a pancreatic cell line. In addition, we showed that Lefty-1 activates MAPK and Akt phosphorylation in these cells. In vivo blockade of endogenous Lefty using neutralizing Lefty-1 monoclonal antibody results in a significantly decreased proliferation of duct epithelial cells during islet regeneration. This is the first study to decipher the expression and function of Nodal and Lefty in pancreatic growth. Importantly, our results highlight a novel function of Nodal-Lefty signaling in the regulation of expansion of pancreatic cells. PMID:18393305

  15. Nodal resonance in a strong standing wave

    NASA Astrophysics Data System (ADS)

    Fernández C., David J.; Mielnik, Bogdan

    1990-06-01

    The motion of charged particles in a standing electromagnetic wave is considered. For amplitudes that are not too high, the wave causes an effect of attraction of particles to the nodal points, resembling the channeling effect reported by Salomon, Dalibard, Aspect, Metcalf, and Cohen-Tannoudji [Phys. Rev. Lett. 59, 1659 (1987)] consistent with the ``high-frequency potential'' of Kapitza [Zh. Eksp. Teor. Fiz. 21, 588 (1951)]. For high-field intensities, however, the nodal points undergo a qualitative metamorphosis, converting themselves from particle attractors into resonant centers. Some chaotic phenomena arise and the description of the oscillating field in terms of an ``effective potential'' becomes inappropriate. The question of a correct Floquet Hamiltonian that could describe the standing wave within this amplitude and frequency regime is open.

  16. Entrainment mapping in patients with sustained atrioventricular nodal reentrant tachycardia: insights into the sites of conduction slowing in the slow atrioventricular nodal pathway.

    PubMed

    Haines, D E; Nath, S; DiMarco, J P; Lobban, J H

    1997-10-01

    The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or

  17. A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

    SciTech Connect

    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Keefe, Stephen M.; Tucker, Kai; Bekelman, Justin E.; Hwang, Wei-Ting; Vaughn, David J.; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common

  18. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    SciTech Connect

    Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

  19. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    SciTech Connect

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak; Petereit, Daniel G.; Hong, Theodore S.; Tome, Wolfgang; Ritter, Mark A.

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  20. Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus

    PubMed Central

    Marjoram, Lindsay; Wright, Christopher

    2011-01-01

    The spatiotemporally dynamic distribution of instructive ligands within embryonic tissue, and their feedback antagonists, including inherent stabilities and rates of clearance, are affected by interactions with cell surfaces or extracellular matrix (ECM). Nodal (here, Xnr1 or Nodal1 in Xenopus) and Lefty interact in a cross-regulatory relationship in mesendoderm induction, and are the conserved instructors of left-right (LR) asymmetry in early somitogenesis stage embryos. By expressing Xnr1 and Lefty proproteins that produce mature functional epitope-tagged ligands in vivo, we found that ECM is a principal surface of Nodal and Lefty accumulation. We detected Lefty moving faster than Nodal, with evidence that intact sulfated proteoglycans in the ECM facilitate the remarkable long distance movement of Nodal. We propose that Nodal autoregulation substantially aided by rapid ligand transport underlies the anteriorward shift of Nodal expression in the left LPM (lateral plate mesoderm), and speculate that the higher levels of chondroitin-sulfate proteoglycan (CSPG) in more mature anterior regions provide directional transport cues. Immunodetection and biochemical analysis showed transfer of Lefty from left LPM to right LPM, providing direct evidence that left-side-derived Lefty is a significant influence in ensuring the continued suppression of right-sided expression of Nodal, maintaining unilateral expression of this conserved determinant of asymmetry. PMID:21205792

  1. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    PubMed Central

    Thottathil, Mujeeburahiman; Verma, Ashish; D’souza, Nischith; Khan, Altaf

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too. PMID:27453671

  2. Plasticity underlies tumor progression: role of Nodal signaling.

    PubMed

    Bodenstine, Thomas M; Chandler, Grace S; Seftor, Richard E B; Seftor, Elisabeth A; Hendrix, Mary J C

    2016-03-01

    The transforming growth factor beta (TGFβ) superfamily member Nodal is an established regulator of early embryonic development, with primary roles in endoderm induction, left-right asymmetry, and primitive streak formation. Nodal signals through TGFβ family receptors at the plasma membrane and induces signaling cascades leading to diverse transcriptional regulation. While conceptually simple, the regulation of Nodal and its molecular effects are profoundly complex and context dependent. Pioneering work by developmental biologists has characterized the signaling pathways, regulatory components, and provided detailed insight into the mechanisms by which Nodal mediates changes at the cellular and organismal levels. Nodal is also an important factor in maintaining pluripotency of embryonic stem cells through regulation of core transcriptional programs. Collectively, this work has led to an appreciation for Nodal as a powerful morphogen capable of orchestrating multiple cellular phenotypes. Although Nodal is not active in most adult tissues, its reexpression and signaling have been linked to multiple types of human cancer, and Nodal has emerged as a driver of tumor growth and cellular plasticity. In vitro and in vivo experimental evidence has demonstrated that inhibition of Nodal signaling reduces cancer cell aggressive characteristics, while clinical data have established associations with Nodal expression and patient outcomes. As a result, there is great interest in the potential targeting of Nodal activity in a therapeutic setting for cancer patients that may provide new avenues for suppressing tumor growth and metastasis. In this review, we evaluate our current understanding of the complexities of Nodal function in cancer and highlight recent experimental evidence that sheds light on the therapeutic potential of its inhibition. PMID:26951550

  3. Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

    SciTech Connect

    Amini, Arya; Xiao Lianchun; Allen, Pamela K.; Suzuki, Akihiro; Hayashi, Yuki; Liao, Zhongxing; Hofstetter, Wayne; Crane, Christopher; Komaki, Ritsuko; Bhutani, Manoop S.; Lee, Jeffrey H.; Ajani, Jaffer A.; Welsh, James

    2012-06-01

    Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment

  4. CAISO flicks switch on nodal scheme and lights stay on

    SciTech Connect

    2009-06-15

    In 2000-01, two years after introducing a competitive wholesale power auction in California - with a separate day-ahead zonal market operated by the California Power Exchange and a zonal market for ancillary services and balancing energy operated by the California Independent System Operator (CAISO) - the California market collapsed from exorbitant prices, flagrant gaming, and abuse of market power. Nine years later, CAISO introduced a nodal pricing auction for the wholesale market in April, replacing the zonal scheme, which was among many causes of the original market's demise. With nearly 3,000 nodes on the network, high prices in one region do not affect prices everywhere on the system. After investing some $200 million to upgrade the software, countless delays, and 18 months of market simulation and testing, the new auction was introduced and nothing unusual happened.

  5. Phonon analogue of topological nodal semimetals

    NASA Astrophysics Data System (ADS)

    Po, Hoi Chun; Bahri, Yasaman; Vishwanath, Ashvin

    2015-03-01

    Recently, Kane and Lubensky proposed a mapping between bosonic phonon problems on isostatic lattices to chiral fermion systems based on factorization of the dynamical matrix [Nat. Phys. 10, 39 (2014)]. The existence of topologically protected zero modes in such mechanical problems is related to their presence in the fermionic system and is dictated by a local index theorem. Here we adopt the proposed mapping to construct a two-dimensional mechanical analogue of a fermionic topological nodal semimetal that hosts a robust bulk node in its linearized phonon spectrum. Such topologically protected soft modes with tunable wavevector may be useful in designing mechanical structures with fault-tolerant properties.

  6. The AN neutron transport by nodal diffusion

    SciTech Connect

    Barbarino, A.; Tomatis, D.

    2013-07-01

    The two group diffusion model combined to a nodal approach in space is the preferred scheme for the industrial simulation of nuclear water reactors. The main selling point is the speed of computation, allowing a large number of parametric studies. Anyway, the drawbacks of the underlying diffusion equation may arise with highly heterogeneous interfaces, often encountered in modern UO{sub 2} and MO{sub x} fuel loading patterns, and boron less controlled systems. This paper aims at showing how the simplified AN transport model, equivalent to the well known SPN, can be implemented in standard diffusion codes with minor modifications. Some numerical results are illustrated. (authors)

  7. Extracellular interactions and ligand degradation shape the nodal morphogen gradient

    PubMed Central

    Wang, Yin; Wang, Xi; Wohland, Thorsten; Sampath, Karuna

    2016-01-01

    The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear. Here, we have measured in vivo for the first time, the binding affinity of Nodal ligands to their major cell surface receptor, Acvr2b, and to the Nodal inhibitor, Lefty, by fluorescence cross-correlation spectroscopy. We examined the diffusion coefficient of Nodal ligands and Lefty inhibitors in live zebrafish embryos by fluorescence correlation spectroscopy. We also investigated the contribution of ligand degradation to the Nodal gradient. We show that ligand clearance via degradation shapes the Nodal gradient and correlates with its signaling range. By computational simulations of gradient formation, we demonstrate that diffusivity, extra-cellular interactions, and selective ligand destruction collectively shape the Nodal morphogen gradient. DOI: http://dx.doi.org/10.7554/eLife.13879.001 PMID:27101364

  8. Unexplained in-vitro fertilization failure: implication of acrosomes with a small reacting region, as revealed by a monoclonal antibody.

    PubMed

    Albert, M; Gallo, J M; Escalier, D; Parseghian, N; Jouannet, P; Schrevel, J; David, G

    1992-10-01

    To determine the acrosomal characteristics related to in-vitro fertilization (IVF) outcome, spermatozoa from 50 men whose wives had resorted to IVF have been studied by indirect immunofluorescence microscopy with anti-human pro-acrosin monoclonal antibody 4D4 (mAb 4D4), prior to and after incubation in a capacitating medium. The antibody labelled only the acrosomal principal region (APR), revealing its shape (i.e. normal, small or amorphous) and its status (i.e. unreacted, partially or totally reacted). The IVF outcome distinguished: (i) spermatozoa which were able to fertilize at least one oocyte in vitro (group I; n = 25) and (ii) spermatozoa which failed to fertilize any oocyte in vitro (group II; n = 25). The semen characteristics of the two sperm groups, including the acrosome morphology, were similar according to conventional analysis. The mAb 4D4 detected in both the whole and the swim-up sperm cell fractions a lower percentage of normal APR in group II (< 50% for 10 patients in group II versus one patient from group I), which was related to a higher percentage of small APR. Moreover, after 21 h incubation, group II had a lower acrosomal loss index. The spermatozoa of five patients of this infertile group II did not undergo acrosomal modification whereas spermatozoa of all group I patients underwent the acrosomal reaction. The data showed that the relationship between acrosomal anomalies and IVF failure is mainly due to an increased incidence of acrosomes with a reduced size of the region involved in the acrosome reaction. Immunodiagnosis of this acrosomal region by means of mAb 4D4 is informative for IVF outcome. PMID:1479007

  9. Laser catheter-induced atrioventricular nodal delays and atrioventricular block in dogs: acute and chronic observations.

    PubMed

    Narula, O S; Boveja, B K; Cohen, D M; Narula, J T; Tarjan, P P

    1985-02-01

    Selective modification of atrioventricular (AV) nodal conduction, that is, induction of varying degrees of AV nodal delays or block (second or third degree), or both, was achieved with a pervenous laser catheter technique. In six adult mongrel dogs anesthetized with pentobarbital (Nembutal), 5F leads were placed through femoral and external jugular veins and placed into the right atrium and His bundle region. Through another femoral vein, a 200 micron optical fiber was inserted by way of a 7F catheter with a preformed curved tip. Guided by fluoroscopy and His bundle electrograms, the fiber's tip was positioned in the AV nodal region. After autonomic blockade was achieved with intravenous propranolol (5 mg) and atropine (1 mg), AV conduction was analyzed. An argon laser delivered 3 to 4 watts into the fiber in bursts of 10 seconds' duration until the desired degree of AV nodal delay or block (second or third degree) was manifested. Monitoring of His bundle electrograms was continued for 2 hours. Four weekly serial electrocardiograms were recorded, after which electrophysiologic studies were repeated. Acute post-lasing studies showed that: in all six dogs, the mean PR interval was prolonged from 116 ms (range 100 to 135) to 153 ms (range 120 to 185), with the prolongation being caused exclusively by AH lengthening from 68 ms (range 50 to 90) to 105 ms (range 65 to 140); the mean effective refractory period of the AV node increased from less than 185 ms (range less than 150 to less than 200) to 215 ms (range 190 to 280); and the mean atrial pacing cycle length, at which second degree AV nodal block was manifested, increased from 210 ms (range 160 to 260) to 261 ms (range 205 to 320).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3968310

  10. Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts.

    PubMed

    Sarkar, Prasenjit; Randall, Shan M; Collier, Timothy S; Nero, Anthony; Russell, Teal A; Muddiman, David C; Rao, Balaji M

    2015-04-01

    Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. PMID:25670856

  11. Activin/Nodal Signaling Switches the Terminal Fate of Human Embryonic Stem Cell-derived Trophoblasts*

    PubMed Central

    Sarkar, Prasenjit; Randall, Shan M.; Collier, Timothy S.; Nero, Anthony; Russell, Teal A.; Muddiman, David C.; Rao, Balaji M.

    2015-01-01

    Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. PMID:25670856

  12. Minimizing the caliber of myelinated axons by means of nodal constrictions.

    PubMed

    Johnson, Christopher; Holmes, William R; Brown, Anthony; Jung, Peter

    2015-09-01

    In myelinated axons, most of the voltage-gated ion channels are concentrated at the nodes of Ranvier, which are short gaps in the myelin sheath. This arrangement leads to saltatory conduction and a larger conduction velocity than in nonmyelinated axons. Intriguingly, axons in the peripheral nervous system that exceed about 2 μm in diameter exhibit a characteristic narrowing of the axon at nodes that results in a local reduction of the axonal cross-sectional area. The extent of constriction increases with increasing internodal axonal caliber, reaching a threefold reduction in diameter for the largest axons. In this paper, we use computational modeling to investigate the effect of nodal constrictions on axonal conduction velocity. For a fixed number of ion channels, we find that there is an optimal extent of nodal constriction which minimizes the internodal axon caliber that is required to achieve a given target conduction velocity, and we show that this is sensitive to the precise geometry of the axon and myelin sheath in the flanking paranodal regions. Thus axonal constrictions at nodes of Ranvier appear to be a biological adaptation to minimize axonal volume, thereby maximizing the spatial and metabolic efficiency of these processes, which can be a significant evolutionary constraint. We show that the optimal nodal morphologies are relatively insensitive to changes in the number of nodal sodium channels. PMID:26224772

  13. Two novel nodal-related genes initiate early inductive events in Xenopus Nieuwkoop center.

    PubMed

    Takahashi, S; Yokota, C; Takano, K; Tanegashima, K; Onuma, Y; Goto, J; Asashima, M

    2000-12-01

    In vertebrates, Nodal-related protein plays crucial roles in mesoderm and endoderm induction. Here we describe two novel Xenopus nodal-related genes, Xnr5 and Xnr6, which are first zygotically expressed at the mid-blastula transition, in the dorsal-vegetal region including the Nieuwkoop center. Xnr5 and Xnr6 were isolated by expression screening of a library enriched with immediate-early-type transcripts, and are strong inducers of both mesoderm and endoderm. They also induce the other nodal-related genes in the animal cap. In embryos, cerberus-short (nodal-specific inhibitor) can inhibit Xnr1 and Xnr2 express to the same extent goosecoid, but not Xnr5 and Xnr6 transcription. Xnr5 and Xnr6 are regulated completely cell autonomously, differently from other Xnrs in the cell-dissociated embryos. The expression of Xnr5 and Xnr6 is regulated by maternal VegT and (beta)-catenin, but does not require TGF-(beta) signaling. Therefore, expression of Xnr5 and Xnr6 is controlled by different mechanisms from other Xnr family genes. PMID:11076754

  14. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  15. Influence of Pathological Nodal Status and Maximal Standardized Uptake Value of the Primary Tumor and Regional Lymph Nodes on Treatment Plans in Patients With Advanced Oral Cavity Squamous Cell Carcinoma

    SciTech Connect

    Liao, C.-T.; Wang, H.-M.; Chang, Joseph Tung-Chieh; Lin, C.-Y.; Ng, S.-H.; Huang, S.-F.; Chen, I.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2010-06-01

    Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients.

  16. Market redesign and technology upgrade: a nodal implementation

    SciTech Connect

    Isemonger, Alan G.

    2009-10-15

    The California ISO and its market participants collectively cut over to a new nodal-based market on April 1, largely without incident and 11 years to the day from the initial startup in 1998. Thus far, the new nodal framework has proven robust, and the inevitable design and implementation issues that have emerged since cutover have been manageable. (author)

  17. Radar response from vegetation with nodal structure

    NASA Technical Reports Server (NTRS)

    Blanchard, B. J.; Oneill, P. E.

    1984-01-01

    Radar images from the SEASAT synthetic aperture radar (SAR) produced unusually high returns from corn and sorghum fields, which seem to indicate a correlation between nodal separation in the stalk and the wavelength of the radar. These images also show no difference in return from standing or harvested corn. Further investigation using images from the Shuttle Imaging Radar (SIR-A) substantiated these observations and showed a degradation of the high return with time after harvest. From portions of corn and sweet sorghum stalks that were sampled to measure stalk water content, it was determined that near and after maturity the water becomes more concentrated in the stalk nodes. The stalk then becomes a linear sequence of alternating dielectrics as opposed to a long slender cylinder with uniform dielectric properties.

  18. Nodal aberration theory applied to freeform surfaces

    NASA Astrophysics Data System (ADS)

    Fuerschbach, Kyle; Rolland, Jannick P.; Thompson, Kevin P.

    2014-12-01

    When new three-dimensional packages are developed for imaging optical systems, the rotational symmetry of the optical system is often broken, changing its imaging behavior and making the optical performance worse. A method to restore the performance is to use freeform optical surfaces that compensate directly the aberrations introduced from tilting and decentering the optical surfaces. In order to effectively optimize the shape of a freeform surface to restore optical functionality, it is helpful to understand the aberration effect the surface may induce. Using nodal aberration theory the aberration fields induced by a freeform surface in an optical system are explored. These theoretical predications are experimentally validated with the design and implementation of an aberration generating telescope.

  19. Experience with advanced nodal codes at YAEC

    SciTech Connect

    Cacciapouti, R.J.

    1990-01-01

    Yankee Atomic Electric Company (YAEC) has been performing reload licensing analysis since 1969. The basic pressurized water reactor (PWR) methodology involves the use of LEOPARD for cross-section generation, PDQ for radial power distributions and integral control rod worth, and SIMULATE for axial power distributions and differential control rod worth. In 1980, YAEC began performing reload licensing analysis for the Vermont Yankee boiling water reactor (BWR). The basic BWR methodology involves the use of CASMO for cross-section generation and SIMULATE for three-dimensional power distributions. In 1986, YAEC began investigating the use of CASMO-3 for cross-section generation and the advanced nodal code SIMULATE-3 for power distribution analysis. Based on the evaluation, the CASMO-3/SIMULATE-3 methodology satisfied all requirements. After careful consideration, the cost of implementing the new methodology is expected to be offset by reduced computing costs, improved engineering productivity, and fuel-cycle performance gains.

  20. Loop-Nodal and Point-Nodal Semimetals in Three-Dimensional Honeycomb Lattices

    NASA Astrophysics Data System (ADS)

    Ezawa, Motohiko

    2016-03-01

    A honeycomb structure has a natural extension to three dimensions. Simple examples are hyperhoneycomb and stripy-honeycomb lattices, which are realized in β -Li2IrO3 and γ -Li2IrO3 , respectively. We propose a wide class of three-dimensional (3D) honeycomb lattices which are loop-nodal semimetals. Their edge states have intriguing properties similar to the two-dimensional honeycomb lattice in spite of a dimensional difference. Partial flat bands emerge at the zigzag or bearded edge of the 3D honeycomb lattice, whose boundary is given by the Fermi loop in the bulk spectrum. On the other hand, perfect flat bands emerge in the zigzag-bearded edge or when the anisotropy is large. The loop-nodal structure is destroyed once staggered potential or antiferromagnetic order is introduced. All these 3D honeycomb lattices become strong topological insulators with the inclusion of the spin-orbit interaction (SOI). Furthermore, point-nodal semimetals may be realized in the presence of both antiferromagnetic order and the SOI. We construct the effective four-band theory with the SOI to understand the physics near the Fermi level, based upon which the density of states and the dc conductivity are calculated.

  1. Loop-Nodal and Point-Nodal Semimetals in Three-Dimensional Honeycomb Lattices.

    PubMed

    Ezawa, Motohiko

    2016-03-25

    A honeycomb structure has a natural extension to three dimensions. Simple examples are hyperhoneycomb and stripy-honeycomb lattices, which are realized in β-Li_{2}IrO_{3} and γ-Li_{2}IrO_{3}, respectively. We propose a wide class of three-dimensional (3D) honeycomb lattices which are loop-nodal semimetals. Their edge states have intriguing properties similar to the two-dimensional honeycomb lattice in spite of a dimensional difference. Partial flat bands emerge at the zigzag or bearded edge of the 3D honeycomb lattice, whose boundary is given by the Fermi loop in the bulk spectrum. On the other hand, perfect flat bands emerge in the zigzag-bearded edge or when the anisotropy is large. The loop-nodal structure is destroyed once staggered potential or antiferromagnetic order is introduced. All these 3D honeycomb lattices become strong topological insulators with the inclusion of the spin-orbit interaction (SOI). Furthermore, point-nodal semimetals may be realized in the presence of both antiferromagnetic order and the SOI. We construct the effective four-band theory with the SOI to understand the physics near the Fermi level, based upon which the density of states and the dc conductivity are calculated. PMID:27058097

  2. EXTENSION OF THE 1D FOUR-GROUP ANALYTIC NODAL METHOD TO FULL MULTIGROUP

    SciTech Connect

    B. D. Ganapol; D. W. Nigg

    2008-09-01

    In the mid 80’s, a four-group/two-region, entirely analytical 1D nodal benchmark appeared. It was readily acknowledged that this special case was as far as one could go in terms of group number and still achieve an analytical solution. In this work, we show that by decomposing the solution to the multigroup diffusion equation into homogeneous and particular solutions, extension to any number of groups is a relatively straightforward exercise using the mathematics of linear algebra.

  3. Vaccine Failures in Patients Properly Vaccinated with 13-Valent Pneumococcal Conjugate Vaccine in Catalonia, a Region with Low Vaccination Coverage.

    PubMed

    Moraga-Llop, Fernando; Garcia-Garcia, Juan-Jose; Díaz-Conradi, Alvaro; Ciruela, Pilar; Martínez-Osorio, Johanna; González-Peris, Sebastià; Hernández, Sergi; de Sevilla, Mariona Fernández; Uriona, Sonia; Izquierdo, Conchita; Selva, Laura; Campins, Magda; Codina, Gemma; Batalla, Joan; Esteva, Cristina; Domínguez, Àngela; Muñoz-Almagro, Carmen

    2016-04-01

    Vaccine failures occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in 3 pediatric hospitals in Barcelona (2012-2013) are described. PCV13 vaccine failure was defined as the occurrence of an invasive pneumococcal infection in children properly vaccinated by PCV13. Among 84 patients with invasive pneumococcal infection, 32 had received at least one dose of PCV13. Seventeen of them had invasive pneumococcal infection produced by a PCV13 serotype. Among those, 9 patients were considered to have a PCV13 vaccine failure. Serotype 3 was isolated in 6 patients, serotype 19A in 2 and serotype 6B in 1. PMID:26658626

  4. An analytical discrete ordinates solution for a nodal model of a two-dimensional neutron transport problem

    SciTech Connect

    Filho, J. F. P.

    2013-07-01

    In this work, an analytical discrete ordinates method is used to solve a nodal formulation of a neutron transport problem in x, y-geometry. The proposed approach leads to an important reduction in the order of the associated eigenvalue systems, when combined with the classical level symmetric quadrature scheme. Auxiliary equations are proposed, as usually required for nodal methods, to express the unknown fluxes at the boundary introduced as additional unknowns in the integrated equations. Numerical results, for the problem defined by a two-dimensional region with a spatially constant and isotropically emitting source, are presented and compared with those available in the literature. (authors)

  5. NODAL — The second life of the accelerator control language

    NASA Astrophysics Data System (ADS)

    Cuisinier, G.; Perriollat, F.; Ribeiro, P.; Kagarmanov, A.; Kovaltsov, V.

    1994-12-01

    NODAL has been a popular interpreter language for accelerator controls since the beginning of the 1970s. NODAL has been rewritten in the C language to be easily portable to the different computer platforms which are in use in accelerator controls. The paper describes the major features of this new version of NODAL, the major software packages which are available through this implementation, the platforms on which it is currently running, and some relevant performances. The experience gained during the rejuvenation project of the CERN accelerator control systems is presented. The benefit of this is discussed, in particular in a view of the prevailing strong constraints in personnel and money resources.

  6. Optimal Hedge for Nodal Price Risk using FTR

    NASA Astrophysics Data System (ADS)

    Tanaka, Hiroaki; Makino, Michiko; Ichida, Yoshio; Akiyoshi, Masanori

    As the deregulation of electric business proceeds, each company needs to construct a risk hedging system. So far many companies have not been taking much care of this suffciently. In this paper, we address the nodal price hedge issue. Most companies have risks for the nodal prices which tend to be highly volatile. There's almost no doubt that such a company actually needs hedge products to make profits stable. We suggest the usage of FTR for this purpose. First, we briefly note the mechanisms of nodal price in PJM market and FTR, and suggest the mathematical formulations. Then we show some numerical examples and discuss our findings.

  7. Tunable Weyl Points in Periodically Driven Nodal Line Semimetals.

    PubMed

    Yan, Zhongbo; Wang, Zhong

    2016-08-19

    Weyl semimetals and nodal line semimetals are characterized by linear band touching at zero-dimensional points and one-dimensional lines, respectively. We predict that a circularly polarized light drives nodal line semimetals into Weyl semimetals. The Floquet Weyl points thus obtained are tunable by the incident light, which enables investigations of them in a highly controllable manner. The transition from nodal line semimetals to Weyl semimetals is accompanied by the emergence of a large and tunable anomalous Hall conductivity. Our predictions are experimentally testable by transport measurement in film samples or by pump-probe angle-resolved photoemission spectroscopy. PMID:27588882

  8. Myocardial Regional Interstitial Fibrosis is Associated With Left Intra-Ventricular Dyssynchrony in Patients With Heart Failure: A Cardiovascular Magnetic Resonance Study

    PubMed Central

    Lin, Lian-Yu; Wu, Cho-Kai; Juang, Jyh-Ming Jimmy; Wang, Yi-Chih; Su, Mao-Yuan Marine; Lai, Ling-Ping; Hwang, Juey-Jen; Chiang, Fu-Tien; Tseng, Wen-Yih Issac; Lin, Jiunn-Lee

    2016-01-01

    Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failure (HF). The mechanisms leading to LV dyssynchrony are not fully elucidated. This study evaluates whether myocardium regional variation in interstitial fibrosis is associated with LV dyssynchrony. Forty-two patients with systolic heart failure (SHF), 76 patients with heart failure with preserved ejection fraction (HFpEF) and 20 patients without HF received cardiovascular magnetic resonance imaging (MRI) study. LV was divided into 18 segments by short-axis view. In each segment, regional extracellular volume fraction (ECV) and the time taken to reach minimum regional volume (Tmv) were derived. Intra-LV dyssynchrony were represented by maximum difference (Dysyn_max) and standard deviation (Dysyn_sd) of all Tmv. The results showed that among the covariates, only age (1.87, 95% CI: 0.61–3.13, p = 0.004) and ECV (3.77, 95% CI: 2.72–4.81, p < 0.001) were positively associated with Tmv. The results remained robust in certain subgroups. In conclusion, we demonstrated that LV myocardium regional variation in interstitial fibrosis is closely related to LV intra-ventricular dyssynchrony irrespective of the LV global function. These data might help explain the pathophysiology of LV dyssynchrony and it’s underlying mechanisms leading to poor prognosis. PMID:26846306

  9. Error estimation and adaptive order nodal method for solving multidimensional transport problems

    SciTech Connect

    Zamonsky, O.M.; Gho, C.J.; Azmy, Y.Y.

    1998-01-01

    The authors propose a modification of the Arbitrarily High Order Transport Nodal method whereby they solve each node and each direction using different expansion order. With this feature and a previously proposed a posteriori error estimator they develop an adaptive order scheme to automatically improve the accuracy of the solution of the transport equation. They implemented the modified nodal method, the error estimator and the adaptive order scheme into a discrete-ordinates code for solving monoenergetic, fixed source, isotropic scattering problems in two-dimensional Cartesian geometry. They solve two test problems with large homogeneous regions to test the adaptive order scheme. The results show that using the adaptive process the storage requirements are reduced while preserving the accuracy of the results.

  10. The ancestral role of nodal signalling in breaking L/R symmetry in the vertebrate forebrain.

    PubMed

    Lagadec, Ronan; Laguerre, Laurent; Menuet, Arnaud; Amara, Anis; Rocancourt, Claire; Péricard, Pierre; Godard, Benoît G; Rodicio, Maria Celina; Rodriguez-Moldes, Isabel; Mayeur, Hélène; Rougemont, Quentin; Mazan, Sylvie; Boutet, Agnès

    2015-01-01

    Left-right asymmetries in the epithalamic region of the brain are widespread across vertebrates, but their magnitude and laterality varies among species. Whether these differences reflect independent origins of forebrain asymmetries or taxa-specific diversifications of an ancient vertebrate feature remains unknown. Here we show that the catshark Scyliorhinus canicula and the lampreys Petromyzon marinus and Lampetra planeri exhibit conserved molecular asymmetries between the left and right developing habenulae. Long-term pharmacological treatments in these species show that nodal signalling is essential to their generation, rather than their directionality as in teleosts. Moreover, in contrast to zebrafish, habenular left-right differences are observed in the absence of overt asymmetry of the adjacent pineal field. These data support an ancient origin of epithalamic asymmetry, and suggest that a nodal-dependent asymmetry programme operated in the forebrain of ancestral vertebrates before evolving into a variable trait in bony fish. PMID:25819227

  11. Cryopreservation of Passiflora pohlii nodal segments and assessment of genetic stability of regenerated plants.

    PubMed

    Merhy, T S M; Vianna, M G; Garcia, R O; Pacheco, G; Mansur, E

    2014-01-01

    Passiflora pohlii is a wild species native to Brazil, with a potential agronomic interest due to its tolerance to soil-borne pathogens that cause damage to the passion fruit culture, and could be used in breeding. Because this species occurs in impacted regions, the goal of this study was the development of in vitro conservation strategies, using nodal segments from axenic plants. Encapsulation-vitrification and vitrification techniques were tested for cryopreservation of nodal segments. The highest recovery (65%) was obtained with the vitrification technique using treatment with the PVS3 vitrification solution from 30 to 120 min. Post-rewarming recovery was achieved on MSM medium supplemented with 30.8 μM BAP with incubation in the dark for 30 days before transfer in the presence of light. No differences were detected between control and cryopreserved materials as assayed by RAPD and ISSR. PMID:24997838

  12. Characterization and genomic structure of Dnah9, and its roles in nodal signaling pathways in the Japanese flounder (Paralichthys olivaceus).

    PubMed

    Niu, Jingjing; Liu, Conghui; Yang, Fang; Wang, Zhenwei; Wang, Bo; Zhang, Quanqi; He, Yan; Qi, Jie

    2016-02-01

    The nodal signaling pathway has been shown to play crucial roles in inducing and patterning the mesoderm and endoderm, as well as in regulating neurogenesis and left-right axis asymmetry. Here, we present the first complete cDNA and genomic sequences as well as the promoter predication of the Dnah9 gene in the Japanese flounder. The 15,558-bp-long cDNA is divided into 96 exons and spread over 138 kb of genomic DNA. Protein sequence comparison showed that it shares higher identity with other vertebrate orthologs, with an ATP binding dynein motor, AAA domain and microtubule binding stalk of dynein motor. Dnah9 exhibited maternal and ubiquitous expression in all cells of the early development stages, but became concentrated in the head at 1 DAH, as identified by qRT-PCR and in situ hybridization methods. Furthermore, after nodal signaling was inhibited, the level of Southpaw did not change significantly at early development stage (50 % epiboly) but increased significantly at late stages (27-somite stages and 1 DAH), as well as the expression of Lefty, an inhibitor of nodal signaling, increased continuously. On the other hand, the expression level of Dnah9 decreased. The transcription factor binding site of FAST-1 (SMAD interacting protein) was identified in the transcription region of Dnah9 by the promoter analysis, which might format the complexes of SMADs, FAST-1 and the transcription region of Dnah9 served as a bridge of Dnah9 and nodal signaling. All evidences indicated that Dnah9 might be downstream of nodal during the early development stages, and an indirect function through SMADs for nodal signaling pathway. PMID:26377939

  13. The Lunar Nodal Cycle and the Bidecadal Climate Variability in Precipitation and Tropospheric Circulation Over Southern South America

    NASA Astrophysics Data System (ADS)

    Agosta, E.

    2013-05-01

    The present work will show for first time some statistical evidences that the lunar nodal cycle can influence the low-frequency variability of summer rainfalls in the plains to the east of subtropical Andes, a region known as 'Nuevo Cuyo' (NC) in South America. The link can be established through the sea surface temperature (SST) modulation that is induced by the nodal amplitudes of diurnal tides over the southwestern South Atlatnci (SWSA) region. In years of strong (weak) diurnal tides, nodal tide-induced diapycnical mixing makes SST cooler (warmer) that are accompanied by negative (positive) sea level pressure (SLP) anomalies affecting the mid-latitudes low-level tropospheric circulation. The SST variations would presumably affect the lower tropospheric baroclinicity in the surroundings of the Malvinas/Falklands Islands in the SWSA, which in turn would induce shifts of mid-latitude stormtracks. Tropospheric circulation anomalies being located over the SWSA directly affect the interannual variability of summer rainfalls in NC. It is further shown that such an influence can be extended to the bidecadal variability observed in the summer rainfalls owing to the nodal modulation effect. The identification of the nodal periodicity in the NC summer rainfall variability is statistically robust. Although the 1976/77 climate shift has mitigated the bidecadal component of the summer rainfalls until the early 2000s, the nodal cycle has always been present. Hence it could improve the interdecadal predictability of the mean conditions of summer rainfalls and of those socio-economic variables being sensitive to precipitation such as grape yield in the Mendoza Province.

  14. Concomitant Wolff-Parkinson-White and Atrioventricular Nodal Reentrant Tachycardia: Which Pathway to Ablate?

    PubMed Central

    Sarsam, Sinan; Sidiqi, Ibrahim; Shah, Dipak; Zughaib, Marcel

    2015-01-01

    Patient: Male, 54 Final Diagnosis: WPW and AVNRT Symptoms: Palpitations • shorthness of breath Medication: — Clinical Procedure: EP Study/Radiofrequency Ablation Specialty: Cardiology Objective: Rare co-existance of disease or pathology Background: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common form of supraventricular tachycardia. In contrast, Wolff-Parkinson-White (WPW) pattern consists of an accessory pathway, which may result in the development of ventricular arrhythmias. Frequent tachycardia caused by AVNRT and accessory pathways may play a role in left ventricular systolic dysfunction. Case Report: A 54-year-old man presented with palpitations and acute decompensated congestive heart failure. His baseline EKG showed Wolff-Parkinson-White (WPW) pattern. While hospitalized, he had an episode of atrioventricular nodal reentrant tachycardia (AVNRT). He underwent radiofrequency catheter ablation for AVNRT, and his accessory pathway was also ablated even though its conduction was found to be weak. He was clinically doing well on follow-up visit, with resolution of his heart failure symptoms and normalization of left ventricular function on echocardiography. Conclusions: This case raises the question whether the accessory pathway plays a role in the development of systolic dysfunction, and if there is any role for ablation in patients with asymptomatic WPW pattern. PMID:26655223

  15. Present Status of GNF New Nodal Simulator

    SciTech Connect

    Iwamoto, T.; Tamitani, M.; Moore, B.

    2001-06-17

    This paper presents core simulator consolidation work done at Global Nuclear Fuel (GNF). The unified simulator needs to supercede the capabilities of past simulator packages from the original GNF partners: GE, Hitachi, and Toshiba. At the same time, an effort is being made to produce a simulation package that will be a state-of-the-art analysis tool when released, in terms of the physics solution methodology and functionality. The core simulator will be capable and qualified for (a) high-energy cycles in the U.S. markets, (b) mixed-oxide (MOX) introduction in Japan, and (c) high-power density plants in Europe, etc. The unification of the lattice physics code is also in progress based on a transport model with collision probability methods. The AETNA core simulator is built upon the PANAC11 software base. The goal is to essentially replace the 1.5-energy-group model with a higher-order multigroup nonlinear nodal solution capable of the required modeling fidelity, while keeping highly automated library generation as well as functionality. All required interfaces to PANAC11 will be preserved, which minimizes the impact on users and process automation. Preliminary results show statistical accuracy improvement over the 1.5-group model.

  16. Intensity-Modulated Radiotherapy for Tumors of the Nasal Cavity and Paranasal Sinuses: Clinical Outcomes and Patterns of Failure

    SciTech Connect

    Wiegner, Ellen A.; Daly, Megan E.; Murphy, James D.; Abelson, Jonathan; Chapman, Chris H.; Chung, Melody; Yu, Yao; Colevas, A. Dimitrios; Kaplan, Michael J.; Fischbein, Nancy; Le, Quynh-Thu; Chang, Daniel T.

    2012-05-01

    Purpose: To report outcomes in patients treated with intensity-modulated radiotherapy (IMRT) for tumors of the paranasal sinuses and nasal cavity (PNS/NC). Methods/Materials: Between June 2000 and December 2009, 52 patients with tumors of the PNS/NC underwent postoperative or definitive radiation with IMRT. Twenty-eight (54%) patients had squamous cell carcinoma (SCC). Twenty-nine patients (56%) received chemotherapy. The median follow-up was 26.6 months (range, 2.9-118.4) for all patients and 30.9 months for living patients. Results: Eighteen patients (35%) developed local-regional failure (LRF) at median time of 7.2 months. Thirteen local failures (25%) were observed, 12 in-field and 1 marginal. Six regional failures were observed, two in-field and four out-of-field. No patients treated with elective nodal radiation had nodal regional failure. Two-year local-regional control (LRC), in-field LRC, freedom from distant metastasis (FFDM), and overall survival (OS) were 64%, 74%, 71%, and 66% among all patients, respectively, and 43%, 61%, 61%, and 53% among patients with SCC, respectively. On multivariate analysis, SCC and >1 subsite involved had worse LRC (p = 0.0004 and p = 0.046, respectively) and OS (p = 0.003 and p = 0.046, respectively). Cribriform plate invasion (p = 0.005) and residual disease (p = 0.047) also had worse LRC. Acute toxicities included Grade {>=}3 mucositis in 19 patients (37%), and Grade 3 dermatitis in 8 patients (15%). Six patients had Grade {>=}3 late toxicity including one optic toxicity. Conclusions: IMRT for patients with PNS/NC tumors has good outcomes compared with historical series and is well tolerated. Patients with SCC have worse LRC and OS. LRF is the predominant pattern of failure.

  17. Classification, Electrophysiological Features and Therapy of Atrioventricular Nodal Reentrant Tachycardia

    PubMed Central

    Josephson, Mark E

    2016-01-01

    Atrioventricular nodal reentrant tachycardia (AVNRT) should be classified as typical or atypical. The term ‘fast-slow AVNRT’ is rather misleading. Retrograde atrial activation during tachycardia should not be relied upon as a diagnostic criterion. Both typical and atypical atrioventricular nodal reentrant tachycardia are compatible with varying retrograde atrial activation patterns. Attempts at establishing the presence of a ‘lower common pathway’ are probably of no practical significance. When the diagnosis of AVNRT is established, ablation should be only directed towards the anatomic position of the slow pathway. If right septal attempts are unsuccessful, the left septal side should be tried. Ablation targeting earliest atrial activation sites during typical atrioventricular nodal reentrant tachycardia or the fast pathway in general for any kind of typical or atypical atrioventricular nodal reentrant tachycardia, are not justified. In this review we discuss current concepts about the tachycardia circuit, electrophysiologic diagnosis, and ablation of this arrhythmia.

  18. Nodal analysis for reactor kinetics and stability. [PWR; BWR

    SciTech Connect

    Park, J.K.; Becker, M.; Park, G.C.

    1983-07-01

    General space kinetics models have been developed for more accurate stability analysis utilizing nodal analysis, a commonly used technique for analyzing power distributions in large power reactors. Kinetics parameters for use in these kinetics models have been properly derived by utilizing self-consistent nodal data and power distributions. The procedure employed in the nodal code SIMULATE has been utilized for power distribution, since that methodology is general and includes various commonly used nodal methods as special cases. Cross sections are correlated as functions of void fraction and exposure. A computer program investigating thermo-hydrodynamic stability, NUFREQ has been modified to accommodate general spatial kinetics models with an improved thermal-hydraulics model. Stability analyses have been performed for density wave oscillations for a representative operating BWR system. Spatial coupling effects on the stability margins were found to be significant.

  19. BEACON: An application of nodal methods for operational support

    SciTech Connect

    Boyd, W.A.; Nguyen, T.Q. )

    1992-01-01

    A practical application of nodal methods is on-line plant operational support. However, to enable plant personnel to take full advantage of a nodal model to support plant operations, (a) a core nodal model must always be up to date with the current core history and conditions, (b) the nodal methods must be fast enough to allow numerous core calculations to be performed in minutes to support engineering decisions, and (c) the system must be easily accessible to engineering personnel at the reactor, their offices, or any other location considered appropriate. A core operational support package developed by Westinghouse called BEACON (best estimate analysis of core operations - nuclear) has been installed at several plants. Results from these plants and numerous in-core flux maps analyzed have demonstrated the accuracy of the model and the effectiveness of the methodology

  20. Bilinear nodal transport method in weighted diamond difference form

    SciTech Connect

    Azmy, Y.Y.

    1987-01-01

    Nodal methods have been developed and implemented for the numerical solution of the discrete ordinates neutron transport equation. Numerical testing of these methods and comparison of their results to those obtained by conventional methods have established the high accuracy of nodal methods. Furthermore, it has been suggested that the linear-linear approximation is the most computationally efficient, practical nodal approximation. Indeed, this claim has been substantiated by comparing the accuracy in the solution, and the CPU time required to achieve convergence to that solution by several nodal approximations, as well as the diamond difference scheme. Two types of linear-linear nodal methods have been developed in the literature: analytic linear-linear (NLL) methods, in which the transverse-leakage terms are derived analytically, and approximate linear-linear (PLL) methods, in which these terms are approximated. In spite of their higher accuracy, NLL methods result in very complicated discrete-variable equations that exhibit a high degree of coupling, thus requiring special solution algorithms. On the other hand, the sacrificed accuracy in PLL methods is compensated for by the simple discrete-variable equations and diamond-difference-like solution algorithm. In this paper the authors outline the development of an NLL nodal method, the bilinear method, which can be written in a weighted diamond difference form with one spatial weight per dimension that is analytically derived rather than preassigned in an ad hoc fashion.

  1. Assessment of the magnitude and associated factors of immunological failure among adult and adolescent HIV-infected patients in St. Luke and Tulubolo Hospital, Oromia Region, Ethiopia

    PubMed Central

    Bayou, Bekelech; Sisay, Abay; Kumie, Abera

    2015-01-01

    Introduction The use of antiretroviral therapy (ART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to ART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to assess the magnitude and associated factors of Immunological failure among adult and adolescent HIV infected Patients (with age ‘15yrs) on Highly Active Antiretroviral Therapy (HAART) in St. Luke and Tulu Bolo Hospitals, Oromia Region, Ethiopia. Methods A retrospective follow-up study was conducted among HIV-infected patients initiated 1st line ART at St. Luke and Tulu Bolo Hospitals, South West Shoa Zone, Oromia, Ethiopia. Results A total of 828 patient charts were reviewed. 477(57.6%) were female and the median age was 32 years. The median baseline CD4 count was 148cells/mm3. The most common prescribed ART was TDF based (36.7%). Out of 828 patients chart reviewed 6.8% (56) were developed immunological failure. Out of them only 20 (2.4%) were detected and put on second line regimen. The incidence of immunological failure was 1.8 cases per 100 person years of follow-up. Patients who had not disclosed their HIV status to any one had high risk of immunological failure compared with patients those who had disclosed their HIV status (AHR, 0.429; 95% CI 0.206 - 0.893; P-value=0.024). Conclusion Non disclosures of HIV status and with ambulatory of baseline functional status were found to be predictors of immunological failure. Most of the immunological failure cases were not detected early and not switched to second line ARV regimen. So patients with the above risk factors should be considered for a timely switch to second line HAART. PMID:26587140

  2. Students' Failure to Submit Research Projects on Time: A Case Study from Masvingo Regional Centre at Zimbabwe Open University

    ERIC Educational Resources Information Center

    Chabaya, Owence; Chiome, Chrispen; Chabaya, Raphinos A.

    2009-01-01

    The study sought to determine lecturers' and students' perceptions of factors contributing to students' failure to submit research projects on time in three departments of the Zimbabwe Open University. The study employed a descriptive survey design and was both quantitative and qualitative. The questionnaire used as a data-gathering instrument had…

  3. An amphioxus nodal gene (AmphiNodal) with early symmetrical expression in the organizer and mesoderm and later asymmetrical expression associated with left-right axis formation

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Linda Z.; Holland, Nicholas D.

    2002-01-01

    The full-length sequence and zygotic expression of an amphioxus nodal gene are described. Expression is first detected in the early gastrula just within the dorsal lip of the blastopore in a region of hypoblast that is probably comparable with the vertebrate Spemann's organizer. In the late gastrula and early neurula, expression remains bilaterally symmetrical, limited to paraxial mesoderm and immediately overlying regions of the neural plate. Later in the neurula stage, all neural expression disappears, and mesodermal expression disappears from the right side. All along the left side of the neurula, mesodermal expression spreads into the left side of the gut endoderm. Soon thereafter, all expression is down-regulated except near the anterior and posterior ends of the animal, where transcripts are still found in the mesoderm and endoderm on the left side. At this time, expression also begins in the ectoderm on the left side of the head, in the region where the mouth later forms. These results suggest that amphioxus and vertebrate nodal genes play evolutionarily conserved roles in establishing Spemann's organizer, patterning the mesoderm rostrocaudally and setting up the asymmetrical left-right axis of the body.

  4. A Computational Model of Dynein Activation Patterns that Can Explain Nodal Cilia Rotation

    PubMed Central

    Chen, Duanduan; Zhong, Yi

    2015-01-01

    Normal left-right patterning in vertebrates depends on the rotational movement of nodal cilia. In order to produce this ciliary motion, the activity of axonemal dyneins must be tightly regulated in a temporal and spatial manner; the specific activation pattern of the dynein motors in the nodal cilia has not been reported. Contemporary imaging techniques cannot directly assess dynein activity in a living cilium. In this study, we establish a three-dimensional model to mimic the ciliary ultrastructure and assume that the activation of dynein proteins is related to the interdoublet distance. By employing finite-element analysis and grid deformation techniques, we simulate the mechanical function of dyneins by pairs of point loads, investigate the time-variant interdoublet distance, and simulate the dynein-triggered ciliary motion. The computational results indicate that, to produce the rotational movement of nodal cilia, the dynein activity is transferred clockwise (looking from the tip) between the nine doublet microtubules, and along each microtubule, the dynein activation should occur faster at the basal region and slower when it is close to the ciliary tip. Moreover, the time cost by all the dyneins along one microtubule to be activated can be used to deduce the dynein activation pattern; it implies that, as an alternative method, measuring this time can indirectly reveal the dynein activity. The proposed protein-structure model can simulate the ciliary motion triggered by various dynein activation patterns explicitly and may contribute to furthering the studies on axonemal dynein activity. PMID:26153700

  5. SU-F-BRD-16: Under Dose Regions Recalculated by Monte Carlo Cannot Predict the Local Failure for NSCLC Patients Treated with SBRT

    SciTech Connect

    Liu, H; Cherian, S; Stephans, K; Videtic, G; Qi, P; Xia, P; Zhuang, T

    2014-06-15

    Purpose: To investigate whether Monte Carlo (MC) recalculated dose distributions can predict the geometric location of the recurrence for nonsmall cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Methods: Thirty NSCLC patients with local recurrence were retrospectively selected for this study. The recurred gross target volumes (rGTV) were delineated on the follow-up CT/PET images and then rigidly transferred via imaging fusion to the original planning CTs. Failure pattern was defined according to the overlap between the rGTV and planning GTV (pGTV) as: (a) in-field failure (≥80%), (b) marginal failure (20%–80%), and (c) out-of-field failure (≤20%). All clinical plans were calculated initially with pencil beam (PB) with or without heterogeneity correction dependent of protocols. These plans were recalculated with MC with heterogeneity correction. Because of non-uniform dose distributions in the rGTVs, the rGTVs were further divided into four regions: inside the pGTV (GTVin), inside the PTV (PTVin), outside the pGTV (GTVout), and outside the PTV (PTVout). The mean doses to these regions were reported and analyzed separately. Results: Among 30 patients, 10 patients had infield recurrences, 15 marginal and 5 out-of-field failures. With MC calculations, D95 and D99 of the PTV were reduced by (10.6 ± 7.4)% and (11.7 ± 7.9)%. The average MC calculated mean doses of GTVin, GTVout, PTVin and PTVout were 48.2 ± 5.3 Gy, 48.2 ± 5.5 Gy, 46.3 ± 6.2 Gy and 46.6 ± 5.6 Gy, respectively. No significant dose differences between GTVin and GTVout (p=0.65), PTVin and PTVout (p=0.19) were observed, using the paired students t-test. Conclusion: Although the PB calculations underestimated the tumor target doses, the geometric location of the recurrence did not correlate with the mean doses of subsections of the recurrent GTV. Under dose regions recalculated by MC cannot predict the local failure for NSCLC patients treated with SBRT.

  6. Accuracy of Computed Tomography for Predicting Pathologic Nodal Extracapsular Extension in Patients With Head-and-Neck Cancer Undergoing Initial Surgical Resection

    SciTech Connect

    Prabhu, Roshan S.; Magliocca, Kelly R.; Hanasoge, Sheela; Aiken, Ashley H.; Hudgins, Patricia A.; Hall, William A.; Chen, Susie A.; Eaton, Bree R.; Higgins, Kristin A.; Saba, Nabil F.; Beitler, Jonathan J.

    2014-01-01

    Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initial surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.

  7. Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

    SciTech Connect

    Morikawa, Lisa K.; Roach, Mack

    2011-05-01

    Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostate cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.

  8. Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells

    PubMed Central

    Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

    2014-01-01

    Summary Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. PMID:24936448

  9. Predictors of failure of awake regional anesthesia for neonatal hernia repair: data from the General Anesthesia compared to Spinal anesthesia (GAS) study: comparing apnoea and neurodevelopmental outcomes

    PubMed Central

    Frawley, Geoff; Bell, Graham; Disma, Nicola; Withington, Davinia E.; de Graaff, Jurgen C.; Morton, Neil S.; McCann, Mary Ellen; Arnup, Sarah J.; Bagshaw, Oliver; Wolfler, Andrea; Bellinger, David; Davidson, Andrew J.

    2015-01-01

    Background Awake regional anesthesia (RA) is a viable alternative to general anesthesia (GA) for infants undergoing lower abdominal surgery. Benefits include lower incidence of postoperative apnea and avoidance of anesthetic agents that may increase neuroapoptosis and worsen neurocognitive outcomes. The General Anesthesia compared to Spinal anesthesia (GAS) study compares neurodevelopmental outcomes following awake RA or GA in otherwise healthy infants. Our aim was to describe success and failure rates of RA in this study and report factors associated with failure. Methods This was a nested cohort study within a prospective randomized, controlled, observer blind, equivalence trial. Seven hundred twenty two infants ≤ 60 weeks postmenstrual age, scheduled for herniorrhaphy under anesthesia were randomly assigned to receive RA (spinal, caudal epidural or combined spinal caudal anesthetic) or GA with sevoflurane. The data of 339 infants, where spinal or combined spinal caudal anesthetic was attempted, was analyzed. Possible predictors of failure were assessed including: patient factors, technique, experience of site and anesthetist and type of local anesthetic. Results RA was sufficient for the completion of surgery in 83.2% of patients. Spinal anesthesia was successful in 86.9% of cases and combined spinal caudal anesthetic in 76.1%. Thirty four patients required conversion to GA and an additional 23 (6.8%) required brief sedation. Bloody tap on the first attempt at lumbar puncture was the only risk factor significantly associated with block failure (OR = 2.46). Conclusions The failure rate of spinal anesthesia was low. Variability in application of combined spinal caudal anesthetic limited attempts to compare the success of this technique to spinal alone. PMID:26001028

  10. Nodal endoplasmic reticulum, a specialized form of endoplasmic reticulum found in gravity-sensing root tip columella cells

    NASA Technical Reports Server (NTRS)

    Zheng, H. Q.; Staehelin, L. A.

    2001-01-01

    The endoplasmic reticulum (ER) of columella root cap cells has been postulated to play a role in gravity sensing. We have re-examined the ultrastructure of columella cells in tobacco (Nicotiana tabacum) root tips preserved by high-pressure freezing/freeze-substitution techniques to gain more precise information about the organization of the ER in such cells. The most notable findings are: the identification of a specialized form of ER, termed "nodal ER," which is found exclusively in columella cells; the demonstration that the bulk of the ER is organized in the form of a tubular network that is confined to a peripheral layer under the plasma membrane; and the discovery that this ER-rich peripheral region excludes Golgi stacks, vacuoles, and amyloplasts but not mitochondria. Nodal ER domains consist of an approximately 100-nm-diameter central rod composed of oblong subunits to which usually seven sheets of rough ER are attached along their margins. These domains form patches at the interface between the peripheral ER network and the ER-free central region of the cells, and they occupy defined positions within central and flanking columella cells. Over one-half of the nodal ER domains are located along the outer tangential walls of the flanking cells. Cytochalasin D and latrunculin A cause an increase in size and a decrease in numbers of nodal ER domains. We postulate that the nodal ER membranes locally modulate the gravisensing signals produced by the sedimenting amyloplasts, and that the confinement of all ER membranes to the cell periphery serves to enhance the sedimentability of the amyloplasts in the central region of columella cells.

  11. Mathematical embryology: the fluid mechanics of nodal cilia

    NASA Astrophysics Data System (ADS)

    Smith, D. J.; Smith, A. A.; Blake, J. R.

    2011-07-01

    Left-right symmetry breaking is critical to vertebrate embryonic development; in many species this process begins with cilia-driven flow in a structure termed the `node'. Primary `whirling' cilia, tilted towards the posterior, transport morphogen-containing vesicles towards the left, initiating left-right asymmetric development. We review recent theoretical models based on the point-force stokeslet and point-torque rotlet singularities, explaining how rotation and surface-tilt produce directional flow. Analysis of image singularity systems enforcing the no-slip condition shows how tilted rotation produces a far-field `stresslet' directional flow, and how time-dependent point-force and time-independent point-torque models are in this respect equivalent. Associated slender body theory analysis is reviewed; this approach enables efficient and accurate simulation of three-dimensional time-dependent flow, time-dependence being essential in predicting features of the flow such as chaotic advection, which have subsequently been determined experimentally. A new model for the nodal flow utilising the regularized stokeslet method is developed, to model the effect of the overlying Reichert's membrane. Velocity fields and particle paths within the enclosed domain are computed and compared with the flow profiles predicted by previous `membrane-less' models. Computations confirm that the presence of the membrane produces flow-reversal in the upper region, but no continuous region of reverse flow close to the epithelium. The stresslet far-field is no longer evident in the membrane model, due to the depth of the cavity being of similar magnitude to the cilium length. Simulations predict that vesicles released within one cilium length of the epithelium are generally transported to the left via a `loopy drift' motion, sometimes involving highly unpredictable detours around leftward cilia [truncated

  12. Deep seated tectonic-gravitive failure and large landslide in the area from Scilla to Punta Pezzo (Calabria region South Italy)

    NASA Astrophysics Data System (ADS)

    Guerricchio, A.; Doglioni, A.; Simeone, V.

    2012-04-01

    A critical analysis of the morphological characters of the Southern Calabria region in the area from Scilla (RC province- Southern Italy) to Messina Strait show some geomorphological anomalies due to deep tectonic-gravitational failures and landslides induced by the uplift of the same area. The above mentioned phenomena involve, in fact the whole structure of the ridge included between the coastline and Fiumara di Catona (Catona Torrent), starting from Melia Highland (Pian della Melia) towards the promontory of Punta Pezzo on Messina Strait; and have a severe influence on the morphological forms of the territory, on the surface and coastal erosion phenomena and probably, also on the effect of seismic shocks on large engineering works, as the-to-be built Messina Strait bridge, which is very close to Scilla and Punta Pezzo area. The evidence of these failure can be recognized in the arched morphological steps breaking down the crystalline rock masses, but specially in the hydrographic stream network that is so deep and irregular in crystalline rocks that cannot be imputed only to surficial erosion. In fact at the end of the main streams or torrents as Santa Trara or San Gregorio torrents (fiumare) there are not relevant alluvial fan deposits. These tectonic-gravitative failure have been favored by the presence of biotitic schists underlying gneiss and granite rock masses. The first ones has a stiffness lower than the seconds, so they are more deformable. It is also possible that schist rock masses overlie the more deformable phyllite rocks, not outcropping in the area, as it happen in other zones of Calabria region (Guerricchio e Al., 2007). Tectonic-gravitative failures have broken and disarticulated also the terraces of Late Pleistocene deposits lying over the crystalline basement multiplied by these failures, so that may seem terraces of different order. The coastal slope between Gioia Tauro and Scilla is quite high and in a sudden way changes its form just in the

  13. Nodal signaling promotes a tumorigenic phenotype in human breast cancer.

    PubMed

    Kirsammer, Gina; Strizzi, Luigi; Margaryan, Naira V; Gilgur, Alina; Hyser, Matthew; Atkinson, Janis; Kirschmann, Dawn A; Seftor, Elisabeth A; Hendrix, Mary J C

    2014-12-01

    The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF-β family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1 cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins post-translationally and that this cascade is essential for aggressive breast tumor behavior in vivo. As the MAPK pathway is an important target for treating triple-negative breast cancers, upstream Nodal signaling may represent a promising target for breast cancer diagnosis and combined therapies aimed at blocking ERK pathway activation. PMID:25073112

  14. Nodal signaling promotes a tumorigenic phenotype in human breast cancer

    PubMed Central

    Kirsammer, Gina; Strizzi, Luigi; Margaryan, Naira V.; Gilgur, Alina; Hyser, Matthew; Atkinson, Janis; Kirschmann, Dawn A.; Seftor, Elisabeth A.; Hendrix, Mary J.C.

    2014-01-01

    The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF-β family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1 cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins post-translationally and that this cascade is essential for aggressive breast tumor behavior in vivo. As the MAPK pathway is an important target for treating triple-negative breast cancers, upstream Nodal signaling may represent a promising target for breast cancer diagnosis and combined therapies aimed at blocking ERK pathway activation. PMID:25073112

  15. A computational study of nodal-based tetrahedral element behavior.

    SciTech Connect

    Gullerud, Arne S.

    2010-09-01

    This report explores the behavior of nodal-based tetrahedral elements on six sample problems, and compares their solution to that of a corresponding hexahedral mesh. The problems demonstrate that while certain aspects of the solution field for the nodal-based tetrahedrons provide good quality results, the pressure field tends to be of poor quality. Results appear to be strongly affected by the connectivity of the tetrahedral elements. Simulations that rely on the pressure field, such as those which use material models that are dependent on the pressure (e.g. equation-of-state models), can generate erroneous results. Remeshing can also be strongly affected by these issues. The nodal-based test elements as they currently stand need to be used with caution to ensure that their numerical deficiencies do not adversely affect critical values of interest.

  16. Super-nodal methods for space-time kinetics

    NASA Astrophysics Data System (ADS)

    Mertyurek, Ugur

    The purpose of this research has been to develop an advanced Super-Nodal method to reduce the run time of 3-D core neutronics models, such as in the NESTLE reactor core simulator and FORMOSA nuclear fuel management optimization codes. Computational performance of the neutronics model is increased by reducing the number of spatial nodes used in the core modeling. However, as the number of spatial nodes decreases, the error in the solution increases. The Super-Nodal method reduces the error associated with the use of coarse nodes in the analyses by providing a new set of cross sections and ADFs (Assembly Discontinuity Factors) for the new nodalization. These so called homogenization parameters are obtained by employing consistent collapsing technique. During this research a new type of singularity, namely "fundamental mode singularity", is addressed in the ANM (Analytical Nodal Method) solution. The "Coordinate Shifting" approach is developed as a method to address this singularity. Also, the "Buckling Shifting" approach is developed as an alternative and more accurate method to address the zero buckling singularity, which is a more common and well known singularity problem in the ANM solution. In the course of addressing the treatment of these singularities, an effort was made to provide better and more robust results from the Super-Nodal method by developing several new methods for determining the transverse leakage and collapsed diffusion coefficient, which generally are the two main approximations in the ANM methodology. Unfortunately, the proposed new transverse leakage and diffusion coefficient approximations failed to provide a consistent improvement to the current methodology. However, improvement in the Super-Nodal solution is achieved by updating the homogenization parameters at several time points during a transient. The update is achieved by employing a refinement technique similar to pin-power reconstruction. A simple error analysis based on the relative

  17. A transient, quadratic nodal method for triangular-Z geometry

    SciTech Connect

    DeLorey, T.F.

    1993-06-01

    Many systematically-derived nodal methods have been developed for Cartesian geometry due to the extensive interest in Light Water Reactors. These methods typically model the transverse-integrated flux as either an analytic or low order polynomial function of position within the node. Recently, quadratic nodal methods have been developed for R-Z and hexagonal geometry. A static and transient quadratic nodal method is developed for triangular-Z geometry. This development is particularly challenging because the quadratic expansion in each node must be performed between the node faces and the triangular points. As a consequence, in the 2-D plane, the flux and current at the points of the triangles must be treated. Quadratic nodal equations are solved using a non-linear iteration scheme, which utilizes the corrected, mesh-centered finite difference equations, and forces these equations to match the quadratic equations by computing discontinuity factors during the solution. Transient nodal equations are solved using the improved quasi-static method, which has been shown to be a very efficient solution method for transient problems. Several static problems are used to compare the quadratic nodal method to the Coarse Mesh Finite Difference (CMFD) method. The quadratic method is shown to give more accurate node-averaged fluxes. However, it appears that the method has difficulty predicting node leakages near reactor boundaries and severe material interfaces. The consequence is that the eigenvalue may be poorly predicted for certain reactor configurations. The transient methods are tested using a simple analytic test problem, a heterogeneous heavy water reactor benchmark problem, and three thermal hydraulic test problems. Results indicate that the transient methods have been implemented correctly.

  18. Kidney Failure

    MedlinePlus

    ... if You Have Kidney Disease Kidney Failure Expand Dialysis Kidney Transplant Preparing for Kidney Failure Treatment Choosing Not to Treat with Dialysis or Transplant Paying for Kidney Failure Treatment Contact ...

  19. Chiral Spin-Orbital Liquids with Nodal Lines

    NASA Astrophysics Data System (ADS)

    Natori, W. M. H.; Andrade, E. C.; Miranda, E.; Pereira, R. G.

    2016-07-01

    Strongly correlated materials with strong spin-orbit coupling hold promise for realizing topological phases with fractionalized excitations. Here, we propose a chiral spin-orbital liquid as a stable phase of a realistic model for heavy-element double perovskites. This spin liquid state has Majorana fermion excitations with a gapless spectrum characterized by nodal lines along the edges of the Brillouin zone. We show that the nodal lines are topological defects of a non-Abelian Berry connection and that the system exhibits dispersing surface states. We discuss some experimental signatures of this state and compare them with properties of the spin liquid candidate Ba2YMoO6.

  20. Long period nodal motion of sun synchronous orbits

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1975-01-01

    An approximative model is formulated for assessing these perturbations that significantly affect long term modal motion of sun synchronous orbits. Computer simulations with several independent computer programs consider zonal and tesseral gravitational harmonics, third body gravitational disturbances induced by the sun and the moon, and atmospheric drag. A pendulum model consisting of evenzonal harmonics through order 4 and solar gravity dominated nodal motion approximation. This pendulum motion results from solar gravity inducing an inclination oscillation which couples into the nodal precession induced by the earth's oblateness. The pendulum model correlated well with simulations observed flight data.

  1. Risk factors for tuberculosis treatment failure among pulmonary tuberculosis patients in four health regions of Burkina Faso, 2009: case control study

    PubMed Central

    Sawadogo, Bernard; Tint, Khin San; Tshimanga, Mufuta; Kuonza, Lazarus; Ouedraogo, Laurent

    2015-01-01

    Introduction In Burkina Faso, the tuberculosis (TB) treatment failure rate increased from 2.5% in 2000 to 8.3% in 2006. The risk factors for TB treatment failure in the country are not well known. The study aims to determine the risk factors for treatment failure among pulmonary tuberculosis patients in four health region of Burkina Faso and to recommend appropriate interventions. Methods A case control study was conducted among pulmonary TB patients who began TB treatment in 2009. A case was any patient who remained smear-positive at fifth month of TB treatment and a control was a patient who tested smear-negative at fifth month of treatment. A structured questionnaire was administered to one hundred cases and one hundred controls to collect information on exposure factors. Odds ratio were calculated using bivariate and multivariate analysis to determine the association between exposures and outcome. Results Multivariate analysis showed that independent risk factors for TB treatment failure were fail to take TB drugs for more than 14 consecutive days (OR = 18.53; 95% CI:4.56 - 75.22), sputum smear-positive at two months of treatment (OR = 11.52; 95%CI:5.18-25.60), existence of comorbidity (OR = 5.74; 95%CI:1.69-19.44), and use of traditional medicines or herbs (OR = 2.97; 95%CI:1.12-7.85). Conclusion Early identification of patients with the above risk factors for intense case management will improve TB treatment outcome. Patient with smear positive at 2ndnd month of treatment require more intense follow-up, and involving traditional healers who provide traditional medicines or herbs in the educational programme on TB are required. The national referral laboratory capacity needs to be strengthened to do drug susceptibility testing and routine drug monitoring on cases of non conversion at 2nd month of treatment. PMID:26327989

  2. Squamous Cell Carcinoma of the Anal Canal: Patterns and Predictors of Failure and Implications for Intensity-Modulated Radiation Treatment Planning

    SciTech Connect

    Wright, Jean L.; Patil, Sujata M.; Temple, Larissa K.F.; Minsky, Bruce D.; Saltz, Leonard B.; Goodman, Karyn A.

    2010-11-15

    Purpose: Intensity-modulated radiation treatment (IMRT) is increasingly used in the treatment of squamous cell carcinoma of the anal canal (SCCAC). Prevention of locoregional failure (LRF) using IMRT requires appropriate clinical target volume (CTV) definition. To better define the CTV for IMRT, we evaluated patterns and predictors of LRF in SCCAC patients given conventional radiation treatment. Methods and Materials: We reviewed records of 180 SCCAC patients treated with conventional radiation with or without chemotherapy at our institution between January 1990 and March 2007. All patients received radiation; the median primary tumor dose was 45 Gy. A total of 173 patients also received mitomycin-based chemotherapy. Results: Median follow-up was 40 months. Actuarial 3-year colostomy-free survival was 89% and overall survival (OS) 88%. Actuarial 3-year LRF was 23%. A total of 45 patients had LRF, with 35 (78%) occurring locally in the primary site (25 local only, 10 local and regional); however, 20 (44%) had regional components of failure within the pelvis or inguinal nodes (10 regional only, 10 local and regional). Cumulative sites of LRF (patients may have one or more site of failure) were as follows: primary, 35; inguinal, 8; external perianal, 5; common iliac, 4; presacral, 3; distal rectum, 2; external iliac, 2; and internal iliac, 2. All patients with common iliac failure had cT3 or N+ disease. Conclusions: The observed patterns of failure support inclusion of the inguinal and all pelvic nodal groups in the CTV for IMRT. In patients with advanced tumor or nodal stage, common iliac nodes should also be included in the CTV.

  3. Clinical and Therapeutic Profiles of Heart Failure Patients admitted to a Tertiary Hospital, Aseer Region, Saudi Arabia

    PubMed Central

    Assiri, Abdullah S

    2011-01-01

    Objectives: This study aimed to investigate the clinical and therapeutic profiles of heart failure (HF) cases admitted to Aseer Central Hospital (ACH), Saudi Arabia. Methods: A retrospective cohort of 300 consecutive patients admitted with the diagnosis of HF to ACH from 1 June 2007 to 31 May 2009 were included in the study. Data on demographic variables, aetiologic factors, risk factors, and therapeutic profiles of patients with HF were collected and analysed. Results: The patients’ mean age was 67.4 ± 13.7 years and 68.7% of them were male. The commonest aetiologies for HF were ischaemic heart disease (IHD) and hypertension in 38.3% and 33.3% of patients, respectively. A total of 61.3% of patients were diabetics. Other risk factors for HF included renal failure in 9.7%, atrial fibrillation in 13%, and anaemia in 48.3% of patients. Echocardiography was performed in 98.7% of cases: the average ejection fraction (EF) was 33% ± 17. Angiotensin converting enzyme inhibitors (ACEI) or angiotensin 2 receptor blockers were used in 68.3% of cases, β-blockers in 51.6% of cases and digoxin in 28.3% of cases. Conclusion: The major causes of HF in our study were IHD and hypertension. Diabetes and anaemia were common risk factors. The cohort constituted an intermediate HF risk group (ejection fraction (EF) 33%). Important therapeutic agents like angiotensin converting enzyme inhibitor I, β-blockers and digoxin were underutilised. Fostering such therapy in practice will lead to a better outcome in the management of HF patients. Anaemia was a significant risk factor in our HF patients and should be managed properly. PMID:21969895

  4. A transient, Hex-Z nodal code corrected by discontinuity factors. Volume 1: The transient nodal code; Final report

    SciTech Connect

    Shatilla, Y.A.M.; Henry, A.F.

    1993-12-31

    This document constitutes Volume 1 of the Final Report of a three-year study supported by the special Research Grant Program for Nuclear Energy Research set up by the US Department of Energy. The original motivation for the work was to provide a fast and accurate computer program for the analysis of transients in heavy water or graphite-moderated reactors being considered as candidates for the New Production Reactor. Thus, part of the funding was by way of pass-through money from the Savannah River Laboratory. With this intent in mind, a three-dimensional (Hex-Z), general-energy-group transient, nodal code was created, programmed, and tested. In order to improve accuracy, correction terms, called {open_quotes}discontinuity factors,{close_quotes} were incorporated into the nodal equations. Ideal values of these factors force the nodal equations to provide node-integrated reaction rates and leakage rates across nodal surfaces that match exactly those edited from a more exact reference calculation. Since the exact reference solution is needed to compute the ideal discontinuity factors, the fact that they result in exact nodal equations would be of little practical interest were it not that approximate discontinuity factors, found at a greatly reduced cost, often yield very accurate results. For example, for light-water reactors, discontinuity factors found from two-dimensional, fine-mesh, multigroup transport solutions for two-dimensional cuts of a fuel assembly provide very accurate predictions of three-dimensional, full-core power distributions. The present document (volume 1) deals primarily with the specification, programming and testing of the three-dimensional, Hex-Z computer program. The program solves both the static (eigenvalue) and transient, general-energy-group, nodal equations corrected by user-supplied discontinuity factors.

  5. Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

    PubMed

    Chen, Hui; Zhang, Ji; Cao, Guang; Liu, Peng; Xu, Haifeng; Wang, Xiaodong; Zhu, Xu; Gao, Song; Guo, Jianhai; Zhu, Linzhong; Zhang, Pengjun

    2016-02-01

    Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials. PMID:26566233

  6. PoroTomo Subtask 6.3 Nodal Seismometers Metadata

    DOE Data Explorer

    Lesley Parker

    2016-03-28

    Metadata for the nodal seismometer array deployed at the POROTOMO's Natural Laboratory in Brady Hot Spring, Nevada during the March 2016 testing. Metadata includes location and timing for each instrument as well as file lists of data to be uploaded in a separate submission.

  7. Bud emergence and shoot growth from mature citrus nodal segments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bud emergence and shoot growth from adult phase citrus nodal cultures were studied using Citrus mitis (calamondin), Citrus paradisi (grapefruit), and Citrus sinensis (sweet orange). The effects of 6-benzylaminopurine (BA), indole 3-acetic acid (IAA), and citrus type on shoot quality and growth fro...

  8. Nodal Structure and the Partitioning of Equivalence Classes

    ERIC Educational Resources Information Center

    Fields, Lanny; Watanabe-Rose, Mari

    2008-01-01

    By definition, all of the stimuli in an equivalence class have to be functionally interchangeable with each other. The present experiment, however, demonstrated that this was not the case when using post-class-formation dual-option response transfer tests. With college students, two 4-node 6-member equivalence classes with nodal structures of…

  9. Nodal-mediated epigenesis requires dynamin-mediated endocytosis

    PubMed Central

    Ertl, Robin P.; Robertson, Anthony J.; Saunders, Diane; Coffman, James A.

    2011-01-01

    Nodal proteins are diffusible morphogens that drive pattern formation via short-range feedback activation coupled to long-range Lefty-mediated inhibition. In the sea urchin embryo, specification of the secondary (oral-aboral) axis occurs via zygotic expression of nodal, which is localized to the prospective oral ectoderm at early blastula stage. In mid-blastula stage embryos treated with low micromolar nickel or zinc, nodal expression expands progressively beyond the confines of this localized domain to encompass the entire equatorial circumference of the embryo, producing radialized embryos lacking an oral-aboral axis. RNAseq analysis of embryos treated with nickel, zinc or cadmium (which does not radialize embryos) showed that several genes involved in endocytosis were similarly perturbed by nickel and zinc but not cadmium. Inhibiting dynamin, a GTPase required for receptor-mediated endocytosis, phenocopies the effects of nickel and zinc, suggesting that dynamin-mediated endocytosis is required as a sink to limit the range of Nodal signaling. PMID:21337468

  10. Effects of Out-of-Plane Disorder on the Nodal Quasiparticle and Superconducting Gap in Single-Layer Bi_2Sr_1.6Ln_0.4CuO_6 delta (Ln = La, Nd, Gd)

    SciTech Connect

    Hashimoto, M.

    2011-01-04

    How out-of-plane disorder affects the electronic structure has been investigated for the single-layer cuprates Bi{sub 2}Sr{sub 1.6}Ln{sub 0.4}CuO{sub 6+{delta}} (Ln = La, Nd, Gd) by angle-resolved photoemission spectroscopy. We have observed that, with increasing disorder, while the Fermi surface shape and band dispersions are not affected, the quasi-particle width increases, the anti-nodal gap is enhanced and the superconducting gap in the nodal region is depressed. The results indicate that the superconductivity is significantly depressed by out-of-plane disorder through the enhancement of the anti-nodal gap and the depression of the superconducting gap in the nodal region.

  11. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Digital Electronic Message Service Nodal... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may...

  12. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Digital Electronic Message Service Nodal... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may...

  13. Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

    PubMed Central

    Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

    2015-01-01

    Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (p<0.01) compared to photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. Lung V20 and mean lung dose decreased 18% (p<0.01) and 36% (p<0.01), respectively, with proton IFRT and 11% (p=0.03) and 26% (p<0.01) with ENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all p<0.01). Conclusions This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

  14. Total Gross Tumor Volume Is an Independent Prognostic Factor in Patients Treated With Selective Nodal Irradiation for Stage I to III Small Cell Lung Cancer

    SciTech Connect

    Reymen, Bart; Van Loon, Judith; Baardwijk, Angela van; Wanders, Rinus; Borger, Jacques; Dingemans, Anne-Marie C.; Bootsma, Gerben; Pitz, Cordula; Lunde, Ragnar; Geraedts, Wiel; Lambin, Philippe; De Ruysscher, Dirk

    2013-04-01

    Purpose: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. Methods and Materials: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). Results: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. Conclusions: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

  15. Wave pinning and spatial patterning in a mathematical model of Antivin/Lefty-Nodal signalling.

    PubMed

    Middleton, A M; King, J R; Loose, M

    2013-12-01

    Nodal signals are key regulators of mesoderm and endoderm development in vertebrate embryos. It has been observed experimentally that in Xenopus embryos the spatial range of Nodal signals is restricted by the signal Antivin (also known as Lefty). Nodal signals can activate both Nodal and Antivin, whereas Antivin is thought to antagonise Nodal by binding either directly to it or to its receptor. In this paper we develop a mathematical model of this signalling network in a line of cells. We consider the heterodimer and receptor-mediated inhibition mechanisms separately and find that, in both cases, the restriction by Antivin to the range of Nodal signals corresponds to wave pinning in the model. Our analysis indicates that, provided Antivin diffuses faster than Nodal, either mechanism can robustly account for the experimental data. We argue that, in the case of Xenopus development, it is wave pinning, rather than Turing-type patterning, that is underlying Nodal-Antivin dynamics. This leads to several experimentally testable predictions, which are discussed. Furthermore, for heterodimer-mediated inhibition to prevent waves of Nodal expression from propagating, the Nodal-Antivin complex must be turned over, and diffusivity of the complex must be negligible. In the absence of molecular mechanisms regulating these, we suggest that Antivin restricts Nodal signals via receptor-mediated, and not heterodimer-mediated, inhibition. PMID:23070212

  16. Post-radiotherapy neck dissection improves control at non-regional disease sites after definitive chemoradiation for squamous cell carcinoma of the head and neck

    PubMed Central

    Ranck, Mark C.; Abundo, Rainier; Jefferson, Gina; Kolokythas, Antonia; Wenig, Barry L.; Weichselbaum, Ralph R.; Spiotto, Michael T.

    2015-01-01

    Importance After chemoradiation for head and neck cancer, over ninety percent of patients who achieved a complete response by imaging were regionally controlled without post-radiotherapy neck dissections (PRND). Since several groups have reported that lymph node involvement also predicted failure at both primary and distant sites, it remains unclear the extent to which PRND impacts non-regional sites of disease. Objective Here, we evaluated how PRND impacted local and distant control in patients who achieved a clinical complete response. Design We retrospectively reviewed patients treated for stage III/IV disease with definitive chemoradiation between 1990 to 2012. Setting University of Illinois at Chicago. Participants 287 patients were treated with definitive CRT, of whom seventy-four underwent PRND. Median follow up was 25.4 months. Interventions Chemoradiation followed by lymph node dissection or observation. Main Outcomes and Measures Endpoints evaluated included local control (LC), regional control (RC), freedom from distant metastasis (FFDM), progression free survival (PFS) and overall survival (OS) using first-failure analysis. Results Patients with advanced nodal disease (≥N2b; n=176) had improved PFS (74.6% vs. 39.1%; P<.001) while patients with lesser nodal disease had similar PFS. For patients with advanced nodal disease, PRND improved 2-year LC (85.5 vs. 53.5%; p<.001), locoregional control with PRND (78.9% vs. 45.7%; P<.001), FFDM (79.5% vs. 67.5%%; P=.03) and OS (84.5% vs. 61.7%; P=.004) but not RC (96.9% vs. 90.1%; P=.21) The benefit in LC (87.4% vs. 66.2%; P=.02) and PFS (80.7% vs. 53.4%; P=.01) persisted for those with negative post-treatment imaging who underwent PRND. On univariate analysis, PRND, alcohol use, nodal stage and chemoradiation significantly impacted 2 year LC and/or PFS. On multivariate analysis, PRND remained strongly prognostic for 2 year LC (HR 0.22; P=.0007) and PFS (HR 0.42; P=.002). Conclusions and Relevance PRND improved

  17. Kidney Failure

    MedlinePlus

    ... enough red blood cells. This is called kidney failure. If your kidneys fail, you need treatment to ... providers, family, and friends, most people with kidney failure can lead full and active lives. NIH: National ...

  18. Respiratory Failure

    MedlinePlus

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  19. Intensity-Modulated Radiotherapy for Oral Cavity Squamous Cell Carcinoma: Patterns of Failure and Predictors of Local Control

    SciTech Connect

    Daly, Megan E.; Le, Quynh-Thu; Kozak, Margaret M.; Maxim, Peter G.; Murphy, James D.; Hsu, Annie; Loo, Billy W.; Kaplan, Michael J.; Fischbein, Nancy J.; Chang, Daniel T.

    2011-08-01

    Purpose: Few studies have evaluated the use of intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report clinical outcomes and failure patterns for these patients. Methods and Materials: Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87 months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7 weeks). Results: Thirteen patients experienced local-regional failure at a median of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced local recurrence between surgery and RT. Seven local failures occurred in-field (one with simultaneous nodal and distant disease) and two at the margin. Four regional failures occurred, two in-field and two out-of-field, one with synchronous metastases. Six patients experienced distant failure. The 3-year actuarial estimates of local control, local-regional control, freedom from distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive patients. Four patients developed Grade {>=}2 chronic toxicity. Increased surgery to RT interval predicted for decreased LRC (p = 0.04). Conclusions: Local-regional control for SCC of the OC treated with IMRT with or without surgery remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity profiles. A surgery-to-RT interval of <6 weeks improves local-regional control. The predominant failure pattern was local, suggesting that both improvements in target delineation and radiosensitization and/or dose escalation are needed.

  20. The Impact of the Size of Nodal Metastases on Recurrence Risk in Breast Cancer Patients With 1-3 Positive Axillary Nodes After Mastectomy

    SciTech Connect

    Harris, Eleanor E.R.; Freilich, Jessica; Lin, Hui-Yi; Chuong, Michael; Acs, Geza

    2013-03-01

    Purpose: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients with 1-3 positive nodes is controversial. The objective of this study was to determine whether the size of nodal metastases in this subset could predict who would benefit from PMRT. Methods and Materials: We analyzed 250 breast cancer patients with 1-3 positive nodes after mastectomy treated with contemporary surgery and systemic therapy at our institution. Of these patients, 204 did not receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were stratified by the size of the largest nodal metastasis measured as less than or equal to 5 mm or greater than 5 mm. Results: The median follow-up was 65.6 months. In the whole group, regional recurrences occurred in 2% of patients in whom the largest nodal metastasis measured 5 mm or less vs 6% for those with metastases measuring greater than 5 mm. For non-irradiated patients only, regional recurrence rates were 2% and 9%, respectively. Those with a maximal nodal size greater than 5 mm had a significantly higher cumulative incidence of regional recurrence (P=.013). The 5-year cumulative incidence of a regional recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI], 0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%) for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for metastasis size greater than 10 mm. The impact of the maximal nodal size on regional recurrences became insignificant in the multivariable model. Conclusions: In patients with 1-3 positive lymph nodes undergoing mastectomy without radiation, nodal metastasis greater than 5 mm was associated with regional recurrence after mastectomy, but its effect was modified by other factors (such as tumor stage). The size of the largest nodal metastasis may be useful to identify high-risk patients who may benefit from radiation therapy after mastectomy.

  1. Off-diagonal Jacobian support for Nodal BCs

    SciTech Connect

    Peterson, John W.; Andrs, David; Gaston, Derek R.; Permann, Cody J.; Slaughter, Andrew E.

    2015-01-01

    In this brief note, we describe the implementation of o-diagonal Jacobian computations for nodal boundary conditions in the Multiphysics Object Oriented Simulation Environment (MOOSE) [1] framework. There are presently a number of applications [2{5] based on the MOOSE framework that solve complicated physical systems of partial dierential equations whose boundary conditions are often highly nonlinear. Accurately computing the on- and o-diagonal Jacobian and preconditioner entries associated to these constraints is crucial for enabling ecient numerical solvers in these applications. Two key ingredients are required for properly specifying the Jacobian contributions of nonlinear nodal boundary conditions in MOOSE and nite element codes in general: 1. The ability to zero out entire Jacobian matrix rows after \

  2. Long-range Coulomb interaction in nodal-ring semimetals

    NASA Astrophysics Data System (ADS)

    Huh, Yejin; Moon, Eun-Gook; Kim, Yong Baek

    2016-01-01

    Recently there have been several proposals of materials predicted to be nodal-ring semimetals, where zero energy excitations are characterized by a nodal ring in the momentum space. This class of materials falls between the Dirac-like semimetals and the more conventional Fermi-surface systems. As a step towards understanding this unconventional system, we explore the effects of the long-range Coulomb interaction. Due to the vanishing density of states at the Fermi level, Coulomb interaction is only partially screened and remains long-ranged. Through renormalization group and large-Nf computations, we have identified a nontrivial interacting fixed point. The screened Coulomb interaction at the interacting fixed point is an irrelevant perturbation, allowing controlled perturbative evaluations of physical properties of quasiparticles. We discuss unique experimental consequences of such quasiparticles: acoustic wave propagation, anisotropic dc conductivity, and renormalized phonon dispersion as well as energy dependence of quasiparticle lifetime.

  3. Anomalous contagion and renormalization in networks with nodal mobility

    NASA Astrophysics Data System (ADS)

    Manrique, Pedro D.; Qi, Hong; Zheng, Minzhang; Xu, Chen; Hui, Pak Ming; Johnson, Neil F.

    2016-07-01

    A common occurrence in everyday human activity is where people join, leave and possibly rejoin clusters of other individuals —whether this be online (e.g. social media communities) or in real space (e.g. popular meeting places such as cafes). In the steady state, the resulting interaction network would appear static over time if the identities of the nodes are ignored. Here we show that even in this static steady-state limit, a non-zero nodal mobility leads to a diverse set of outbreak profiles that is dramatically different from known forms, and yet matches well with recent real-world social outbreaks. We show how this complication of nodal mobility can be renormalized away for a particular class of networks.

  4. Concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma.

    PubMed

    Geurten, Claire; Thiry, Albert; Jamblin, Paul; Demarche, Martine; Hoyoux, Claire

    2015-12-01

    A 10-year-old girl with a family history of Hodgkin's lymphoma presented with a 2 month history of cervical lymphadenopathy and weight loss. Biopsy indicated concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma. Such an association is rare, especially so in children, but is not an isolated phenomenon, thereby prompting the question of whether Langerhans cell histiocytosis is a reactive or a neoplastic process. PMID:26556799

  5. NODAL PATHWAY GENES ARE DOWNREGULATED IN FACIAL ASYMMETRY

    PubMed Central

    Nicot, Romain; Hottenstein, Molly; Raoul, Gwenael; Ferri, Joel; Horton, Michael; Tobias, John W.; Barton, Elisabeth; Gelé, Patrick; Sciote, James J.

    2014-01-01

    Purpose Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes which are down regulated in facial asymmetry patients. Material and Methods Masseter muscle samples were collected during BSSO orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as Class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. Results Overall gene expression was different for asymmetric patients compared to other malocclusion classifications by principal component analysis (P<0.05). We identified differences in the nodal signaling pathway (NSP) which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39–1.84 fold greater (P<3.41×10−5) whereas integral membrane Nodal-modulators Nomo1,2,3 were −5.63 to −5.81 (P<3.05×10−4) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of −7.02 to −2.47 (P<0.003). Finally Pitx2, a upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P<0.05). Conclusions When facial asymmetry is part of skeletal malocclusion there are decreases of NSP genes in masseter muscle. This data suggests that the NSP is down regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition. PMID:25364968

  6. Nodal Basin Recurrence After Sentinel Lymph Node Biopsy for Melanoma

    PubMed Central

    Kretschmer, Lutz; Bertsch, Hans Peter; Zapf, Antonia; Mitteldorf, Christina; Satzger, Imke; Thoms, Kai-Martin; Völker, Bernward; Schön, Michael Peter; Gutzmer, Ralf; Starz, Hans

    2015-01-01

    Abstract The objective of this study was to analyze different types of nodal basin recurrence after sentinel lymph node biopsy (SLNB) for melanoma. Patients and Methods: Kaplan–Meier estimates and the Cox proportional hazards model were used to study 2653 patients from 3 German melanoma centers retrospectively. The estimated 5-year negative predictive value of SLNB was 96.4%. The estimated false-negative (FN) rates after 1, 2, 3, 5, and 10 years were 2.5%, 4.6%, 6.4%, 8.7%, and 12.6%, respectively. Independent factors associated with false negativity were older age, fewer SLNs excised, and head or neck location of the primary tumor. Compared with SLN-positive patients, the FNs had a significantly lower survival. In SLN-positive patients undergoing completion lymphadenectomy (CLND), the 5-year nodal basin recurrence rate was 18.3%. The recurrence rates for axilla, groin, and neck were 17.2%, 15.5%, and 44.1%, respectively. Significant factors predicting local relapse after CLND were older age, head, or neck location of the primary tumor, ulceration, deeper penetration of the metastasis into the SLN, tumor-positive CLND, and >2 lymph node metastases. All kinds of nodal relapse were associated with a higher prevalence of in-transit metastases. The FN rate after SLNB steadily increases over the observation period and should, therefore, be estimated by the Kaplan–Meier method. False-negativity is associated with fewer SLNs excised. The beneficial effect of CLND on nodal basin disease control varies considerably across different risk groups. This should be kept in mind about SLN-positive patients when individual decisions on prophylactic CLND are taken. PMID:26356697

  7. LSST Telescope Alignment Plan Based on Nodal Aberration Theory

    NASA Astrophysics Data System (ADS)

    Sebag, J.; Gressler, W.; Schmid, T.; Rolland, J. P.; Thompson, K. P.

    2012-04-01

    The optical alignment of the Large Synoptic Survey Telescope (LSST) is potentially challenging, due to its fast three-mirror optical design and its large 3.5° field of view (FOV). It is highly advantageous to align the three-mirror optical system prior to the integration of the complex science camera on the telescope, which corrects the FOV via three refractive elements and includes the operational wavefront sensors. A telescope alignment method based on nodal aberration theory (NAT) is presented here to address this challenge. Without the science camera installed on the telescope, the on-axis imaging performance of the telescope is diffraction-limited, but the field of view is not corrected. The nodal properties of the three-mirror telescope design have been analyzed and an alignment approach has been developed using the intrinsically linear nodal behavior, which is linked via sensitivities to the misalignment parameters. Since mirror figure errors will exist in any real application, a methodology to introduce primary-mirror figure errors into the analysis has been developed and is also presented.

  8. Upper bound shakedown analysis with the nodal natural element method

    NASA Astrophysics Data System (ADS)

    Zhou, Shutao; Liu, Yinghua; Wang, Dongdong; Wang, Kai; Yu, Suyuan

    2014-11-01

    In this paper, a novel numerical solution procedure is developed for the upper bound shakedown analysis of elastic-perfectly plastic structures. The nodal natural element method (nodal-NEM) combines the advantages of the NEM and the stabilized conforming nodal integration scheme, and is used to discretize the established mathematical programming formulation of upper bound shakedown analysis based on Koiter's theorem. In this formulation, the displacement field is approximated by using the Sibson interpolation and the difficulty caused by the time integration is solved by König's technique. Meanwhile, the nonlinear and non-differentiable characteristic of objective function is overcome by distinguishing non-plastic areas from plastic areas and modifying associated constraint conditions and goal function at each iteration step. Finally, the objective function subjected to several equality constraints is linearized and the upper bound shakedown load multiplier is obtained. This direct iterative process can ensure the shakedown load to monotonically converge to the upper bound of true solution. Several typical numerical examples confirm the efficiency and accuracy of the proposed method.

  9. A nodal domain theorem for integrable billiards in two dimensions

    SciTech Connect

    Samajdar, Rhine; Jain, Sudhir R.

    2014-12-15

    Eigenfunctions of integrable planar billiards are studied — in particular, the number of nodal domains, ν of the eigenfunctions with Dirichlet boundary conditions are considered. The billiards for which the time-independent Schrödinger equation (Helmholtz equation) is separable admit trivial expressions for the number of domains. Here, we discover that for all separable and non-separable integrable billiards, ν satisfies certain difference equations. This has been possible because the eigenfunctions can be classified in families labelled by the same value of mmodkn, given a particular k, for a set of quantum numbers, m,n. Further, we observe that the patterns in a family are similar and the algebraic representation of the geometrical nodal patterns is found. Instances of this representation are explained in detail to understand the beauty of the patterns. This paper therefore presents a mathematical connection between integrable systems and difference equations. - Highlights: • We find that the number of nodal domains of eigenfunctions of integrable, planar billiards satisfy a class of difference equations. • The eigenfunctions labelled by quantum numbers (m,n) can be classified in terms of mmodkn. • A theorem is presented, realising algebraic representations of geometrical patterns exhibited by the domains. • This work presents a connection between integrable systems and difference equations.

  10. Anomalous scaling of the penetration depth in nodal superconductors

    NASA Astrophysics Data System (ADS)

    She, Jian-Huang; Lawler, Michael J.; Kim, Eun-Ah

    2015-07-01

    Recent findings of anomalous superlinear scaling of low-temperature (T ) penetration depth (PD) in several nodal superconductors near putative quantum critical points suggest that the low-temperature PD can be a useful probe of quantum critical fluctuations in a superconductor. On the other hand, cuprates, which are poster child nodal superconductors, have not shown any such anomalous scaling of PD, despite growing evidence of quantum critical points (QCP). Then it is natural to ask when and how can quantum critical fluctuations cause anomalous scaling of PD? Carrying out the renormalization group calculation for the problem of two-dimensional superconductors with point nodes, we show that quantum critical fluctuations associated with a point group symmetry reduction result in nonuniversal logarithmic corrections to the T dependence of the PD. The resulting apparent power law depends on the bare velocity anisotropy ratio. We then compare our results to data sets from two distinct nodal superconductors: YBa2Cu3O6.95 and CeCoIn5. Considering all symmetry-lowering possibilities of the point group of interest, C4 v, we find our results to be remarkably consistent with YBa2Cu3O6.95 being near a vertical nematic QCP and CeCoIn5 being near a diagonal nematic QCP. Our results motivate a search for diagonal nematic fluctuations in CeCoIn5.

  11. The Titan -1:0 Nodal Bending Wave in Saturn's Ring C.

    PubMed

    Rosen, P A; Lissauer, J J

    1988-08-01

    The most prominent oscillatory feature observed in the Voyager 1 radio occultation of Saturn's rings is identified as a one-armed spiral bending wave excited by Titan's -1:0 nodal inner vertical resonance. Ring partides in a bending wave move in coherently inclined orbits, warping the local mean plane of the rings. The Titan -1:0 wave is the only known bending wave that propagates outward, away from Saturn, and the only spiral wave yet observed in which the wave pattern rotates opposite to the orbital direction of the ring particles. It is also the first bending wave identified in ring C. Modeling the observed feature with existing bending wave theory gives a surface mass density of approximately 0.4 g/cm(2) outside the wave region and a local ring thickness of [unknown]5 meters, and suggests that surface mass density is not constant in the wave region. PMID:17839081

  12. The Titan-1:0 nodal bending wave in Saturn's Ring C

    NASA Technical Reports Server (NTRS)

    Rosen, Paul A.; Lissauer, Jack J.

    1988-01-01

    The most prominent oscillatory feature observed in the Voyager 1 radio occultation of Saturn's rings is identified as a one-armed spiral bending wave excited by Titan's-1:0 nodal inner vertical resonance. Ring particles in a bending wave move in coherently inclined orbits, warping the local mean plane of the rings. The Titan-1:0 wave is the only known bending wave that propagates outward, away from Saturn, and the only spiral wave yet observed in which the wave pattern rotates opposite to the orbital direction of the ring particles. It is also the first bending wave identified in ring C. Modeling the observed feature with existing bending wave theory gives a surface mass density of about 0.4 g/sq cm outside the wave region and a local ring thickness of less than about 5 meters, and suggests that surface mass density is not constant in the wave region.

  13. Response of millet and sorghum to a varying water supply around the primary and nodal roots

    PubMed Central

    Rostamza, M.; Richards, R. A.; Watt, M.

    2013-01-01

    Background and Aims Cereals have two root systems. The primary system originates from the embryo when the seed germinates and can support the plant until it produces grain. The nodal system can emerge from stem nodes throughout the plant's life; its value for yield is unclear and depends on the environment. The aim of this study was to test the role of nodal roots of sorghum and millet in plant growth in response to variation in soil moisture. Sorghum and millet were chosen as both are adapted to dry conditions. Methods Sorghum and millet were grown in a split-pot system that allowed the primary and nodal roots to be watered separately. Key Results When primary and nodal roots were watered (12 % soil water content; SWC), millet nodal roots were seven times longer than those of sorghum and six times longer than millet plants in dry treatments, mainly from an 8-fold increase in branch root length. When soil was allowed to dry in both compartments, millet nodal roots responded and grew 20 % longer branch roots than in the well-watered control. Sorghum nodal roots were unchanged. When only primary roots received water, nodal roots of both species emerged and elongated into extremely dry soil (0·6–1·5 % SWC), possibly with phloem-delivered water from the primary roots in the moist inner pot. Nodal roots were thick, short, branchless and vertical, indicating a tropism that was more pronounced in millet. Total nodal root length increased in both species when the dry soil was covered with plastic, suggesting that stubble retention or leaf mulching could facilitate nodal roots reaching deeper moist layers in dry climates. Greater nodal root length in millet than in sorghum was associated with increased shoot biomass, water uptake and water use efficiency (shoot mass per water). Millet had a more plastic response than sorghum to moisture around the nodal roots due to (1) faster growth and progression through ontogeny for earlier nodal root branch length and (2

  14. Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

    PubMed Central

    Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

    2015-01-01

    Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

  15. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    PubMed

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth. PMID:21195476

  16. Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system

    PubMed Central

    Müller, Patrick; Rogers, Katherine W.; Jordan, Ben M.; Lee, Joon S.; Robson, Drew; Ramanathan, Sharad; Schier, Alexander F.

    2012-01-01

    Biological systems involving short-range activators and long-range inhibitors can generate complex patterns. Reaction-diffusion models postulate that differences in signaling range are caused by differential diffusivity of inhibitor and activator. Other models suggest that differential clearance underlies different signaling ranges. To test these models, we measured the biophysical properties of the Nodal/Lefty activator/inhibitor system during zebrafish embryogenesis. Analysis of Nodal and Lefty gradients reveals that Nodals have a shorter range than Lefty proteins. Pulse-labelinganalysis indicates that Nodals and Leftys have similar clearance kinetics, whereas fluorescence recovery assays reveal that Leftys have a higher effective diffusion coefficient than Nodals. These results indicate that differential diffusivity is the major determinant of the differences in Nodal/Lefty range and provide biophysical support for reaction-diffusion models of activator/inhibitor-mediated patterning. PMID:22499809

  17. Productive Failure

    ERIC Educational Resources Information Center

    Kapur, Manu

    2008-01-01

    This study demonstrates an existence proof for "productive failure": engaging students in solving complex, ill-structured problems without the provision of support structures can be a productive exercise in failure. In a computer-supported collaborative learning setting, eleventh-grade science students were randomly assigned to one of two…

  18. Approximate Schur complement preconditioning of the lowest order nodal discretizations

    SciTech Connect

    Moulton, J.D.; Ascher, U.M.; Morel, J.E.

    1996-12-31

    Particular classes of nodal methods and mixed hybrid finite element methods lead to equivalent, robust and accurate discretizations of 2nd order elliptic PDEs. However, widespread popularity of these discretizations has been hindered by the awkward linear systems which result. The present work exploits this awkwardness, which provides a natural partitioning of the linear system, by defining two optimal preconditioners based on approximate Schur complements. Central to the optimal performance of these preconditioners is their sparsity structure which is compatible with Dendy`s black box multigrid code.

  19. Dosimetric evaluation of the feasibility of stereotactic body radiotherapy for primary lung cancer with lobe-specific selective elective nodal irradiation

    PubMed Central

    Komatsu, Tetsuya; Kunieda, Etsuo; Kitahara, Tadashi; Akiba, Takeshi; Nagao, Ryuta; Fukuzawa, Tsuyoshi

    2016-01-01

    More than 10% of all patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer develop regional lymph node recurrence. We evaluated the dosimetric feasibility of SBRT with lobe-specific selective elective nodal irradiation (ENI) on dose–volume histograms. A total of 21 patients were treated with SBRT for Stage I primary lung cancer between January 2010 and June 2012 at our institution. The extents of lobe-specific selective ENI fields were determined with reference to prior surgical reports. The ENI fields included lymph node stations (LNS) 3 + 4 + 11 for the right upper lobe tumors, LNS 7 + 11 for the right middle or lower lobe tumors, LNS 5 + 11 for the left upper lobe tumors, and LNS 7 + 11 for the left lower lobe tumors. A composite plan was generated by combining the ENI plan and the SBRT plan and recalculating for biologically equivalent doses of 2 Gy per fraction, using a linear quadratic model. The V20 of the lung, D1cm3 of the spinal cord, D1cm3 and D10cm3 of the esophagus and D10cm3 of the tracheobronchial wall were evaluated. Of the 21 patients, nine patients (43%) could not fulfill the dose constraints. In all these patients, the distance between the planning target volume (PTV) of ENI (PTVeni) and the PTV of SBRT (PTVsrt) was ≤2.0 cm. Of the three patients who developed regional metastasis, two patients had isolated lymph node failure, and the lymph node metastasis was included within the ENI field. When the distance between the PTVeni and PTVsrt is >2.0 cm, SBRT with selective ENI may therefore dosimetrically feasible. PMID:26566656

  20. Nodal systems with maximal domain of exactness for Gaussian quadrature formulas

    NASA Astrophysics Data System (ADS)

    Berriochoa, E.; Cachafeiro, A.

    2008-03-01

    The aim of this work is to study quadrature formulas for measures on the complex plane. The novelty of our contribution is to consider the exactness on subspaces of polynomials on the variables z and . Using this approach we characterize, in a unified way, the classical nodal systems for measures on the real line and the nodal systems for measures on the unit circle, which are based on para-orthogonal polynomials. We also characterize the nodal systems on the unit circle, which are not based on para-orthogonal polynomials (only for the case of nodal systems with 1 or 2 points).

  1. Nodal line optimization and its application to violin top plate design

    NASA Astrophysics Data System (ADS)

    Yu, Yonggyun; Jang, In Gwun; Kim, In Kyum; Kwak, Byung Man

    2010-10-01

    In the literature, most problems of structural vibration have been formulated to adjust a specific natural frequency: for example, to maximize the first natural frequency. In musical instruments like a violin; however, mode shapes are equally important because they are related to sound quality in the way that natural frequencies are related to the octave. The shapes of nodal lines, which represent the natural mode shapes, are generally known to have a unique feature for good violins. Among the few studies on mode shape optimization, one typical study addresses the optimization of nodal point location for reducing vibration in a one-dimensional beam structure. However, nodal line optimization, which is required in violin plate design, has not yet been considered. In this paper, the central idea of controlling the shape of the nodal lines is proposed and then applied to violin top plate design. Finite element model for a violin top plate was constructed using shell elements. Then, optimization was performed to minimize the square sum of the displacement of selected nodes located along the target nodal lines by varying the thicknesses of the top plate. We conducted nodal line optimization for the second and the fifth modes together at the same time, and the results showed that the nodal lines obtained match well with the target nodal lines. The information on plate thickness distribution from nodal line optimization would be valuable for tailored trimming of a violin top plate for the given performances.

  2. Translational significance of Nodal, Cripto-1 and Notch4 in adult nevi

    PubMed Central

    Strizzi, Luigi; Margaryan, Naira V.; Gerami, Pedram; Haghighat, Zahra; Harms, Paul W.; Madonna, Gabriele; Botti, Gerardo; Ascierto, Paolo A.; Hendrix, Mary J.C.

    2016-01-01

    The TGF-β associated growth factor Nodal is highly expressed in aggressive metastatic melanoma. Determining the risk for melanomagenesis from Nodal expression in nevi prior to the development of melanoma may be useful for both the screening and prevention of melanoma. Tissue sections of human adult nevi with or without a history of melanoma were stained by immunohistochemistry (IHC) for Nodal, the Nodal co-receptor Cripto-1, and Notch4, which have previously been shown to be associated with Nodal expression in melanoma. The degree of Nodal, Cripto-1 and Notch4 staining was scored and correlated with available clinical data. Median IHC scores for Nodal, Cripto-1 and Notch4 expression were significantly higher in nevi removed from patients who eventually developed melanoma compared with nevi from patients with no history of melanoma. In addition, the degree of Nodal expression in nevi from patients who eventually developed melanoma correlated significantly with the Breslow depth of the melanoma. Expression of Nodal and components of its signaling pathway in nevi may represent a biomarker for selecting a unique subset of patients requiring increased surveillance for screening and prevention of melanoma.

  3. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  4. Comparison of two methods for landslide susceptibility mapping in the Champagne region (France) where viticultural activity is threatened by slope failure

    NASA Astrophysics Data System (ADS)

    van den Eeckhaut, M.; Marre, A.; Poesen, J.

    2009-04-01

    The vineyards of the Champagne region are planted on steep south-oriented cuesta fronts receiving a maximum of sun radiation. However, due to the location of the vineyards on steep hillslopes, the viticultural activity is threatened by slope failures. In this study we attempt to better understand the spatial variability of landslides by comparing two techniques for landslide susceptibility assessment in a 1120 km² study area in the Champagne Ardenne. The first landslide susceptibility map was derived from an heuristic model adopted from the Bureau de Recherches Géologiques et Minières, geomorphologists of Reims University and the Comité Interprofessionnel du Vin de Champagne. In this qualitative model expert knowledge of the Champagne region was used to assign weights to all slope classes and lithologies located in the area. The second landslide susceptibility map was developed in this study by the application of a statistical model, logistic regression, to a calibration dataset of ‘old' (Holocene) landslides. This map was successfully evaluated using ROC curves and κ values. Both models indicate that present and future landslides are mainly controlled by slope gradient and lithology. However, the comparison of the two landslide susceptibility maps through (1) evaluation with the location of mapped ‘old' (Holocene) landslides and through (2) temporal validation with spatial data of ‘recent' (between forty and ten years old) and ‘very recent' (less than ten years old) landslides showed that the statistical model produced in this study allowed better prediction of sites already affected by landslides. In total the statistically-derived susceptibility map succeeded in correctly classifying 83.2% of the ‘old' and 84.0% of the ‘recent' and ‘very recent' landslides. The heuristic model on the other hand classified only 50.6% of the ‘old' and 58.5% of the ‘recent' and ‘very recent' landslides correctly as unstable. Taking into account the

  5. Long-Term Efficacy and Patterns of Failure After Accelerated Partial Breast Irradiation: A Molecular Assay-Based Clonality Evaluation

    SciTech Connect

    Vicini, Frank A. . E-mail: fvicini@beaumont.edu; Antonucci, J. Vito; Wallace, Michelle R.N.; Gilbert, Samuel; Goldstein, Neal S.; Kestin, Larry; Chen, Peter; Kunzman, Jonathan; Boike, Thomas; Benitez, Pamela; Martinez, Alvaro

    2007-06-01

    Purpose: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. Methods and Materials: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for {>=}10 years. Results: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. Conclusions: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.

  6. Symmetry Breaking in a Model for Nodal Cilia

    NASA Astrophysics Data System (ADS)

    Brokaw, Charles J.

    2005-03-01

    Nodal cilia are very short cilia found in the embryonic node on the ventral surface of early mammalian embryos. They create a right to left fluid flow that is responsible for determining the normal asymmetry of the internal organs of the mammalian body. To do this, the distal end of the cilium must circle in a counterclockwise sense. Computer simulations with 3-dimensional models of flagella allow examination of 3-dimensional movements such as those of nodal cilia. 3-dimensional circling motions of short cilia can be achieved with velocity controlled models, in which dynein activity is regulated by sliding velocity. If dyneins on one outer doublet are controlled by the sliding velocity experienced by that doublet, the system is symmetric, and the 3-dimensional models can show either clockwise or counterclockwise circling. My computer simulations have examined two possible symmetry breaking mechanisms: 1) dyneins on doublet N are regulated by a mixture of the sliding velocities experienced by doublets N and N+1 (numbered in a clockwise direction, looking from the base). or 2) symmetry is broken by an off-axis force that produces a right-handed twist of the axoneme, consistent with observations that some dyneins can rotate their substrate microtubules in a clockwise direction.

  7. Amyloid precursor protein at node of Ranvier modulates nodal formation.

    PubMed

    Xu, De-En; Zhang, Wen-Min; Yang, Zara Zhuyun; Zhu, Hong-Mei; Yan, Ke; Li, Shao; Bagnard, Dominique; Dawe, Gavin S; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2014-01-01

    Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination. PMID:25482638

  8. Testicular failure

    MedlinePlus

    ... Blood tests may show a low level of testosterone and high levels of prolactin, FSH , and LH . ... testes will be ordered. Testicular failure and low testosterone level may be hard to diagnose in older ...

  9. Heart Failure

    MedlinePlus

    ... together. About Rise Above HF Rise Above Heart Failure seeks to increase the dialogue about HF and improve the lives of people affected by the condition through awareness, education and support. Through the initiative, AHA strives to ...

  10. Distal end of the atrioventricular nodal artery predicts the risk of atrioventricular block during slow pathway catheter ablation of atrioventricular nodal re-entrant tachycardia

    PubMed Central

    Lin, J; Huang, S; Lai, L; Lin, L; Chen, J; Tseng, Y; Lien, W

    2000-01-01

    OBJECTIVE—To search for a reliable anatomical landmark within Koch's triangle to predict the risk of atrioventricular (AV) block during radiofrequency slow pathway catheter ablation of AV nodal re-entrant tachycardia (AVNRT).
PATIENTS AND METHODS—To test the hypothesis that the distal end of the AV nodal artery represents the anatomical location of the AV node, and thus could be a useful landmark for predicting the risk of AV block, 128 consecutive patients with AVNRT receiving slow pathway catheter ablation were prospectively studied in two phases. In phase I (77 patients), angiographic demonstration of the AV nodal artery and its ending was performed at the end of the ablation procedure, whereas in the subsequent phase II study (51 patients), the angiography was performed immediately before catheter ablation to assess the value of identifying this new landmark in reducing the risk of AV block. Multiple electrophysiologic and anatomical parameters were analysed. The former included the atrial activation sequence between the His bundle recording site (HBE) and the coronary sinus orifice or the catheter ablation site, either during AVNRT or during sinus rhythm. The latter included the spatial distances between the distal end of the AV nodal artery and the HBE and the final catheter ablation site, and the distance between the HBE and the tricuspid border at the coronary sinus orifice floor.
RESULTS—In phase I, nine of the 77 patients had complications of transient (seven patients) or permanent (two patients) complete AV block during stepwise, anatomy guided slow pathway catheter ablation. These nine patients had a wider distance between the HBE and the distal end of the AV nodal artery, and a closer approximation of the catheter ablation site to the distal end of the AV nodal artery, which independently predicted the risk of AV block. In contrast, none of the available electrophysiologic parameters were shown to be reliable. When the distance between

  11. Can we omit prophylactic inguinal nodal irradiation in anal cancer patients?

    PubMed Central

    Kim, Hakyoung; Park, Hee Chul; Choi, Doo Ho; Ahn, Yong Chan; Kim, Seung Tae; Park, Joon Oh; Park, Young Suk; Kim, Hee Cheol

    2015-01-01

    Purpose To evaluate the appropriateness of prophylactic inguinal nodal irradiation (PINI), we analyzed patterns of failure in anal cancer patients who were inguinal node-negative at presentation and did not receive PINI. Materials and Methods We retrospectively reviewed the records of 33 anal cancer patients treated by definitive concurrent chemoradiation therapy (CCRT) between 1994 and 2013. Radiotherapy consisted of a total dose of 44-45 Gy (22-25 fractions in 5 weeks) on the whole pelvis, anus, and perineum. Except inguinal lymphadenopathy was present at initial diagnosis, the entire inguinal chain was not included in the radiation field. In other words, there was no PINI. Results The median follow-up duration was 50 months (range, 4 to 218 months). Median survival and progression-free survival (PFS) were 57 months (range, 10 to 218 months) and 50 months (range, 4 to 218 months), respectively. Among the survival, the median follow-up duration was 51 months (range, 12 to 218 months). The 5-year overall survival and PFS rates were 93.4% and 88.8%, respectively. Although none of the patients received inguinal node irradiation for prophylactic purposes, there was no inguinal recurrence. Conclusion Treatment of anal cancer by omitting PINI might be considered in selected patients with clinically uninvolved inguinal nodes. PMID:26157677

  12. A Temporal Window for Signal Activation Dictates the Dimensions of a Nodal Signaling Domain

    PubMed Central

    van Boxtel, Antonius L.; Chesebro, John E.; Heliot, Claire; Ramel, Marie-Christine; Stone, Richard K.; Hill, Caroline S.

    2015-01-01

    Summary Morphogen signaling is critical for the growth and patterning of tissues in embryos and adults, but how morphogen signaling gradients are generated in tissues remains controversial. The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty. Here we use a specific zebrafish Nodal biosensor combined with immunofluorescence for phosphorylated Smad2 to demonstrate that endogenous Nodal is unlikely to diffuse over a long range. Instead, short-range Nodal signaling activation in a temporal window is sufficient to determine the dimensions of the Nodal signaling domain. The size of this temporal window is set by the differentially timed production of Nodal and Lefty, which arises mainly from repression of Lefty translation by the microRNA miR-430. Thus, temporal information is transformed into spatial information to define the dimensions of the Nodal signaling domain and, consequently, to specify mesendoderm. PMID:26506307

  13. A Temporal Window for Signal Activation Dictates the Dimensions of a Nodal Signaling Domain.

    PubMed

    van Boxtel, Antonius L; Chesebro, John E; Heliot, Claire; Ramel, Marie-Christine; Stone, Richard K; Hill, Caroline S

    2015-10-26

    Morphogen signaling is critical for the growth and patterning of tissues in embryos and adults, but how morphogen signaling gradients are generated in tissues remains controversial. The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty. Here we use a specific zebrafish Nodal biosensor combined with immunofluorescence for phosphorylated Smad2 to demonstrate that endogenous Nodal is unlikely to diffuse over a long range. Instead, short-range Nodal signaling activation in a temporal window is sufficient to determine the dimensions of the Nodal signaling domain. The size of this temporal window is set by the differentially timed production of Nodal and Lefty, which arises mainly from repression of Lefty translation by the microRNA miR-430. Thus, temporal information is transformed into spatial information to define the dimensions of the Nodal signaling domain and, consequently, to specify mesendoderm. PMID:26506307

  14. Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles

    PubMed Central

    Liu, Rong; Gilmore, Denis M.; Zubris, Kimberly Ann V.; Xu, Xiaoyin; Catalano, Paul J.; Padera, Robert F.; Grinstaff, Mark W.; Colson, Yolonda L.

    2012-01-01

    Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin. PMID:23228419

  15. Nodal promotes invasive phenotypes via a Mitogen Activated Protein Kinase-dependent pathway

    PubMed Central

    Quail, DF; Zhang, G; Findlay, SD; Hess, DA; Postovit, LM

    2016-01-01

    The progression of cancer from localized to invasive disease is requisite for metastasis, and is often characterized by epithelial-to-mesenchymal transition (EMT) and alterations in cellular adhesion and migration. Studies have shown that this transition is associated with an up-regulation of embryonic stem cell-associated genes, resulting in a dedifferentiated phenotype and poor patient prognosis. Nodal is an embryonic factor that plays a critical role in promoting early invasive events during development. Nodal is silenced as stem cells differentiate; however, it re-emerges in adult life during placentation and mammary gland development, and is aberrantly expressed in many cancers. Here, we show that Nodal over-expression, in poorly-invasive breast cancer and choriocarcinoma cells, causes increased invasion and migration in vitro. Furthermore, we show that Nodal over-expression in these epithelial cancer types induces an EMT-like event concomitant with the internalization of E-Cadherin. This ability of Nodal to promote cellular invasion and EMT-like phenomena is dependent upon the phosphorylation of ERK1/2. Since Nodal normally signals through SMADs, these findings lend insight into an alternative pathway that is hijacked by this protein in cancer. To evaluate the clinical implications of our results, we show that Nodal inhibition reduces liver tumor burden in a model of spontaneous breast cancer metastasis in vivo, and that Nodal loss-of-function in aggressive breast cancer lines results in a decrease in invasive phenotypes. Our results demonstrate that Nodal is involved in promoting invasion in multiple cellular contexts, and that Nodal inhibition may be useful as a therapeutic target for patients with progressive disease. PMID:23334323

  16. Nodal weighting factor method for ex-core fast neutron fluence evaluation

    SciTech Connect

    Chiang, R. T.

    2012-07-01

    The nodal weighting factor method is developed for evaluating ex-core fast neutron flux in a nuclear reactor by utilizing adjoint neutron flux, a fictitious unit detector cross section for neutron energy above 1 or 0.1 MeV, the unit fission source, and relative assembly nodal powers. The method determines each nodal weighting factor for ex-core neutron fast flux evaluation by solving the steady-state adjoint neutron transport equation with a fictitious unit detector cross section for neutron energy above 1 or 0.1 MeV as the adjoint source, by integrating the unit fission source with a typical fission spectrum to the solved adjoint flux over all energies, all angles and given nodal volume, and by dividing it with the sum of all nodal weighting factors, which is a normalization factor. Then, the fast neutron flux can be obtained by summing the various relative nodal powers times the corresponding nodal weighting factors of the adjacent significantly contributed peripheral assembly nodes and times a proper fast neutron attenuation coefficient over an operating period. A generic set of nodal weighting factors can be used to evaluate neutron fluence at the same location for similar core design and fuel cycles, but the set of nodal weighting factors needs to be re-calibrated for a transition-fuel-cycle. This newly developed nodal weighting factor method should be a useful and simplified tool for evaluating fast neutron fluence at selected locations of interest in ex-core components of contemporary nuclear power reactors. (authors)

  17. Efficient Meshfree Large Deformation Simulation of Rainfall Induced Soil Slope Failure

    NASA Astrophysics Data System (ADS)

    Wang, Dongdong; Li, Ling

    2010-05-01

    An efficient Lagrangian Galerkin meshfree framework is presented for large deformation simulation of rainfall-induced soil slope failure. Detailed coupled soil-rainfall seepage equations are given for the proposed formulation. This nonlinear meshfree formulation is featured by the Lagrangian stabilized conforming nodal integration method where the low cost nature of nodal integration approach is kept and at the same time the numerical stability is maintained. The initiation and evolution of progressive failure in the soil slope is modeled by the coupled constitutive equations of isotropic damage and Drucker-Prager pressure-dependent plasticity. The gradient smoothing in the stabilized conforming integration also serves as a non-local regularization of material instability and consequently the present method is capable of effectively capture the shear band failure. The efficacy of the present method is demonstrated by simulating the rainfall-induced failure of two typical soil slopes.

  18. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma.

    PubMed

    Na'ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  19. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma

    PubMed Central

    Na’ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  20. Space-angle approximations in the variational nodal method.

    SciTech Connect

    Lewis, E. E.; Palmiotti, G.; Taiwo, T.

    1999-03-12

    The variational nodal method is formulated such that the angular and spatial approximations maybe examined separately. Spherical harmonic, simplified spherical harmonic, and discrete ordinate approximations are coupled to the primal hybrid finite element treatment of the spatial variables. Within this framework, two classes of spatial trial functions are presented: (1) orthogonal polynomials for the treatment of homogeneous nodes and (2) bilinear finite subelement trial functions for the treatment of fuel assembly sized nodes in which fuel-pin cell cross sections are represented explicitly. Polynomial and subelement trial functions are applied to benchmark water-reactor problems containing MOX fuel using spherical harmonic and simplified spherical harmonic approximations. The resulting accuracy and computing costs are compared.

  1. ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm.

    PubMed

    Ellis, Pamela S; Burbridge, Sarah; Soubes, Sandrine; Ohyama, Kyoji; Ben-Haim, Nadav; Chen, Canhe; Dale, Kim; Shen, Michael M; Constam, Daniel; Placzek, Marysia

    2015-11-15

    The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we show that in the embryonic chick, Shh is expressed transiently in prechordal mesoderm, and is governed by unprocessed Nodal. Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained through canonical signalling, Nodal signals through a non-canonical route to maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co-immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression. Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3 siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA to prechordal mesoderm in vivo results in premature Shh downregulation without affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3 signalling is downregulated. PMID:26417042

  2. ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

    PubMed Central

    Ellis, Pamela S.; Burbridge, Sarah; Soubes, Sandrine; Ohyama, Kyoji; Ben-Haim, Nadav; Chen, Canhe; Dale, Kim; Shen, Michael M.; Constam, Daniel; Placzek, Marysia

    2015-01-01

    The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we show that in the embryonic chick, Shh is expressed transiently in prechordal mesoderm, and is governed by unprocessed Nodal. Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained through canonical signalling, Nodal signals through a non-canonical route to maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co-immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression. Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3 siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA to prechordal mesoderm in vivo results in premature Shh downregulation without affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3 signalling is downregulated. PMID:26417042

  3. Compression failure of composite laminates

    NASA Technical Reports Server (NTRS)

    Pipes, R. B.

    1983-01-01

    This presentation attempts to characterize the compressive behavior of Hercules AS-1/3501-6 graphite-epoxy composite. The effect of varying specimen geometry on test results is examined. The transition region is determined between buckling and compressive failure. Failure modes are defined and analytical models to describe these modes are presented.

  4. Respiratory Failure

    MedlinePlus

    ... from inhaling smoke or harmful fumes Treatment for respiratory failure depends on whether the condition is acute (short-term) or chronic (ongoing) and how severe it is. It also depends on the underlying cause. You may receive oxygen therapy and other treatment to help you breathe. NIH: ...

  5. Heart Failure

    MedlinePlus

    ... Tiredness and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and diabetes. It is more common in people who are 65 years old or older, African Americans, people who are overweight, and people who have ...

  6. Patterns of Local-Regional Failure in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer Cases: Implications for Postoperative Radiation Therapy Clinical Target Volume Design

    SciTech Connect

    Feng, Wen; Fu, Xiao-Long; Cai, Xu-Wei; Yang, Huan-Jun; Wu, Kai-Liang; Fan, Min; Xiang, Jia-Qing; Zhang, Ya-Wei; Chen, Hai-Quan

    2014-04-01

    Purpose: To analyze patterns of local-regional failure (LRF) for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients treated in our hospital and to propose a clinical target volume (CTV) for postoperative radiation therapy (PORT) in these patients. Methods and Materials: From 2005 to 2011, consecutive patients with pT1-3N2 NSCLC who underwent complete resection in our hospital but who did not receive PORT were identified. The patterns of first LRF were assessed and evaluated as to whether these areas would be encompassed by our proposed PORT CTV. Results: With a median follow-up of 24 months, 173 of 250 patients (69.2%) experienced disease recurrence. Of the 54 patients with LRF as the first event, 48 (89%) had recurrence within the proposed PORT CTV, and 6 (11%) had failures occurring both within and outside the proposed CTV (all of which occurred in patients with right-lung cancer). Ninety-three percent of failure sites (104 of 112) would have been contained within the proposed PORT CTV. For left-sided lung cancer, the most common lymph node station failure site was 4R, followed by 7, 4L, 6, 10L, and 5. For right-sided lung cancer, the most common site was station 2R, followed by 10R, 4R, and 7. Conclusions: LRF following complete surgery was an important and potentially preventable pattern of failure in stage IIIA(N2) patients. Ipsilateral superior mediastinal recurrences dominated for right-sided tumors, whereas left-sided tumors frequently involved the bilateral superior mediastinum. Most of the LRF sites would have been covered by the proposed PORT CTV. A prospective investigation of patterns of failure after PORT (following our proposed CTV delineation guideline) is presently underway and will be reported in a separate analysis.

  7. Drumhead surface states and topological nodal-line fermions in TlTaSe2

    NASA Astrophysics Data System (ADS)

    Bian, Guang; Chang, Tay-Rong; Zheng, Hao; Velury, Saavanth; Xu, Su-Yang; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Sanchez, Daniel S.; Belopolski, Ilya; Alidoust, Nasser; Chen, Peng-Jen; Chang, Guoqing; Bansil, Arun; Jeng, Horng-Tay; Lin, Hsin; Hasan, M. Zahid

    2016-03-01

    A topological nodal-line semimetal is a state of matter with one-dimensional bulk nodal lines and two-dimensional so-called drumhead surface bands. Based on first-principles calculations and an effective k .p model, we theoretically propose the existence of topological nodal-line fermions in the ternary transition-metal chalcogenide TlTaSe2. The noncentrosymmetric structure and strong spin-orbit coupling give rise to spinful nodal-line bulk states which are protected by a mirror reflection symmetry of this compound. This is remarkably distinguished from other proposed nodal-line semimetals such as Cu3NPb (Zn) in which the nodal line exists only in the limit of vanishing spin-orbit coupling and thus is not as robust. In addition, we show that the drumhead surface states in TlTaSe2, which are associated with the topological nodal lines, exhibit an unconventional chiral spin texture and an exotic Lifshitz transition as a consequence of the linkage among multiple drumhead surface-state pockets.

  8. Xantivin suppresses the activity of EGF-CFC genes to regulate nodal signaling.

    PubMed

    Tanegashima, Kousuke; Haramoto, Yoshikazu; Yokota, Chika; Takahashi, Shuji; Asashima, Makoto

    2004-06-01

    Lefty, antivin and related genes act in a feedback inhibition mechanism for nodal signaling at a number of stages of vertebrate embryogenesis. To analyze the function of the feedback inhibitor of nodal signaling, Xantivin in Xenopus embryos, we designed a morpholino antisense oligonucleotide (XatvMO) for this gene. XatvMO caused the expansion of mesodermal tissue and head defects. XatvMO-injected gastrulae showed up-regulated expression of the mesodermal markers Xbra, Xwnt8, Xnot, and Chordin, suggesting expansion of the trunk-tail organizer. As expected, depletion of Xantivin also up-regulated nodal signaling as confirmed by the enhanced ectopic expression of Xantivin mRNA, a known target gene of nodal signaling. Furthermore, we investigated the relationship between Xantivin and the EGF-CFC gene FRL-1, which is a component of the nodal receptor. In animal cap assays, FRL-1 could not induce expression of nodal-responsive genes, but could up-regulate expression of these genes when FRL-1 was coinjected with a low dose of Xnr1; coinjection of Xantivin suppressed this up-regulation by FRL-1. We also found that Xantivin can rescue the caudalized phenotype induced by overexpression of FRL-1. Co-immunoprecipitation assays showed that Xantivin interacted with the EGF-CFC proteins, FRL-1 and cripto. Taken together, these results suggest that Xantivin opposes the activity of EGF-CFC genes and thereby antagonizes nodal signaling. PMID:15300508

  9. Effect of interfractional shoulder motion on low neck nodal targets for patients treated using volumetric-modulated arc therapy (VMAT).

    PubMed

    Casey, Kevin E; Wong, Pei-Fong; Tung, Samuel S

    2015-01-01

    VMAT is an important tool in the treatment of head and neck cancers, many of which also require treatment to the supraclavicular lymph nodes. However, full VMAT arcs treating this nodal region necessarily cause entrance beam to pass through patients' shoulders. Thus, interfractional variations in shoulder position may cause unwanted dose perturbations. To assess this possibility, six patients undergoing treatment at our institution for head and neck cancers with associated supraclavicular lymph node treatment were imaged with in-room CT-on-rails during the course of their treatments. This allowed for the establishment of a true record of the actual shoulder position during selected treatment fractions. Then, a full VMAT plan and a plan with VMAT arcs superior to the shoulder and a static anteroposterior field inferiorly were copied onto the patients' weekly image sets. The average one-dimensional shoulder motion was generally within 10 mm of the simulated position, with some notable exceptions. The standard deviation in week-to-week shoulder position relative to simulation was 4.3 mm and 4.2 mm in the SI and AP dimensions, respectively. The average nodal target mean dose across all fractions sampled was within 5% of planned for all patients and both plans. Similarly, the average D95 for the nodal target was within 5% of planned across all fractions sampled, with the single exception of the full VMAT plan for one patient. In most cases, the standard deviation in both target mean dose and D95 was smaller with the VMAT+static AP field plan than it was with the full VMAT plan. PMID:26218996

  10. Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma

    PubMed Central

    Melchers, LJ; Clausen, MJAM; Mastik, MF; Slagter-Menkema, L; van der Wal, JE; Wisman, GBA; Roodenburg, JLN; Schuuring, E

    2015-01-01

    Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed. PMID:26213212

  11. Nodal expression in triple-negative breast cancer: Cellular effects of its inhibition following doxorubicin treatment.

    PubMed

    Bodenstine, Thomas M; Chandler, Grace S; Reed, David W; Margaryan, Naira V; Gilgur, Alina; Atkinson, Janis; Ahmed, Nida; Hyser, Matthew; Seftor, Elisabeth A; Strizzi, Luigi; Hendrix, Mary J C

    2016-05-01

    Triple-negative breast cancer (TNBC) represents an aggressive cancer subtype characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The independence of TNBC from these growth promoting factors eliminates the efficacy of therapies which specifically target them, and limits TNBC patients to traditional systemic neo/adjuvant chemotherapy. To better understand the growth advantage of TNBC - in the absence of ER, PR and HER2, we focused on the embryonic morphogen Nodal (associated with the cancer stem cell phenotype), which is re-expressed in aggressive breast cancers. Most notably, our previous data demonstrated that inhibition of Nodal signaling in breast cancer cells reduces their tumorigenic capacity. Furthermore, inhibiting Nodal in other cancers has resulted in improved effects of chemotherapy, although the mechanisms for this remain unknown. Thus, we hypothesized that targeting Nodal in TNBC cells in combination with conventional chemotherapy may improve efficacy and represent a potential new strategy. Our preliminary data demonstrate that Nodal is highly expressed in TNBC when compared to invasive hormone receptor positive samples. Treatment of Nodal expressing TNBC cell lines with a neutralizing anti-Nodal antibody reduces the viability of cells that had previously survived treatment with the anthracycline doxorubicin. We show that inhibiting Nodal may alter response mechanisms employed by cancer cells undergoing DNA damage. These data suggest that development of therapies which target Nodal in TNBC may lead to additional treatment options in conjunction with chemotherapy regimens - by altering signaling pathways critical to cellular survival. PMID:27007464

  12. Nodal signaling is required for closure of the anterior neural tube in zebrafish

    PubMed Central

    Aquilina-Beck, Allisan; Ilagan, Kristine; Liu, Qin; Liang, Jennifer O

    2007-01-01

    Background Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. Results We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish. Conclusion This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain. PMID:17996054

  13. The accuracy of preoperative axillary nodal staging in primary breast cancer by ultrasound is modified by nodal metastatic load and tumor biology.

    PubMed

    Dihge, Looket; Grabau, Dorthe A; Rasmussen, Rogvi W; Bendahl, Pär-Ola; Rydén, Lisa

    2016-08-01

    Background The outcome of axillary ultrasound (AUS) with fine-needle aspiration biopsy (FNAB) in the diagnostic work-up of primary breast cancer has an impact on therapy decisions. We hypothesize that the accuracy of AUS is modified by nodal metastatic burden and clinico-pathological characteristics. Material and methods The performance of AUS and AUS-guided FNAB for predicting nodal metastases was assessed in a prospective breast cancer cohort subjected for surgery during 2009-2012. Predictors of accuracy were included in multivariate analysis. Results AUS had a sensitivity of 23% and a specificity of 95%, while AUS-guided FNAB obtained 73% and 100%, respectively. AUS-FNAB exclusively detected macro-metastases (median four metastases) and identified patients with more extensive nodal metastatic burden in comparison with sentinel node biopsy. The accuracy of AUS was affected by metastatic size (OR 1.11), obesity (OR 2.46), histological grade (OR 4.43), and HER2-status (OR 3.66); metastatic size and histological grade were significant in the multivariate analysis. Conclusions The clinical utility of AUS in low-risk breast cancer deserves further evaluation as the accuracy decreased with a low nodal metastatic burden. The diagnostic performance is modified by tumor and clinical characteristics. Patients with nodal disease detected by AUS-FNAB represent a group for whom neoadjuvant therapy should be considered. PMID:27050668

  14. Embryonic Morphogen Nodal Is Associated with Progression and Poor Prognosis of Hepatocellular Carcinoma

    PubMed Central

    Jia, Wei-Dong; Xu, Ge-Liang; Ma, Jin-Liang; Ren, Yun; Chen, Hao; Sun, Si-Nan; Huang, Mei; Li, Jian-Sheng

    2014-01-01

    Background Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear. Methods We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters. Results Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC. Conclusions Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis

  15. Simulation of turbulent flows using nodal integral method

    NASA Astrophysics Data System (ADS)

    Singh, Suneet

    Nodal methods are the backbone of the production codes for neutron-diffusion and transport equations. Despite their high accuracy, use of these methods for simulation of fluid flow is relatively new. Recently, a modified nodal integral method (MNIM) has been developed for simulation of laminar flows. In view of its high accuracy and efficiency, extension of this method for the simulation of turbulent flows is a logical step forward. In this dissertation, MNIM is extended in two ways to simulate incompressible turbulent flows---a new MNIM is developed for the 2D k-epsilon equations; and 3D, parallel MNIM is developed for direct numerical simulations. Both developments are validated, and test problems are solved. In this dissertation, a new nodal numerical scheme is developed to solve the k-epsilon equations to simulate turbulent flows. The MNIM developed earlier for laminar flow equations is modified to incorporate eddy viscosity approximation and coupled with the above mentioned schemes for the k and epsilon equations, to complete the implementation of the numerical scheme for the k-epsilon model. The scheme developed is validated by comparing the results obtained by the developed method with the results available in the literature obtained using direct numerical simulations (DNS). The results of current simulations match reasonably well with the DNS results. The discrepancies in the results are mainly due to the limitations of the k-epsilon model rather than the deficiency in the developed MNIM. A parallel version of the MNIM is needed to enhance its capability, in order to carry out DNS of the turbulent flows. The parallelization of the scheme, however, presents some unique challenges as dependencies of the discrete variables are different from those that exist in other schemes (for example in finite volume based schemes). Hence, a parallel MNIM (PMNIM) is developed and implemented into a computer code with communication strategies based on the above mentioned

  16. Metallization failures

    NASA Technical Reports Server (NTRS)

    Beatty, R.

    1971-01-01

    Metallization-related failure mechanisms were shown to be a major cause of integrated circuit failures under accelerated stress conditions, as well as in actual use under field operation. The integrated circuit industry is aware of the problem and is attempting to solve it in one of two ways: (1) better understanding of the aluminum system, which is the most widely used metallization material for silicon integrated circuits both as a single level and multilevel metallization, or (2) evaluating alternative metal systems. Aluminum metallization offers many advantages, but also has limitations particularly at elevated temperatures and high current densities. As an alternative, multilayer systems of the general form, silicon device-metal-inorganic insulator-metal, are being considered to produce large scale integrated arrays. The merits and restrictions of metallization systems in current usage and systems under development are defined.

  17. Quantum oscillation signatures of spin-orbit interactions controlling the residual nodal bilayer-splitting in underdoped high-Tc cuprates

    NASA Astrophysics Data System (ADS)

    Harrison, Neil; Shekhter, Arkady

    2015-03-01

    We investigate the origin of the small residual nodal bilayer-splitting in the underdoped high-Tc superconductor YBa2Cu3O6+x using the results of recently published angle-resolved quantum oscillation data [Sebastian et al., Nature 511, 61 (2014)]. A crucial clue to the origin of the residual bilayer-splitting is found to be provided by the anomalously small Zeeman-splitting of some of the observed cyclotron orbits. We show that such an anomalously Zeeman-splitting (or small effective g-factor) for a subset of orbits can be explained by spin-orbit interactions, which become significant in the nodal regions as a result of the vanishing bilayer coupling. The primary effect of spin-orbit interactions is to cause quasiparticles traversing the nodal region of the Brillouin zone to undergo a spin flip. We suggest that the Rashba-like spin-orbit interactions, naturally present in bilayer systems, have the right symmetry and magnitude to give rise to a network of coupled orbits consistent with experimental observations in underdoped YBa2Cu3O6+x. This work is supported by the DOEm BES proposal LANLF100, while the magnet lab is supported by the NSF and Florida State.

  18. Barriers to intramolecular rotation determined from the temperature dependence of the Henry constant in the region of adsorbed molecule rigidity failure

    NASA Astrophysics Data System (ADS)

    Dolgonosov, A. M.; Prudkovskii, A. G.

    2008-05-01

    A distribution for the rigid and nonrigid adsorbed molecule forms was found. Adsorbed molecule rigidity failure was shown to be accompanied by a weak nonlinear effect, which manifested itself as a temperature dependence of the Henry constant. A method for the determination of the barrier to intramolecular rotation from the temperature dependence of the molecule adsorption constant was suggested. Barriers to rotation about the C-C and C-O bonds were determined for several molecules.

  19. Topological nodal Cooper pairing in doped Weyl metals

    NASA Astrophysics Data System (ADS)

    Li, Yi; Haldane, F. D. M.

    We generalize the concept of Berry connection of the single-electron band structure to the two-particle Cooper pair states between two Fermi surfaces with opposite Chern numbers. Because of underlying Fermi surface topology, the pairing Berry phase acquires non-trivial monopole structure. Consequently, pairing gap functions have the topologically-protected nodal structure as vortices in the momentum space with the total vorticity solely determined by the monopole charge qp. The pairing nodes behave as the Weyl-Majorana points of the Bogoliubov-de Gennes pairing Hamiltonian. Their relation with the connection patterns of the surface modes from theWeyl band structure and the Majorana surface modes inside the pairing gap is also discussed. Under the approximation of spherical Fermi surfaces, the pairing symmetry are represented by monopole harmonic functions. The lowest possible pairing channel carries angular momentum number j =|qp|, and the corresponding gap functions are holomorphic or anti-holomorphic functions on Fermi surfaces. F.D.M.H. acknowledges the support from MRSEC NSF-DMR-1420541 and the W. M. Keck Foundation.

  20. Micropropagation of Calophyllum brasiliense (Cambess.) from nodal segments.

    PubMed

    Silveira, S S; Cordeiro-Silva, R; Degenhardt-Goldbach, J; Quoirin, M

    2016-05-01

    Micropropagation of Calophyllum brasiliense Cambess. (Clusiaceae) is a way to overcome difficulties in achieving large-scale plant production, given the recalcitrant nature of the seeds, irregular fructification and absence of natural vegetative propagation of the species. Cultures were established using nodal segments 2 cm in length, obtained from 1-2 year old seedlings, maintained in a greenhouse. Mercury chloride and Plant Preservative Mixture™ were used in the surface sterilizing stage, better results being achieved with Plant Preservative Mixture™ incorporation in culture medium, at any concentration. Polyvinylpyrrolidone, activated charcoal, cysteine, ascorbic acid or citric acid were added to the culture medium to avoid oxidation. After 30 days of culture, polyvinylpirrolidone and ascorbic acid gave better results, eliminating oxidation in most explants. For shoot multiplication, benzylaminopurine was used in concentrations of 4.4 and 8.8 µM in Woody Plant Medium, resulting in an average of 4.43 and 4.68 shoots per explant, respectively, after 90 days. Indole-3-butyric acid and α-naphthalene acetic acid were used to induce root formation, reaching a maximum rooting rate of 24% with 20µM α-naphthalene acetic acid. For acclimatization. the rooted plants were transferred to Plantmax® substrate and cultured in a greenhouse, reaching 79% of survival after 30 days and 60% after one year. PMID:27143061

  1. Relation between finite element methods and nodal methods in transport theory

    SciTech Connect

    Walters, W.F.

    1985-01-01

    This paper examines the relationship between nodal methods and finite-element methods for solving the discrete-ordinates form of the transport equation in x-y geometry. Specifically, we will examine the relation of three finite-element schemes to the linear-linear (LL) and linear-nodal (LN) nodal schemes. The three finite-element schemes are the linear-continuous-diamond-difference (DD) scheme, the linear-discontinuous (LD) scheme, and the quadratic-discontinuous (QD) scheme. A brief derivation of the (LL) and (LN) nodal schemes is given in the third section of this paper. The approximations that cause the LL scheme to reduce to the DD, LD, and QD schemes are then indicated. An extremely simple method of deriving the finite-element schemes is then introduced.

  2. Topological Nodal-Line Superfluid in Spin-Orbit Coupled Cold Atomic Systems

    NASA Astrophysics Data System (ADS)

    He, Wen-Yu; Xu, Dong-Hui; Zhou, Tong; Law, K. T.; Hong Kong University of Science; Technology Collaboration

    Topological nodal line superconductivity or superfluidity is a fascinating topological gapless phase which hosts bulk Weyl ring degeneracy in the quasiparticle excitation spectrum and supports Majorana zero bound modes with a large density of states at the edge. In this work, based on the experimental realized 1D spin orbit coupling, we show the emergence of topological nodal line superfluid phase in Fermionic atoms trapped in 3D cubic optical lattice when the s wave pairing field is introduced through Feshbach resonance between the two atomic hyperfine spin states. The nodal line degeneracy is further found to evolve into Weyl nodes once another component of spin orbit coupling field enters to break the chiral symmetry. The momentum resolved radio frequency spectroscopy is suggested to manifest the topological nodal line superfluid phase.

  3. Dose-dependent Nodal/Smad signals pattern the early mouse embryo.

    PubMed

    Robertson, Elizabeth J

    2014-08-01

    Nodal signals in the early post-implantation stage embryo are essential to establish initial proximal-distal (P-D) polarity and generate the final anterior-posterior (A-P) body axis. Nodal signaling in the epiblast results in the phosphorylation of Smad2 in the overlying visceral endoderm necessary to induce the AVE, in part via Smad2-dependent activation of the T-box gene Eomesodermin. Slightly later following mesoderm induction a continuum of dose-dependent Nodal signaling during the process of gastrulation underlies specification of mesodermal and definitive endoderm progenitors. Dynamic Nodal expression during the critical 72 h time window immediately following implantation, accomplished by a series of feed-back and feed-forward mechanisms serves to provide key positional cues required for establishment of the body plan and controls cell fate decisions in the early mammalian embryo. PMID:24704361

  4. ANOVA-HDMR structure of the higher order nodal diffusion solution

    SciTech Connect

    Bokov, P. M.; Prinsloo, R. H.; Tomasevic, D. I.

    2013-07-01

    Nodal diffusion methods still represent a standard in global reactor calculations, but employ some ad-hoc approximations (such as the quadratic leakage approximation) which limit their accuracy in cases where reference quality solutions are sought. In this work we solve the nodal diffusion equations utilizing the so-called higher-order nodal methods to generate reference quality solutions and to decompose the obtained solutions via a technique known as High Dimensional Model Representation (HDMR). This representation and associated decomposition of the solution provides a new formulation of the transverse leakage term. The HDMR structure is investigated via the technique of Analysis of Variance (ANOVA), which indicates why the existing class of transversely-integrated nodal methods prove to be so successful. Furthermore, the analysis leads to a potential solution method for generating reference quality solutions at a much reduced calculational cost, by applying the ANOVA technique to the full higher order solution. (authors)

  5. The Impact of Preradiation Residual Disease Volume on Time to Locoregional Failure in Cutaneous Merkel Cell Carcinoma—A TROG Substudy

    SciTech Connect

    Finnigan, Renee; Hruby, George; Wratten, Chris; Keller, Jacqui; Tripcony, Lee; Dickie, Graeme; Rischin, Danny; Poulsen, Michael

    2013-05-01

    Purpose: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). Methods and Materials: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. Results: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. Conclusions: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

  6. Effects of a novel Nodal-targeting monoclonal antibody in melanoma

    PubMed Central

    Margaryan, Naira V.; Focà, Annalia; Sanguigno, Luca; Bodenstine, Thomas M.; Chandler, Grace S.; Reed, David W.; Gilgur, Alina; Seftor, Elisabeth A.; Seftor, Richard E.B.; Khalkhali-Ellis, Zhila; Leonardi, Antonio; Ruvo, Menotti; Hendrix, Mary J.C.

    2015-01-01

    Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers. PMID:26460952

  7. Disrupting Foxh1-Groucho Interaction Reveals Robustness of Nodal-Based Embryonic Patterning

    PubMed Central

    Halstead, Angela M.; Wright, Christopher V. E.

    2016-01-01

    The winged-helix transcription factor Foxh1 is an essential regulator of Nodal signaling during the key developmental processes of gastrulation, anterior-posterior (A-P) patterning, and the derivation of left-right (L-R) asymmetry. Current models have Foxh1 bound to phospho-Smad2/3 (pSmad2/3) as a central transcriptional activator for genes targeted by Nodal signaling including Nodal itself, the feedback inhibitor Lefty2, and the positive transcriptional effector Pitx2. However, the conserved Engrailed homology-1 (EH1) motif present in Foxh1 suggests that modulated interaction with Groucho (Grg) co-repressors would allow Foxh1 to function as a transcriptional switch, toggling between transcriptional on and off states via pSmad2-Grg protein-switching, to ensure the properly timed initiation and suppression, and/or amplitude, of expression of Nodal and its target genes. We minimally mutated the Foxh1 EH1 motif, creating a novel Foxh1mEH1 allele to test directly the contribution of Foxh1-Grg–mediated repression on the transient, dynamic pattern of Nodal signaling in mice. All aspects of Nodal and its target gene expression in Foxh1mEH1/mEH1 embryos were equivalent to wild type. A-P patterning and organ situs in homozygous embryos and adult mice were also unaffected. The finding that Foxh1-Grg–mediated repression is not essential for Nodal expression during mouse embryogenesis suggests that other regulators compensate for the loss of repressive regulatory input that is mediated by Grg interactions. We suggest that the pervasive inductive properties of Nodal signaling exist within the context of a strongly buffered regulatory system that contributes to resilience and accuracy of its dynamic expression pattern. PMID:25511461

  8. Supraglottic carcinoma: Impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease

    SciTech Connect

    Devineni, V.R.; Simpson, J.R.; Sessions, D.; Spector, J.G.; Hayden, R.; Fredrickson, J.; Fineberg, B. )

    1991-07-01

    Seventy-nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty-five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft-tissue or adjacent organ invasion, referred to in composite as grave signs. The median follow-up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease-free survival for all patients was 76% at 2 years and 71% at 3 years. The locoregional control rate for all patients was 70%. This study demonstrates that there is no difference in local recurrence or disease-free survival, or time to recurrence relative to the status of the surgical margins, which may be a benefit of the postoperative radiation therapy. This study also demonstrates that there is an increase in the number of patients with grave signs with increasing nodal stage. The rate of neck recurrence in patients with grave signs was substantially higher (54%) than in patients without grave signs (8%), even though these patients also had positive lymph nodes. Interestingly, there was also a higher rate of local recurrence among patients who had grave signs. Patients receiving doses higher than 6000 cGy to the primary site had fewer local failures, although within each group of patients with positive or negative surgical margins the differences in survival were minimal.

  9. Solution and Study of the Two-Dimensional Nodal Neutron Transport Equation

    SciTech Connect

    Panta Pazos, Ruben; Biasotto Hauser, Eliete; Tullio de Vilhena, Marco

    2002-07-01

    In the last decade Vilhena and coworkers reported an analytical solution to the two-dimensional nodal discrete-ordinates approximations of the neutron transport equation in a convex domain. The key feature of these works was the application of the combined collocation method of the angular variable and nodal approach in the spatial variables. By nodal approach we mean the transverse integration of the SN equations. This procedure leads to a set of one-dimensional S{sub N} equations for the average angular fluxes in the variables x and y. These equations were solved by the old version of the LTS{sub N} method, which consists in the application of the Laplace transform to the set of nodal S{sub N} equations and solution of the resulting linear system by symbolic computation. It is important to recall that this procedure allow us to increase N the order of S{sub N} up to 16. To overcome this drawback we step forward performing a spectral painstaking analysis of the nodal S{sub N} equations for N up to 16 and we begin the convergence of the S{sub N} nodal equations defining an error for the angular flux and estimating the error in terms of the truncation error of the quadrature approximations of the integral term. Furthermore, we compare numerical results of this approach with those of other techniques used to solve the two-dimensional discrete approximations of the neutron transport equation. (authors)

  10. The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development

    PubMed Central

    Deshwar, Ashish R; Chng, Serene C; Ho, Lena; Reversade, Bruno; Scott, Ian C

    2016-01-01

    The Apelin receptor (Aplnr) is essential for heart development, controlling the early migration of cardiac progenitors. Here we demonstrate that in zebrafish Aplnr modulates Nodal/TGFβ signaling, a key pathway essential for mesendoderm induction and migration. Loss of Aplnr function leads to a reduction in Nodal target gene expression whereas activation of Aplnr by a non-peptide agonist increases the expression of these same targets. Furthermore, loss of Aplnr results in a delay in the expression of the cardiogenic transcription factors mespaa/ab. Elevating Nodal levels in aplnra/b morphant and double mutant embryos is sufficient to rescue cardiac differentiation defects. We demonstrate that loss of Aplnr attenuates the activity of a point source of Nodal ligands Squint and Cyclops in a non-cell autonomous manner. Our results favour a model in which Aplnr is required to fine-tune Nodal output, acting as a specific rheostat for the Nodal/TGFβ pathway during the earliest stages of cardiogenesis. DOI: http://dx.doi.org/10.7554/eLife.13758.001 PMID:27077952

  11. Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model''

    SciTech Connect

    Dmitriy Y. Anistratov; Marvin L. Adams; Todd S. Palmer; Kord S. Smith; Kevin Clarno; Hikaru Hiruta; Razvan Nes

    2003-08-04

    OAK (B204) Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model'' The present generation of reactor analysis methods uses few-group nodal diffusion approximations to calculate full-core eigenvalues and power distributions. The cross sections, diffusion coefficients, and discontinuity factors (collectively called ''group constants'') in the nodal diffusion equations are parameterized as functions of many variables, ranging from the obvious (temperature, boron concentration, etc.) to the more obscure (spectral index, moderator temperature history, etc.). These group constants, and their variations as functions of the many variables, are calculated by assembly-level transport codes. The current methodology has two main weaknesses that this project addressed. The first weakness is the diffusion approximation in the full-core calculation; this can be significantly inaccurate at interfaces between different assemblies. This project used the nodal diffusion framework to implement nodal quasidiffusion equations, which can capture transport effects to an arbitrary degree of accuracy. The second weakness is in the parameterization of the group constants; current models do not always perform well, especially at interfaces between unlike assemblies. The project developed a theoretical foundation for parameterization and homogenization models and used that theory to devise improved models. The new models were extended to tabulate information that the nodal quasidiffusion equations can use to capture transport effects in full-core calculations.

  12. A quasi-static polynomial nodal method for nuclear reactor analysis

    SciTech Connect

    Gehin, J.C.

    1992-09-01

    Modern nodal methods are currently available which can accurately and efficiently solve the static and transient neutron diffusion equations. Most of the methods, however, are limited to two energy groups for practical application. The objective of this research is the development of a static and transient, multidimensional nodal method which allows more than two energy groups and uses a non-linear iterative method for efficient solution of the nodal equations. For both the static and transient methods, finite-difference equations which are corrected by the use of discontinuity factors are derived. The discontinuity factors are computed from a polynomial nodal method using a non-linear iteration technique. The polynomial nodal method is based upon a quartic approximation and utilizes a quadratic transverse-leakage approximation. The solution of the time-dependent equations is performed by the use of a quasi-static method in which the node-averaged fluxes are factored into shape and amplitude functions. The application of the quasi-static polynomial method to several benchmark problems demonstrates that the accuracy is consistent with that of other nodal methods. The use of the quasi-static method is shown to substantially reduce the computation time over the traditional fully-implicit time-integration method. Problems involving thermal-hydraulic feedback are accurately, and efficiently, solved by performing several reactivity/thermal-hydraulic updates per shape calculation.

  13. Mediastinal Single Nodal Relapse of a Nasal Nk/T cell Lymphoma

    PubMed Central

    Rhee, Kyoung Hoon; Hong, Seok Chan; An, Jeong Min; Huh, Jooryung; Sook, Ryu Jin; Lee, Jin Seong

    2007-01-01

    A nasal NK/T cell lymphoma is a very aggressive form of lymphoma. Patterns of relapse after treatment have not been systematically evaluated, and mediastinal nodal relapse at a primary site has never been documented. We describe here a 40-year old man who presented with a nasal obstruction caused by a protruding mass that was identified as a nasal NK/T cell lymphoma. The initial work-up, including chest and abdominopelvic computed tomography (CT) and positron emission tomography (PET), showed no regional or distant metastasis. A CT scan performed following three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) showed that the mass had nearly disappeared. Radiation therapy undertaken following chemotherapy was given to the primary site. However, PET performed following radiotherapy revealed a single mediastinal lymphadenopathy, with no evidence of residual tumor in the nasal cavity. A biopsy using video-assisted thoracoscopy (VATS) showed the presence of a recurrent NK/T cell lymphoma with an immunophenotype identical to that of the primary nasal lymphoma. An additional three cycles of CHOP chemotherapy were administered, and the patient remains alive, with no evidence of disease 30 months after the initial relapse. These findings indicate that early detection with PET and prompt surgical excision with the use of VATS can lead to successful treatment of a relapsed nasal NK/T cell lymphoma. PMID:17939339

  14. Mediastinal single nodal relapse of a nasal NK/T cell lymphoma.

    PubMed

    Rhee, Kyoung Hoon; Hong, Seok Chan; An, Jeong Min; Huh, Jooryung; Sook, Ryu Jin; Lee, Jin Seong; Suh, Cheolwon

    2007-09-01

    A nasal NK/T cell lymphoma is a very aggressive form of lymphoma. Patterns of relapse after treatment have not been systematically evaluated, and mediastinal nodal relapse at a primary site has never been documented. We describe here a 40-year old man who presented with a nasal obstruction caused by a protruding mass that was identified as a nasal NK/T cell lymphoma. The initial work-up, including chest and abdominopelvic computed tomography (CT) and positron emission tomography (PET), showed no regional or distant metastasis. A CT scan performed following three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) showed that the mass had nearly disappeared. Radiation therapy undertaken following chemotherapy was given to the primary site. However, PET performed following radiotherapy revealed a single mediastinal lymphadenopathy, with no evidence of residual tumor in the nasal cavity. A biopsy using video-assisted thoracoscopy (VATS) showed the presence of a recurrent NK/T cell lymphoma with an immunophenotype identical to that of the primary nasal lymphoma. An additional three cycles of CHOP chemotherapy were administered, and the patient remains alive, with no evidence of disease 30 months after the initial relapse. These findings indicate that early detection with PET and prompt surgical excision with the use of VATS can lead to successful treatment of a relapsed nasal NK/T cell lymphoma. PMID:17939339

  15. Isolated local-regional recurrence of breast cancer following mastectomy: Radiotherapeutic management

    SciTech Connect

    Halverson, K.J.; Perez, C.A.; Kuske, R.R.; Garcia, D.M.; Simpson, J.R.; Fineberg, B. )

    1990-10-01

    Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment.

  16. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    SciTech Connect

    Sun, Jing; Liu, Su-zhi; Lin, Yan; Cao, Xiao-pan; Liu, Jia-ming

    2014-01-17

    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.

  17. Cluster analysis of contaminated sediment data: nodal analysis.

    PubMed

    Hartwell, S Ian; Claflin, Larry W

    2005-07-01

    The objective of the present study was to explore the use of multivariate statistical methods as a means to discern relationships between contaminants and biological and/or toxicological effects in a representative data set from the National Status and Trends (NS&T) Program. Data from the National Oceanic and Atmospheric Administration, NS&T Program's Bioeffects Survey of Delaware Bay, USA, were examined using various univariate and multivariate statistical techniques, including cluster analysis. Each approach identified consistent patterns and relationships between the three types of triad data. The analyses also identified factors that bias the interpretation of the data, primarily the presence of rare and unique species and the dependence of species distributions on physical parameters. Sites and species were clustered with the unweighted pair-group method using arithmetic averages clustering with the Jaccard coefficient that clustered species and sites into mutually consistent groupings. Pearson product moment correlation coefficients, normalized for salinity, also were clustered. The most informative analysis, termed nodal analysis, was the intersection of species cluster analysis with site cluster analysis. This technique produced a visual representation of species association patterns among site clusters. Site characteristics, such as salinity and grain size, not contaminant concentrations, appeared to be the primary factors determining species distributions. This suggests the sediment-quality triad needs to use physical parameters as a distinct leg from chemical concentrations to improve sediment-quality assessments in large bodies of water. Because the Delaware Bay system has confounded gradients of contaminants and physical parameters, analyses were repeated with data from northern Chesapeake Bay, USA, with similar results. PMID:16050601

  18. Short-Term Displacement and Reproducibility of the Breast and Nodal Targets Under Active Breathing Control

    SciTech Connect

    Moran, Jean M. . E-mail: jmmoran@med.umich.edu; Balter, James M.; Ben-David, Merav A.; Marsh, Robin B. C; Herk, Marcel van; Pierce, Lori J.

    2007-06-01

    Purpose: The short-term displacement and reproducibility of the breast or chest wall, and the internal mammary (IM), infraclavicular (ICV), and supraclavicular (SCV) nodal regions have been assessed as a function of breath-hold state using an active breathing control (ABC) device for patients receiving loco-regional breast radiation therapy. Methods and Materials: Ten patients underwent computed tomographic scanning using an ABC device at breath-hold states of end-exhale and 20%, 40%, 60%, and 80% of vital capacity (VC). Patients underwent scanning before treatment and at one third and two thirds of the way through treatment. A regional registration was performed for each target using a rigid-body transformation with mutual information as a metric. Results: Between exhale and 40% of VC, the mean displacement was 0.27/0.34, 0.24/0.31, 0.22/0.19, and 0.13/0.19 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. At 80% of VC, the mean displacement from exhale was 0.84/.88, 0.76/.79, 0.70/0.79, and 0.54/0.56 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. The short-term reproducibility (standard deviation) was <0.3 and {<=}0.4 cm for 40% and 80% of VC, respectively. Displacements up to 1.9 cm were observed for individual patients. Conclusions: The short-term reproducibility of target position is {<=}0.4 cm using ABC for all structures for all breath-hold states. This information can be used to guide treatment planning optimization studies that consider the effect of motion on target and normal tissue doses with and without active breathing control.

  19. Extra Nodal Rosai-Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy) Presenting as Asymmetric Bilateral Optic Atrophy : An Atypical Ocular Presentation.

    PubMed

    Shukla, Eesha; Nicholson, Anjali; Agrawal, Anamika; Rathod, Darshana

    2016-09-01

    Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy, SHML) is a rare, non-hereditary, benign histiocytic proliferative disorder, presenting as painless bilateral cervical lymphadenopathy, with systemic symptoms. Extra nodal manifestations have been reported in 28-43 % cases with rare ocular involvement. We report a case of a 57 year old female presenting with gradual progressive decrease of vision OU since 8 months associated with epistaxis. Fundus examination revealed established optic atrophy in right eye with features of chronic papilloedema in left eye suggestive of compressive lesion. CT of brain, paranasal sinuses confirmed the presence of homogenously enhancing mass in left ethmoid sinus, left sphenoid sinus extending into suprasellar region. The biopsy of this mass revealed extra nodal SHML with tissue sections being S100 and CD68 positive with emperipolesis noted. Here we describe this atypical ocular presentation of extra nodal SHML to highlight that this rare disease can manifest as an aggressive sight threatening entity, even in older age group. PMID:27091209

  20. Heavy fermions: From nodal metals to super-spins

    NASA Astrophysics Data System (ADS)

    Ramires Neves de Oliveira, Aline

    Condensed matter physics is an area of research which lies at a sweet spot between two complementary perspectives: the atomistic point of view which takes into account all the details of the system of interest; and the framework of universality and emergent phenomena, which allows us to make drastic simplifications to the microscopic description of materials while still being able to explain much of the experimentally observed phenomena. This thesis addresses problems from both perspectives, focusing on heavy fermion systems. Heavy fermion systems are prototype materials for the study of strongly correlations and quantum criticality. Theoretical understanding of these systems is important for the design of new materials and for the fundamental understanding of quantum critical phenomena. This thesis is strongly motivated by recent experiments in an intrinsically quantum critical material, beta-YbAlB 4. This system shows anomalous critical exponents in transport and thermodynamics. In Chapter 2 we construct a phenomenological theory for the heavy fermion metal beta-YbAlB4 based on the Anderson model, taking into account the peculiarities of this specific material. We analyze the consequences of a non-trivial, momentum-dependent, hybridization matrix between f-electrons and conduction electrons, which gives rise to a nodal metal with unusual dispersion and singular thermodynamic properties, in accordance with experiments. In Chapter 3 we analyze the Electron Spin Resonance experiments in this same material and propose a theory including spin-orbit coupling, crystal electric fields and hyperfine coupling which can account for many of the features of the experimentally observed signal. Within a broader perspective on heavy fermion systems, the absence of a single unified theoretical description which can account for the plethora of phenomena observed in this class of materials also motivates us to consider new theoretical approaches. In Chapter 4 we generalize the

  1. Temporal and spatial requirements for Nodal-induced anterior mesendoderm and mesoderm in anterior neurulation.

    PubMed

    Gonsar, Ngawang; Coughlin, Alicia; Clay-Wright, Jessica A; Borg, Bethanie R; Kindt, Lexy M; Liang, Jennifer O

    2016-01-01

    Zebrafish with defective Nodal signaling have a phenotype analogous to the fatal human birth defect anencephaly, which is caused by an open anterior neural tube. Previous work in our laboratory found that anterior open neural tube phenotypes in Nodal signaling mutants were caused by lack of mesendodermal/mesodermal tissues. Defects in these mutants are already apparent at neural plate stage, before the neuroepithelium starts to fold into a tube. Consistent with this, we found that the requirement for Nodal signaling maps to mid-late blastula stages. This timing correlates with the timing of prechordal plate mesendoderm and anterior mesoderm induction, suggesting these tissues act to promote neurulation. To further identify tissues important for neurulation, we took advantage of the variable phenotypes in Nodal signaling-deficient sqt mutant and Lefty1-overexpressing embryos. Statistical analysis indicated a strong, positive correlation between a closed neural tube and presence of several mesendoderm/mesoderm-derived tissues (hatching glands, cephalic paraxial mesoderm, notochord, and head muscles). However, the neural tube was closed in a subset of embryos that lacked any one of these tissues. This suggests that several types of Nodal-induced mesendodermal/mesodermal precursors are competent to promote neurulation. PMID:26528772

  2. Topological nodal-line fermions in spin-orbit metal PbTaSe2.

    PubMed

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M Zahid

    2016-01-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID:26829889

  3. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    PubMed Central

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S.; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M. Zahid

    2016-01-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID:26829889

  4. Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

    PubMed Central

    van den Brand, Michiel; van Krieken, J. Han J.M.

    2013-01-01

    The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity. PMID:23813646

  5. Zeeman Field-Induced Nodal Structures in Rashba-Type Noncentrosymmetric Superconductors

    NASA Astrophysics Data System (ADS)

    Chen, Chongju; Jin, Biao

    2016-02-01

    We study theoretically the effect of Zeeman field on the Bogoliubov-de Gennes quasiparticle excitation spectrum of a three-dimensional noncentrosymmetric (s+p)-wave model. The quasiparticle excitation spectrum may possess line nodes due to the mixing of s-wave and p-wave pairing in the absence of Zeeman field. Our calculations show that, depending on the magnitude and the orientation of an applied Zeeman field, a variety of nodal structures including nodal points, nodal lines, and nodal surfaces may be generated in the excitation spectrum. These results are corroborated by numerical computations of the low-temperature electronic specific heat. Specifically, we demonstrate rigorously that the zero-field nodal lines will be robust against a weak z-axis oriented Zeeman field. It is also found that the electronic specific heat calculated for a Zeeman field in the x- y plane may qualitatively account for the novel feature of specific heat observed experimentally in CePt_3Si.

  6. The impact of surgical technique on neck dissection nodal yield: making a difference.

    PubMed

    Lörincz, Balazs B; Langwieder, Felix; Möckelmann, Nikolaus; Sehner, Susanne; Knecht, Rainald

    2016-05-01

    The nodal yield of neck dissections is an independent prognostic factor in several types of head and neck cancer. The authors aimed to determine whether the applied dissection technique has a significant impact on nodal yield. This is a single-institution, prospective study with internal control group (level of evidence: 2A). Data of 150 patients undergoing 223 neck dissections between February 2011 and March 2013 have been collected in a comprehensive cancer centre. Eighty-two patients underwent neck dissection with unwrapping the cervical fascia from lateral to medial, while 68 patients were operated without specifically unwrapping the fascia, in a caudal to cranial fashion. The standardised, horizontal neck dissection technique along the fascial planes resulted in a significantly higher nodal count in Levels I, II, III and IV, as well as in terms of overall nodal yield (mean: n = 22.53) than that of the vertical dissection applied in the control group (mean: n = 15.00). This is the first publication showing a direct correlation between neck dissection nodal yield and surgical technique. Therefore, it is paramount to optimise the applied surgical concept to maximise the oncological benefit. PMID:25784183

  7. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    DOE PAGESBeta

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; et al

    2016-02-02

    Here we discuss how topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterizedmore » by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.« less

  8. Tumor microvessel density–associated mast cells in canine nodal lymphoma

    PubMed Central

    Mann, Elizabeth; Whittington, Lisa

    2014-01-01

    Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4) was significantly higher (p < 0.05) than that in the control (0.83 ± 0.3) and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009). Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended. PMID:26770752

  9. Angle Resolved Thermal Conductivity of Superconducting CeCoIn5 along the Nodal Direction

    NASA Astrophysics Data System (ADS)

    Movshovich, Roman; Kim, Duk Y.; Lin, Shizeng; Weickert, Franziska; Bauer, Eric D.; Ronning, Filip; Thompson, Joe D.

    The thermal conductivity measurement in a rotating magnetic field is a powerful probe of the structure of the superconducting energy gap. The four-fold oscillation in thermal conductivity of CeCoIn5, with the heat current in the anti-nodal direction, has revealed the d-wave nature of its order parameter. We have measured the thermal conductivity with the heat current along the [110] (nodal) direction and the magnetic field rotating in the ab-plane. In contrast to the smooth oscillation found with the heat current along the anti-nodal direction, a sharp increase of thermal conductivity was observed when the magnetic field is also in the [110] direction, parallel to the heat current. This suggests that the scattering of the nodal quasiparticle is strongly suppressed along the magnetic field direction. In addition, a smaller increase of the thermal conductivity was observed when the magnetic field is approximately 30 degree away from the nodal direction, perhaps due to a Fermi surface anomaly. Work at Los Alamos was performed under the auspices of the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering.

  10. On mechanisms triggering the levees failure along the Foenna stream on 1st January 2006 and which caused the flooding in the urban area of Sinalunga, Tuscany Region (Italy). A case study

    NASA Astrophysics Data System (ADS)

    Camici, Stefania; Moramarco, Tommaso; Brocca, Luca; Melone, Florisa; Lapenna, Vincenzo; Perrone, Angela; Loperte, Antonio

    2010-05-01

    On 1st January 2006, during an ordinary flood event, a levee failure along the Foenna stream caused the flooding in the urban area of Sinalunga, a small town located in Tuscany region (Italy). The event was monitored by a public agency with the responsibility for the control and maintenance of the natural channel networks. Long time before of flooding, people living in the surrounding area of the stream blamed the presence of wild animals and of numerous burrows along the levees. Although the numerous actions of maintenance along the levees mainly for removing the burrows, a levee seepage occurred during that flood. The presence of an outflow located on the downstream face, almost 2 m below the levee top, caused the spurt of brown water denoting the presence of sediment erosion. On the upstream face of levee, a little hole of about 30 cm at the same height of the outflow was discovered. Although the agency workers tried to close the hole by using appropriate blankets, in short time the top of the levee subsided and the overtopping flow caused a trapezoidal breach typical for an earth-fill embankment. The formation of breach was so fast that in a little more of one hour the urban area near to the Foenna stream was flooded causing high economic damages. Mechanisms triggered the levees failure are the object of this work. The analysis of the event has been first addressed to assess the state of-fact of levees conditions along the Foenna stream, thus to understand how much the activity of wild animals, in particular that of porcupine, may have affected the hydraulic safety of the embankment. At the purpose, after the event, topographical surveys of cross sections have been done along with tomographic surveys by geoelectric technique for investigating the possible presence, besides of burrows, also of tunnels dug into the levees by animals. Then, the analysis of hydrometeorological conditions of the event has allowed to better understand the evolution of the flood and