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Sample records for receiving zoledronic acid

  1. Zoledronic Acid Injection

    MedlinePlus

    ... acid (Reclast) is used to prevent or treat osteoporosis (condition in which the bones become thin and ... Zoledronic acid (Reclast) is also used to treat osteoporosis in men, and to prevent or treat osteoporosis ...

  2. Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

    PubMed Central

    Sun, Shengliang; Wang, Fuchao; Dou, Honglei; Zhang, Longqiang; Li, Jiwen

    2016-01-01

    Background This study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole. Methods One hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations. Results Patients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%). Conclusion AI-associated bone loss

  3. Re-treatment of relapsed Paget's disease of bone with zoledronic acid: results from an open-label study.

    PubMed

    Reid, Ian R; Brown, Jacques P; Levitt, Naomi; Román Ivorra, José A; Bachiller-Corral, Javier; Ross, Ian L; Su, Guoqin; Antunez-Flores, Oscar; Aftring, R Paul

    2013-01-01

    Six patients from the phase 3 trials of zoledronic acid in Paget's disease, who had received zoledronic acid initially and had subsequently relapsed, were entered into an open re-treatment study. Following re-treatment, each patient reached similar absolute nadirs of serum alkaline phosphatase to those recorded after their first dose. No significant adverse events were reported. It is concluded that, while re-treatment of Paget's disease with zoledronic acid is rarely needed, it is safe and effective, with no evidence of treatment resistance based on this small cohort. PMID:24422139

  4. Study of Adverse Effect Profile of Parenteral Zoledronic Acid in Female Patients with Osteoporosis

    PubMed Central

    Kotian, Prem; Sreenivasan, Sushanth

    2016-01-01

    Introduction Osteoporosis is still a under recognized entity in the population. Osteoporosis-related fractures can be prevented if people at risk can be screened, diagnosed and treated early. Bisphosphonates remain the mainstay of osteoporosis treatment as they have multimodal action. Oral bisphosphonate therapy has, significant gastrointestinal side effects leading to noncompliance. Of late parenteral Zoledronic Acid is being used as once or twice yearly infusion for the treatment of osteoporosis. Aim Our article studies the side effect profile and tolerability of parenteral Zoledronic Acid, one of the most potent bisphosphonate used in clinical practice in patients with osteoporosis. Materials and Methods This study was done in KMC hospitals where 49 patients diagnosed with osteoporosis were included for the study. After obtaining a written informed consent each patient received one infusion of 5 mg Zoledronic Acid as per standard treatment protocol. Patient was monitored for clinical improvement and development of any adverse effects. Conclusion In our study all subjects reported significant pain relief after infusion of Zoledronic Acid. Zoledronic Acid had very few serious adverse effects that can be prevented through pre-infusion screening, maintaining good hydration and careful patient monitoring. In our population the patients only experienced mild symptoms of pyrexia, arthralgia myalgia and influenza like symptoms which resolved with symptomatic treatment. PMID:26894105

  5. Comparative Effectiveness on Survival of Zoledronic Acid versus Pamidronate in Multiple Myeloma

    PubMed Central

    Sanfilippo, KM; Gage, B; Luo, S; Weilbaecher, K; Tomasson, M; Vij, R; Colditz, G; Carson, K

    2015-01-01

    Zoledronic acid and pamidronate are the two bisphosphonates approved to reduce multiple myeloma skeletal complications in the United States. Little prior evidence exists comparing survival outcomes between the two. We evaluated the incidence of skeletal related events and overall survival in myeloma patients treated with zoledronic acid versus pamidronate using a cohort of 1,018 United States Veterans. At median follow-up of 26.9 months, patients receiving zoledronic acid had a 22% reduction in risk of death compared to pamidronate (hazard ratio (HR) 0.78; 95% CI, 0.67–0.92). The benefit persisted after controlling for potential confounders. Adjusted Cox modeling with inverse probability weighting and propensity score matching supported these findings. Zoledronic acid was also associated with a 25% decrease in skeletal-related events. Zoledronic acid is associated with increased overall survival and decreased skeletal related events compared to pamidronate in patients with multiple myeloma and should become the preferred bisphosphonate. PMID:24844358

  6. EFFECTS OF ZOLEDRONIC ACID ON OOFORECTOMIZED RATS' TIBIAE: A PROSPECTIVE AND RANDOMIZED STUDY

    PubMed Central

    Alves Pereira, Fernando Roberto; Dutra, Ricardo César; Reis Olímpio, Thiago César; Müller, Sérgio Swain; Palacio, Evandro Pereira

    2015-01-01

    To investigate clinical, biomechanic and histomorphometric effects of zoledronic acid on osteoporotic rats’ tibiae after bilateral ooforectomy. Methods: 40 female Wistar (Rattus novergicus albinus) rats were prospectively studied. On the 60th day of life, the animals were randomized into two groups according to the surgical procedure: bilateral ooforectomy (O) (n=20) and sham surgery (“sham”) (P) (n=20). After 30 days, the animals were divided into four groups, according to the administration of zoledronic acid (ZA) 0.1mg/kg or distilled water (DW): OZA (n=10), ODW (n=10), PZA (n=10) and PDW (n=10). After 12 months, the animals were sacrificed, and had their tibiae assessed. In the clinical study, animals’ weight was considered; in the biomechanical study, compressive assays were applied and, in the histomorphometric analysis, the bone trabecular area was determined. Results: “O” groups showed a significantly greater weight gain than “P” groups (p=0.005). Groups OZA and PZA showed an insignificant weight gain when compared to ODW (p=0.47) and PDW (p=0.68). The groups receiving zoledronic acid and distilled water were able to bear maximum load, similar (p=0.2), at the moment of fracture. In the groups receiving zoledronic acid, an insignificant increase of the bone trabecular area was found when compared to the groups receiving distilled water (p=0.21). There was a positive correlation between trabecular area and maximum load (p=0.04; r=0.95). Conclusion: Zoledronic acid did not significantly influence animals’ weight. The results showed an insignificant increase both of the tibial shaft bone resistance and the bone trabecular area. PMID:26998455

  7. Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia

    PubMed Central

    Rossin, Sara; Divisic, Antuan; De Gregorio, Alesandra; Agosto, Caterina; Catalano, Igor; Mazza, Alessandro; Sartori, Leonardo; Benini, Franca

    2016-01-01

    We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD) with severe and chronic pain who was successfully treated with zoledronic acid (ZOL): a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population. PMID:27747122

  8. Safety & Efficacy of Cyclic Zoledronic Acid Therapy on Pediatric Secondary Osteoporosis

    PubMed Central

    Al-Agha, Abdulmoein E.; Shaikhain, Talal A.; Ashour, Abdullah A.

    2016-01-01

    Background/Aim: Osteoporosis is a systemic disease characterized by decreased bone density and increased tendency to develop fractures. Osteoporosis in children and adolescents is a rare disease usually secondary to Medical conditions or medications given to children. The condition affects normal bone growth and development and carries with it multiple morbidities (physical and psychological) if not corrected promptly. This study aims to share our experience with Zoledronic Acid Therapy in Pediatric patients with secondary osteoporosis. Method: A retrospective study which included 46 patients aged 3 to 18 years. All patients received specific doses of Zoledronic acid and were followed up at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Clinical and laboratory data were collected for each patient from their files. Adverse events were also recorded. Results: The use of Zoledronic Acid in children and adolescents appears to be statically significant reduce fracture rate (p=0.005), bone turnover markers (Osteocalcin p= 0.003, CTX p= 0.008) and pain frequency in symptomatic individuals (p=0.000). Careful selection of cases is required to provide maximum benefits compared to risks associated with therapy. Conclusion: This study demonstrates that Zoledronic acid has positive effects on clinical outcome and bone marker level as well as quality of life for Pediatric patients with Osteoporosis and their families, with no long-term side effects.

  9. Dosing of zoledronic acid with its anti-tumor effects in breast cancer

    PubMed Central

    Zhao, Xinmin; Hu, Xichun

    2015-01-01

    Bisphosphonates have played an important role in the treatment of breast cancer, mainly in patients with bone metastasis, by reducing the risk of fracture, spinal cord compression, and hypercalcemia. Zoledronic acid, the most frequently used intravenous agent, has been traditionally administered on a monthly dosing schedule. Preclinical studies have demonstrated that zoledronic acid can inhibit angiogenesis, invasion, and adhesion of tumor cells. Several clinical studies of different timings and schedules of zoledronic acid therapy have demonstrated its anti-tumor effects, as well as its protective effect on bone health, in postmenopausal women during adjuvant breast cancer therapy. In general, early initiation of zoledronic acid, concomitantly with adjuvant therapy, has been found to be most beneficial. However, questions remain over the most effective schedule of treatment and relative potency of zoledronic acid. Therefore, we review the existing clinical studies to examine the influence of dosing of zoledronic acid therapy on clinical outcomes in patients with breast cancer. PMID:26587376

  10. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma.

    PubMed

    Salaroglio, Iris Chiara; Campia, Ivana; Kopecka, Joanna; Gazzano, Elena; Orecchia, Sara; Ghigo, Dario; Riganti, Chiara

    2015-01-20

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  11. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    PubMed Central

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  12. The anti-tumor potential of zoledronic acid.

    PubMed

    Croucher, P; Jagdev, S; Coleman, R

    2003-08-01

    Bone is a favorable microenvironment for tumor cell colonization because of abundant growth factors released during active bone resorption. Bisphosphonates can dramatically affect the ability of tumor cells to grow in bone by inhibiting osteoclast-mediated bone resorption and by depriving tumors of growth-promoting signals. Moreover, bisphosphonates have direct anti-tumor effects in vitro via induction of apoptosis. Zoledronic acid is a nitrogen-containing bisphosphonate that has demonstrated potent anti-tumor activity in vitro and in vivo. In vitro studies have provided important clues as to the molecular mechanisms by which zoledronic acid induces apoptosis of human breast cancer cell lines. Studies in multiple myeloma and breast cancer models have shed further light on the possible mechanisms underlying the in vivo anti-tumor effects of zoledronic acid. These studies have led to the development of novel strategies to target specific molecular pathways involved in osteoclast maturation and activity, tumor cell metastasis, and tumor growth and survival. The clinical application of these strategies may ultimately prevent bone metastasis.

  13. Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury.

    PubMed

    Shapiro, J; Smith, B; Beck, T; Ballard, P; Dapthary, M; BrintzenhofeSzoc, K; Caminis, J

    2007-05-01

    Acute spinal cord injury is associated with rapid bone loss and an increased risk of fracture. In this double-blind, randomized, placebo-controlled trial, 17 patients were followed for 1 year after administration of either 4 or 5 mg of zoledronic acid or placebo. Bone mineral density (BMD) and structural analyses of the proximal femur were performed using the hip structural analysis program at entry, 6 months, and 12 months. The 17 subjects completed 12 months of observation, nine receiving placebo and eight zoledronic acid. The placebo group showed a decrease in BMD, cross-sectional area, and section modulus and an increase in buckling ratio at each proximal femur site at 6 and 12 months. Six months after zoledronic acid, BMD, cross-sectional area, and section modulus increased at the femoral neck and intertrochanteric regions and buckling ratio decreased consistent with improved bone stability. However, at 12 months, the femoral narrow-neck values declined to baseline. In contrast to placebo, the intertrochanteric region and femur shaft were maintained at or near baseline through 12 months in the zoledronic acid-treated group. Urine N-telopeptide excretion was increased at baseline and declined in both the placebo and treatment groups during the 12 months of observation. We conclude that a single administration of zoledronic acid will ameliorate bone loss and maintain parameters of bone strength at the three proximal femur sites for 6 months and at the femur intertrochanteric and shaft sites for 12 months.

  14. Phase II trial of weekly Docetaxel, Zoledronic acid, and Celecoxib for castration-resistant prostate cancer.

    PubMed

    Kattan, Joseph; Bachour, Marwan; Farhat, Fadi; El Rassy, Elie; Assi, Tarek; Ghosn, Marwan

    2016-08-01

    Background Treatment options for patients with metastatic castration-resistance prostate cancer are unsatisfactory. Docetaxel monotherapy offers promising results with a tolerable toxicity profile. However, enhancing the clinical index of Docetaxel-based therapy remains the ultimate goal. Methods We conducted a phase II, open label, multinational prospective trial to evaluate the efficacy of weekly Docetaxel combined with Zoledronic acid and Celecoxib. Eligible patients received 25 mg/m(2) Docetaxel weekly for 3 consecutive weeks every 4 weeks, 4 mg Zoledronic acid every 4 weeks, and 200 mg oral Celecoxib twice daily. Enrollment was terminated prematurely upon the publication of reports of cardiac toxicity associated with cyclooxygenase (COX) 2 inhibitors. Results Our study enrolled 22 patients with a median of 4.7 cycles per patient. The median overall survival (OS) was 9.8 months (range 0.7 to 24.1 months) with 36 % and 4.5 % survival rates at 1 and 2 years, respectively. Our patients had a biologic response in 40.1 % of cases and a palliative response in 72.7 %. Among the eight patients with measurable disease, three had partial responses, two had stable disease, and three had progressive disease, leading to a response rate (RR) of 62.5 %. The observed toxicities were mild and limited to grade 3 events. Nine patients had anemia (40.1 %), 5 had sensory neuropathy (22.7 %) and 2 had stomatitis (9.1 %). Conclusion The combination of Docetaxel, Celecoxib, and Zoledronic acid failed to improve OS or to offer an acceptable biologic response. We do not believe that there is compelling evidence to include either Celecoxib or Zoledronic acid in further phase II/III trials. PMID:27159981

  15. Once-yearly zoledronic acid and days of disability, bed rest, and back pain: randomized, controlled HORIZON Pivotal Fracture Trial.

    PubMed

    Cauley, Jane A; Black, Dennis; Boonen, Steven; Cummings, Steven R; Mesenbrink, Peter; Palermo, Lisa; Man, Zulema; Hadji, Peyman; Reid, Ian R

    2011-05-01

    The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90-0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87-1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR = 0.58, 95% CI 0.47-0.72) and 7 or more limited-activity days owing to a fracture (RR = 0.67, 95% CI 0.58-0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the

  16. A single intravenous administration of zoledronic acid prevents the bone loss and mechanical compromise induced by aromatase inhibition in rats.

    PubMed

    Gasser, Jürg A; Green, Jonathan R; Shen, Victor; Ingold, Peter; Rebmann, Andrea; Bhatnagar, Ajay S; Evans, Dean B

    2006-10-01

    Recent evidence has demonstrated that long-term estrogen deprivation using aromatase inhibitor therapy in postmenopausal women with breast cancer results in bone loss and increased fracture risk. Bisphosphonates are potent inhibitors of bone resorption and have demonstrated efficacy in preventing bone loss in postmenopausal women with low bone mineral density (BMD) and in patients with breast cancer receiving estrogen deprivation therapy. Therefore, this study investigated the effects of the bisphosphonate zoledronic acid on BMD and bone strength in rats treated with the aromatase inhibitor, letrozole. Peripheral quantitative computed tomography demonstrated that treatment of rats with daily oral letrozole (1 mg/kg) induced significant bone loss and cortical thinning compared with control animals (P < 0.01). A single prior intravenous dose of zoledronic acid dose dependently protected against letrozole-induced bone loss and cortical thinning, with the highest evaluated dose (20 microg/kg) resulting in BMD values that were not significantly different from controls over the 24 weeks of letrozole treatment. Furthermore, biomechanical testing of the distal femoral metaphysis demonstrated that zoledronic acid (20 microg/kg) significantly prevented the decrease in stiffness and elastic modulus induced by letrozole treatment. Taken together, these data support the use of zoledronic acid for the prevention of bone loss in women with breast cancer receiving aromatase inhibitor therapy.

  17. Analgesic efficacy of zoledronic acid and its effect on functional status of prostate cancer patients with metastasis

    PubMed Central

    Gálvez, Rafael; Ribera, Victoria; González-Escalada, José Ramón; Souto, Alicia; Cánovas, María Luz; Castro, Andrés; Herrero, Begoña; de los Ángeles Maqueda, María; Castilforte, Matilde; Marco-Martínez, José Javier; Pérez, Concepción; Vicente-Fatela, Lorenza; MD, Consuelo Nieto; Orduña, Maria José; Padrol, Anna; Reig, Enrique; Carballido, Joaquín; Cózar, José Manuel

    2008-01-01

    Objectives A multi-centered observational study evaluated the efficacy of zoledronic acid for improving pain and mobility, and preventing skeletal-related events (SRE) (fracture, spinal compression, pain-relieving radiotherapy), in patients with prostate cancer and bone metastasis. Materials and Methods Males (n = 218) with prostate cancer and bone metastasis undergoing oncologic therapy received zoledronic acid (4 mg iv/month) for 6 months. Parameters evaluated were: 1) pain and movement after 2 consecutive doses; 2) quality of life; 3) SRE incidence and time-to-appearance. Medication tolerance and treatment satisfaction were assessed using a questionnaire. Results A total of 170 that matched all the inclusion criteria (78%) out of 218 were evaluable for efficacy. There was a measurable statistically significant reduction in pain at rest and on movement as well as an improvement in the quality of life compared with baseline. Best results were obtained with early treatment. Overall incidence of bone events was 11.2%. Of the 212 patients (97.2%) evaluable for safety, 16% suffered adverse events and 66% expressed satisfaction with the treatment Discussion Zoledronic acid is effective for reducing pain, improving mobility, and increasing the quality of life in patients with prostate cancer with bone metastasis. Its easy administration and good tolerability make zoledronic acid one of the principal therapeutic tools in the management of patients with pain associated with bone metastasis from prostate cancer. PMID:19920966

  18. Cathepsin K in treatment monitoring following intravenous zoledronic acid

    PubMed Central

    JAHN, OLIVER; WEX, THOMAS; KLOSE, SILKE; KROPF, SIEGFRIED; ADOLF, DANIELA; PIATEK, STEFAN

    2014-01-01

    Cathepsin K (CatK) is mainly expressed by osteoclasts and plays an important role in bone resorption. As CatK is expressed and secreted by osteoclasts during active bone resorption, it may be a useful and specific biochemical marker of osteoclastic activity. Therefore, CatK serum levels were studied for monitoring the treatment of females with postmenopausal osteoporosis by zoledronic acid. The serum CatK levels were determined in nine postmenopausal females before and after 3, 6 and 12 months of treatment. The levels were significantly reduced after 3 and 6 months (P<0.05), whereas they returned to baseline after 1 year. Taken together, the serum level of CatK may be suitable for monitoring anti-osteoporotic therapy in association with treatment response. PMID:25279169

  19. Randomized Controlled Trial of Early Zoledronic Acid in Men With Castration-Sensitive Prostate Cancer and Bone Metastases: Results of CALGB 90202 (Alliance)

    PubMed Central

    Smith, Matthew R.; Halabi, Susan; Ryan, Charles J.; Hussain, Arif; Vogelzang, Nicholas; Stadler, Walter; Hauke, Ralph J.; Monk, J. Paul; Saylor, Philip; Bhoopalam, Nirmala; Saad, Fred; Sanford, Ben; Kelly, W. Kevin; Morris, Michael; Small, Eric J.

    2014-01-01

    Purpose Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown. This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer. Patients and Methods Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo. After their disease progressed to castration-resistant status, all patients received open-label treatment with zoledronic acid. The primary end point was time to first SRE, defined as radiation to bone, clinical fracture, spinal cord compression, surgery to bone, or death as a result of prostate cancer. Target accrual was 680 patients. Primary analysis was planned after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs) after the corporate supporter withdrew study drug supply. Results Early zoledronic acid was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to 40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio, 0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P = .29). Rates of adverse events were similar between the groups. Conclusion In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs. PMID:24590644

  20. [Separation of zoledronic acid and its related substances by ion-pair reversed-phase high performance liquid chromatography].

    PubMed

    Zhang, Xiaoqing; Jiang, Ye; Xu, Zhiru

    2004-07-01

    A rapid and simple ion-pair reversed-phase high performance liquid chromatographic method (HPLC) has been established for the routine analysis of zoledronic acid and its related substances. The chromatographic conditions were optimized based on the satisfactory separation of zoledronic acid from imidazol-1-ylacetic acid, their retention times and peak shape. The excellent separation of zoledronic acid from its related substances, including the remaining imidazol-1-ylacetic acid used in the synthesis of zoledronic acid and other impurities of oxidation and decomposition, was achieved within 9 min on a Hypersil C8 column with UV detection at 220 nm. The mobile phase was a mixture of methanol (20%) and 5 mmo/L phosphate buffer (80%) that contains 6 mmol/L tetrabutylammonium bromide. The resolution factor of zoledronic acid from its adjacent peak was more than 2.5. This is a simple and rapid method for the routine assay of zoledronic acid.

  1. [Zoledronic Acid Administration is Effective for Hematopoiesis Management in a Patient with Primary Myelofibrosis].

    PubMed

    Sugama, Yusuke; Kuroda, Hiroyuki; Horiguchi, Hiroto; Yamauchi, Natsumi; Sato, Ken; Yamada, Michiko; Hamaguchi, Kohta; Nakamura, Hajime; Abe, Tomoyuki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Koguma, Masato; Koguma, Tetsuhiko; Kato, Junji

    2016-09-01

    An 80-year-old man received a diagnosis of anemia and a decreased platelet count from his physician in 2008, and was referred to our department where primary myelofibrosis was diagnosed.The patient was classified into the lower risk group according to the International Prognostic Scoring System(IPSS), and was followed up without treatment.In June 2010, pancytopenia progressed, and the patient was reclassified into the higher risk group.Blood count did not increase with metenolone treatment, but increased with zoledronic acid(ZA)that he started receiving from January 2012. After ZA treatment, circulating levels of vascular endothelial growth factor(VEGF)and transforming growth factor-b(TGF-b)decreased, and bone marrow biopsy showed an absence of reticular fibers and collagen fibers.In the present case, we observed that the blood count increased because of ZA-induced improvements in myelofibrosis. PMID:27628559

  2. Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.

    PubMed

    Wang, I-Te; Chou, Shou-Chu; Lin, Ying-Chin

    2014-12-01

    Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

  3. Molecular interactions between zoledronic acid and bone: An in vitro Raman microspectroscopic study.

    PubMed

    Juillard, Audrey; Falgayrac, Guillaume; Cortet, Bernard; Vieillard, Marie-Hélène; Azaroual, Nathalie; Hornez, Jean-Christophe; Penel, Guillaume

    2010-11-01

    The aim of this study was to investigate molecular interactions between a bisphosphonate (BP), zoledronic acid, and bone tissue by the use of Raman microspectroscopy. In this way, samples of hydroxyapatite (HA), as a bone model, and Wistar rat femurs were soaking in zoledronic acid solutions. Sample surfaces were studied by Environmental Scanning Electron Microscopy and Raman spectroscopy. The amount of zoledronic acid incorporated onto the samples and the inorganic phosphate released in solution were determined by (31)P NMR spectroscopy. Total carbonate content in solution was evaluated by inorganic carbon analyser. After impregnation new Raman bands with frequencies close to characteristic peaks of zoledronic acid (in particular phosphate moieties and imidazole ring of the R2 side-chain) were observed on both types of samples. Physico-chemical parameters of the bone were also significantly modified (P<0.0001). The mineral to organic ratio and the carbonate to phosphate ratio decreased and the crystallinity increased. Released inorganic phosphate and carbonate were detected in the solutions. The Raman shift of the bands corresponding to the phosphate groups and the imidazole ring of the BP highlight their implication in the binding to the mineral. The detection of released inorganic phosphate and carbonate in solution, the modifications of the mineral to phosphate ratio and the carbonate to phosphate ratio reveal that BP decrease the amount of inorganic phosphate and limit the dissolution of bone mineral. The increase of the crystallinity after BP binding shows a re-organisation of the lattice with a higher symmetry. Thus, it seems that zoledronic acid has an important contribution on the increase of crystallinity. The use of Raman spectrometry brings new and complementary information on the impact of zoledronic acid on bone composition at molecular level. Raman spectrometry could help to understand by which way BPs improve bone strength and decrease fracture risk

  4. Transient changes in thyroid functions tests after zoledronic acid infusion.

    PubMed

    Karga, Helen; Giagourta, Irene; Papaioannou, Garyphallia; Katsichti, Paraskevi; Pardalakis, Argyris; Kassi, Georgia; Zagoreou, Apostolia; Triantaphyllopoulou, Maria; Zerva, Cherry

    2011-01-01

    Zoledronic acid (ZA) induces an acute phase response in association with elevation of serum cytokines, which possibly alter the 3 types of iodothyronine deiodinase activity. We therefore studied the possible alteration in thyroid function tests by ZA. We investigated the acute changes in serum thyroid hormones, TSH, cortisol, white blood cells, CRP, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), before (0) and 1, 2 and 3 days after iv infusion of 5 mg ZA in 24 asymptomatic postmenopausal women with osteoporosis (ZA group) in comparison with a placebo group. In the majority of patients the ZA infusion was associated with acute phase response and fever within 24h after infusion which became attenuated on day three. Concurrently with increase in serum cortisol, CRP, IL-6 and TNF-α, on day 1 and 2, total serum T3 (TT3), free T3 (fT3), total T4 (TT4) and fT4 decreased with a nadir on day 2 in association with an increase in the fT4/fT3 ratio and reverse T3 (rT3) levels. All thyroid function changes returned to the baseline levels on day 3, with cytokines still at higher levels, although lower than those on day 2. Serum TSH remained essentially unchanged throughout the study. The changes in thyroid hormones were at least in part explained by the increased TNF-α, but not by IL-6. ZA induces short term changes in thyroid hormones, characteristic of nonthyroidal illness syndrome (NTIS), in association with an increase in TNF-α and IL-6.

  5. Self-assembling nanoparticles encapsulating zoledronic acid revert multidrug resistance in cancer cells

    PubMed Central

    Gazzano, Elena; Salzano, Giuseppina; Giordano, Antonio; Desiderio, Vincenzo; Ghigo, Dario; Caraglia, Michele; De Rosa, Giuseppe; Riganti, Chiara

    2015-01-01

    The overexpression of ATP binding cassette (ABC) transporters makes tumor cells simultaneously resistant to several cytotoxic drugs. Impairing the energy metabolism of multidrug resistant (MDR) cells is a promising chemosensitizing strategy, but many metabolic modifiers are too toxic in vivo. We previously observed that the aminobisphosphonate zoledronic acid inhibits the activity of hypoxia inducible factor-1α (HIF-1α), a master regulator of cancer cell metabolism. Free zoledronic acid, however, reaches low intratumor concentration. We synthesized nanoparticle formulations of the aminobisphosphonate that allow a higher intratumor delivery of the drug. We investigated whether they are effective metabolic modifiers and chemosensitizing agents against human MDR cancer cells in vitro and in vivo. At not toxic dosage, nanoparticles carrying zoledronic acid chemosensitized MDR cells to a broad spectrum of cytotoxic drugs, independently of the type of ABC transporters expressed. The nanoparticles inhibited the isoprenoid synthesis and the Ras/ERK1/2-driven activation of HIF-1α, decreased the transcription and activity of glycolytic enzymes, the glucose flux through the glycolysis and tricarboxylic acid cycle, the electron flux through the mitochondrial respiratory chain, the synthesis of ATP. So doing, they lowered the ATP-dependent activity of ABC transporters, increasing the chemotherapy efficacy in vitro and in vivo. These effects were more pronounced in MDR cells than in chemosensitive ones and were due to the inhibition of farnesyl pyrophosphate synthase (FPPS), as demonstrated in FPPS-silenced tumors. Our work proposes nanoparticle formulations of zoledronic acid as the first not toxic metabolic modifiers, effective against MDR tumors. PMID:26372812

  6. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study

    PubMed Central

    Fizazi, Karim; Carducci, Michael; Smith, Matthew; Damião, Ronaldo; Brown, Janet; Karsh, Lawrence; Milecki, Piotr; Shore, Neal; Rader, Michael; Wang, Huei; Jiang, Qi; Tadros, Sylvia; Dansey, Roger; Goessl, Carsten

    2011-01-01

    Summary Background Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. Methods In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. Findings 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9–18·5) for patients on denosumab and 11·2 months (IQR 5·6–17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8–24·9) with denosumab compared with 17·1

  7. Evaluation of safety and analgesic consumption in patients with advanced cancer treated with zoledronic acid

    PubMed Central

    Kmetec, Andrej; Hajdinjak, Tine

    2013-01-01

    Background The aim of the study was evaluation of zoledronic acid with regard to safety, effect on analgesic consumption and impact on occurrence of skeletal related events in patients with bone lesions from solid tumors and multiple myeloma. Methods We conducted an observational, 12-month, phase IV and multi-center study. One hundred and twenty-five symptomatic (pain) bone-metastatic patients were included between 2007 and 2009: 92 prostate cancers, 28 multiple myelomas, 5 others. They were prescribed monthly infusions of zoledronic acid in accordance to each disease’s treatment guidelines. Analgesics consumption, pain and laboratory values were evaluated. Results Zoledronic acid was prescribed concurrent to initial therapy for myeloma and only in late stage of prostate cancer. With treatment, percentage of patients on analgesics decreased in myeloma group (from 57% to 24%) and increased in prostate cancer group (from 70% to 88%). In patients with any analgesics, the use of opiates’ prescription dropped from 72.9% to 64%, percentages of non-steroidal analgesics and other mild analgesics increased slightly. Pain score (Visual Analog Scale, VAS) decreased non significantly (by 22%) in prostate cancer but significantly in myeloma (by 97%). Hypocalcaemia grade 3 or 4 was observed in 4% of patients. Deviations in creatinine remained stable throughout. A total of 31 skeletal related events were reported for 10 patients (8%). Conclusions Zoledronic acid was safe medication. Different response of pain was seen between prostate cancer and myeloma patients, which might be due to different stages of disease where it was prescribed according to present guidelines. Possibility of earlier start of treatment should be explored in prostate cancer. PMID:24133394

  8. Systemic and local zoledronic acid treatment with hydroxyapatite bone graft: A histological and histomorphometric experimental study

    PubMed Central

    Günes, Nedim; Dundar, Serkan; Saybak, Arif; Artas, Gökhan; Acikan, Izzet; Ozercan, I. Hanifi; Atilgan, Serhat; Yaman, Ferhan

    2016-01-01

    In this study, the aim was to compare the relative efficacy of systemic and local zoledronic acid (ZA) on a hydroxyapatite (HA) bone graft in a rat critical-size calvarial bone defect. In total, 84 female rats were divided into four groups: Empty control (EC) group with no treatment applied; HA group, in which only HA bone graft material was used in the calvarium; and HA plus local ZA (HA+LZA) and HA plus systemic ZA (HA+SZA) groups, in which animals received ZA locally or systemically, respectively, with HA bone graft material in the calvarium. A 5-mm standardised critical-size calvarial bone defect was created with a standard trephine drill and the respective treatment was applied. Rats were sacrificed 7, 14 and 28 days later. The numbers of osteoclasts and osteoblasts, and degree of bone formation were evaluated histopathologically and histomorphometrically. Statistically significant differences were detected between the HA, HA+LZA and HA+SZA groups and the EC group for new bone formation (P<0.05). Osteoblast numbers in the HA+LZA and HA+SZA groups were significantly higher compared with those in the EC and HA groups (P<0.05). No statistically significant difference was detected between the HA+LZA and HA+SZA groups in new bone formation or osteoblast number (P>0.05). Bone formation was significantly higher in the HA group than in the EC group (P<0.05). The numbers of osteoclasts in the HA+LZA and HA+SZA groups were significantly higher than those in the groups EC and HA (P<0.05); however, there was no significant difference between groups HA+LZA and HA+SZA (P>0.05). Within the limitations of this study, systemic or local administration of ZA enhanced new bone formation with a HA bone graft in a rat critical-size calvarial defect model. PMID:27698743

  9. Systemic and local zoledronic acid treatment with hydroxyapatite bone graft: A histological and histomorphometric experimental study

    PubMed Central

    Günes, Nedim; Dundar, Serkan; Saybak, Arif; Artas, Gökhan; Acikan, Izzet; Ozercan, I. Hanifi; Atilgan, Serhat; Yaman, Ferhan

    2016-01-01

    In this study, the aim was to compare the relative efficacy of systemic and local zoledronic acid (ZA) on a hydroxyapatite (HA) bone graft in a rat critical-size calvarial bone defect. In total, 84 female rats were divided into four groups: Empty control (EC) group with no treatment applied; HA group, in which only HA bone graft material was used in the calvarium; and HA plus local ZA (HA+LZA) and HA plus systemic ZA (HA+SZA) groups, in which animals received ZA locally or systemically, respectively, with HA bone graft material in the calvarium. A 5-mm standardised critical-size calvarial bone defect was created with a standard trephine drill and the respective treatment was applied. Rats were sacrificed 7, 14 and 28 days later. The numbers of osteoclasts and osteoblasts, and degree of bone formation were evaluated histopathologically and histomorphometrically. Statistically significant differences were detected between the HA, HA+LZA and HA+SZA groups and the EC group for new bone formation (P<0.05). Osteoblast numbers in the HA+LZA and HA+SZA groups were significantly higher compared with those in the EC and HA groups (P<0.05). No statistically significant difference was detected between the HA+LZA and HA+SZA groups in new bone formation or osteoblast number (P>0.05). Bone formation was significantly higher in the HA group than in the EC group (P<0.05). The numbers of osteoclasts in the HA+LZA and HA+SZA groups were significantly higher than those in the groups EC and HA (P<0.05); however, there was no significant difference between groups HA+LZA and HA+SZA (P>0.05). Within the limitations of this study, systemic or local administration of ZA enhanced new bone formation with a HA bone graft in a rat critical-size calvarial defect model.

  10. Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer.

    PubMed

    Melisi, Davide; Caputo, Rosa; Damiano, Vincenzo; Bianco, Roberto; Veneziani, Bianca Maria; Bianco, A Raffaele; De Placido, Sabino; Ciardiello, Fortunato; Tortora, Giampaolo

    2005-12-01

    Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting.

  11. Data in support of the bone analysis of NOD-SCID mice treated with zoledronic acid and prednisolone.

    PubMed

    Hori, Naoko; Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-06-01

    This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled "Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli" [1]. The present data and the NOD-SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment.

  12. Locally administered zoledronic Acid therapy for giant cell tumor of bone.

    PubMed

    Nishisho, Toshihiko; Hanaoka, Naoyoshi; Endo, Kenji; Takahashi, Mitsuhiko; Yasui, Natsuo

    2011-07-07

    Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.

  13. Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells.

    PubMed

    Heino, Terhi J; Alm, Jessica J; Halkosaari, Heikki J; Välimäki, Ville-Valtteri

    2016-08-01

    Background and purpose - Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods - A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (μCT), and histology. Results - Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation - Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID:27196705

  14. Detecting Early Biomechanical Effects of Zoledronic Acid on Femurs of Osteoporotic Female Rats

    PubMed Central

    Palacio, Evandro Pereira; Müller, Sérgio Swain; Sardenberg, Trajano; Mizobuchi, Roberto Ryuiti; Galbiatti, José Antônio; Durigan, Alcides; Savarese, Aniello; Ortolan, Érika Veruska Paiva

    2012-01-01

    Aim. To investigate the biomechanical effects of zoledronic acid (ZA) on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O) (n = 40) and sham surgery (S) (n = 40). At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1 mg/kg of ZA or distilled water (DW) was intraperitoneally administered: OZA (n = 20), ODW (n = 20), SZA (n = 20), and SDW (n = 20). The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N), yield point (N), and stiffness coefficient (N/mm) of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1 mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy. PMID:23304634

  15. Synergistic anti-tumor effects of zoledronic acid and radiotherapy against metastatic hepatocellular carcinoma.

    PubMed

    Morii, Kazuhiko; Aoyama, Yuhki; Nakamura, Shinichiro; Okushin, Hiroaki

    2015-01-01

    A 72-year-old man with advanced hepatocellular carcinoma and decompensated hepatitis C virus-related cirrhosis suffered from a metastatic femoral fracture. After undergoing radiotherapy, he was only treated with supportive care, except for the administration of zoledronic acid (ZA). Thereafter, the initially elevated serum α-fetoprotein and des-gamma carboxyprothrombin levels declined to within the normal ranges. Hepatic and metastatic adrenal tumors, distant from the radiation field, exhibited a surprising regression. ZA is known to inhibit the activity of osteoclasts, bone-residential macrophages, and has been reported to have a direct anti-tumor effect. ZA may adjust the immunological milieu in tumor microenvironments by inhibiting the tumor-associated macrophages. Because radiotherapy can enhance the presentation of tumor-associated antigens, ZA and radiotherapy may exert synergistic anti-tumor effects. PMID:26466697

  16. Zoledronic acid enhances Vδ2 T-lymphocyte antitumor response to human glioma cell lines.

    PubMed

    Cimini, E; Piacentini, P; Sacchi, A; Gioia, C; Leone, S; Lauro, G M; Martini, F; Agrati, C

    2011-01-01

    Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain tumor in humans, responds modestly to treatment: most patients survive less than one year after diagnosis, despite both classical and innovative treatment approaches. A recent paper focused on γδ T-cell response in GBM patients, suggesting the application of an immunomodulating strategy based on γδ T-cells which is already in clinical trials for other tumors. Human Vγ2 T-cells recognize changes in the mevalonate metabolic pathway of transformed cells by activating cytotoxic response, and by cytokine and chemokine release. Interestingly, this activation may also be induced in vivo by drugs, such as zoledronic acid, that induce the accumulation of Vγ2 T-cell ligand Isopentenyl-pyrophosphate by blocking the farnesyl pyrophosphate synthase enzyme. The aim of our work is to confirm whether bisphosphonate treatment would make glioma cell lines more susceptible to lysis by in vitro expanded γδ T-cells, improving their antitumor activity. We expanded in vitro human Vγ2 T-cells by phosphoantigen stimulation and tested their activity against glioma cell lines. Co-culture with glioma cells induced Vγ2 T-cell differentiation in effector/memory cells, killing glioma cells by the release of perforin. Interestingly, glioma cells were directly affected by zoledronic acid; moreover, treatment increased their activating ability on Vγ2 T-cells, inducing an effective antitumor cytotoxic response. Taken together, our results show that aminobisphosphonate drugs may play a dual role against GBM, by directly affecting tumor cells, and by enhancing the antitumor response of Vγ2 T-cells. Our results confirm the practicability of this approach as a new immunotherapeutic strategy for GBM treatment.

  17. Multiple cranial neuropathies following zoledronic acid infusion: a relationship? Clinical features and pathogenic discussion concerning a case.

    PubMed

    Deshayes, S; Martin Silva, N; Cogez, J; Baldolli, A; Fedrizzi, S; Bienvenu, B; Aouba, A

    2016-08-01

    The widespread use of bisphosphonates, especially in osteoporosis, has led to a greater number of reports of side effects. We describe for the first time a case of a 75-year-old female patient with a history of indolent sicca syndrome who developed multiple cranial neuropathies after zoledronic acid infusion. In this case, the elimination of the main causes of multiple cranial neuropathies, the chronology with zoledronic acid infusion, the absence of secondary complications of the Sjögren's syndrome, reported cases of similar peripheral nerve injuries with interferon infusions, the spontaneous remission of this multiple cranial neuropathy in parallel with the induced flu-like syndrome, argue for its iatrogenic origin, probably by a great release of inflammatory mediators in this particular background of primary Sjögren's syndrome. PMID:26980457

  18. The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis.

    PubMed

    Hadji, P; Coleman, R; Gnant, M; Green, J

    2012-11-01

    Recent data from the AZURE, ABCSG-12, and ZO-FAST clinical trials have challenged our understanding of the potential anticancer activity of zoledronic acid (ZOL). Although the results of these studies may appear to be conflicting on the surface, a deeper look into commonalities among the patient populations suggest that some host factors (i.e. patient age and endocrine status) may contribute to the anticancer activity of ZOL. Indeed, data from these large clinical trials suggest that the potential anticancer activity of ZOL may be most robust in a low-estrogen environment. However, this may be only part of the story and many questions remain to be answered to fully explain the phenomenon. Does estrogen override the anticancer activity of ZOL seen in postmenopausal women? Are hormones other than estrogen involved that contribute to this effect? Does the role of bone turnover in breast cancer (BC) growth and progression differ in the presence of various estrogen levels? Here, we present a review of the multitude of factors affected by different endocrine environments in women with BC that may influence the potential anticancer activity of ZOL.

  19. Effect of zoledronic acid on spinal fusion outcomes in an ovariectomized rat model of osteoporosis.

    PubMed

    Yasen, Miersalijiang; Li, Xiangqian; Jiang, Libo; Yuan, Wei; Che, Wu; Dong, Jian

    2015-09-01

    To evaluate the effect of zoledronic acid (ZA) on spinal fusion in ovariectomized (OVX) rats. Female SD rats (n = 50) were OVX or sham-operated and randomized into five groups: Sham, OVX control, ZOL-20 (20 µg/kg), ZOL-100 (100 µg/kg), and ZOL-500 (500 µg/kg). Eight weeks after OVX, bilateral lumbar spinal fusion was performed using autologous iliac bone with ZA or saline according to the grouping. The lumbar spines were harvested at 8 weeks and subjected to radiographic, manual palpation, micro-computed tomographic (micro-CT), and histological analysis. The manual palpation result differed significantly only between the ZOL-500 (fused: partially fused: not fused, 9:0:0) and OVX control (4:2:3) (p < 0.05). The radiographic scales were also differed significantly only between these two groups. According to the micro-CT results, the bone volume fraction (BV/TV) were significantly higher in all ZA-treated groups (54.2%, 65.9%, and 73.6%) than OVX control (43.7%) (p < 0.01). At clinical dose or lower, ZA didn't alter the spinal fusion, but a higher dose increased the spinal fusion rate significantly. This study suggests ZA may have a positive effect on spinal fusion in the presence of osteoporosis, and spinal fusion surgery outcome is not likely to be altered by ZA at clinical dose.

  20. Compromised Osseous Healing of Dental Extraction Sites in Zoledronic Acid-Treated Dogs

    PubMed Central

    Allen, Matthew R.; Kubek, Daniel J.; Burr, David B.; Ruggiero, Salvatore L.; Chu, Tien-Min Gabriel

    2010-01-01

    PURPOSE The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction. METHODS Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the 4th premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using micro-computed tomography (micro-CT) and dynamic histomorphometry. RESULTS The initial infilling of the extraction socket with bone was not affected by ZOL but subsequent removal of this bone was significantly suppressed compared to CON. After 8-weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of ~50%/year in CON animals while ZOL-treated animals had a rate of < 1%/year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw. CONCLUSIONS These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw. PMID:20458574

  1. p53-independent anti-tumor effects of the nitrogen-containing bisphosphonate zoledronic acid.

    PubMed

    Kuroda, Junya; Kimura, Shinya; Segawa, Hidekazu; Sato, Kiyoshi; Matsumoto, Seiji; Nogawa, Masaki; Yuasa, Takeshi; Kobayashi, Yutaka; Yoshikawa, Toshikazu; Ottmann, Oliver G; Maekawa, Taira

    2004-02-01

    Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, exerts anti-tumor effects by inhibiting the prenylation of small GTPases. We have also reported that ZOL shows an anti-leukemic effect by inducing apoptosis throughout the S phase to the G(2) / M boundary. Here, we studied the effects of ZOL on various cell cycle regulators, including p53, cyclin-dependent kinases (CDKs), CDK inhibitors and cyclins, using BV173 leukemia and HCT116 colorectal carcinoma cell lines, harboring wild-type (wt-) p53. ZOL induced the accumulation of neither p53 nor p21(WAF1/CIP1) during the execution of apoptosis in BV173 cells. Therefore, we investigated the dependence of ZOL-induced apoptosis on intact p53 by using wt-p53 HCT116 and a p53-degraded HCT116 subline, and observed no significant difference. p57(KIP2) was upregulated by ZOL in BV173 cells, but not in HCT116 cells. Flow cytometric analyses showed that ZOL also impaired the cell cycle-dependent expression patterns of cyclins A, B and D3 in BV173. In conclusion, the p53-independent anti-tumor activities of ZOL suggest that it may be an attractive agent for treating cancers, including those with chemoresistance resulting from the loss of p53 function. ZOL also affected the coordinate expression patterns of several cell cycle regulators during the execution of anti-tumor activity.

  2. Lip ulceration associated with intravenous administration of zoledronic acid: report of a case.

    PubMed

    Andreadis, Dimitrios; Mauroudis, Stergios; Poulopoulos, Athanasios; Markopoulos, Anastasios; Epivatianos, Apostolos

    2012-06-01

    Although osteonecrosis of the jaw is a well-known adverse reaction of bisphosphonates (BPs), random cases of oral mucosal ulceration after per os administration of BP-aledronate have been attributed to prolonged mucosal irritation. This report, for the first time, describes the mucosal ulceration related to intravenous use of zoledronic acid (ZA). A 52-year-old female patient presented with painful ulcers on both cutaneous/mucosal surfaces of the lower lip and a 2-month history of osteonecrosis of the mandible beside the right lower canine. Her medical record included intravenous administration of ZA for 10 months for primary breast cancer metastatic to bone. Examination of the peripheral blood showed severe anemia and a slightly increased white blood cell count, due to urinary tract infection by E. coli, but no evidence of a viral infection. The treatment of anemia and E. coli infection did not improve the labial ulcers. Biopsy from the mucosal lesion revealed a non-specific ulceration with moderate inflammatory infiltration. There was no evidence of infection or malignancy. ZA administration was discontinued and within 3 months the lesions were resolved after treatment with systemic antibiotics (amoxicillin), vitamins A and E, chlorexidine and H(2)O(2) (hydrogen peroxide) solutions and local pantothenic acid/vitamin A creams. Recurrence was detected a month after ZA re-administration. Nevertheless, after new treatment, the patient was free of oral/skin lesions 18 months later. This case, which is the first report of ulceration associated with intravenous administration of bisphosphonates, suggests that systemic mechanisms may be implicated in BP-induced oral mucosal ulceration. Furthermore, ZA appears to cause the same oral mucosal manifestations as alendronate. This emphasizes the need for oral examination in all cases of BP therapy, whether per os or intravenously administrated. PMID:22105344

  3. The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.

    PubMed

    Saghieh, Said; Khoury, Nabil J; Tawil, Ayman; Masrouha, Karim Z; Musallam, Khaled M; Khalaf, Kinda; Dosh, Laura; Jaouhari, Rosemarie Reich; Birjawi, Ghina; El-Hajj-Fuleihan, Ghada

    2010-02-01

    We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established.

  4. Dose-dependent inhibitory effects of zoledronic acid on osteoblast viability and function in vitro

    PubMed Central

    HUANG, XIN; HUANG, SHILONG; GUO, FENGJIN; XU, FEI; CHENG, PENG; YE, YAPING; DONG, YONGHUI; XIANG, WEI; CHEN, ANMIN

    2016-01-01

    Zoledronic acid (ZA), which is one of the most potent and efficacious bisphosphonates, has been commonly used in clinical practice for the treatment of various bone disorders. The extensive use of ZA has been associated with increasing occurrence of jaw complications, now known as bisphosphonate-associated osteonecrosis of the jaw (BRONJ). However, the mechanism underlying BRONJ remains to be fully elucidated. The aim of the present study was to investigate the effects of different concentrations of ZA on the MC3T3-E1 murine preosteoblast cell line cells and examine the possible pathogenesis of BRONJ. In the present study, the effect of ZA on the viability, apoptosis, differentiation and maturation of MC3T3-E1 cells, as well as its relevant molecular mechanism, were examined The results of a Cell Counting Kit 8 assay, a flow cytometric Annexin-V/propidium iodide assay and western blot analysis demonstrated that ZA exhibited a significant inhibition of cell viability and induction of apoptosis at concentrations >10 µM. Subsequently, the effect of ZA on cell differentiation at concentrations <1 µM were investigated. In this condition, ZA inhibited bone nodule formation and decreased the activity of alkaline phosphatase. The results of reverse transcription-quantitative polymerase chain reaction and western blot analyses indicated that ZA downregulated the expression levels of the marker genes and proteins associated with osteogenic differentiation. Further investigation revealed that the suppression of differentiation by ZA was associated with decreased expression of bone morphogenetic protein-2 (BMP-2) and downregulation of the phosphorylation levels in the downstream extracellular signal-regulated kinase 1/2 and p38 pathways. These adverse effects of ZA were observed to be concentration-dependent. The results from the present study suggested that ZA at higher concentrations induces cytotoxicity towards osteoblasts, and ZA at lower concentrations suppresses

  5. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

    PubMed Central

    Pannacciulli, N.; Brown, J. P.; Czerwinski, E.; Nedergaard, B. S.; Bolognese, M. A.; Malouf, J.; Bone, H. G.; Reginster, J.-Y.; Singer, A.; Wang, C.; Wagman, R. B.; Cummings, S. R.

    2016-01-01

    Context: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. Objective: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. Design and Setting: This was an international, multicenter, randomized, double-blind trial. Participants: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. Interventions: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. Main Outcome Measures: Changes in BMD and bone turnover markers were measured. Results: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs −0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). Conclusions: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL. PMID:27270237

  6. Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

    PubMed

    Baklaushev, V P; Grinenko, N F; Yusubalieva, G M; Gubskii, I L; Burenkov, M S; Rabinovich, E Z; Ivanova, N V; Chekhonin, V P

    2016-08-01

    The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer. PMID:27590765

  7. Transferrin-Targeted Nanoparticles Containing Zoledronic Acid as a Potential Tool to Inhibit Glioblastoma Growth.

    PubMed

    Salzano, G; Zappavigna, S; Luce, A; D'Onofrio, N; Balestrieri, M L; Grimaldi, A; Lusa, S; Ingrosso, D; Artuso, S; Porru, M; Leonetti, C; Caraglia, M; De Rosa, G

    2016-04-01

    The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM. Our group previously developed self-assembling nanoparticles, also named PLCaPZ NPs, to use ZOL in the treatment of prostate cancer. Here, we updated the previously developed nanoparticles (NPs) by designing transferrin (Tf)-targeted self-assembling NPs, also named Tf-PLCaPZ NPs, to use ZOL in the treatment of brain tumors, e.g., GBM. The efficacy of Tf-PLCaPZ NPs was evaluated in different GBM cell lines and in an animal model of GBM, in comparison with PLCaPZ NPs and free ZOL. Tf-PLCaPZ NPs were characterized by a narrow size distribution and a high incorporation efficiency of ZOL. Moreover, the presence of Tf significantly reduced the hemolytic activity of the formulation. In vitro, in LN229 cells, a significant uptake and cell growth inhibition after treatment with Tf-PLCaPZ NPs was achieved. Moreover, the sequential therapy of TMZ and Tf-PLCaPZ NPs lead to a superior therapeutic activity compared to their single administration. The results obtained in mice xenografted with U373MG, revealed a significant anticancer activity of Tf-PLCaPZ NPs, while the tumors remained unaffected with free TMZ. These promising results introduce a novel type of easy-to-obtain NPs for the delivery of ZOL in the treatment of GBM tumors.

  8. Transferrin-Targeted Nanoparticles Containing Zoledronic Acid as a Potential Tool to Inhibit Glioblastoma Growth.

    PubMed

    Salzano, G; Zappavigna, S; Luce, A; D'Onofrio, N; Balestrieri, M L; Grimaldi, A; Lusa, S; Ingrosso, D; Artuso, S; Porru, M; Leonetti, C; Caraglia, M; De Rosa, G

    2016-04-01

    The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM. Our group previously developed self-assembling nanoparticles, also named PLCaPZ NPs, to use ZOL in the treatment of prostate cancer. Here, we updated the previously developed nanoparticles (NPs) by designing transferrin (Tf)-targeted self-assembling NPs, also named Tf-PLCaPZ NPs, to use ZOL in the treatment of brain tumors, e.g., GBM. The efficacy of Tf-PLCaPZ NPs was evaluated in different GBM cell lines and in an animal model of GBM, in comparison with PLCaPZ NPs and free ZOL. Tf-PLCaPZ NPs were characterized by a narrow size distribution and a high incorporation efficiency of ZOL. Moreover, the presence of Tf significantly reduced the hemolytic activity of the formulation. In vitro, in LN229 cells, a significant uptake and cell growth inhibition after treatment with Tf-PLCaPZ NPs was achieved. Moreover, the sequential therapy of TMZ and Tf-PLCaPZ NPs lead to a superior therapeutic activity compared to their single administration. The results obtained in mice xenografted with U373MG, revealed a significant anticancer activity of Tf-PLCaPZ NPs, while the tumors remained unaffected with free TMZ. These promising results introduce a novel type of easy-to-obtain NPs for the delivery of ZOL in the treatment of GBM tumors. PMID:27301207

  9. Cost–utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels

    PubMed Central

    Lamond, N.W.D.; Skedgel, C.; Rayson, D.; Younis, T.

    2015-01-01

    Background Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost–utility (cu) of this therapy could help to determine its role in clinical practice. Methods Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters. Results Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained. Conclusions Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds. PMID:26300674

  10. Osteoclasts but not osteoblasts are affected by a calcified surface treated with zoledronic acid in vitro

    SciTech Connect

    Schindeler, Aaron . E-mail: AaronS@chw.edu.au; Little, David G.

    2005-12-16

    Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. Recent interest has centered on the effects of bisphosphonates on osteoblasts. Chronic dosing of osteoblasts with solubilized bisphosphonates has been reported to enhance osteogenesis and mineralization in vitro. However, this methodology poorly reflects the in vivo situation, where free bisphosphonate becomes rapidly bound to mineralized bone surfaces. To establish a more clinically relevant cell culture model, we cultured bone cells on calcium phosphate coated quartz discs pre-treated with the potent nitrogen-containing bisphosphonate, zoledronic acid (ZA). Binding studies utilizing [{sup 14}C]-labeled ZA confirmed that the bisphosphonate bound in a concentration-dependent manner over the 1-50 {mu}M dose range. When grown on ZA-treated discs, the viability of bone-marrow derived osteoclasts was greatly reduced, while the viability and mineralization of the osteoblastic MC3T3-E1 cell line were largely unaffected. This suggests that only bone resorbing cells are affected by bound bisphosphonate. However, this system does not account for transient exposure to unbound bisphosphonate in the hours following a clinical dosing. To model this event, we transiently treated osteoblasts with ZA in the absence of a calcified surface. Osteoblasts proved highly resistant to all transitory treatment regimes, even when utilizing ZA concentrations that prevented mineralization and/or induced cell death when dosed chronically. This study represents a pharmacologically more relevant approach to modeling bisphosphonate treatment on cultured bone cells and implies that bisphosphonate therapies may not directly affect osteoblasts at bone surfaces.

  11. Cancellous bone healing around strontium-doped hydroxyapatite in osteoporotic rats previously treated with zoledronic acid.

    PubMed

    Li, Yunfeng; Shui, Xueping; Zhang, Li; Hu, Jing

    2016-04-01

    Bisphosphonates (BPs) are potent anti-osteoporotic agents. Strontium-doped hydroxyapatite (HA) (SrHA) has been reported to increase bone density and improve trabecular microarchitecture in osteoporotic animals. But information about the effect of SrHA on the surrounding bone tissue in osteoporotic animals previously on BPs treatment is limited. We hypothesize that SrHA will induce increased bone density in the vicinity of the material when compared to HA, even in osteoporotic animals previously treated with BPs. HA and 10%SrHA (HA with 10 mol % calcium substituted by strontium) implants were prepared and characterized by scanning electronic microscopy (SEM), X-ray photoemission spectroscopy (XPS), and X-ray diffraction (XRD). Osteoporotic animal model was established by bilateral ovariectomy. Twelve weeks later, all OVX rats accepted subcutaneous injection of zoledronic acid (ZOL) at the dose of 1.5 μg/kg weekly for another twelve weeks. Subsequently, rod-shaped HA and SrHA implants were inserted in the distal femur of the OVX animals previously treated with ZOL. Eight weeks after implantation, specimens were harvested for histological and micro-computed tomography (micro-CT) analysis. Compared to HA, 10%SrHA raised the percent bone volume by 32.7%, the mean trabecular thickness by 36.5%, the mean trabecular number by 34.3%, the mean connectivity density by 38.4%, while the mean trabecular separation showed no significant difference. 10%SrHA also increased the bone area density by 36.3% in histological analysis. Results from this study indicated that 10%SrHA increased bone density and improved trabecular microarchitecture around implants in osteoporotic animals previously treated with ZOL when compared to HA. PMID:25891947

  12. Guided bone regeneration with local zoledronic acid and titanium barrier: An experimental study

    PubMed Central

    Dundar, Serkan; Ozgur, Cem; Yaman, Ferhan; Cakmak, Omer; Saybak, Arif; Ozercan, Ibrahim Hanifi; Alan, Hilal; Artas, Gokhan; Nacakgedigi, Onur

    2016-01-01

    The aim of this study was to evaluate the effects on new bone formation of autogenous blood alone or in combination with zoledronic acid (ZA), a β-tricalcium phosphate (β-TCP) graft or ZA plus a β-TCP graft placed under titanium barriers. For this purpose, eight adult male New Zealand white rabbits were used in the study, each with four titanium barriers fixed around four sets of nine holes drilled in the calvarial bones. The study included four groups, each containing 2 rabbits. In the autogenous blood (AB group), only autogeneous blood was placed under the titanium barriers. The three experimental groups were the AB+ZA group, with autogenous blood plus ZA, the AB+β-TCP group, with autogeneous blood plus a β-TCP graft, and the AB+β-TCP+ZA group, with autogeneous blood plus a β-TCP graft and ZA mixture under the titanium barriers. The animals were sacrificed after 3 months. The amounts of new bone formation identified histomorphometrically were found to be higher after 3 months than at the time of surgery in all groups. The differences between the groups were examined with histomorphometric analysis, and statistically significant differences were identified at the end of the 3 months. The bone formation rate in the AB+β-TCP+ZA group was determined to be significantly higher than that in the other groups (P<0.05). In the AB+ZA and AB+β-TCP groups, the bone formation rate was determined to be significantly higher than that in the AB group (P<0.05). No statistically significant difference in bone formation rate was observed between the AB+β-TCP and AB+ZA groups. Local ZA used with autogeneous blood and/or graft material appears to be a more effective method than the use of autogeneous blood or graft alone in bone augmentation executed with a titanium barrier. PMID:27698687

  13. Guided bone regeneration with local zoledronic acid and titanium barrier: An experimental study

    PubMed Central

    Dundar, Serkan; Ozgur, Cem; Yaman, Ferhan; Cakmak, Omer; Saybak, Arif; Ozercan, Ibrahim Hanifi; Alan, Hilal; Artas, Gokhan; Nacakgedigi, Onur

    2016-01-01

    The aim of this study was to evaluate the effects on new bone formation of autogenous blood alone or in combination with zoledronic acid (ZA), a β-tricalcium phosphate (β-TCP) graft or ZA plus a β-TCP graft placed under titanium barriers. For this purpose, eight adult male New Zealand white rabbits were used in the study, each with four titanium barriers fixed around four sets of nine holes drilled in the calvarial bones. The study included four groups, each containing 2 rabbits. In the autogenous blood (AB group), only autogeneous blood was placed under the titanium barriers. The three experimental groups were the AB+ZA group, with autogenous blood plus ZA, the AB+β-TCP group, with autogeneous blood plus a β-TCP graft, and the AB+β-TCP+ZA group, with autogeneous blood plus a β-TCP graft and ZA mixture under the titanium barriers. The animals were sacrificed after 3 months. The amounts of new bone formation identified histomorphometrically were found to be higher after 3 months than at the time of surgery in all groups. The differences between the groups were examined with histomorphometric analysis, and statistically significant differences were identified at the end of the 3 months. The bone formation rate in the AB+β-TCP+ZA group was determined to be significantly higher than that in the other groups (P<0.05). In the AB+ZA and AB+β-TCP groups, the bone formation rate was determined to be significantly higher than that in the AB group (P<0.05). No statistically significant difference in bone formation rate was observed between the AB+β-TCP and AB+ZA groups. Local ZA used with autogeneous blood and/or graft material appears to be a more effective method than the use of autogeneous blood or graft alone in bone augmentation executed with a titanium barrier.

  14. Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts

    PubMed Central

    KOMATSU, YUKO; IBI, MIHO; CHOSA, NAOYUKI; KYAKUMOTO, SEIKO; KAMO, MASAHARU; SHIBATA, TOSHIYUKI; SUGIYAMA, YOSHIKI; ISHISAKI, AKIRA

    2016-01-01

    Bisphosphonates (BPs) are analogues of pyro-phosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF-β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF-β-induced promotion of cell viability, ii) the TGF-β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF-β-induced migratory activity of hGFs and iv) the expression level of TGF-β type I receptor on the surfaces of hGFs, as well as the TGF-β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF-β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad-dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. PMID:27176567

  15. A successful treatment of hypercalcemia with zoledronic acid in a 15-year-old boy with acute lymphoblastic leukemia

    PubMed Central

    Park, Hye-Jin; Choi, Eun-Jin

    2016-01-01

    Severe hypercalcemia in children is a rare medical emergency. We present a case of a 15-year-old boy with hypercalcemia (total calcium level, 14.2 mg/dL) with a normal complete blood count, no circulating blasts in the peripheral blood film, and no other signs of acute lymphoblastic leukemia (ALL), including no signs of lymphadenopathy or hepatosplenomegaly. The hypercalcemia was successfully treated with zoledronic acid. As hypercalcemia can be the only presenting symptom of ALL in children, the diagnosis is often delayed. In children presenting with hypercalcemia, malignancies must be considered in the differential diagnosis. PMID:27462588

  16. Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws

    PubMed Central

    Sarkarat, Farzin; Kalantar Motamedi, Mohammad Hosein; Jahanbani, Jahanfar; Sepehri, Dena; Kahali, Roozbeh; Nematollahi, Zahra

    2014-01-01

    Background: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a well-known challenging entity warranting management. Platelet-Rich Plasma (PRP) plays an important role in bone biology by enhancing bone repair and regeneration. Objectives: The aim of this animal study was to evaluate the effects of PRP on zoledronic acid-induced BRONJ. Materials and Methods: Seven rats were given 0.04 mg Zoledronic acid intravenously once a week for five weeks. Two weeks later, the animals underwent extraction of their first lower molars, bilaterally. After clinical confirmation of the osteonecrosis, PRP was injected randomly into one of the extraction sockets of each rat. Three weeks later, all rats were sacrificed in order to obtain histological sections. The analysis of epithelialization was performed by McNamar’s test, and the analysis of osteogenesis and angiogenesis was performed by the Wilcoxon Sign Rank test. P value was set at 0.05. Results: We found no significant differences between the two groups regarding the amount of epithelialization, angiogenesis or sequestrum formation (P > 0.05), but a significant difference was seen between the two groups regarding the amount of existing vital bone (P < 0.05). Conclusions: Our study demonstrates positive results (preservation or regeneration of bone) using PRP in treatment of BRONJ. Although PRP may enhance osseous regeneration, long-term follow-ups are required to confirm its benefits. PMID:25032151

  17. [Evidences of safety and tolerability of the zoledronic acid 5 mg yearly in the post-menopausal osteoporosis: the HORIZON project].

    PubMed

    Dalle Carbonare, L; Bertoldo, F; Lo Cascio, V

    2009-01-01

    Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Despite evidence supporting the anti-fracture efficacy of aminobisphosphonates approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within the first year. Poor compliance is associated with negative outcomes, including increased fracture risk. Tolerability and safety are among the causes of poor compliance. Intravenous bisphosphonates avoids the gastrointestial intolerance and the complex dosing instruction of the oral route ensuring full compliance which may provide improved efficacy. However, there are some concerns regarding potent intravenous bisphosphonates as zoledronic acid with respect to tolerability, mainly the acute phase response and to safety, mainly a theoretical risk of over suppression of bone turnover, renal toxicity and osteonecrosis of the jaw. In the HORIZON study, 152 patients on active treatment (82) or placebo (70) underwent to a bone biopsy after double tetracycline labeling. Bone biopsies (iliac crest) were obtained at the final visit at month 36, 1 year after the last infusion. The biopsies were analyzed by histomorphometry on bone sections and by micro-CT (microCT) analysis. One hundred forthy-three biopsies (76 zoledronic acid, 67 placebo) had at least one microCT parameter measured and 111 were available for quantitative histomorphometry (59 zoledronic acid, 52 placebo). Micro-CT analysis of bone structure revealed higher trabecular bone volume (BV/TV), decreased trabecular separation (Tb.Sp), and a strong trend towards improvement in connectivity density in biopsies obtained from patients treated with zoledronic acid, indicating preservation of trabecular bone structure with respect to placebo. Histomorphometric analysis obtained from patients treated with zoledronic acid exhibited reduction of bone turnover, as suggested by decreased activation frequency (Ac.F) by 63%, mineralizing

  18. Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits.

    PubMed

    Qi, Mengchun; Hu, Jing; Li, Jianping; Li, Jinyuan; Dong, Wei; Feng, Xiaojie; Yu, Jing

    2012-01-01

    One main problem associated with alveolar bone augmentation in implant dentistry is resorption of grafted bone, which may be further compromised by systemic skeletal disorders such as osteoporosis. Zoledronate acid (ZOL) is the most potent bisphosphonate to treat osteoporosis and therefore it is hypothesized to be able to invert the negative effect of osteoporosis on osseointegration and fixation of dental implants in autologous bone grafts. In this study, 56 rabbits received bilateral ovariectomy (OVX) (40 rabbits) or sham operation (16 rabbits). Three months later, 8 animals from each group were sacrificed for bone mineral density (BMD) examination. Then the remaining animals underwent bilateral autologous iliac bone grafting with simultaneous implantation of titanium implants in tibiae and were divided into 5 groups (n=8): Sham, OVX, Loc-ZOL (local treatment), Sys-ZOL (systemic treatment) and Loc+Sys-ZOL (local plus systemic) group. At 3 months after implantation, all animals were sacrificed and specimens were harvested for examinations. Both BMD and histological examinations of femurs showed osteoporotic changes after ovariectomy, while systemic treatment with ZOL restored mineralized bone. Micro-CT examination demonstrated that OVX group showed significant decrease of mineralized bone and implant-bone contact when compared with sham control, whereas both systemic and local treatments of ZOL significantly increased mineralized bone and implant-bone contact in ovariectomized animals. However, the best effects were observed in Loc+Sys-ZOL group (combined use of ZOL) and most of bone indices were similar to (IBCR, p>0.05) or higher than (BV/TV, Conn.D and Tb.N) (p<0.01) those of the sham group, except Tb.Th, which was still significantly lower (p<0.01), and Tb.Sp, which was further decreased (p<0.01). The aforementioned effects were also confirmed by histomorphometric analysis of bone indices on implant-bone contact and mineralized bone. In addition, biomechanical

  19. Efficacy and Safety of Single Dose Zoledronic Acid for Osteoporosis in Frail Seniors: A Randomized Clinical Trial

    PubMed Central

    Greenspan, Susan L.; Perera, Subashan; Ferchak, Mary Anne; Nace, David A.; Resnick, Neil M.

    2016-01-01

    Importance 85% of institutionalized elderly have osteoporosis, with fracture rates 8–9 fold higher than observed among community-dwelling elderly. Yet most are untreated and excluded from pivotal osteoporosis trials. Objective Determine the efficacy and safety of zoledronic acid in frail elderly women. Design 2-year, randomized, placebo-controlled, double-blinded study conducted between December 2007 and March 2012. Setting Nursing home and assisted living facilities. Participants 181 women ≥ age 65 with osteoporosis including those with cognitive impairment, immobility, and multimorbidity. Intervention One 5 mg dose of zoledronic acid or placebo IV and daily calcium and vitamin D. Main Outcomes (1) Hip and spine bone mineral density (BMD) at 12 and 24 months and (2) adverse events. Results There were no baseline differences in age (mean=85.4±0.6 years), BMD, or functional or cognitive status, but the treatment group included more subjects with frailty, falls history, diabetes, and anticonvulsant use. BMD was available for 87% of participants at 12 months and 73% at 24 months. BMD changes were greater in the treatment group (p< 0.01): 3.2 ± 0.7 and 3.9 ± 0.7 percentage point differences (mean ± SE) in the total hip at 12 and 24 months respectively, and 1.8 ± 0.7 and 3.6 ± 0.7 at the spine (p<0.01); adjusted analyses were similar. The treatment and placebo groups’ fracture rates were 20% and 16%, respectively (OR=1.30; 95% CI=0.61–2.78); mortality rates were 16% and 13% (OR=1.24; 95% CI=0.54–2.86). Groups did not differ in the proportion of single fallers (28% vs. 24%; OR=1.24; 95% CI=0.64–2.42; p=0.52) but more subjects in the treatment group had multiple falls (49% vs. 35%; OR=1.83; 95% CI=1.01–3.33; p=0.047); this was no longer significant when adjusted for baseline frailty. Conclusions and Relevance In this group of frail, osteoporotic women, one dose of zoledronic acid improved BMD over 2 years. The clinical importance of nonsignificant

  20. Mechanisms of the antitumor activity of human Vγ9Vδ2 T cells in combination with zoledronic acid in a preclinical model of neuroblastoma.

    PubMed

    Di Carlo, Emma; Bocca, Paola; Emionite, Laura; Cilli, Michele; Cipollone, Giuseppe; Morandi, Fabio; Raffaghello, Lizzia; Pistoia, Vito; Prigione, Ignazia

    2013-05-01

    Low expression of surface major histocompatibility complex (MHC) class I molecules and defects in antigen processing machinery make human neuroblastoma (NB) cells appropriate targets for MHC unrestricted immunotherapeutic approaches. Human T-cell receptor (TCR) Vγ9Vδ2 lymphocytes exert MHC-unrestricted antitumor activity and are activated by phosphoantigens, whose expression in cancer cells is increased by aminobisphosphonates. With this background, we have investigated the in vivo anti-NB activity of human Vγ9Vδ2 lymphocytes and zoledronic acid (ZOL). SH-SY-5Y human NB cells were injected in the adrenal gland of immunodeficient mice. After 3 days, mice received ZOL or human Vγ9Vδ2 T cells or both agents by intravenous administration once a week for 4 weeks. A significantly improved overall survival was observed in mice receiving Vγ9Vδ2 T cells in combination with ZOL. Inhibition of tumor cell proliferation, angiogenesis and lymphangiogenesis, and increased tumor cell apoptosis were detected. Vγ9Vδ2 T lymphocytes were attracted to NB-tumor masses of mice receiving ZOL where they actively modified tumor microenvironment by producing interferon-γ (IFN-γ), that in turn induced CXCL10 expression in NB cells. This study shows that human Vγ9Vδ2 T cells and ZOL in combination inhibit NB growth in vivo and may provide the rationale for a phase I clinical trial in patients with high-risk NB.

  1. The enhancement of radiosensitivity in human esophageal squamous cell carcinoma cells by zoledronic acid and its potential mechanism.

    PubMed

    You, Yanjie; Liu, Jianfeng; Wang, Zhizhong; Zhang, Yuan; Ran, Yonggang; Guo, Xu; Liu, Huimin; Wang, Haibo

    2014-01-01

    Esophageal squamous cell carcinoma (ESCC) has a low 5-year patient survival rate. Radiotherapy, as a preoperative or postoperative treatment of surgery, has a crucial role in improving local control and survival of ESCC. Various chemotherapeutic and biologic agents have been used as radio-sensitizers in combination with radiotherapy. Here, we demonstrate that zoledronic acid (ZOL) has a radio-sensitizing effect on ESCC cells. Exposure of ESCC cancer cells to ZOL plus radiation resulted in increased cell death through arresting the cell cycle between S and G2/M phases. ZOL appeared to inhibit proliferation, tube formation and invasion of endothelial cells. These anti-angiogenetic effects were more marked concurrently with irradiation. In addition, synergistic suppressive effects on VEGF expression were observed after combined treatment. Our data suggest that the combination of ZOL and radiation is a promising therapeutic strategy to enhance radiation therapy for ESCC patients.

  2. Randomized Controlled Trial of Zoledronic Acid plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment of HER2-Negative Primary Breast Cancer (JONIE Study)

    PubMed Central

    Hasegawa, Yoshie; Tanino, Hirokazu; Horiguchi, Jun; Miura, Daishu; Ishikawa, Takashi; Hayashi, Mitsuhiro; Takao, Shintaro; Kim, Seung Jin; Yamagami, Kazuhiko; Miyashita, Masaru; Konishi, Muneharu; Shigeoka, Yasushi; Suzuki, Masato; Taguchi, Tetsuya; Kubota, Tomoyuki; Akazawa, Kouhei; Kohno, Norio

    2015-01-01

    Purpose Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT). Methods Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2), followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug. Results This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher’s exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher’s exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in

  3. Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone

    NASA Astrophysics Data System (ADS)

    Mergoni, Giovanni; Merigo, Elisabetta; Passerini, Pietro; Corradi, Domenico; Maestri, Roberta; Bussolati, Ovidio; Bianchi, Massimiliano; Sala, Roberto; Govoni, Paolo; Namour, Samir; Vescovi, Paolo

    2016-03-01

    Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (P<0.001). Rats of groups L and T+L showed a significant higher expression of osteocalcin compared to rats of groups C and T (C=0.3993; L=1.394; T=0.2922; T+L=1.156; P=0.0001). The expression of osteopontin did not show significant differences in the groups treated with Nd:YAG compared to the ones that did not receive laser irradiation. Conclusion Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of

  4. The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)

    PubMed Central

    Black, Dennis M; Reid, Ian R; Boonen, Steven; Bucci-Rechtweg, Christina; Cauley, Jane A; Cosman, Felicia; Cummings, Steven R; Hue, Trisha F; Lippuner, Kurt; Lakatos, Peter; Leung, Ping Chung; Man, Zulema; Martinez, Ruvie Lou Maria; Tan, Monique; Ruzycky, Mary Ellen; Su, Guoqin; Eastell, Richard

    2012-01-01

    Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue

  5. Differential Effects of Teriparatide and Zoledronic Acid on Bone Mineralization Density Distribution at 6 and 24 Months in the SHOTZ Study.

    PubMed

    Dempster, David W; Roschger, Paul; Misof, Barbara M; Zhou, Hua; Paschalis, Eleftherios P; Alam, Jahangir; Ruff, Valerie A; Klaushofer, Klaus; Taylor, Kathleen A

    2016-08-01

    The Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study assessed the progressive effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone remodeling and material properties in postmenopausal women with osteoporosis. Previously, we reported that biochemical and histomorphometric bone formation indices were significantly higher in patients receiving TPTD versus ZOL. Here we report bone mineralization density distribution (BMDD) results based on quantitative backscattered electron imaging (qBEI). The 12-month primary study was randomized and double blind until the month 6 biopsy, then open label. Patients (TPTD, n = 28; ZOL, n = 31) were then eligible to enter a 12-month open-label extension with their original treatment: TPTD 20 μg/d (subcutaneous injection) or ZOL 5 mg/yr (intravenous infusion). A second biopsy was collected from the contralateral side at month 24 (TPTD, n = 10; ZOL, n = 10). In cancellous bone, ZOL treatment was associated at 6 and 24 months with significantly higher average degree of mineralization (CaMEAN, +2.2%, p = 0.018; +3.9%, p = 0.009, respectively) and with lower percentage of low mineralized areas (CaLOW , -34.6%, p = 0.029; -33.7%, p = 0.025, respectively) and heterogeneity of mineralization CaWIDTH (-12.3%, p = 0.003; -9.9%, p = 0.012, respectively), indicating higher mineralization density and more homogeneous mineral content versus TPTD. Within the ZOL group, significant changes were found in all parameters from month 6 to 24, indicating a progressive increase in mineralization density. In sharp contrast, mineralization density did not increase over time with TPTD, reflecting ongoing deposition of new bone. Similar results were observed in cortical bone. In this study, TPTD stimulated new bone formation, producing a mineralized bone matrix that remained relatively heterogeneous with a stable mean mineral content. ZOL slowed bone turnover

  6. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    PubMed Central

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    %) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23–184). Median follow-up was 43 months (IQR 30–60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79–1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66–0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69–0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3–5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. Funding Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research. PMID:26719232

  7. Concurrent use of Sr-89 chloride with zoledronic acid is safe and effective for breast cancer patients with painful bone metastases

    PubMed Central

    YAMADA, KIMITO; YOSHIMURA, MANA; KAISE, HIROSHI; OGATA, AKIHIKO; UEDA, NAOKO; TOKUUYE, KOICHI; KOHNO, NORIO

    2012-01-01

    Our aim in this study was to examine the safety and efficacy of the concurrent use of the radiopharmaceutical strontium-89 (Sr-89) chloride with zoledronic acid in standard anticancer therapy for breast cancer patients with painful multifocal bone metastases. The study comprised 16 breast cancer patients with painful multifocal bone metastases detected by bone scintigraphy, computed tomography or magnetic resonance imaging. All patients were treated with Sr-89 and zoledronic acid concurrently between March 2007 and February 2011 as part of a standard therapeutic regimen comprising chemotherapy, endocrine therapy, molecular targeting therapy and targeted radiotherapy. Sr-89 was administered intravenously at 2 MBq/kg to a maximum of 141 MBq per person. Safety was evaluated according to myelotoxicity as measured by the Common Terminology Criteria for Adverse Events (v3.0). To assess treatment efficacy, we monitored changes in analgesic drug dosages. Furthermore, bremsstrahlung imaging after the administration of Sr-89 was utilized to examine the relationship between the accumulation of Sr-89 in metastatic sites and treatment efficacy. Based on the results, a total of 14 out of 16 patients (88%) reported bone pain relief, indicating a high efficacy of Sr-89 combined with zoledronic acid. In responsive cases, a strong uptake of Sr-89 was observed on bremsstrahlung imaging at the same sites indicated by 99mTc bone scintigraphy. Moreover, severe myelosuppression (> grade 3) was not observed, and adverse events were tolerable. In conclusion, the use of Sr-89 with zoledronic acid in breast cancer patients with painful bone metastases was safe and effective when administered concurrently with other standard therapies. In the future, the treatment with Sr-89 at the early stage should be considered, and a large-scale clinical study should be conducted. PMID:22969873

  8. Potential Usefulness of BMD and Bone Turnover Monitoring of Zoledronic Acid Therapy Among Women With Osteoporosis: Secondary Analysis of Randomized Controlled Trial Data.

    PubMed

    Bell, Katy Jl; Hayen, Andrew; Glasziou, Paul; Irwig, Les; Eastell, Richard; Harrison, Stephanie L; Black, Dennis M; Bauer, Douglas C

    2016-09-01

    We aimed to compare the clinical validity and the detectability of response of short-term changes in bone mineral density (BMD; hip and spine) and bone turnover markers (serum PINP and CTX) through secondary analysis of trial data. We analyzed data on 7765 women with osteoporosis randomized to 5-mg once-yearly infusions of zoledronic acid or placebo in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT; trial ran from 2002 to 2006) and the first extension trial (trial ran from 2006 to 2009). We assessed the clinical validity and detectability of response for 1-year measurements of the following monitoring tests: total hip and lumbar spine BMD, serum N-terminal propeptide of type I collagen (sPINP), and serum C-telopeptide of type I collagen (sCTX; 6-month measurement used). Clinical validity was assessed by examining prediction of clinical fracture in Cox models; detectability of response to treatment was assessed by the ratio of signal to noise, estimated from the distributions of change in zoledronic acid and placebo groups. Baseline measurements were available for 7683 women with hip BMD, 558 with spine BMD, 1246 with sPINP, and 517 women with sCTX. Hip BMD and sPINP ranked highly for prediction of clinical fracture, whereas sPINP and sCTX ranked highly for detectability of response to treatment. Serum PINP had the highest overall ranking. In conclusion, serum PINP is potentially useful in monitoring response to zoledronic acid. Further research is needed to evaluate the effects of monitoring PINP on treatment decisions and other clinically relevant outcomes. © 2016 American Society for Bone and Mineral Research. PMID:27027655

  9. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    PubMed Central

    Dalle Carbonare, Luca; Zanatta, Mirko; Gasparetto, Adriano; Valenti, Maria Teresa

    2010-01-01

    Bisphosphonates (BPs) are widely used in the treatment of postmenopausal osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively). The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis), and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes. PMID:21701624

  10. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    NASA Astrophysics Data System (ADS)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  11. Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors

    PubMed Central

    Kopecka, Joanna; Porto, Stefania; Lusa, Sara; Gazzano, Elena; Salzano, Giuseppina; Pinzòn-Daza, Martha Leonor; Giordano, Antonio; Desiderio, Vincenzo; Ghigo, Dario; De Rosa, Giuseppe; Caraglia, Michele; Riganti, Chiara

    2016-01-01

    The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking. The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo. We tested its efficacy in combination with doxorubicin in breast tumors refractory to chemotherapy and immune system recognition as a new combinatorial approach to produce chemo- and immunosensitization. NZ reduced the IC50 of doxorubicin in human and murine chemoresistant breast cancer cells and restored the doxorubicin efficacy against chemo-immunoresistant tumors implanted in immunocompetent mice. By reducing the metabolic flux through the mevalonate pathway, NZ lowered the activity of Ras/ERK1/2/HIF-1α axis and the expression of P-glycoprotein, decreased the glycolysis and the mitochondrial respiratory chain, induced a cytochrome c/caspase 9/caspase 3-dependent apoptosis, thus restoring the direct cytotoxic effects of doxorubicin on tumor cell. Moreover, NZ restored the doxorubicin-induced immunogenic cell death and reversed the tumor-induced immunosuppression due to the production of kynurenine, by inhibiting the STAT3/indoleamine 2,3 dioxygenase axis. These events increased the number of dendritic cells and decreased the number of immunosuppressive T-regulatory cells infiltrating the tumors. Our work proposes the use of nanoparticle encapsulating zoledronic acid as an effective tool overcoming at the same time chemoresistance and immunoresistance in breast tumors, thanks to the effects exerted on tumor cell and tumor-infiltrating immune cells. PMID:26980746

  12. Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors.

    PubMed

    Kopecka, Joanna; Porto, Stefania; Lusa, Sara; Gazzano, Elena; Salzano, Giuseppina; Pinzòn-Daza, Martha Leonor; Giordano, Antonio; Desiderio, Vincenzo; Ghigo, Dario; De Rosa, Giuseppe; Caraglia, Michele; Riganti, Chiara

    2016-04-12

    The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking.The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo. We tested its efficacy in combination with doxorubicin in breast tumors refractory to chemotherapy and immune system recognition as a new combinatorial approach to produce chemo- and immunosensitization.NZ reduced the IC50 of doxorubicin in human and murine chemoresistant breast cancer cells and restored the doxorubicin efficacy against chemo-immunoresistant tumors implanted in immunocompetent mice. By reducing the metabolic flux through the mevalonate pathway, NZ lowered the activity of Ras/ERK1/2/HIF-1α axis and the expression of P-glycoprotein, decreased the glycolysis and the mitochondrial respiratory chain, induced a cytochrome c/caspase 9/caspase 3-dependent apoptosis, thus restoring the direct cytotoxic effects of doxorubicin on tumor cell. Moreover, NZ restored the doxorubicin-induced immunogenic cell death and reversed the tumor-induced immunosuppression due to the production of kynurenine, by inhibiting the STAT3/indoleamine 2,3 dioxygenase axis. These events increased the number of dendritic cells and decreased the number of immunosuppressive T-regulatory cells infiltrating the tumors.Our work proposes the use of nanoparticle encapsulating zoledronic acid as an effective tool overcoming at the same time chemoresistance and immunoresistance in breast tumors, thanks to the effects exerted on tumor cell and tumor-infiltrating immune cells. PMID:26980746

  13. Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

    PubMed Central

    Kato, Junko; Kanematsu, Masako; Gaowa, Siqin; Mori, Ryutaro; Tanahashi, Toshiyuki; Matsuhashi, Nobuhisa; Yoshida, Kazuhiro

    2016-01-01

    Targeted molecular therapy is an effective anticancer strategy. Anti‐EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild‐type KRAS. However, their efficacy in patients with KRAS mutations has not been established. Therefore, we investigated whether CTX treatment was effective as a single agent or in combination with zoledronic acid (ZOL) in human CRC cell lines with different KRAS status. CRC cell lines SW48 (wild‐type KRAS) and LS174T (mutant KRAS) were treated with ZOL, CTX and a combination of both drugs. Cytotoxicity was measured using the MTT assay. Changes in the levels of intracellular signaling proteins were evaluated using western blot analysis. Finally, we evaluated the efficacy of the combination treatment in an in vivo xenograft model. We observed that ZOL apparently inhibited growth in both cell lines, whereas CTX showed little effect. ZOL also increased the levels of unprenylated RAS. Combined ZOL and CTX treatment was synergistic in both cell lines and was associated with inhibition of the RAS‐MAPK and AKT‐mTOR signaling pathways. Furthermore, the combination treatment was more effective in suppressing the growth of xenografts derived from both SW48 and LS174T cells; this effect was associated with increased apoptosis. These results demonstrate that ZOL inhibits the growth of colon cancer cells regardless of KRAS status, and combination therapy using ZOL and CTX enhances this growth suppression. These findings suggest a novel strategy for the treatment of CRC independent of KRAS mutational status. PMID:26437179

  14. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer.

    PubMed

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

  15. Effect of a local, one time, low-dose injection of zoledronic acid on titanium implant osseointegration in ovariectomized rats

    PubMed Central

    Ying, Gao; Bo, Lian; Yanjun, Jiao; Lina, Wu

    2016-01-01

    Introduction Local application of bisphosphonates has been proven to be safer than systemic administration to promote implant fixation. The objective of this study was to introduce such a simple, convenient and efficient method to enhance titanium (Ti) implant osseointegration in ovariectomized (OVX) rats. Material and methods Twenty female Sprague-Dawley rats sequentially underwent bilateral ovariectomy and tibia implantation, and injection of 30 µg/implant zoledronic acid (ZOL) at the site of implantation was performed. At the end of the study, the tibiae, mandibles, femurs and vertebrae were harvested for dual energy X-ray absorptiometry, histology and micro-computed tomography examination. Results Ovariectomized rats showed poor bone density, bone mass and trabecular microstructure. OVX + ZOL rats were characterized by significantly improved peri-implant bone area (1.72-fold), bone contact (2.30-fold), bone mineral density (1.57-fold) and bone mineral content (1.67-fold), as well as moderately increased bone volume to total volume ratio (1.34-fold), percentage osteointegration (1.54-fold), connectivity density (1.45-fold), and trabecular number (1.43-fold), but decreased trabecular separation (57.69%) when compared with the control levels (p < 0.05). No histological signs of jaw osteonecrosis were observed in the rats treated with ZOL, and there was no significant difference between the OVX group and OVX + ZOL group in the bone mass of the mandible, femur and 5th lumbar vertebra (p > 0.05). In addition, the overproduction of osteoporosis-induced advanced glycation end-products (AGEs) was completely prevented by local treatment with 30 µg/implant ZOL. Conclusions A local, one time, low-dose injection of ZOL at the site of implantation is able to promote the osseointegration of Ti implants following postmenopausal osteoporosis, and this action may be partly mediated by inhibition of the osteoporosis-induced AGE overproduction in the bone marrow. PMID:27695483

  16. Effect of a local, one time, low-dose injection of zoledronic acid on titanium implant osseointegration in ovariectomized rats

    PubMed Central

    Ying, Gao; Bo, Lian; Yanjun, Jiao; Lina, Wu

    2016-01-01

    Introduction Local application of bisphosphonates has been proven to be safer than systemic administration to promote implant fixation. The objective of this study was to introduce such a simple, convenient and efficient method to enhance titanium (Ti) implant osseointegration in ovariectomized (OVX) rats. Material and methods Twenty female Sprague-Dawley rats sequentially underwent bilateral ovariectomy and tibia implantation, and injection of 30 µg/implant zoledronic acid (ZOL) at the site of implantation was performed. At the end of the study, the tibiae, mandibles, femurs and vertebrae were harvested for dual energy X-ray absorptiometry, histology and micro-computed tomography examination. Results Ovariectomized rats showed poor bone density, bone mass and trabecular microstructure. OVX + ZOL rats were characterized by significantly improved peri-implant bone area (1.72-fold), bone contact (2.30-fold), bone mineral density (1.57-fold) and bone mineral content (1.67-fold), as well as moderately increased bone volume to total volume ratio (1.34-fold), percentage osteointegration (1.54-fold), connectivity density (1.45-fold), and trabecular number (1.43-fold), but decreased trabecular separation (57.69%) when compared with the control levels (p < 0.05). No histological signs of jaw osteonecrosis were observed in the rats treated with ZOL, and there was no significant difference between the OVX group and OVX + ZOL group in the bone mass of the mandible, femur and 5th lumbar vertebra (p > 0.05). In addition, the overproduction of osteoporosis-induced advanced glycation end-products (AGEs) was completely prevented by local treatment with 30 µg/implant ZOL. Conclusions A local, one time, low-dose injection of ZOL at the site of implantation is able to promote the osseointegration of Ti implants following postmenopausal osteoporosis, and this action may be partly mediated by inhibition of the osteoporosis-induced AGE overproduction in the bone marrow.

  17. Comparison of γδ T cell responses and farnesyl diphosphate synthase inhibition in tumor cells pretreated with zoledronic acid

    PubMed Central

    Idrees, Atif S. M.; Sugie, Tomoharu; Inoue, Chiyomi; Murata-Hirai, Kaoru; Okamura, Haruki; Morita, Craig T.; Minato, Nagahiro; Toi, Masakazu; Tanaka, Yoshimasa

    2013-01-01

    Summary Exposing human tumor cells to nitrogen-containing bisphosphonates (N-BPs), such as zoledronic acid (Zol), greatly increases their susceptibility to killing by γδ T cells. Based on this finding and other studies, cancer immunotherapy using γδ T cells and N-BPs has been studied in pilot clinical trials and has shown benefits. Although Zol treatment can render a wide variety of human tumor cells susceptible to γδ T cell killing, there has not been a systematic investigation to determine which types of tumor cells are the most susceptible to γδ T cell-mediated cytotoxicity. In this study, we determined the Zol concentrations required to stimulate half maximal tumor necrosis factor-α production by γδ T cells cultured with various tumor cell lines pretreated with Zol and compared these concentrations with those required for half maximal inhibition of farnesyl diphosphate synthase (FPPS) in the same tumor cell lines. The inhibition of tumor cell growth by Zol was also assessed. We found that FPPS inhibition strongly correlated with γδ T cell activation, confirming that the mechanism underlying γδ T cell activation by Zol is isopentenyl diphosphate (IPP) accumulation due to FPPS blockade. In addition, we showed that γδ TCR-mediated signaling correlated with γδ T cell tumor necrosis factor-α production and cytotoxicity. Some lymphoma, myeloid leukemia, and mammary carcinoma cell lines were relatively resistant to Zol treatment suggesting that assessing tumor sensitivity to Zol may help select those patients most likely to benefit from immunotherapy with γδ T cells. PMID:23387443

  18. Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

    PubMed Central

    Insalaco, Lavinia; Incorvaia, Lorena; Barraco, Nadia; Castiglia, Marta; Rizzo, Sergio; Santini, Daniele; Giordano, Antonio; Castorina, Sergio; Russo, Antonio

    2016-01-01

    Zoledronic acid (ZOL), belonging to third generation bisphosphonate family, is a potent inhibitor of osteoclast-mediated bone resorption, widely used to effectively prevent osteolysis in breast cancer patients who develop bone metastases. Low doses of ZOL have been shown to exhibit a direct anticancer role, by inhibiting cell adhesion, invasion, cytoskeleton remodelling and proliferation in MCF-7 breast cancer cells. In order to identify the molecular mechanisms and signaling pathways underlying the anticancer activity exerted by ZOL, we analyzed for the first time the microRNA expression profile in breast cancer cells. A large-scale microarray analysis of 377 miRNAs was performed on MCF7 cells treated with 10 μM ZOL for 24 h compared to untreated cells. Furthermore, the expression of specific ZOL-induced miRNAs was analyzed in MCF-7 and SkBr3 cells through Real-time PCR. Low-dose treatment with ZOL significantly altered expression of 54 miRNAs. Nine upregulated and twelve downregulated miRNAs have been identified after 24 h of treatment. Also, ZOL induced expression of 11 specific miRNAs and silenced expression of 22 miRNAs. MiRNA data analysis revealed the involvement of differentially expressed miRNAs in PI3K/Akt, MAPK, Wnt, TGF-β, Jak-STAT and mTOR signaling pathways, and regulation of actin cytoskeleton. Our results have been shown to be perfectly coherent with the recent findings reported in literature concerning changes in expression of some miRNAs involved in bone metastasis formation, progression, therapy resistance in breast cancer. In conclusion, this data supports the hypothesis that ZOL-induced modification of the miRNA expression profile contributes to the anticancer efficacy of this agent. PMID:27081088

  19. Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration

    PubMed Central

    2014-01-01

    Background Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Methods Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 106 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 μg/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. Results ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and −9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. Conclusion These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs. PMID:24612486

  20. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer

    PubMed Central

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

  1. L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer.

    PubMed

    Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

    2016-01-01

    Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients.

  2. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    PubMed Central

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  3. Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras-TAp73-G6PD axis in bladder cancer cells.

    PubMed

    Wang, Xiaolin; Wu, Guang; Cao, Guangxin; Yang, Lei; Xu, Haifei; Huang, Jian; Hou, Jianquan

    2015-09-01

    Zoledronic acid (ZA) is the current standard of care for the therapy of patients with bone metastasis or osteoporosis. ZA inhibits the prenylation of small guanosine‑5'-triphosphate (GTP)‑binding proteins, such as Ras, and thus inhibit Ras signaling. The present study demonstrated that ZA inhibited cell proliferation and the pentose phosphate pathway (PPP) in bladder cancer cells. In addition, the expression of glucose‑6‑phosphate dehydrogenase (G6PD, the rate‑limiting enzyme of the PPP) was found to be inhibited by ZA. Furthermore, the stability of TAp73, which activates the expression G6PD was decreased in zoledronic acid treated cells. Decreased levels of Ras‑GTP and phosphorylated‑extracellular signal-regulated kinase 1/2 were also observed following treatment with ZA. This may be due to the fact that activated Ras was reported to stabilize TAp73 inducing its accumulation. The inhibition of Ras activity by PT inhibitor II also significantly reduced the levels of TAp73 and G6PD and the PPP flux. Moreover, knockdown of TAp73, attenuated the PPP flux and eliminated the affection of ZA on the PPP flux. In conclusion, it was proposed that ZA can inhibit stability of TAp73 and attenuate the PPP via blocking Ras signaling in bladder cancer cells.

  4. Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT.

    PubMed

    Hansen, Stinus; Hauge, Ellen M; Beck Jensen, Jens-Erik; Brixen, Kim

    2013-04-01

    Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to detail effects on compartmental geometry, density, and microarchitecture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 µg sc daily, n = 18) or PTH 1-84 (100 µg sc daily, n = 20) for 18 months in an open-label, nonrandomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n = 33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32 ± 37%, PTH 1-84 39 ± 32%, both p < 0.001) and tibia (PTH 1-34 13 ± 27%, PTH 1-84 15 ± 22%, both p < 0.001) with corresponding declines in cortical density. With PTH 1-34, increases in cortical thickness in radius (2.0 ± 3.8%, p < 0.05) and tibia (3.8 ± 10.4%, p < 0.01) were found. Trabecular number increased in tibia with both PTH 1-34 (4.2 ± 7.1%, p < 0.05) and PTH 1-84 (5.3 ± 8.3%, p < 0.01). Zoledronic acid did not impact cortical porosity at either site but increased cortical thickness (3.0 ± 3.5%, p < 0.01), total (2.7 ± 2.5%, p < 0.001) and cortical density (1.5 ± 2.0%, p < 0.01) in tibia as well as trabecular volume fraction in radius (2.5 ± 5.1%, p < 0.05) and tibia (2.2 ± 2.2%, p < 0.01). FE estimated bone strength was preserved, but not increased, with PTH 1-34 and zoledronic acid at both sites, whereas it decreased with PTH 1-84 in radius (-2.8 ± 5.8%, p < 0.05) and tibia (-3.9 ± 4.8%, p < 0.001). Conclusively, divergent treatment-specific effects in cortical

  5. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    PubMed

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H; Hansen, Charlotte T; Jørgensen, Henrik B; Delaissé, Jean-Marie

    2013-08-01

    Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease-specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p < 0.000), osseous lesions (p < 0.001), and the preceding Zol dosing (p < 0.005) (r(2)  = 0.97). Comparing bone scintigrams with CT/X-ray images showed a poor correlation between sites of active bone disease and binding of scintigraphy bisphosphonate in 36% of MM patients and in 13% of BC patients. We conclude that WBrt of Zol is primarily determined by two non-disease related factors and only one disease related, but that there may be differences in retention or drug delivery at individual sites of bone disease between MM and BC patients. In order to find the optimal dosing of Zol, these

  6. Rare Form of Erdheim-Chester Disease Presenting with Isolated Central Skeletal Lesions Treated with a Combination of Alfa-Interferon and Zoledronic Acid

    PubMed Central

    Bulycheva, E. N.; Baykov, V. V.; Zaraĭskiĭ, M. I.; Salogub, G. N.

    2015-01-01

    Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid. PMID:25949835

  7. Effects of Zoledronate on Mortality and Morbidity after Surgical Treatment of Hip Fractures

    PubMed Central

    Cengiz, Ömer; Polat, Gökhan; Karademir, Gökhan; Tunç, Oytun Derya; Erdil, Mehmet; Tuncay, İbrahim; Şen, Cengiz

    2016-01-01

    We aimed to evaluate the effects of intertrochanteric femoral fractures on mortality, morbidity, and cost of zoledronate treatment in elderly patients treated by osteosynthesis. Based on Evans classification, 114 patients with unstable intertrochanteric femoral fractures were treated with osteosynthesis. After the surgical treatment of intertrochanteric fractures, the treatment group (M/F, 24/32; mean age, 76.7 ± SD years) received zoledronate infusion, and the control group (M/F, 20/38; mean age, 80.2 ± SD years) received placebo. Postoperative control visits were performed at 6-week, 3-month, 6-month, and 12-month time points. Functional level of patients was evaluated by the modified Harris hip score and Merle d'Aubigné hip score. By 12 months, the mean HHS in treatment and control groups was 81.93 and 72.9, respectively. For time of death of the patients, mortality was found to be 57.1% (16/28) on the first 3 months and 92.9% (26/28) on the first six months. The mortality rate in the treatment and control groups was 14.3% (8/56) and 34.5% (20/58), respectively. The use of zoledronic acid after surgical treatment of intertrochanteric femoral fractures in osteoporotic elderly patients is a safe treatment modality which helps to reduce mortality, improves functional outcomes, and has less side effects with single dose use per year. PMID:27092280

  8. Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features—An exploratory analysis of placebo-controlled trials

    PubMed Central

    Coleman, Robert E.; Lipton, Allan; Costa, Luis; Cook, Richard J.; Lee, Ker-Ai; Saad, Fred; Brown, Janet E.; Terpos, Evangelos; Major, Pierre P.; Kohno, Norio; Smith, Matthew; Body, Jean-Jacques

    2013-01-01

    Background Zoledronic acid (ZOL) is an important component of therapy for patients with metastatic bone disease (MBD) to reduce the risk of skeletal-related events (SREs). We evaluated overall survival (OS) in patients with MBD secondary to solid tumours included in placebocontrolled ZOL trials. Patients and methods Exploratory analyses were performed using databases from three randomised trials of ZOL versus placebo. 1126 patients (ZOL, n=731; placebo, n=395) with complete baseline data for 18 predefined parameters were evaluated for OS. Relative risks (RRs) with 95% confidence intervals were assessed using stratified and adjusted Cox regression models. Baseline covariates defining patient populations with significantly different effects of ZOL treatment on OS (identified by stepwise backward elimination) were included in multivariate models. Results Although OS was similar between the overall treatment groups, ZOL significantly improved OS in the subset of patients (n=423; 38%) with elevated baseline NTX (≥100 nmol/mmol creatinine; RR, 0.692; P=.0028). Notably, this effect was independent of SRE prevention. Additional covariates associated with OS benefits with ZOL (e.g., low albumin, SRE history, elevated lactate dehydrogenase, shorter cancer duration) were characteristic of advanced disease. Conclusion These exploratory analyses suggest a beneficial effect of ZOL on OS in patients with highly aggressive or advanced MBD. PMID:26909273

  9. Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid.

    PubMed

    Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello

    2015-09-22

    In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression. PMID:26312765

  10. Effect of Zoledronate on Oral Wound Healing in Rats

    PubMed Central

    Yamashita, Junro; Koi, Kiyono; Yang, Dong-Ye; McCauley, Laurie K.

    2010-01-01

    Purpose Osteonecrosis of the jaw (ONJ) is a growing concern in patients who receive bisphosphonates which target osteoclasts. Since osteoclasts play multifunctional roles in the bone marrow, their suppression likely affects bone homeostasis and alters wound healing of the jaw. The objective was to delineate the impact of osteoclast suppression in the bone marrow and wound healing of the jaw. Experimental Design Zoledronate was administered to senile rats for 14 weeks. A portion of the gingiva was removed to denude the palatal bone. Gene expression in the bone marrow was assessed and histologic sections analyzed to determine the wound healing status. Results Angiogenesis-related genes, CD31 and VEGF-A, were not altered by zoledronate. VEGF-C, which plays a role in lymphangiogenesis, was suppressed. There was a decrease in gene expression of Tcirg1 and MMP-13. Bone denudation caused extensive osteocyte death indicative of bone necrosis. In zoledronate-treated rats, the necrotic bone was retained in the wound while, in controls, osteoclastic resorption of the necrotic bone was prominent. Even though large necrotic bone areas existed in zoledronate-treated rats, overlaying soft tissue healed clinically. Immunohistochemical staining showed rich vascularity in the overlaying soft tissue. Conclusions Zoledronate therapy impacts bone marrow by suppressing genes associated with lymphoangiogenesis and tissue remodeling, such as VEGF-C and MMP-13. Zoledronate was associated with impaired osseous wound healing but had no effect on angiogenic markers in the bone marrow or soft tissue wound healing. Zoledronate selectively blunts healing in bone but does not effect soft tissue healing in the oral cavity. PMID:21149614

  11. Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model

    PubMed Central

    Qiao, H; Wang, T-y; Yu, Z-f; Han, X-g; Liu, X-q; Wang, Y-g; Fan, Q-m; Qin, A; Tang, T-t

    2016-01-01

    The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of NF-κB/MAPK (nuclear factor-κB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c-Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N

  12. Panobinostat synergizes with zoledronic acid in prostate cancer and multiple myeloma models by increasing ROS and modulating mevalonate and p38-MAPK pathways

    PubMed Central

    Bruzzese, F; Pucci, B; Milone, M R; Ciardiello, C; Franco, R; Chianese, M I; Rocco, M; Di Gennaro, E; Leone, A; Luciano, A; Arra, C; Santini, D; Caraglia, M; Budillon, A

    2013-01-01

    Patients with advanced prostate cancer (PCa) and multiple myeloma (MM) have limited long-term responses to available therapies. The histone deacetylase inhibitor panobinostat has shown significant preclinical and clinical anticancer activity in both hematological and solid malignancies and is currently in phase III trials for relapsed MM. Bisphosphonates (BPs), such as zoledronic acid (ZOL), inhibit osteoclast-mediated bone resorption and are indicated for the treatment of bone metastasis. BPs, including ZOL, have also shown anticancer activity in several preclinical and clinical studies. In the present report, we found a potent synergistic antiproliferative effect of panobinostat/ZOL treatment in three PCa and three MM cell lines as well as in a PCa ZOL-resistant subline, independently of p53/KRAS status, androgen dependency, or the schedule of administration. The synergistic effect was also observed in an anchorage-independent agar assay in both ZOL-sensitive and ZOL-resistant cells and was confirmed in vivo in a PCa xenograft model. The co-administration of the antioxidant N-acetyl-L-cysteine blocked the increased reactive oxygen species generation and apoptosis observed in the combination setting compared with control or single-agent treatments, suggesting that oxidative injury plays a functional role in the synergism. Proapoptotic synergy was also partially antagonized by the addition of geranyl-geraniol, which bypasses the inhibition of farnesylpyrophosphate synthase by ZOL in the mevalonate pathway, supporting the involvement of this pathway in the synergy. Finally, at the molecular level, the inhibition of basal and ZOL-induced activation of p38-MAPK by panobinostat in sensitive and ZOL-resistant cells and in tumor xenografts could explain, at least in part, the observed synergism. PMID:24157872

  13. 99mTc-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model

    PubMed Central

    2013-01-01

    Background Since proteoglycans (PGs) appear as key partners in chondrosarcoma biology, PG-targeted imaging using the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) developed by our group was previously demonstrated to be a good single-photon emission computed tomography tracer for cartilage neoplasms. We therefore initiated this new preclinical study to evaluate the relevance of 99mTc-NTP 15-5 imaging for the in vivo monitoring and quantitative assessment of chondrosarcoma response to zoledronic acid (ZOL) in the Swarm rat orthotopic model. Findings Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 μg/kg, subcutaneously) or phosphate-buffered saline, twice a week, from day 4 to day 48 post-tumor implantation. 99mTc-NTP 15-5 imaging was performed at regular intervals with the target-to-background ratio (TBR) determined. Tumor volume was monitored using a calliper, and histology was performed at the end of the study. From day 11 to day 48, mean TBR values ranged from 1.7 ± 0.6 to 2.3 ± 0.6 in ZOL-treated rats and from 2.1 ± 1.0 to 4.9 ± 0.9 in controls. Tumor growth inhibition was evidenced using a calliper from day 24 and associated to a decrease in PG content in treated tumor tissues (confirmed by histology). Conclusions This work demonstrated two proofs of concept: (1) biphosphonate therapy could be a promising therapeutic approach for chondrosarcoma; (2) 99mTc-NTP 15-5 is expected to offer a novel imaging modality for the in vivo evaluation of the extracellular matrix features of chondrosarcoma, which could be useful for the follow-up and quantitative assessment of proteoglycan ‘downregulation’ associated to the response to therapeutic attempts. PMID:23688107

  14. Doses effects of zoledronic acid on mineral apatite and collagen quality of newly-formed bone in the rat's calvaria defect.

    PubMed

    Olejnik, Cécile; Falgayrac, Guillaume; During, Alexandrine; Cortet, Bernard; Penel, Guillaume

    2016-08-01

    Due to their inhibitory effects on resorption, bisphosphonates are widely used in the treatment of diseases associated to an extensive bone loss. Yet, little is known about bisphosphonates effects on newly-formed bone quality. In the present study, adult male Sprague-Dawley rats (n=80) with a bone defect calvaria area were used and short-term effects of zoledronic acid (ZA) were studied on the healing bone area. Three ZA treatments were tested by using either: 1°) a low single dose (120μgZA/kg, n=10; equivalent to human osteoporosis treatment), 2°) a low fractionated doses (20μgZA/kg daily for 6days either a total of 120μg/kg, n=15), and 3°) a high fractionated doses, (100μgZA/kg weekly for 6weeks, n=15; equivalent to 6months of human bone metastasis treatment). For each treatment, a control "vehicle" treatment was performed (with an identical number of rats). After ZA administration, the intrinsic bone material properties were evaluated by quantitative backscattered electron imaging (qBEI) and Raman microspectroscopy. Neither single nor fractionated low ZA doses modify the intrinsic bone material properties of the newly-formed bone compared to their respective control animals. On the opposite, the high ZA treatment resulted in a significant decrease of the crystallinity (-25%, P< 0.05) and of the hydroxyproline-to-proline ratio (-30%, P<0.05) in newly-formed bones. Moreover, with the high ZA treatment, the crystallinity was positively correlated with the hydroxyproline-to-proline ratio (ρ=0.78, P<0.0001). The present data highlight new properties for ZA on bone formation in a craniofacial defect model. As such, ZA at high doses disrupted the apatite crystal organization. In addition, we report here for the first time that high ZA doses decreased the hydroxyproline-to-proline ratio suggesting that ZA may affect the early collagen organization during the bone healing. PMID:27168397

  15. Acquired resistance to zoledronic acid and the parallel acquisition of an aggressive phenotype are mediated by p38-MAP kinase activation in prostate cancer cells

    PubMed Central

    Milone, M R; Pucci, B; Bruzzese, F; Carbone, C; Piro, G; Costantini, S; Capone, F; Leone, A; Di Gennaro, E; Caraglia, M; Budillon, A

    2013-01-01

    The nitrogen-containing bisphosphonates (N-BP) zoledronic acid (ZOL) inhibits osteoclast-mediated bone resorption, and it is used to prevent skeletal complications from bone metastases. ZOL has also demonstrated anticancer activities in preclinical models and, recently, in cancer patients, highlighting the interest in determining eventual mechanisms of resistance against this agent. In our study, we selected and characterised a resistant subline of prostate cancer (PCa) cells to better understand the mechanisms, by which tumour cells can escape the antitumour effect of ZOL. DU145R80-resistant cells were selected in about 5 months using stepwise increasing concentrations of ZOL from DU145 parental cells. DU145R80 cells showed a resistance index value of 5.5 and cross-resistance to another N-BP, pamidronate, but not to the non-nitrogen containing BP clodronate. Notably, compared with DU145 parental cells, DU145R80 developed resistance to apoptosis and anoikis, as well as overexpressed the anti-apoptotic protein Bcl-2 and oncoprotein c-Myc. Moreover, DU145R80 cells underwent epithelial to mesenchymal transition (EMT) and showed increased expression of the metalloproteases MMP-2/9, as well as increased invading capability. Interestingly, compared with DU145, DU145R80 cells also increased the gene expression and protein secretion of VEGF and the cytokines Eotaxin-1 and IL-12. At the molecular level, DU145R80 cells showed strong activation of the p38-MAPK-dependent survival pathway compared with parental sensitive cells. Moreover, using the p38-inhibitor SB203580, we completely reversed the resistance to ZOL, as well as EMT marker expression and invasion. Furthermore, SB203580 treatment reduced the expression of VEGF, Eotaxin-1, IL-12, MMP-9, Bcl-2 and c-Myc. Thus, for the first time, we demonstrate that the p38-MAPK pathway can be activated under continuous extensive exposure to ZOL in PCa cells and that the p38-MAPK pathway has a critical role in the induction of

  16. Synthesis, crystal structure and antitumor effect of a novel copper(II) complex bearing zoledronic acid derivative.

    PubMed

    Qiu, Ling; Lv, Gaochao; Guo, Liubin; Chen, Liping; Luo, Shineng; Zou, Meifen; Lin, Jianguo

    2015-01-01

    A great majority of Cu(II) complexes currently studied in the anticancer research field exert their antiproliferative activities through ligand exchange. In this work, we present the synthesis and structural characterization of two novel Cu(II) complexes, {[Cu3(ZL)2(H2O)6]·6H2O}n (1) (ZL = 1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid) and [Cu(IPrDP)2]·3H2O (2) (IPrDP = 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid). Due to the insolubility of polymer 1 in common solvents, only the biological activities of complex 2 were investigated. The antitumor activity of complex 2 was evaluated against a panel of human cancer cell lines, including U2OS, A549, HCT116, MDA-MB-231 and HepG2. Complex 2 exhibited comparable cytotoxic effect to cisplatin (CDDP) against the human colon carcinoma cells HCT116, and superior selectivity for inhibiting human hepatocarcinoma cells rather than normal liver cells. The cell cycle distribution analysis indicates that complex 2 inhibits human carcinoma cells by inducing the cell cycle arrest at the G2/M phase, showing a similar mechanism of action to that of CDDP. The binding interaction of complex 2 with calf thymus DNA (CT-DNA) has been explored by UV-vis absorption and circular dichroism (CD), demonstrating complex 2 has a moderate binding affinity for DNA through intercalation.

  17. Dual-therapy with αvβ3-targeted Sn2 lipase-labile fumagillin-prodrug nanoparticles and zoledronic acid in the Vx2 rabbit tumor model.

    PubMed

    Esser, Alison K; Schmieder, Anne H; Ross, Michael H; Xiang, Jingyu; Su, Xinming; Cui, Grace; Zhang, Huiying; Yang, Xiaoxia; Allen, John S; Williams, Todd; Wickline, Samuel A; Pan, Dipanjan; Lanza, Gregory M; Weilbaecher, Katherine N

    2016-01-01

    Fumagillin, an unstable anti-angiogenesis mycotoxin, was synthesized into a stable lipase-labile prodrug and incorporated into integrin-targeted lipid-encapsulated nanoparticles (αvβ3-Fum-PD NP). Dual anti-angiogenic therapy combining αvβ3-Fum-PD NP with zoledronic acid (ZA), a long-acting osteoclast inhibitor with proposed anti-angiogenic effects, was evaluated. In vitro, αvβ3-Fum-PD NP reduced (P<0.05) endothelial cell viability without impacting macrophage viability. ZA suppressed (P<0.05) macrophage viability at high dosages but not endothelial cell proliferation. 3D MR neovascular imaging of rabbit Vx2 tumors showed no effect with ZA, whereas αvβ3-Fum-PD NP alone and with ZA decreased angiogenesis (P<0.05). Immunohistochemistry revealed decreased (P<0.05) microvascularity with αvβ3-Fum-PD NP and ZA and further microvascular reduction (P<0.05) with dual-therapy. In vivo, ZA did not decrease tumor macrophage numbers nor cancer cell proliferation, whereas αvβ3-Fum-PD-NPs reduced both measures. Dual-therapy with ZA and αvβ3-Fum-PD-NP may provide enhanced neo-adjuvant utility if macrophage ZA uptake is increased. From the Clinical Editor: Although anti-angiogenesis is one of the treatment modalities in the fight against cancer, many cancers become resistant to VEGF pathway inhibitors. In this article, the authors investigated the use of dual therapy using fumagillin, integrin-targeted lipid-encapsulated nanoparticles (αvβ3- Fum-PD NP) and zoledronic acid (ZA), in both in-vitro and in-vivo experiments. This combination approach may provide an insight to the design of future drugs against cancers.

  18. Dual-therapy with αvβ3-targeted Sn2 lipase-labile fumagillin-prodrug nanoparticles and zoledronic acid in the Vx2 rabbit tumor model.

    PubMed

    Esser, Alison K; Schmieder, Anne H; Ross, Michael H; Xiang, Jingyu; Su, Xinming; Cui, Grace; Zhang, Huiying; Yang, Xiaoxia; Allen, John S; Williams, Todd; Wickline, Samuel A; Pan, Dipanjan; Lanza, Gregory M; Weilbaecher, Katherine N

    2016-01-01

    Fumagillin, an unstable anti-angiogenesis mycotoxin, was synthesized into a stable lipase-labile prodrug and incorporated into integrin-targeted lipid-encapsulated nanoparticles (αvβ3-Fum-PD NP). Dual anti-angiogenic therapy combining αvβ3-Fum-PD NP with zoledronic acid (ZA), a long-acting osteoclast inhibitor with proposed anti-angiogenic effects, was evaluated. In vitro, αvβ3-Fum-PD NP reduced (P<0.05) endothelial cell viability without impacting macrophage viability. ZA suppressed (P<0.05) macrophage viability at high dosages but not endothelial cell proliferation. 3D MR neovascular imaging of rabbit Vx2 tumors showed no effect with ZA, whereas αvβ3-Fum-PD NP alone and with ZA decreased angiogenesis (P<0.05). Immunohistochemistry revealed decreased (P<0.05) microvascularity with αvβ3-Fum-PD NP and ZA and further microvascular reduction (P<0.05) with dual-therapy. In vivo, ZA did not decrease tumor macrophage numbers nor cancer cell proliferation, whereas αvβ3-Fum-PD-NPs reduced both measures. Dual-therapy with ZA and αvβ3-Fum-PD-NP may provide enhanced neo-adjuvant utility if macrophage ZA uptake is increased. From the Clinical Editor: Although anti-angiogenesis is one of the treatment modalities in the fight against cancer, many cancers become resistant to VEGF pathway inhibitors. In this article, the authors investigated the use of dual therapy using fumagillin, integrin-targeted lipid-encapsulated nanoparticles (αvβ3- Fum-PD NP) and zoledronic acid (ZA), in both in-vitro and in-vivo experiments. This combination approach may provide an insight to the design of future drugs against cancers. PMID:26515754

  19. Zoledronate Inhibits Ischemia-Induced Neovascularization by Impairing the Mobilization and Function of Endothelial Progenitor Cells

    PubMed Central

    Tsai, Shih-Hung; Huang, Po-Hsun; Chang, Wei-Chou; Tsai, Hsiao-Ya; Lin, Chih-Pei; Leu, Hsin-Bang; Wu, Tao-Cheng; Chen, Jaw-Wen; Lin, Shing-Jong

    2012-01-01

    Background Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs) play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. Methodology/Principal Findings Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg). Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control). Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1+/Flk-1+) after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. Conclusions/Significance Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions. These findings suggest

  20. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

    PubMed Central

    Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  1. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    PubMed

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  2. Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

    PubMed Central

    de la Piedra, C; Alcaraz, A; Bellmunt, J; Meseguer, C; Gómez-Caamano, A; Ribal, M J; Vázquez, F; Anido, U; Samper, P; Esteban, E; Álvarez-Ossorio, J L; Lara, P C; San José, L A; Contreras, J A; del Alba, A G; González-Gragera, B; Tabernero, A J; González-Enguita, C; Fernández, J M; García-Escudero, A; Gómez-Veiga, F; Méndez, M J; Segarra, J; Virizuela, J A; Carles, J; Lassa, A; Calderero, V; Constela, M; Delgado, D; Mañas, A; Murias, A; Reynes, G; Rodriguez, B; Rubio, G; Sánchez, E; Unda, M; Solsona, E; Martínez-Javaloyas, J M; Comet-Batlle, J; Quicios, C; Martín-Fernández, M; Mahillo-Fernández, I; Morote, J

    2013-01-01

    Background: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important. PMID:23722472

  3. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    PubMed Central

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  4. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    PubMed Central

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  5. HANDBOOK FOR CONSTRUCTED WETLANDS RECEIVING ACID MINE DRAINAGE

    EPA Science Inventory

    In the summer of 1987, a pilot constructed wetland was built at the Big Five Tunnel in Idaho Springs, Colorado. This report details the theory, design and construction of wetlands receiving acid mine drainages, based on the second and third year of operation of this wetland, whic...

  6. Zoledronate and ion-releasing resins impair dentin collagen degradation.

    PubMed

    Tezvergil-Mutluay, A; Seseogullari-Dirihan, R; Feitosa, V P; Tay, F R; Watson, T F; Pashley, D H; Sauro, S

    2014-10-01

    This study analyzed the amounts of solubilized telopeptides cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol-primer) pre-treatment. The chemical modification induced following treatments and artificial saliva (AS) storage was also analyzed through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA-demineralized specimens were infiltrated with Res.A or Res.B with or without Zol-primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP release was reduced following infiltration with Res.B and further reduced when Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin. However, when Zol-primer was used with Res.A, the CTX release fell significantly compared to the other tested resin-infiltration methods. In conclusion, zoledronate offers an additional inhibitory effect to the ion-releasing resins in MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction in CTX release only when used with resin-based systems containing no ion-releasing fillers.

  7. Handbook for constructed wetlands receiving acid mine drainage

    SciTech Connect

    Wildeman, T.; Dietz, J.; Gusek, J.; Morea, S.

    1993-09-01

    In the summer of 1987, a pilot constructed wetland was built at the Big Five Tunnel in Idaho Springs, Colorado. The report details the theory, design and construction of wetlands receiving acid mine drainages, based on the second and third year of operation of this wetland, which was funded by the U.S. Environmental Protection Agency under the SITE Emerging Technologies Program. The text is divided into two broad sections: Part A - Theoretical Development, and Part B - Design Consideration. In the latter sections of Part A and through all of Part B the focus is on removal of metals by precipitation of sulfides through the activity of sulfate reducing bacteria.

  8. Zoledronate and ion-releasing resins impair dentin collagen degradation.

    PubMed

    Tezvergil-Mutluay, A; Seseogullari-Dirihan, R; Feitosa, V P; Tay, F R; Watson, T F; Pashley, D H; Sauro, S

    2014-10-01

    This study analyzed the amounts of solubilized telopeptides cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol-primer) pre-treatment. The chemical modification induced following treatments and artificial saliva (AS) storage was also analyzed through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA-demineralized specimens were infiltrated with Res.A or Res.B with or without Zol-primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP release was reduced following infiltration with Res.B and further reduced when Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin. However, when Zol-primer was used with Res.A, the CTX release fell significantly compared to the other tested resin-infiltration methods. In conclusion, zoledronate offers an additional inhibitory effect to the ion-releasing resins in MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction in CTX release only when used with resin-based systems containing no ion-releasing fillers. PMID:25074494

  9. Zoledronate and Ion-releasing Resins Impair Dentin Collagen Degradation

    PubMed Central

    Tezvergil-Mutluay, A.; Seseogullari-Dirihan, R.; Feitosa, V.P.; Tay, F.R.; Watson, T.F.; Pashley, D.H.; Sauro, S.

    2014-01-01

    This study analyzed the amounts of solubilized telopeptides cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and C-terminal crosslinked telopeptide of type I collagen (CTX) derived from matrix-metalloproteinases (MMPs) and cysteine cathepsins (CTPs) subsequent to application of a filler-free (Res.A) or an ion-releasing resin (Res.B) to ethylenediaminetetraacetic acid (EDTA)-demineralized dentin with or without zoledronate-containing primer (Zol-primer) pre-treatment. The chemical modification induced following treatments and artificial saliva (AS) storage was also analyzed through attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Totally EDTA-demineralized specimens were infiltrated with Res.A or Res.B with or without Zol-primer pre-treatment, light-cured, and immersed in AS for up to 4 wk. ICTP release was reduced following infiltration with Res.B and further reduced when Res.B was used with Zol-primer; remarkable phosphate mineral uptake was attained after AS storage. CTX release was increased in Res.A- and Res.B-treated dentin. However, when Zol-primer was used with Res.A, the CTX release fell significantly compared to the other tested resin-infiltration methods. In conclusion, zoledronate offers an additional inhibitory effect to the ion-releasing resins in MMP-mediated collagen degradation. However, Zol-primer induces a modest reduction in CTX release only when used with resin-based systems containing no ion-releasing fillers. PMID:25074494

  10. Intravenous zoledronate for osteoporosis: less might be more

    PubMed Central

    Grey, Andrew

    2016-01-01

    Annual administration of 5 mg intravenous zoledronate is moderately effective in reducing fracture risk in older adults, decreasing the relative risk of clinical fracture by 33%. However, almost 10 years after its approval for use in clinical practice there remain very substantial uncertainties about the optimal treatment regimen, that is, the lowest dose and/or longest dosing interval that is efficacious. Several pieces of clinical research suggest that the current recommendation for annual administration of 5 mg zoledronate might represent overtreatment. Clinical trials to clarify the optimal use of zoledronate for reduction of fracture risk should be undertaken. PMID:27493690

  11. Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

    PubMed Central

    Peng, Jiang; Lu, Qiang; Wang, Yu; Wang, Aiyuan; Guo, Quanyi; Gao, Xupeng; Xu, Wenjing; Lu, Shibi

    2014-01-01

    Bisphosphonates (BPs) have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA) as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol) into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively) than control and low-dose Zol (3 µg PLGA-Zol; p<0.05). Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation. PMID:24618585

  12. Acid neutralization within limestone sand reactors receiving coal mine drainage

    USGS Publications Warehouse

    Watten, B.J.; Sibrell, P.L.; Schwartz, M.F.

    2005-01-01

    Pulsed bed treatment of acid mine drainage (AMD) uses CO2 to accelerate limestone dissolution and intermittent fluidization to abrade and carry away metal hydrolysis products. Tests conducted with a prototype of 60 L/min capacity showed effective removal of H+ acidity over the range 196-584 mg/L (CaCO3) while concurrently generating surplus acid neutralization capacity. Effluent alkalinity (mg/L CaCO3) rose with increases in CO2 (DC, mg/L) according to the model Alkalinity = 31.22 + 2.97(DC)0.5, where DC was varied from 11-726 mg/L. Altering fluidization and contraction periods from 30 s/30 s to 10 s/50 s did not influence alkalinity but did increase energy dissipation and bed expansion ratios. Field trials with three AMD sources demonstrated the process is capable of raising AMD pH above that required for hydrolysis and precipitation of Fe3+ and Al3+ but not Fe2+ and Mn2+. Numerical modeling showed CO2 requirements are reduced as AMD acidity increases and when DC is recycled from system effluent. ?? 2005 Elsevier Ltd. All rights reserved.

  13. Effects of zoledronate on irradiated bone in vivo: analysis of the collagen types I, V and their cross-links lysylpyridinoline, hydroxylysylpyridinoline and hydroxyproline.

    PubMed

    Açil, Yahya; Gierloff, Matthias; Behrens, Carolin; Möller, Björn; Gassling, Volker; Niehoff, Peter; Wiltfang, Jörg; Simon, Maciej

    2013-03-01

    Radiotherapy can lead to a reduction of bone density with an increased risk of pathological fractures. Bisphosphonates may represent a preventive treatment option by increasing the density of anorganic bone mineral. Yet it is unknown how bisphosphonates act on irradiated collagen cross-links, which play an essential role for the mechanical stability of bone. The aim of this study was to evaluate the effects of zoledronate on bone collagens and their cross-links after irradiation. The right femur of 37 rats was irradiated with a single dose of 9.5 Gy at a high dose rate using an afterloading machine. Half of the rats (n=18) received additionally a single dose zoledronate (0.1 mg/kg body weight). Fourteen and 100 days after irradiation the femora were collected for histologic evaluation and determination of the collagen cross-links lysylpyridinoline, hydroxylysylpyridinoline, and hydroxyproline. The collagen types were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Fourteen days after treatment the lysylpyridinoline levels of all treatment groups were significantly lower compared to the untreated control. After 100 days, in the combined radiotherapy+zoledronate group significantly lower lysylpyridinoline values were determined (p=0.009). Radiotherapy and/or zoledronate did not change significantly the level of hydroxylysylpyridinoline. The concentration of hydroxyproline was 14 days after irradiation significantly higher in the combined treatment group compared to the control. No significant differences were observed 100 days after treatment. Zoledronate does not have the ability to restore the physiological bone collagen cross-link levels after radiotherapy. However, this would be necessary for regaining the physiological mechanical stability of bone after irradiation and therefore to prevent effectively radiation-induced fractures.

  14. Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

    NASA Technical Reports Server (NTRS)

    Scott, R. T.; Nalavadi, M. O.; Shirazi-Fard, Y.; Castillo, A. B.; Alwood, J. S.

    2016-01-01

    Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with

  15. Essential fatty acid deficiency while a patient receiving fat regimen total parenteral nutrition

    PubMed Central

    Roongpisuthipong, Wanjarus; Phanachet, Pariya; Roongpisuthipong, Chulaporn; Rajatanavin, Natta

    2012-01-01

    A 32-year-old man was diagnosed with lymphoma and underwent Billroth’s II operation because of upper gastrointestinal haemorrhage. Although the patient received fat regimen total parenteral nutrition (TPN), the patient developed typical skin rash of essential fatty acid deficiency after 2 weeks of starting TPN. The diagnosis was confirmed by biochemical and histological analyses. After increasing the lipid infusion, the rash was gradually improved with complete resolution after 19 days. PMID:22707694

  16. Plasma Amino Acid Concentrations in 108 Children Receiving a Pediatric Amino Acid Formulation as Part of Parenteral Nutrition

    PubMed Central

    Shelton, Chasity M.; Clark, Amanda J.; Storm, Michael C.; Helms, Richard A.

    2010-01-01

    BACKGROUND Plasma amino acid (PAA) levels can be largely normalized during parenteral nutrition (PN) in infants and children using a pediatric-specific amino acid (AA) formulation. However, these previous results were based on individual clinical studies of small populations of neonates and infants. OBJECTIVE We have now examined AA levels in 108 children (0–7 years of age) receiving a pediatric-specific AA formulation in PN using a single analytical methodology. METHODS Infants and children were enrolled in specific protocols and parents/caregivers gave informed consent. Patients were stable and receiving age-appropriate intakes of AA and non-protein calories. Samples were obtained between 8 and10 am, processed immediately, deproteinized, and AA concentrations (μmol/L) were determined on a Beckman 6300 analyzer. Means and SD were calculated for sub-populations stratified by age: 0–1 month (48 patients, n=139), 1–6 months (36 patients, n=124), 7–12 months (11 patients, n=41), and 1–7 years (13 patients, n=51). Z scores were calculated for each amino acid [(observed mean - normal control mean)/normal control SD]. RESULTS When compared to the neonatal reference range, nonessential AA had Z scores that ranged from −1.84 (asparagine) to +1.48 (threonine). Only plasma free cystine, free tyrosine, and phenylalanine had Z scores outside the −2.0 to +2.0 range (95% confidence limits). Plasma free cystine values were low in all groups except neonates. Free tyrosine levels were low in all groups despite the presence of N-acetyl-L-tyrosine in the pediatric AA formulation. Phenylalanine levels were elevated only in neonates. When children 1 to 7 years old were compared with an age-matched reference range, plasma free cystine values were low (Z score −2.47), as were plasma glutamine values (−3.11), but elevations were found in the dicarboxylic amino acids aspartic acid (+2.5) and glutamic acid (+4.27). Regardless of reference range used for comparison, all

  17. Assessment of the microbial community in a constructed wetland that receives acid coal mine drainage

    SciTech Connect

    Nicomrat, D.; Dick, W.A.; Tuovinen, O.H.

    2006-01-15

    Constructed wetlands are used to treat acid drainage from surface or underground coal mines. However, little is known about the microbial communities in the receiving wetland cells. The purpose of this work was to characterize the microbial population present in a wetland that was receiving acid coal mine drainage (AMD). Samples were collected from the oxic sediment zone of a constructed wetland cell in southeastern Ohio that was treating acid drainage from an underground coal mine seep. Samples comprised Fe(Ill) precipitates and were pretreated with ammonium oxalate to remove interfering iron, and the DNA was extracted and purified by agarose gel electrophoresis prior to amplification of portions of the 16S rRNA gene. Amplified products were separated by denaturing gradient gel electrophoresis and DNA from seven distinct bands was excised from the gel and sequenced. The sequences were matched to sequences in the GenBank bacterial 16S rDNA database. The DNA in two of the bands yielded matches with Acidithiobacillus ferrooxidans and the DNA in each of the remaining five bands was consistent with one of the following microorganisms: Acidithiobacillus thiooxidans, strain TRA3-20 (a eubacterium), strain BEN-4 (an arsenite-oxidizing bacterium), an Alcaligenes sp., and a Bordetella sp. Low bacterial diversity in these samples reflects the highly inorganic nature of the oxic sediment layer where high abundance of iron- and sulfur-oxidizing bacteria would be expected. The results we obtained by molecular methods supported our findings, obtained using culture methods, that the dominant microbial species in an acid receiving, oxic wetland are A. thiooxidans and A. ferrooxidans.

  18. Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

    ClinicalTrials.gov

    2014-05-12

    Ductal Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  19. Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

    PubMed Central

    Arun, Mehmet Zuhuri; Reel, Buket; Sala-Newby, Graciela B; Bond, Mark; Tsaousi, Aikaterini; Maskell, Perry; Newby, Andrew C

    2016-01-01

    Background Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs) are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression. Methods Rat VSMCs were stimulated by PDGF (50 ng/mL) plus TNF-α (10 ng/mL) or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 μM) or with apocynin (20 nM) for 2 hours, then zoledronate (100 μM) was added into 2% fetal calf serum containing medium for 24 hours. Results and discussion Using isolated rat VSMCs in culture, zoledronate (100 μM) increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by zoledronate. Conclusion We conclude that zoledronate increases MMP-9 and MMP-13 expressions in rat VSMCs dependent upon stimulation of the NF-κB pathway by reactive oxygen species. Effects on MMP expression may contribute to the pharmacologic profile of bisphosphonates. PMID:27143852

  20. Enhancing the natural removal of As in a reactive fluvial confluence receiving acid drainage

    NASA Astrophysics Data System (ADS)

    Abarca, M. I.; Arce, G.; Montecinos, M.; Guerra, P. A.; Pasten, P.

    2014-12-01

    Fluvial confluences are natural reactors that can determine the fate of contaminants in watersheds receiving acid drainage. Hydrological, hydrodynamic and chemical factors determine distinct conditions for the formation of suspended particles of iron and aluminum oxyhydroxides. The chemical and physical properties of these particle assemblages (e.g. particle size, chemical composition) can vary according to inflow mixing ratios, hydrodynamic velocity profiles, and chemical composition of the flows mixing at the confluence. Due to their capacity to sorb metals, it is important to identify the optimal conditions for removing metals from the aqueous phase, particularly arsenic, a contaminant frequently found in acid drainage. We studied a river confluence in the Lluta watershed, located in the arid Chilean Altiplano. We performed field measurements and laboratory studies to find optimal mixing ratio for arsenic sorption onto oxyhydroxide particles at the confluence between the Azufre (pH=2, As=2 mg/L) and the Caracarani river (pH=8, As<0.1 mg/L). As the contribution of the acidic stream increased, the concentration of Fe and Al in the solid phase reached a peak at different pHs. Although the optimal pH for As sorption was ~3, the overall maximum removal of As at the confluence, ocurred for pH~4. This is produced because optimal As sorption does not occur necessarily for the highest concentrations of particles being formed. We propose that fluvial confluences could be engineered to enhance the natural attenuation of contaminants. An analogy between confluences and coagulation-flocculation-sedimentation drinking water plants could be used to engineer such intervention.Acknowledgements: Proyecto Fondecyt 1130936 and Proyecto CONICYT FONDAP 15110020

  1. Zoledronate as effective treatment for minimal trauma fractures in a child with STAT3 deficiency and osteonecrosis of the hip.

    PubMed

    Staines Boone, Aidé Tamara; Alcántara-Montiel, Julio César; Sánchez-Sánchez, Luz María; Arce-Cano, Marina; García-Campos, Jorge; Lugo Reyes, Saúl Oswaldo

    2016-11-01

    Signal transducer and activator of transcription 3 (STAT3) deficiency is a primary immunodeficiency characterized by eczema, complicated recurrent infections, elevated serum immunoglobulin E (IgE), osteopenia, and minimal trauma fractures. Zoledronic acid (ZA) is a long-acting bisphosphonate that has been successfully used in children with secondary osteoporosis and osteogenesis imperfecta. We describe the case of a 7-year-old male with STAT3 deficiency and minimal trauma fractures, who also developed osteonecrosis of the hip. He responded well to intravenous ZA every 6 months for 18 months. Three years later, he walks independently and unaided, and has not suffered any other fractures. Although more studies are needed, ZA might help reduce minimal trauma fractures in patients with STAT3 deficiency. PMID:27416072

  2. Population Pharmacokinetics and Dose Optimization of Mycophenolic Acid in HCT Recipients Receiving Oral Mycophenolate Mofetil

    PubMed Central

    Li, H; Mager, D E; Sandmaier, B M; Maloney, D G; Bemer, M J; McCune, J S

    2012-01-01

    We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. 4,496 MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance and volume of the central compartment were 24.2 L/hr and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA clearance by 33.8%. The optimal LSS was immediately before and at 0.25, 1.25, 2, and 4hr after oral MMF administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation. PMID:23382105

  3. Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil.

    PubMed

    Li, H; Mager, D E; Sandmaier, B M; Maloney, D G; Bemer, M J; McCune, J S

    2013-04-01

    We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. Four thousand four hundred ninety-six MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance (CL) and volume of the central compartment were 24.2 L/hour and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33.8%. The optimal LSS was immediately before and at 0.25 hours, 1.25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation.

  4. Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil.

    PubMed

    Li, H; Mager, D E; Sandmaier, B M; Maloney, D G; Bemer, M J; McCune, J S

    2013-04-01

    We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i.e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients. Four thousand four hundred ninety-six MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach. MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process. Concomitant cyclosporine and serum albumin were significant covariates. The median MPA clearance (CL) and volume of the central compartment were 24.2 L/hour and 36.4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3.4 g/dL. Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33.8%. The optimal LSS was immediately before and at 0.25 hours, 1.25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration. MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation. PMID:23382105

  5. Strontium and zoledronate hydroxyapatites graded composite coatings for bone prostheses.

    PubMed

    Boanini, Elisa; Torricelli, Paola; Sima, Felix; Axente, Emanuel; Fini, Milena; Mihailescu, Ion N; Bigi, Adriana

    2015-06-15

    Both strontium and zoledronate (ZOL) are known to be useful for the treatment of bone diseases associated to the loss of bone substance. In this work, we applied an innovative technique, Combinatorial Matrix-Assisted Pulsed Laser Evaporation (C-MAPLE), to deposit gradient thin films with variable compositions of Sr-substituted hydroxyapatite (SrHA) and ZOL modified hydroxyapatite (ZOLHA) on Titanium substrates. Compositional gradients were obtained by simultaneous laser vaporization of the two distinct material targets. The coatings display good crystallinity and granular morphology, which do not vary with composition. Osteoblast-like MG63 cells and human osteoclasts were co-cultured on the thin films up to 21 days. The results show that Sr counteracts the negative effect of relatively high concentration of ZOL on osteoblast viability, whereas both Sr and ZOL enhance extracellular matrix deposition. In particular, ZOL promotes type I collagen production, whereas Sr increases the production of alkaline phosphatase. Moreover, ZOL exerts a greater effect than Sr on osteoprotegerin/RANKL ratio and, as a consequence, on the reduction of osteoclast proliferation and activity. The deposition method allows to modulate the composition of the thin films and hence the promotion of bone growth and the inhibition of bone resorption. PMID:25706198

  6. Strontium and zoledronate hydroxyapatites graded composite coatings for bone prostheses.

    PubMed

    Boanini, Elisa; Torricelli, Paola; Sima, Felix; Axente, Emanuel; Fini, Milena; Mihailescu, Ion N; Bigi, Adriana

    2015-06-15

    Both strontium and zoledronate (ZOL) are known to be useful for the treatment of bone diseases associated to the loss of bone substance. In this work, we applied an innovative technique, Combinatorial Matrix-Assisted Pulsed Laser Evaporation (C-MAPLE), to deposit gradient thin films with variable compositions of Sr-substituted hydroxyapatite (SrHA) and ZOL modified hydroxyapatite (ZOLHA) on Titanium substrates. Compositional gradients were obtained by simultaneous laser vaporization of the two distinct material targets. The coatings display good crystallinity and granular morphology, which do not vary with composition. Osteoblast-like MG63 cells and human osteoclasts were co-cultured on the thin films up to 21 days. The results show that Sr counteracts the negative effect of relatively high concentration of ZOL on osteoblast viability, whereas both Sr and ZOL enhance extracellular matrix deposition. In particular, ZOL promotes type I collagen production, whereas Sr increases the production of alkaline phosphatase. Moreover, ZOL exerts a greater effect than Sr on osteoprotegerin/RANKL ratio and, as a consequence, on the reduction of osteoclast proliferation and activity. The deposition method allows to modulate the composition of the thin films and hence the promotion of bone growth and the inhibition of bone resorption.

  7. Bone-Targeted Mesoporous Silica Nanocarrier Anchored by Zoledronate for Cancer Bone Metastasis.

    PubMed

    Sun, Wentong; Han, Yu; Li, Zhenhua; Ge, Kun; Zhang, Jinchao

    2016-09-13

    Once bone metastasis occurs, the chances of survival and quality of life for cancer patients decrease significantly. With the development of nanomedicine, nanocarriers loading bisphosphonates have been built to prevent cancer metastasis based on their enhanced permeability and retention (EPR) effects; however, as a passive mechanism, the EPR effects cannot apply to the metastatic sites because of their lack of leaky vasculature. In this study, we fabricated 40 nm-sized mesoporous silica nanoparticles (MSNs) anchored by zoledronic acid (ZOL) for targeting bone sites and delivered the antitumor drug doxorubicin (DOX) in a spatiotemporally controlled manner. The DOX loading and release behaviors, bone-targeting ability, cellular uptake and its mechanisms, subcellular localization, cytotoxicity, and the antimigration effect of this drug delivery system (DDS) were investigated. The results indicated that MSNs-ZOL had better bone-targeting ability compared with that of the nontargeted MSNs. The maximum loading capacity of DOX into MSNs and MSNs-ZOL was about 1671 and 1547 mg/g, with a loading efficiency of 83.56 and 77.34%, respectively. DOX@MSNs-ZOL had obvious pH-sensitive DOX release behavior. DOX@MSNs-ZOL entered into cells through an ATP-dependent pathway and then localized in the lysosome to achieve effective intracellular DOX release. The antitumor results indicated that DOX@MSNs-ZOL exhibited the best cytotoxicity against A549 cells and significantly decreased cell migration in vitro. This DDS is promising for the treatment of cancer bone metastasis in the future. PMID:27531422

  8. A Model for Osteonecrosis of the Jaw with Zoledronate Treatment following Repeated Major Trauma

    PubMed Central

    Howie, R. Nicole; Borke, James L.; Kurago, Zoya; Daoudi, Asma; Cray, James; Zakhary, Ibrahim E.; Brown, Tara L.; Raley, J. Nathan; Tran, Loan T.; Messer, Regina; Medani, Fardous; Elsalanty, Mohammed E.

    2015-01-01

    This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30% - 60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (IV zoledronate; 80 μg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ. PMID:26186665

  9. Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.

    PubMed

    Sabatino, Raffaella; Antonelli, Antonella; Battistelli, Serafina; Schwendener, Reto; Magnani, Mauro; Rossi, Luigia

    2014-01-01

    Bisphosphonates, besides being important drugs for the treatment of various bone diseases, could also be used to induce apoptosis in macrophage-like and cancer cells. However, their activity in vivo is limited by a short plasma half-life and rapid uptake within bone. Therefore, several delivery systems have been proposed to modify their pharmacokinetic profile and biodistribution. Among these, red blood cells (RBCs) represent one of the most promising biological carriers. The aim of this study was to select the best performing compound among Clodronate, Pamidronate, Ibandronate and Zoledronate in killing macrophages and to investigate RBCs as innovative carrier system to selectively target bisphosphonates to macrophages. To this end, the encapsulation of the selected bisphosphonates in autologous RBCs as well as the effect on macrophages, both in vitro and in vivo were studied. This work shows that, among the tested bisphosphonates, Zoledronate has proven to be the most active molecule. Human and murine RBCs have been successfully loaded with Zoledronate by a procedure of hypotonic dialysis and isotonic resealing, obtaining a dose-dependent drug entrapment with a maximal loading of 7.96±2.03, 6.95±3.9 and 7.0±1.89 µmoles of Zoledronate/ml of packed RBCs for human, Swiss and Balb/C murine RBCs, respectively. Engineered RBCs were able to detach human and murine macrophages in vitro, leading to a detachment of 66±8%, 67±8% and 60.5±3.5% for human, Swiss and Balb/C RBCs, respectively. The in vivo efficacy of loaded RBCs was tested in Balb/C mice administering 59 µg/mouse of RBC-encapsulated Zoledronate. By a single administration, depletion of 29.0±16.38% hepatic macrophages and of 67.84±5.48% spleen macrophages was obtained, confirming the ability of encapsulated Zoledronate to deplete macrophages in vivo. In conclusion, RBCs loaded with Zoledronate should be considered a suitable system for targeted delivery to macrophages, both in vitro and in vivo.

  10. Macrophage Depletion by Free Bisphosphonates and Zoledronate-Loaded Red Blood Cells

    PubMed Central

    Sabatino, Raffaella; Antonelli, Antonella; Battistelli, Serafina; Schwendener, Reto; Magnani, Mauro; Rossi, Luigia

    2014-01-01

    Bisphosphonates, besides being important drugs for the treatment of various bone diseases, could also be used to induce apoptosis in macrophage-like and cancer cells. However, their activity in vivo is limited by a short plasma half-life and rapid uptake within bone. Therefore, several delivery systems have been proposed to modify their pharmacokinetic profile and biodistribution. Among these, red blood cells (RBCs) represent one of the most promising biological carriers. The aim of this study was to select the best performing compound among Clodronate, Pamidronate, Ibandronate and Zoledronate in killing macrophages and to investigate RBCs as innovative carrier system to selectively target bisphosphonates to macrophages. To this end, the encapsulation of the selected bisphosphonates in autologous RBCs as well as the effect on macrophages, both in vitro and in vivo were studied. This work shows that, among the tested bisphosphonates, Zoledronate has proven to be the most active molecule. Human and murine RBCs have been successfully loaded with Zoledronate by a procedure of hypotonic dialysis and isotonic resealing, obtaining a dose-dependent drug entrapment with a maximal loading of 7.96±2.03, 6.95±3.9 and 7.0±1.89 µmoles of Zoledronate/ml of packed RBCs for human, Swiss and Balb/C murine RBCs, respectively. Engineered RBCs were able to detach human and murine macrophages in vitro, leading to a detachment of 66±8%, 67±8% and 60.5±3.5% for human, Swiss and Balb/C RBCs, respectively. The in vivo efficacy of loaded RBCs was tested in Balb/C mice administering 59 µg/mouse of RBC-encapsulated Zoledronate. By a single administration, depletion of 29.0±16.38% hepatic macrophages and of 67.84±5.48% spleen macrophages was obtained, confirming the ability of encapsulated Zoledronate to deplete macrophages in vivo. In conclusion, RBCs loaded with Zoledronate should be considered a suitable system for targeted delivery to macrophages, both in vitro and in vivo. PMID

  11. Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

    PubMed Central

    Bonnet, Nicolas; Lesclous, Philippe; Saffar, Jean Louis; Ferrari, Serge

    2013-01-01

    Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 µg/kg/month) and Zol 1W (100 µg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn+/+ and Postn−/− (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn−/−. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn−/− and Postn+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn−/− vs Postn+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn−/− and Postn+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn−/−, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn−/− mice, zoledronate is not sufficient to induce bone necrosis. PMID:23505553

  12. Rumen fermentation and microbial population in lactating dairy cows receiving diets containing oilseeds rich in C-18 fatty acids.

    PubMed

    Ivan, M; Petit, H V; Chiquette, J; Wright, A-D G

    2013-04-14

    Sixteen Holstein rumen-cannulated primiparous milking dairy cows were fed a control diet (CN) based on maize silage and soyabean meal during a 4-week period before the start of a 21-d experiment with oilseeds containing high concentration of linoleic acid (Linola™) or linolenic acid (NuLin™). Thereafter, four cows received ad libitum one of each of four dietary treatments comprising of CN, Linola (LN), NuLin (NL) and LN/NL (50/50 % combination). Each LN, NL and LN/NL treatment contained 6 % oil of DM. Rumen digesta samples were collected on days 6, 11, 16 and 21 and milk samples on days 13, 15 and 17. There were no effects (P>0.05) of the oilseeds on pH and concentrations of NH3-N and total volatile fatty acids, while the acetate:propionate ratio was decreased (P< 0.05). The oilseeds also decreased (P< 0.05) protozoa and increased (P< 0.1) total cellulolytic bacteria in rumen fluid, especially when containing high dietary linoleic acid (P< 0.05). The milk protein concentration was increased (P< 0.1) by the dietary linoleic acid, which produced most beneficial results. It was concluded that supplements of linoleic acid in diets of ruminants might contribute to better digestion of dietary fibre and increased quality of milk.

  13. Effect of acidity and elevated PCO2 on acid. Neutralization within pulsed limestone bed reactors receiving coal mine drainage

    USGS Publications Warehouse

    Watten, B.J.; Sibrell, P.L.; Schwartz, M.F.

    2004-01-01

    Limestone has potential for reducing reagent costs and sludge volume associated with the treatment of acid mine drainage (AMD), but its use has been restricted by slow dissolution rates and sensitivity to scale forming reactions that retard transport of H+ at the solid-liquid interface. We evaluated a pulsed limestone bed (PLB) remediation process designed to circumvent these problems through use of intermittently fluidized beds of granular limestone and elevated carbon dioxide pressure. PLB limestone dissolution (LD, mg/L), and effluent alkalinity (Alk, mg/L) were correlated with reactor pressure (PCO2, kPa), influent acidity (Acy, mg/L) and reactor bed height (H, cm) using a prototype capable of processing 10 L/min. The PLB process effectively neutralized sulfuric acid acidity over the range of 6-1033 mg/L (as CaCO3) while generating high concentrations of alkalinity (36-1086 mg/L) despite a hydraulic residence time of just 4.2-5.0 min. Alk and LD (mg/L CaCO3) rose with increases in influent acidity and PCO2 (p < 0.001) according to the models: Alk = 58 + 38.4 (PCO2)0.5 + 0.080 (Acy) - 0.0059(PCO2) 0.5 (Acy); LD = 55 + 38.3 (PCO2)0.5 + 1.08 (Acy) - 0.0059 (PCO2)0.5 (Acy). Alkalinity decreased at an increasing rate with reductions in H over the range of 27.3-77.5 cm (p < 0.001). Carbon dioxide requirements (Q(avg)CO2, L/min) increased with PCO2 (p < 0.001) following the model Q(avg)CO2 = 0.858 (PCO2)0.620, resulting in a greater degree of pH buffering (depression) within the reactors, a rise in limestone solubility and an increase in limestone dissolution related to carbonic acid attack. Corresponding elevated concentrations of effluent alkalinity allow for sidestream treatment with blending. Numerical modeling demonstrated that carbon dioxide requirements are reduced as influent acidity rises and when carbon dioxide is recovered from system effluent and recycled. Field trials demonstrated that the PLB process is capable of raising the pH of AMD above that

  14. Total alkalinity versus buffer value (capacity) as a sensitivity indicator for fresh waters receiving acid rain

    SciTech Connect

    Faust, S.D.

    1983-09-01

    The frequently stated idea that total alkalinity is a measure of the buffer capacity of a natural water is refuted. Total alkalinity is a measure of the acid neutralizing capacity, equivalents/liter, of a water. In natural waters, the carbonate system provides most of this neutralizing capacity. In as much as the pH values of natural fresh waters lie below 8.3, the total alkalinity is, for all intents and purposes, the total bicarbonate content. Any contributions of carbonate and hydroxide to total alkalinity are nil. The buffer capacity or buffer value is the relation between the increment of a strong base, or strong acid, that causes a one unit change in the pH value. The values of total alkalinity and pH, considered individually cannot give an accurate assessment of the impact of acid deposition on a natural water. Rather it is necessary to combine the pH and alkalinity values into the beta concept in order to assess accurately and to calculate the capacity of a natural water to resist the impact of acid deposition. An analytical determination of total alkalinity is given with an application of the beta value. 17 references, 2 figures, 4 tables.

  15. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing.

    PubMed

    Valenzuela, Rodrigo; Bascuñán, Karla; Chamorro, Rodrigo; Barrera, Cynthia; Sandoval, Jorge; Puigrredon, Claudia; Parraguez, Gloria; Orellana, Paula; Gonzalez, Valeria; Valenzuela, Alfonso

    2015-08-01

    α-Linolenic acid (ALA) is the precursor of docosahexaenoic acid (DHA) in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L.), a plant native to some Latin American countries, is high in ALA (up to 60%) and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22-35 years old) tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21) and a chia group (n = 19), which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i) a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA) ingestion, no showing modification of arachidonic acid (AA), eicosapentaenoic acid (EPA) and DHA; (ii) a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii) a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA. PMID:26247968

  16. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing

    PubMed Central

    Valenzuela, Rodrigo; Bascuñán, Karla A.; Chamorro, Rodrigo; Barrera, Cynthia; Sandoval, Jorge; Puigrredon, Claudia; Parraguez, Gloria; Orellana, Paula; Gonzalez, Valeria; Valenzuela, Alfonso

    2015-01-01

    α-Linolenic acid (ALA) is the precursor of docosahexaenoic acid (DHA) in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L.), a plant native to some Latin American countries, is high in ALA (up to 60%) and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22–35 years old) tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21) and a chia group (n = 19), which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i) a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA) ingestion, no showing modification of arachidonic acid (AA), eicosapentaenoic acid (EPA) and DHA; (ii) a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii) a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA. PMID:26247968

  17. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing.

    PubMed

    Valenzuela, Rodrigo; Bascuñán, Karla; Chamorro, Rodrigo; Barrera, Cynthia; Sandoval, Jorge; Puigrredon, Claudia; Parraguez, Gloria; Orellana, Paula; Gonzalez, Valeria; Valenzuela, Alfonso

    2015-08-04

    α-Linolenic acid (ALA) is the precursor of docosahexaenoic acid (DHA) in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L.), a plant native to some Latin American countries, is high in ALA (up to 60%) and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22-35 years old) tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21) and a chia group (n = 19), which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i) a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA) ingestion, no showing modification of arachidonic acid (AA), eicosapentaenoic acid (EPA) and DHA; (ii) a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii) a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA.

  18. Using a mass balance to understand the geology and geochemistry of a reservoir receiving and discharging acid mine drainage

    SciTech Connect

    Turney, D.C.; Edwards, K.

    1996-11-01

    Howard-Williams Lake is a 14.5 acre reservoir located in an abandoned coal mine in Perry County, Ohio. With a pH of 3.0 and acidity values of 300--400 mg/L, the reservoir has no plants or fish currently surviving in the lake. Reclamation of spoil piles adjacent to the lake to the north in the late 1980s was not successful in reducing the acidity of the lake. Currently, papermill sludge is being used on the reclaimed area to the north to promote vegetation, but the reservoir has shown no signs of improving. The goal of this project is to transform the lake into a fishable and swimmable one. The reservoir is receiving about 175 gallons per minute of acid mine drainage, not including seepage into the lake, from eight different sources. Three of the sources account for about 165 gallons per minute of the surface water that enters the lake. These inflows have relatively low acidity readings, which range from 66 mg/L to 568 mg/L. The other five sources of acid mine drainage have much lower flowrates, but have acidity values as high as 3,000 mg/L. Samples of all of the surface inflows and the outflow of the lake were taken and sent to a laboratory and tested for the following parameters: total acidity as CaCO{sub 3}, total alkalinity as CaCO{sub 2}, specific conductivity, total suspended solids, sulfate, chloride calcium, magnesium, sodium, potassium, total iron, total manganese, aluminum, and hardness. During sampling of the surface inflows, volumetric flowrates were measured for each inflow. Once the flowrates and the concentrations of the various parameters were known, a mass balance could be constructed which would show how much of each parameter was entering the lake each day. These data were then used to gain an understanding of the geochemistry and geology of the site.

  19. Natural attenuation processes in two water reservoirs receiving acid mine drainage.

    PubMed

    Sarmiento, Aguasanta M; Olías, Manuel; Nieto, José Miguel; Cánovas, Carlos R; Delgado, Joquín

    2009-03-01

    Characteristics of water profiles and sulphide formation processes in sediments were studied in two water reservoirs affected by acid mine drainage in order to investigate the mechanisms controlling the physical and chemical processes that, under favourable conditions, act to reduce the toxicity, mobility and concentration of metals and metalloids in the water column. Water columns and pore-waters from sediments were analysed for Fe species, trace elements (As, Cd, Co, Cu, Mn, Ni, Pb, Zn, Cr), sulphide, sulphate and bicarbonate. Inorganic reduced sulphur compounds (acid volatile sulphur, pyrite sulphur and elemental sulphur) and reactive Fe were determined in the sediments. A sequential extraction was also performed. Both reservoirs behave like holomictic and monomictic lakes, with a summer thermal stratification that disappears during winter. pH values between 4 and 7 can be observed along the water columns. Pore-water concentrations of up to 25 mg/l of Fe, 4 mg/l of Al, 1.3 mg/l of Zn, 170 microg/l of Pb, 11 microg/l of As, etc. have been found. The results suggest that toxic elements such as Cu, Zn, Co, Pb, Cr, As, etc. are mainly found in the bioavailable fraction which is the most hazardous for the environment. The calculated degree of sulphidization (DOS) and degree of pyritization (DOP) values indicates that removal of trace elements from anoxic pore-waters occurs by coprecipitation and/or adsorption on newly formed Fe sulphides (framboidal pyrite), attenuating the contamination. However oxidation of the sediments during turnover periods also occurs, which releases toxic elements back into the water column. PMID:19073338

  20. Leaching behavior of heavy metals and transformation of their speciation in polluted soil receiving simulated acid rain.

    PubMed

    Zheng, Shun-an; Zheng, Xiangqun; Chen, Chun

    2012-01-01

    Heavy metals that leach from contaminated soils under acid rain are of increasing concern. In this study, simulated acid rain (SAR) was pumped through columns of artificially contaminated purple soil. Column leaching tests and sequential extraction were conducted for the heavy metals Cu, Pb, Cd, and Zn to determine the extent of their leaching as well as to examine the transformation of their speciation in the artificially contaminated soil columns. Results showed that the maximum leachate concentrations of Cu, Pb, Cd, and Zn were less than those specified in the Chinese Quality Standards for Groundwater (Grade IV), thereby suggesting that the heavy metals that leached from the polluted purple soil receiving acid rain may not pose as risks to water quality. Most of the Pb and Cd leachate concentrations were below their detection limits. By contrast, higher Cu and Zn leachate concentrations were found because they were released by the soil in larger amounts as compared with those of Pb and Cd. The differences in the Cu and Zn leachate concentrations between the controls (SAR at pH 5.6) and the treatments (SAR at pH 3.0 and 4.5) were significant. Similar trends were observed in the total leached amounts of Cu and Zn. The proportions of Cu, Pb, Cd, and Zn in the EXC and OX fractions were generally increased after the leaching experiment at three pH levels, whereas those of the RES, OM, and CAR fractions were slightly decreased. Acid rain favors the leaching of heavy metals from the contaminated purple soil and makes the heavy metal fractions become more labile. Moreover, a pH decrease from 5.6 to 3.0 significantly enhanced such effects.

  1. Leaching behavior of heavy metals and transformation of their speciation in polluted soil receiving simulated acid rain.

    PubMed

    Zheng, Shun-an; Zheng, Xiangqun; Chen, Chun

    2012-01-01

    Heavy metals that leach from contaminated soils under acid rain are of increasing concern. In this study, simulated acid rain (SAR) was pumped through columns of artificially contaminated purple soil. Column leaching tests and sequential extraction were conducted for the heavy metals Cu, Pb, Cd, and Zn to determine the extent of their leaching as well as to examine the transformation of their speciation in the artificially contaminated soil columns. Results showed that the maximum leachate concentrations of Cu, Pb, Cd, and Zn were less than those specified in the Chinese Quality Standards for Groundwater (Grade IV), thereby suggesting that the heavy metals that leached from the polluted purple soil receiving acid rain may not pose as risks to water quality. Most of the Pb and Cd leachate concentrations were below their detection limits. By contrast, higher Cu and Zn leachate concentrations were found because they were released by the soil in larger amounts as compared with those of Pb and Cd. The differences in the Cu and Zn leachate concentrations between the controls (SAR at pH 5.6) and the treatments (SAR at pH 3.0 and 4.5) were significant. Similar trends were observed in the total leached amounts of Cu and Zn. The proportions of Cu, Pb, Cd, and Zn in the EXC and OX fractions were generally increased after the leaching experiment at three pH levels, whereas those of the RES, OM, and CAR fractions were slightly decreased. Acid rain favors the leaching of heavy metals from the contaminated purple soil and makes the heavy metal fractions become more labile. Moreover, a pH decrease from 5.6 to 3.0 significantly enhanced such effects. PMID:23185399

  2. Leaching Behavior of Heavy Metals and Transformation of Their Speciation in Polluted Soil Receiving Simulated Acid Rain

    PubMed Central

    Zheng, Shun-an; Zheng, Xiangqun; Chen, Chun

    2012-01-01

    Heavy metals that leach from contaminated soils under acid rain are of increasing concern. In this study, simulated acid rain (SAR) was pumped through columns of artificially contaminated purple soil. Column leaching tests and sequential extraction were conducted for the heavy metals Cu, Pb, Cd, and Zn to determine the extent of their leaching as well as to examine the transformation of their speciation in the artificially contaminated soil columns. Results showed that the maximum leachate concentrations of Cu, Pb, Cd, and Zn were less than those specified in the Chinese Quality Standards for Groundwater (Grade IV), thereby suggesting that the heavy metals that leached from the polluted purple soil receiving acid rain may not pose as risks to water quality. Most of the Pb and Cd leachate concentrations were below their detection limits. By contrast, higher Cu and Zn leachate concentrations were found because they were released by the soil in larger amounts as compared with those of Pb and Cd. The differences in the Cu and Zn leachate concentrations between the controls (SAR at pH 5.6) and the treatments (SAR at pH 3.0 and 4.5) were significant. Similar trends were observed in the total leached amounts of Cu and Zn. The proportions of Cu, Pb, Cd, and Zn in the EXC and OX fractions were generally increased after the leaching experiment at three pH levels, whereas those of the RES, OM, and CAR fractions were slightly decreased. Acid rain favors the leaching of heavy metals from the contaminated purple soil and makes the heavy metal fractions become more labile. Moreover, a pH decrease from 5.6 to 3.0 significantly enhanced such effects. PMID:23185399

  3. Apoptosis repressor with caspase recruitment domain enhances survival and promotes osteogenic differentiation of human osteoblast cells under Zoledronate treatment

    PubMed Central

    Hu, Longwei; Han, Jing; Yang, Xi; Wang, Yang; Pan, Hongya; Xu, Liqun

    2016-01-01

    Zoledronate is one of the most potent nitrogen-containing bisphosphonates which has been demonstrated to result in osteoblast apoptosis and impact osteogenic differentiation in vitro. This effect of Zoledronate on osteoblasts may partially explain bisphosphonate-associated osteonecrosis of the jaw, a serious complication associated with treatment with bisphosphonates. Apoptosis repressor with caspase recruitment domain (ARC) is a multifunctional inhibitor of apoptosis that is physiologically expressed predominantly in post-mitotic cells such as cardiomyocytes, neurons and skeletal muscle cells. However, its effect on human osteoblasts remains unclear. The current study aimed to investigate the effects of ARC on human osteoblasts under the treatment of high concentrations of Zoledronate. ARC-overexpressed human osteoblasts were established and were exposed to Zoledronate with different concentrations (0, 1 and 5 µM) in vitro. Cell numbers were detected using the MTT assay, and flow cytometry was used to identity cell apoptosis. Alkaline phosphatase staining, quantitative analysis and ectopic osteogenesis in nude mice were used to evaluate the osteogenic differentiation of ARC-overexpressed osteoblasts. It was observed that ARC is able to reverse the inhibitory effect of Zoldronate on osteoblasts. ARC is additionally able to promote osteogenic differentiation of osteoblasts and inhibit their apoptosis. These observations suggest a critical role for ARC in the regulation of human osteoblasts under Zoledronate treatment. PMID:27573706

  4. Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid

    PubMed Central

    Li, Hongliang; Wang, Xueding; Zhou, Yafang; Ni, Guanzhong; Su, Qibiao; Chen, Ziyi; Chen, Zhuojia; Li, Jiali; Chen, Xinmeng; Hou, Xiangyu; Xie, Wen; Xin, Shuang; Zhou, Liemin

    2015-01-01

    Background: Weight gain is the most frequent adverse effect of valproic acid (VPA) treatment, resulting in poor compliance and many endocrine disturbances. Similarities in the weight change of monozygotic twins receiving VPA strongly suggests that genetic factors are involved in this effect. However, few studies have been conducted to identify the relevant genetic polymorphisms. Additionally, the causal relationship between the VPA concentration and weight gain has been controversial. Thus, we investigated the effects of single nucleotide polymorphisms (SNPs) in several appetite stimulation and energy homeostasis genes and the steady state plasma concentrations (Css) of VPA on the occurrence of weight gain in patients. Methods: A total of 212 epilepsy patients receiving VPA were enrolled. Nineteen SNPs in 11 genes were detected using the Sequenom MassArray iPlex platform, and VPA Css was determined by high-performance liquid chromatography (HPLC). Results: After 6 months of treatment, 20.28% of patients were found to gain a significant amount of weight (weight gained ≥7%). Three SNPs in the leptin receptor (LEPR), ankyrin repeat kinase domain containing 1 (ANKK1), and α catalytic subunit of adenosine monophosphate-activated protein kinase (AMPK) showed significant associations with VPA-induced weight gain (p < 0.001, p = 0.017 and p = 0.020, respectively). After Bonferroni correction for multiple tests, the genotypic association of LEPR rs1137101, the allelic association of LEPR rs1137101, and ANKK1 rs1800497 with weight gain remained significant. However, the VPA Css in patents who gained weight were not significantly different from those who did not gain weight (p = 0.121). Conclusions: LEPR and ANKK1 genetic polymorphisms may have value in predicting VPA-induced weight gain. PMID:25740917

  5. Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: a case-control study.

    PubMed

    Montes, Felix R; Pardo, Daniel F; Carreño, Marisol; Arciniegas, Catalina; Dennis, Rodolfo J; Umaña, Juan P

    2012-01-01

    Antifibrinolytic agents are used during cardiac surgery to minimize bleeding and reduce exposure to blood products. Several reports suggest that tranexamic acid (TA) can induce seizure activity in the postoperative period. To examine factors associated with postoperative seizures in patients undergoing cardiac surgery who received TA. University-affiliated hospital. Case-control study. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) between January 2008 and December 2009 were identified. During this time, all patients undergoing heart surgery with CPB received TA. Cases were defined as patients who developed seizures that required initiation of anticonvulsive therapy within 48 h of surgery. Exclusion criteria included subjects with preexisting epilepsy and patients in whom the convulsive episode was secondary to a new ischemic lesion on brain imaging. Controls who did not develop seizures were randomly selected from the initial cohort. From an initial cohort of 903 patients, we identified 32 patients with postoperative seizures. Four patients were excluded. Twenty-eight cases and 112 controls were analyzed. Cases were more likely to have a history of renal impairment and higher preoperative creatinine values compared with controls (1.39 ± 1.1 vs. 0.98 ± 0.02 mg/dL, P = 0.02). Significant differences in the intensive care unit, postoperative and total lengths of stay were observed. An association between high preoperative creatinine value and postoperative seizure was identified. TA may be associated with the development of postoperative seizures in patients with renal dysfunction. Doses of TA should be reduced or even avoided in this population. PMID:22234015

  6. Combined effect of strontium and zoledronate on hydroxyapatite structure and bone cell responses.

    PubMed

    Boanini, Elisa; Torricelli, Paola; Gazzano, Massimo; Della Bella, Elena; Fini, Milena; Bigi, Adriana

    2014-07-01

    The influence of the simultaneous presence of the two inhibitors of bone degradation, strontium and zoledronate, on the direct synthesis of hydroxyapatite was explored in the range of Sr concentration up to 50 atom% at two different bisphosphonate concentrations (ZOL7 and ZOL14). The results of structural analysis indicated that HA can be obtained as a single crystalline phase up to a Sr concentration in solution of 20 and 10 atom% within the ZOL7 and ZOL14 series respectively. Both Sr substitution and ZOL incorporation affect the length of the coherently scattering crystalline domains and the dimensions of HA nanocrystals. At greater Sr content, XRD full profile fitting data indicate that zoledronate provokes the segregation of Sr in two crystalline apatitic phases, at different strontium content. Co-cultures of osteoblast-like MG63 cells and human osteoclast show that ZOL displays a greater inhibitory influence than Sr on osteoclast proliferation and activity. On the other hand, the results obtained on osteoblast surnatant and on gene expression indicate that Sr exerts a greater promotion on osteoblast proliferation and differentiation. The co-presence of Sr and ZOL has a combined effect on the differentiation markers, so that HA containing about 4 wt% ZOL and 4 Sr atom%, and even more HA containing about 4 wt% ZOL and 8 Sr atom%, result the best compromise for osteoblast promotion and osteoclast inhibition.

  7. Combined effect of strontium and zoledronate on hydroxyapatite structure and bone cell responses.

    PubMed

    Boanini, Elisa; Torricelli, Paola; Gazzano, Massimo; Della Bella, Elena; Fini, Milena; Bigi, Adriana

    2014-07-01

    The influence of the simultaneous presence of the two inhibitors of bone degradation, strontium and zoledronate, on the direct synthesis of hydroxyapatite was explored in the range of Sr concentration up to 50 atom% at two different bisphosphonate concentrations (ZOL7 and ZOL14). The results of structural analysis indicated that HA can be obtained as a single crystalline phase up to a Sr concentration in solution of 20 and 10 atom% within the ZOL7 and ZOL14 series respectively. Both Sr substitution and ZOL incorporation affect the length of the coherently scattering crystalline domains and the dimensions of HA nanocrystals. At greater Sr content, XRD full profile fitting data indicate that zoledronate provokes the segregation of Sr in two crystalline apatitic phases, at different strontium content. Co-cultures of osteoblast-like MG63 cells and human osteoclast show that ZOL displays a greater inhibitory influence than Sr on osteoclast proliferation and activity. On the other hand, the results obtained on osteoblast surnatant and on gene expression indicate that Sr exerts a greater promotion on osteoblast proliferation and differentiation. The co-presence of Sr and ZOL has a combined effect on the differentiation markers, so that HA containing about 4 wt% ZOL and 4 Sr atom%, and even more HA containing about 4 wt% ZOL and 8 Sr atom%, result the best compromise for osteoblast promotion and osteoclast inhibition. PMID:24731709

  8. Osteonecrosis of the Jaw in Patients Receiving Bone-Targeted Therapies: An Overview--Part I.

    PubMed

    Turner, Bruce; Drudge-Coates, Lawrence; Ali, Sacha; Pati, Jhumur; Nargund, Vinod; Ali, Enamul; Cheng, Leo; Wells, Paula

    2016-01-01

    Urologic patients receiving bone-targeted therapies are at risk of developing osteonecrosis of the jaw (ONJ). ONJ has historically been associated with bisphosphonate therapy. More recently, RANK-Ligand inhibitors (denosumab) have also been used to reduce the risk of skeletal-related events in patients who have advanced cancers with bone metastases. More than 65% of men with metastatic prostate cancer and nearly 75% of women with metastatic breast cancer are affected by bone metastases. The literature has described ONJ associated with bisphosphonate therapy as bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, with evidence also linking the use of RANK-Ligand inhibitors with osteonecrosis of the jaw, we advocate use of the term "anti-bone resorption therapy-related osteonecrosis of the jaw" (ABRT-ONJ). The term "medication-related osteonecrosis of the jaw" (MRONJ) is now becoming more widespread. There is not a universally accepted definition of ABRT-ONJ, which may have hindered recognition and reporting of the condition. In Part I of this article, a review of current knowledge around the etiology of ABRT-ONJ and incidence data are provided. In Part II, we provide an audit of ONJ in a nurse consultant-led bone support clinic. In the article, we refer to zoledronic acid because this is the bisphosphonate of choice for use in men with prostate cancer in the United Kingdom. PMID:27501591

  9. Applying low-intensity pulsed ultrasounds (LIPUS) to a zoledronate-associated atypical femoral shaft fracture without cessation of zoledronate therapy for 3 years follow up: a case report

    PubMed Central

    Arakawa, Shoutaro; Saito, Mitsuru; Kubota, Makoto; Suzuki, Hidehiko; Tsuchida, Shigeki; Hashimoto, Kurando; Marumo, Keishi

    2015-01-01

    Summary Reports are increasing regarding atypical femoral fractures (AFFs) caused by minor trauma in patients using bisphosphonates (BPs) for long periods. Patients with malignant skeletal metastases potentially are at greater risk for these AFFs, especially considering the high dose and the duration of treatment with BPs. We evaluated a case of atypical femoral shaft fracture treated with an intramedullary nail in a patient treated for five years with zoledronate who had breast cancer with metastases to bone. Although bone union was achieved without cessation of zoledronate therapy by applying low-intensity pulsed ultrasounds (LIPUS), the remodeling phase of the fracture healing process was delayed. For BPs-associated AFFs, LIPUS is an alternative to parathyroid hormone (PTH) analogs such as teriparatide that are contraindicated in patients with malignant skeletal metastases. LIPUS is an effective treatment for fracture healing and may avoid the necessity to discontinue BP therapy. PMID:26811711

  10. Supplemental branched-chain amino acids improve performance and immune response of newly-received feedlot calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Supplemental branched-chain AA (BCAA) improved N balance of steers during a simulated pathogen challenge. The objective of this study was to determine the effect of supplemental BCAA on growth and health of newly-received feedlot steers. Steers (n = 120; initial BW = 376 ± 5 kg) were blocked by BW a...

  11. Zoledronate derivatives as potential inhibitors of uridine diphosphate-galactose ceramide galactosyltransferase 8: A combined molecular docking and dynamic study.

    PubMed

    Pannuzzo, Giovanna; Graziano, Adriana Carol Eleonora; Pannuzzo, Martina; Masman, Marcelo Fabricio; Avola, Rosanna; Cardile, Venera

    2016-11-01

    Krabbe's disease is a neurodegenerative disorder caused by deficiency of galactocerebrosidase activity that affects the myelin sheath of the nervous system, involving dysfunctional metabolism of sphingolipids. It has no cure. Because substrate inhibition therapy has been shown to be effective in some human lysosomal storage diseases, we hypothesize that a substrate inhibition therapeutic approach might be appropriate to allow correction of the imbalance between formation and breakdown of glycosphingolipids and to prevent pathological storage of psychosine. The enzyme responsible for the biosynthesis of galactosylceramide and psychosine is uridine diphosphate-galactose ceramide galactosyltransferase (2-hydroxyacylsphingosine 1-β-galactosyltransferase; UGT8; EC 2.4.1.45), which catalyzes the transferring of galactose from uridine diphosphate-galactose to ceramide or sphingosine, an important step of the biosynthesis of galactosphingolipids. Because some bisphosphonates have been identified as selective galactosyltransferase inhibitors, we verify the binding affinity to a generated model of the enzyme UGT8 and investigate the molecular mechanisms of UGT8-ligand interactions of the bisphosphonate zoledronate by a multistep framework combining homology modeling, molecular docking, and molecular dynamics simulations. From structural information on UGTs' active site stereochemistry, charge density, and access through the hydrophobic environment, the molecular docking procedure allowed us to identify zoledronate as a potential inhibitor of human ceramide galactosyltransferase. More importantly, zoledronate derivates were designed through computational modeling as putative new inhibitors. Experiments in vivo and in vitro have been planned to verify the possibility of using zoledronate and/or the newly identified inhibitors of UGT8 for a substrate inhibition therapy useful for treatment of Krabbe's disease and/or other lysosomal disorders. © 2016 Wiley Periodicals, Inc.

  12. Zoledronate derivatives as potential inhibitors of uridine diphosphate-galactose ceramide galactosyltransferase 8: A combined molecular docking and dynamic study.

    PubMed

    Pannuzzo, Giovanna; Graziano, Adriana Carol Eleonora; Pannuzzo, Martina; Masman, Marcelo Fabricio; Avola, Rosanna; Cardile, Venera

    2016-11-01

    Krabbe's disease is a neurodegenerative disorder caused by deficiency of galactocerebrosidase activity that affects the myelin sheath of the nervous system, involving dysfunctional metabolism of sphingolipids. It has no cure. Because substrate inhibition therapy has been shown to be effective in some human lysosomal storage diseases, we hypothesize that a substrate inhibition therapeutic approach might be appropriate to allow correction of the imbalance between formation and breakdown of glycosphingolipids and to prevent pathological storage of psychosine. The enzyme responsible for the biosynthesis of galactosylceramide and psychosine is uridine diphosphate-galactose ceramide galactosyltransferase (2-hydroxyacylsphingosine 1-β-galactosyltransferase; UGT8; EC 2.4.1.45), which catalyzes the transferring of galactose from uridine diphosphate-galactose to ceramide or sphingosine, an important step of the biosynthesis of galactosphingolipids. Because some bisphosphonates have been identified as selective galactosyltransferase inhibitors, we verify the binding affinity to a generated model of the enzyme UGT8 and investigate the molecular mechanisms of UGT8-ligand interactions of the bisphosphonate zoledronate by a multistep framework combining homology modeling, molecular docking, and molecular dynamics simulations. From structural information on UGTs' active site stereochemistry, charge density, and access through the hydrophobic environment, the molecular docking procedure allowed us to identify zoledronate as a potential inhibitor of human ceramide galactosyltransferase. More importantly, zoledronate derivates were designed through computational modeling as putative new inhibitors. Experiments in vivo and in vitro have been planned to verify the possibility of using zoledronate and/or the newly identified inhibitors of UGT8 for a substrate inhibition therapy useful for treatment of Krabbe's disease and/or other lysosomal disorders. © 2016 Wiley Periodicals, Inc

  13. Selected resin acids in effluent and receiving waters derived from a bleached and unbleached kraft pulp and paper mill

    USGS Publications Warehouse

    Quinn, B.P.; Booth, M.M.; Delfino, J.J.; Holm, S.E.; Gross, T.S.

    2003-01-01

    Water samples were collected on three dates at 24 sites influenced by effluent from Georgia-Pacific's Palatka Pulp and Paper Mill Operation, a bleached and unbleached kraft mill near Palatka, Florida, USA. The sampling sites were located within the mill retention ponds, Rice Creek, and the St. John's River. Samples were analyzed by gas chromatography-mass spectrometry for abietic, dehydroabietic, and isopimaric acids, all of which are potentially toxic by-products of pulp production. Isopimaric acid concentrations greater than 12 mg/L were measured at the mill's effluent outfall but were less than 20 ??g/L at the end of Rice Creek. This result indicates that the waters of Rice Creek provide dilution or conditions conducive for degradation or sorption of these compounds. Large differences in resin acid concentrations were observed between sampling events. In two sampling events, the maximum observed concentrations were less than 2 mg/L for each analyte. In a third sampling event, all of the compounds were detected at concentrations greater than 10 mg/L. Data from the three sample dates showed that resin acid concentrations were below 20 ??g/L before the confluence of Rice Creek and the St. John's River in all cases.

  14. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    ClinicalTrials.gov

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  15. Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet.

    PubMed

    Porta, Natacha; Vallée, Louis; Boutry, Elisabeth; Fontaine, Monique; Dessein, Anne-Frédérique; Joriot, Sylvie; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; Auvin, Stéphane

    2009-06-01

    The ketogenic diet (KD) and the modified Atkins diet are effective therapies for intractable epilepsy. We compared retrospectively the KD and modified Atkins diet in 27 children and also assessed serum long chain fatty acid profiles. After 3 months, using an intent-to-treat analysis, the KD was more successful, with >50% seizure reduction in 11/17 (65%) vs. 2/10 (20%) with the modified Atkins diet, p=0.03. After 6 months, however, the difference was no longer significant: 7/17 (41%) vs. 2/10 (20%) (p=0.24). We observed a preventive effect of both diets on the occurrence of status epilepticus. After 1 and 3 months of either diet, responders experienced a significant decrease in serum arachidonic acid concentration compared to non-responders. The KD and modified Atkins diet led to seizure reduction in this small pilot series, with slightly better results after 3 months with the KD, but not after 6 months. The decrease of serum arachidonic acid levels might be involved in the anticonvulsive effects of KD or modified Atkins diet.

  16. Performance, Carcass Quality and Fatty Acid Profile of Crossbred Wagyu Beef Steers Receiving Palm and/or Linseed Oil.

    PubMed

    Suksombat, Wisitiporn; Meeprom, Chayapol; Mirattanaphrai, Rattakorn

    2016-10-01

    The objective of this study was to determine the effect of palm and/or linseed oil (LSO) supplementation on carcass quality, sensory evaluation and fatty acid profile of beef from crossbred Wagyu beef steers. Twenty four fattening Wagyu crossbred beef steers (50% Wagyu), averaging 640±18 kg live weight (LW) and approximately 30 mo old, were stratified and randomly assigned in completely randomized design into 3 treatment groups. All steers were fed approximately 7 kg/d of 14% crude protein concentrate with ad libitum rice straw and had free access to clean water and were individually housed in a free-stall unit. The treatments were i) control concentrate plus 200 g/d of palm oil; ii) control concentrate plus 100 g/d of palm oil and 100 g/d of LSO, iii) control concentrate plus 200 g/d of LSO. This present study demonstrated that supplementation of LSO rich in C18:3n-3 did not influence feed intakes, LW changes, carcass and muscle characteristics, sensory and physical properties. LSO increased C18:3n-3, C22:6n-3, and n-3 polyunsaturated fatty acids (PUFA), however, it decreased C18:1t-11, C18:2n-6, cis-9, trans-11, and trans-10,cis-12 conjugated linoleic acids, n-6 PUFA and n-6:n-3 ratio in Longissimus dorsi and Semimembranosus muscles.

  17. Performance, Carcass Quality and Fatty Acid Profile of Crossbred Wagyu Beef Steers Receiving Palm and/or Linseed Oil

    PubMed Central

    Suksombat, Wisitiporn; Meeprom, Chayapol; Mirattanaphrai, Rattakorn

    2016-01-01

    The objective of this study was to determine the effect of palm and/or linseed oil (LSO) supplementation on carcass quality, sensory evaluation and fatty acid profile of beef from crossbred Wagyu beef steers. Twenty four fattening Wagyu crossbred beef steers (50% Wagyu), averaging 640±18 kg live weight (LW) and approximately 30 mo old, were stratified and randomly assigned in completely randomized design into 3 treatment groups. All steers were fed approximately 7 kg/d of 14% crude protein concentrate with ad libitum rice straw and had free access to clean water and were individually housed in a free-stall unit. The treatments were i) control concentrate plus 200 g/d of palm oil; ii) control concentrate plus 100 g/d of palm oil and 100 g/d of LSO, iii) control concentrate plus 200 g/d of LSO. This present study demonstrated that supplementation of LSO rich in C18:3n-3 did not influence feed intakes, LW changes, carcass and muscle characteristics, sensory and physical properties. LSO increased C18:3n-3, C22:6n-3, and n-3 polyunsaturated fatty acids (PUFA), however, it decreased C18:1t-11, C18:2n-6, cis-9, trans-11, and trans-10,cis-12 conjugated linoleic acids, n-6 PUFA and n-6:n-3 ratio in Longissimus dorsi and Semimembranosus muscles. PMID:26954221

  18. Performance, Carcass Quality and Fatty Acid Profile of Crossbred Wagyu Beef Steers Receiving Palm and/or Linseed Oil.

    PubMed

    Suksombat, Wisitiporn; Meeprom, Chayapol; Mirattanaphrai, Rattakorn

    2016-10-01

    The objective of this study was to determine the effect of palm and/or linseed oil (LSO) supplementation on carcass quality, sensory evaluation and fatty acid profile of beef from crossbred Wagyu beef steers. Twenty four fattening Wagyu crossbred beef steers (50% Wagyu), averaging 640±18 kg live weight (LW) and approximately 30 mo old, were stratified and randomly assigned in completely randomized design into 3 treatment groups. All steers were fed approximately 7 kg/d of 14% crude protein concentrate with ad libitum rice straw and had free access to clean water and were individually housed in a free-stall unit. The treatments were i) control concentrate plus 200 g/d of palm oil; ii) control concentrate plus 100 g/d of palm oil and 100 g/d of LSO, iii) control concentrate plus 200 g/d of LSO. This present study demonstrated that supplementation of LSO rich in C18:3n-3 did not influence feed intakes, LW changes, carcass and muscle characteristics, sensory and physical properties. LSO increased C18:3n-3, C22:6n-3, and n-3 polyunsaturated fatty acids (PUFA), however, it decreased C18:1t-11, C18:2n-6, cis-9, trans-11, and trans-10,cis-12 conjugated linoleic acids, n-6 PUFA and n-6:n-3 ratio in Longissimus dorsi and Semimembranosus muscles. PMID:26954221

  19. Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids

    PubMed Central

    Amminger, G P; Mechelli, A; Rice, S; Kim, S-W; Klier, C M; McNamara, R K; Berk, M; McGorry, P D; Schäfer, M R

    2015-01-01

    Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre–post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the

  20. Stratification of Metal and Sulphate Loads in Acid Mine Drainage Receiving Water Dams - Variables Regionalization by Cluster Analysis.

    PubMed

    Grande, J A; de la Torre, M L; Valente, T; Fernández, J P; Borrego, J; Santisteban, M; Cerón, J C; Sánchez-Rodas, D

    2015-07-01

    The Sancho Reservoir (Iberian Pyrite Belt, SW Spain) is nourished by the waters of the river Meca, which is affected by acid mine drainage (AMD) processes from the abandoned Tharsis mine. The aim of the present work is to study the hydrochemical variations in this reservoir, in order to define potential stratification processes in metal load and sulphates. A stratified sampling from the surface, with one meter deep intervals to the bottom of the dam, was performed. The results show a clear stratification of temperature, pH, electric conductivity, dissolved oxygen, metal and sulphate loads associated with depth. There is an increase of metal loads at the bottom of the reservoir, though previous studies only detect iron. The proximity between pH and aluminium suggests that water chemistry is strongly influenced by aluminium precipitation processes. This indicates the buffer effect that aluminium exercises, which precipitates as amorphous or low crystalline phases, introducing hydrogen ions to the system, while alkalinity input tends to raise pH. PMID:26163498

  1. Serum α-1 acid glycoprotein and serum amyloid A concentrations in cats receiving antineoplastic treatment for lymphoma.

    PubMed

    Winkel, Valter M; Pavan, Tatiana L R; Wirthl, Vera A B F; Alves, Ana L N; Lucas, Silvia R R

    2015-11-01

    OBJECTIVE To characterize serum α-1 acid glycoprotein (AGP) and serum amyloid A (SAA) concentrations at diagnosis and during treatment in cats with lymphoma. ANIMALS 16 cats with various anatomic forms of lymphoma and 25 healthy cats. PROCEDURES Blood samples were collected from healthy cats once and from cats with lymphoma at diagnosis and 2-week intervals until the 12th week of antineoplastic treatment. Serum harvested from blood samples was assessed for AGP and SAA concentrations. Differences in serum AGP and SAA values were investigated between healthy cats and cats with lymphoma (at diagnosis) and, for cats with lymphoma, between diagnosis and various points during treatment. RESULTS Serum AGP and SAA concentrations were higher in cats with lymphoma at diagnosis (median, 832.60 and 1.03 μg/mL, respectively), compared with those in healthy cats (median, 269.85 and 0.10 μg/mL). Treatment resulted in a gradual decrease in serum AGP concentration after 4 weeks and in SAA concentration after 8 weeks of treatment, and these concentrations returned to values comparable with those of healthy cats by 12 weeks of treatment, by which point all cats had achieved complete remission of the disease. CONCLUSIONS AND CLINICAL RELEVANCE Serum AGP and SAA concentrations in cats with lymphoma were higher at diagnosis than after antineoplastic treatment. Decreases to values established for healthy cats corresponded with achievement of complete disease remission. Serum AGP and SAA may be useful protein markers for monitoring of antineoplastic treatment in cats with lymphoma.

  2. Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis mediated by human γδ T cells.

    PubMed

    Nishio, Nobuhiro; Fujita, Mitsugu; Tanaka, Yoshimasa; Maki, Hiroyuki; Zhang, Rong; Hirosawa, Tomoya; Demachi-Okamura, Ayako; Uemura, Yasushi; Taguchi, Osamu; Takahashi, Yoshiyuki; Kojima, Seiji; Kuzushima, Kiyotaka

    2012-10-01

    Neuroblastoma is the most common extracranial solid tumor in children that is refractory to intensive multimodal therapy. In particular, tumor-initiating cells (TICs) derived from neuroblastoma are believed responsible for tumor formation and resistance to the conventional therapy; an optimal strategy therefore should target this population. Technically, TICs can be enriched from neuroblastoma-derived spheres when the tumor cells are cultured in a serum-free medium supplemented with certain growth factors. Recently, a line of evidence has suggested antitumor potential of Vγ9Vδ2 T cells (γδ T cells), a T-cell population that recognizes and kills target cells independent of surface HLA expressions. Furthermore, a mevalonate pathway inhibitor, zoledronate, has been reported to enhance cytolytic activity of γδ T cells. On the basis of these findings, we hypothesized that zoledronate would sensitize neuroblastoma TICs to γδ T-cell-mediated cytolysis and promote therapeutic efficacy against neuroblastoma. In the current study, we show that zoledronate efficiently sensitizes both neuroblastoma-derived adherent cells and sphere-forming cells to γδ T-cell-mediated cytolysis. Subsequently, in vitro colony formation inhibition assay and in vivo animal studies reveal that the presence of γδ T cells decelerates outgrowth of neuroblastoma TICs. We finally show that addition of interleukin-15 and/or interleukin-18 in culture enhances the cytolytic activity of γδ T cells. On the basis of these data, we conclude that ex vivo expanded γδ T cells are a promising tool for antineuroblastoma immunotherapy with options for further improvement.

  3. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats.

    PubMed

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei

    2012-06-01

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery.

  4. Effects of oil and natural or synthetic vitamin E on ruminal and milk fatty acid profiles in cows receiving a high-starch diet.

    PubMed

    Zened, A; Troegeler-Meynadier, A; Najar, T; Enjalbert, F

    2012-10-01

    Among trans fatty acids, trans-10,cis-12 CLA has negative effects on cow milk fat production and can affect human health. In high-yielding dairy cows, a shift from the trans-11 to the trans-10 pathway of biohydrogenation (BH) can occur in the rumen of cows receiving high-concentrate diets, especially when the diet is supplemented with unsaturated fat sources. In some but not all experiments, vitamin E has been shown to control this shift. To ascertain the effects of vitamin E on this shift of BH pathway, 2 studies were conducted. The first study explored in vitro the effects of addition of natural (RRR-α-tocopherol acetate) and synthetic (dl-α-tocopherol acetate) vitamin E. Compared with control and synthetic vitamin E, the natural form resulted in a greater trans-10/trans-11 ratio; however, the effect was very low, suggesting that vitamin E was neither a limiting factor for rumen BH nor a modulator of the BH pathway. An in vivo study investigated the effect of natural vitamin E (RRR-α-tocopherol) on this shift and subsequent milk fat depression. Six rumen-fistulated lactating Holstein cows were assigned to a 2×2 crossover design. Cows received 20-kg DM of a control diet based on corn silage with 22% of wheat, and after 2 wk of adaptation, the diet was supplemented with 600 g of sunflower oil for 2 more weeks. During the last week of this 4-wk experimental period, cows were divided into 2 groups: an unsupplemented control group and a group receiving 11 g of RRR-α-tocopherol acetate per day. A trans-10 shift of ruminal BH associated with milk fat depression due to oil supplementation of a high-wheat diet was observed, but vitamin E supplementation of dairy cows did not result in a reversal toward a trans-11 BH pathway, and did not restore milk fat content.

  5. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits.

    PubMed

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  6. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits

    PubMed Central

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  7. CALUTRON RECEIVER

    DOEpatents

    Barnes, S.W.

    1959-08-25

    An improvement in a calutron receiver for collecting the isotopes ts described. The electromagnetic separation of the isotopes produces a mass spectrum of closely adjacent beams of ions at the foci regions, and a dividing wall between the two pockets is arranged at an angle. Substantially all of the tons of the less abundant isotope enter one of the pockets and strike one side of the wall directly, while substantially none of the tons entering the other pocket strikes the wall directly.

  8. TRC150094, a novel functional analog of iodothyronines, reduces adiposity by increasing energy expenditure and fatty acid oxidation in rats receiving a high-fat diet.

    PubMed

    Cioffi, Federica; Zambad, Shitalkumar P; Chhipa, Laxmikant; Senese, Rosalba; Busiello, Rosa Anna; Tuli, Davinder; Munshi, Siralee; Moreno, Maria; Lombardi, Assunta; Gupta, Ramesh C; Chauthaiwale, Vijay; Dutt, Chaitanya; de Lange, Pieter; Silvestri, Elena; Lanni, Antonia; Goglia, Fernando

    2010-09-01

    Chronic overnutrition and modern lifestyles are causing a worldwide epidemic of obesity and associated comorbidities, which is creating a demand to identify underlying biological mechanisms and to devise effective treatments. In rats receiving a high-fat diet (HFD), we analyzed the effects of a 4-wk administration of a novel functional analog of iodothyronines, TRC150094 (TRC). HFD-TRC rats exhibited increased energy expenditure (+24% vs. HFD rats; P<0.05) and body weight (BW) gain comparable to that of standard chow-fed (N) rats [N, HFD, and HFD-TRC rats, +97 g, +140 g (P<0.05 vs. N), and +98 g (P<0.05 vs. HFD)]. HFD-TRC rats had significantly less visceral adipose tissue (vs. HFD rats) and exhibited altered metabolism in two major tissues that are very active metabolically. In liver, mitochondrial fatty acid import and oxidation were increased (+56 and +32%, respectively; P<0.05 vs. HFD rats), and consequently the hepatic triglyceride content was lower (-35%; P<0.05 vs. HFD rats). These effects were independent of the AMP-activated protein kinase-acetyl CoA-carboxylase-malonyl CoA pathway but involved sirtuin 1 activation. In skeletal muscle, TRC induced a fiber shift toward the oxidative type in tibialis anterior muscle, increasing its capacity to oxidize fatty acids. HFD-TRC rats had lower (vs. HFD rats) plasma cholesterol and triglyceride concentrations. If reproduced in humans, these results will open interesting possibilities regarding the counteraction of metabolic dysfunction associated with ectopic/visceral fat accumulation.

  9. Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cells metastasis by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways

    PubMed Central

    Cheng, Hsin-Lin; Lin, Chiao-Wen; Yang, Jia-Sin; Hsieh, Ming-Ju; Yang, Shun-Fa; Lu, Ko-Hsiu

    2016-01-01

    Zoledronate is a standard treatment for preventing skeletal complications of osteoporosis and some types of cancer associated with bone metastases, but we little know whether the effect of zoledronate on metastasis of osteosarcoma. Here, we investigated the inhibitory effects of zoledronate on cell viability, motility, migration and invasion of 4 osteosarcoma cell lines (Saos2, MG-63, HOS and U2OS) by affecting cell morphology, epithelial-mesenchymal transition (EMT) and cytoskeletal organization as well as induction of E-cadherin and reduction of N-cadherin with activation of transcription factors Slug and Twist, especially in U2OS cells. Zoledronate decreased JNK and p38 phosphorylation and upper streams of focal adhesion kinase (FAK) and Src to suppress the motility, invasiveness and migration of U2OS cells. In addition to zoledronate-inhibited Rho A and Cdc42 membrane translocation and GTPγS activities, the anti-metastatic effects in U2OS cells including inhibition of adhesion were reversed by geranylgeraniol, but not farnesol. In conclusion, Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cell-matrix and cell-cell interactions, migration potential, the invasive activity, and the adhesive ability by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. PMID:26848867

  10. Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cells metastasis by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways.

    PubMed

    Cheng, Hsin-Lin; Lin, Chiao-Wen; Yang, Jia-Sin; Hsieh, Ming-Ju; Yang, Shun-Fa; Lu, Ko-Hsiu

    2016-03-01

    Zoledronate is a standard treatment for preventing skeletal complications of osteoporosis and some types of cancer associated with bone metastases, but we little know whether the effect of zoledronate on metastasis of osteosarcoma. Here, we investigated the inhibitory effects of zoledronate on cell viability, motility, migration and invasion of 4 osteosarcoma cell lines (Saos2, MG-63, HOS and U2OS) by affecting cell morphology, epithelial-mesenchymal transition (EMT) and cytoskeletal organization as well as induction of E-cadherin and reduction of N-cadherin with activation of transcription factors Slug and Twist, especially in U2OS cells. Zoledronate decreased JNK and p38 phosphorylation and upper streams of focal adhesion kinase (FAK) and Src to suppress the motility, invasiveness and migration of U2OS cells. In addition to zoledronate-inhibited Rho A and Cdc42 membrane translocation and GTPγS activities, the anti-metastatic effects in U2OS cells including inhibition of adhesion were reversed by geranylgeraniol, but not farnesol. In conclusion, Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cell-matrix and cell-cell interactions, migration potential, the invasive activity, and the adhesive ability by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. PMID:26848867

  11. Pathogen translocation and histopathological lesions in an experimental model of Salmonella Dublin infection in calves receiving lactic acid bacteria and lactose supplements

    PubMed Central

    Zbrun, María V.; Soto, Lorena P.; Bertozzi, Ezequiel; Sequeira, Gabriel J.; Marti, Luis E.; Signorini, Marcelo L.; Armesto, Roberto Rodríguez; Rosmini, Marcelo R.

    2012-01-01

    The purpose of this study was to evaluate the capacity of a lactic acid bacteria (LAB) inoculum to protect calves with or without lactose supplements against Salmonella Dublin infection by evaluating histopathological lesions and pathogen translocation. Fifteen calves were divided into three groups [control group (C-G), a group inoculated with LAB (LAB-G), and a group inoculated with LAB and given lactose supplements (L-LAB-G)] with five, six, and four animals, respectively. The inoculum, composed of Lactobacillus (L.) casei DSPV 318T, L. salivarius DSPV 315T, and Pediococcus acidilactici DSPV 006T, was administered with milk replacer. The LAB-G and L-LAB-G received a daily dose of 109 CFU/kg body weight of each strain throughout the experiment. Lactose was provided to the L-LAB-G in doses of 100 g/day. Salmonella Dublin (2 × 1010 CFU) was orally administered to all animals on day 11 of the experiment. The microscopic lesion index values in target organs were 83%, 70%, and 64.3% (p < 0.05) for the C-G, LAB-G, and L-LAB-G, respectively. Administration of the probiotic inoculum was not fully effective against infection caused by Salmonella. Although probiotic treatment was unable to delay the arrival of pathogen to target organs, it was evident that the inoculum altered the response of animals against pathogen infection. PMID:23000583

  12. Radiation receiver

    DOEpatents

    Hunt, Arlon J.

    1983-01-01

    The apparatus for collecting radiant energy and converting same to alternate energy form includes a housing having an interior space and a radiation transparent window allowing, for example, solar radiation to be received in the interior space of the housing. Means are provided for passing a stream of fluid past said window and for injecting radiation absorbent particles in said fluid stream. The particles absorb the radiation and because of their very large surface area, quickly release the heat to the surrounding fluid stream. The fluid stream particle mixture is heated until the particles vaporize. The fluid stream is then allowed to expand in, for example, a gas turbine to produce mechanical energy. In an aspect of the present invention properly sized particles need not be vaporized prior to the entrance of the fluid stream into the turbine, as the particles will not damage the turbine blades. In yet another aspect of the invention, conventional fuel injectors are provided to inject fuel into the fluid stream to maintain the proper temperature and pressure of the fluid stream should the source of radiant energy be interrupted. In yet another aspect of the invention, an apparatus is provided which includes means for providing a hot fluid stream having hot particles disbursed therein which can radiate energy, means for providing a cooler fluid stream having cooler particles disbursed therein, which particles can absorb radiant energy and means for passing the hot fluid stream adjacent the cooler fluid stream to warm the cooler fluid and cooler particles by the radiation from the hot fluid and hot particles.

  13. Radiation receiver

    DOEpatents

    Hunt, A.J.

    1983-09-13

    The apparatus for collecting radiant energy and converting same to alternate energy form includes a housing having an interior space and a radiation transparent window allowing, for example, solar radiation to be received in the interior space of the housing. Means are provided for passing a stream of fluid past said window and for injecting radiation absorbent particles in said fluid stream. The particles absorb the radiation and because of their very large surface area, quickly release the heat to the surrounding fluid stream. The fluid stream particle mixture is heated until the particles vaporize. The fluid stream is then allowed to expand in, for example, a gas turbine to produce mechanical energy. In an aspect of the present invention properly sized particles need not be vaporized prior to the entrance of the fluid stream into the turbine, as the particles will not damage the turbine blades. In yet another aspect of the invention, conventional fuel injectors are provided to inject fuel into the fluid stream to maintain the proper temperature and pressure of the fluid stream should the source of radiant energy be interrupted. In yet another aspect of the invention, an apparatus is provided which includes means for providing a hot fluid stream having hot particles disbursed therein which can radiate energy, means for providing a cooler fluid stream having cooler particles disbursed therein, which particles can absorb radiant energy and means for passing the hot fluid stream adjacent the cooler fluid stream to warm the cooler fluid and cooler particles by the radiation from the hot fluid and hot particles. 5 figs.

  14. Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.

    PubMed

    Tripathi, Ranu; Singh, Preeti; Singh, Aru; Chagtoo, Megha; Khan, Sajid; Tiwari, Swasti; Agarwal, Gaurav; Meeran, Syed Musthapa; Godbole, Madan M

    2016-01-01

    Women consuming molecular iodine (I2) through seaweeds suffer the least from breast cancers. Zoledronate (Zol) is in clinical use for alleviation of bone pain in cancer patients. Triple negative breast cancers exhibit high mortality due to lack of neoadjuvant chemotherapy. I2 and Zol independently cause weak antiproliferative and apoptotic effect. So far, their combined effects have not been tested. We analyzed the effect of combination of I2 with Zol as a potent adjuvant therapeutic agent for triple negative breast cancer cells (MDA-MBA-231) and in the mice model of breast cancer. Cell viability, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Western blotting, real-time PCR, flow cytometry, and other assays were performed for assessing cell death, calcium levels, and migration potential, respectively, in treated cells. The increased caspase 8, increased [Ca(2+)]c levels, and endoplasmic reticulum (ER) stress resulted in apoptosis. Real time and fluorescence-based analysis demonstrated that the combination treatment targets ER Ca(2+) homeostasis chaperons leading to apoptosis. Combination therapy reduces metalloproteinases 2 and 9, inhibits invasion/migration of cells, and prevents growth of tumor in mice. I2 + Zol combination treatment induces synergistic increase in ER-mediated apoptosis, reduces invasion/migration potential of MDA-MB-231 cells, and exhibits antiproliferative property in vivo demonstrating its potential as combination therapy.

  15. [Corrigendum] Cisplatin in combination with zoledronic acid: A synergistic effect in triple-negative breast cancer cell lines.

    PubMed

    Ibrahim, Toni; Liverani, Chiara; Mercatali, Laura; Sacanna, Emanuele; Zanoni, Michele; Fabbri, Francesco; Zoli, Wainer; Amadori, Dino

    2016-09-01

    Following the publication of the above article, an interested reader drew an anomaly associated with the presentation of Fig. 7 to our attention. Essentially, the panel showing the Cis 0.001 data at T0 for the BRC-230 cell line was the same as that showing the Cis 0.01 data. After having re-examined our data, we realized that an error must have occurred when preparing Fig. 7. A duplication of the photo corresponding to BRC-230 Cis 0.001 T0 was incorrectly placed in the position corresponding to BRC-230 Cis 0.01 T0, while the correct BRC-230 Cis 0.01 T0 figure was erroneously positioned in the BRC-230 Cis 0.01 T1 slot. Fortunately, we had retained all of the data on our computer and were able to find the correct photos representing the conditions of BRC-230 Cis 0.01 T0 and T1. The findings and conclusions of this paper are still supported by our experimental data and are not affected by this error. We sincerely apologize for this oversight and thank the reader for drawing this matter to our attention. We regret any inconvenience caused by our mistake. [the original article was published in the International Journal of Oncology 42: 1263-1270, 2013; DOI: 10.3892/ijo.2013.1809].

  16. [Corrigendum] Cisplatin in combination with zoledronic acid: A synergistic effect in triple-negative breast cancer cell lines.

    PubMed

    Ibrahim, Toni; Liverani, Chiara; Mercatali, Laura; Sacanna, Emanuele; Zanoni, Michele; Fabbri, Francesco; Zoli, Wainer; Amadori, Dino

    2016-09-01

    Following the publication of the above article, an interested reader drew an anomaly associated with the presentation of Fig. 7 to our attention. Essentially, the panel showing the Cis 0.001 data at T0 for the BRC-230 cell line was the same as that showing the Cis 0.01 data. After having re-examined our data, we realized that an error must have occurred when preparing Fig. 7. A duplication of the photo corresponding to BRC-230 Cis 0.001 T0 was incorrectly placed in the position corresponding to BRC-230 Cis 0.01 T0, while the correct BRC-230 Cis 0.01 T0 figure was erroneously positioned in the BRC-230 Cis 0.01 T1 slot. Fortunately, we had retained all of the data on our computer and were able to find the correct photos representing the conditions of BRC-230 Cis 0.01 T0 and T1. The findings and conclusions of this paper are still supported by our experimental data and are not affected by this error. We sincerely apologize for this oversight and thank the reader for drawing this matter to our attention. We regret any inconvenience caused by our mistake. [the original article was published in the International Journal of Oncology 42: 1263-1270, 2013; DOI: 10.3892/ijo.2013.1809]. PMID:27573164

  17. Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

    PubMed

    Babenko, Nataliya A; Garkavenko, Vladimir V; Storozhenko, Galina V; Timofiychuk, Olga A

    2016-04-01

    Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID:26830134

  18. Fat-soluble vitamins and plasma and erythrocyte membrane fatty acids in chylothorax pediatric patients receiving a medium-chain triglyceride-rich diet

    PubMed Central

    Densupsoontorn, Narumon; Jirapinyo, Pipop; Tirapongporn, Hathaichanok; Wongarn, Renu; Chotipanang, Kwanjai; Phuangphan, Phakkanan; Chongviriyaphan, Nalinee

    2014-01-01

    Post-operative chylothorax can be cured by a medium-chain triglyceride (MCT)-rich diet. However, there is concern that an MCT-rich diet results in clinical and biochemical deficiencies in fat-soluble vitamins and fatty acids. We compared fat-soluble vitamins status and fatty acids status before and after administration of an MCT-rich diet. Nine children with congenital heart disease developed chylothorax after cardiac surgery. Blood samples were drawn from each subject twice, first prior to administration of an MCT-rich diet and secondly when the chylothorax was clinically cured and the MCT diet discontinued. Both blood samples were analyzed for retinol and 25-hydroxy vitamin D concentrations, the ratio of α-tocopherol to total lipids (α-TE/TL), coagulogram, and the fatty acid composition in plasma and erythrocyte membrane phospholipids. In spite of a decrease in the α-TE/TL ratio (3.78 ± 0.89 vs 2.36 ± 0.44 mg/g, p<0.05), this decrease did not reach the deficiency cut-off level. Linoleic acid in both plasma and erythrocyte membrane lipids decreased significantly (25.25 ± 8.06 vs 14.25 ± 2.88%, and 11.19 ± 2.15 vs 6.89 ± 2.45%, respectively). Administration of an MCT-rich diet for treatment of postoperative chylothorax caused a reduction in vitamin E status and linoleic acid, but without any symptoms of deficiency. PMID:25411522

  19. The combined use of Camellia sinensis and metronomic zoledronate in 4T1 mouse carcinoma against tumor growth and metastasis.

    PubMed

    Luo, Ke-Wang; Yue, Grace Gar-Lee; Ko, Chun-Hay; Gao, Si; Lee, Julia Kin-Ming; Li, Gang; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara Bik-San

    2015-07-01

    In previous studies, we demonstrated that the green tea Camellia sinensis (CS) water extract had potent antitumor and antimetastatic effects on 4T1 breast cancer. The metronomic regimen (0.0125 mg/kg twice a week for 4 weeks) of zoledronate (ZOL) was found to be effective in decreasing tumor burden and metastasis as compared with conventional regimen. The aim of the present study was to investigate the antitumor, antimetastatic and anti-osteolytic effects of the combined use of CS water extract and metronomic ZOL against 4T1 breast carcinoma in vitro and in vivo. The results demonstrated that the combination of CS+ZOL exerted a more potent effect on lung and liver by decreasing tumor burden and metastasis, when compared to CS or metronomic ZOL as monotherapies. The combination of CS+ZOL demonstrated optimal bone protection against breast cancer-induced osteolysis for the three groups of CS, ZOL and CS+ZOL. The in vitro results further demonstrated that ZOL enhanced CS-induced apoptosis in 4T1 cells as assessed by the Annexin V-FITC/PI staining and caspase-3 activity assays. In addition, the combined use of CS+ZOL significantly inhibited 4T1 cell migration. Mechanistic studies showed that the enzyme levels of matrix metalloproteinases (MMP)-2 and MMP-9 were suppressed significantly by CS+ZOL. In conclusion, to the best of our knowledge, this is the first study to investigate the novel combined application of herbal extract CS and chemotherapy ZOL in 4T1 breast cancer. The combination of CS plus metronomic ZOL demonstrated significant antitumor, antimetastatic and anti-osteolytic effects against breast cancer, and suggested potential clinical application for breast cancer patients.

  20. Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis.

    PubMed

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Ionescu, Claudio; Dartizio, Carmela; Troplini, Sonila; Kunnathully, Vidya; Adami, Silvano; Rossini, Maurizio

    2014-10-01

    The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/b-catenin signaling. We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 74 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100mg/week (CLO) (N=36), and yearly intravenous therapy with 5mg zoledronate (ZOL) (N=18) and placebo (N=20). Bone turnover markers (intact N-propeptide of type I collagen [P1NP], C-terminal telopeptide of type I collagen [CTX]) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, versus both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12months of treatment both versus placebo group (p<0,005), baseline (p<0,001) and ZOL treated group. In the ZOL group, DKK1 levels increased significantly within one month and for the following 6months and it fell back to baseline values at 12months. The second ZOL infusion was again associated with an increase in DKK1 a month later, although to a lesser extent. In conclusion, in this study we have found that the treatment of postmenopausal osteoporosis with intermittent yearly ZOL is associated with transient and declining increases in DKK1 while continuous treatment with CLO, results in a late increase in serum SOST. These preliminary results and further ad hoc studies might contribute to shed light on our understanding of the bone coupling effects taking place during treatment of osteoporosis with different anti-resorbers or with different treatment regimens.

  1. Combined electron microscopy and spectroscopy characterization of as-received, acid purified, and oxidized HiPCO single-wall carbon nanotubes

    SciTech Connect

    Rosario-Castro, Belinda I.; Contes, Enid J.; Lebron-Colon, Marisabel; Meador, Michael A.; Sanchez-Pomales, Germarie; Cabrera, Carlos R.

    2009-12-15

    Single-wall carbon nanotubes (SWCNTs) are very important materials due to their combination of unique structure, dimension, strength, chemical stability, and electronic properties. Nevertheless, SWCNTs from commercial sources usually contain several impurities, which are usually removed by a purification process that includes reflux in acids and strong oxidation. This strong chemical procedure may alter the nanotube properties and it is thus important to control the extent of functionalization and oxidation during the purification procedure. In this report, we provide a comprehensive study of the structure and physical composition of SWCNTs during each step of the purification process. Techniques such as Raman spectroscopy, transmission electron microscopy, scanning electron microscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy and Infrared spectroscopy were used to track the SWCNTs structure, in terms of length and diameter distribution, and surface chemical modifications during each purification stage.

  2. Effects of incremental amounts of extruded linseed on the milk fatty acid composition of dairy cows receiving hay or corn silage.

    PubMed

    Ferlay, A; Doreau, M; Martin, C; Chilliard, Y

    2013-10-01

    The effect of supplementation of increasing amounts of extruded linseed in diets based on hay (H; experiment 1) or corn silage (CS; experiment 2) was investigated in regard to dairy performance and the milk fatty acid (FA) composition. In each experiment, 4 lactating multiparous Holstein cows were used in a 4 × 4 Latin square design (28-d periods). The cows were fed a diet (50:50 and 40:60 concentrate:forage ratio for experiments 1 and 2, respectively; dry matter basis) without supplementation (H0 or CS0) or supplemented with 5% (H5 or CS5), 10% (H10 or CS10), or 15% (H15 or CS15) of extruded linseed. Regardless of the forage type, diet supplementation with increasing amounts of extruded linseed had no effect on the dry matter intake, milk yield, or protein content or yield. In contrast, the milk fat content decreased progressively from H0 to H10 diets, and then decreased strongly with the H15 diet in response to increasing amounts of extruded linseed. For CS diets, the milk fat content initially decreased from CS0 to CS10, but then increased with the CS15 diet. For the H diets, the milk saturated FA decreased (-24.1g/100g of FA) linearly with increasing amounts of extruded linseed, whereas the milk monounsaturated FA (+19.0 g/100 g), polyunsaturated FA (+4.9 g/100 g), and total trans FA (+14.7 g/100 g) increased linearly. For the CS diets, the extent of the changes in the milk FA composition was generally lower than for the H diets. Milk 12:0 to 16:0 decreased in a similar manner in the 2 experiments with increasing amounts of extruded linseed intake, whereas 18:0 and cis-9 18:1 increased. The response of total trans 18:1 was slightly higher for the CS than H diets. The milk trans-10 18:1 content increased more with the CS than the H diets. The milk cis-9,trans-11 conjugated linoleic acid response to increasing amounts of extruded linseed intake was linear and curvilinear for the H diets, whereas it was only linear for the CS diets. The milk 18:3n-3 percentage

  3. Additive effect of PTH (1-34) and zoledronate in the prevention of disuse osteopenia in rats.

    PubMed

    Vegger, Jens Bay; Nielsen, Esben Sommer; Brüel, Annemarie; Thomsen, Jesper Skovhus

    2014-09-01

    Immobilization is known to cause a rapid bone loss due to increased osteoclastic bone resorption and decreased osteoblastic bone formation. Zoledronate (Zln) is a potent anti-resorptive pharmaceutical, while intermittent PTH is a potent bone anabolic agent. The aim of the present study was to investigate whether PTH or Zln alone or in combination could prevent immobilization-induced osteopenia. Immobilization was achieved by injecting 4IU Botox (BTX) into the right hind limb musculature. Seventy-two 16-week-old female Wistar rats were randomized into 6 groups; baseline (Base), control (Ctrl), BTX, BTX+PTH, BTX+Zln, and BTX+PTH+Zln. PTH (1-34) (80μg/kg) was given 5days/week and Zln (100μg/kg) was given once at study start. The animals were killed after 4weeks of treatment. The bone properties were evaluated using DEXA, μCT, dynamic bone histomorphometry, and mechanical testing. BTX resulted in lower femoral trabecular bone volume fraction (BV/TV) (-25%, p<0.05), lower tibial trabecular bone formation rate (BFR/BS) (-29%, p<0.05), and lower bone strength (Fmax) at the distal femur (-19%, p<0.001) compared with Ctrl. BTX+PTH resulted in higher femoral BV/TV (+31%, p<0.05), higher tibial trabecular BFR/BS (+297%, p<0.05), and higher Fmax at the distal femur (+11%, p<0.05) compared with BTX. BTX+Zln resulted in higher femoral BV/TV (+36%, p<0.05), lower tibial trabecular BFR/BS (-93%, p<0.05), and higher Fmax at the distal femur (+10%, p<0.05) compared with BTX. BTX+PTH+Zln resulted in higher femoral BV/TV (+70%, p<0.001), higher tibial trabecular BFR/BS (+59%, p<0.05), and higher Fmax at the distal femur (+32%, p<0.001) compared with BTX. In conclusion, BTX-induced immobilization led to lower BV/TV, BFR/BS, and Fmax. In general, PTH or Zln alone prevented the BTX-induced osteopenia, whereas PTH and Zln given in combination not only prevented, but also increased BV/TV and BFR/BS, and maintained Fmax at the distal femoral metaphysis compared with Ctrl. PMID:24970039

  4. Tocopherols and tocotrienols in serum and liver of dairy cows receiving conjugated linoleic acids or a control fat supplement during early lactation.

    PubMed

    Sadri, H; Dänicke, S; Meyer, Ulrich; Rehage, J; Frank, J; Sauerwein, H

    2015-10-01

    The fat-soluble vitamin E comprises the 8 structurally related compounds (congeners) α-, β-, γ-, and δ-tocopherol (with a saturated side chain) and α-, β-, γ-, and δ-tocotrienol (with a 3-fold unsaturated side chain). Little is known regarding the blood and liver concentrations of the 8 vitamin E congeners during the transition from pregnancy to lactation in dairy cows. We thus quantified tocopherols (T) and tocotrienols (T3) in serum and liver and hepatic expression of genes involved in vitamin E metabolism in pluriparous German Holstein cows during late gestation and early lactation and investigated whether dietary supplementation (from d 1 in milk) with conjugated linoleic acids (CLA; 100g/d; each 12% of trans-10,cis-12 and cis-9,trans-11 CLA; n=11) altered these compared with control-fat supplemented cows (CTR; n=10). Blood samples and liver biopsies were collected on d -21, 1, 21, 70, and 105 (liver only) relative to calving. In both groups, the serum concentrations of αT, γT, βT3, and δT3 increased from d -21 to d 21 and remained unchanged between d 21 and 70, but were unaffected by CLA. The concentrations of the different congeners of vitamin E in liver did not differ between the CTR and the CLA groups. In both groups, the concentrations of the vitamin E forms in liver changed during the course of the study. The hepatic mRNA abundance of genes controlling vitamin E status did not differ between groups, but α-tocopherol transfer protein and tocopherol-associated protein mRNA increased with time of lactation in both. In conclusion, the concentrations of vitamin E congeners and the expression of genes related to vitamin E status follow characteristic time-related changes during the transition from late gestation to early lactation but are unaffected by CLA supplementation at the dosage used.

  5. Folate-targeted pH-responsive calcium zoledronate nanoscale metal-organic frameworks: Turning a bone antiresorptive agent into an anticancer therapeutic.

    PubMed

    Au, Kin Man; Satterlee, Andrew; Min, Yuanzeng; Tian, Xi; Kim, Young Seok; Caster, Joseph M; Zhang, Longzhen; Zhang, Tian; Huang, Leaf; Wang, Andrew Z

    2016-03-01

    Zoledronate (Zol) is a third-generation bisphosphonate that is widely used as an anti-resorptive agent for the treatment of cancer bone metastasis. While there is preclinical data indicating that bisphosphonates such as Zol have direct cytotoxic effects on cancer cells, such effect has not been firmly established in the clinical setting. This is likely due to the rapid absorption of bisphosphonates by the skeleton after intravenous (i.v.) administration. Herein, we report the reformulation of Zol using nanotechnology and evaluation of this novel nanoscale metal-organic frameworks (nMOFs) formulation of Zol as an anticancer agent. The nMOF formulation is comprised of a calcium zoledronate (CaZol) core and a polyethylene glycol (PEG) surface. To preferentially deliver CaZol nMOFs to tumors as well as facilitate cellular uptake of Zol, we incorporated folate (Fol)-targeted ligands on the nMOFs. The folate receptor (FR) is known to be overexpressed in several tumor types, including head-and-neck, prostate, and non-small cell lung cancers. We demonstrated that these targeted CaZol nMOFs possess excellent chemical and colloidal stability in physiological conditions. The release of encapsulated Zol from the nMOFs occurs in the mid-endosomes during nMOF endocytosis. In vitro toxicity studies demonstrated that Fol-targeted CaZol nMOFs are more efficient than small molecule Zol in inhibiting cell proliferation and inducing apoptosis in FR-overexpressing H460 non-small cell lung and PC3 prostate cancer cells. Our findings were further validated in vivo using mouse xenograft models of H460 and PC3. We demonstrated that Fol-targeted CaZol nMOFs are effective anticancer agents and increase the direct antitumor activity of Zol by 80-85% in vivo through inhibition of tumor neovasculature, and inhibiting cell proliferation and inducing apoptosis.

  6. Spaceborne receivers: Basic principles

    NASA Technical Reports Server (NTRS)

    Stacey, J. M.

    1984-01-01

    The underlying principles of operation of microwave receivers for space observations of planetary surfaces were examined. The design philosophy of the receiver as it is applied to operate functionally as an efficient receiving system, the principle of operation of the key components of the receiver, and the important differences among receiver types are explained. The operating performance and the sensitivity expectations for both the modulated and total power receiver configurations are outlined. The expressions are derived from first principles and are developed through the important intermediate stages to form practicle and easily applied equations. The transfer of thermodynamic energy from point to point within the receiver is illustrated. The language of microwave receivers is applied statistics.

  7. Solar heat receiver

    DOEpatents

    Hunt, Arlon J.; Hansen, Leif J.; Evans, David B.

    1985-01-01

    A receiver for converting solar energy to heat a gas to temperatures from 700.degree.-900.degree. C. The receiver is formed to minimize impingement of radiation on the walls and to provide maximum heating at and near the entry of the gas exit. Also, the receiver is formed to provide controlled movement of the gas to be heated to minimize wall temperatures. The receiver is designed for use with gas containing fine heat absorbing particles, such as carbon particles.

  8. Solar heat receiver

    DOEpatents

    Hunt, A.J.; Hansen, L.J.; Evans, D.B.

    1982-09-29

    A receiver is described for converting solar energy to heat a gas to temperatures from 700 to 900/sup 0/C. The receiver is formed to minimize impingement of radiation on the walls and to provide maximum heating at and near the entry of the gas exit. Also, the receiver is formed to provide controlled movement of the gas to be heated to minimize wall temperatures. The receiver is designed for use with gas containing fine heat absorbing particles, such as carbon particles.

  9. Hybrid receiver study

    NASA Technical Reports Server (NTRS)

    Stone, M. S.; Mcadam, P. L.; Saunders, O. W.

    1977-01-01

    The results are presented of a 4 month study to design a hybrid analog/digital receiver for outer planet mission probe communication links. The scope of this study includes functional design of the receiver; comparisons between analog and digital processing; hardware tradeoffs for key components including frequency generators, A/D converters, and digital processors; development and simulation of the processing algorithms for acquisition, tracking, and demodulation; and detailed design of the receiver in order to determine its size, weight, power, reliability, and radiation hardness. In addition, an evaluation was made of the receiver's capabilities to perform accurate measurement of signal strength and frequency for radio science missions.

  10. Data-fusion receiver

    SciTech Connect

    Gabelmann, Jeffrey M.; Kattner, J. Stephen; Houston, Robert A.

    2006-12-19

    This invention is an ultra-low frequency electromagnetic telemetry receiver which fuses multiple input receive sources to synthesize a decodable message packet from a noise corrupted telemetry message string. Each block of telemetry data to be sent to the surface receiver from a borehole tool is digitally encoded into a data packet prior to transmission. The data packet is modulated onto the ULF EM carrier wave and transmitted from the borehole to the surface and then are simultaneously detected by multiple receive sensors disbursed within the rig environment. The receive sensors include, but are not limited to, electric field and magnetic field sensors. The spacing of the surface receive elements is such that noise generators are unequally coupled to each receive element due to proximity and/or noise generator type (i.e. electric or magnetic field generators). The receiver utilizes a suite of decision metrics to reconstruct the original, non noise-corrupted data packet from the observation matrix via the estimation of individual data frames. The receiver will continue this estimation process until: 1) the message validates, or 2) a preset "confidence threshold" is reached whereby frames within the observation matrix are no longer "trusted".

  11. CALUTRON RECEIVER STRUCTURE

    DOEpatents

    Roush, J.L.

    1959-09-01

    A receiver is described for collecting isotopes in a calutron The receiver has several compartments, formed by a sertes of parallel metal plates and an open front. Each plate has flanges which space it from the other plates and a flexible extension pressing against a common supporting red to maintain the plate in assembled relation when all but the last rod is removed. The plates may be removed individualy from the front of the receiver, cleaned ard replaced without disturbing the alignment of the other plates.

  12. Ultrasonic pulser-receiver

    DOEpatents

    Taylor, Steven C.

    2006-09-12

    Ultrasonic pulser-receiver circuitry, for use with an ultrasonic transducer, the circuitry comprising a circuit board; ultrasonic pulser circuitry supported by the circuit board and configured to be coupled to an ultrasonic transducer and to cause the ultrasonic transducer to emit an ultrasonic output pulse; receiver circuitry supported by the circuit board, coupled to the pulser circuitry, including protection circuitry configured to protect against the ultrasonic pulse and including amplifier circuitry configured to amplify an echo, received back by the transducer, of the output pulse; and a connector configured to couple the ultrasonic transducer directly to the circuit board, to the pulser circuitry and receiver circuitry, wherein impedance mismatches that would result if the transducer was coupled to the circuit board via a cable can be avoided.

  13. Solar energy receiver

    DOEpatents

    Schwartz, Jacob

    1978-01-01

    An improved long-life design for solar energy receivers provides for greatly reduced thermally induced stress and permits the utilization of less expensive heat exchanger materials while maintaining receiver efficiencies in excess of 85% without undue expenditure of energy to circulate the working fluid. In one embodiment, the flow index for the receiver is first set as close as practical to a value such that the Graetz number yields the optimal heat transfer coefficient per unit of pumping energy, in this case, 6. The convective index for the receiver is then set as closely as practical to two times the flow index so as to obtain optimal efficiency per unit mass of material.

  14. Receiver Gain Modulation Circuit

    NASA Technical Reports Server (NTRS)

    Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

    2011-01-01

    A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

  15. The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering.

    PubMed

    Li, Peiqi; Hashimoto, Yoshiya; Honda, Yoshitomo; Arima, Yoshiyuki; Matsumoto, Naoyuki

    2015-10-26

    Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS). At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment) groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption.

  16. The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering

    PubMed Central

    Li, Peiqi; Hashimoto, Yoshiya; Honda, Yoshitomo; Arima, Yoshiyuki; Matsumoto, Naoyuki

    2015-01-01

    Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS). At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment) groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption. PMID:26516841

  17. Central solar energy receiver

    DOEpatents

    Drost, M. Kevin

    1983-01-01

    An improved tower-mounted central solar energy receiver for heating air drawn through the receiver by an induced draft fan. A number of vertically oriented, energy absorbing, fin-shaped slats are radially arranged in a number of concentric cylindrical arrays on top of the tower coaxially surrounding a pipe having air holes through which the fan draws air which is heated by the slats which receive the solar radiation from a heliostat field. A number of vertically oriented and wedge-shaped columns are radially arranged in a number of concentric cylindrical clusters surrounding the slat arrays. The columns have two mirror-reflecting sides to reflect radiation into the slat arrays and one energy absorbing side to reduce reradiation and reflection from the slat arrays.

  18. Silicon Photo-Receivers

    NASA Astrophysics Data System (ADS)

    Zimmermann, Horst

    The properties of photodiodes being exploitable in standard bipolar, CMOS, and BiCMOS technologies are summarized. In addition examples of advanced photodiodes will be introduced in order to show how the properties of integrated photodiodes can be improved significantly by minor process modifications. Furthermore, examples of optoelectronic integrated circuits (OEICs) for such important applications like optical storage systems and optical fiber receivers are described. New trends for the circuit topology of digital-video-disk (DVD) and digital-video-recording (DVR) read-OEICs are covered. Progress of OEIC receivers for optical data transmission and communication as well as optical interconnects is also summarized.

  19. Zero-power receiver

    DOEpatents

    Brocato, Robert W.

    2016-10-04

    An unpowered signal receiver and a method for signal reception detects and responds to very weak signals using pyroelectric devices as impedance transformers and/or demodulators. In some embodiments, surface acoustic wave devices (SAW) are also used. Illustrative embodiments include satellite and long distance terrestrial communications applications.

  20. Submillimeter wave heterodyne receiver

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Goutam (Inventor); Manohara, Harish (Inventor); Siegel, Peter H. (Inventor); Ward, John (Inventor)

    2011-01-01

    In an embodiment, a submillimeter wave heterodyne receiver includes a finline ortho-mode transducer comprising thin tapered metallic fins deposited on a thin dielectric substrate to separate a vertically polarized electromagnetic mode from a horizontally polarized electromagnetic mode. Other embodiments are described and claimed.

  1. Simplified OMEGA receivers

    NASA Technical Reports Server (NTRS)

    Burhans, R. W.

    1974-01-01

    The details are presented of methods for providing OMEGA navigational information including the receiver problem at the antenna and informational display and housekeeping systems based on some 4 bit data processing concepts. Topics discussed include the problem of limiters, zero crossing detectors, signal envelopes, internal timing circuits, phase counters, lane position displays, signal integrators, and software mapping problems.

  2. Olympus beacon receiver

    NASA Technical Reports Server (NTRS)

    Ostergaard, Jens

    1988-01-01

    A medium-size Beacon Receiving System for reception and processing of the B1 (20 GHz) and B2 (30 GHz) beacons from Olympus has been developed. Integration of B1 and B2 receiving equipment into one system using one antenna and a common computer for control and data processing provides the advantages of a compact configuration and synchronization of the two receiver chains. Range for co-polar signal attenuation meaurement is about 30 dB for both beacons, increasing to 40 dB for B2 if the receivers are synchronized to B1. The accuracy is better than 0.5 dB. Cross-polarization discriminations of the order of 10 to 30 dB may be determined with an accuracy of 1 to 2 dB. A number of radiometers for complementary measurements of atmospheric attenuation of 13 to 30 GHz has also been constructed. A small multi-frequency system for operation around 22 GHz and 31 GHz is presently under development.

  3. Hanson receives Macelwane Medal

    NASA Astrophysics Data System (ADS)

    Ravishankara, A. R.; Hanson, David R.

    At the 1996 Spring Meeting in Baltimore, Maryland, David R. Hanson received the 1996 James B. Macelwane Medal, which recognizes significant contributions to the geophysical sciences by a young scientist of outstanding ability. The medal citation and Hanson's response are given here.

  4. A digital beacon receiver

    NASA Technical Reports Server (NTRS)

    Ransome, Peter D.

    1988-01-01

    A digital satellite beacon receiver is described which provides measurement information down to a carrier/noise density ratio approximately 15 dB below that required by a conventional (phase locked loop) design. When the beacon signal fades, accuracy degrades gracefully, and is restored immediately (without hysteresis) on signal recovery, even if the signal has faded into the noise. Benefits of the digital processing approach used include the minimization of operator adjustments, stability of the phase measuring circuits with time, repeatability between units, and compatibility with equipment not specifically designed for propagation measuring. The receiver has been developed for the European Olympus satellite which has continuous wave (CW) beacons at 12.5 and 29.7 GHz, and a switched polarization beacon at 19.8 GHz approximately, but the system can be reconfigured for CW and polarization-switched beacons at other frequencies.

  5. Multichannel homodyne receiver

    DOEpatents

    Landt, Jeremy A.

    1982-01-01

    A homodyne radar transmitter/receiver device which produces a single combined output which contains modulated backscatter information for all phase conditions of both modulated and unmodulated backscatter signals. The device utilizes taps along coaxial transmission lines, strip transmission line, and waveguides which are spaced by 1/8 wavelength or 1/6 wavelength, etc. This greatly reduces costs by eliminating separate transmission and reception antennas and an expensive arrangement of power splitters and mixers utilized in the prior art.

  6. Multichannel homodyne receiver

    DOEpatents

    Landt, J.A.

    1981-01-19

    A homodyne radar transmitter/receiver device which produces a single combined output which contains modulated backscatter information for all phase conditions of both modulated and unmodulated backscatter signals is described. The device utilizes taps along coaxial transmission lines, strip transmission line, and waveguides which are spaced by 1/8 wavelength or 1/6 wavelength, etc. This greatly reduces costs by eliminating separate transmission and reception antennas and an expensive arrangement of power splitters and mixers utilized in the prior art.

  7. Design of radar receivers

    NASA Astrophysics Data System (ADS)

    Sokolov, M. A.

    This handbook treats the design and analysis of of pulsed radar receivers, with emphasis on elements (especially IC elements) that implement optimal and suboptimal algorithms. The design methodology is developed from the viewpoint of statistical communications theory. Particular consideration is given to the synthesis of single-channel and multichannel detectors, the design of analog and digital signal-processing devices, and the analysis of IF amplifiers.

  8. Ultra-wideband receiver

    DOEpatents

    McEwan, Thomas E.

    1996-01-01

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, .+-.UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals.

  9. Ultra-wideband receiver

    DOEpatents

    McEwan, Thomas E.

    1994-01-01

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, .+-.UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals.

  10. Ultra-wideband receiver

    DOEpatents

    McEwan, T.E.

    1996-06-04

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, {+-}UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals. 21 figs.

  11. Ultra-wideband receiver

    DOEpatents

    McEwan, T.E.

    1994-09-06

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, [+-] UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals. 16 figs.

  12. Central receiver technology

    SciTech Connect

    Holl, R.L. )

    1989-09-01

    The research and development described in this document was conducted within the US Department of Energy's (DOE) Solar Thermal Technology Program. The goal of this program is to advance the engineering and scientific understanding of solar thermal technology and to establish the technology base from which private industry can develop solar thermal power production options for introduction into the competitive energy market. This report describes central receiver technology: its accomplishments to date, its current technology status, and the efforts still necessary to fully exploit it.

  13. Hyperammonemia in neonates receiving intravenous nutrition.

    PubMed

    Thomas, D W; Sinatra, F R; Hack, S L; Smith, T M; Platzker, A C; Merritt, R J

    1982-01-01

    Inadequate arginine intake has been suggested as an etiology for hyperammonemia in neonates on parenteral nutrition. We randomized 26 nonasphyxiated neonates to receive amino acid solutions containing either 3.6 or 10.4% of total nitrogen as arginine when intravenous nutrition (IVN) therapy was initiated. Neonates in both amino acid solution study groups were observed to have significantly elevated blood ammonia (BA) concentrations during IVN (p less than 0.01) as compared to pre-IVN levels. Blood ammonia concentrations tended to be higher in infants receiving the 3.6% arginine amino acid solution. Septic infants were at particular risk for hyperammonemia as compared to nonseptic patients (p less than 0.025). Other clinical parameters including birth weight, gestational age, oxygen requirements, enteral nutritional intake, congenital anomalies, and heart disease did not appear to be related to BA concentration.

  14. Weather Data Receiver

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Northern Video Graphics, Inc. developed a low-cost satellite receiving system for users such as independent meteorologists, agribusiness firms, small airports or flying clubs, marine vessels and small TV stations. Called Video Fax, it is designed for use with certain satellites; the GOES (Geostationary Operational Environmental Satellite) spacecraft operated by the National Oceanic and Atmospheric Administration, the European Space Agency's Meteosat and Japan's Geostationary Meteorological Satellite. By dictum of the World Meteorological Organization, signals from satellites are available to anyone without cost so the Video Fax user can acquire signals directly from the satellite and cut out the middle man, enabling savings. Unit sells for about one-fifth the cost of the equipment used by TV stations. It consists of a two-meter antenna; a receiver; a microprocessor-controlled display computer; and a video monitor. Computer stores data from the satellites and converts it to an image which is displayed on the monitor. Weather map can be preserved as signal data on tape, or it can be stored in a video cassette as a permanent image.

  15. Digital Receiver Phase Meter

    NASA Technical Reports Server (NTRS)

    Marcin, Martin; Abramovici, Alexander

    2008-01-01

    The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density <5 microcycle/(Hz)1/2 and to be capable of determining the power spectral density of the phase difference over the frequency range from 1 mHz to 1 Hz. Such a phase meter could also be used on Earth to perform similar measurements in laser metrology of moving bodies. To illustrate part of the principle of operation of the phase meter, the figure includes a simplified block diagram of a basic singlechannel digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

  16. Garcinia Cambogia–Induced Acute Hepatitis; Varenicline-Induced Parkinsonism; Resistant Hypocalcemia After Zoledronic Acid Administration; Zonisamide-Induced Acute Kidney Injury; Psychosis Associated with Guanfacine;

    PubMed Central

    Mancano, Michael A.

    2015-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) Med Watch program (800-FDA-1088). If you have reported an interesting, preventable ADR to Med Watch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s Med Watch program and Temple University School of Pharmacy. ISMP is an FDA Med Watch partner. PMID:26448666

  17. The Combination Therapy with Zoledronic Acid and Propranolol Improves the Trabecular Microarchitecture and Mechanical Property in an Rat Model of Postmenopausal Osteoporosis

    PubMed Central

    Razdan, Rema; Mahapatra, D. Roy

    2014-01-01

    We conducted the present study to investigate the therapeutic effects of propranolol (PRO), alone and in combination with the antiresorptive agent ZOL, in a rat model of postmenopausal osteoporosis. Female Wistar rats were OVX or sham-operated at 3 months of age. Twelve weeks after surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 μg/kg, i.v. single dose), (4) OVX + ZOL (50 μg/kg, i.v. single dose), (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week), and (6) OVX + ZOL (50 μg/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. At the end of treatment study, various bone parameters were evaluated. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and PRO was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL and PRO preserved the trabecular microarchitecture better than single-drug therapy using ZOL or PRO in OVX rats. These data suggest that combination therapy with ZOL plus PRO represents a potentially useful therapeutic option for patients with osteoporosis. PMID:24800099

  18. Solar thermal energy receiver

    NASA Technical Reports Server (NTRS)

    Baker, Karl W. (Inventor); Dustin, Miles O. (Inventor)

    1992-01-01

    A plurality of heat pipes in a shell receive concentrated solar energy and transfer the energy to a heat activated system. To provide for even distribution of the energy despite uneven impingement of solar energy on the heat pipes, absence of solar energy at times, or failure of one or more of the heat pipes, energy storage means are disposed on the heat pipes which extend through a heat pipe thermal coupling means into the heat activated device. To enhance energy transfer to the heat activated device, the heat pipe coupling cavity means may be provided with extensions into the device. For use with a Stirling engine having passages for working gas, heat transfer members may be positioned to contact the gas and the heat pipes. The shell may be divided into sections by transverse walls. To prevent cavity working fluid from collecting in the extensions, a porous body is positioned in the cavity.

  19. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Ledvina, Brent M. (Inventor); Psiaki, Mark L. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2007-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  20. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Ledvina, Brent M. (Inventor); Psiaki, Mark L. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2006-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  1. High temperature solar thermal receiver

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A design concept for a high temperature solar thermal receiver to operate at 3 atmospheres pressure and 2500 F outlet was developed. The performance and complexity of windowed matrix, tube-header, and extended surface receivers were evaluated. The windowed matrix receiver proved to offer substantial cost and performance benefits. An efficient and cost effective hardware design was evaluated for a receiver which can be readily interfaced to fuel and chemical processes or to heat engines for power generation.

  2. High-temperature ceramic receivers

    SciTech Connect

    Jarvinen, P. O.

    1980-01-01

    An advanced ceramic dome cavity receiver is discussed which heats pressurized gas to temperatures above 1800/sup 0/F (1000/sup 0/C) for use in solar Brayton power systems of the dispersed receiver/dish or central receiver type. Optical, heat transfer, structural, and ceramic material design aspects of the receiver are reported and the development and experimental demonstration of a high-temperature seal between the pressurized gas and the high-temperature silicon carbide dome material is described.

  3. Bragg-cell receiver study

    NASA Technical Reports Server (NTRS)

    Wilson, Lonnie A.

    1987-01-01

    Bragg-cell receivers are employed in specialized Electronic Warfare (EW) applications for the measurement of frequency. Bragg-cell receiver characteristics are fully characterized for simple RF emitter signals. This receiver is early in its development cycle when compared to the IFM receiver. Functional mathematical models are derived and presented in this report for the Bragg-cell receiver. Theoretical analysis is presented and digital computer signal processing results are presented for the Bragg-cell receiver. Probability density function analysis are performed for output frequency. Probability density function distributions are observed to depart from assumed distributions for wideband and complex RF signals. This analysis is significant for high resolution and fine grain EW Bragg-cell receiver systems.

  4. Low cost omega navigation receiver

    NASA Technical Reports Server (NTRS)

    Lilley, R. W.

    1974-01-01

    The development of a low cost Omega navigation receiver is discussed. Emphasis is placed on the completion and testing of a modular, multipurpose Omega receiver which utilizes a digital memory-aided, phase-locked loop to provide phase measurement data to a variety of applications interfaces. The functional units contained in the prototype device are described. The receiver is capable of receiving and storing phase measurements for up to eight Omega signals and computes two switch-selectable lines of position, displaying this navigation data in chart-recorded form.

  5. Receiver design and performance characteristics

    NASA Technical Reports Server (NTRS)

    Simon, M. K.; Yuen, J. H.

    1982-01-01

    The basic design, principles of operation, and characteristics of deep space communications receivers are examined. In particular, the basic fundamentals of phase-locked loop and Costas loop receivers used for synchronization, tracking, and demodulation of phase-coherent signals in residual carrier and suppressed carrier systems are addressed.

  6. Receiver design and performance characteristics

    NASA Astrophysics Data System (ADS)

    Simon, M. K.; Yuen, J. H.

    1982-07-01

    The basic design, principles of operation, and characteristics of deep space communications receivers are examined. In particular, the basic fundamentals of phase-locked loop and Costas loop receivers used for synchronization, tracking, and demodulation of phase-coherent signals in residual carrier and suppressed carrier systems are addressed.

  7. UWB delay and multiply receiver

    DOEpatents

    Dallum, Gregory E.; Pratt, Garth C.; Haugen, Peter C.; Romero, Carlos E.

    2013-09-10

    An ultra-wideband (UWB) delay and multiply receiver is formed of a receive antenna; a variable gain attenuator connected to the receive antenna; a signal splitter connected to the variable gain attenuator; a multiplier having one input connected to an undelayed signal from the signal splitter and another input connected to a delayed signal from the signal splitter, the delay between the splitter signals being equal to the spacing between pulses from a transmitter whose pulses are being received by the receive antenna; a peak detection circuit connected to the output of the multiplier and connected to the variable gain attenuator to control the variable gain attenuator to maintain a constant amplitude output from the multiplier; and a digital output circuit connected to the output of the multiplier.

  8. Noise Stability of SIS Receivers

    NASA Astrophysics Data System (ADS)

    Kooi, J. W.; Chattopadhyay, G.; Thielman, M.; Phillips, T. G.; Schieder, R.

    2000-05-01

    There is a strong interest in the submillimeter astronomy community to increase the IF bandwidth of SIS receivers in order to better facilitate broad spectral linewidth and continuum observations of extragalactic sources. However, with an increase in receiver IF bandwidth there is a decrease in the mixer stability. This in turn effects the integration efficiency and quality of the measurement. In order to better understand the noise mechanisms responsible for reducing the receiver stability, we employed a technique first described by D.W. Allan and later elaborated upon by Schieder et al. In this paper we address a variety of factors that degrade the noise stability of SIS receivers. The goal of this exercise is to make recommendations aimed at maximizing SIS receiver stability.

  9. Customizable Digital Receivers for Radar

    NASA Technical Reports Server (NTRS)

    Moller, Delwyn; Heavey, Brandon; Sadowy, Gregory

    2008-01-01

    Compact, highly customizable digital receivers are being developed for the system described in 'Radar Interferometer for Topographic Mapping of Glaciers and Ice Sheets' (NPO-43962), NASA Tech Briefs, Vol. 31, No. 7 (August 2007), page 72. The receivers are required to operate in unison, sampling radar returns received by the antenna elements in a digital beam-forming (DBF) mode. The design of these receivers could also be adapted to commercial radar systems. At the time of reporting the information for this article, there were no commercially available digital receivers capable of satisfying all of the operational requirements and compact enough to be mounted directly on the antenna elements. A provided figure depicts the overall system of which the digital receivers are parts. Each digital receiver includes an analog-to-digital converter (ADC), a demultiplexer (DMUX), and a field-programmable gate array (FPGA). The ADC effects 10-bit band-pass sampling of input signals having frequencies up to 3.5 GHz. The input samples are demultiplexed at a user-selectable rate of 1:2 or 1:4, then buffered in part of the FPGA that functions as a first-in/first-out (FIFO) memory. Another part of the FPGA serves as a controller for the ADC, DMUX, and FIFO memory and as an interface between (1) the rest of the receiver and (2) a front-panel data port (FPDP) bus, which is an industry-standard parallel data bus that has a high data-rate capability and multichannel configuration suitable for DBF. Still other parts of the FPGA in each receiver perform signal-processing functions. The digital receivers can be configured to operate in a stand-alone mode, or in a multichannel mode as needed for DBF. The customizability of the receiver makes it applicable to a broad range of system architectures. The capability for operation of receivers in either a stand-alone or a DBF mode enables the use of the receivers in an unprecedentedly wide variety of radar systems.

  10. Sensitivity of terahertz photonic receivers

    NASA Astrophysics Data System (ADS)

    Matsko, A. B.; Strekalov, D. V.; Yu, N.

    2008-04-01

    We theoretically discuss sensitivity limitations of a THz receiver which is based on up-conversion of the THz radiation into optical domain using high quality factor crystalline whispering gallery mode resonators. We show that the sensitivity of the receiver operating in the nonlinear regime approaches the sensitivity of an ideal THz photon counter. Thermal noise of the counter can be substantially reduced because of transparency of the nonlinear material in the THz frequency range. We also show that the density of power fluctuations of the receiver operating in the linear regime is given by the THz shot noise.

  11. Effect of the level and type of starchy concentrate on tissue lipid metabolism, gene expression and milk fatty acid secretion in Alpine goats receiving a diet rich in sunflower-seed oil.

    PubMed

    Bernard, L; Leroux, C; Rouel, J; Bonnet, M; Chilliard, Y

    2012-04-01

    The potential benefits on human health have prompted an interest in developing nutritional strategies for reducing saturated and increasing specific unsaturated fatty acids (FA) in ruminant milk. The impact of the level and type of starchy concentrate added to diets supplemented with sunflower-seed oil on caprine milk FA composition and on mammary, omental and perirenal adipose, and liver lipid metabolism was examined in fourteen Alpine goats in a replicated 3 × 3 Latin square with 21 d experimental periods. Treatments were a grass hay-based diet with a high level of forage (F) or a high level of concentrate with either maize grain (CM) or flattened wheat (CW) as source of starch and supplemented with 130 g/d sunflower-seed oil. Milk yield was enhanced (P<0·01) and milk fat content was decreased on the CM and CW diets compared with the F diet, resulting in similar milk fat secretion. Both high-concentrate diets increased (P<0·05) milk yield of 10 : 0-16 : 0 and decreased trans-9,11-18 : 1 and cis-9, trans-11-18 : 2. The CW diet decreased (P<0·05) the output of ΣC18 and Σcis-18 : 1 and increased (P<0·05) the output of trans-10-18 : 1 in milk. The expression and/or activity of fourteen proteins involved in the major lipogenic pathways in mammary tissues and of lipogenic genes in adipose and liver tissues were similar among treatments. In conclusion, high starch concentrates alter milk FA yield via mechanisms independent of changes in mammary, liver or adipose tissue lipogenic gene expression. Furthermore, data provided indications that mammary lipogenic responses to starch-rich diets differ between caprine and bovine ruminants.

  12. Coe Receives 2007 Gilbert Award

    NASA Astrophysics Data System (ADS)

    Bogue, Scott W.; Coe, Robert S.

    2008-05-01

    Robert S. Coe received the 2007 William Gilbert Award at the 2007 AGU Fall Meeting in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  13. Stevenson received the Whipple award

    NASA Astrophysics Data System (ADS)

    Shoemaker, Eugene M.; Stevenson, David J.

    1996-02-01

    David J. Stevenson received the Whipple Award at the 1994 Spring Meeting in Baltimore. The award is given for outstanding scientific contributions to the field of planetology. The citation and Stevenson's response are given here.

  14. Streak camera receiver definition study

    NASA Technical Reports Server (NTRS)

    Johnson, C. B.; Hunkler, L. T., Sr.; Letzring, S. A.; Jaanimagi, P.

    1990-01-01

    Detailed streak camera definition studies were made as a first step toward full flight qualification of a dual channel picosecond resolution streak camera receiver for the Geoscience Laser Altimeter and Ranging System (GLRS). The streak camera receiver requirements are discussed as they pertain specifically to the GLRS system, and estimates of the characteristics of the streak camera are given, based upon existing and near-term technological capabilities. Important problem areas are highlighted, and possible corresponding solutions are discussed.

  15. Solar dynamic heat receiver technology

    NASA Technical Reports Server (NTRS)

    Sedgwick, Leigh M.

    1991-01-01

    A full-size, solar dynamic heat receiver was designed to meet the requirements specified for electrical power modules on the U.S. Space Station, Freedom. The heat receiver supplies thermal energy to power a heat engine in a closed Brayton cycle using a mixture of helium-xenon gas as the working fluid. The electrical power output of the engine, 25 kW, requires a 100 kW thermal input throughout a 90 minute orbit, including when the spacecraft is eclipsed for up to 36 minutes from the sun. The heat receiver employs an integral thermal energy storage system utilizing the latent heat available through the phase change of a high-temperature salt mixture. A near eutectic mixture of lithium fluoride and calcium difluoride is used as the phase change material. The salt is contained within a felt metal matrix which enhances heat transfer and controls the salt void distribution during solidification. Fabrication of the receiver is complete and it was delivered to NASA for verification testing in a simulated low-Earth-orbit environment. This document reviews the receiver design and describes its fabrication history. The major elements required to operate the receiver during testing are also described.

  16. UWB communication receiver feedback loop

    DOEpatents

    Spiridon, Alex; Benzel, Dave; Dowla, Farid U.; Nekoogar, Faranak; Rosenbury, Erwin T.

    2007-12-04

    A novel technique and structure that maximizes the extraction of information from reference pulses for UWB-TR receivers is introduced. The scheme efficiently processes an incoming signal to suppress different types of UWB as well as non-UWB interference prior to signal detection. Such a method and system adds a feedback loop mechanism to enhance the signal-to-noise ratio of reference pulses in a conventional TR receiver. Moreover, sampling the second order statistical function such as, for example, the autocorrelation function (ACF) of the received signal and matching it to the ACF samples of the original pulses for each transmitted bit provides a more robust UWB communications method and system in the presence of channel distortions.

  17. Central solar-energy receiver

    DOEpatents

    Not Available

    1981-10-27

    An improved tower-mounted central solar energy receiver for heating air drawn through the receiver by an induced draft fan is described. A number of vertically oriented, energy absorbing, fin-shaped slats are radially arranged in a number of concentric cylindrical arrays on top of the tower coaxially surrounding a pipe having air holes through which the fan draws air which is heated by the slats which receive the solar radiation from a heliostat field. A number of vertically oriented and wedge-shaped columns are radially arranged in a number of concentric cylindrical clusters surrounding the slat arrays. The columns have two mirror-reflecting sides to reflect radiation into the slat arrays and one energy absorbing side to reduce reradiation and reflection from the slat arrays.

  18. Organic Rankine cycle receiver development

    NASA Technical Reports Server (NTRS)

    Haskins, H. J.

    1981-01-01

    The selected receiver concept is a direct-heated, once-through, monotube boiler operated at supercritical pressure. The cavity is formed by a cylindrical copper shell and backwall, with stainless steel tubing brazed to the outside surface. This core is surrounded by lightweight refractory insulation, load-bearing struts, and an outer case. The aperture plate is made of copper to provide long life by conduction and reradiation of heat away from the aperture lip. The receiver thermal efficiency is estimated to be 97 percent at rated conditions (energy transferred to toluene divided by energy incident on aperture opening). Development of the core manufacturing and corrosion protection methods is complete.

  19. The GBT 4mm Receiver

    NASA Astrophysics Data System (ADS)

    Frayer, David T.; White, S.; Watts, G.; Stennes, M.; Maddalena, R. J.; Simon, R.; Pospieszalski, M.; Bryerton, E.

    2013-01-01

    The new 4mm receiver (67--93 GHz) for the Robert C. Byrd Green Bank Telescope (GBT) was built to take advantage of the improved surface accuracy of the dish. The low frequency end of the 3mm atmospheric window is not available with ALMA (<84 GHz), and the sensitivity of the GBT is better than any other facility within this band. We discuss the design and performance of this new receiver for the GBT, and highlight the science opportunities available with the instrument. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.

  20. Uncooled receivers for CO2 laser radiation

    NASA Astrophysics Data System (ADS)

    Granovskii, A. B.; Iakovlev, V. A.

    1986-01-01

    Published data on low-inertia, uncooled, single-element and matrix-type radiation receivers that have a high degree of reliability and are immune from interference from various external sources are systematically summarized. Three basic types of receivers are examined: photonic receivers, thermal receivers, and receivers based on wave interaction. Principal attention is given to the CO2 laser radiation receiver.

  1. STAR: SOFIA terahertz array receiver

    NASA Astrophysics Data System (ADS)

    Graf, Urs U.; Heyminck, Stefan; Rabanus, D.; Jacobs, Karl; Schieder, Rudolf T.; Stutzki, Juergen

    2003-02-01

    We present the concept for KOSMA's 16 element 1.9 THz heterodyne array STAR (SOFIA Terahertz Array Receiver) which is being developed for SOFIA. The instrument will consist of two interleaved sub-arrays of 8 pixels each. Together we will have a 4 × 4 pixel array with a beam spacing on the sky of approximately 1.5 times the beam size of 15 arcsec (FWHM). The receiver is mainly targeted at measuring the fine structure transition of ionized atomic carbon at 1.9 THz (158 microns). STAR's optics setup is modeled after the successful design used in KOSMA's SMART receiver. It will contain a K-mirror type beam rotator, a Martin-Puplett diplexer for LO coupling and an LO multiplexer using imaging Fourier gratings. Complete optical sub-assemblies will be machined monolithically as integrated optics units, to reduce the need for optical alignment. STAR will probably use waveguide mixers with diffusion cooled hot electron bolometers, which are being developed at KOSMA. The receiver backends will be KOSMA Array-AOSs. Local oscillator power will be provided by a backward wave oscillator (BWO), followed by a frequency tripler.

  2. Advances in SIS receiver technology

    NASA Technical Reports Server (NTRS)

    Frerking, M. A.

    1988-01-01

    Significant advances in SIS receiver technology since the last Asilomar meeting include: superconductor materials, integrated inductive tuning elements, and planar mounting structures. The effect of these advances is to push the upper frequency operating limit from about 600 to 1500 GHz, and to enhance the feasibility of focal plane arrays of heterodyne receivers. A fundamental high frequency operating limit of SIS mixers is set by the superconducting energy gap. A practical limitation for high frequency operation of SIS junctions is their parasitic capacitance and resistance. The performance of the mixer will be degraded by the Resistor-Capacitor rolloff. Several designs were reported for inductive elements integrated on the same substrate as the SIS junctions to tune out the bulk junction capacitance. Most millimeter SIS-based heterodyne receivers have used waveguide coupling structures. Technology has advanced to the state where programs that have a high probability of success can be defined to produce arrays of SIS receivers for frequencies as high as 1500 GHz.

  3. Microwave blackbodies for spaceborne receivers

    NASA Technical Reports Server (NTRS)

    Stacey, J. M.

    1985-01-01

    The properties of microwave blackbody targets are explained as they apply to the calibration of spaceborne receivers. Also described are several practicable, blackbody targets used to test and calibrate receivers in the laboratory and in the thermal vacuum chamber. Problems with the precision and the accuracy of blackbody targets, and blackbody target design concepts that overcome some of the accuracy limitations present in existing target designs, are presented. The principle of the Brewster angle blackbody target is described where the blackbody is applied as a fixed-temperature test target in the laboratory and as a variable-temperature target in the thermal vacuum chamber. The reflectivity of a Brewster angle target is measured in the laboratory. From this measurement, the emissivity of the target is calculated. Radiatively cooled thermal suspensions are discussed as the coolants of blackbody targets and waveguide terminations that function as calibration devices in spaceborne receivers. Examples are given for the design of radiatively cooled thermal suspensions. Corrugated-horn antennas used to observe the cosmic background and to provide a cold-calibration source for spaceborne receivers are described.

  4. Clark Receives Ocean Sciences Award

    NASA Astrophysics Data System (ADS)

    Roman, Michael R.; Clark, H. Lawrence

    2008-09-01

    H. Lawrence Clark received the 2008 Ocean Sciences Award at the 2008 Ocean Sciences Meeting, held 2-7 March 2008 in Orlando, Fla. The award is given in recognition of outstanding and long-standing service to the ocean sciences.

  5. RFID receiver apparatus and method

    DOEpatents

    Scott, Jeffrey Wayne

    2006-12-26

    An RFID backscatter interrogator for transmitting data to an RFID tag, generating a carrier for the tag, and receiving data from the tag modulated onto the carrier, the interrogator including a single grounded-coplanar wave-guide circuit board and at least one surface mount integrated circuit supported by the circuit board.

  6. Vergano Receives David Perlman Award

    NASA Astrophysics Data System (ADS)

    Kelly, Sue

    2006-08-01

    Dan Vergano received the Perlman Award at the Joint Assembly Honors Ceremony, whichwas held on 25 May 2006 in Baltimore, Md. Vergano was honored for `The Debate's over:Globe is warming,' which describes the linkages between the science of climate change andthe complexity of technical and economic decisions facing its mitigation.

  7. Receivers for modulated digital signals

    NASA Astrophysics Data System (ADS)

    Troendle, K.; Huber, J.

    The realization principles for coherent and incoherent receivers for modulated digital signal transmission are presented. From these principles, the digital amplitude, phase, and frequency modulation are treated. Expressions for the error probabilities in these systems are given, and their required bandwidths and noise sensitivities are compared. Principles of system realization for time-variant channels and methods of clock and carrier recovery are explained.

  8. Scintillation-Hardened GPS Receiver

    NASA Technical Reports Server (NTRS)

    Stephens, Donald R.

    2015-01-01

    CommLargo, Inc., has developed a scintillation-hardened Global Positioning System (GPS) receiver that improves reliability for low-orbit missions and complies with NASA's Space Telecommunications Radio System (STRS) architecture standards. A software-defined radio (SDR) implementation allows a single hardware element to function as either a conventional radio or as a GPS receiver, providing backup and redundancy for platforms such as the International Space Station (ISS) and high-value remote sensing platforms. The innovation's flexible SDR implementation reduces cost, weight, and power requirements. Scintillation hardening improves mission reliability and variability. In Phase I, CommLargo refactored an open-source GPS software package with Kalman filter-based tracking loops to improve performance during scintillation and also demonstrated improved navigation during a geomagnetic storm. In Phase II, the company generated a new field-programmable gate array (FPGA)-based GPS waveform to demonstrate on NASA's Space Communication and Navigation (SCaN) test bed.

  9. Femtosecond Photon-Counting Receiver

    NASA Technical Reports Server (NTRS)

    Krainak, Michael A.; Rambo, Timothy M.; Yang, Guangning; Lu, Wei; Numata, Kenji

    2016-01-01

    An optical correlation receiver is described that provides ultra-precise distance and/or time/pulse-width measurements even for weak (single photons) and short (femtosecond) optical signals. A new type of optical correlation receiver uses a fourth-order (intensity) interferometer to provide micron distance measurements even for weak (single photons) and short (femtosecond) optical signals. The optical correlator uses a low-noise-integrating detector that can resolve photon number. The correlation (range as a function of path delay) is calculated from the variance of the photon number of the difference of the optical signals on the two detectors. Our preliminary proof-of principle data (using a short-pulse diode laser transmitter) demonstrates tens of microns precision.

  10. SAW correlator spread spectrum receiver

    DOEpatents

    Brocato, Robert W

    2014-04-01

    A surface acoustic wave (SAW) correlator spread-spectrum (SS) receiver is disclosed which utilizes a first demodulation stage with a chip length n and a second demodulation stage with a chip length m to decode a transmitted SS signal having a code length l=n.times.m which can be very long (e.g. up to 2000 chips or more). The first demodulation stage utilizes a pair of SAW correlators which demodulate the SS signal to generate an appropriate code sequence at an intermediate frequency which can then be fed into the second demodulation stage which can be formed from another SAW correlator, or by a digital correlator. A compound SAW correlator comprising two input transducers and a single output transducer is also disclosed which can be used to form the SAW correlator SS receiver, or for use in processing long code length signals.

  11. Thompson receives 1994 Bowen award

    NASA Astrophysics Data System (ADS)

    Green, David H.; Thompson, Alan Bruce

    At the Spring Meeting in Baltimore, May 23, 1994, Alan Bruce Thompson of the Eidgenossiche Technische Hochschule, Zurich, received the 1994 N. L. Bowen Award of the Volcanology, Geochemsitry, and Petrology section, which is given for a single outstanding contribution to volcanology, geochemistry, or petrology made during the preceding 5 years. The award was presented by David H. Green of the Research School of Earth Sciences. The citation and response are given here.

  12. Digital-data receiver synchronization

    DOEpatents

    Smith, Stephen F.; Turner, Gary W.

    2005-08-02

    Digital-data receiver synchronization is provided with composite phase-frequency detectors, mutually cross-connected comparison feedback or both to provide robust reception of digital data signals. A single master clock can be used to provide frequency signals. Advantages can include fast lock-up time in moderately to severely noisy conditions, greater tolerance to noise and jitter when locked, and improved tolerance to clock asymmetries.

  13. Chip Advancer For GPS Receiver

    NASA Technical Reports Server (NTRS)

    Meehan, Thomas K.; Srinivasan, Jeffrey M.; Thomas, J. Brooks

    1989-01-01

    Instrument errors made negligible. For each integration interval, both delay and rate of change of delay initialized to small fraction of chip - for example, to order of 10 to the negative 7th power - thereby making feedback control and extraction of delay highly accurate and flexible. With appropriate selection of sampling rate relative to chip rate, commensurability errors reduced to extremely small levels. In Global Positioning System (GPS) receiver, pseudorandom code sequence generated by simple digital logic incorporating effects of time, delay, and rate of change of delay. Flexibility in starting time and sum interval very useful in aligning correlation interval with beginnings and endings of data bits.

  14. Stennis group receives NESC award

    NASA Technical Reports Server (NTRS)

    2009-01-01

    The NASA Engineering & Safety Center recently presented its Group Achievement Award to a Stennis team in recognition of technical excellence in evaluating the operational anomalies and reliability improvements associated with the space shuttle engine cut-off system. Stennis employees receiving the award were: (standing, l to r) Freddie Douglas (NASA), George Drouant (Jacobs Technology Inc.), Fred Abell (Jacobs), Robert Drackett (Jacobs) and Mike Smiles (NASA); (seated, l to r): Binh Nguyen (Jacobs), Stennis Director Gene Goldman and Joseph Lacker (NASA). Phillip Hebert of NASA is not pictured.

  15. Digital receiver study and implementation

    NASA Technical Reports Server (NTRS)

    Fogle, D. A.; Lee, G. M.; Massey, J. C.

    1972-01-01

    Computer software was developed which makes it possible to use any general purpose computer with A/D conversion capability as a PSK receiver for low data rate telemetry processing. Carrier tracking, bit synchronization, and matched filter detection are all performed digitally. To aid in the implementation of optimum computer processors, a study of general digital processing techniques was performed which emphasized various techniques for digitizing general analog systems. In particular, the phase-locked loop was extensively analyzed as a typical non-linear communication element. Bayesian estimation techniques for PSK demodulation were studied. A hardware implementation of the digital Costas loop was developed.

  16. Front end for GPS receivers

    NASA Technical Reports Server (NTRS)

    Thomas, Jr., Jess Brooks (Inventor)

    1999-01-01

    The front end in GPS receivers has the functions of amplifying, down-converting, filtering and sampling the received signals. In the preferred embodiment, only two operations, A/D conversion and a sum, bring the signal from RF to filtered quadrature baseband samples. After amplification and filtering at RF, the L1 and L2 signals are each sampled at RF at a high selected subharmonic rate. The subharmonic sample rates are approximately 900 MHz for L1 and 982 MHz for L2. With the selected subharmonic sampling, the A/D conversion effectively down-converts the signal from RF to quadrature components at baseband. The resulting sample streams for L1 and L2 are each reduced to a lower rate with a digital filter, which becomes a straight sum in the simplest embodiment. The frequency subsystem can be very simple, only requiring the generation of a single reference frequency (e.g. 20.46 MHz minus a small offset) and the simple multiplication of this reference up to the subharmonic sample rates for L1 and L2. The small offset in the reference frequency serves the dual purpose of providing an advantageous offset in the down-converted carrier frequency and in the final baseband sample rate.

  17. Reconfigurable optical transmitters and receivers

    NASA Astrophysics Data System (ADS)

    Freude, Wolfgang; Schmogrow, René; Hillerkuss, David; Meyer, Joachim; Dreschmann, Michael; Nebendahl, Bernd; Huebner, Michael; Becker, Juergen; Koos, Christian; Leuthold, Juerg

    2012-01-01

    Recent advances in electronic data processing allow constructing reconfigurable optical transmitters and receivers, where modulation formats and symbol rates are set by software-controlled field programmable gate arrays (FPGA). We report on such a real-time optical transmitter for 8 modulation formats, which can be swapped in 5 ns without data loss. With single-polarization 64QAM symbols generated at 28 GBd, we transmit data at 168 Gbit/s in real time. A similar arrangement defines a single-polarization orthogonal frequency division multiplexing (OFDM) transmitter for a data rate of 101.5 Gbit/s, where 58 subcarriers are encoded with 16QAM data. With a different software setup, the FPGA realizes an optical 56 Gbit/s transmitter for sinc-shaped so-called Nyquist pulses, the spectrum of which is rectangular having the minimum theoretically achievable bandwidth (suitable for Nyquist wavelength division multiplexing, N-WDM). For terabit OFDM reception, optical pre-processing is required to demultiplex high-bitrate signals down to lower-bitrate tributaries, which then can be processed electronically. We discuss a 10.8 Tbit/s (26 Tbit/s) receiver employing an all-optical fast Fourier transform to demultiplex 75 (325) optical subcarriers modulated with 16QAM-formated symbols at a rate of 18 GBd (10 GBd). Groups with any number of subcarriers can be selected with a simple hardware reconfiguration step.

  18. Sheeley Receives 2009 Hale Prize

    NASA Astrophysics Data System (ADS)

    Tretkoff, Ernie

    2009-05-01

    Neil Sheeley Jr., of the Space Science Division of the Naval Research Laboratory (NRL), has been awarded the 2009 George Ellery Hale Prize by the Solar Physics Division of the American Astronomical Society (AAS). The international award recognizes work in solar astronomy done over an extended period of time. Sheeley will receive the award in June at the AAS meeting in Pasadena, Calif. Sheeley is cited "for his continuing outstanding contributions to our understanding of the solar magnetic field, coronal holes, and coronal mass ejections. His wide-ranging observational and theoretical work has laid the foundation for much current research in solar and heliospheric physics, and continues to have important applications in space weather prediction."

  19. POVM Receivers for Quantum Cryptography

    NASA Astrophysics Data System (ADS)

    Brandt, H. E.

    1997-04-01

    Positive operator valued measures (POVMs) are finding increasing use in quantum cryptography.(A. Peres, Quantum Theory: Concepts and Methods, Kluwer Academic Publishers, Boston (1993).) I present quantum circuit analyses of two recently proposed (H. E. Brandt, J. M. Myers, and S. J. Lomonaco Jr., "New Results in Entangled Translucent Eavesdropping in Quantum Cryptography," in Photonic Quantum Computing, S. P. Hotaling and A. R. Pirich, Editors, Proc. SPIE 3076 (1997)) all-optical designs for POVM receivers to be used in conjunction with Bennett's B92 protocol for key distribution based on two photon polarization states. Expectation values for the POVM operators are calculated and shown to be faithfully realized by the POVM detectors.

  20. A cryogenic receiver for EPR.

    PubMed

    Narkowicz, R; Ogata, H; Reijerse, E; Suter, D

    2013-12-01

    Cryogenic probes have significantly increased the sensitivity of NMR. Here, we present a compact EPR receiver design capable of cryogenic operation. Compared to room temperature operation, it reduces the noise by a factor of ≈2.5. We discuss in detail the design and analyze the resulting noise performance. At low microwave power, the input noise density closely follows the emission of a cooled 50Ω resistor over the whole measurement range from 20K up to room temperature. To minimize the influence of the microwave source noise, we use high microwave efficiency (≈1.1-1.7mTW(-1/2)) planar microresonators. Their efficient conversion of microwave power to magnetic field permits EPR measurements with very low power levels, typically ranging from a few μW down to fractions of nW.

  1. Preamplifier Noise in VLF Receivers

    NASA Technical Reports Server (NTRS)

    Burhans, R. W.

    1978-01-01

    Noise specifications for junction field-effect transistors are presented in different ways depending on the particular semiconductor manufacturer. Arithmetic involved in converting these specifications to equivalent RMS noise in microvolts developed at the preamplifier input terminal is reviewed. These methods were useful for estimating the noise performance of high input impedance preamplifiers used with E-field antennas operating in the range of 1 KHz to 10 MHz. Both the JFET MPF-102 transistor and the COS/MOS CA3600 transistor array provided amplification for VLF receivers where the internally generated noise was well below the atmospheric noise level. The CA3600 transistor array provided better performance because of the more symmetrical complementary MOS transistor transfer characteristics than a single N-type biased JFET transistor. The CMOS amplifier resulted in self-compensating gain characteristics over a very wide temperature range from -55 to +125 C.

  2. 13 CFR 120.1723 - Pool Loan receivables received by Seller.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Pool Loan receivables received by... LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan Pools § 120.1723 Pool Loan receivables received by Seller. Any Pool Loan Receivables received by Seller...

  3. 13 CFR 120.1723 - Pool Loan receivables received by Seller.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Pool Loan receivables received by... LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan Pools § 120.1723 Pool Loan receivables received by Seller. Any Pool Loan Receivables received by Seller...

  4. 13 CFR 120.1723 - Pool Loan receivables received by Seller.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Pool Loan receivables received by... LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan Pools § 120.1723 Pool Loan receivables received by Seller. Any Pool Loan Receivables received by Seller...

  5. 13 CFR 120.1723 - Pool Loan receivables received by Seller.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Pool Loan receivables received by... LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan Pools § 120.1723 Pool Loan receivables received by Seller. Any Pool Loan Receivables received by Seller...

  6. 13 CFR 120.1723 - Pool Loan receivables received by Seller.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pool Loan receivables received by... LOANS Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan Pools § 120.1723 Pool Loan receivables received by Seller. Any Pool Loan Receivables received by Seller...

  7. Fluid absorption solar energy receiver

    NASA Technical Reports Server (NTRS)

    Bair, Edward J.

    1993-01-01

    A conventional solar dynamic system transmits solar energy to the flowing fluid of a thermodynamic cycle through structures which contain the gas and thermal energy storage material. Such a heat transfer mechanism dictates that the structure operate at a higher temperature than the fluid. This investigation reports on a fluid absorption receiver where only a part of the solar energy is transmitted to the structure. The other part is absorbed directly by the fluid. By proportioning these two heat transfer paths the energy to the structure can preheat the fluid, while the energy absorbed directly by the fluid raises the fluid to its final working temperature. The surface temperatures need not exceed the output temperature of the fluid. This makes the output temperature of the gas the maximum temperature in the system. The gas can have local maximum temperatures higher than the output working temperature. However local high temperatures are quickly equilibrated, and since the gas does not emit radiation, local high temperatures do not result in a radiative heat loss. Thermal radiation, thermal conductivity, and heat exchange with the gas all help equilibrate the surface temperature.

  8. Recent developments in superconducting receivers

    SciTech Connect

    Richards, P.L.

    1990-09-01

    A description is given of recent work at Berkeley on superconducting mixers and detectors for infrared and millimeter wavelengths. The first report is a review article which summarizes the status of development of superconducting components for infrared and millimeter wave receivers. The next report describes accurate measurements and also theoretical modeling of an SIS quasiparticle waveguide mixer for W-band which uses very high quality Ta junctions. The best mixer noise is only 1.3 times the quantum limit. Both the mixer gain and the noise are in quantitative agreement with the quantum theory. Next, a report is given on measurements and theoretical modeling of the absorptivity (surface resistance) of high quality epitaxial films of the high {Tc} superconductor YBCO from 750 GHz to 21 THz. Finally, there are reports on the design and experimental performance of two different types of high {Tc} bolometric detectors. One is a conventional bolometer with a gold-black absorber. The other is an antenna coupled microbolometer.

  9. Lunar Receiving Laboratory Project History

    NASA Technical Reports Server (NTRS)

    Mangus, Susan; Larsen, William

    2004-01-01

    As early as 1959, the Working Group on Lunar Exploration within NASA advocated that 'one of the prime objectives of the first lunar landing mission should be the collection of samples for return to Earth, where they could be subjected to detailed study and analysis.' Within NASA, neither this group nor any other scientists working with the Agency were concerned about back contamination issues. Outside of NASA, back contamination concerns had been raised as early as 1960. Although NASA did not seem to pay any attention to the concerns at that time, the scientific community continued to be interested in the topic. In 1962 and again in 1963, as the Apollo Program loomed large, further discussions were held. These early discussions of back contamination did not make their way into NASA's administration, however, and when Manned Spacecraft Center personnel began to articulate early concepts for the Lunar Receiving Laboratory (LRL), the back contamination issue was not considered. Once this concern became a major focus, however, the LRL's development became increasingly complex. This is the history of that development.

  10. Thermal resistance model for CSP central receivers

    NASA Astrophysics Data System (ADS)

    de Meyer, O. A. J.; Dinter, F.; Govender, S.

    2016-05-01

    The receiver design and heliostat field aiming strategy play a vital role in the heat transfer efficiency of the receiver. In molten salt external receivers, the common operating temperature of the heat transfer fluid or molten salt ranges between 285°C to 565°C. The optimum output temperature of 565°C is achieved by adjusting the mass flow rate of the molten salt through the receiver. The reflected solar radiation onto the receiver contributes to the temperature rise in the molten salt by means of heat transfer. By investigating published work on molten salt external receiver operating temperatures, corresponding receiver tube surface temperatures and heat losses, a model has been developed to obtain a detailed thermographic representation of the receiver. The steady state model uses a receiver flux map as input to determine: i) heat transfer fluid mass flow rate through the receiver to obtain the desired molten salt output temperature of 565°C, ii) receiver surface temperatures iii) receiver tube temperatures iv) receiver efficiency v) pressure drop across the receiver and vi) corresponding tube strain per panel.

  11. Design, fabrication, and bench testing of a solar chemical receiver

    NASA Technical Reports Server (NTRS)

    Summers, W. A.; Pierre, J. F.

    1981-01-01

    Solar thermal energy can be effectively collected, transported, stored, and utilized by means of a chemical storage and transport system employing the reversible SO2 oxidation reaction. A solar chemical receiver for SO3 thermal decomposition to SO2 and oxygen was analyzed. Bench tests of a ten foot section of a receiver module were conducted with dissociated sulfuric acid (SO3 and H2O) in an electrical furnace. Measured percent conversion of SO3 was 85% of the equilibrium value. Methods were developed to fabricate and assemble a complete receiver module. These methods included applying an aluminide coating to certain exposed surfaces, assembling concentric tubes with a wire spacer, applying a platinum catalyst to the tubing wall, and coiling the entire assembly into the desired configuration.

  12. Percentage of Surgical Patients Receiving Recommended Care

    MedlinePlus

    ... Recommended Care Percentage of Surgical Patients Receiving Recommended Care This is a composite measure based on individual ... Age Group Percentage of Surgical Patients Receiving Recommended Care by Age Group uzrc-9bvr Download these data » ...

  13. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Irwin, S. H.; NELSON; Roleyni, G.

    1977-01-01

    Optimal design studies of MLS angle-receivers and a theoretical design-study of MLS DME-receivers are reported. The angle-receiver results include an integration of the scan data processor and tracking filter components of the optimal receiver into a unified structure. An extensive simulation study comparing the performance of the optimal and threshold receivers in a wide variety of representative dynamical interference environments was made. The optimal receiver was generally superior. A simulation of the performance of the threshold and delay-and-compare receivers in various signal environments was performed. An analysis of combined errors due to lateral reflections from vertical structures with small differential path delays, specular ground reflections with neglible differential path delays, and thermal noise in the receivers is provided.

  14. The First Six ALMA Band 10 Receivers

    NASA Astrophysics Data System (ADS)

    Fujii, Y.; Gonzalez, A.; Kroug, M.; Kaneko, K.; Miyachi, A.; Yokoshima, T.; Kuroiwa, K.; Ogawa, H.; Makise, K.; Wang, Z.; Uzawa, Y.

    2013-01-01

    The first six Atacama Large Millimeter/submillimeter Array (ALMA) Band 10 (787-950 GHz) receivers have been developed and characterized during the receiver preproduction phase. State-of-the-art measurement systems at THz frequencies have been implemented and successfully used to measure the performance of the first six receivers. Extensive tests ranging from receiver sensitivity and stability to optical aperture efficiency on the secondary antenna have been performed. Performance of all six receivers is well within the stringent ALMA requirements. Moreover, our extensive tests have shown that there are no big performance differences between receivers. These results indicate that the ALMA Band 10 receiver is ready for the production phase, during which an additional 67 receivers will be produced and characterized.

  15. High speed receiver for capsule endoscope.

    PubMed

    Woo, S H; Yoon, K W; Moon, Y K; Lee, J H; Park, H J; Kim, T W; Choi, H C; Won, C H; Cho, J H

    2010-10-01

    In this study, a high-speed receiver for a capsule endoscope was proposed and implemented. The proposed receiver could receive 20 Mbps data that was sufficient to receive images with a higher resolution than conventional receivers. The receiver used a 1.2 GHz band to receive radio frequency (RF) signal, and demodulated the signal to an intermediate frequency (IF) stage (150 MHz). The demodulated signal was amplified, filtered, and under-sampled by a high-speed analog-to-digital converter (ADC). In order to decode the under-sampled data in real time, a simple frequency detection algorithm was selected and was implemented by using a FPGA. The implemented system could receive 20 Mbps data.

  16. Trough Receiver Heat Loss Testing (Presentation)

    SciTech Connect

    Lewandowski, A.; Feik, C.; Hansen, R.; Phillips, S.; Bingham, C.; Netter, J.; Forristal, R.; Burkholder, F.; Meglan, B.; Wolfrum, E.

    2006-02-01

    This presentation describes the design, fabrication, and qualification of an experimental capability for thermal loss testing of full-size trough receiver elements; and the testing on a variety of receivers.

  17. How To Improve You Shipping and Receiving.

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    2001-01-01

    Discusses how two universities improved their shipping and receiving operations and cut costs. Examples from the University of Texas at Dallas and John Hopkins University, Baltimore, Maryland, illustrate how they established greater shipping and receiving department efficiencies. (GR)

  18. Telemetry Tests Of The Advanced Receiver II

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami M.; Bevan, Roland P.; Marina, Miguel

    1993-01-01

    Report describes telemetry tests of Advanced Receiver II (ARX-II): digital radio receiving subsystem operating on intermediate-frequency output of another receiving subsystem called "multimission receiver" (MMR), detecting carrier, subcarrier, and data-symbol signals transmitted by spacecraft, and extracts Doppler information from signals. Analysis of data shows performance of MMR/ARX-II system comparable and sometimes superior to performances of Blk-III/BPA and Blk-III/SDA/SSA systems.

  19. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  20. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  1. Battle Keeps Solar Energy in Receiver

    NASA Technical Reports Server (NTRS)

    Mcdougal, A. R.; Hale, R. R.

    1982-01-01

    Mirror structure in solar concentrator reduces heat loss by reflection and reradiation. Baffle reflects entering rays back and forth in solar-concentrator receiver until they reach heat exchanger. Similarly, infrared energy reradiated by heat exchanger is prevented from leaving receiver. Surfaces of baffle and inside wall of receiver are polished and highly reflective at solar and infrared wavelengths.

  2. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Receiver. 80.1013 Section 80.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be...

  3. 49 CFR 393.88 - Television receivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a...

  4. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... volts if the receiver is designed to operate from nominal 110 to 120 root mean square volt power sources. If the receiver is designed to operate from a power source having some voltage other than from... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Television receivers. 1020.10 Section 1020.10...

  5. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... volts if the receiver is designed to operate from nominal 110 to 120 root mean square volt power sources. If the receiver is designed to operate from a power source having some voltage other than from... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Television receivers. 1020.10 Section 1020.10...

  6. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... volts if the receiver is designed to operate from nominal 110 to 120 root mean square volt power sources. If the receiver is designed to operate from a power source having some voltage other than from... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Television receivers. 1020.10 Section 1020.10...

  7. 49 CFR 393.88 - Television receivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a...

  8. 49 CFR 393.88 - Television receivers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a...

  9. 49 CFR 393.88 - Television receivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a...

  10. 49 CFR 393.88 - Television receivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a...

  11. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  12. 49 CFR 236.730 - Coil, receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Coil, receiver. 236.730 Section 236.730 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Coil, receiver. Concentric layers of insulated wire wound around the core of a receiver of an...

  13. 49 CFR 236.730 - Coil, receiver.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Coil, receiver. 236.730 Section 236.730 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Coil, receiver. Concentric layers of insulated wire wound around the core of a receiver of an...

  14. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Receiver. 80.1013 Section 80.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be...

  15. A zero-power radio receiver.

    SciTech Connect

    Brocato, Robert Wesley

    2004-09-01

    This report describes both a general methodology and some specific examples of passive radio receivers. A passive radio receiver uses no direct electrical power but makes sole use of the power available in the radio spectrum. These radio receivers are suitable as low data-rate receivers or passive alerting devices for standard, high power radio receivers. Some zero-power radio architectures exhibit significant improvements in range with the addition of very low power amplifiers or signal processing electronics. These ultra-low power radios are also discussed and compared to the purely zero-power approaches.

  16. More Efficient Solar Thermal-Energy Receiver

    NASA Technical Reports Server (NTRS)

    Dustin, M. O.

    1987-01-01

    Thermal stresses and reradiation reduced. Improved design for solar thermal-energy receiver overcomes three major deficiencies of solar dynamic receivers described in literature. Concentrator and receiver part of solar-thermal-energy system. Receiver divided into radiation section and storage section. Concentrated solar radiation falls on boiling ends of heat pipes, which transmit heat to thermal-energy-storage medium. Receiver used in number of applications to produce thermal energy directly for use or to store thermal energy for subsequent use in heat engine.

  17. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Highfill, J. H., III

    1979-01-01

    The angle tracking problems in microwave landing system receivers along with a receiver design capable of optimal performance in the multipath environments found in air terminal areas were studied. Included were various theoretical and evaluative studies like: (1) signal model development; (2) derivation of optimal receiver structures; and (3) development and use of computer simulations for receiver algorithm evaluation. The development of an experimental receiver for flight testing is presented. An overview of the work and summary of principal results and conclusions are reported.

  18. A minimalist approach to receiver architecture

    NASA Technical Reports Server (NTRS)

    Collins, O.

    1991-01-01

    New signal processing techniques are described for Deep Space Network radios and a proposed receiver architecture is presented, as well as experimental results on this new receiver's analog front end. The receiver's design employs direct downconversion rather than high speed digitization, and it is just as suitable for use as a space based probe relay receiver as it is for installation at a ground antenna. The advantages of having an inexpensive, shoe box size receiver, which could be carried around to antennas of opportunity, used for spacecraft testing or installed in the base of every antenna in a large array are the force behind this project.

  19. Integration Window Position Estimation in TR Receivers

    SciTech Connect

    Nekoogar, F; Dowla, F; Spiridon, A

    2005-03-15

    Transmitted-reference (TR) receivers avoid the stringent synchronization requirements that exist in conventional pulse detection schemes. However, the performance of such receivers is highly sensitive to precise timing acquisition and tracking as well as the length of their integration window. This window in TR receivers defines the limits of the finite integrator prior to the final decision making block. In this paper, we propose a novel technique that allows us to extract the timing information of the integration window very accurately in UWB-TR receivers in the presence of channel noise. The principles of the method are presented and the BER performance of a modified UWB-TR receiver is investigated by computer simulation. Our studies show that the proposed estimation technique adds value to the conventional TR receiver structure with modest increase in complexity.

  20. Quantity of acid in acid fog

    SciTech Connect

    Deal, W.J.

    1983-07-01

    The chemical composition of fog particles has become of considerable interest, because of both the possibility of interpreting atmospheric- chemistry processes in fog particles in terms of the principles of aqueous chemistry and the potential health effects of species present in fog particles. The acidity of fog particles has received wide attention. This communication noted the actual magnitude of the excess acidity in acidic fog particles and suggested a possible line of inquiry into the health effects of such fog so that it can be determined whether a typical fog is detrimental or beneficial relative to dry air. (DP)

  1. RF subsystem design for microwave communication receivers

    NASA Astrophysics Data System (ADS)

    Bickford, W. J.; Brodsky, W. G.

    A system review of the RF subsystems of (IFF) transponders, tropscatter receivers and SATCOM receivers is presented. The quantity potential for S-band and X-band IFF transponders establishes a baseline requirement. From this, the feasibility of a common design for these and other receivers is evaluated. Goals are established for a GaAs MMIC (monolithic microwave integrated circuit) device and related local oscillator preselector and self-test components.

  2. Absolute flux density calibrations: Receiver saturation effects

    NASA Technical Reports Server (NTRS)

    Freiley, A. J.; Ohlson, J. E.; Seidel, B. L.

    1978-01-01

    The effect of receiver saturation was examined for a total power radiometer which uses an ambient load for calibration. Extension to other calibration schemes is indicated. The analysis shows that a monotonic receiver saturation characteristic could cause either positive or negative measurement errors, with polarity depending upon operating conditions. A realistic model of the receiver was made by using a linear-cubic voltage transfer characteristic. The evaluation of measurement error for this model provided a means for correcting radio source measurements.

  3. Costas loop analysis for coherent optical receivers

    NASA Astrophysics Data System (ADS)

    Hodgkinson, T. G.

    1986-03-01

    A homodyne Costas loop receiver is analyzed taking both shot and laser phase noise sources into acount. The reciever performance is compared with that of a heterodyne receiver using an electrical Costas loop and that of a coherent receiver using a pilot carrier phase-locked loop. It is shown that, to avoid large performance penalties, beat linewidth to bit-rate ratios smaller than 0.05 percent and 0.5 percent are needed for PSK homodyne and heterodyne systems, respectively.

  4. Ceramic high temperature receiver design and tests

    NASA Technical Reports Server (NTRS)

    Davis, S. B.

    1982-01-01

    The High Temperature Solar Thermal Receiver, which was tested a Edwards AFB, CA during the winter of 1980-1981, evolved from technologies developed over a five year period of work. This receiver was tested at the Army Solar Furnace at White Sands, NM in 1976. The receiver, was tested successfully at 1768 deg F and showed thermal efficiencies of 85%. The results were sufficiently promising to lead ERDA to fund our development and test of a 250 kW receiver to measure the efficiency of an open cavity receiver atop a central tower of a heliostat field. This receiver was required to be design scalable to 10, 50, and 100 MW-electric sizes to show applicability to central power tower receivers. That receiver employed rectagular silicon carbide panels and vertical stanchions to achieve scalability. The construction was shown to be fully scalable; and the receiver was operated at temperatures up to 2000 deg F to achieve the performance goals of the experiment during tests at the GIT advanced components test facility during the fall of 1978.

  5. Ceramic high temperature receiver design and tests

    SciTech Connect

    Davis, S.B.

    1982-07-01

    The High Temperature Solar Thermal Receiver, which was tested a Edwards AFB, CA during the winter of 1980-1981, evolved from technologies developed over a five year period of work. This receiver was tested at the Army Solar Furnace at White Sands, NM in 1976. The receiver, was tested successfully at 1768 deg F and showed thermal efficiencies of 85%. The results were sufficiently promising to lead ERDA to fund our development and test of a 250 kW receiver to measure the efficiency of an open cavity receiver atop a central tower of a heliostat field. This receiver was required to be design scalable to 10, 50, and 100 MW-electric sizes to show applicability to central power tower receivers. That receiver employed rectangular silicon carbide panels and vertical stanchions to achieve scalability. The construction was shown to be fully scalable, and the receiver was operated at temperatures up to 2000 deg F to achieve the performance goals of the experiment during tests at the GIT advanced components test facility during the fall of 1978.

  6. False lock performance of quadriphase receivers

    NASA Technical Reports Server (NTRS)

    Simon, M. K.

    1979-01-01

    Quadriphase receivers, like biphase receivers, have the ability to false lock on a sideband on the data modulation. The theory associated with this phenomenon for receivers of binary phase-shift-keying (BPSK), using Costas loop demodulation, has recently been documented in the literature. This paper considers the corresponding theory for receivers of balanced quadriphase-shift-keying (QPSK) employing a quadriphase Costas loop (or equivalent fourth-power loop) for demodulation. Specific closed form expressions for false lock performance are developed and numerically evaluated for the particular case of single pole arm filters and an NRZ data format for each of the two statistically independent quadrature modulations.

  7. Nursing process approach improves receivables management.

    PubMed

    Dias, K; Stockamp, D

    1992-09-01

    The "nursing process" is a systematic decision-making approach to problem solving based on open-system theory. This theory assumes that there is an on-going interchange between all system components. Components cannot be viewed in isolation, because decisions regarding one component will affect other components. Receivables management is similar to the nursing process, in that it involves constant diagnosis, assessment, and intervention in the work in process during all phases of the receivables cycle. In experiments that applied the nursing process concept to the management of accounts receivable in several hospitals, gross days in accounts receivable were reduced and cash flow was increased. PMID:10145682

  8. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed...

  9. 7 CFR 1230.632 - Receiving ballots.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Producers. A ballot shall be considered to be received on time if: (1) It was cast in-person in the county...; or (2) It was cast as an absentee ballot, having a postmarked date not later than the last day of the... day of the in-person voting period and was received in the FSA headquarters office in Washington,...

  10. 7 CFR 1230.632 - Receiving ballots.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Producers. A ballot shall be considered to be received on time if: (1) It was cast in-person in the county...; or (2) It was cast as an absentee ballot, having a postmarked date not later than the last day of the... day of the in-person voting period and was received in the FSA headquarters office in Washington,...

  11. 7 CFR 1230.632 - Receiving ballots.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Producers. A ballot shall be considered to be received on time if: (1) It was cast in-person in the county...; or (2) It was cast as an absentee ballot, having a postmarked date not later than the last day of the... day of the in-person voting period and was received in the FSA headquarters office in Washington,...

  12. 7 CFR 1230.632 - Receiving ballots.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Producers. A ballot shall be considered to be received on time if: (1) It was cast in-person in the county...; or (2) It was cast as an absentee ballot, having a postmarked date not later than the last day of the... day of the in-person voting period and was received in the FSA headquarters office in Washington,...

  13. 7 CFR 1230.632 - Receiving ballots.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Producers. A ballot shall be considered to be received on time if: (1) It was cast in-person in the county...; or (2) It was cast as an absentee ballot, having a postmarked date not later than the last day of the... day of the in-person voting period and was received in the FSA headquarters office in Washington,...

  14. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Highfill, J. H., III; Irwin, S. H.; Padgett, J. E.

    1975-01-01

    A receiver is designed for aircraft (A/C), which, as a component of the proposed Microwave Landing System (MLS), is capable of optimal performance in the multipath environments found in air terminal areas. Topics discussed include: the angle-tracking problem of the MLS receiver; signal modeling; preliminary approaches to optimal design; suboptimal design; and simulation study.

  15. Liquid cooled fiber thermal radiation receiver

    DOEpatents

    Butler, Barry L.

    1987-01-01

    A radiation-to-thermal receiver apparatus for collecting radiation and converting it to thermal energy is disclosed. The invention includes a fibrous mat material which captures radiation striking the receiver. Captured radiation is removed from the fibrous mat material by a transparent fluid within which the material is bathed.

  16. Liquid cooled fiber thermal radiation receiver

    DOEpatents

    Butler, B.L.

    1985-03-29

    A radiation-to-thermal receiver apparatus for collecting radiation and converting it to thermal energy is disclosed. The invention includes a fibrous mat material which captures radiation striking the receiver. Captured radiation is removed from the fibrous mat material by a transparent fluid within which the material is bathed.

  17. Heat-Energy Analysis for Solar Receivers

    NASA Technical Reports Server (NTRS)

    Lansing, F. L.

    1982-01-01

    Heat-energy analysis program (HEAP) solves general heat-transfer problems, with some specific features that are "custom made" for analyzing solar receivers. Can be utilized not only to predict receiver performance under varying solar flux, ambient temperature and local heat-transfer rates but also to detect locations of hotspots and metallurgical difficulties and to predict performance sensitivity of neighboring component parameters.

  18. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be capable of reception of G3E emission on the navigational frequency...

  19. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be capable of reception of G3E emission on the navigational frequency...

  20. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be capable of reception of G3E emission on the navigational frequency...

  1. 17 CFR 256.143 - Accounts receivable.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Accounts receivable. 256.143... SYSTEM OF ACCOUNTS FOR MUTUAL SERVICE COMPANIES AND SUBSIDIARY SERVICE COMPANIES, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 3. Current and Accrued Assets § 256.143 Accounts receivable. This account...

  2. 17 CFR 256.143 - Accounts receivable.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Accounts receivable. 256.143... SYSTEM OF ACCOUNTS FOR MUTUAL SERVICE COMPANIES AND SUBSIDIARY SERVICE COMPANIES, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 3. Current and Accrued Assets § 256.143 Accounts receivable. This account...

  3. 29 CFR 1910.169 - Air receivers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Compressed Gas and Compressed Air Equipment § 1910.169 Air receivers. (a) General requirements—(1) Application. This section applies to compressed air receivers, and other equipment used in providing and utilizing compressed air for performing operations such as...

  4. Advanced heat receiver conceptual design study

    NASA Technical Reports Server (NTRS)

    Kesseli, James; Saunders, Roger; Batchelder, Gary

    1988-01-01

    Solar Dynamic space power systems are candidate electrical power generating systems for future NASA missions. One of the key components of the solar dynamic power system is the solar receiver/thermal energy storage (TES) subsystem. Receiver development was conducted by NASA in the late 1960's and since then a very limited amount of work has been done in this area. Consequently the state of the art (SOA) receivers designed for the IOC space station are large and massive. The objective of the Advanced Heat Receiver Conceptual Design Study is to conceive and analyze advanced high temperature solar dynamic Brayton and Stirling receivers. The goal is to generate innovative receiver concepts that are half of the mass, smaller, and more efficient than the SOA. It is also necessary that these innovative receivers offer ease of manufacturing, less structural complexity and fewer thermal stress problems. Advanced Brayton and Stirling receiver storage units are proposed and analyzed in this study which can potentially meet these goals.

  5. 47 CFR 32.1170 - Receivables.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... enable the company to make the following analysis: (1) Amounts due from customers who are receiving... FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.1170 Receivables. (a) This account shall include all amounts due from customers for services rendered or billed and...

  6. 7 CFR 966.124 - Approved receiver.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and..., as an approved receiver, tomatoes for purposes as set forth in § 966.120(a), shall annually, prior... specified purpose is to occur; (4) Whether or not the receiver packs, repacks or sells fresh tomatoes; (5)...

  7. 7 CFR 966.124 - Approved receiver.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and..., as an approved receiver, tomatoes for purposes as set forth in § 966.120(a), shall annually, prior... specified purpose is to occur; (4) Whether or not the receiver packs, repacks or sells fresh tomatoes; (5)...

  8. 7 CFR 966.124 - Approved receiver.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and..., as an approved receiver, tomatoes for purposes as set forth in § 966.120(a), shall annually, prior... specified purpose is to occur; (4) Whether or not the receiver packs, repacks or sells fresh tomatoes; (5)...

  9. 7 CFR 966.124 - Approved receiver.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and..., as an approved receiver, tomatoes for purposes as set forth in § 966.120(a), shall annually, prior... specified purpose is to occur; (4) Whether or not the receiver packs, repacks or sells fresh tomatoes; (5)...

  10. 7 CFR 966.124 - Approved receiver.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and..., as an approved receiver, tomatoes for purposes as set forth in § 966.120(a), shall annually, prior... specified purpose is to occur; (4) Whether or not the receiver packs, repacks or sells fresh tomatoes; (5)...

  11. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... transportation applications as railways, vehicles or cranes. (b) Gauges and valves. (1) Air receivers shall be equipped with indicating pressure gauges and spring-loaded safety valves. Safety valves shall prevent receiver pressure from exceeding 110 percent of the maximum allowable working pressure. (2) No other...

  12. OMEGA timing receiver, design and system test

    NASA Technical Reports Server (NTRS)

    Wilson, J. J.; Britt, J. E.; Chi, A.

    1972-01-01

    The design of a two frequency OMEGA Timing Receiver is discussed. The receiver tracks the arrival time of the signals by precise phase matching at the receiving antenna. Provision is made for inserting a propagation delay correction for each signal path. Time is measured as the difference between the zero crossing coincidence of the corrected signals and the local time. This number is displayed on the front panel in microseconds. The receiver can also function as a precise phase tracking receiver for collection of propagation data essential to augmenting the propagation corrections. All phase and time information is made available in a BCD format for flexibility in interfacing with other equipment. Results of preliminary tests using experimental transmissions are given. Preliminary results indicate time may be transferred by this technique to an accuracy of a few microseconds.

  13. EHF low-noise FET receiver

    NASA Technical Reports Server (NTRS)

    Schellenberg, J. M.; Watkins, E. T.

    1983-01-01

    Extremely high frequency (EHF) receivers for military and NASA programs must be small, lightweight, and highly reliable. In connection with recent advances in the development of mm-wave FET devices and circuits, a basis has been obtained for the eventual replacement of diode mixer front-ends by FET preamplifiers in receivers up to 94 GHz. By placing a low noise amplifier in front of the mixer it is possible to achieve a lower system noise figure than that found in conventional mm-wave receivers. A broader bandwidth can also be provided. Attention is given to the receiver configuration, a low noise FET amplifier, an image rejection filter, a dual-gate FET mixer, a FET local oscillator, and a FET receiver.

  14. Temperature influences in receiver clock modelling

    NASA Astrophysics Data System (ADS)

    Wang, Kan; Meindl, Michael; Rothacher, Markus; Schoenemann, Erik; Enderle, Werner

    2016-04-01

    In Precise Point Positioning (PPP), hardware delays at the receiver site (receiver, cables, antenna, …) are always difficult to be separated from the estimated receiver clock parameters. As a result, they are partially or fully contained in the estimated "apparent" clocks and will influence the deterministic and stochastic modelling of the receiver clock behaviour. In this contribution, using three years of data, the receiver clock corrections of a set of high-precision Hydrogen Masers (H-Masers) connected to stations of the ESA/ESOC network and the International GNSS Service (IGS) are firstly characterized concerning clock offsets, drifts, modified Allan deviations and stochastic parameters. In a second step, the apparent behaviour of the clocks is modelled with the help of a low-order polynomial and a known temperature coefficient (Weinbach, 2013). The correlations between the temperature and the hardware delays generated by different types of antennae are then analysed looking at daily, 3-day and weekly time intervals. The outcome of these analyses is crucial, if we intend to model the receiver clocks in the ground station network to improve the estimation of station-related parameters like coordinates, troposphere zenith delays and ambiguities. References: Weinbach, U. (2013) Feasibility and impact of receiver clock modeling in precise GPS data analysis. Dissertation, Leibniz Universität Hannover, Germany.

  15. Terahertz Array Receivers with Integrated Antennas

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Goutam; Llombart, Nuria; Lee, Choonsup; Jung, Cecile; Lin, Robert; Cooper, Ken B.; Reck, Theodore; Siles, Jose; Schlecht, Erich; Peralta, Alessandro; Thomas, Bertrand; Mehdi, Imran

    2011-01-01

    Highly sensitive terahertz heterodyne receivers have been mostly single-pixel. However, now there is a real need of multi-pixel array receivers at these frequencies driven by the science and instrument requirements. In this paper we explore various receiver font-end and antenna architectures for use in multi-pixel integrated arrays at terahertz frequencies. Development of wafer-level integrated terahertz receiver front-end by using advanced semiconductor fabrication technologies has progressed very well over the past few years. Novel stacking of micro-machined silicon wafers which allows for the 3-dimensional integration of various terahertz receiver components in extremely small packages has made it possible to design multi-pixel heterodyne arrays. One of the critical technologies to achieve fully integrated system is the antenna arrays compatible with the receiver array architecture. In this paper we explore different receiver and antenna architectures for multi-pixel heterodyne and direct detector arrays for various applications such as multi-pixel high resolution spectrometer and imaging radar at terahertz frequencies.

  16. Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies.

    PubMed

    Deprèle, Sylvine; Kashemirov, Boris A; Hogan, James M; Ebetino, Frank H; Barnett, Bobby L; Evdokimov, Artem; McKenna, Charles E

    2008-05-01

    The complex formed from crystallization of human farnesyl pyrophosphate synthase (hFPPS) from a solution of racemic [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501, 8), a chiral analog of the anti-osteoporotic drug risedronate, contained the R enantiomer in the enzyme active site. This enantiospecificity was assessed by computer modeling of inhibitor-active site interactions using Autodock 3, which was also evaluated for predictive ability in calculations of the known configurations of risedronate, zoledronate, and minodronate complexed in the active site of hFPPS. In comparison with these structures, the 8 complex exhibited certain differences, including the presence of only one Mg(2+), which could contribute to its 100-fold higher IC(50). An improved synthesis of 8 is described, which decreases the number of steps from 12 to 8 and increases the overall yield by 17-fold.

  17. The Los Alamos beacon receiver array

    SciTech Connect

    Carlos, R.C.; Massey, R.S. )

    1994-07-01

    The authors are interested in studying both the natural background of acoustic and acoustic-gravity waves, for which the sources are not generally known, as well as waves produced by known sources such as large explosions and launches of large rockets. The authors describe radio receivers that monitor transmissions from beacons on geosynchronous satellites. The receivers can detect perturbations of a 300--3,000 s period in the electron density integrated from beacon to receiver, for amplitudes as low as (1--2) [times] 10[sup 13] m[sup [minus]2]. Data are used in studies of atmospheric acoustic and acoustic-gravity waves.

  18. Global Positioning System receiver evaluation results

    SciTech Connect

    Byrne, R.H.

    1993-09-01

    A Sandia project currently uses an outdated Magnavox 6400 Global Positioning System (GPS) receiver as the core of its navigation system. The goal of this study was to analyze the performance of the current GPS receiver compared to newer, less expensive models and to make recommendations on how to improve the performance of the overall navigation system. This paper discusses the test methodology used to experimentally analyze the performance of different GPS receivers, the test results, and recommendations on how an upgrade should proceed. Appendices contain detailed information regarding the raw data, test hardware, and test software.

  19. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... frequencies authorized pursuant to § 80.855(a). (b) One or more loudspeakers capable of being used to maintain... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  20. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... public coast stations serving the area in which the vessel is navigated. (d) One or more loudspeakers... at the receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a...

  1. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... public coast stations serving the area in which the vessel is navigated. (d) One or more loudspeakers... at the receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a...

  2. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... frequencies authorized pursuant to § 80.855(a). (b) One or more loudspeakers capable of being used to maintain... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  3. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... frequencies authorized pursuant to § 80.855(a). (b) One or more loudspeakers capable of being used to maintain... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  4. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... public coast stations serving the area in which the vessel is navigated. (d) One or more loudspeakers... at the receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a...

  5. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... frequencies authorized pursuant to § 80.855(a). (b) One or more loudspeakers capable of being used to maintain... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  6. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... public coast stations serving the area in which the vessel is navigated. (d) One or more loudspeakers... at the receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a...

  7. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... public coast stations serving the area in which the vessel is navigated. (d) One or more loudspeakers... at the receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a...

  8. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... frequencies authorized pursuant to § 80.855(a). (b) One or more loudspeakers capable of being used to maintain... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  9. Collector/Receiver Characterization (Fact Sheet)

    SciTech Connect

    Not Available

    2010-08-01

    Fact sheet describing NREL CSP Program capabilities for collector/receiver characterization: determining optical efficiency, measuring heat loss, developing and testing concentrators, concentrating the sun's power, and optically characterizing CSP plants.

  10. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... components of the receiver except that portion of the neck and socket of the cathode-ray tube which normally... of a circuit or shield component. The warning label shall include the specification of operating...

  11. First Public Library Satellite Receiver System.

    ERIC Educational Resources Information Center

    Donaldson, Marion F.

    1982-01-01

    Description of video services at Lake County Public Library, Indiana, highlights the installation of a satellite receiver system and notes funding and justification, components of a satellite system, decisions and sources of assistance, programming available, and future considerations. (EJS)

  12. Digital Signal Processing Based Biotelemetry Receivers

    NASA Technical Reports Server (NTRS)

    Singh, Avtar; Hines, John; Somps, Chris

    1997-01-01

    This is an attempt to develop a biotelemetry receiver using digital signal processing technology and techniques. The receiver developed in this work is based on recovering signals that have been encoded using either Pulse Position Modulation (PPM) or Pulse Code Modulation (PCM) technique. A prototype has been developed using state-of-the-art digital signal processing technology. A Printed Circuit Board (PCB) is being developed based on the technique and technology described here. This board is intended to be used in the UCSF Fetal Monitoring system developed at NASA. The board is capable of handling a variety of PPM and PCM signals encoding signals such as ECG, temperature, and pressure. A signal processing program has also been developed to analyze the received ECG signal to determine heart rate. This system provides a base for using digital signal processing in biotelemetry receivers and other similar applications.

  13. A C-Band satellite receiver

    NASA Astrophysics Data System (ADS)

    Lupinetti, F.; Ingels, F.

    1985-12-01

    The design concept of a 24-channel C-band receiver for satellite TV signals is presented. The system comprises a low-noise amplifier, a 3.7-4.2-GHz/450-910-MHz block down converter, the receiver proper (a modified analog UNF tuner at IF = 45 MHz and a digital channel selector), and an RF modulator providing video and audio on channels 3 or 4. The operation of the receiver is described and illustrated with block diagrams and tables of specifications. A prototype receiver has been found to give good video quality and definition with clear 20-20,000-Hz audio when used with a 4-ft dish antenna.

  14. 49 CFR 236.788 - Receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.788 Receiver. A device on a locomotive, so placed that it is in position to be influenced inductively or actuated by...

  15. NASA Dryden Receives 'New' F-15Ds

    NASA Video Gallery

    NASA's Dryden Flight Research Center has received three F-15D Eagle aircraft from the U.S. Air Force for flight research and mission support duties. The demilitarized high-performance aircraft were...

  16. A 30 GHz monolithic receive module

    NASA Technical Reports Server (NTRS)

    Mondal, J.; Contolatis, T.; Geddes, J.; Bauhahn, P.; Sokolov, V.

    1990-01-01

    The technical achievements and deliveries made during the duration of the program to develop a 30 GHz monolithic receive module for communication feed array applications and to deliver submodules and 30 GHz monolithic receive modules for experimental evaluation are discussed. Key requirements include an overall receive module noise figure of 5 dB, a 30 dB RF-to-RF gain with six levels of intermediate gain control, a five bit phase shifter, and a maximum power consumption of 250 mW. In addition, the monolithic receive module design addresses a cost goal of less than one thousand dollars (1980 dollars) per module in unit buys of 5,000 or more, and a mechanical configuration that is applicable to a spaceborne phase array system. An additional task for the development and delivery of 32 GHz phase shifter integrated circuit (IC) for deep space communication is also described.

  17. High dynamic GPS receiver validation demonstration

    NASA Technical Reports Server (NTRS)

    Hurd, W. J.; Statman, J. I.; Vilnrotter, V. A.

    1985-01-01

    The Validation Demonstration establishes that the high dynamic Global Positioning System (GPS) receiver concept developed at JPL meets the dynamic tracking requirements for range instrumentation of missiles and drones. It was demonstrated that the receiver can track the pseudorange and pseudorange rate of vehicles with acceleration in excess of 100 g and jerk in excess of 100 g/s, dynamics ten times more severe than specified for conventional High Dynamic GPS receivers. These results and analytic extensions to a complete system configuration establish that all range instrumentation requirements can be met. The receiver can be implemented in the 100 cu in volume required by all missiles and drones, and is ideally suited for transdigitizer or translator applications.

  18. Stanley receives 2010 William Gilbert Award: Citation

    NASA Astrophysics Data System (ADS)

    Weiss, Benjamin P.

    2011-06-01

    Sabine Stanley received the William Gilbert Award at the 2010 AGU Fall Meeting, held 13-17 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  19. Kirschvink receives 2011 William Gilbert Award: Citation

    NASA Astrophysics Data System (ADS)

    Weiss, Benjamin P.

    2012-04-01

    Joseph Kirschvink received the William Gilbert Award at the 2011 AGU Fall Meeting, held 5-9 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  20. Kirschvink receives 2011 William Gilbert Award: Response

    NASA Astrophysics Data System (ADS)

    Kirschvink, Joseph L.

    2012-04-01

    Joseph Kirschvink received the William Gilbert Award at the 2011 AGU Fall Meeting, held 5-9 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  1. Dennis Kent Receives 2009 William Gilbert Award

    NASA Astrophysics Data System (ADS)

    Tauxe, Lisa; Kent, Dennis

    2010-06-01

    Dennis Kent received the William Gilbert Award at the 2009 AGU Fall Meeting, held 14-18 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  2. Lagroix Receives 2008 William Gilbert Award

    NASA Astrophysics Data System (ADS)

    Moskowitz, Bruce M.; Banerjee, Subir K.; Lagroix, France

    2009-04-01

    France Lagroix received the William Gilbert Award at the 2008 AGU Fall Meeting Honors Ceremony, held 17 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  3. Stanley receives 2010 William Gilbert Award: Response

    NASA Astrophysics Data System (ADS)

    Stanley, Sabine

    2011-06-01

    Sabine Stanley received the William Gilbert Award at the 2010 AGU Fall Meeting, held 13-17 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  4. Go International! Build a Simplified Shortwave Receiver

    ERIC Educational Resources Information Center

    Homoly, Clarke

    2008-01-01

    This article presents a plan for building a shortwave receiver that is doable, educational and has reasonable performance. The project, says the author, can give students years of listening fun without a major financial investment. Potential project improvements are included.

  5. 47 CFR 32.1170 - Receivables.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FOR TELECOMMUNICATIONS COMPANIES Instructions for Balance Sheet Accounts § 32.1170 Receivables. (a... of interest accrued to the date of the balance sheet on bonds, notes, and other commercial...

  6. Solar central receiver systems comparative economics

    SciTech Connect

    Eicker, P J

    1980-04-01

    Several major conceptual design studies of solar central receiver systems and components have been completed in the last year. The results of these studies are used to compare the projected cost of electric power generation using central receiver systems with that of more conventional power generation. The cost estimate for a molten salt central receiver system is given. Levelized busbar energy cost is shown as a function of annual capacity factor indicating the fraction of the cost due to each of the subsystems. The estimated levelized busbar energy cost for a central receiver (70 to 90 mills per kilowatt hour) is compared with the levelized busbar energy cost for a new coal fired Rankine cycle plant. Sensitivities to the initial cost of coal and the delta fuel escalation are shown. (WHK)

  7. Comparing Drug Use between Welfare-Receiving Arrestees and Non-Welfare-Receiving Arrestees.

    ERIC Educational Resources Information Center

    Yacoubian, George S., Jr.; Peters, Ronald J., Jr.; Urbach, Blake J.; Johnson, Regina J.

    2002-01-01

    Compares drug-positive rates between welfare-receiving arrestees, non-welfare receiving arrestees living below the poverty level, and non-welfare arrestees living above the poverty level. Welfare-receiving arrestees were more likely to be female, older, less educated, and to test positive for opiates and benzodiazepines than the other subgroups.…

  8. Flexible receiver adapter formal design review

    SciTech Connect

    Krieg, S.A.

    1995-06-13

    This memo summarizes the results of the Formal (90%) Design Review process and meetings held to evaluate the design of the Flexible Receiver Adapters, support platforms, and associated equipment. The equipment is part of the Flexible Receiver System used to remove, transport, and store long length contaminated equipment and components from both the double and single-shell underground storage tanks at the 200 area tank farms.

  9. Single-Receiver GPS Phase Bias Resolution

    NASA Technical Reports Server (NTRS)

    Bertiger, William I.; Haines, Bruce J.; Weiss, Jan P.; Harvey, Nathaniel E.

    2010-01-01

    Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ftp

  10. A handbook for solar central receiver design

    SciTech Connect

    Falcone, P.K.

    1986-12-01

    This Handbook describes central receiver technology for solar thermal power plants. It contains a description and assessment of the major components in a central receiver system configured for utility scale production of electricity using Rankine-cycle steam turbines. It also describes procedures to size and optimize a plant and discussed examples from recent system analyses. Information concerning site selection criteria, cost estimation, construction, and operation and maintenance is also included, which should enable readers to perform design analyses for specific applications.

  11. Submillimeter-wave receivers - A status report

    NASA Technical Reports Server (NTRS)

    Wilson, W. J.

    1983-01-01

    A development status assessment is presented for the work of U.S. and Western European research groups on heterodyne sub-mm receivers in the 300-1000 GHz frequency range. The applications driving sub-mm receiver and local oscillator source technologies are radio astronomy, atmospheric measurements, plasma diagnostics, and laboratory spectroscopy. Progress is concentrated in two areas, cooled Schottky diode mixers and solid state local oscillators employing frequency multipliers.

  12. Adaptive Detector Arrays for Optical Communications Receivers

    NASA Technical Reports Server (NTRS)

    Vilnrotter, V.; Srinivasan, M.

    2000-01-01

    The structure of an optimal adaptive array receiver for ground-based optical communications is described and its performance investigated. Kolmogorov phase screen simulations are used to model the sample functions of the focal-plane signal distribution due to turbulence and to generate realistic spatial distributions of the received optical field. This novel array detector concept reduces interference from background radiation by effectively assigning higher confidence levels at each instant of time to those detector elements that contain significant signal energy and suppressing those that do not. A simpler suboptimum structure that replaces the continuous weighting function of the optimal receiver by a hard decision on the selection of the signal detector elements also is described and evaluated. Approximations and bounds to the error probability are derived and compared with the exact calculations and receiver simulation results. It is shown that, for photon-counting receivers observing Poisson-distributed signals, performance improvements of approximately 5 dB can be obtained over conventional single-detector photon-counting receivers, when operating in high background environments.

  13. Low-temperature volumetric receiver concept

    NASA Astrophysics Data System (ADS)

    Drost, M. K.

    1988-09-01

    This document describes an alternative solar central receiver concept that offers the potential for a substantial reduction in the cost of electrical energy. The concept consists of a low temperature volumetric receiver which supplies 1100 F air to a Kalina cycle heat engine. Hot air can also be supplied to a packed bed of Dresser basalt where the hot air is used to heat the bed. The thermal energy stored in the bed can be extracted and supplied to the Kalina cycle during periods of low insolation. Previous investigations of the volumetric receiver concentrated on high temperature applications. The results showed that the volumetric concept could be very efficient, but the receiver was expensive and there were significant technical problems. Areas of technical uncertainty included fiber durability, the feasibility of inducing a preswirl and cost effective applications. The use of the volumetric receiver to produce low temperature will avoid the problems identified in the high temperature studies. The attractiveness of the low temperature concept is enhanced by the availability of the Kalina cycle. This heat engine was developed as a bottoming cycle for Brayton and Rankine cycle power plants. The key feature of the Kalina cycle is its ability to efficiently utilize the energy in a relatively low temperature heat source. The combination of the low temperature volumetric receiver and the Kalina cycle is particularly interesting.

  14. Low-temperature volumetric receiver concept

    SciTech Connect

    Drost, M.K.

    1988-09-01

    This document describes an alternative solar central receiver concept that offers the potential for a substantial reduction in the cost of electrical energy. The concept consists of a low temperature volumetric receiver which supplies 1100/degree/F air to a Kalina cycle heat engine. Hot air can also be supplied to a packed bed of Dresser basalt where the hot air is used to heat the bed. The thermal energy stored in the bed can be extracted and supplied to the Kalina cycle during periods of low insolation. Previous investigations of the volumetric receiver concentrated on high temperature applications. The results showed that the volumetric concept could be very efficient, but the receiver was expensive and there were significant technical problems. Areas of technical uncertainty included fiber durability, the feasibility of inducing a preswirl and cost effective applications. The use of the volumetric receiver to produce low temperature will avoid the problems identified in the high temperature studies. The attractiveness of the low temperature concept is enhanced by the availability of the Kalina cycle. This heat engine was developed as a bottoming cycle for Brayton and Rankine cycle power plants. The key feature of the Kalina cycle is its ability to efficiently utilize the energy in a relatively low temperature heat source. The combination of the low temperature volumetric receiver and the Kalina cycle is particularly interesting. 7 refs., 2 figs., 3 tabs.

  15. Internal Film Receiver systems assessment study

    SciTech Connect

    Anderson, J.V.

    1988-03-01

    This report documents SERI's Internal Film Receiver (IFR) design study and system assessment effort; and it compares the performance and economic potential of this system to conventional salt-in-tube receivers and to systems with the direct absorption receiver (DAR). SPECO, Inc., under contract to SERI, performed the receiver configuration work and their final report is included as Appendix A. The IFR is similar to the DAR in that both use films flowing over nearly vertical plates to absorb the solar energy. However, in the IFR the radiation strikes the outside of the absorber plate and the working fluid flows down the inside. The results of the system-level assessment indicate that the IFR concept has the potential to deliver levelized energy costs (LEC) on the order of 5%--7% lower than the salt-in-tube receiver. Although the potential economic benefits of the IFR are not as great as those for the DAR, which shows more than a 15% improvement in LEC over the salt-in-tube receiver system, this may be offset by the lower technical risks with the IFR. 3 refs., 2 figs., 7 tabs.

  16. Receiver functions: An exploration seismic perspective

    NASA Astrophysics Data System (ADS)

    van Manen, Dirk-Jan; Curtis, Andrew; Robertsson, Johan

    2015-04-01

    The receiver function technique is arguably the most successful technique in seismology for crustal and upper mantle characterisation. Prompted by the successful application of the receiver function method to multi-component seabed seismic data to derive shear-wave statics, we explore to what extent the receiver function method can be used for general multi-component reflection seismic data processing and vice-versa. We show that the work in the seismological community on moveout correction and stacking of receiver functions can be extended significantly, building on results from the exploration seismic community. We introduce a novel type of space-time domain receiver function, computed by 2D deconvolution, which treats the spatial aspects of mode-conversion completely analogously to the temporal aspects. Thus, the receiver function becomes a two-dimensional transfer function, which shows how far the P-waves have to be shifted in space and delayed in time to match the corresponding PS-converted waves. In addition, series expansions of the traveltime differences lead naturally to two-term moveout approximations and Dix-Krey-type velocity inversion formulae for both the conventional (i.e., time difference as a function of slowness) as well as novel (i.e., time difference as a function of offset) receiver functions. The two approaches, and the required data pre-processing, are illustrated using synthetic multi-component seismic data. We also introduce a model-independent method for reflection receiver function computation, based on stationary phase analysis, which can be used for deconvolution of anelastic and all other propagation effects. This method is inspired by, and closely related to, interferometry and relies on matching the slowness of a particular PP-reflected wave to the slowness of the corresponding PS-converted wave on the source side, and exploiting the fact that the traveltime difference is stationary for the PP- and PS-wave that is reflected and mode

  17. Iron and manganese diagenesis in constructed wetlands receiving mine drainage

    SciTech Connect

    Tarutis, W.J. Jr.

    1993-01-01

    The chemical diagenesis of iron and manganese was studied in two constructed wetlands receiving coal mine drainage and in laboratory wetland mesocosms exposed to synthetic acidic mine waters, and the release of soluble metals from natural and synthetic metal oxides of differing crystallinity was studied in laboratory incubations in the presence and absence of bacterial sulfate reduction. Soil chemical characterization indicated that the formation of potentially reducible, oxide-bound precipitates accounted for the majority of iron and manganese removed in the two wetlands studied. Depth profiles revealed diagenetic remobilization of iron and manganese to the soil interstitial water due to the reductive dissolution of oxidized metals initially deposited on the wetland surface. Sulfate reduction and pyrite formation contributed little to metal removal due to organic carbon limitation in the subsurface soils. Iron and manganese in synthetic acidic mine water added to anoxic wetland mesocosms acted synergistically with respect to metal removal. The inclusion of sulfate in synthetic mine water caused a slightly greater, but statistically significant, iron removal in mesocosms relative to mesocosms not receiving sulfate. Sulfate addition had no effect on manganese removal. Iron was much more reactive than manganese towards sulfide in laboratory incubations in which sulfate reduction was allowed to occur. Liberation of iron and manganese in the absence of sulfate reduction decreased with increasing crystallinity of each metal oxide tested and was attributed to higher activation energies characteristic of a surface-reaction-controlled dissolution mechanisms.

  18. Performance outlook of the SCRAP receiver

    NASA Astrophysics Data System (ADS)

    Lubkoll, Matti; von Backström, Theodor W.; Harms, Thomas M.

    2016-05-01

    A combined cycle (CC) concentrating solar power (CSP) plant provides significant potential to achieve an efficiency increase and an electricity cost reduction compared to current single-cycle plants. A CC CSP system requires a receiver technology capable of effectively transferring heat from concentrated solar irradiation to a pressurized air stream of a gas turbine. The small number of pressurized air receivers demonstrated to date have practical limitations, when operating at high temperatures and pressures. As yet, a robust, scalable and efficient system has to be developed and commercialized. A novel receiver system, the Spiky Central Receiver Air Pre-heater (SCRAP) concept has been proposed to comply with these requirements. The SCRAP system is conceived as a solution for an efficient and robust pressurized air receiver that could be implemented in CC CSP concepts or standalone solar Brayton cycles without a bottoming Rankine cycle. The presented work expands on previous publications on the thermal modeling of the receiver system. Based on the analysis of a single heat transfer element (spike), predictions for its thermal performance can be made. To this end the existing thermal model was improved by heat transfer characteristics for the jet impingement region of the spike tip as well as heat transfer models simulating the interaction with ambient. While the jet impingement cooling effect was simulated employing a commercial CFD code, the ambient heat transfer model was based on simplifying assumptions in order to employ empirical and analytical equations. The thermal efficiency of a spike under design conditions (flux 1.0 MW/m2, air outlet temperature just below 800 °C) was calculated at approximately 80 %, where convective heat losses account for 16.2 % of the absorbed radiation and radiative heat losses for a lower 2.9 %. This effect is due to peak surface temperatures occurring at the root of the spikes. It can thus be concluded that the geometric

  19. Sexual function in women receiving maintenance dialysis.

    PubMed

    Seethala, Srikanth; Hess, Rachel; Bossola, Maurizio; Unruh, Mark L; Weisbord, Steven D

    2010-01-01

    While substantial attention has been paid to the issue of sexual dysfunction in men on chronic dialysis, less is known about this problem in women with end-stage renal disease. We sought to assess sexual dysfunction in women on chronic dialysis and determine whether patients discuss this problem with their providers and receive treatment. We prospectively enrolled women receiving chronic hemodialysis or peritoneal dialysis in Pittsburgh, PA. We asked patients to complete the 19-item Female Sexual Function Index (FSFI) to assess sexual function and a 5-item survey that assessed whether patients had discussed sexual dysfunction with their providers and/or received treatment for this problem in the past. We enrolled 66 patients; 59 (89%) on hemodialysis and 7 (11%) on peritoneal dialysis. All patients completed the FSFI, of whom 53 (80%) had FSFI scores <26.55, consistent with the presence of sexual dysfunction. Of 37 patients who were married or residing with a significant other, 27 (73%) had sexual dysfunction. Among 24 participants who reported having been sexually active over the previous 4 weeks, 11 (46%) had sexual dysfunction. Only 21% of patients with sexual dysfunction had discussed this problem with their gynecologist, renal or primary provider, and 3 (6%) reported having received treatment. Sexual dysfunction is common in women on dialysis, even among patients who are married or residing with a significant other and those who are sexually active. However, few women discuss this issue with their providers or receive treatment.

  20. GPS high dynamic receiver tracking demonstration results

    NASA Technical Reports Server (NTRS)

    Hurd, W. J.; Statman, J. I.; Vilnrotter, V. A.

    1985-01-01

    Demonstration results are presented for a high dynamic GPS receiver. The receiver tested is a breadboard unit capable of tracking one simulated satellite signal in pseudorange and range rate. The receiver makes approximate maximum likelihood estimates of pseudorange and range rate each 20 ms, and tracks these observables using a third order filter with a time constant of 0.14 s. Carrier phase is not tracked, which eliminates the typical failure mode of loss of carrier lock associated with PLLs at high dynamics. The receiver tracks with pseudorange lag errors of under 0.06 m when subjected to simulated 50 g turns with 40 g/s peak jerk. Pseudorange errors due to receiver noise alone are approximately 0.6 m rms at a carrier power to noise spectral density ratio of 34 dB-Hz. The tracking threshold SNR is approximately 28 dB-Hz, which provides 12 dB margin relative to the 40 dB-Hz that occurs with minimum specified satellite signal strength, 3.5 dB system noise figure, and 0 dBi antenna gain.

  1. Dish/stirling hybrid-receiver

    DOEpatents

    Mehos, Mark S.; Anselmo, Kenneth M.; Moreno, James B.; Andraka, Charles E.; Rawlinson, K. Scott; Corey, John; Bohn, Mark S.

    2002-01-01

    A hybrid high-temperature solar receiver is provided which comprises a solar heat-pipe-receiver including a front dome having a solar absorber surface for receiving concentrated solar energy, a heat pipe wick, a rear dome, a sidewall joining the front and the rear dome, and a vapor and a return liquid tube connecting to an engine, and a fossil fuel fired combustion system in radial integration with the sidewall for simultaneous operation with the solar heat pipe receiver, the combustion system comprising an air and fuel pre-mixer, an outer cooling jacket for tangentially introducing and cooling the mixture, a recuperator for preheating the mixture, a burner plenum having an inner and an outer wall, a porous cylindrical metal matrix burner firing radially inward facing a sodium vapor sink, the mixture ignited downstream of the matrix forming combustion products, an exhaust plenum, a fossil-fuel heat-input surface having an outer surface covered with a pin-fin array, the combustion products flowing through the array to give up additional heat to the receiver, and an inner surface covered with an extension of the heat-pipe wick, a pin-fin shroud sealed to the burner and exhaust plenums, an end seal, a flue-gas diversion tube and a flue-gas valve for use at off-design conditions to limit the temperature of the pre-heated air and fuel mixture, preventing pre-ignition.

  2. Direct broadcast satellite-radio, receiver development

    NASA Astrophysics Data System (ADS)

    Vaisnys, A.; Bell, D.; Gevargiz, J.; Golshan, Nasser

    The status of the ongoing Direct Broadcast Satellite-Radio (DBS-R) Receiver Development Task being performed at the Jet Propulsion Laboratory, California Institute of Technology (JPL) is reported. This work is sponsored by the Voice of America/U.S. Information Agency through an agreement with NASA. The objective of this task is to develop, build, test, and demonstrate a prototype receiver that is compatible with reception of digital audio programs broadcast via satellites. The receiver is being designed to operate under a range of reception conditions, including fixed, portable, and mobile, as well as over a sufficiently wide range of bit rates to accommodate broadcasting systems with different cost/audio quality objectives. While the requirements on the receiver are complex, the eventual goal of the design effort is to make the design compatible with low cost production as a consumer product. One solution may be a basic low cost core design suitable for a majority of reception conditions, with optional enhancements for reception in especially difficult environments. Some of the receiver design parameters were established through analysis, laboratory tests, and a prototype satellite experiment accomplished in late 1991. Many of the necessary design trades will be made during the current simulation effort, while a few of the key design options will be incorporated into the prototype for evaluation during the planned satellite field trials.

  3. Schottky Heterodyne Receivers With Full Waveguide Bandwidth

    NASA Technical Reports Server (NTRS)

    Hesler, Jeffrey; Crowe, Thomas

    2011-01-01

    Compact THz receivers with broad bandwidth and low noise have been developed for the frequency range from 100 GHz to 1 THz. These receivers meet the requirements for high-resolution spectroscopic studies of planetary atmospheres (including the Earth s) from spacecraft, as well as airborne and balloon platforms. The ongoing research is significant not only for the development of Schottky mixers, but also for the creation of a receiver system, including the LO chain. The new receivers meet the goals of high sensitivity, compact size, low total power requirement, and operation across complete waveguide bands. The exceptional performance makes these receivers ideal for the broader range of scientific and commercial applications. These include the extension of sophisticated test and measurement equipment to 1 THz and the development of low-cost imaging systems for security applications and industrial process monitoring. As a particular example, a WR-1.9SHM (400-600 GHz) has been developed (see Figure 1), with state-of-the-art noise temperature ranging from 1,000-1,800 K (DSB) over the full waveguide band. Also, a Vector Network Analyzer extender has been developed (see Figure 2) for the WR1.5 waveguide band (500 750 GHz) with 100-dB dynamic range.

  4. Direct broadcast satellite-radio, receiver development

    NASA Technical Reports Server (NTRS)

    Vaisnys, A.; Bell, D.; Gevargiz, J.; Golshan, Nasser

    1993-01-01

    The status of the ongoing Direct Broadcast Satellite-Radio (DBS-R) Receiver Development Task being performed at the Jet Propulsion Laboratory, California Institute of Technology (JPL) is reported. This work is sponsored by the Voice of America/U.S. Information Agency through an agreement with NASA. The objective of this task is to develop, build, test, and demonstrate a prototype receiver that is compatible with reception of digital audio programs broadcast via satellites. The receiver is being designed to operate under a range of reception conditions, including fixed, portable, and mobile, as well as over a sufficiently wide range of bit rates to accommodate broadcasting systems with different cost/audio quality objectives. While the requirements on the receiver are complex, the eventual goal of the design effort is to make the design compatible with low cost production as a consumer product. One solution may be a basic low cost core design suitable for a majority of reception conditions, with optional enhancements for reception in especially difficult environments. Some of the receiver design parameters were established through analysis, laboratory tests, and a prototype satellite experiment accomplished in late 1991. Many of the necessary design trades will be made during the current simulation effort, while a few of the key design options will be incorporated into the prototype for evaluation during the planned satellite field trials.

  5. Liquid cooled, linear focus solar cell receiver

    DOEpatents

    Kirpich, A.S.

    1983-12-08

    Separate structures for electrical insulation and thermal conduction are established within a liquid cooled, linear focus solar cell receiver for use with parabolic or Fresnel optical concentrators. The receiver includes a V-shaped aluminum extrusion having a pair of outer faces each formed with a channel receiving a string of solar cells in thermal contact with the extrusion. Each cell string is attached to a continuous glass cover secured within the channel with spring clips to isolate the string from the external environment. Repair or replacement of solar cells is effected simply by detaching the spring clips to remove the cover/cell assembly without interrupting circulation of coolant fluid through the receiver. The lower surface of the channel in thermal contact with the cells of the string is anodized to establish a suitable standoff voltage capability between the cells and the extrusion. Primary electrical insulation is provided by a dielectric tape disposed between the coolant tube and extrusion. Adjacent solar cells are soldered to interconnect members designed to accommodate thermal expansion and mismatches. The coolant tube is clamped into the extrusion channel with a releasably attachable clamping strip to facilitate easy removal of the receiver from the coolant circuit.

  6. Liquid cooled, linear focus solar cell receiver

    DOEpatents

    Kirpich, Aaron S.

    1985-01-01

    Separate structures for electrical insulation and thermal conduction are established within a liquid cooled, linear focus solar cell receiver for use with parabolic or Fresnel optical concentrators. The receiver includes a V-shaped aluminum extrusion having a pair of outer faces each formed with a channel receiving a string of solar cells in thermal contact with the extrusion. Each cell string is attached to a continuous glass cover secured within the channel with spring clips to isolate the string from the external environment. Repair or replacement of solar cells is effected simply by detaching the spring clips to remove the cover/cell assembly without interrupting circulation of coolant fluid through the receiver. The lower surface of the channel in thermal contact with the cells of the string is anodized to establish a suitable standoff voltage capability between the cells and the extrusion. Primary electrical insulation is provided by a dielectric tape disposed between the coolant tube and extrusion. Adjacent solar cells are soldered to interconnect members designed to accommodate thermal expansion and mismatches. The coolant tube is clamped into the extrusion channel with a releasably attachable clamping strip to facilitate easy removal of the receiver from the coolant circuit.

  7. The ARSQ: the athletes' received support questionnaire.

    PubMed

    Freeman, Paul; Coffee, Pete; Moll, Tjerk; Rees, Tim; Sammy, Nadine

    2014-04-01

    To address calls for context-specific measurement of social support, this article reports the development of the Athletes' Received Support Questionnaire (ARSQ) and demonstrates initial evidence for its validity. Across four studies there was support for a four-dimensional structure reflecting emotional, esteem, informational, and tangible received support. There was also support for unidimensional and higher-order models. Further, Study 3 provided some support for convergent validity, with significant correlations between the corresponding dimensions of the ARSQ and the Inventory of Socially Supportive Behaviors. Study 4 provided evidence for the nomological validity of the ARSQ. Emotional and esteem support significantly predicted self-confidence and positive affect, and tangible support significantly moderated the relationship between stress and negative affect. Collectively, these results provide initial evidence for the validity of the ARSQ, and offer researchers flexibility to adopt either a multidimensional or aggregated approach to measuring received support. PMID:24686955

  8. Dental extraction in patients receiving dual antiplatelet therapy

    PubMed Central

    Sánchez-Palomino, Paulino; Sánchez-Cobo, Paulino; Rodriguez-Archilla, Alberto; González-Jaranay, Maximino; Moreu, Gerardo; Calvo-Guirado, José-Luis; Peñarrocha-Diago, Miguel

    2015-01-01

    Background Dual anti platelet therapy consists of administering antiplatelet (antiaggregant) drugs (clopidogrel and aspirin) to prevent thrombotic processes, as a preventative measure in patients with acute coronary disease, or in patients subjected to percutaneous coronary intervention. Objectives The purpose of this study was to evaluate the efficacy of a protocol for performing dental extraction in patients receiving dual anti platelet therapy. Material and Methods Thirty-two patients undergoing dental extractions were included in the study. The variables evaluated were: collagen-epinephrine fraction, collagen- adenosine diphosphate fraction, surgical surface, post-surgical measures, and adverse effects. Alveolar sutures and gauzes impregnated with an antifibrinolytic agent (tranexamic acid), which the patient pressed in place for 30 minutes, were applied to all patients as post-surgical measures. Descriptive statistics were calculated and analyzed with Student’s t-test to compare pairs of quantitative variables; simple regression analysis was performed using Pearson’s correlation coefficient. Statistical significance was set at p<0.05. Results Collagen/epinephrine fraction was 264.53±55.624 seconds with a range of 135 to 300 seconds, and collagen/ADP fraction was 119.41±44.216 seconds, both values being higher than normal. As a result of the post-surgical measures taken, no patients presented postoperative bleeding, hematoma or infection. Conclusions Dental extraction was safe for patients receiving dual anti-platelet therapy when using sutures and gauze impregnated with tranexamic acid, which the patient pressed in place for 30 minutes. Key words: Aspirin, clopidogrel, tranexamic acid, dental extraction, platelet function. PMID:26241454

  9. Optical Receiver Based On Luminescent Light Trapping

    NASA Technical Reports Server (NTRS)

    Perry, Joseph W.; Cole, Terry; Zewail, Ahmed H.

    1991-01-01

    Experiment demonstrates feasibility of optical-communication receiver based on luminescent light trapping. Light-gathering element plate of transparent material impregnated with laser dye. Light from distant laser transmitter falls on plate and absorbed by dye molecules, which become excited and reradiate. Reradiated light confined within plate by total internal reflection as it propagates toward edge of plate. Light arriving at edge escapes from plate and detected by small, high-speed, high-gain photomultiplier tubes or other photosensitive devices. Simple, inexpensive, and accepts light from almost any angle. Receiver of this configuration supports reception of data at rate of 13 MHz and higher.

  10. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Highfill, J. H., III

    1976-01-01

    The design of a microwave landing system (MLS) aircraft receiver, capable of optimal performance in multipath environments found in air terminal areas, is reported. Special attention was given to the angle tracking problem of the receiver and includes tracking system design considerations, study and application of locally optimum estimation involving multipath adaptive reception and then envelope processing, and microcomputer system design. Results show processing is competitive in this application with i-f signal processing performance-wise and is much more simple and cheaper. A summary of the signal model is given.

  11. Avalanche Photodiode Arrays for Optical Communications Receivers

    NASA Technical Reports Server (NTRS)

    Srinivasan, M.; Vilnrotter, V.

    2001-01-01

    An avalanche photodiode (APD) array for ground-based optical communications receivers is investigated for the reception of optical signals through the turbulent atmosphere. Kolmogorov phase screen simulations are used to generate realistic spatial distributions of the received optical field. It is shown that use of an APD array for pulse-position modulation detection can improve performance by up to 4 dB over single APD detection in the presence of turbulence, but that photon-counting detector arrays yield even greater gains.

  12. Infrared receiver having a cooled radiation detector

    SciTech Connect

    Van Antwerpen, H. C.

    1985-04-09

    An infrared receiver having an infrared radiation detector cooled by means of a cold-gas engine, the thermal contact between a cooling surface of the cold-gas engine and the radiation detector being obtained by an elastic thermally conducting bridge. The cylindrical bridge is comprised of a plurality of turns of a metal strip. Due to the presence of the bridge, a good thermal conduction and further a compensation for differences in thermal expansion coefficients of the materials used are obtained. The infrared receiver is particularly suitable for night vision apparatus.

  13. Turbulent flow inside a solar concentrator receiver

    NASA Astrophysics Data System (ADS)

    Ramirez, Manuel; Ramos, Eduardo

    2014-11-01

    A solar concentrator receiver is a heat exchanger designed to absorb a beam of radiant heat coming from a field of heliostats. Inside the device, a slow forced flow generated bye an external pressure gradient is present, together with a natural convective a turbulent flow produced by the large temperature gradients due to intense heating. We present a model of this device based on the numerical solution of the mass, momentum and energy conservation equations. We consider heating conditions that lead to turbulence convective flow. For this season, a large eddy simulation model is incorporated. The results are potentially useful for the design of solar concentrator receivers.

  14. Downhole receiver function: A case study

    USGS Publications Warehouse

    Mehta, K.; Snieder, R.; Graizer, V.

    2007-01-01

    Receiver function is defined as the spectral ratio of the radial component and the vertical component of the ground motion. It is used to characterize converted waves. We extend the use of the receiver function to downhole data using waves recorded in a borehole, excited by an earthquake of magnitude 4.0 near San Francisco, California, on 26 June 1994. The focal depth of the event was 6.6 km and the epicenter was located at a distance of 12.6 km from the borehole array. Six three-component sensors were located at different depths in a borehole. To extract a coherent response of the near-surface from the incoherent earthquake waves, we deconvolve the waves recorded by the sensors at different depths with the waves recorded by the sensor on the surface. Deconvolution applied to the waves in the S-time window recorded by the radial component result in an upgoing and a downgoing wave propagating with S-wave velocity. For the waves in the P-time window recorded by the radial component, deconvolution also gives an upgoing and a down-going wave propagating with S-wave velocity. This interesting result suggests a P-to-S conversion at a depth below the deepest sensor. To diagnose this we compute the receiver function for the borehole recording of the earthquake waves. The receiver function shows an upgoing wave with an arrival close to time t = 0 for the deepest sensor. The agreement of the upgoing wave in the receiver function with the travel-time curve for the P-to-S converted wave, calculated using the P- and the S-wave velocity profile, supports the hypothesis of a pronounced P-to-S conversion. We present a synthetic example to illustrate that the first arrival of the receiver function applied to borehole data gives the upward-propagating P-to-S converted wave. To corroborate the observation of the mode conversion, we apply receiver function to a different earthquake data recorded by the same borehole array in 1998. The focal depth of the event was 6.9 km and the

  15. PiVoT GPS Receiver

    NASA Technical Reports Server (NTRS)

    Wennersten, Miriam Dvorak; Banes, Anthony Vince; Boegner, Gregory J.; Dougherty, Lamar; Edwards, Bernard L.; Roman, Joseph; Bauer, Frank H. (Technical Monitor)

    2001-01-01

    NASA Goddard Space Flight Center has built an open architecture, 24 channel space flight GPS receiver. The CompactPCI PiVoT GPS receiver card is based on the Mitel/GEC Plessey Builder-2 board. PiVoT uses two Plessey 2021 correlators to allow tracking of up to 24 separate GPS SV's on unique channels. Its four front ends can support four independent antennas, making it a useful card for hosting GPS attitude determination algorithms. It has been built using space quality, radiation tolerant parts. The PiVoT card will track a weaker signal than the original Builder 2 board. It also hosts an improved clock oscillator. The PiVoT software is based on the original Plessey Builder 2 software ported to the Linux operating system. The software is POSIX complaint and can easily be converted to other POSIX operating systems. The software is open source to anyone with a licensing agreement with Plessey. Additional tasks can be added to the software to support GPS science experiments or attitude determination algorithms. The next generation PiVoT receiver will be a single radiation hardened CompactPCI card containing the microprocessor and the GPS receiver optimized for use above the GPS constellation. PiVoT was flown successfully on a balloon in July, 2001, for its first non-simulated flight.

  16. 7 CFR 29.42 - Receiving station.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.42 Receiving station. Points at which producer tobacco is offered for marketing (other than sale at auction on a designated market), including tobacco auction warehouses,...

  17. Reasons Parents Exempt Children from Receiving Immunizations

    ERIC Educational Resources Information Center

    Luthy, Karlen E.; Beckstrand, Renea L.; Callister, Lynn C.; Cahoon, Spencer

    2012-01-01

    School nurses are on the front lines of educational efforts to promote childhood vaccinations. However, some parents still choose to exempt their children from receiving vaccinations for personal reasons. Studying the beliefs of parents who exempt vaccinations allows health care workers, including school nurses, to better understand parental…

  18. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... extends beyond the plane surfaces of the enclosure. (2) Maximum test voltage means 130 root mean square volts if the receiver is designed to operate from nominal 110 to 120 root mean square volt power sources... nominal 110 to 120 root mean square volts, maximum test voltage means 110 percent of the nominal root...

  19. Hybrid receiver conceptual design and test report

    NASA Technical Reports Server (NTRS)

    Klare, S. W.; Crawford, J. J.

    1978-01-01

    The Hybrid Receiver described uses an acquisition and demodulation scheme tailored to the Jovian environment. The large Doppler offsets expected during initial acquisition led to development of the Hilbert Acquisition Aid, which provides for rapid acquisition for low signal to noise densities.

  20. Developmental trends in radio receiver design

    NASA Astrophysics Data System (ADS)

    Chistyakov, N. I.

    1984-03-01

    A historical review of the development of shortwave receiver design is followed by an enumeration of the characteristics of the state of the art in shortwave reception equipment: (1) the problem of band coverage, for example in marine receivers from 10 KHz to 30 MHz, has been resolved by the use of infradyne circuits with an IF of 40 to 80 MHz and a broadband preselector; such designs also make it possible to base the local oscillator on a phase-locked loop; (20 suppression of spurious frequencies is improved by placing them outside the working band through the use of a high first IF; (3) enhanced linearity of the broadband RF amplifier and converter has extended the dynamic range of receivers, and eliminated the need for a narrow band preselector with the use of simple suboctave filters and low pass filters at the input; and (4) the use of a decade frequency synthesizer based on a variable divisor frequency divider, highly stable master crystal oscillators, electronic varactor tuning of the local oscillator and Phase-locked loops provide for precise tuning to the requisite frequency, which is also improved by digital tuning and displays. A major aspect of present design work is the application of microprocessors to automatic tuning, programmed frequency setting and the performance of a variety of diagnostic functions in the receiver.

  1. Global lithospheric imaging using teleseismic receiver functions

    NASA Astrophysics Data System (ADS)

    Rondenay, S.; Spieker, K.; Halpaap, F.; Farestveit, M.; Sawade, L.; Zijerveld, L.

    2015-12-01

    Project GLImER (Global Lithospheric Imagining using Earthquake Recordings) aims to conduct a global survey of lithospheric interfaces using converted teleseismic body waves. Data from permanent and temporary seismic networks worldwide will be processed automatically to produce global maps of key interfaces (Moho, intra-lithospheric interfaces, lithosphere-asthenosphere boundary). In this presentation, we discuss the challenges associated with automating the analysis of converted waves and the potential of the resulting data products to be used in novel imaging approaches. With regards to automation, we address in particular the search for an optimal deconvolution method in receiver function analysis. To do so, we carry out a systematic comparison of various commonly used deconvolution methods and find that all methods produce equally robust receiver functions provided that a suitable regularization parameter is found. We further note that a suitable regularization can be found objectively for most approaches, thus challenging the belief that only time-domain deconvolution is a viable option for receiver function automation. With regards to imaging applications, we investigate how the resulting global database of receiver functions will be amenable to existing processing approaches as well as new approaches adapted from seismic exploration, including industry-based interpretation tools.

  2. Kopp Receives 2012 William Gilbert Award: Citation

    NASA Astrophysics Data System (ADS)

    Kirschvink, Joseph L.

    2013-10-01

    Robert E. Kopp received the 2012 William Gilbert Award at the 2012 AGU Fall Meeting, held 3-7 December in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  3. Determining the response of an FM receiver

    NASA Technical Reports Server (NTRS)

    Perry, J. C.

    1979-01-01

    Frequency response to frequency-modulation (FM) receiver is measured with aid of phase-modulation (PM) transmitter by applying correction to output power level. As modulating frequency is increased, output level obtained in response to PM input is reduced by 6 db per octane.

  4. Antennas For Receiving Signals Broadcast Via Satellites

    NASA Technical Reports Server (NTRS)

    Wu, Te-Kao; Huang, John

    1996-01-01

    Four different antennas designed for use in receiving radio AM and FM signals broadcast via Earth-orbiting satellites at carrier frequency of 2.05 GHz in right-hand circular polarization. Antennas small, lightweight, inexpensive units with low-to-medium-gain, quasi-omnidirectional radiation patterns. Designed for outdoor and indoor uses.

  5. The new MTLRS-1 receiving system

    NASA Technical Reports Server (NTRS)

    Sperber, Peter; Hessels, U.; Motz, R.; Guether, H.-M.

    1993-01-01

    In this report, we are giving a detailed description of the new receiving system of the German Modular Transportable Laser Ranging System MTLRS-1, consisting of a spectral time and field of view filter and a Single Photon Avalanche Diode (SPAD) as a single photon detector. The system gives full day and night ranging capability to all satellites with cm accuracy.

  6. Vulcan: A deep-towed CSEM receiver

    NASA Astrophysics Data System (ADS)

    Constable, Steven; Kannberg, Peter K.; Weitemeyer, Karen

    2016-03-01

    We have developed a three-axis electric field receiver designed to be towed behind a marine electromagnetic transmitter for the purpose of mapping the electrical resistivity in the upper 1000 m of seafloor geology. By careful adjustment of buoyancy and the use of real-time monitoring of depth and altitude, we are able to deep-tow multiple receivers on arrays up to 1200 m long within 50 m of the seafloor, thereby obtaining good coupling to geology. The rigid body of the receiver is designed to reduce noise associated with lateral motion of flexible antennas during towing, and allows the measurement of the vertical electric field component, which modeling shows to be particularly sensitive to near-seafloor resistivity variations. The positions and orientations of the receivers are continuously measured, and realistic estimates of positioning errors can be used to build an error model for the data. During a test in the San Diego Trough, offshore California, inversions of the data were able to fit amplitude and phase of horizontal electric fields at three frequencies on three receivers to about 1% in amplitude and 1° in phase and vertical fields to about 5% in amplitude and 5° in phase. The geological target of the tests was a known cold seep and methane vent in 1000 m water depth, which inversions show to be associated with a 1 km wide resistor at a depth between 50 and 150 m below seafloor. Given the high resistivity (30 Ωm) and position within the gas hydrate stability field, we interpret this to be massive methane hydrate.

  7. The 30-GHz monolithic receive module

    NASA Technical Reports Server (NTRS)

    Bauhahn, P.; Geddes, J.; Sokolov, V.; Contolatis, T.

    1988-01-01

    The fourth year progress is described on a program to develop a 27.5 to 30 GHz GaAs monolithic receive module for spaceborne-communication antenna feed array applications, and to deliver submodules for experimental evaluation. Program goals include an overall receive module noise figure of 5 dB, a 30 dB RF to IF gain with six levels of intermediate gain control, a five bit phase shifter, and a maximum power consumption of 250 mW. Submicron gate length single and dual gate FETs are described and applied in the development of monolithic gain control amplifiers and low noise amplifiers. A two-stage monolithic gain control amplifier based on ion implanted dual gate MESFETs was designed and fabricated. The gain control amplifier has a gain of 12 dB at 29 GHz with a gain control range of over 13 dB. A two-stage monolithic low noise amplifier based on ion implanted MESFETs which provides 7 dB gain with 6.2 dB noise figure at 29 GHz was also developed. An interconnected receive module containing LNA, gain control, and phase shifter submodules was built using the LNA and gain control ICs as well as a monolithic phase shifter developed previously under this program. The design, fabrication, and evaluation of this interconnected receiver is presented. Progress in the development of an RF/IF submodule containing a unique ion implanted diode mixer diode and a broadband balanced mixer monolithic IC with on-chip IF amplifier and the initial design of circuits for the RF portion of a two submodule receiver are also discussed.

  8. Second-generation central receiver technology comparison

    NASA Astrophysics Data System (ADS)

    Klimas, P. C.; Becker, M.

    Fifteen years of solar thermal technology development have produced a considerable amount of knowledge relating to the production of electricity from central receiver power plants. This body of knowledge is under examination by researchers from the United States and the Federal Republic of Germany for the purpose of defining the next generation central receiver electricity producers. This second generation power plant is expected to represent a significant step towards commercialization of these systems. During the course of the study, specific activities needed to realize this next-step technology are being defined. The study is an international team effort. Under the International Energy Agency Small Solar Power Systems project, researchers from DLR, Interatom, Sandia National Laboratories, and Bechtel have designed a study in which technologies relating to existing systems are quantified, logical next-step systems are characterized, and future potential advances are identified. The receiver concepts under investigation are: salt-in-tube, volumetric, and direct absorption. Two plant performance levels are examined, 30 and 100 MW(sub e). Each concept is applied with common capacity factors, solar multiples, and types and sizes of heliostats at each performance level. Availability and uncertainty analyses are also performed. Annual energy production figures are calculated using the SOLERGY computer code. Capital and Operation and Maintenance cost methodologies are mutually agreed upon in order that levelized energy cost calculations will be consistent for each power plant. During the course of this effort, further potential advances in central receiver technology have continued to become apparent. These possible areas for improvement will be described. An additional comparison is being made between central receivers and trough-based systems.

  9. Social effects of migration in receiving countries.

    PubMed

    Ohndorf, W

    1989-06-01

    This paper examines the impact of post-1945 migration into Western, Middle, and Northern Europe from Southern Europe, Turkey, and Northern Africa, and migration to the traditional immigration countries by Asian and Latin American immigrants, on the social structures of receiving countries. Between 1955 and 1974, 1) traditional migration to the US and Australia became less important for European countries while traditional receiving countries accepted many immigrants from developing countries; and 2) rapid economic revival in Western and Northern Europe caused a considerable labor shortage which was filled by migrant workers especially from Southern Europe, Turkey, and Northern Africa, who stayed only until they reached their economic goals. Since 1974, job vacancies have declined and unemployment has soared. This employment crisis caused some migrants 1) to return to their countries of origin, 2) to bring the rest of their families to the receiving country, or 3) to lengthen their stay considerably. The number of refugees has also significantly increased since the mid-970s, as has the number of illegal migrants. After the mid-1970s, Europe began to experience integration problems. The different aspects of the impact of migration on social structures include 1) improvement of the housing situation for foreigners, 2) teaching migrants the language of the receiving country, 3) solving the unemployment problem of unskilled migrants, 4) improvement of educational and vocational qualifications of 2nd generation migrants, 5) development of programs to help unemployed wives of migrants to learn the language and meet indigenous women, 6) encouraging migrants to maintain their cultural identity and assisting them with reintegration if they return to their original country, 7) coping with the problems of refugees, and 8) solving the problems of illegal migration. Almost all receiving countries now severely restrict further immigration. [Those policies should result in

  10. A GPS Receiver for Lunar Missions

    NASA Technical Reports Server (NTRS)

    Bamford, William A.; Heckler, Gregory W.; Holt, Greg N.; Moreau, Michael C.

    2008-01-01

    Beginning with the launch of the Lunar Reconnaissance Orbiter (LRO) in October of 2008, NASA will once again begin its quest to land humans on the Moon. This effort will require the development of new spacecraft which will safely transport people from the Earth to the Moon and back again, as well as robotic probes tagged with science, re-supply, and communication duties. In addition to the next-generation spacecraft currently under construction, including the Orion capsule, NASA is also investigating and developing cutting edge navigation sensors which will allow for autonomous state estimation in low Earth orbit (LEO) and cislunar space. Such instruments could provide an extra layer of redundancy in avionics systems and reduce the reliance on support and on the Deep Space Network (DSN). One such sensor is the weak-signal Global Positioning System (GPS) receiver "Navigator" being developed at NASA's Goddard Space Flight Center (GSFC). At the heart of the Navigator is a Field Programmable Gate Array (FPGA) based acquisition engine. This engine allows for the rapid acquisition/reacquisition of strong GPS signals, enabling the receiver to quickly recover from outages due to blocked satellites or atmospheric entry. Additionally, the acquisition algorithm provides significantly lower sensitivities than a conventional space-based GPS receiver, permitting it to acquire satellites well above the GPS constellation. This paper assesses the performance of the Navigator receiver based upon three of the major flight regimes of a manned lunar mission: Earth ascent, cislunar navigation, and entry. Representative trajectories for each of these segments were provided by NASA. The Navigator receiver was connected to a Spirent GPS signal generator, to allow for the collection of real-time, hardware-in-the-loop results for each phase of the flight. For each of the flight segments, the Navigator was tested on its ability to acquire and track GPS satellites under the dynamical

  11. Integrated Microphotonic Receiver for Ka-Band

    NASA Technical Reports Server (NTRS)

    Levi, A. F. J.

    2005-01-01

    This report consists of four main sections. Part I: LiNbO3 microdisk resonant optical modulator. Brief review of microdisk optical resonator and RF ring resonator. Microwave and photonic design challenges for achieving simultaneous RF-optical resonance are addressed followed by our solutions. Part II: Experimental demonstration of LiNbO3 microdisk modulator performance in wired and wireless RF-optical links. Part III: Microphotonic RF receiver architecture that exploits the nonlinear modulation in the LiNbO3 microdisk modulator to achieve direct photonic down-conversion from RF carrier without using any high-speed electronic elements. Part IV: Ultimate sensitivity of the microdisk photonic receiver and the future road map toward a practical device.

  12. Cryogenic Amplifier Based Receivers at Submillimeter Wavelengths

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Goutam; Reck, Theodore and; Schlecht, Erich; Lin, Robert; Deal, William

    2012-01-01

    The operating frequency of InP high electron mobility transistor (HEMT) based amplifiers has moved well in the submillimeter-wave frequencies over the last couple of years. Working amplifiers with usable gain in waveguide packages has been reported beyond 700 GHz. When cooled cryogenically, they have shown substantial improvement in their noise temperature. This has opened up the real possibility of cryogenic amplifier based heterodyne receivers at submillimeter wavelengths for ground-based, air-borne, and space-based instruments for astrophysics, planetary, and Earth science applications. This paper provides an overview of the science applications at submillimeter wavelengths that will benefit from this technology. It also describes the current state of the InP HEMT based cryogenic amplifier receivers at submillimeter wavelengths.

  13. Fused silica windows for solar receiver applications

    NASA Astrophysics Data System (ADS)

    Hertel, Johannes; Uhlig, Ralf; Söhn, Matthias; Schenk, Christian; Helsch, Gundula; Bornhöft, Hansjörg

    2016-05-01

    A comprehensive study of optical and mechanical properties of quartz glass (fused silica) with regard to application in high temperature solar receivers is presented. The dependence of rupture strength on different surface conditions as well as high temperature is analyzed, focussing particularly on damage by devitrification and sandblasting. The influence of typical types of contamination in combination with thermal cycling on the optical properties of fused silica is determined. Cleaning methods are compared regarding effectiveness on contamination-induced degradation for samples with and without antireflective coating. The FEM-aided design of different types of receiver windows and their support structure is presented. A large-scale production process has been developed for producing fused silica dome shaped windows (pressurized window) up to a diameter of 816 mm. Prototypes were successfully pressure-tested in a test bench and certified according to the European Pressure Vessel Directive.

  14. Sense and sensitivity: How ALMA receivers work

    NASA Astrophysics Data System (ADS)

    Wilson, T. L.; Mauersberger, R.; Hales, A.

    2010-09-01

    In previous articles, we described how electromagnetic waves emitted from objects in the sky are collected by the ALMA antennas (Anatomy of ALMA), and how they are combined in order to produce images. Before these images can be processed, they are picked up by the antennas and concentrated by the large main mirror and a smaller secondary mirror in the so called focal point of each antenna. In order to process the data they must be first converted to electromagnetic waves of a lower frequency and amplified. This is the role of the ALMA receivers. In principle they work like a normal FM receiver, but at much higher frequencies. Here we describe how they work and what makes them special.

  15. Screen-printed flexible MRI receive coils

    NASA Astrophysics Data System (ADS)

    Corea, Joseph R.; Flynn, Anita M.; Lechêne, Balthazar; Scott, Greig; Reed, Galen D.; Shin, Peter J.; Lustig, Michael; Arias, Ana C.

    2016-03-01

    Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners.

  16. Screen-printed flexible MRI receive coils.

    PubMed

    Corea, Joseph R; Flynn, Anita M; Lechêne, Balthazar; Scott, Greig; Reed, Galen D; Shin, Peter J; Lustig, Michael; Arias, Ana C

    2016-01-01

    Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners. PMID:26961073

  17. Graphene radio frequency receiver integrated circuit.

    PubMed

    Han, Shu-Jen; Garcia, Alberto Valdes; Oida, Satoshi; Jenkins, Keith A; Haensch, Wilfried

    2014-01-01

    Graphene has attracted much interest as a future channel material in radio frequency electronics because of its superior electrical properties. Fabrication of a graphene integrated circuit without significantly degrading transistor performance has proven to be challenging, posing one of the major bottlenecks to compete with existing technologies. Here we present a fabrication method fully preserving graphene transistor quality, demonstrated with the implementation of a high-performance three-stage graphene integrated circuit. The circuit operates as a radio frequency receiver performing signal amplification, filtering and downconversion mixing. All circuit components are integrated into 0.6 mm(2) area and fabricated on 200 mm silicon wafers, showing the unprecedented graphene circuit complexity and silicon complementary metal-oxide-semiconductor process compatibility. The demonstrated circuit performance allow us to use graphene integrated circuit to perform practical wireless communication functions, receiving and restoring digital text transmitted on a 4.3-GHz carrier signal.

  18. North Dakota geology school receives major gift

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-10-01

    Petroleum geology and related areas of study at the University of North Dakota (UND) received a huge financial boost with the announcement on 24 September of $14 million in private and public partnership funding. The university announced the naming of the Harold Hamm School of Geology and Geological Engineering, formerly a department within the College of Engineering and Mines, in recognition of $10 million provided as a gift by oilman Harold Hamm and Continental Resources, Inc. Hamm is the chair and chief executive officer of Continental, the largest leaseholder in the Bakken Play oil formation in North Dakota and Montana, and he is also an energy policy advisor to Republican presidential candidate Mitt Romney. UND also received $4 million from the Oil and Gas Research Program of the North Dakota Industrial Commission to support geology and geological engineering education and research.

  19. ICESat-2 / ATLAS Flight Science Receiver Algorithms

    NASA Astrophysics Data System (ADS)

    Mcgarry, J.; Carabajal, C. C.; Degnan, J. J.; Mallama, A.; Palm, S. P.; Ricklefs, R.; Saba, J. L.

    2013-12-01

    NASA's Advanced Topographic Laser Altimeter System (ATLAS) will be the single instrument on the ICESat-2 spacecraft which is expected to launch in 2016 with a 3 year mission lifetime. The ICESat-2 orbital altitude will be 500 km with a 92 degree inclination and 91-day repeat tracks. ATLAS is a single photon detection system transmitting at 532nm with a laser repetition rate of 10 kHz and a 6 spot pattern on the Earth's surface. Without some method of eliminating solar background noise in near real-time, the volume of ATLAS telemetry would far exceed the normal X-band downlink capability. To reduce the data volume to an acceptable level a set of onboard Receiver Algorithms has been developed. These Algorithms limit the daily data volume by distinguishing surface echoes from the background noise and allow the instrument to telemeter only a small vertical region about the signal. This is accomplished through the use of an onboard Digital Elevation Model (DEM), signal processing techniques, and an onboard relief map. Similar to what was flown on the ATLAS predecessor GLAS (Geoscience Laser Altimeter System) the DEM provides minimum and maximum heights for each 1 degree x 1 degree tile on the Earth. This information allows the onboard algorithm to limit its signal search to the region between minimum and maximum heights (plus some margin for errors). The understanding that the surface echoes will tend to clump while noise will be randomly distributed led us to histogram the received event times. The selection of the signal locations is based on those histogram bins with statistically significant counts. Once the signal location has been established the onboard Digital Relief Map (DRM) is used to determine the vertical width of the telemetry band about the signal. The ATLAS Receiver Algorithms are nearing completion of the development phase and are currently being tested using a Monte Carlo Software Simulator that models the instrument, the orbit and the environment

  20. External ground monitoring v. receiver monitoring

    NASA Astrophysics Data System (ADS)

    Johannessen, R.

    1991-01-01

    The high levels of integrity required by civil aviation in the use of satellite navigation entails that satellite warning messages be augmented by some secondary form of monitoring. The alternatives presently considered are (1) ground monitoring, in which a monitor at some fixed and surveyed ground location broadcasts a warning to the navigating aircraft when there is a malfunction; and (2) 'receiver autonomous integrity monitoring' (RAIM), in which the navigating receiver conducts its own internal monitoring. While the former can be achieved with fewer navigation satellites, RAIM has the singular advantage of requiring no additional investment for a ground-monitoring system. The present evaluation of the alternatives discusses the factors of satellite visibility, the definition of 'good' geometry, and the duration of integrity outages and their significance.

  1. VLBI2010 Receiver Back End Comparison

    NASA Technical Reports Server (NTRS)

    Petrachenko, Bill

    2013-01-01

    VLBI2010 requires a receiver back-end to convert analog RF signals from the receiver front end into channelized digital data streams to be recorded or transmitted electronically. The back end functions are typically performed in two steps: conversion of analog RF inputs into IF bands (see Table 2), and conversion of IF bands into channelized digital data streams (see Tables 1a, 1b and 1c). The latter IF systems are now completely digital and generically referred to as digital back ends (DBEs). In Table 2 two RF conversion systems are compared, and in Tables 1a, 1b, and 1c nine DBE systems are compared. Since DBE designs are advancing rapidly, the data in these tables are only guaranteed to be current near the update date of this document.

  2. Solar receiver performance of point focusing collector system

    NASA Technical Reports Server (NTRS)

    Wu, Y. C.; Wen, L. C.

    1978-01-01

    The solar receiver performance of cavity receivers and external receivers used in dispersed solar power systems was evaluated for the temperature range 300-1300 C. Several parameters of receiver and concentrator are examined. It was found that cavity receivers are generally more efficient than external receivers, especially at high temperatures which require a large heat transfer area. The effects of variation in the ratio of receiver area to aperture area are considered.

  3. Digital Signal Processor For GPS Receivers

    NASA Technical Reports Server (NTRS)

    Thomas, J. B.; Meehan, T. K.; Srinivasan, J. M.

    1989-01-01

    Three innovative components combined to produce all-digital signal processor with superior characteristics: outstanding accuracy, high-dynamics tracking, versatile integration times, lower loss-of-lock signal strengths, and infrequent cycle slips. Three components are digital chip advancer, digital carrier downconverter and code correlator, and digital tracking processor. All-digital signal processor intended for use in receivers of Global Positioning System (GPS) for geodesy, geodynamics, high-dynamics tracking, and ionospheric calibration.

  4. Counterrotator And Correlator For GPS Receivers

    NASA Technical Reports Server (NTRS)

    Thomas, J. Brooks; Srinivasan, Jeffrey M.; Meehan, Thomas K.

    1989-01-01

    Accurate, all-digital, high-speed processor comprising correlator and down-converter developed for receivers in Global Positioning System (GPS). Processor reduces roundoff and commensurability errors to extremely small values. Use of digital chip and phase advancers provides outstanding control and accuracy in phase and feedback. Great flexibility imparted by provision for arbitrary starting time and integration length. Minimum-bit design requires minimum number of logical elements, thereby reducing size, power, and cost.

  5. Integrated solar upper stage alternate receiver

    SciTech Connect

    Streckert, H.H.; Begg, L.L.; Heffernan, T.F.; Horner, M.H.

    1997-12-31

    The Integrated Solar Upper Stage (ISUS) receiver is a compact orbital transfer vehicle designed to generate thrust to boost transfer payloads from low earth orbit to Molniya or geosynchronous orbits. It can provide thrust by collecting and concentrating solar flux and heating hydrogen to {approximately} 2,500 K. Simultaneously, the ISUS receiver radiates heat into an array of thermionic converters to produce electrical power. The central component consists of a graphite body with rhenium lined internal passages. The alternate receiver relies on wrought rhenium that is rolled, machined and electron-beam welded to form a complex rhenium liner system within the graphite body. All machining operations were performed by molybdenum wire electron discharge machining. The tube forming procedure was performed to minimize the amount of cold work before annealing. Electron-beam welding was performed at a current density range of {approximately} 2 to 10 A/cm{sup 2} depending on material thickness, which melts the rhenium locally and results in a fine grained weld zone. A simplified Demonstration Test Assembly was fabricated and tested. The unit consisted of an inlet structure welded to a manifold with a simplified exhaust nozzle system and contained in a machined graphite body. The external graphite surfaces were coated with plasma sprayed rhenium for protection from graphite erosion. Testing included a hot hydrogen flow test to {approximately} 2,500 K. The main ISUS Alternate Receiver was designed and built according to the same procedures as the demonstration unit. However, the inlet and outlet plenums are more complex and are connected by 195 channels to efficiently transfer heat to the flowing hydrogen. An outlet tube containing a sonic orifice mates to the exhaust plenum.

  6. Armstrong Receives Space Medal of Honor

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Astronaut Neil A. Armstrong receives the first Congressional Space Medal of Honor from President Jimmy Carter, assisted by Captain Robert Peterson. Armstrong, one of six astronauts to be presented the medal during ceremonies held in the Vehicle Assembly Building (VAB), was awarded for his performance during the Gemini 8 mission and the Apollo 11 mission when he became the first human to set foot upon the Moon.

  7. Optical antenna gain. II - Receiving antennas

    NASA Technical Reports Server (NTRS)

    Degnan, J. J.; Klein, B. J.

    1974-01-01

    Expressions are developed for the gain of a centrally obscured, circular optical antenna used as the collecting and focusing optics in a laser receiver, involving losses due to (1) incoming light blockage by central obscuration, (2) energy spillover at the detector, and (3) the effect of local oscillator distribution in the case of heterodyne or homodyne detection. Numerical results are presented for direct detection and for three types of local oscillator distribution (uniform, Gaussian, and matched).

  8. Solar central receiver integration with Hoover Dam

    SciTech Connect

    Remmers, H.E.; Zelenka, R.L.; Kitchen, J.H.

    1980-01-01

    The technical and economic feasibility of integrating a 100 MWe solar central receiver powerplant located in Yuma, Arizona with the Hoover Dam hydroelectric power system is discussed. Technical feasibility was determined by evaluating the effects of integration on the hydrologic and power operations of the existing hydro system. Economic feasibility was determined by comparing the costs of the integrated system with that of the most likely alternative source of power generation--an oil-fired,combined-cycle plant.

  9. Hansen receives 2001 Roger Revelle Medal

    NASA Astrophysics Data System (ADS)

    Prather, Michael J.; Hansen, James E.

    James E. Hansen received the Roger Revelle Medal at the 2001 Fall Meeting Honors Ceremony on 12 December in San Francisco, California. The medal is given for outstanding contributions toward an understanding of the Earth's atmospheric processes, including its dynamics, chemistry, and radiation; the roles of atmosphere, atmosphere-ocean coupling, or atmosphere-land coupling in determining the climate, biogeochemical cycles, or other key elements of the integrated climate system.

  10. Air Brayton Solar Receiver, phase 1

    NASA Technical Reports Server (NTRS)

    Zimmerman, D. K.

    1979-01-01

    A six month analysis and conceptual design study of an open cycle Air Brayton Solar Receiver (ABSR) for use on a tracking, parabolic solar concentrator are discussed. The ABSR, which includes a buffer storage system, is designed to provide inlet air to a power conversion unit. Parametric analyses, conceptual design, interface requirements, and production cost estimates are described. The design features were optimized to yield a zero maintenance, low cost, high efficiency concept that will provide a 30 year operational life.

  11. Robust quantum receivers for coherent state discrimination

    NASA Astrophysics Data System (ADS)

    Becerra, Francisco Elohim

    2014-05-01

    Quantum state discrimination is a central task for quantum information and is a fundamental problem in quantum mechanics. Nonorthogonal states, such as coherent states which have intrinsic quantum noise, cannot be discriminated with total certainty because of their intrinsic overlap. This nonorthogonality is at the heart of quantum key distribution for ensuring absolute secure communications between a transmitter and a receiver, and can enable many quantum information protocols based on coherent states. At the same time, while coherent states are used for communications because of their robustness to loss and simplicity of generation and detection, their nonorthogonality inherently produces errors in the process of decoding the information. The minimum error probability in the discrimination of nonorthogonal coherent states measured by an ideal lossless and noiseless conventional receiver is given by the standard quantum limit (SQL). This limit sets strict bounds on the ultimate performance of coherent communications and many coherent-state-based quantum information protocols. However, measurement strategies based on the quantum properties of these states can allow for better measurements that surpass the SQL and approach the ultimate measurement limits allowed by quantum mechanics. These measurement strategies can allow for optimally extracting information encoded in these states for coherent and quantum communications. We present the demonstration of a receiver based on adaptive measurements and single-photon counting that unconditionally discriminates multiple nonorthogonal coherent states below the SQL. We also discuss the potential of photon-number-resolving detection to provide robustness and high sensitivity under realistic conditions for an adaptive coherent receiver with detectors with finite photon-number resolution.

  12. Anticoagulation: monitoring of patients receiving anticoagulation.

    PubMed

    Hawes, Emily M; Viera, Anthony J

    2014-07-01

    For patients with acute venous thromboembolism treated with warfarin, parenteral anticoagulation should be continued for a minimum of 5 days and until the international normalized ratio (INR) is 2 or greater for at least 24 hours. Early initiation of warfarin therapy is recommended. The goal therapeutic INR range for patients treated with warfarin is most commonly 2 to 3. During maintenance warfarin therapy, validated decision-support tools should be used to guide dosing. For patients with stable INRs, frequency of INR testing can be extended from every 4 weeks to up to 12 weeks. Self-testing and self-management can be safe options for patients receiving warfarin who are motivated and show competence. Patients starting anticoagulation therapy should receive education on treatment goals, adverse effects, and monitoring strategy. Physicians deciding whether to prescribe one of the new oral anticoagulants instead of warfarin should assess for possible drug interactions and for renal and hepatic impairment and should consider the financial cost to the patient. No routine coagulation assay monitoring is required for patients receiving apixaban, dabigatran, or rivaroxaban. Physicians who oversee oral anticoagulation therapy should do so in a systematic and coordinated fashion.

  13. Transient simulation of molten salt central receiver

    NASA Astrophysics Data System (ADS)

    Doupis, Dimitri; Wang, Chuan; Carcorze-Soto, Jorge; Chen, Yen-Ming; Maggi, Andrea; Losito, Matteo; Clark, Michael

    2016-05-01

    Alstom is developing concentrated solar power (CSP) utilizing 60/40wt% NaNO3-KNO3 molten salt as the working fluid in a tower receiver for the global renewable energy market. In the CSP power generation cycle, receivers undergo a daily cyclic operation due to the transient nature of solar energy. Development of robust and efficient start-up and shut-down procedures is critical to avoiding component failures due to mechanical fatigue resulting from thermal transients, thus maintaining the performance and availability of the CSP plant. The Molten Salt Central Receiver (MSCR) is subject to thermal transients during normal daily operation, a cycle that includes warmup, filling, operation, draining, and shutdown. This paper describes a study to leverage dynamic simulation and finite element analysis (FEA) in development of start-up, shutdown, and transient operation concepts for the MSCR. The results of the FEA also verify the robustness of the MSCR design to the thermal transients anticipated during the operation of the plant.

  14. On the nonuniqueness of receiver function inversions

    SciTech Connect

    Ammon, C.J. ); Randall, G.E. ); Zandt, G. )

    1990-09-10

    To study the resolving power of teleseismic P waveforms for receiver structure, the authors model synthetic waveforms using a time domain waveform inversion scheme beginning with a range of initial models to estimate the range of acceptable velocity structures. To speed up the waveform inversions, they implement Randall's (1989) efficient algorithms for calculating differential seismograms and include a smoothness constraint on all the resulting velocity models utilizing the jumping inversion technique of Shaw and Orcutt (1985). They present the results of more than 235 waveform inversions for one-dimensional velocity structures that indicate that the primary sensitivity of a receiver function is to high wavenumber velocity changes, and a depth-velocity product, not simply velocity. The range of slownesses in a typical receiver function study does not appear to be broad enough to remove the depth-velocity ambiguity; the inclusion of a priori information is necessary. They also present inversion results for station RSCP, located in the Cumberland Plateau, Tennessee. The results are similar to those from a previous study by Owens et al. (1984) and demonstrate the uncertainties in the resulting velocity estimate more clearly.

  15. Radio Astronomy Software Defined Receiver Project

    SciTech Connect

    Vacaliuc, Bogdan; Leech, Marcus; Oxley, Paul; Flagg, Richard; Fields, David

    2011-01-01

    The paper describes a Radio Astronomy Software Defined Receiver (RASDR) that is currently under development. RASDR is targeted for use by amateurs and small institutions where cost is a primary consideration. The receiver will operate from HF thru 2.8 GHz. Front-end components such as preamps, block down-converters and pre-select bandpass filters are outside the scope of this development and will be provided by the user. The receiver includes RF amplifiers and attenuators, synthesized LOs, quadrature down converters, dual 8 bit ADCs and a Signal Processor that provides firmware processing of the digital bit stream. RASDR will interface to a user s PC via a USB or higher speed Ethernet LAN connection. The PC will run software that provides processing of the bit stream, a graphical user interface, as well as data analysis and storage. Software should support MAC OS, Windows and Linux platforms and will focus on such radio astronomy applications as total power measurements, pulsar detection, and spectral line studies.

  16. Terahertz Superconducting Hot Electron Bolometer Heterodyne Receivers

    NASA Astrophysics Data System (ADS)

    Gao, J. R.; Hajenius, M..; Yang, Z. Q.; Baselmans, J. J. A.; Khosropanah, P..; Barends, R..; Klapwijk, T. M.

    2007-06-01

    We highlight the progress on NbN hot electron bolometer (HEB) mixers achieved through fruitful collaboration between SRON Netherlands Institute for Space Research and Delft University of Technology, the Netherlands. This includes the best receiver noise temperatures of 700 K at 1.63 THz using a twin-slot antenna mixer and 1050 K at 2.84 THz using a spiral antenna coupled HEB mixer. The mixers are based on thin NbN films on Si and fabricated with a new contact-process and-structure. By reducing their areas HEB mixers have shown an LO power requirement as low as 30 nW. Those small HEB mixers have demonstrated equivalent sensitivity as those with large areas provided the direct detection effect due to broadband radiation is removed. To manifest that a HEB based heterodyne receiver can in practice be used at arbitrary frequencies above 2 THz, we demonstrate a 2.8 THz receiver using a THz quantum cascade laser (QCL) as local oscillator.

  17. Towards Self-Clocked Gated OCDMA Receiver

    NASA Astrophysics Data System (ADS)

    Idris, S.; Osadola, T.; Glesk, I.

    2013-02-01

    A novel incoherent OCDMA receiver with incorporated all-optical clock recovery for self-synchronization of a time gate for the multi access interferences (MAI) suppression and minimizing the effect of data time jitter in incoherent OCDMA system was successfully developed and demonstrated. The solution was implemented and tested in a multiuser environment in an out of the laboratory OCDMA testbed with two-dimensional wavelength-hopping time-spreading coding scheme and OC-48 (2.5 Gbp/s) data rate. The self-clocked all-optical time gate uses SOA-based fibre ring laser optical clock, recovered all-optically from the received OCDMA traffic to control its switching window for cleaning the autocorrelation peak from the surrounding MAI. A wider eye opening was achieved when the all-optically recovered clock from received data was used for synchronization if compared to a static approach with the RF clock being generated by a RF synthesizer. Clean eye diagram was also achieved when recovered clock is used to drive time gating.

  18. Submillimeter heterodyne receiver for the CSO telescope

    NASA Technical Reports Server (NTRS)

    Gulkis, S.

    1988-01-01

    This task is to build a cryogenically cooled 620 to 700 GHz astronomical receiver that will be used as a facility instrument at the CalTech Submillimeter Observatory (CSO) on Mauna Kea, Hawaii. The receiver will have applications as a very high resolution spectrometer to investigate spectral lines in planetary and satellite atmospheres, and comets. The receiver will also be used to make continuum measurements of planets, satellites, and asteroids. During FY88, a scale model (200 GHz) SIS mixer radiometer was built and intrgrated into a cryostat designed for use on the CSO telescope. This system will serve as a model to guide the work on the higher frequency mixer. A solid state local oscillator source that covers two bands in the 600 to 700 GHz has been developed under contract JPL and will be delivered before the end of the year. Work has continued on the SIS materials needed for the 620 to 700 GHz mixer. Test hardware has been developed which allow the 1 to 5 curves for SIS material to be easily measured.

  19. TDRSS S-shuttle unique receiver equipment

    NASA Technical Reports Server (NTRS)

    Weinberg, A.; Schwartz, J. J.; Spearing, R.

    1985-01-01

    Beginning with STS-9, the Tracking and Date Relay Satellite system (TDRSS) will start providing S- and Ku-band communications and tracking support to the Space Shuttle and its payloads. The most significant element of this support takes place at the TDRSS White Sands Ground Terminal, which processes the Shuttle return link S- and Ku-band signals. While Ku-band hardware available to other TDRSS users is also applied to Ku-Shuttle, stringent S-Shuttle link margins have precluded the application of the standard TDRSS S-band processing equipment to S-Shuttle. It was therfore found necessary to develop a unique S-Shuttle Receiver that embodies state-of-the-art digital technology and processing techniques. This receiver, developed by Motorola, Inc., enhances link margins by 1.5 dB relative to the standard S-band equipment and its bit error rate performance is within a few tenths of a dB of theory. An overview description of the Space Shuttle Receiver Equipment (SSRE) is presented which includes the presentation of block diagrams and salient design features. Selected, measured performance results are also presented.

  20. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  1. Sensitive Broadband Receivers for Microwave Limb Sounding

    NASA Astrophysics Data System (ADS)

    Ward, J. S.; Lee, K. A.; Kawamura, J.; Chattopadhyay, G.; Stek, P. C.

    2007-12-01

    Microwave limb sounding is a proven remote-sensing technique that resolves the spectra of microwave thermal emission along a limb view of the earth's atmosphere with a cold space background. The temperature and composition of the atmosphere as a function of altitude is retrieved by analyzing the spectra returned from a vertical scan of the limb. The Microwave Limb Sounder (MLS) instrument on the NASA Upper Atmosphere Research Satellite (UARS) was the first experiment to study the microwave limb from space, and was followed by the current EOS MLS instrument on the Aura spacecraft. We are developing a new class of highly-sensitive broadband receivers for a next-generation microwave limb sounder that scans the limb in elevation and azimuth to generate a 3-D map of atmospheric composition. Sensitive receivers are needed to reduce integration times to allow the addition of rapid horizontal scanning while maintaining high measurement precision. The Scanning Microwave Limb Sounder (SMLS) will sample a 6000 km cross track swath with 50 km resolution while doubling the vertical resolution of its predecessor, Aura MLS. The wide swath allows for six or more daily samples for most of the mid latitudes. These frequent measurements, combined with the good horizontal and high vertical resolution of SMLS are key to enabling the study of fast processes in the upper troposphere affecting chemistry, climate, and air quality. Two receivers are being developed for SMLS: a 230 GHz channel will be used to study the upper troposphere and a 640 GHz channel will focus on measurements of the stratosphere. Both receivers feature broad tunable bandwidth (100 GHz each) to enable measurements of many important species including water, ozone, CO, HCN, NO, SO2, and acetone. Each receiver will downconvert the signal using a superconductor-insulator- superconductor (SIS) heterodyne mixer to achieve sensitivities of 100 K and 200 K for the 230 GHz and 640 GHz channels, respectively. The high spectral

  2. Cryogenic 160-GHz MMIC Heterodyne Receiver Module

    NASA Technical Reports Server (NTRS)

    Samoska, Lorene A.; Soria, Mary M.; Owen, Heather R.; Dawson, Douglas E.; Kangaslahti, Pekka P.; Gaier, Todd C.; Voll, Patricia; Lau, Judy; Sieth, Matt; Church, Sarah

    2011-01-01

    A cryogenic 160-GHz MMIC heterodyne receiver module has demonstrated a system noise temperature of 100 K or less at 166 GHz. This module builds upon work previously described in Development of a 150-GHz MMIC Module Prototype for Large-Scale CMB Radiation (NPO-47664), NASA Tech Briefs, Vol. 35, No. 8 (August 2011), p. 27. In the original module, the local oscillator signal was saturating the MMIC low-noise amplifiers (LNAs) with power. In order to suppress the local oscillator signal from reaching the MMIC LNAs, the W-band (75 110 GHz) signal had to be filtered out before reaching 140 170 GHz. A bandpass filter was developed to cover 120 170 GHz, using microstrip parallel-coupled lines to achieve the desired filter bandwidth, and ensure that the unwanted W-band local oscillator signal would be sufficiently suppressed. With the new bandpass filter, the entire receiver can work over the 140 180-GHz band, with a minimum system noise temperature of 460 K at 166 GHz. The module was tested cryogenically at 20 K ambient temperature, and it was found that the receiver had a noise temperature of 100 K over an 8-GHz bandwidth. The receiver module now includes a microstrip bandpass filter, which was designed to have a 3-dB bandwidth of approximately 120-170 GHz. The filter was fabricated on a 3-mil-thick alumina substrate. The filter design was based on a W-band filter design made at JPL and used in the QUIET (Q/U Imaging ExperimenT) radiometer modules. The W-band filter was scaled for a new center frequency of 150 GHz, and the microstrip segments were changed accordingly. Also, to decrease the bandwidth of the resulting scaled design, the center gaps between the microstrip lines were increased (by four micrometers in length) compared to the gaps near the edges. The use of the 150-GHz bandpass filter has enabled the receiver module to function well at room temperature. The system noise temperature was measured to be less than 600 K (at room temperature) from 154 to 168 GHz

  3. Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer.

    PubMed

    Zhang, Qian; Du, Yang; Jing, Lijia; Liang, Xiaolong; Li, Yaqian; Li, Xiaofeng; Dai, Zhifei; Tian, Jie

    2016-03-01

    Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA. PMID:27280247

  4. Folic Acid

    MedlinePlus

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  5. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  6. 24 CFR 982.355 - Portability: Administration by receiving PHA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... receiving PHA, the receiving PHA must promptly inform the initial PHA whether the receiving PHA will bill... §§ 982.552 and 982.553. (10) When the family has a right to lease a unit in the receiving PHA... portable family, the receiving PHA may bill the initial PHA for housing assistance payments...

  7. Amino acids

    MedlinePlus

    ... amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan , and valine. Nonessential amino acids "Nonessential" means that our bodies produce an amino ...

  8. Receivers Gather Data for Climate, Weather Prediction

    NASA Technical Reports Server (NTRS)

    2012-01-01

    Signals from global positioning system (GPS) satellites are now being used for more than just location and navigation information. By looking at the radio waves from GPS satellites, a technology developed at NASA s Jet Propulsion Laboratory (JPL) not only precisely calculates its position, but can also use a technique known as radio occultation to help scientists study the Earth s atmosphere and gravity field to improve weather forecasts, monitor climate change, and enhance space weather research. The University Corporation for Atmospheric Research (UCAR), a nonprofit group of universities in Boulder, Colorado, compares radio occultation to the appearance of a pencil when viewed though a glass of water. The water molecules change the path of visible light waves so that the pencil appears bent, just like molecules in the air bend GPS radio signals as they pass through (or are occulted by) the atmosphere. Through measurements of the amount of bending in the signals, scientists can construct detailed images of the ionosphere (the energetic upper part of the atmosphere) and also gather information about atmospheric density, pressure, temperature, and moisture. Once collected, this data can be input into weather forecasting and climate models for weather prediction and climate studies. Traditionally, such information is obtained through the use of weather balloons. In 1998, JPL started developing a new class of GPS space science receivers, called Black Jack, that could take precise measurements of how GPS signals are distorted or delayed along their way to the receiver. By 2006, the first demonstration of a GPS radio occultation constellation was launched through a collaboration among Taiwan s National Science Council and National Space Organization, the U.S. National Science Foundation, NASA, the National Oceanic and Atmospheric Administration (NOAA), and other Federal entities. Called the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC

  9. Carboplatin pharmacokinetics in a patient receiving hemodialysis.

    PubMed

    Fong, Mei Ka; Fetterly, Gerald J; McDougald, Lori J; Iyer, Renuka V

    2014-02-01

    With refinements and advances in hemodialysis techniques, survival for patients with end-stage renal disease has improved significantly. To our knowledge, however, no prospective trials have been performed in patients receiving hemodialysis who are also diagnosed with cancer and are candidates for chemotherapy. We describe a 73-year-old man who was diagnosed with high-grade neuroendocrine carcinoma, metastatic to the bone and lymph nodes, and was undergoing hemodialysis. Although cisplatin is more commonly used in the treatment of metastatic neuroendocrine cancers, it may not be the best option in patients who suffer from renal insufficiency. Carboplatin is a second-generation, nonnephrotoxic platinum analog that can be hemodialyzed, although no formal guidelines are available regarding the dosing for patients receiving hemodialysis. This case describes a patient who was treated with five cycles of combination carboplatin 115 mg/m(2) on day 1 and etoposide 50 mg/m(2) on day 1 and day 3 of a 28-day cycle. Dialysis was performed for 3.5 hours starting 90 minutes after completion of carboplatin on day 1. Pharmacokinetic assessments were performed at 1, 2, 4, and 12 hours after chemotherapy infusion on day 1 of cycle 1. Total carboplatin concentrations in plasma and platinum ultrafiltrate were measured. The plasma concentration of free platinum at the end of the infusion was 31,000 ng/ml, and the area under the plasma concentration-time curve was 2.9 minute·mg/ml. No significant carboplatin-related toxicities were reported. This case report indicates that carboplatin can be safely administered in patients receiving hemodialysis.

  10. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...; replacing a plug-in semiconductor chip; or programming a semiconductor chip using special access codes or an external device, such as a personal computer. Scanning receivers, and frequency converters designed for...

  11. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; replacing a plug-in semiconductor chip; or programming a semiconductor chip using special access codes or an external device, such as a personal computer. Scanning receivers, and frequency converters designed for...

  12. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...; replacing a plug-in semiconductor chip; or programming a semiconductor chip using special access codes or an external device, such as a personal computer. Scanning receivers, and frequency converters designed for...

  13. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...; replacing a plug-in semiconductor chip; or programming a semiconductor chip using special access codes or an external device, such as a personal computer. Scanning receivers, and frequency converters designed for...

  14. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...; replacing a plug-in semiconductor chip; or programming a semiconductor chip using special access codes or an external device, such as a personal computer. Scanning receivers, and frequency converters designed for...

  15. Line Focus Receiver Infrared Temperature Survey System

    SciTech Connect

    Wendelin, Tim

    2010-06-01

    For ongoing maintenance and performance purposes, solar parabolic trough field operators desire to know that the Heat Collection Elements (HCEs) are performing properly. Measuring their temperature is one way of doing this One 30MW field can contain approximately 10,000 HCE's. This software interfaces with a GPS receiver and an infrared camera. It takes global positioning data from the GPS and uses this information to automate the infrared image capture and temperature analysis of individual solar parabolic HCEs in a solar parabolic trough field With this software system an entire 30MW field can be surveyed in 2-3 days.

  16. Reconfigurable Advanced Receiver Design and Implementation

    NASA Technical Reports Server (NTRS)

    Xu, Jianjing

    2005-01-01

    While the demand for real-time broadband information access has grown and continues to grow at a rapid Pace, the need for a reconfigurable receiver system has increased. To achieve the goal to communicate with multiple shuttles at a time, a filter bank in polyphase structure is introduced. This paper presents the design and implementation for high-speed, high-performance, and fixed-point polyphase filter banks. The polyphase filter structure is designed such that the use of a fixed-point system has minimum impact on the performance of the filter. The final hardware implementation is done on a Xilinx FPGA chip.

  17. Thatcher Receives 2004 Charles A. Whitten Medal

    NASA Astrophysics Data System (ADS)

    Stein, Ross

    2005-02-01

    Wayne Thatcher received the Whitten Medal at the 2004 Fall Meeting Honors Ceremony on 15 December, in San Francisco, California. The medal is given for outstanding achievement in research on the form and dynamics of the Earth and planets. Citation. Armed with geodesy, Wayne Thatcher has probed the behavior of great earthquakes, concentrating on the two sites where large events are frequent and the geodetic record is lush: the western United States and Japan. From this, he has garnered deep insights into the earthquake cycle-the pattern of strain accumulation and release of which an earthquake is only the most visible part.

  18. Line Focus Receiver Infrared Temperature Survey System

    2010-06-01

    For ongoing maintenance and performance purposes, solar parabolic trough field operators desire to know that the Heat Collection Elements (HCEs) are performing properly. Measuring their temperature is one way of doing this One 30MW field can contain approximately 10,000 HCE's. This software interfaces with a GPS receiver and an infrared camera. It takes global positioning data from the GPS and uses this information to automate the infrared image capture and temperature analysis of individual solarmore » parabolic HCEs in a solar parabolic trough field With this software system an entire 30MW field can be surveyed in 2-3 days.« less

  19. Advanced motor driven clamped borehole seismic receiver

    DOEpatents

    Engler, Bruce P.; Sleefe, Gerard E.; Striker, Richard P.

    1993-01-01

    A borehole seismic tool including a borehole clamp which only moves perpendicular to the borehole. The clamp is driven by an electric motor, via a right angle drive. When used as a seismic receiver, the tool has a three part housing, two of which are hermetically sealed. Accelerometers or geophones are mounted in one hermetically sealed part, the electric meter in the other hermetically sealed part, and the clamp and right angle drive in the third part. Preferably the tool includes cable connectors at both ends. Optionally a shear plate can be added to the clamp to extend the range of the tool.

  20. Advanced motor driven clamped borehole seismic receiver

    DOEpatents

    Engler, B.P.; Sleefe, G.E.; Striker, R.P.

    1993-02-23

    A borehole seismic tool is described including a borehole clamp which only moves perpendicular to the borehole. The clamp is driven by an electric motor, via a right angle drive. When used as a seismic receiver, the tool has a three part housing, two of which are hermetically sealed. Accelerometers or geophones are mounted in one hermetically sealed part, the electric motor in the other hermetically sealed part, and the clamp and right angle drive in the third part. Preferably the tool includes cable connectors at both ends. Optionally a shear plate can be added to the clamp to extend the range of the tool.

  1. Solar energy receiver for a Stirling engine

    NASA Technical Reports Server (NTRS)

    Selcuk, M. K. (Inventor)

    1980-01-01

    A solar energy receiver includes a separable endless wall formed of a ceramic material in which a cavity of substantially cylindrical configuration is defined for entrapping solar flux. An acceptance aperture is adapted to admit to the cavity a concentrated beam of solar energy. The wall is characterized by at least one pair of contiguously related segments separated by lines of cleavage intercepting the aperture. At least one of the segments is supported for pivotal displacement. A thermal-responsive actuator is adapted to respond to excessive temperatures within the cavity for initiating pivoted displacement of one segment, whereby thermal flux is permitted to escape from the cavity.

  2. Evaluation of advanced sodium receiver losses during operation of the IEA/SSPS central receiver system

    SciTech Connect

    Carmona, R.; Rosa, F.; Jacobs, H.; Sanchez, M.

    1989-02-01

    This article presents the measurements and experiments conducted on the external receiver: the so-called Advanced Sodium Receiver (ASR) of the Small Solar Power Systems (SSPS) Project of the International Energy Agency (IEA) in southern Spain. The basis of this experiment was to provide loss measurements for later use in determining receiver performance. The tests to evaluate thermal losses consisted in operating the receiver with the doors open and circulating the sodium in normal and reverse flow without providing any incident power from the heliostat field (flux-off technique). In this way, total thermal losses are calculated as the energy lost by the sodium. Radiative losses have been calculated based on theoretical calculations and some results have been compared with infrared thermography measurements. Conductive losses are small and have been estimated by flux-off experiments with the receiver doors closed. Convective losses were evaluated subtracting radiative and conductive losses from the total thermal losses. Optical losses were assessed using absorptance measurements of the receiver coating. A simplified analytical model has been developed to calculate losses and ASR efficiency during operation. In spite of the method's simplicity, the results are very similar to those found by other investigators, verified simulation programs and test results.

  3. Full-wave receiver architecture for the homodyne motion sensor

    SciTech Connect

    Haugen, Peter C; Dallum, Gregory E; Welsh, Patrick A; Romero, Carlos E

    2013-11-19

    A homodyne motion sensor or detector based on ultra-wideband radar utilizes the entire received waveform through implementation of a voltage boosting receiver. The receiver includes a receiver input and a receiver output. A first diode is connected to the receiver output. A first charge storage capacitor is connected from between the first diode and the receiver output to ground. A second charge storage capacitor is connected between the receiver input and the first diode. A second diode is connected from between the second charge storage capacitor and the first diode to ground. The dual diode receiver performs voltage boosting of a RF signal received at the receiver input, thereby enhancing receiver sensitivity.

  4. Full-wave receiver architecture for the homodyne motion sensor

    SciTech Connect

    Haugen, Peter C.; Dallum, Gregory E.; Welsh, Patrick A.; Romero, Carlos E.

    2015-09-29

    A homodyne motion sensor or detector based on ultra-wideband radar utilizes the entire received waveform through implementation of a voltage boosting receiver. The receiver includes a receiver input and a receiver output. A first diode is connected to the receiver output. A first charge storage capacitor is connected from between the first diode and the receiver output to ground. A second charge storage capacitor is connected between the receiver input and the first diode. A second diode is connected from between the second charge storage capacitor and the first diode to ground. The dual diode receiver performs voltage boosting of a RF signal received at the receiver input, thereby enhancing receiver sensitivity.

  5. The 30-GHz monolithic receive module

    NASA Technical Reports Server (NTRS)

    Sokolov, V.; Geddes, J.; Bauhahn, P.

    1983-01-01

    Key requirements for a 30 GHz GaAs monolithic receive module for spaceborne communication antenna feed array applications include an overall receive module noise figure of 5 dB, a 30 dB RF to IF gain with six levels of intermediate gain control, a five-bit phase shifter, and a maximum power consumption of 250 mW. The RF designs for each of the four submodules (low noise amplifier, some gain control, phase shifter, and RF to IF sub-module) are presented. Except for the phase shifter, high frequency, low noise FETs with sub-half micron gate lengths are employed in the submodules. For the gain control, a two stage dual gate FET amplifier is used. The phase shifter is of the passive switched line type and consists of 5-bits. It uses relatively large gate width FETs (with zero drain to source bias) as the switching elements. A 20 GHz local oscillator buffer amplifier, a FET compatible balanced mixer, and a 5-8 GHz IF amplifier constitute the RF/IF sub-module. Phase shifter fabrication using ion implantation and a self-aligned gate technique is described. Preliminary RF results obtained on such phase shifters are included.

  6. Woese on the received view of evolution.

    PubMed

    Sarkar, Sahotra

    2014-01-01

    As part of his attempt to reconstruct the earliest phase of the evolution of life on Earth, Woese produced a compelling critique of the received view of evolution from the 20th century. This paper explicitly articulates two related features of that critique that are fundamental but the first of which has not been sufficiently clearly recognized in the context of evolutionary theorizing: (1) according to Woese's scenario of communal evolution during life's earliest phase (roughly, the first billion years of life on Earth), well-defined biological individuals (and, thus, individual lineages) did not exist; and (2) during that phase, evolutionary change took place through ubiquitous horizontal gene transfer (HGT) rather than through vertical transmission of features (including genes) and the combinatorics of HGT was the dominant mechanism of evolutionary change. Both factors present serious challenges to the received view of evolution and that framework would have to be radically altered to incorporate these factors. The extent to which this will be necessary will depend on whether Woese's scenario of collective early evolution is correct.

  7. Advanced Stirling receiver development program, phase 1

    NASA Technical Reports Server (NTRS)

    Lurio, Charles A.

    1990-01-01

    Critical technology experiments were designed and developed to evaluate the Stirling cavity heat pipe receiver for a space solar power system. Theoretical criteria were applied to the design of a module for containing energy storage phase change material while avoiding thermal ratcheting. Zero-g drop tower tests, without phase change, were conducted to affirm that the bubble location required to avoid ratcheting could be achieved without the use of container materials that are wetted by the phase change material. A full scale module was fabricated, but not tested. A fabrication method was successfully developed for the sodium evaporator dome, with a sintered screen wick, to be used as the focal point for the receiver. Crushing of the screen during hydroforming was substantially reduced over the results of other researchers by using wax impregnation. Superheating of the sodium in the wick under average flux conditions is expected to be under 10K. A 2000K furnace which will simulate solar flux conditions for testing the evaporator dome was successfully built and tested.

  8. Solar central receiver heliostat reflector assembly

    DOEpatents

    Horton, Richard H.; Zdeb, John J.

    1980-01-01

    A heliostat reflector assembly for a solar central receiver system comprises a light-weight, readily assemblable frame which supports a sheet of stretchable reflective material and includes mechanism for selectively applying tension to and positioning the sheet to stretch it to optical flatness. The frame is mounted on and supported by a pipe pedestal assembly that, in turn, is installed in the ground. The frame is controllably driven in a predetermined way by a light-weight drive system so as to be angularly adjustable in both elevation and azimuth to track the sun and efficiently continuously reflect the sun's rays to a focal zone, i.e. central receiver, which forms part of a solar energy utilization system, such as a solar energy fueled electrical power generation system. The frame may include a built-in system for testing for optical flatness of the reflector. The preferable geometric configuration of the reflector is octagonal; however, it may be other shapes, such as hexagonal, pentagonal or square. Several different embodiments of means for tensioning and positioning the reflector to achieve optical flatness are disclosed. The reflector assembly is based on the stretch frame concept which provides an extremely light-weight, simple, low-cost reflector assembly that may be driven for positioning and tracking by a light-weight, inexpensive drive system.

  9. Woese on the received view of evolution

    PubMed Central

    Sarkar, Sahotra

    2014-01-01

    As part of his attempt to reconstruct the earliest phase of the evolution of life on Earth, Woese produced a compelling critique of the received view of evolution from the 20th century. This paper explicitly articulates two related features of that critique that are fundamental but the first of which has not been sufficiently clearly recognized in the context of evolutionary theorizing: (1) according to Woese’s scenario of communal evolution during life’s earliest phase (roughly, the first billion years of life on Earth), well-defined biological individuals (and, thus, individual lineages) did not exist; and (2) during that phase, evolutionary change took place through ubiquitous horizontal gene transfer (HGT) rather than through vertical transmission of features (including genes) and the combinatorics of HGT was the dominant mechanism of evolutionary change. Both factors present serious challenges to the received view of evolution and that framework would have to be radically altered to incorporate these factors. The extent to which this will be necessary will depend on whether Woese’s scenario of collective early evolution is correct. PMID:24572738

  10. Woese on the received view of evolution.

    PubMed

    Sarkar, Sahotra

    2014-01-01

    As part of his attempt to reconstruct the earliest phase of the evolution of life on Earth, Woese produced a compelling critique of the received view of evolution from the 20th century. This paper explicitly articulates two related features of that critique that are fundamental but the first of which has not been sufficiently clearly recognized in the context of evolutionary theorizing: (1) according to Woese's scenario of communal evolution during life's earliest phase (roughly, the first billion years of life on Earth), well-defined biological individuals (and, thus, individual lineages) did not exist; and (2) during that phase, evolutionary change took place through ubiquitous horizontal gene transfer (HGT) rather than through vertical transmission of features (including genes) and the combinatorics of HGT was the dominant mechanism of evolutionary change. Both factors present serious challenges to the received view of evolution and that framework would have to be radically altered to incorporate these factors. The extent to which this will be necessary will depend on whether Woese's scenario of collective early evolution is correct. PMID:24572738

  11. Steam Rankine Solar Receiver, phase 2

    NASA Technical Reports Server (NTRS)

    Deanda, L. E.; Faust, M.

    1981-01-01

    A steam rankine solar receiver (SRSR) based on a tubular concept was designed and developed. The SRSR is an insulated, cylindrical coiled tube boiler which is mounted at the focal plane of a fully tracking parabolic solar reflector. The concentrated solar energy received at the focal plane is then transformed to thermal energy through steam generation. The steam is used in a small Rankine cycle heat engine to drive a generator for the production of electrical energy. The SRSR was designed to have a dual mode capability, performing as a once through boiler with and without reheat. This was achieved by means of two coils which constitute the boiler. The boiler core size of the SRSR is 17.0 inches in diameter and 21.5 inches long. The tube size is 7/16 inch I.D. by 0.070 inch wall for the primary, and 3/4 inch I.D. by 0.125 inch wall for the reheat section. The materials used were corrosion resistant steel (CRES) type 321 and type 347 stainless steel. The core is insulated with 6 inches of cerablanket insulation wrapped around the outer wall. The aperture end and the reflector back plate at the closed end section are made of silicon carbide. The SRSR accepts 85 kwth and has a design life of 10,000 hrs when producing steam at 1400 F and 2550 psig.

  12. Agile multiple aperture imager receiver development

    NASA Astrophysics Data System (ADS)

    Lees, David E. B.; Dillon, Robert F.

    1990-02-01

    A variety of unconventional imaging schemes have been investigated in recent years that rely on small, unphased optical apertures (subaperture) to measure properties of an incoming optical wavefront and recover images of distant objects without using precisely figured, large aperture optical elements. Such schemes offer several attractive features. They provide the potential to create very lare effective aperture that are expandable over time and can be launched into space in small pieces. Since the subapertures are identical in construction, they may be mass producible at potentially low cost. A preliminary design for a practical low cost optical receiver is presented. The multiple aperture design has high sensitivity, wide field-of-view, and is lightweight. A combination of spectral, temporal, and spatial background suppression are used to achieve daytime operation at low signal levels. Modular packaging to make the number of receiver subapertures conveniently scalable is also presented. The design is appropriate to a ground-base proof-of-concept experiment for long range active speckle imaging.

  13. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  14. Acid rain

    SciTech Connect

    Not Available

    1985-01-01

    This report has four parts: they discuss acid rain in relation to acid soils, agriculture, forests, and aquatic ecosystems. Among findings: modern sources of acid deposition from the atmosphere for all the acid soils in the world, nor even chiefly responsible for those of northern U.S. Agriculture has its problems, but acid precipitation is probably not one of them. More research is needed to determine to what extent acid precipitation is responsible for forest declines and for smaller detrimental effects on forest growth where no damage to the foliage is evident. Many lakes and streams are extremely sensitive to added acids.

  15. Three Specialized Innovations for FAST Wideband Receiver

    NASA Astrophysics Data System (ADS)

    Zhang, Xia; Yu, Xinying; Duan, Ran; Hao, Jie; Li, Di

    2015-08-01

    The National Astronomical Observatories of the Chinese Academy of Sciences (NAOC) will soon finish the largest antenna in the world. Known as FAST, the Five-hundred-meter Aperture Spherical Radio Telescope will be the most sensitive single-dish radio telescope in the low frequency radio bands between 70 MHz and 3 GHz.To take advantage of its giant aperture, all relevant cutting-edge technology should be applied to FAST to ensure that it achieves the best possible overall performance. The wideband receiver that is currently under development can not only be directly applied to FAST, but also used for other Chinese radio telescopes, such as the Shanghai 65-meter telescope and the Xinjiang 110-meter telescope, to ensure that these telescopes are among the best in the world. Recently, rapid development related to this wideband receiver has been underway. In this paper, we will introduce three key aspects of the FAST wideband receiver project. First is the use of a high-performance analog-to-digital converter (ADC). With the cooperation of Hao Jie’s team from the Institute of Automation of the Chinese Academy of Sciences(CASIA), we have developed 3-Gsps,12-bit ADCs, which have not been used previously in astronomy, and we expect to realize the 3-GHz bandwidth in a single step by covering the entire bandwidth via interleaving or a complex fast Fourier transform (FFT).Second is the front-end analog signal integrated circuit board. We wish to achieve a series of amplification, attenuation, and mixing filtering operations on a single small board, thereby achieving digital control of the bandpass behavior both flexibly and highly-efficiently. This design will not only greatly reduce the required cost and power but will also make the best use of the digital-system’s flexibility. Third is optimization of the FFT: the existing FFT is not very efficient; therefore, we will optimize the FFT for large-scale operation. For this purpose, we intend to cascade two FFTs. Another

  16. QUALZICE: A QUALitative exploration of the experiences of the participants from the ZICE clinical trial (metastatic breast cancer) receiving intravenous or oral bisphosphonates

    PubMed Central

    2013-01-01

    Background This qualitative sub-study aimed to explore the experiences of participants on the National Cancer Research Institute ZICE clinical trial, a randomised trial assessing two types of bisphosphonate treatment in breast cancer patients with bone metastases. Participants in the clinical trial were randomly allocated to receive either zoledronate, delivered by an intravenous (IV) infusion at clinic, or oral ibandronate, taken at home. Methods Qualitative research interviews were conducted with participant groups organised by treatment and location. Interviews covered experiences and understanding of bisphosphonate treatment, the experience of the delivery mechanisms (IV or oral), side effects and benefits, and quality of life issues. The analytic framework was interpretative phenomenological analysis. Results This paper reports on one of four superordinate themes: participants’ experience of the ZICE trial, which explores the participants’ experiences with clinical trial-related processes. Results show that participants were generally satisfied with their randomised treatment, although most participants had an initial preference for oral bisphosphonates. Some difficulties were reported from participants for both interventions: needle phobia, poor veins, difficulty with swallowing and gastric side effects, but pain control was improved with both modes of delivery. However, the infused bisphosphonate was reported to lose effectiveness after three weeks for some participants, whereas the oral bisphosphonate was reported to give consistent pain control. Geographical location and distance to travel made little difference to convenience of access to clinic as the reported lengths of travel time were similar due to traffic congestion in the urban areas. Most participants understood the trial processes, such as randomisation, and information about bisphosphonates but some participants showed little understanding of certain aspects of the trial. Some participants

  17. Ceramic technology for solar thermal receivers

    NASA Technical Reports Server (NTRS)

    Kudirka, A. A.; Smoak, R. H.

    1981-01-01

    The high-temperature capability, resistance to corrosive environments and non-strategic nature of ceramics have prompted applications in the solar thermal field whose advantages over metallic devices of comparable performance may begin to be assessed. It is shown by a survey of point-focusing receiver designs employing a variety of ceramic compositions and fabrication methods that the state-of-the-art in structural ceramics is not sufficiently advanced to fully realize the promised benefits of higher temperature capabilities at lower cost than metallic alternatives. The ceramics considered include alumina, berylia, magnesia, stabilized zirconia, fused silica, silicon nitride, silicon carbide, mullite and cordierite, processed by such methods as isostatic pressing, dry pressing, slip casting, extrusion, calendaring and injection molding.

  18. Morel Receives 2005 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Schrag, Daniel P.; Morel, François M. M.

    2006-02-01

    François M. M. Morel received the Ewing Medal at the AGU Fall Meeting Honors Ceremony, which was held on 7 December 2005, in San Francisco, Calif. The medal is given for significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering, technology, and instrumentation; and for outstanding service to marine sciences. François Morel has led the search to understand the role of metals in the ocean, starting with a focus on inorganic processes and aquatic chemistry, and leading to a blend of geochemistry, microbiology, biochemistry, and genetics. His influence comes from his research and from the way he has educated an entire community of scientists with his textbooks, with his teaching, and through his former students and postdocs who hold faculty positions at universities throughout the world.

  19. New Packing Structure of Concentration Solar Receiver

    SciTech Connect

    Tsai, Shang-Yu; Lee, Yueh-Mu; Shih, Zun-Hao; Hong, Hwen-Fen; Shin, Hwa-Yuh; Kuo, Cherng-Tsong

    2010-10-14

    This paper presents a solution to the temperature issue in High Concentration Photovoltaic (HCPV) module device by using different thermal conductive material and packing structure. In general, the open-circuited voltage of a device reduces with the increase of temperature and therefore degrades its efficiency. The thermal conductive material we use in this paper, silicon, has a high thermal conductive coefficient (149 W/m{center_dot}K) and steady semiconductor properties which are suitable for the application of solar receiver in HCPV module. Solar cell was soldered on a metal-plated Si substrate with a thicker SiO{sub 2} film which acts as an insulating layer. Then it was mounted on an Al-based plate to obtain a better heat dissipating result.

  20. Modular design of receiver coil arrays.

    PubMed

    De Zanche, Nicola; Massner, Jurek A; Leussler, Christoph; Pruessmann, Klaas P

    2008-07-01

    We describe a modular and hence flexible system for connecting MR surface coils to create a receiver array. Up to 16 individual coils of different size and shape depending on the application are plugged into a connector box that houses the control electronics. Preamplification, matching and detuning circuitry are housed on a circuit board directly attached to each coil loop. Electrical adjustments for tuning or decoupling for each coil configuration are not needed thanks to effective preamplifier decoupling provided through a Pi matching network. Radio-frequency safety and electrically stable cabling are ensured by multiple radio-frequency traps. Array modules for 1.5 and 3 T have been simulated, constructed, tested, and used for imaging experiments.

  1. Sleep Issues with Patients Receiving Hemodialysis.

    PubMed

    Tocco, Kathleen; Rowder, Cheryl; VanNoord, Mary

    2015-01-01

    Poor sleep among the general population is understudied, unrecognized, and often not assessed This is especially true for patients receiving hemodialysis. This study used a case study design to examine the impact of hemodialysis treatments on the sleep of two patients as measured by actigraphy and self-reported sleep logs. Patient 1 experienced an average sleep efficiency of 82.3% on non-hemodialysis days compared to 75.0% on dialysis days, which resulted in a 7.3 percentage point change and 9.7% better sleep efficiency on non-hemodialysis days. Patient 2 reported sleep efficiency 76.6% on non-hemodialysis days compared to 70.5% dialysis on days, resulting in a 6.1 percentage point change and 8.7% better sleep efficiency on non-hemodialysis days. Actigraphy sleep patterns provided an initial move toward best practice for sleep evaluation in this population.

  2. Kopp Receives 2012 William Gilbert Award: Response

    NASA Astrophysics Data System (ADS)

    Kopp, Robert E.

    2013-10-01

    I have many people to thank for the honor of receiving the William Gilbert Award. Joe Kirschvink must sit at the top of the list, not just for the generosity—I hope at least partially deserved!—of his citation but also for his role as my Ph.D. mentor. During the 5 years I spent working with him at Caltech, Joe was always supportive; was as generous with his time as he has been in his words; and served as a role model for me in the way he fearlessly marched through our planet's history, building bridges between magnetism and our understanding of climate, the biosphere, and the Earth system as a whole.

  3. Remote bistatic receiver synchronization using DLL techniques

    NASA Astrophysics Data System (ADS)

    Aguasca, A.; Broquetas, A.; Fdez de Muniain, J.; Ambros, A.

    An experimental staggered pulse repetition frequency synchronizer, based on a delay-lock loop (DLL) was tested using a transmitter signal simulator that simulates the staggering sequence windowed by the antenna beam. The measured system performance ensures synchronization with a 30-ms direct illumination, with an accumulated delay error in the order of the resolution cell positioning error in range. An artificial time expansion of the received pulses is performed in order to reduce the acquisition time synchronization. A bistatic radar synchronization method based on DLL was is analyzed by linearization of the different parts and signals involved. The parameters that degrade system performance are obtained. And some solutions are represented in order to minimize their effects.

  4. Partitioned-Interval Quantum Optical Communications Receiver

    NASA Technical Reports Server (NTRS)

    Vilnrotter, Victor A.

    2013-01-01

    The proposed quantum receiver in this innovation partitions each binary signal interval into two unequal segments: a short "pre-measurement" segment in the beginning of the symbol interval used to make an initial guess with better probability than 50/50 guessing, and a much longer segment used to make the high-sensitivity signal detection via field-cancellation and photon-counting detection. It was found that by assigning as little as 10% of the total signal energy to the pre-measurement segment, the initial 50/50 guess can be improved to about 70/30, using the best available measurements such as classical coherent or "optimized Kennedy" detection.

  5. Receiver for digital radio broadcasting via satellite

    NASA Astrophysics Data System (ADS)

    Degraaf, C. R.

    1984-10-01

    Quadrature Phase Shift Keying (QPSK) demodulators were investigated; a differential-coherent demodulator (with delay-line) for a 20.48 Mbit/sec and 118 MHz medium frequency was developed. A modified professional coherent demodulator (With Costas-loop carrier wave regaining) (CD), was compared with the DQPSK. At the cost of higher circuit complexity and more adjustings, the CD shows better performances; both demodulators show deviation values 2dB. Applied bit error detection and correction methods were investigated and decoding tables were developed. In cases of high system reserves (e.g., central antenna installations of TV-receiver installations) the cheaper DQPSK is recommended. A prefabricated delay-line (and medium frequency filter) in surface acoustic wave technique is recommended to avoid complicated adjusting procedures.

  6. Sleep Issues with Patients Receiving Hemodialysis.

    PubMed

    Tocco, Kathleen; Rowder, Cheryl; VanNoord, Mary

    2015-01-01

    Poor sleep among the general population is understudied, unrecognized, and often not assessed This is especially true for patients receiving hemodialysis. This study used a case study design to examine the impact of hemodialysis treatments on the sleep of two patients as measured by actigraphy and self-reported sleep logs. Patient 1 experienced an average sleep efficiency of 82.3% on non-hemodialysis days compared to 75.0% on dialysis days, which resulted in a 7.3 percentage point change and 9.7% better sleep efficiency on non-hemodialysis days. Patient 2 reported sleep efficiency 76.6% on non-hemodialysis days compared to 70.5% dialysis on days, resulting in a 6.1 percentage point change and 8.7% better sleep efficiency on non-hemodialysis days. Actigraphy sleep patterns provided an initial move toward best practice for sleep evaluation in this population. PMID:26875228

  7. PERFLUOROOCTANOIC ACID AND PERFLUORONONANOIC ACID IN FETAL AND NEONATAL MICE FOLLOWING IN UTERO EXPOSURE TO 8-2 FLUOROTELOMER ALCOHOL

    EPA Science Inventory

    8-2 fluorotelomer alcohol (FTOH) and its metabolites, perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), are developmental toxicants, but metabolism and distribution during pregnancy is not known. To examine this, timed-pregnant mice received a single gavage dose (...

  8. Listeriosis in patients receiving biologic therapies.

    PubMed

    Bodro, M; Paterson, D L

    2013-09-01

    The evolution of inflammatory diseases has radically changed since the introduction of biologic therapies, such as tumour necrosis factor alpha inhibitors (anti-TNFα). They, therefore, represent a widely used therapeutic modality. Nevertheless, post-marketing studies reveal an increased risk of infection in patients taking these drugs, especially granulomatous infections such as listeriosis. We aimed to evaluate the reported cases of listeriosis in patients treated with biologic treatments. We used the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) from 2004 to 2011. We also perform a literature review of previously reported cases of listeriosis in patients taking biologic therapies. We identified 266 cases of Listeria monocytogenes infection associated with biologic therapies. The majority of patients were receiving infliximab (77.1 %), followed by etanercept (11.7 %), adalimumab (9.8 %), rituximab (4.1 %), abatacept (0.4 %) and golimumab (0.4 %). Indications for the use of biologics were as follows: 47.7 % for rheumatologic diseases, 38 % for inflammatory bowel diseases, 3.4 % for haematological diseases and 10.5 % for other indications. Seventy-three percent of the patients were receiving concomitant immunosuppressant drugs, especially steroids (56 %) and methotrexate (31.6 %). The median time to the onset of infection was 184 days. Mortality rates range from 11.1 % in adalimumab-treated patients to 27.3 % in rituximab-treated patients (p = 0.7). Listeriosis is common in biologics-treated patients, especially related to infliximab use given concomitantly with other immunosuppressive therapies. Infections after treatment with biologics mostly occurred in the first year after initiating treatment. PMID:23568606

  9. 47 CFR 15.117 - TV broadcast receivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false TV broadcast receivers. 15.117 Section 15.117... TV broadcast receivers. (a) All TV broadcast receivers shipped in interstate commerce or imported... receivers also includes devices, such as TV interface devices and set-top devices that are intended...

  10. 47 CFR 15.117 - TV broadcast receivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false TV broadcast receivers. 15.117 Section 15.117... TV broadcast receivers. (a) All TV broadcast receivers shipped in interstate commerce or imported... receivers also includes devices, such as TV interface devices and set-top devices that are intended...

  11. 47 CFR 15.117 - TV broadcast receivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false TV broadcast receivers. 15.117 Section 15.117... TV broadcast receivers. (a) All TV broadcast receivers shipped in interstate commerce or imported... receivers also includes devices, such as TV interface devices and set-top devices that are intended...

  12. Exposures to acidic aerosols.

    PubMed

    Spengler, J D; Keeler, G J; Koutrakis, P; Ryan, P B; Raizenne, M; Franklin, C A

    1989-02-01

    Ambient monitoring of acid aerosols in four U.S. cities and in a rural region of southern Ontario clearly show distinct periods of strong acidity. Measurements made in Kingston, TN, and Steubenville, OH, resulted in 24-hr H+ ion concentrations exceeding 100 nmole/m3 more than 10 times during summer months. Periods of elevated acidic aerosols occur less frequently in winter months. The H+ determined during episodic conditions in southern Ontario indicates that respiratory tract deposition can exceed the effects level reported in clinical studies. Observed 12-hr H+ concentrations exceeded 550 nmole/m3 (approximately 27 micrograms/m3 H2SO4). The maximum estimated 1-hr concentration exceeded 1500 nmole/m3 for H+ ions. At these concentrations, an active child might receive more than 2000 nmole of H+ ion in 12 hr and in excess of 900 nmole during the hour when H2SO4 exceeded 50 micrograms/m3.

  13. Integrated Submm Wave Receiver: Development and Applications

    NASA Astrophysics Data System (ADS)

    Koshelets, Valery P.; Birk, Manfred; Boersma, Dick; Dercksen, Johannes; Dmitriev, Pavel; Ermakov, Andrey B.; Filippenko, Lyudmila V.; Golstein, Hans; Hoogeveen, Ruud W. M.; de Jong, Leo; Khudchenko, Andrey V.; Kinev, Nickolay V.; Kiselev, Oleg S.; Kudryashov, Pavel V.; Van Kuik, Bart; de Lange, Arno; de Lange, Gert; L. Lapitsky, Irina; I. Pripolzin, Sergey; van Rantwijk, Joris; Selig, Avri M.; Sobolev, Alexander S.; Torgashin, Mikhail Yu; Vaks, Vladimir L.; de Vries, Ed; Wagner, Georg; Yagoubov, Pavel A.

    A superconducting integrated receiver (SIR) comprises in a single chip a planar antenna combined with a superconductor-insulator-superconductor (SIS) mixer, a superconducting Flux Flow Oscillator (FFO) acting as a Local Oscillator (LO) and a second SIS harmonic mixer (HM) for the FFO phase locking. In this report, an overview of the SIR and FFO developments and optimizations is presented. Improving on the fully Nb-based SIR we have developed and studied Nb-AlN-NbN circuits, which exhibit an extended operation frequency range. Continuous tuning of the phase locked frequency has been experimentally demonstrated at any frequency in the range 350-750 GHz. The FFO free-running linewidth has been measured between 1 and 5 MHz, which allows to phase lock up to 97% of the emitted FFO power. The output power of the FFO is sufficient to pump the matched SIS mixer. Therefore, it is concluded that the Nb-AlN-NbN FFOs are mature enough for practical applications.These achievements enabled the development of a 480-650 GHz integrated receiver for the atmospheric-research instrument TErahertz and submillimeter LImb Sounder (TELIS). This balloon-borne instrument is a three-channel superconducting heterodyne spectrometer for the detection of spectral emission lines of stratospheric trace gases that have their rotational transitions at THz frequencies. One of the channels is based on the SIR technology. We demonstrate for the first time the capabilities of the SIR technology for heterodyne spectroscopy in general, and atmospheric limb sounding in particular. We also show that the application of SIR technology is not limited to laboratory environments, but that it is well suited for remote operation under harsh environmental conditions. Light weight and low power consumption combined with broadband operation and nearly quantum limited sensitivity make the SIR a perfect candidate for future airborne and space-borne missions. The noise temperature of the SIR was measured to be as low as

  14. Animal choruses emerge from receiver psychology

    PubMed Central

    Greenfield, Michael D.; Esquer-Garrigos, Yareli; Streiff, Réjane; Party, Virginie

    2016-01-01

    Synchrony and alternation in large animal choruses are often viewed as adaptations by which cooperating males increase their attractiveness to females or evade predators. Alternatively, these seemingly composed productions may simply emerge by default from the receiver psychology of mate choice. This second, emergent property hypothesis has been inferred from findings that females in various acoustic species ignore male calls that follow a neighbor’s by a brief interval, that males often adjust the timing of their call rhythm and reduce the incidence of ineffective, following calls, and from simulations modeling the collective outcome of male adjustments. However, the purported connection between male song timing and female preference has never been tested experimentally, and the emergent property hypothesis has remained speculative. Studying a distinctive katydid species genetically structured as isolated populations, we conducted a comparative phylogenetic analysis of the correlation between male call timing and female preference. We report that across 17 sampled populations male adjustments match the interval over which females prefer leading calls; moreover, this correlation holds after correction for phylogenetic signal. Our study is the first demonstration that male adjustments coevolved with female preferences and thereby confirms the critical link in the emergent property model of chorus evolution. PMID:27670673

  15. Social Interactions Receive Priority to Conscious Perception.

    PubMed

    Su, Junzhu; van Boxtel, Jeroen J A; Lu, Hongjing

    2016-01-01

    Humans are social animals, constantly engaged with other people. The importance of social thought and action is hard to overstate. However, is social information so important that it actually determines which stimuli are promoted to conscious experience and which stimuli are suppressed as invisible? To address this question, we used a binocular rivalry paradigm, in which the two eyes receive different action stimuli. In two experiments we measured the conscious percept of rival actions and found that actions engaged in social interactions are granted preferential access to visual awareness over non-interactive actions. Lastly, an attentional task that presumably engaged the mentalizing system enhanced the priority assigned to social interactions in reaching conscious perception. We also found a positive correlation between human identification of interactive activity and the promotion of socially-relevant information to visual awareness. The present findings suggest that the visual system amplifies socially-relevant sensory information and actively promotes it to consciousness, thereby facilitating inferences about social interactions. PMID:27509028

  16. Harrison Receives 2006 William Gilbert Award

    NASA Astrophysics Data System (ADS)

    McEnroe, Suzanne A.; Harrison, Richard J.

    2007-04-01

    Richard J. Harrison received the William Gilbert Award at the 2006 AGU Fall Meeting. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets. This year the Gilbert Award is given to an outstanding young scientist under the age of 35. Richard Harrison easily fulfills the first criterion and just makes the second. He is now 34. As I reviewed Richard's accomplishments, I was once again impressed with his scope and level of research. He has 50 papers published, or in press, and all of them are of the same high scientific caliber. Many of you know Richard's cutting-edge research with electron holography showing magnetic interactions across magnetite-ulvospinel intergrowths, and are familiar with his groundbreaking research on lamellar magnetism. His TEM observations, combined with extensive Monte Carlo simulations of atomic interactions in hematite-ilmenite interfaces, which took both electrostatic and magnetic interactions into consideration, have developed the idea of contact layers as a magnetic substructure of defect moments at the interfaces. This was followed by work that showed that contact layers reduce charge imbalance at the interfaces.

  17. Social Interactions Receive Priority to Conscious Perception

    PubMed Central

    Su, Junzhu; van Boxtel, Jeroen J. A.; Lu, Hongjing

    2016-01-01

    Humans are social animals, constantly engaged with other people. The importance of social thought and action is hard to overstate. However, is social information so important that it actually determines which stimuli are promoted to conscious experience and which stimuli are suppressed as invisible? To address this question, we used a binocular rivalry paradigm, in which the two eyes receive different action stimuli. In two experiments we measured the conscious percept of rival actions and found that actions engaged in social interactions are granted preferential access to visual awareness over non-interactive actions. Lastly, an attentional task that presumably engaged the mentalizing system enhanced the priority assigned to social interactions in reaching conscious perception. We also found a positive correlation between human identification of interactive activity and the promotion of socially-relevant information to visual awareness. The present findings suggest that the visual system amplifies socially-relevant sensory information and actively promotes it to consciousness, thereby facilitating inferences about social interactions. PMID:27509028

  18. Dish stirling solar receiver combustor test program

    NASA Technical Reports Server (NTRS)

    Bankston, C. P.; Back, L. H.

    1981-01-01

    The operational and energy transfer characteristics of the Dish Stirling Solar Receiver (DSSR) combustor/heat exchanger system was evaluated. The DSSR is designed to operate with fossil fuel augmentation utilizing a swirl combustor and cross flow heat exchanger consisting of a single row of 4 closely spaced tubes that are curved into a conical shape. The performance of the combustor/heat exchanger system without a Stirling engine was studied over a range of operating conditions and output levels using water as the working fluid. Results show that the combustor may be started under cold conditions, controlled safety, and operated at a constant air/fuel ratio (10 percent excess air) over the required range of firing rates. Furthermore, nondimensional heat transfer coefficients based on total heat transfer are plotted versus Reynolds number and compared with literature data taken for single rows of closely spaced tubes perpendicular to cross flow. The data show enhanced heat transfer for the present geometry and test conditions. Analysis of the results shows that the present system meets specified thermal requirements, thus verifying the feasibility of the DSSR combustor design for final prototype fabrication.

  19. 41 CFR 302-6.16 - May I receive a TQSE allowance if I am receiving another subsistence expenses allowance?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false May I receive a TQSE allowance if I am receiving another subsistence expenses allowance? 302-6.16 Section 302-6.16 Public... SUBSISTENCE EXPENSES General Rules § 302-6.16 May I receive a TQSE allowance if I am receiving...

  20. Aminocaproic Acid

    MedlinePlus

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...