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Sample records for analog som230 pasireotide

  1. Effect of SOM230 (pasireotide) on corticotropic cells: action in dogs with Cushing's disease.

    PubMed

    Castillo, Victor; Theodoropoulou, Marily; Stalla, Johanna; Gallelli, Maria Florencia; Cabrera-Blatter, Maria Fernanda; Haedo, Mariana R; Labeur, Marta; Schmid, Herbert A; Stalla, Günter K; Arzt, Eduardo

    2011-01-01

    SOM230 (pasireotide) is a multiligand somatostatin (SRIF) analog able to bind to somatostatin receptor (SSTR) subtypes 1, 2, 3 and 5, and trigger antisecretory and antiproliferative signaling cascades. Canines have become in vivo models to test the pharmacological treatment of corticotropinomas because they frequently develop Cushing's disease in a spontaneous manner, due to adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Different levels of expression of SSTR2 and SSTR5 have been shown in both mouse AtT20 cells and canine tumoral corticotropinoma cells. The objective of this study was to evaluate whether SOM230 controls both tumor cell growth and hormone synthesis, therefore controlling the disease. SOM230 was tested in dogs suffering from Cushing's disease (10 animals were treated continuously during 6 months, and another 10 were treated with 3 cycles consisting of 2 months of treatment followed by a 2-month rest period). A significant decrease in ACTH, urinary cortisol creatinine ratio, adenoma size (magnetic nuclear resonance) and improvement of clinical signs were obtained, without side effects. AtT20 cells treated with SOM230 suppressed pro-opiomelanocortin (POMC) promoter activity through SSTR2, via the G(i) α-subunit, and reduced Nur77/Nurr1 transcriptional activity. We conclude that SOM230, in addition to its well-described antisecretory effects, inhibits, as shown in AtT20 cells, ACTH synthesis at the POMC transcriptional level, an effect mediated mainly through SSTR2, and limits tumor growth. The controlled Cushing's disease in the dogs that received the treatment indicates that SOM230 has a potential therapeutic use in humans suffering from Cushing's disease. Copyright © 2011 S. Karger AG, Basel.

  2. Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma

    PubMed Central

    Norden, Andrew D.; Ligon, Keith L.; Hammond, Samantha N.; Muzikansky, Alona; Reardon, David A.; Kaley, Thomas J.; Batchelor, Tracy T.; Plotkin, Scott R.; Raizer, Jeffrey J.; Wong, Eric T.; Drappatz, Jan; Lesser, Glenn J.; Haidar, Sam; Beroukhim, Rameen; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Gaffey, Sarah C.; Gerard, Mary; Smith, Katrina H.; McCluskey, Christine; Phuphanich, Surasak

    2015-01-01

    Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Results: Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8–20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12–43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor–1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. Classification of evidence: This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months. PMID:25527270

  3. Absence of somatostatin SST(2) receptor internalization in vivo after intravenous SOM230 application in the AR42J animal tumor model.

    PubMed

    Waser, Beatrice; Cescato, Renzo; Tamma, Maria-Luisa; Maecke, Helmut R; Reubi, Jean Claude

    2010-10-10

    Among clinically relevant somatostatin functions, agonist-induced somatostatin receptor subtype 2 (sst(2)) internalization is a potent mechanism for tumor targeting with sst(2) affine radioligands such as octreotide. Since, as opposed to octreotide, the second generation multi-somatostatin analog SOM230 (pasireotide) exhibits strong functional selectivity, it appeared of interest to evaluate its ability to affect sst(2) internalization in vivo. Rats bearing AR42J tumors endogenously expressing somatostatin sst(2) receptors were injected intravenously with SOM230 or with the [Tyr(3), Thr(8)]-octreotide (TATE) analog; they were euthanized at various time points; tumors and pancreas were analyzed by immunohistochemistry for the cellular localization of somatostatin sst(2) receptors. SOM230-induced sst(2) internalization was also evaluated in vitro by immunofluorescence microscopy in AR42J cells. At difference to the efficient in vivo sst(2) internalization triggered by intravenous [Tyr(3), Thr(8)]-octreotide, intravenous SOM230 did not elicit sst(2) internalization: immunohistochemically stained sst(2) in AR42J tumor cells and pancreatic cells were detectable at the cell surface at 2.5min, 10min, 1h, 6h, or 24h after SOM230 injection while sst(2) were found intracellularly after [Tyr(3), Thr(8)]-octreotide injection. The inability of stimulating sst(2) internalization by SOM230 was confirmed in vitro in AR42J cells by immunofluorescence microscopy. Furthermore, SOM230 was unable to antagonize agonist-induced sst(2) internalization, neither in vivo, nor in vitro. Therefore, SOM230 does not induce sst(2) internalization in vivo or in vitro in AR42J cells and pancreas, at difference to octreotide derivatives with comparable sst(2) binding affinities. These characteristics may point towards different tumor targeting but also to different desensitization properties of clinically applied SOM230. Copyright 2010 Elsevier B.V. All rights reserved.

  4. Osilodrostat (LCI699), a potent 11β-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats

    SciTech Connect

    Li, Li; Vashisht, Kapil; Boisclair, Julie; Li, Wenkui; Lin, Tsu-han; Schmid, Herbert A.; Kluwe, William; Schoenfeld, Heidi; Hoffmann, Peter

    2015-08-01

    The somatostatin analog pasireotide and the 11β-hydroxylase inhibitor osilodrostat (LCI699) reduce cortisol levels by distinct mechanisms of action. There exists a scientific rationale to investigate the clinical efficacy of these two agents in combination. This manuscript reports the results of a toxicology study in rats, evaluating different doses of osilodrostat and pasireotide alone and in combination. Sixty male and 60 female rats were randomized into single-sex groups to receive daily doses of pasireotide (0.3 mg/kg/day, subcutaneously), osilodrostat (20 mg/kg/day, orally), osilodrostat/pasireotide in combination (low dose, 1.5/0.03 mg/kg/day; mid-dose, 5/0.1 mg/kg/day; or high dose, 20/0.3 mg/kg/day), or vehicle for 13 weeks. Mean body-weight gains from baseline to Week 13 were significantly lower in the pasireotide-alone and combined-treatment groups compared to controls, and were significantly higher in female rats receiving osilodrostat monotherapy. Osilodrostat and pasireotide monotherapies were associated with significant changes in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone was associated with adrenocortical hypertrophy and hepatocellular hypertrophy. In combination, osilodrostat/pasireotide did not exacerbate any target organ changes and ameliorated the liver and adrenal gland changes observed with monotherapy. C{sub max} and AUC{sub 0–24h} of osilodrostat and pasireotide increased in an approximately dose-proportional manner. In conclusion, the pasireotide and osilodrostat combination did not exacerbate changes in target organ weight or toxicity compared with either monotherapy, and had an acceptable safety profile; addition of pasireotide to the osilodrostat regimen may attenuate potential adrenal gland hyperactivation and hepatocellular hypertrophy, which are potential side effects of osilodrostat monotherapy. - Highlights: • We examined the target organ toxicity of SOM230

  5. Inhibitory effects of SOM230 on adrenocorticotropic hormone production and corticotroph tumor cell proliferation in vitro and in vivo.

    PubMed

    Murasawa, Shingo; Kageyama, Kazunori; Sugiyama, Aya; Ishigame, Noriko; Niioka, Kanako; Suda, Toshihiro; Daimon, Makoto

    2014-08-25

    Adrenocorticotropic hormone (ACTH) production by pituitary corticotroph adenomas is the main cause of Cushing's disease. A drug that targets pituitary ACTH-secreting adenomas would aid treatment of Cushing's disease. Octreotide, a somatostatin receptor type 2 (SSTR2)-preferring somatostatin analogue, has no effect on ACTH secretion in patients with Cushing's disease. The multiligand SOM230 (pasireotide) displays a much higher affinity for SSTR1 and SSTR5 than octreotide and suppresses ACTH secretion in cultures of human corticotroph tumors to a greater extent than octreotide. In the present in vitro and in vivo study, we determined the effect of SOM230 on ACTH production and cell proliferation of AtT-20 corticotroph tumor cells. SOM230 decreased proopiomelanocortin (POMC) mRNA levels in AtT-20 cells and ACTH levels in the culture medium of these cells, suggesting that SOM230 suppresses ACTH synthesis and secretion in corticotroph tumor cells. SOM230 also decreased cell proliferation and both cyclic adenosine monophosphate response element-binding protein and Akt phosphorylation in AtT-20 cells. SSTR5 knockdown inhibited the SOM230-induced decreases in cell proliferation. Fluorescence-activated cell sorting analyses revealed that SOM230 did not attenuate cell cycle progression. Tumor weight in mice xenografted with AtT-20 cells and treated with SOM230 was significantly lower than in AtT-20-xenografted control mice. SOM230 also significantly decreased plasma ACTH levels, and POMC and pituitary tumor transforming gene mRNA levels in the tumor cells. Thus, SOM230 inhibits ACTH production and corticotroph tumor cell proliferation in vitro and in vivo.

  6. A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome.

    PubMed

    Deloose, E; Bisschops, R; Holvoet, L; Arts, J; De Wulf, D; Caenepeel, P; Lannoo, M; Vanuytsel, T; Andrews, C; Tack, J

    2014-06-01

    Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and delayed hypoglycemia (HG). Treatment is based on dietary measures and somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing (OGTT), abdominal ultrasound, and dumping symptom severity score (DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 μg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying (GE) were obtained. Baseline OGTT was pathological in all patients based on PR (n = 5), HT (n = 1) or HG (n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. Pasireotide affects pathophysiological features of both early and late dumping syndrome. © 2014 John Wiley & Sons Ltd.

  7. Preclinical evaluation of Som230 as a radiation mitigator in a mouse model: postexposure time window and mechanisms of action.

    PubMed

    Fu, Qiang; Berbée, Maaike; Wang, Wenze; Boerma, Marjan; Wang, Junru; Schmid, Herbert A; Hauer-Jensen, Martin

    2011-06-01

    The somatostatin analog SOM230 has potent radioprophylactic and radiation mitigating properties that are unrelated to cytoprotection but appear to be due to suppression of secretion of pancreatic enzymes into the intestinal lumen. To determine the maximal postirradiation time window for administration, male CD2F1 mice were exposed to 8.5-11 Gy total-body radiation; SOM230 (0.5, 2 or 5 mg/kg) or vehicle was given by twice daily subcutaneous injections for 14 days, beginning 24-72 h after irradiation, and 30-day animal survival was recorded. The contribution of the gut to systemic cytokine levels was estimated by analyzing plasma samples obtained simultaneously from the portal vein and carotid artery. The effect of SOM230 on cell trypsin secretion was assessed in vitro and intestinal proteolytic activity was measured in vivo. SOM230 was associated with a 40-60% absolute improvement in overall postirradiation survival when treatment was started 48 h after irradiation and even exhibited a statistically significant survival benefit when started at 72 h. SOM230 ameliorated the radiation-induced decrease in chemokine (C-X-C motif) ligand 9 (CXCL9). SOM230 inhibited pancreatic acinar cell trypsin secretion in vitro in a dose-dependent fashion and reduced intraluminal and intestinal tissue proteolytic activity in vivo. SOM230 is an excellent radiation mitigator with a postirradiation time window in excess of 48 h. The mechanism likely involves preservation of intestinal barrier function due to decreased secretion of pancreatic enzymes into the bowel lumen.

  8. Clinical review: Current scientific rationale for the use of somatostatin analogs and mTOR inhibitors in neuroendocrine tumor therapy.

    PubMed

    Bousquet, Corinne; Lasfargues, Charline; Chalabi, Mounira; Billah, Siham Moatassim; Susini, Christiane; Vezzosi, Delphine; Caron, Philippe; Pyronnet, Stéphane

    2012-03-01

    Among the innovative molecules used to manage neuroendocrine tumors, there is growing interest in combining the somatostatin analogs octreotide or pasireotide (SOM230) and everolimus (RAD001), an inhibitor that targets the protein kinase mammalian target of rapamycin (mTOR). The aims of this review were to describe the signaling pathways targeted independently by somatostatin analogs and everolimus and to summarize the scientific rationale for the potential additive or synergistic antitumor effects of combined therapy. The somatostatin analogs (octreotide and lanreotide) have potent inhibitory effects on hypersecretion, thereby alleviating the symptoms associated with neuroendocrine tumors. Furthermore, the antitumor potential of octreotide is now well documented. Pasireotide, a somatostatin analog, has the advantage of targeting a wider range of somatostatin receptors (subtypes 1, 2, 3, and 5) than the analogs previously used in clinical practice (which preferentially target subtype 2) and thus has a broader spectrum of activity. Everolimus is a rapamycin analog that inhibits mTOR, but it is more soluble than rapamycin and can be administered orally. mTOR is a protein kinase involved in many signaling pathways, primarily those initiated by tyrosine kinase receptors. Sustained mTOR activity leads to the induction of cell growth, proliferation, and cell survival. Everolimus therefore has obvious potential in cancer therapy. The combination of somatostatin analogs and everolimus in therapeutic trials offers a promising treatment option for neuroendocrine tumors.

  9. Pituitary-directed medical therapy with pasireotide for a corticotroph macroadenoma: pituitary volume reduction and literature review.

    PubMed

    Shimon, Ilan; Rot, Liat; Inbar, Edna

    2012-12-01

    Hypercortisolism due to an ACTH-secreting pituitary adenoma (Cushing's disease) is a chronic condition associated with high morbidity and mortality if inadequately managed. Pasireotide is a multireceptor-targeted somatostatin analogue and is the only approved medical therapy for Cushing's disease that treats the underlying cause of the disorder. This paper reviews the available literature for medical-therapy-induced adenoma volume reduction in patients with Cushing's disease and reports the experience of a 53-year-old surgically, radiologically and medically naïve (de novo) female with a pituitary macroadenoma who declined surgery. This patient was treated with pasireotide as first-line therapy as part of the largest randomized Phase III study evaluating a medical therapy in patients with Cushing's disease (SOM230B2305 trial). Subcutaneous pasireotide significantly decreased tumor volume, suppressed cortisol secretion, and improved clinical signs and symptoms of Cushing's disease in this patient. Based on this experience, first-line pasireotide has the potential to achieve substantial tumor volume reduction in addition to significant improvements in cortisol levels and signs and symptoms in patients with Cushing's disease for whom surgery is not an option.

  10. Somatostatin analog octreotide LAR in gastro-entero-pancreatic tumors.

    PubMed

    Oberg, Kjell

    2009-05-01

    Neuroendocrine tumors (NETs) are considered to be rare but, during the last two decades, their incidence and prevalence has considerably increased in gastro-entero-pancreatic (GEP) NETs. Most GEP-NETs express somatostatin receptors, which could be targets for treatment. The development of somatostatin analogs for treatment of functioning NETs was a revolution in the treatment of these patients and is still a cornerstone for managing hormone-related clinical symptoms. Furthermore, somatostatin analogs have also demonstrated an anti-tumor effect, with stabilization of tumor growth over long periods of time. The development of a long-acting formulation of octreotide long-acting release (LAR) significantly improved the quality of life for patients with functioning NETs in terms of necessitating only monthly injections. The side effects are few and easily manageable. In the future, somatostatin analogs will continue to be a major treatment option for functioning NETs, but will be combined with other biologicals, such as a-interferons, mTOR inhibitors and VEGF inhibitors. A new multireceptor somatostatin analog, SOM230 (pasireotide), as well as chimeric molecules, such as dopastatin (a combination of a somatostatin analogue plus a dopamine agonist), will come into the clinical management of GEP-NETs.

  11. Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.

    PubMed

    Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

    2014-06-15

    Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis.

  12. Managing hyperglycemia in patients with Cushing's disease treated with pasireotide: medical expert recommendations.

    PubMed

    Colao, Annamaria; De Block, Christophe; Gaztambide, Maria Sonia; Kumar, Sudhesh; Seufert, Jochen; Casanueva, Felipe F

    2014-04-01

    To recommend an approach to monitoring and treating hyperglycemia in pasireotide-treated patients with Cushing's disease, a severe clinical condition caused by a pituitary adenoma hypersecreting adrenocorticotropic hormone. Advisory Board meeting of ten European experts in pituitary disease and diabetes mellitus in Munich, Germany, on February 23, 2012, to obtain expert recommendations. Cushing's disease presents a number of management challenges. Pasireotide, a novel agent for the treatment of Cushing's disease with proven biochemical and clinical efficacy, improves outcomes and expands treatment options. Clinical trials have shown that the pasireotide adverse event profile is similar to that of other somatostatin analogs, except for a higher frequency of hyperglycemia. Mechanistic studies in healthy volunteers suggest that pasireotide-associated hyperglycemia is due to reduced secretion of glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide, and insulin; however, it is associated with intact postprandial glucagon secretion. Individual patients' results demonstrate effective hyperglycemia management by following standard guidelines for the treatment of diabetes mellitus with individual adaptation to the specific underlying pathophysiology, i.e., preferential use of GLP-1 based-medications. Patients on pasireotide treatment should be monitored for changes in glucose metabolism and hyperglycemia. Diabetes mellitus should be managed by initiation of medical therapy with metformin and staged treatment intensification with a dipeptidyl peptidase-4 inhibitor, with a switch to a GLP-1 receptor agonist and initiation of insulin, as required, to achieve and maintain glycemic control. Further research into hyperglycemia following pasireotide treatment will help refine the optimal strategy in Cushing's disease.

  13. Pasireotide for the treatment of acromegaly.

    PubMed

    Wildemberg, Luiz Eduardo; Gadelha, Mônica R

    2016-01-01

    Acromegaly is a chronic disease with high morbidity and enhanced mortality if left untreated. Treatment options include surgery, medical therapy (somatostatin analogues (SA), dopamine agonists (DA) and growth hormone receptor antagonists) and radiotherapy. Despite these treatment options, "real-life" studies have shown that approximately 50% of patients are not controlled. In this scenario, a next-generation SA, pasireotide, has recently been approved for the treatment of acromegaly. 1) pasireotide's pharmacokinetics and pharmacodynamics; 2) pasireotide's anti-secretory and anti-proliferative effects, from preclinical studies up to phase III clinical trials; and 3) the adverse effects of pasireotide, focusing on hyperglycemia; 4) biomarkers of response to SA treatment. surgery is the primary treatment for most patients with acromegaly; however, approximately half of them will need adjuvant therapy. At present, the decision of this adjuvant treatment is made on a "trial-and-error" fashion. Nevertheless, in recent years, efforts have been made to establish biomarkers for the response to drugs involved in the treatment of acromegaly, which will change the treatment of acromegaly towards a more personalized therapeutic decision-making process. In the near future, the establishment of pasireotide response biomarkers will allow us to identify good candidates for first-line medical monotherapy with pasireotide.

  14. Expression of somatostatin receptors in human melanoma cell lines: effect of two different somatostatin analogues, octreotide and SOM230, on cell proliferation.

    PubMed

    Martinez-Alonso, M; Llecha, N; Mayorga, M E; Sorolla, A; Dolcet, X; Sanmartin, V; Abal, L; Casanova, J M; Baradad, M; Yeramian, A; Egido, R; Puig, S; Vilella, R; Matias-Guiu, X; Marti, R M

    2009-01-01

    Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.

  15. The role of an acute pasireotide suppression test in predicting response to treatment in patients with Cushing's disease: findings from a pilot study.

    PubMed

    Trementino, L; Zilio, M; Marcelli, G; Michetti, G; Barbot, M; Ceccato, F; Boscaro, M; Scaroni, C; Arnaldi, G

    2015-09-01

    Pasireotide is a multireceptor-targeted somatostatin analog effective in the treatment of Cushing's disease (CD). We evaluate the value of an acute pasireotide suppression test (PST) in predicting response to medium/long-term treatment in CD. Nineteen patients with active CD were prospectively investigated at two referral centers from May 2013 to August 2014. Follow-up data (median 6 months; range 1-9 months) were available for sixteen patients. All patients received at 09:00 h a single subcutaneous (sc) injection of 600 μg pasireotide. Serum cortisol and plasma ACTH were assessed before, and every 2 h for 8 h after, drug administration. Late-night salivary cortisol (LNSC) was assessed before and after pasireotide administration. After acute PST, all patients were continued on pasireotide 600 μg sc twice a day. During PST, cortisol and ACTH levels quickly decreased in all patients except one with a mean percentage fall, respectively, of 48.9 ± 24.3 and 48.1 ± 25.4 % compared to baseline. LNSC decreased in about 82 % of patients (14/17) achieving a normalization in five of them. Pasireotide treatment was associated with a normalization of 24-h urinary-free cortisol at last follow-up in about 68 % of patients. A fall >27 % of LNSC during PST calculated by ROC curve was the best parameter in predicting a positive response to treatment with pasireotide (sensitivity 91 %; specificity 100 %; positive predictive value 100 %; negative predictive value 75 %). Acute PST may be useful to identify CD patients who will benefit from pasireotide treatment. A LNSC fall >27 % as well as a LNSC normalization during PST is associated with a probability of 100 % of achieving a favorable response to pasireotide treatment in the medium/long term.

  16. Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

    PubMed

    Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P

    2016-11-01

    Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca(2+) signaling ([Ca(2+)]i), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca(2+)]i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca(2+)]i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

  17. Medical Therapy with Pasireotide in Recurrent Cushing’s Disease: Experience of Patients Treated for At Least 1 Year at a Single Center

    PubMed Central

    Yedinak, Chris G.; Hopkins, Sarah; Williams, Jessica; Ibrahim, Aly; Cetas, Justin Schultz; Fleseriu, Maria

    2017-01-01

    Subcutaneous (SC) injection of pasireotide, a somatostatin analog, is approved for the treatment of adults with Cushing’s disease (CD) for whom pituitary surgery was unsuccessful or is not an option. We highlight the symptomatic and biochemical improvement of six patients with recurrent CD treated with pasireotide SC at a single center for at least 1 year. Patients were treated either through commercial use (n = 5) or through the Phase 3 trial (n = 1; http://ClinicalTrials.gov identifier, NCT00434148; study number, B2305). Most patients (n = 5) were female, and the mean age at diagnosis was 35.8 years. All patients demonstrated biochemical control at 1 year of treatment. Three of the five real-world patients followed for more than 1 year remain on pasireotide SC and are controlled. Two patients discontinued pasireotide SC; one patient because of persistently elevated urinary-free cortisol levels and gallstones, and the other because of treatment for an unrelated brain tumor. Symptomatic improvement varied, but all patients demonstrated weight loss. Nausea and mild, transient injection-site reactions were the most frequently reported adverse events. Although glycated hemoglobin (HbA1c) increased after treatment initiation, four of five patients maintained HbA1c levels ≤7.0% while receiving pasireotide SC and concomitant individualized diabetes medication, if necessary. In patients who discontinued pasireotide SC, HbA1c levels decreased within 6 weeks. This report documents real-world use of pasireotide SC and indicates its effectiveness as a long-term treatment option for patients with CD. Although hyperglycemia was observed in most patients, it was managed with appropriate monitoring and treatment and was reversible upon discontinuation of pasireotide SC. PMID:28289402

  18. Medical Therapy with Pasireotide in Recurrent Cushing's Disease: Experience of Patients Treated for At Least 1 Year at a Single Center.

    PubMed

    Yedinak, Chris G; Hopkins, Sarah; Williams, Jessica; Ibrahim, Aly; Cetas, Justin Schultz; Fleseriu, Maria

    2017-01-01

    Subcutaneous (SC) injection of pasireotide, a somatostatin analog, is approved for the treatment of adults with Cushing's disease (CD) for whom pituitary surgery was unsuccessful or is not an option. We highlight the symptomatic and biochemical improvement of six patients with recurrent CD treated with pasireotide SC at a single center for at least 1 year. Patients were treated either through commercial use (n = 5) or through the Phase 3 trial (n = 1; http://ClinicalTrials.gov identifier, NCT00434148; study number, B2305). Most patients (n = 5) were female, and the mean age at diagnosis was 35.8 years. All patients demonstrated biochemical control at 1 year of treatment. Three of the five real-world patients followed for more than 1 year remain on pasireotide SC and are controlled. Two patients discontinued pasireotide SC; one patient because of persistently elevated urinary-free cortisol levels and gallstones, and the other because of treatment for an unrelated brain tumor. Symptomatic improvement varied, but all patients demonstrated weight loss. Nausea and mild, transient injection-site reactions were the most frequently reported adverse events. Although glycated hemoglobin (HbA1c) increased after treatment initiation, four of five patients maintained HbA1c levels ≤7.0% while receiving pasireotide SC and concomitant individualized diabetes medication, if necessary. In patients who discontinued pasireotide SC, HbA1c levels decreased within 6 weeks. This report documents real-world use of pasireotide SC and indicates its effectiveness as a long-term treatment option for patients with CD. Although hyperglycemia was observed in most patients, it was managed with appropriate monitoring and treatment and was reversible upon discontinuation of pasireotide SC.

  19. Clinical use of pasireotide for Cushing’s disease in adults

    PubMed Central

    Ceccato, Filippo; Scaroni, Carla; Boscaro, Marco

    2015-01-01

    Cushing’s disease Excessive corticotroph hormone levels sustained by an adrenocorticotropic hormone-secreting pituitary adenoma lead to a severe clinical condition caused by excess cortisol secretion, called Cushing’s disease (CD). Neurosurgery and radiotherapy are used to treat the pituitary adenoma directly, but new medical treatments targeting the corticotroph cells have recently become available. Pasireotide This is a novel multireceptor ligand somatostatin (SST) analog with a high binding affinity for SST receptor 5, the predominant receptor in human corticotroph adenomas that is not downregulated by high cortisol levels (as SST receptor 2 is). Pasireotide has been recently approved by the European Medical Agency and the US Food and Drug Administration for treating adults with CD with recurrent hypercortisolism after surgery, or for whom surgery is not an option. A dose of 600–1,200 μg twice a day can normalize urinary free cortisol levels after 3 months of treatment in up to 28% of patients, reducing their blood pressure and improving their weight, lipid profile, and quality of life. Combining pasireotide with cabergoline to achieve a greater hormone response can normalize cortisol secretion in 50% of patients, and adding ketoconazole induces biochemical control in most patients with CD. Safety and hyperglycemia The adverse effects of pasireotide are similar to those of other SST analogs, including diarrhea, nausea, and biliary sludge or gallstones. Hyperglycemia is common during pasireotide treatment, which affects the secretion of pancreatic insulin and intestinal glucagon-like peptide 1. Self-monitoring is essential to achieve good metabolic control, and endocrinologists should first administer metformin if insulin resistance is evident and then add dipeptidyl peptidase 4 inhibitors/glucagon-like peptide 1 receptor agonists or insulin. Conclusion In recent years, medical treatment with pasireotide has been proposed as monotherapy for adults with CD

  20. Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures.

    PubMed

    Mohamed, Amira; Blanchard, Marie-Pierre; Albertelli, Manuela; Barbieri, Federica; Brue, Thierry; Niccoli, Patricia; Delpero, Jean-Robert; Monges, Genevieve; Garcia, Stephane; Ferone, Diego; Florio, Tullio; Enjalbert, Alain; Moutardier, Vincent; Schonbrunn, Agnes; Gerard, Corinne; Barlier, Anne; Saveanu, Alexandru

    2014-10-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) raise difficult therapeutic problems despite the emergence of targeted therapies. Somatostatin analogs (SSA) remain pivotal therapeutic drugs. However, the tachyphylaxis and the limited antitumoral effects observed with the classical somatostatin 2 (sst2) agonists (octreotide and lanreotide) led to the development of new SSA, such as the pan sst receptor agonist pasireotide. Our aim was to compare the effects of pasireotide and octreotide on cell survival, chromogranin A (CgA) secretion, and sst2 phosphorylation/trafficking in pancreatic NET (pNET) primary cells from 15 tumors. We established and characterized the primary cultures of human pancreatic tumors (pNETs) as powerful preclinical models for understanding the biological effects of SSA. At clinically relevant concentrations (1-10 nM), pasireotide was at least as efficient as octreotide in inhibiting CgA secretion and cell viability through caspase-dependent apoptosis during short treatments, irrespective of the expression levels of the different sst receptors or the WHO grade of the parental tumor. Interestingly, unlike octreotide, which induces a rapid and persistent partial internalization of sst2 associated with its phosphorylation on Ser341/343, pasireotide did not phosphorylate sst2 and induced a rapid and transient internalization of the receptor followed by a persistent recycling at the cell surface. These results provide the first evidence, to our knowledge, of striking differences in the dynamics of sst2 trafficking in pNET cells treated with the two SSAs, but with similar efficiency in the control of CgA secretion and cell viability.

  1. Pasireotide: a review of its use in Cushing's disease.

    PubMed

    McKeage, Kate

    2013-05-01

    Pasireotide (Signifor(®)) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of corticotropin from the pituitary adenoma in patients with Cushing's disease. Pasireotide has a receptor binding profile that is distinct from that of other somatostatin analogues, binding with high affinity to somatostatin receptor subtype 5, which is strongly over expressed in corticotroph adenoma cells. Pasireotide is the first pituitary-directed agent to be approved for use in Cushing's disease. In a phase III clinical trial in patients with Cushing's disease, twice-daily pasireotide 600 or 900 μg for 6 months led to normalization of urinary free cortisol (UFC) levels in up to a quarter of all patients (primary endpoint) and significantly reduced mean UFC levels. The reduction in UFC levels is rapid (within one to two months) and sustained (up to 24 months). Most patients who do not have an early response to pasireotide do not respond at a later time point. Decreases in UFC levels achieved during pasireotide treatment are accompanied by decreases in serum and salivary cortisol levels, as well as improvements in clinical signs and symptoms, including body weight, blood pressure and health-related quality-of-life. Pasireotide has a generally similar tolerability profile to that of other somatostatin analogues, but is associated with a relatively high incidence of hyperglycaemia, requiring the addition or intensification of glucose-lowering medication in a substantial proportion of patients. Thus, pasireotide, together with on-going patient monitoring, provides a promising new option for the medical management of Cushing's disease.

  2. Successful Medical Treatment of Adult Nesidioblastosis With Pasireotide over 3 Years

    PubMed Central

    Schwetz, Verena; Horvath, Karl; Kump, Patrizia; Lackner, Carolin; Perren, Aurel; Forrer, Flavio; Pieber, Thomas R.; Treiber, Gerlies; Sourij, Harald; Mader, Julia K.

    2016-01-01

    Abstract Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce. In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed. The histopathologic examination revealed beta cell hyperplasia and microadenomas expressing glucagon. After surgery, the patient was free of symptoms for 6 months, after which hypoglycemic episodes recurred. After unsuccessful treatment with corticosteroids and somatostatin analogs, treatment with pasireotide, a novel somatostatin analog with high affinity to somatostatin receptor 5 and a possible side effect of hyperglycemia, was initiated (0.6 mg BID). To date, our patient has been free of severe hypoglycemic episodes ever since. Yearly repeated imaging procedures have shown no abnormities over the last 3 years. We report for the first time that pasireotide was successfully used in the treatment of adult nesidioblastosis. PMID:27057885

  3. Medical treatment of Cushing's disease: somatostatin analogues and pasireotide.

    PubMed

    Pedroncelli, Alberto M

    2010-01-01

    Cushing's disease is Cushing's syndrome caused by an adrenocorticotropic hormone-secreting pituitary adenoma and, in the absence of adequate treatment, can be fatal. Cushing's disease represents an unmet medical need, with no approved medical therapies. Pasireotide is a novel multi-receptor-targeted somatostatin analogue with high affinity for sst(1,2,3) and sst(5). Compared with octreotide, pasireotide has an in vitro binding affinity 40-, 30- and 5-fold higher for sst(5,) sst(1) and sst(3), respectively, and 2-fold lower for sst(2). Adrenocorticotropic hormone-secreting pituitary adenomas predominantly express sst(5), followed by sst(2) and sst(1), suggesting that pasireotide may be effective in the treatment of Cushing's disease. In a 15-day phase II trial of pasireotide 600 μg s.c. b.i.d. in patients with de novo or persistent/recurrent Cushing's disease, 22 of 29 patients (76%) achieved reduced urinary free cortisol (UFC) levels, 5 of whom (17%) achieved normalized UFC. Patients who achieved normalized UFC had a significantly greater reduction in serum cortisol than those who did not (p = 0.04), and minimum pasireotide plasma concentrations appeared to be higher in responders. Based on these results, a randomized, double-blind phase III study comparing pasireotide 600 μg b.i.d. and 900 μg b.i.d. was initiated and is ongoing. This is the largest ever phase III study in patients with Cushing's disease. The primary end point of this study is normalization of UFC after 6 months of treatment. Finally, preliminary results from a study on 17 patients with Cushing's disease suggest that the combined use of pasireotide, cabergoline and low-dose ketoconazole may have additive beneficial effects in the medical treatment of Cushing's disease. Copyright © 2010 S. Karger AG, Basel.

  4. Pasireotide: a novel treatment for patients with acromegaly.

    PubMed

    Cuevas-Ramos, Daniel; Fleseriu, Maria

    2016-01-01

    Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be

  5. Pasireotide: a novel treatment for patients with acromegaly

    PubMed Central

    Cuevas-Ramos, Daniel; Fleseriu, Maria

    2016-01-01

    Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%–70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%–90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to

  6. Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study.

    PubMed

    Fleseriu, Maria; Rusch, Elisha; Geer, Eliza B

    2017-01-01

    Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected. Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication. Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.

  7. Effect of verapamil on the pharmacokinetics of pasireotide in healthy volunteers.

    PubMed

    Kornberger, Ruediger; Ting, Lillian S L; Tripathi, Anadya P; Rodrigues, Heidi; Nesheiwat, Dalal; Passos, Vanessa Q; Hu, Ke

    2014-11-01

    We evaluated the drug-drug interaction between pasireotide SC and verapamil, a known P-glycoprotein inhibitor. Subjects received pasireotide SC (single dose, 600 μg) on day 1, and samples for pharmacokinetics evaluation were collected from days 1 to 8. Subjects received an oral dose of verapamil 240 mg/d for 10 days (days 15-24). On day 18, subjects also received pasireotide SC 600 μg. Pharmacokinetic sampling for pasireotide SC and verapamil was done during days 18 to 25 and days 15 to 21, respectively. Safety evaluations were performed throughout the study period, including a 30-day post-treatment follow-up. Pharmacokinetic profiles of pasireotide SC alone and in combination with verapamil sustained-release (SR) were superimposable with the geometric mean ratios (90% confidence interval [CI]) of 0.98 (0.91-1.06) for C(max), 0.97 (0.90-1.04) for AUC(last), and 0.98 (0.92-1.05) for AUC(inf). Exploratory analyses showed a 17% (90% CI, 0.72-0.94) reduction in C(trough) and 31% (0.58-0.82) reduction in C(max) (8 hours post-dose) for verapamil SR with pasireotide SC versus verapamil alone. Pasireotide SC with or without verapamil was well tolerated. In conclusion, there was no change in the rate of pasireotide absorption and elimination or extent of exposure following concomitant administration with verapamil.

  8. Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly.

    PubMed

    Silverstein, Julie M

    2016-10-01

    Cushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia. Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed. The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3-67.0 %) than in patients with CD treated with pasireotide SC (68.4-73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791-799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875-884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320-326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914-924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues. Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly

  9. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center.

    PubMed

    Ceccato, Filippo; Lombardi, Giuseppe; Manara, Renzo; Emanuelli, Enzo; Denaro, Luca; Milanese, Laura; Gardiman, Marina Paola; Bertorelle, Roberta; Scanarini, Massimo; D'Avella, Domenico; Occhi, Gianluca; Boscaro, Marco; Zagonel, Vittorina; Scaroni, Carla

    2015-03-01

    Aggressive pituitary adenomas (PAs) are clinically challenging for endocrinologists and neurosurgeons due to their locally invasive nature and resistance to standard treatment (surgery, medical or radiotherapy). Two pituitary-directed drugs have recently been proposed: temozolomide (TMZ) for aggressive PA, and pasireotide for ACTH-secreting PA. We describe the experience of our multidisciplinary team of endocrinologists, neurosurgeons, neuroradiologists, oncologists, otolaryngologists and pathologists with TMZ and pasireotide treatment for aggressive PAs in terms of their radiological shrinkage and genetic features. We considered five patients with aggressive PA, three of them non-secreting (two ACTH-silent and one becoming ACTH secreting), and two secreting (one GH and one ACTH). TMZ was administrated orally at 150-200 mg/m(2) daily for 5 days every 28 days to all 5 patients, and 2 of them also received pasireotide 600-900 µg bid sc. We assessed the MRI at the baseline and during TMZ or pasireotide treatment. We also checked for MGMT promoter methylation and IDH, BRAF and kRAS mutations. Considering TMZ, two patients showed PA progression, one stable disease and two achieved radiological and clinical response. Pasireotide was effective in reducing hypercortisolism and mass volume, combined with TMZ in one case. Both treatments were generally well tolerated; one patient developed a grade 2 TMZ-induced thrombocytopenia. None of patients developed hypopituitarism while taking TMZ or pasireotide treatment. No genetic anomalies were identified in the adenoma tissue. TMZ and pasireotide may be important therapies for aggressive PA, alone or in combination.

  10. Cost-effectiveness comparison of prophylactic octreotide and pasireotide for prevention of fistula after pancreatic surgery.

    PubMed

    Welsch, Thilo; Müssle, Benjamin; Distler, Marius; Knoth, Holger; Weitz, Jürgen; Häckl, Dennis

    2016-11-01

    Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis. A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration. Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide. Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

  11. Loss of Efficacy of Pasireotide After its Re-Administration: is There a Reason Why?

    PubMed Central

    Mandanas, Stylianos; Mathiopoulou, Lemonia; Boudina, Maria; Chrisoulidou, Alexandra

    2016-01-01

    Pasireotide is a recently approved medical treatment for persistent or recurrent Cushing’s disease (CD). However, an escape from the initial successful response has not yet been described. A 42-year-old female presented with several symptoms indicative of hypercortisolism. Biochemical evaluation and imaging were consistent with CD due to a pituitary adenoma. Surgical excision of the adenoma was unsuccessful and gamma-knife radiosurgery was followed. Our patient remained hypercortisolemic thus treatment with pasireotide (900 mg subcutaneously twice daily) was decided. Biochemical and clinical remission was noted shortly thereafter. Moderate adverse events led to dose reduction to 600 mg subcutaneously twice daily. The patient remained in remission for 6 months, when treatment was discontinued due to cholecystitis. One month after cholecystectomy, pasireotide was restarted with no clinical or biochemical benefit that time. Pasireotide is an effective medical treatment for CD. Nevertheless, a loss of its initial efficacy may rarely be described. PMID:28191290

  12. Pasireotide for the Prevention of Pancreatic Fistula Following Pancreaticoduodenectomy: A Cost-effectiveness Analysis.

    PubMed

    Goyert, Nik; Eeson, Gareth; Kagedan, Daniel J; Behman, Ramy; Lemke, Madeline; Hallet, Julie; Mittmann, Nicole; Law, Calvin; Karanicolas, Paul J; Coburn, Natalie G

    2017-01-01

    To determine the cost-effectiveness of perioperative administration of pasireotide for reduction of pancreatic fistula (PF). PF is a major complication following pancreaticoduodenectomy (PD), associated with significant morbidity and healthcare-related costs. Pasireotide is a novel multireceptor ligand somatostatin analogue, which has been demonstrated to reduce the incidence of PF following pancreas resection; however, the drug cost is significant. This study sought to estimate the cost-effectiveness of routine administration of pasireotide to patients undergoing PD, compared with no intervention from the perspective of the hospital system. A decision-analytic model was developed to compare costs for perioperative administration of pasireotide versus no pasireotide. The model was populated using an institutional database containing all PDs performed 2002 to 2012 at a single institution, including data regarding clinically significant PF (International Study Group on Pancreatic Fistula Grade B or C) and hospital-related inpatient costs for 90 days following PD, converted to 2014 $USD. Relative risk of PF associated with pasireotide was estimated from the published literature. Deterministic and probabilistic sensitivity analyses were performed to test robustness of the model. Mean institutional cost of index admissions was $67,417 and $31,950 for patients with and without PF, respectively. Pasireotide was the dominant strategy, associated with savings of $1685, and a mean reduction of 1.5 days length of stay. Univariate sensitivity analyses demonstrated cost-savings down to a PF rate of 5.6%, up to a relative risk of PF of 0.775, and up to a drug cost of $2817. Probabilistic sensitivity analysis showed 79% of simulations were cost saving. Pasireotide appears to be a cost-saving treatment following PD across a wide variation of clinical and cost scenarios.

  13. Effectiveness of low-dose pasireotide in a patient with Cushing’s disease: antiproliferative effect and predictivity of a short pasireotide suppression test

    PubMed Central

    Grossrubatscher, Erika; Zampetti, Benedetta; Dalino Ciaramella, Paolo; Doneda, Paola; Loli, Paola

    2015-01-01

    Key Clinical Message This case shows efficacy of low-dose pasireotide in biochemical and clinical control of severe hypercortisolism and in tumor volume reduction in a patient with an ACTH-secreting macroadenoma. The drug may be an option for long-term treatment in some patients where control of tumor mass is an important clinical endpoint. PMID:26331021

  14. Effectiveness of low-dose pasireotide in a patient with Cushing's disease: antiproliferative effect and predictivity of a short pasireotide suppression test.

    PubMed

    Grossrubatscher, Erika; Zampetti, Benedetta; Dalino Ciaramella, Paolo; Doneda, Paola; Loli, Paola

    2015-08-01

    This case shows efficacy of low-dose pasireotide in biochemical and clinical control of severe hypercortisolism and in tumor volume reduction in a patient with an ACTH-secreting macroadenoma. The drug may be an option for long-term treatment in some patients where control of tumor mass is an important clinical endpoint.

  15. Pasireotide and mifepristone: new options in the medical management of Cushing's disease.

    PubMed

    Cohan, Pejman

    2014-01-01

    To review and evaluate medical therapies for Cushing's disease (CD), with an emphasis on recent clinical trial experience with pasireotide and mifepristone, and to discuss the therapeutic potential and appropriate selection of these compounds in this patient population. Recently published Phase III trial data for each compound are reviewed and assessed, and relative benefits and risks are examined and compared where possible. Mifepristone and pasireotide are both potentially beneficial for CD patients but have greatly dissimilar mechanisms of action and adverse event (AE) profiles. Pasireotide acts at the level of the pituitary adenoma, reducing cortisol levels through inhibition of adrenocorticotropic hormone (ACTH) release. However, pasireotide reduces insulin secretion and incretin hormone response and is associated with significant risk for new or worsening hyperglycemia. Mifepristone ameliorates the signs and symptoms of hypercortisolemia via glucocorticoid receptor (GR2) blockade, but this approach raises serum cortisol levels and increases risk for adrenal insufficiency (AI), hypokalemia, and endometrial thickening. While response to pasireotide can be monitored via measurements of serum, urine, or late-night salivary cortisol, evaluation of response to mifepristone is solely based on changes in clinical parameters (e.g., hyperglycemia, hypertension, body weight/composition). Management of persistent CD is challenging, and the decision to initiate medical treatment hinges on many factors. Pasireotide may be a more attractive option for most patients due to its action at the underlying tumor and the ability to monitor biochemical responses. However, mifepristone may be more appropriate when it is necessary to avoid or minimize risk for hyperglycemia-related complications.

  16. Budget impact of pasireotide LAR for the treatment of acromegaly, a rare endocrine disorder.

    PubMed

    Zhang, J J; Nellesen, D; Ludlam, W H; Neary, M P

    2016-01-01

    Acromegaly is a rare disorder characterized by the over-production of growth hormone (GH). Patients often experience a range of chronic comorbidities including hypertension, cardiac dysfunction, diabetes, osteoarthropathy, and obstructive sleep apnea. Untreated or inadequately controlled patients incur substantial healthcare costs, while normalization of GH levels may reduce morbidity and mortality rates to be comparable to the general population. To assess the 3-year budget impact of pasireotide LAR on a US managed care health plan following pasireotide LAR availability. Two separate economic models were developed: one from the perspective of an entire health plan and another from the perspective of a pharmacy budget. The total budget impact model includes costs of drug therapies and other costs for treatment, monitoring, management of adverse events, and comorbidities. The pharmacy cost calculator only considers drug costs. The total estimated budget impact associated with the introduction of pasireotide LAR is 0.31 cents ($0.0031) per member per month (PMPM) in the first year, 0.78 cents ($0.0078) in the second year, and 1.42 cents ($0.0142) in the third year following FDA approval. Costs were similar or lower from a pharmacy budget impact perspective. For each patient achieving disease control, cost savings from reduced comorbidities amounted to $10,240 per year. Published data on comorbidities for acromegaly are limited. In the absence of data on acromegaly-related costs for some comorbidities, comorbidity costs for the general population were used (may be under-estimates). The budget impact of pasireotide LAR is expected to be modest, with an expected increase of 1.42 cents PMPM on the total health plan budget in the third year after FDA approval. The efficacy of pasireotide LAR in acromegaly, as demonstrated in head-to-head trials compared with currently available treatment options, is expected to be associated with a reduction of the prevalence of

  17. Budget impact of pasireotide for the treatment of Cushing's disease, a rare endocrine disorder associated with considerable comorbidities.

    PubMed

    Truong, H L; Nellesen, D; Ludlam, W H; Neary, M P

    2014-04-01

    Cushing's disease (CD) is a rare condition with a prevalence of roughly 39 cases per million in the general population. Healthcare costs are substantial for CD patients with either untreated or inadequately controlled disease. This study assesses the 3-year budget impact of pasireotide on a US managed care health plan following pasireotide (Signifor) availability. Two scenarios were evaluated to understand the differences in costs associated with the introduction of pasireotide. The first scenario evaluates the budget impact of pasireotide from the perspective of an entire health plan (total budget impact) and the second from the perspective of the pharmacy budget (pharmacy budget impact). Both scenarios evaluate the annual incremental budget impact with and without pasireotide. Scenario 1 includes costs for medical procedures, drug therapies, monitoring, surgical complications, comorbidities for patients with controlled or uncontrolled CD, and adverse events. Procedures include transsphenoidal surgery, bilateral adrenalectomy, radiotherapy and radiosurgery. Drugs include pasireotide (indicated for CD), mifepristone (indicated to control hyperglycemia secondary to hypercortisolism in patients with Cushing's syndrome) as well as several off-label treatments (ketoconazole, cabergoline, mitotane). Scenario 2 considers costs solely from the perspective of a health plan pharmacy. Costs are in $2013. The estimated total budget impact is $0.0115 per-member per-month (PMPM) in the first year following FDA approval, $0.0184 in the second year, and $0.0194 in the third year. Introduction of pasireotide is expected to increase the pharmacy budget by $0.0257 PMPM in the first year, $0.0363 in the second year, and $0.0360 in the third year. Model inputs rely on the small body of literature available for Cushing's disease. Cushing's disease is severe disease with debilitating comorbidities and substantial healthcare costs when untreated or inadequately controlled. The inclusion

  18. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial.

    PubMed

    Gadelha, Mônica R; Bronstein, Marcello D; Brue, Thierry; Coculescu, Mihail; Fleseriu, Maria; Guitelman, Mirtha; Pronin, Vyacheslav; Raverot, Gérald; Shimon, Ilan; Lievre, Kayo Kodama; Fleck, Juergen; Aout, Mounir; Pedroncelli, Alberto M; Colao, Annamaria

    2014-11-01

    Many patients with acromegaly do not achieve biochemical control despite receiving high doses of the first-generation somatostatin analogues octreotide or lanreotide. In the PAOLA trial, we aimed to assess the efficacy and safety of two different doses of the somatostatin analogue pasireotide long-acting release compared with active control (octreotide or lanreotide) in patients with inadequately controlled acromegaly. In a multicentre, randomised, phase 3 trial, we enrolled eligible patients aged 18 years or older with acromegaly who were inadequately controlled (5-point, 2 h mean growth hormone concentration >2·5 μg/L and insulin-like growth factor 1 [IGF-1] concentration >1·3 times the upper normal limit) and had received 30 mg octreotide long-acting repeatable or 120 mg lanreotide (Somatuline Autogel; Ipsen, UK) as monotherapy for 6 months or longer. We randomly assigned patients in a 1:1:1 ratio with an interactive voice-web response system to receive 40 mg pasireotide long-acting release once every 28 days for 24 weeks, 60 mg pasireotide long-acting release once every 28 days for 24 weeks, or continued treatment with octreotide or lanreotide (active control). Patients were stratified according to previous treatment (octreotide or lanreotide) and growth hormone concentrations at screening (2·5-10 μg/L and >10 μg/L). Patients and study investigators were not masked to study drug assignment but were masked to pasireotide dose allocation. The primary endpoint was number of patients achieving biochemical control, defined as mean growth hormone concentration less than 2·5 μg/L and normalised IGF-1 concentration. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01137682. Between Dec 17, 2010, and Aug 6, 2012, 198 patients were enrolled and randomly assigned to pasireotide 40 mg (n=65), pasireotide 60 mg (n=65), or active control (n=68) groups. At 24 weeks, ten (15%) patients in the pasireotide 40

  19. FGFR4 polymorphic alleles modulate mitochondrial respiration: A novel target for somatostatin analog action in pituitary tumors.

    PubMed

    Ezzat, Shereen; Wang, Ri; Pintilie, Melania; Asa, Sylvia L

    2017-01-10

    We reported that a single nucleotide polymorphism (SNP) at codon 388 of the fibroblast growth factor receptor 4 (FGFR4-Gly388Arg) can result in distinct proteins that alter pituitary cell growth and function. Here, we examined the differential properties of the available therapeutic somatostatin analogs, octreotide and pasireotide, in pituitary tumor cells expressing the different FGFR4 isoforms. Consistent with their enhanced growth properties, FGFR4-R388-expressing cells show higher mitochondrial STAT3 serine phosphorylation driving basal and maximal oxygen consumption rate (OCR) than pituitary cells expressing the more common FGFR4-G388 isoform. While both somatostatin analogs reduce the OCR in FGFR4-G388 cells, pasireotide was more effective in decreasing OCR in cells expressing the variant FGFR4-R388 isoform. Down-regulation of somatostatin receptor 5 (SSTR5) abrogated the effect of pasireotide, demonstrating its involvement in mediating this action. The effects on OCR were recapitulated by introducing a constitutively active serine STAT3 but not by a tyrosine-active mutant. Moreover, pharmacologic inhibition demonstrated the role for the phosphatase PP2A in mediating the dephosphorylation of STAT3-S727 by pasireotide. Our data indicate that FGFR4 polymorphic isoforms mediate signaling that yields mitochondrial therapeutic targets of relevance to the actions of different somatostatin analogs.

  20. FGFR4 polymorphic alleles modulate mitochondrial respiration: A novel target for somatostatin analog action in pituitary tumors

    PubMed Central

    Ezzat, Shereen; Wang, Ri; Pintilie, Melania; Asa, Sylvia L

    2017-01-01

    We reported that a single nucleotide polymorphism (SNP) at codon 388 of the fibroblast growth factor receptor 4 (FGFR4-Gly388Arg) can result in distinct proteins that alter pituitary cell growth and function. Here, we examined the differential properties of the available therapeutic somatostatin analogs, octreotide and pasireotide, in pituitary tumor cells expressing the different FGFR4 isoforms. Consistent with their enhanced growth properties, FGFR4-R388-expressing cells show higher mitochondrial STAT3 serine phosphorylation driving basal and maximal oxygen consumption rate (OCR) than pituitary cells expressing the more common FGFR4-G388 isoform. While both somatostatin analogs reduce the OCR in FGFR4-G388 cells, pasireotide was more effective in decreasing OCR in cells expressing the variant FGFR4-R388 isoform. Down-regulation of somatostatin receptor 5 (SSTR5) abrogated the effect of pasireotide, demonstrating its involvement in mediating this action. The effects on OCR were recapitulated by introducing a constitutively active serine STAT3 but not by a tyrosine-active mutant. Moreover, pharmacologic inhibition demonstrated the role for the phosphatase PP2A in mediating the dephosphorylation of STAT3-S727 by pasireotide. Our data indicate that FGFR4 polymorphic isoforms mediate signaling that yields mitochondrial therapeutic targets of relevance to the actions of different somatostatin analogs. PMID:27966451

  1. Management of hyperglycaemia in Cushing's disease: experts' proposals on the use of pasireotide.

    PubMed

    Reznik, Y; Bertherat, J; Borson-Chazot, F; Brue, T; Chanson, P; Cortet-Rudelli, C; Delemer, B; Tabarin, A; Bisot-Locard, S; Vergès, B

    2013-02-01

    Cushing's disease causes considerable morbidity and mortality, including cardiovascular, metabolic, respiratory and psychiatric complications, bone demineralization and increased susceptibility to infections. Metabolic complications include a high prevalence of impaired glucose tolerance, fasting hyperglycaemia and diabetes. Although pituitary surgery is the gold-standard treatment, other treatment strategies such as radiotherapy and medical therapy to reduce cortisol synthesis may be proposed in the event of recurrence or failure, or when surgery is not an option. Bilateral adrenalectomy can also be considered. One of the medical treatments used in Cushing's disease is the somatostatin analogue pasireotide, which acts on adrenocorticotropic hormone (ACTH) secretion by the pituitary. Its efficacy in reducing urinary free cortisol, plasma cortisol and ACTH, and in improving the clinical signs of the disease has been demonstrated. Its observed adverse effects are similar to the known effects of first-generation somatostatin analogues, although disturbances of carbohydrate metabolism are more frequent and more severe with pasireotide. The aim of the present review was to summarize the epidemiology and pathophysiology of the disturbances of glucose metabolism that arise in Cushing's disease, and to propose recommendations for detecting and monitoring glucose abnormalities and for managing pasireotide-induced hyperglycaemia. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Effect of AP102, a subtype 2 and 5 specific somatostatin analog, on glucose metabolism in rats.

    PubMed

    Tarasco, Erika; Seebeck, Petra; Pfundstein, Svende; Daly, Adrian F; Eugster, Philippe J; Harris, Alan G; Grouzmann, Eric; Lutz, Thomas A; Boyle, Christina N

    2017-08-18

    Somatostatin analogs are widely used to treat conditions associated with hormonal hypersecretion such as acromegaly and metastatic neuroendocrine tumors. First generation somatostatin analogs, such as octreotide and lanreotide, have high affinity for somatostatin receptor subtype 2 (SSTR2), but have incomplete efficacy in many patients. Pasireotide targets multiple SSTRs, having the highest affinity for SSTR5, but causes hyperglycemia and diabetes mellitus in preclinical and clinical studies. AP102 is a new somatostatin analogs with high affinity at both SSTR2 and SSTR5. We aimed to characterize the effects of AP102 vs. pasireotide on random and dynamic glucose levels, glucoregulatory hormone concentrations and growth axis measures in healthy Sprague-Dawley rats. Three doses of each compound were evaluated under acute conditions (1, 10, and 30 µg/kg s.c.), and two doses during a chronic (4-week) infusion (3 and 10 µg/kg/h s.c.). Neither acute nor chronic AP102 administration altered blood glucose concentrations or dynamic responses following an intraperitoneal glucose tolerance test. In contrast, acute and chronic pasireotide dosing increased random and post-intraperitoneal glucose tolerance test blood glucose measures, compared to vehicle-treated controls. Both AP102 and pasireotide acutely suppressed growth hormone levels, although insulin-like growth factor-1 and somatic growth was suppressed to a greater extent with pasireotide. AP102 is a new dual SSTR2/SSTR5-specific somatostatin analog that acutely reduces growth hormone but does not cause hyperglycemia during acute or chronic administration in a healthy rat model. Further studies in diabetic animals and in humans are necessary to determine the potential utility of AP102 in the clinical setting.

  3. Structural determinants of agonist-selective signaling at the sst(2A) somatostatin receptor.

    PubMed

    Nagel, Falko; Doll, Christian; Pöll, Florian; Kliewer, Andrea; Schröder, Helmut; Schulz, Stefan

    2011-05-01

    The clinically used somatostatin (SS-14) analogs octreotide and pasireotide (SOM230) stimulate distinct species-specific patterns of sst(2A) somatostatin receptor phosphorylation and internalization. Like SS-14, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues, namely S341, S343, T353, T354, T356, and T359, which in turn leads to a robust endocytosis of both rat and human sst(2A) receptors. Unlike SS-14, pasireotide fails to induce any substantial phosphorylation or internalization of the rat sst(2A) receptor. Nevertheless, pasireotide is able to stimulate a selective phosphorylation of S341 and S343 of the human sst(2A) receptor followed by a clearly detectable receptor sequestration. Here, we show that transplantation of amino acids 1-180 of the human sst(2A) receptor to the rat sst(2A) receptor facilitates pasireotide-induced internalization. Conversely, construction of a rat-human sst(2A) chimera conferred resistance to pasireotide-induced internalization. We then created a series of site-directed mutants leading to the identification of amino acids 27, 30, 163, and 164 that when exchanged to their human counterparts facilitated pasireotide-driven S341/S343 phosphorylation and internalization of the rat sst(2A) receptor. Exchange of these amino acids to their rat counterparts completely blocked the pasireotide-mediated internalization of the human sst(2A) receptor. Notably, octreotide and SS-14 stimulated a full phosphorylation and internalization of all mutant sst(2A) receptors tested. Together, these findings suggest that pasireotide activates the sst(2A) receptor via a molecular switch that is structurally and functionally distinct from that turned on during octreotide-driven sst(2A) activation.

  4. Effects of subcutaneous pasireotide on cardiac repolarization in healthy volunteers: A single-center, phase I, randomized, four-way crossover study

    PubMed Central

    Breitschaft, Astrid; Hu, Ke; Darstein, Christelle; Ligueros-Saylan, Monica; Jordaan, Pierre; Song, Dongweon; Hudson, Michelle; Shah, Rashmi

    2014-01-01

    The aim of this study was to evaluate the effects of subcutaneous pasireotide on cardiac repolarization in healthy volunteers. Healthy volunteers were randomized to one of four treatment sequences (n = 112) involving four successive treatments in different order: pasireotide 600 µg (therapeutic dose) or 1,950 µg (maximum tolerated dose) bid by subcutaneous injection (sc), placebo injection and oral moxifloxacin. Maximum ΔΔQTcI occurred 2 hours post-dose for both doses of pasireotide. Mean ΔΔQTcI was 13.2 milliseconds (90% CI: 11.4, 15.0) and 16.1 milliseconds (90% CI: 14.3, 17.9) for the 600 and 1,950 µg bid doses, respectively. Maximal placebo-subtracted change in QTcI from baseline for moxifloxacin was 11.1 (90% CI: 9.3, 12.9) milliseconds. Both pasireotide doses caused a reduction in heart rate: maximal heart rate change compared with placebo occurred at 1 hour for pasireotide 600 µg bid and at 0.5 hours for pasireotide 1,950 µg bid, with heart rate reductions of 10.4 and 14.9 bpm, respectively. At the therapeutic dose of 600 µg, pasireotide has a modest QT-prolonging effect. The relatively small increase of ∼3 milliseconds in ΔΔQTcI in the presence of a 3.25-fold increase in dose suggests a relatively flat dose–effect relationship of pasireotide on ΔΔQTcI in healthy volunteers. No safety concerns for pasireotide were identified during the study. PMID:24242903

  5. Extended treatment of Cushing's disease with pasireotide: results from a 2-year, Phase II study.

    PubMed

    Boscaro, M; Bertherat, J; Findling, J; Fleseriu, M; Atkinson, A B; Petersenn, S; Schopohl, J; Snyder, P; Hughes, G; Trovato, A; Hu, K; Maldonado, M; Biller, B M K

    2014-08-01

    In a previous 15-day, Phase II study of patients with de novo or persistent/recurrent Cushing's disease (core study), treatment with pasireotide 600 μg sc bid reduced urinary free cortisol (UFC) levels in 76% of patients and normalized UFC in 17%. The objective of this study was to evaluate the efficacy and safety of extended treatment with pasireotide. This was a planned, open-ended, single-arm, multicenter extension study (primary endpoint: 6 months). Patients aged ≥18 years with Cushing's disease who completed the core study could enter the extension if they achieved UFC normalization at core study end and/or obtained significant clinical benefit. Of the 38 patients who completed the core study, 19 entered the extension and 18 were included in the efficacy analyses (three responders, 11 reducers, four non-reducers in the core study). At data cut-off, median treatment duration in the extension was 9.7 months (range: 2 months to 4.8 years). At extension month 6, 56% of the 18 patients had lower UFC than at core baseline and 22% had normalized UFC. Of the four patients who remained on study drug at month 24, one had normalized UFC. Reductions in serum cortisol, plasma adrenocorticotropic hormone, body weight and diastolic blood pressure were observed. The most common adverse events were mild-to-moderate gastrointestinal disorders and hyperglycemia. Pasireotide offers a tumor-directed medical therapy that may be effective for the extended treatment of some patients with Cushing's disease.

  6. Somatostatin receptor imaging-guided pasireotide therapy in medullary thyroid cancer with ectopic adrenocorticotropin production.

    PubMed

    Verburg, Frederik A; Anlauf, Martin; Mottaghy, Felix M; Karges, Wolfram

    2015-01-01

    A 51-year-old man with a history of metastatic medullary thyroid cancer (MTC) presented with high adrenocorticotropin (ACTH) and urinary free cortisol levels. The diagnosis of ectopic ACTH production, a rare MTC complication, was established in this patient. PET/CT using the somatostatin analogue DOTA-(Tyr)-octreotate labeled with gallium (Ga-DOTATATE) was performed, showing positive radionuclide uptake in multiple MTC metastases. After this therapy with the novel somatostatin analogue, pasireotide was initiated after which urinary free cortisol and ACTH levels decreased. The present case thus illustrates a potential theranostic use of Ga-DOTATATE PET/CT in MTC.

  7. A 12-month phase 3 study of pasireotide in Cushing's disease.

    PubMed

    Colao, Annamaria; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Schoenherr, Ulrike; Mills, David; Salgado, Luiz Roberto; Biller, Beverly M K

    2012-03-08

    Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg (82 patients) or 900 μg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 μg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. The significant decrease in cortisol levels in patients

  8. From bulk to plasmonic nanoparticle surfaces: the behavior of two potent therapeutic peptides, octreotide and pasireotide.

    PubMed

    Hernández, Belén; López-Tobar, Eduardo; Sanchez-Cortes, Santiago; Coïc, Yves-Marie; Baron, Bruno; Chenal, Alexandre; Kruglik, Sergei G; Pflüger, Fernando; Cohen, Régis; Ghomi, Mahmoud

    2016-09-21

    Octreotide and pasireotide are two cyclic somatostatin analogues with an important clinical use in the treatment and diagnosis of neuroendocrine tumors. Herein, by the combined use of several techniques (UV-visible absorption, fluorescence, circular dichroism, ζ-potential, transmission electron microscopy, Raman scattering, surface-enhanced Raman scattering, and quantum mechanical calculations) we have followed the structural dynamics of these analogues in the bulk, as well as their binding sites on plasmonic (gold and silver) colloids. In contrast to the previously derived conclusions, the two peptides seem to possess completely different conformational features. Octreotide, a cyclic octapeptide, is formed by a moderately flexible type-II'β-turn maintained by a deformable disulfide linkage. Pasireotide, in which the cyclic character is made possible by peptide bonds, manifests a rigid backbone formed by two oppositely placed tight turns of different types, i.e.γ-turn and type-I β-turn. Owing to their cationic character, both analogues induce aggregation of negatively charged gold and silver colloids. Nevertheless, despite their notable structural differences, both peptides bind onto gold nanoparticles through their unique d-Trp residue. In contrast, their binding to silver colloids seems to be of electrostatic nature, as formed through monodentate or bidentate ionic pairs.

  9. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues

    PubMed Central

    Wolin, Edward M; Jarzab, Barbara; Eriksson, Barbro; Walter, Thomas; Toumpanakis, Christos; Morse, Michael A; Tomassetti, Paola; Weber, Matthias M; Fogelman, David R; Ramage, John; Poon, Donald; Gadbaw, Brian; Li, Jiang; Pasieka, Janice L; Mahamat, Abakar; Swahn, Fredrik; Newell-Price, John; Mansoor, Wasat; Öberg, Kjell

    2015-01-01

    In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 – not reached) with pasireotide versus 6.8 months (5.6 – not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR. PMID:26366058

  10. Effective long-term treatment of Cushing's disease with pasireotide: a case report.

    PubMed

    Lu, Lin; Duan, Lian; Jin, Zimeng; Lu, Zhaolin; Gu, Feng

    2013-01-01

    Cushing's disease is a rare, devastating condition associated with high morbidity and increased mortality. Primary treatment for Cushing's disease is transsphenoidal surgery to remove the pituitary adenoma; however, recurrence can occur in up to 25% of patients. Second-line medical therapies do not directly target the pituitary tumor. Thus, normalization of adrenocorticotropic hormone (ACTH) and inhibition of tumor growth is not usually achieved. In this case report, we present a de novo patient with a pituitary macroadenoma who was randomized to receive treatment with subcutaneous twice-daily injections of pasireotide 900 μg as part of the double-blind, Phase III CSOM230B2305 clinical trial. Around one month after treatment initiation, the patient's urinary free cortisol (UFC) level showed a dramatic reduction (from 151.1 to 7.4 μg/24h) necessitating a dose reduction to 600 μg to relieve the symptoms of corticosteroid withdrawal. One month after dose reduction, the patient's UFC levels remained stable and were associated with improvements in clinical signs and symptoms. These improvements continued into the 12-month extension phase following a dose increase to 900 μg and were accompanied by a significant reduction in tumor volume (from 0.797 cm3 at baseline to 0.359 and 0.365 cm3 at months 18 and 24, respectively). UFC remained normalized throughout the extension period. During the study, the patient developed hyperglycemia, which was effectively controlled with diet and then medication. In this case study, long-term pasireotide treatment as first-line therapy led to normalization of UFC, reduction of tumor volume and significant improvement in the clinical signs and symptoms of Cushing's disease.

  11. Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing's disease: results from an open-ended, open-label extension trial.

    PubMed

    Schopohl, Jochen; Gu, Feng; Rubens, Robert; Van Gaal, Luc; Bertherat, Jérôme; Ligueros-Saylan, Monica; Trovato, Andrew; Hughes, Gareth; Salgado, Luiz R; Boscaro, Marco; Pivonello, Rosario

    2015-10-01

    Report the efficacy and safety of pasireotide sc in patients with Cushing's disease during an open-ended, open-label extension to a randomized, double-blind, 12-month, Phase III study. 162 patients entered the core study. 58 patients who had mean UFC ≤ ULN at month 12 or were benefiting clinically from pasireotide entered the extension. Patients received the same dose of pasireotide as at the end of the core study (300-1,200 μg bid). Dose titration was permitted according to efficacy or drug-related adverse events. 40 patients completed 24 months' treatment. Of the patients who entered the extension, 50.0% (29/58) and 34.5% (20/58) had controlled UFC (UFC ≤ ULN) at months 12 and 24, respectively. The mean percentage decrease in UFC was 57.3% (95% CI 40.7-73.9; n = 52) and 62.1% (50.8-73.5; n = 33) after 12 and 24 months' treatment, respectively. Improvements in clinical signs of Cushing's disease were sustained up to month 24. The most frequent drug-related adverse events in patients who received ≥1 dose of pasireotide (n = 162) from core baseline until the 24-month cut-off were diarrhea (55.6%), nausea (48.1%), hyperglycemia (38.9%), and cholelithiasis (31.5%). No new safety issues were identified during the extension. Reductions in mean UFC and improvements in clinical signs of Cushing's disease were maintained over 24 months of pasireotide treatment. The safety profile of pasireotide is typical for a somatostatin analogue, except for the frequency and degree of hyperglycemia; patients should be monitored for changes in glucose homeostasis. Pasireotide represents the first approved pituitary-targeted treatment for patients with Cushing's disease.

  12. Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study.

    PubMed

    Pivonello, Rosario; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Trovato, Andrew; Hughes, Gareth; Salgado, Luiz R; Lacroix, André; Schopohl, Jochen; Biller, Beverly M K

    2014-09-01

    Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Phase III study with double-blind randomization of two pasireotide doses. Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 μg bid). At month 3, patients with UFC ≤2 × ULN and not exceeding the baseline value continued their randomized dose; all others received 300 μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72·8% of patients. In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. © 2014 John Wiley & Sons Ltd.

  13. Clinical management of critically ill patients with Cushing's disease due to ACTH-secreting pituitary macroadenomas: effectiveness of presurgical treatment with pasireotide.

    PubMed

    Cannavo, S; Messina, E; Albani, A; Ferrau, F; Barresi, V; Priola, S; Esposito, F; Angileri, F

    2016-06-01

    The management of critically ill Cushing's disease (CD) patients is extremely challenging. Pasireotide is indicated for the treatment of CD patients when pituitary surgery is unfeasible or has not been curative, but no data are available about the use of this drug as pre-operative treatment in critically ill patients. We report the effects of presurgical pasireotide therapy in CD patients in whom hypercortisolism caused life-threatening hypokalemia, alkalosis, and cardio-respiratory complications precluding surgical approach. Clinical, biochemical, and radiological data of two critically ill patients with ACTH-secreting pituitary macroadenoma, before and during first-line presurgical pasireotide treatment (600 μg s.c. bid). During the first 21 days of treatment, pasireotide therapy induced a rapid, partial decrease of plasma ACTH, serum cortisol, and urinary free cortisol levels, with the consequent normalization of serum potassium concentration and arterial blood gases parameters, in both the patients. They did not experience unmanageable side effects and underwent endoscopic transsphenoidal surgery after 4 weeks of effective treatment. Pre-operative MRI evaluation did not show pituitary tumor shrinkage. Surgical cure of CD was obtained in the first patient, while debulking allowed the pharmacological control of hypercortisolism in the second case. We suggest that pasireotide can induce a rapid improvement of clinical and metabolic conditions in critically ill CD patients in whom surgical approach is considered hazardous and need to be delayed.

  14. Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

    PubMed

    Petersenn, S; Salgado, L R; Schopohl, J; Portocarrero-Ortiz, L; Arnaldi, G; Lacroix, A; Scaroni, C; Ravichandran, S; Kandra, A; Biller, B M K

    2017-07-01

    Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was -82.6% (-89.0, -41.9) and -81.8% (-89.8, -67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. This represents the longest prospective trial of a medical therapy for Cushing's disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing's disease.

  15. The treatment with pasireotide in Cushing's disease: effects of long-term treatment on tumor mass in the experience of a single center.

    PubMed

    Simeoli, Chiara; Auriemma, Renata Simona; Tortora, Fabio; De Leo, Monica; Iacuaniello, Davide; Cozzolino, Alessia; De Martino, Maria Cristina; Pivonello, Claudia; Mainolfi, Ciro Gabriele; Rossi, Riccardo; Cirillo, Sossio; Colao, Annamaria; Pivonello, Rosario

    2015-12-01

    Pasireotide is the first medical therapy officially approved for the treatment of adult patients with Cushing's disease (CD) who experienced a failure of pituitary surgery or are not candidates for surgery and require medical therapeutic intervention. The current study aimed at investigating the effects of long-term treatment with pasireotide (up to 24 months) on tumor mass in a group of patients with CD, participating to a phase III study. Fourteen CD patients entered the phase III clinical trial CSOM230B2305 at Naples Center, and eight (seven women, one man, aged 38.9 ± 17.6 years), including seven with a microadenoma and one with a macroadenoma, received treatment with pasireotide at the dose of 600-1200 µg bid for at least 6 months, and were considered for the analysis of the study. These eight patients were subjected to the evaluation of pituitary tumor volume by pituitary MRI, together with the evaluation of urinary cortisol levels, at baseline and every 6 months for the entire period of treatment. Pasireotide treatment induced full disease control in 37.5 % and partial disease control in 37.5 % after 6 months, whereas full and partial disease control after 12 months was obtained in 28.6 % and in 57.1 % of patients, respectively. A significant (>25 %) reduction in tumor volume was found in 62.5 % and in 100 % of patients, after 6 and 12 months, respectively. In particular, after 6 months, a slight tumor shrinkage (between 25.1 and 50 %) was observed in 25 %, moderate (50.1-75 %) in 25 %, and marked (>75 %) in 12.5 % of patients, whereas after 12 months, a slight tumor shrinkage was observed in 43 %, moderate in 14 %, and marked in 43 % of patients. In 25 % of patients (two patients), a marked tumor shrinkage was recorded, with tumor mass disappearance in one case; this tumor shrinkage was associated to rapid and sustained biochemical remission up to 24 months of continuous pasireotide treatment. These two cases represent the first cases with a documentation

  16. Somatostatin Agonist Pasireotide Promotes a Physiological State Resembling Short-Day Acclimation in the Photoperiodic Male Siberian Hamster (Phodopus sungorus).

    PubMed

    Dumbell, R A; Scherbarth, F; Diedrich, V; Schmid, H A; Steinlechner, S; Barrett, P

    2015-07-01

    The timing of growth in seasonal mammals is inextricably linked to food availability. This is exemplified in the Siberian hamster (Phodopus sungorus), which uses the annual cycle of photoperiod to optimally programme energy expenditure in anticipation of seasonal fluctuations in food resources. During the autumn, energy expenditure is progressively minimised by physiological adaptations, including a 30% reduction in body mass, comprising a reduction in both fat and lean tissues. However, the mechanistic basis of this adaptation is still unexplained. We hypothesised that growth hormone (GH) was a likely candidate to underpin these reversible changes in body mass. Administration of pasireotide, a long-acting somatostatin receptor agonist developed for the treatment of acromegaly, to male hamsters under a long-day (LD) photoperiod produced a body weight loss. This comprised a reduction in lean and fat mass, including kidneys, testes and brown adipose tissue, typically found in short-day (SD) housed hamsters. Furthermore, when administered to hamsters switched from SD to LD, pasireotide retarded the body weight increase compared to vehicle-treated hamsters. Pasireotide did not alter photoperiod-mediated changes in hypothalamic energy balance gene expression but altered the expression of Srif mRNA expression in the periventricular nucleus and Ghrh mRNA expression in the arcuate nucleus consistent with a reduction in GH feedback and concurrent with reduced serum insulin-like growth factor-1. Conversely, GH treatment of SD hamsters increased body mass, which included increased mass of liver and kidneys. Together, these data indicate a role for the GH axis in the determination of seasonal body mass of the Siberian hamster.

  17. Carboxyl-terminal multi-site phosphorylation regulates internalization and desensitization of the human sst2 somatostatin receptor.

    PubMed

    Lehmann, Andreas; Kliewer, Andrea; Schütz, Dagmar; Nagel, Falko; Stumm, Ralf; Schulz, Stefan

    2014-04-25

    The somatostatin receptor 2 (sst2) is the pharmacological target of somatostatin analogs that are widely used in the diagnosis and treatment of human neuroendocrine tumors. We have recently shown that the stable somatostatin analogs octreotide and pasireotide (SOM230) stimulate distinct patterns of sst2 receptor phosphorylation and internalization. Like somatostatin, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues namely S341, S343, T353, T354, T356 and T359, which in turn leads to a robust receptor endocytosis. Unlike somatostatin, pasireotide stimulates a selective phosphorylation of S341 and S343 of the human sst2 receptor followed by a partial receptor internalization. Here, we show that exchange of S341 and S343 by alanine is sufficient to block pasireotide-driven internalization, whereas mutation of T353, T354, T356 and T359 to alanine is required to strongly inhibited both octreotide- and somatostatin-induced internalization. Yet, combined mutation of T353, T354, T356 and T359 is not sufficient to prevent somatostatin-driven β-arrestin mobilization and receptor desensitization. Replacement of all fourteen carboxyl-terminal serine and threonine residues by alanine completely abrogates sst2 receptor internalization and β-arrestin mobilization in HEK293 cells. Together, our findings demonstrate for the first time that agonist-selective sst2 receptor internalization is regulated by multi-site phosphorylation of its carboxyl-terminal tail.

  18. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  19. Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

    PubMed

    Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

    2017-07-28

    A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GH<2.5μg/L and IGF-1< lower limit of normal). Reductions in the median GH and IGF-1 levels observed at month 3 were maintained up to month 12; the median percent change from baseline to month 12 in GH and IGF-1 levels were -74.71% and -59.33%, respectively. Twenty-nine patients completed the 12-month core phase, 1 withdrew consent, and 3 discontinued treatment due to adverse events (AEs; diabetes mellitus, hyperglycemia, liver function abnormality, n=1 each). Almost all patients (97%; 32/33) experienced AEs; the most common AEs were nasopharyngitis (48.5%), hyperglycemia (42.4%), diabetes mellitus (24.2%), constipation (18.2%), and hypoglycemia (15.2%). Serious AEs were reported in 7 patients with the most common being hyperglycemia (n=2). Long-acting pasireotide demonstrated clinically relevant efficacy and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

  20. Analog earthquakes

    SciTech Connect

    Hofmann, R.B.

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  1. Triptycene analogs

    NASA Technical Reports Server (NTRS)

    Hua, Duy (Inventor); Perchellet, Jean-Pierre (Inventor)

    2004-01-01

    This invention provides analogs of triptycene which are useful as anticancer drugs, as well as for other uses. The potency of these compounds is in a similar magnitude as daunomycin, a currently used anticancer drug. Each compound of the invention produces one or more desired effects (blocking nucleoside transport, inhibiting nucleic acid or protein syntheses, decreasing the proliferation and viability of cancer cells, inducing DNA fragmentation or retaining their effectiveness against multidrug-resistant tumor cells).

  2. Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.

    PubMed

    Findling, James W; Fleseriu, Maria; Newell-Price, John; Petersenn, Stephan; Pivonello, Rosario; Kandra, Albert; Pedroncelli, Alberto M; Biller, Beverly M K

    2016-11-01

    Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements. Of 162 enrolled patients, baseline LNSC was measured in 93. Sixty-seven patients had levels above the upper limit of normal (ULN); median baseline levels were 19.7 and 20.7 nmol/L in the groups subsequently randomized to 600 μg (n = 40) and 900 μg (n = 27), respectively. Median LNSC levels decreased from baseline to month 12; median changes in patients who had baseline LNSC > ULN in the 600 and 900 μg groups were -13.4 nmol/L (-52.6 %; n = 19) and -11.8 nmol/L (-56.1 %; n = 14), respectively. LNSC normalized at months 6 and 12 in 25/67 (37.3 %) and 13/67 (19.4 %) patients, respectively; 10/25 and 8/13 patients also had normalized UFC, and 7/25 and 4/13 had partial UFC control (UFC > ULN and ≥50 % decrease from baseline). There was a moderate correlation (r = 0.55) on the log scale between individual patient LNSC and UFC values when all time points were pooled. Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simple, convenient biomarker for assessing treatment response in patients with Cushing's disease.

  3. Occurrence of De Quervain's Thyroiditis after Resolution of Hypercortisolism following Pasireotide Treatment for Cushing's Disease and Surgery for an Adrenocortical Adenoma: Report of Two Cases.

    PubMed

    Efstathiadou, Zoe A; Sykja, Albana; Anagnostis, Panagiotis; Panagiotou, Athanasios; Kita, Marina

    2014-03-01

    An increased prevalence of thyroid autoimmunity has been observed after successful treatment of Cushing's syndrome. On the other hand, De Quervain's thyroiditis (DQT), in which autoimmunity is not a pathogenetic contributor, has not been reported during recovery from Cushing's syndrome. We describe 2 female patients with DQT coinciding with the resolution of hypercortisolism after treatment of Cushing's syndrome/disease. The first patient had been diagnosed with Cushing's disease due to a corticotroph pituitary microadenoma, declined neurosurgery, and was receiving pharmacological treatment with pasireotide. Her hypercortisolism was optimally controlled with a minimum dose. The second patient had undergone unilateral adrenalectomy due to a cortisol-secreting adenoma and was on tapering doses of hydrocortisone due to a suppressed corticotroph axis. Both patients presented with clinical, functional, and imaging features of DQT at a time when their endogenous glucocorticoid levels were very low. Oral glucocorticoid treatment was administered in both cases, resulting in prompt recovery. The incidence of DQT following the resolution of hypercortisolism, either medical or surgical, has not been previously described. The exact pathogenetic mechanism can only be speculated on. Perhaps the relative or absolute glucocorticoid deficiency after effective treatment of hypercortisolism alters immunologic responses and renders patients more vulnerable to thyrolytic processes.

  4. When Gesture Becomes Analogy.

    PubMed

    Cooperrider, Kensy; Goldin-Meadow, Susan

    2017-07-01

    Analogy researchers do not often examine gesture, and gesture researchers do not often borrow ideas from the study of analogy. One borrowable idea from the world of analogy is the importance of distinguishing between attributes and relations. Gentner (, ) observed that some metaphors highlight attributes and others highlight relations, and called the latter analogies. Mirroring this logic, we observe that some metaphoric gestures represent attributes and others represent relations, and propose to call the latter analogical gestures. We provide examples of such analogical gestures and show how they relate to the categories of iconic and metaphoric gestures described previously. Analogical gestures represent different types of relations and different degrees of relational complexity, and sometimes cohere into larger analogical models. Treating analogical gestures as a distinct phenomenon prompts new questions and predictions, and illustrates one way that the study of gesture and the study of analogy can be mutually informative. Copyright © 2017 Cognitive Science Society, Inc.

  5. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

    An improved subranging or comparator circuit is provided for an analog-to-digital converter. As a subranging circuit, the circuit produces a residual signal representing the difference between an analog input signal and an analog of a digital representation. This is achieved by subdividing the digital representation into two or more parts and subtracting from the analog input signal analogs of each of the individual digital portions. In another aspect of the present invention, the subranging circuit comprises two sets of differential input pairs in which the transconductance of one differential input pair is scaled relative to the transconductance of the other differential input pair. As a consequence, the same resistor string may be used for two different digital-to-analog converters of the subranging circuit.

  6. Learning by Analogy: Discriminating between Potential Analogs

    ERIC Educational Resources Information Center

    Richland, Lindsey E.; McDonough, Ian M.

    2010-01-01

    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  7. Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?

    PubMed

    Mohamed, Amira; Romano, David; Saveanu, Alexandru; Roche, Catherine; Albertelli, Manuela; Barbieri, Federica; Brue, Thierry; Niccoli, Patricia; Delpero, Jean-Robert; Garcia, Stephane; Ferone, Diego; Florio, Tullio; Moutardier, Vincent; Poizat, Flora; Barlier, Anne; Gerard, Corinne

    2017-06-20

    Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition. Combined inhibition of Akt might then improve everolimus antitumoral effect. In this regard, the somatostatin analog (SSA) octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms caused by peptide release in patients carrying functional GEP-NETs. We have recently established and characterized primary cultures of human pNETs and demonstrated the anti-proliferative effects of both octreotide and pasireotide. In this study, we aim at determining the antitumor efficacy of everolimus alone or in combination with the SSAs octreotide and pasireotide in primary cultures of pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and upregulated Akt activity in single treatment. Its anti-proliferative and anti-secretory efficacy was not improved combined with the SSAs. Both SSAs did not overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent apoptosis induced by SSAs was lost in combined treatments. These molecular events provide the first evidence supporting the lack of marked benefit in patients co-treated with everolimus and SSA.

  8. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  9. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  10. The Analogical Mind.

    ERIC Educational Resources Information Center

    Holyoak, Keith J.; Thagard, Paul

    1997-01-01

    The use of analogy in human thinking is examined from the perspective of a multiconstraint theory that postulates similarity, structure, and purpose as three kinds of constraints. The theory has been implemented in computational simulations of the analogical human mind using the Analogical Mapping by Constraint Satisfaction (ACME) model. (SLD)

  11. Analog Frame Store Memory.

    DTIC Science & Technology

    1980-01-15

    information in analog form for periods up to ten (i0)seconds. The storage element is a state-of-the-art monolithic charge coupled device (CCD) which...Analog Field Storage Device The Analog Field Storage Device is a solid state monolithic array operating on the "charge coupled" principle. It consists...the implementation of the corrective action. A three-month slip in delivery of the full system will result with integration test taking place in June

  12. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

    A nonvolatile analog memory uses pairs of ferroelectric field effect transistors (FFETs). Each pair is defined by a first FFET and a second FFET. When an analog value is to be stored in one of the pairs, the first FFET has a saturation voltage applied thereto, and the second FFET has a storage voltage applied thereto that is indicative of the analog value. The saturation and storage voltages decay over time in accordance with a known decay function that is used to recover the original analog value when the pair of FFETs is read.

  13. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  14. Analog without fear

    NASA Technical Reports Server (NTRS)

    Delagrange, A. D.

    1977-01-01

    Analog circuitry, also referred to as Linear, has been nearly run over by the digital/computer bandwagon. This is unfortunate because tremendous advances are being made in the field of analog integrated circuitry. Each year's progress raises the state-of-the-art, bringing achievements not possible even the year before. Many of the traditional prejudices against analog circuitry are no longer valid. This report attempts to summarize what is available now and what can (and can't) be done with analog integrated circuitry.

  15. Biological targeted therapies in patients with advanced enteropancreatic neuroendocrine carcinomas.

    PubMed

    Fazio, Nicola; Cinieri, Saverio; Lorizzo, Katia; Squadroni, Michela; Orlando, Laura; Spada, Francesca; Maiello, Evaristo; Bodei, Lisa; Paganelli, Giovanni; Delle Fave, Gianfranco; de Braud, Filippo

    2010-11-01

    Enteropancreatic (EP) neuroendocrine carcinomas (NECs) represent relatively rare and heterogeneous malignancies. They are the most common group among neuroendocrine tumors (NETs). In most cases they are advanced at diagnosis and slow-growing, therefore conditioning a better prognosis compared with non neuroendocrine carcinomas from the same sites. No standard medical therapy exists, except for somatostatin analogs in functioning tumors, and octreotide LAR in functioning or non functioning well differentiated NECs from small bowel. Several systemic therapeutic options exist, including chemotherapy, somatostatin analog, interferon, peptide receptor radionuclide therapy (PRRT), and molecular targeted drugs. Among them some therapies have specific biological tumor targets and can be defined as "biological targeted therapies". This review focuses on the status of EP NECs targeted therapies in the light of recent advances. Somatostatin receptors (SSTRs) are the first therapeutic target detected in EP NECs. Through them SS analogs and PRRT act, producing symptomatic, biochemical, and, to a lesser extent, antiproliferative effects. New SS analogs, covering a higher number of SSTR subtypes, were developed, including pasireotide (SOM230), which controls 25% of carcinoid syndromes resistant to full dose octreotide LAR. Chimeric analogs, which bind SSTR2/SSTR5 and dopamine-2 receptor subtype (D2), are in preclinical phase of development. Among the numerous molecular targeted agents investigated in NETs, mTOR inhibitors and VEGF/VEGFR/PDGFR inhibitors are in most advanced clinical phase of investigation. In particular, everolimus, sunitinib, and bevacizumab are all studied in phase III trials. Both everolimus and sunitinib produced significant survival benefit versus placebo in advanced progressing well-differentiated pancreatic NECs. Sunitinib data have been presented at the last ASCO in June 2010, and everolimus data will be presented at next ESMO in September 2010. Copyright

  16. Analogies for Avogadro's Number.

    ERIC Educational Resources Information Center

    Poskozim, Paul S.; And Others

    1986-01-01

    Reviews analogies used to try to capture the concept of the magnitude of Avogadro's number, including analogies related to small/tiny objects, counting, people, water, and money. Also presents several new ones which are based on modern computers and printers. (JN)

  17. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  18. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  19. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  20. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  1. Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Alexander, Patricia A.; And Others

    1987-01-01

    Experiments involving a componential approach to analogy training were conducted with 36 fourth, 34 eighth, and 96 tenth graders. Results indicate a significant positive effect on all students' verbal analogy skills and no significant effect on fourth graders' inferential skills. In-class training and reading/language arts instruction implications…

  2. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  3. Analog pulse processor

    DOEpatents

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

    A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

  4. Meat analog: a review.

    PubMed

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  5. Challenges in Using Analogies

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-11-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features.1-7 One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  6. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  7. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  8. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  9. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  10. Digital and analog communication systems

    NASA Technical Reports Server (NTRS)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  11. Analogical Reasoning in Geometry Education

    ERIC Educational Resources Information Center

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  12. Electrical analogous in viscoelasticity

    NASA Astrophysics Data System (ADS)

    Ala, Guido; Di Paola, Mario; Francomano, Elisa; Li, Yan; Pinnola, Francesco P.

    2014-07-01

    In this paper, electrical analogous models of fractional hereditary materials are introduced. Based on recent works by the authors, mechanical models of materials viscoelasticity behavior are firstly approached by using fractional mathematical operators. Viscoelastic models have elastic and viscous components which are obtained by combining springs and dashpots. Various arrangements of these elements can be used, and all of these viscoelastic models can be equivalently modeled as electrical circuits, where the spring and dashpot are analogous to the capacitance and resistance, respectively. The proposed models are validated by using modal analysis. Moreover, a comparison with numerical experiments based on finite difference time domain method shows that, for long time simulations, the correct time behavior can be obtained only with modal analysis. The use of electrical analogous in viscoelasticity can better reveal the real behavior of fractional hereditary materials.

  13. Analog Optical Links

    NASA Astrophysics Data System (ADS)

    Cox, Charles H., III

    2004-05-01

    Unlike books that focus on the devices used in links, such as lasers and photodiodes, among others, this text focuses on the next level. It covers the collection of devices that form a link, how the individual device performance affects the link performance, or the reverse. Analog links are used for the distribution of cable TV signals, and in conveying the signals to and from antennas (so called antenna remoting). The design of analog links differs significantly from digital links which are primarily used in telecommunications.

  14. Caffeine analogs: biomedical impact.

    PubMed

    Daly, J W

    2007-08-01

    Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.

  15. Analogy, explanation, and proof

    PubMed Central

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  16. Are Scientific Analogies Metaphors?

    DTIC Science & Technology

    1981-02-01

    psychospiritual processes. A more modern example of unclarified analogy is Freud’s (1973; reprinted from 1955) discussion of anal- eroticism , in which...299-304. Freud, S. On transformations of instinct as exemplified in anal eroticism . In J. Strachey (Ed.), The standard 37 edition of the complete

  17. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  18. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  19. An Interesting Analogy

    ERIC Educational Resources Information Center

    Pacheco, Jose M.; Fernandez, Isabel

    2002-01-01

    The aim of this note is to give some insight into the formal unity of a very applicable area of mathematics by showing an interesting analogy between the weak part of the Rouche-Frobenius theorem and the existence result for the initial value problem for the general first-order linear two-dimensional PDE.

  20. Analogy, explanation, and proof.

    PubMed

    Hummel, John E; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  1. Reasoning through Instructional Analogies

    ERIC Educational Resources Information Center

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  2. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  3. How Analogy Drives Physics

    SciTech Connect

    Hofstadter, Doug

    2004-05-05

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  4. Terrestrial analogs to Mars

    NASA Technical Reports Server (NTRS)

    Farr, T. G.; Arcone, S.; Arvidson, R.; Baker, V.; Barlow, N.; Beaty, D.; Bell, M.; Blankenship, D.; Bridges, N.; Briggs, G.; hide

    2002-01-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing.

  5. New analogs of trimethoprim.

    PubMed

    Then, R L; Böhni, E; Angehrn, P; Plozza-Nottebrock, H; Stoeckel, K

    1982-01-01

    Possible goals and recent developments in the field of antimicrobial 2,4-diamino-5-benzylpyrimidines are discussed. Three analogs of trimethoprim--all bearing different substituents at position 4 of the benzyl moiety and one also having the methoxy groups replaced by ethoxy substituents--are characterized in some detail. These analogs exhibit physicochemical properties different from those of trimethoprim and are potent inhibitors of several dihydrofolate reductases. Because they differ from trimethoprim in lipophilicity, their in vitro activity, spectrum of activity, and pharmacokinetic properties also differ from those of trimethoprim. These differences are judged to be the reason for enhanced in vivo efficacy against several experimental infections. Distinct pharmacokinetic differences observed in dogs include a longer elimination half-life and a larger volume of distribution. These favorable properties indicate the potential value of further studies in humans.

  6. Terrestrial Spaceflight Analogs: Antarctica

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  7. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  8. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  9. VIIP Bedrest Analog Roadmap

    NASA Technical Reports Server (NTRS)

    Villarreal, Jennifer D.

    2014-01-01

    The objective is to define successive bed rest campaigns leading to a potential VIIP (Vision Impairment and Intracranial Pressure) countermeasure. To determine if the analog is successful, changes need to occur in the following outcome measures (dependent variables): Intracranial pressure; Retinal nerve fiber layer; Choroidal engorgement; Globe flattening; Axial biometry; Optic nerve sheath diameter distention; Cycloplegic refraction; Visual acuity. Study parameters (independent variables) to include: CO2; Sodium; Exercise (resistive & aerobic); Strict tilt angle.

  10. Analog storage integrated circuit

    DOEpatents

    Walker, J. T.; Larsen, R. S.; Shapiro, S. L.

    1989-01-01

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks.

  11. Antarctic analogs for Enceladus

    NASA Astrophysics Data System (ADS)

    Murray, A. E.; Andersen, D. T.; McKay, C. P.

    2014-12-01

    Enceladus is a new world for Astrobiology. The Cassini discovery of the icy plume emanating from the South Polar region indicates an active world, where detection of water, organics, sodium, and nano-particle silica in the plume strongly suggests that the source is a subsurface salty ocean reservoir. Recent gravity data from Cassini confirms the presence of a regional sea extending north to 50°S. An ocean habitat under a thick ice cover is perhaps a recurring theme in the Outer Solar System, but what makes Enceladus unique is that the plume jetting out into space is carrying samples of this ocean. Therefore, through the study of Enceladus' plumes we can gain new insights not only of a possible habitable world in the Solar Systems, but also about the formation and evolution of other icy-satellites. Cassini has been able to fly through this plume - effectively sampling the ocean. It is time to plan for future missions that do more detailed analyses, possibly return samples back to Earth and search for evidence of life. To help prepare for such missions, the need for earth-based analog environments is essential for logistical, methodological (life detection) and theoretical development. We have undertaken studies of two terrestrial environments that are close analogs to Enceladus' ocean: Lake Vida and Lake Untersee - two ice-sealed Antarctic lakes that represent physical, chemical and possibly biological analogs for Enceladus. By studying the diverse biology and physical and chemical constraints to life in these two unique lakes we will begin to understand the potential habitability of Enceladus and other icy moons, including possible sources of nutrients and energy, which together with liquid water are the key ingredients for life. Analog research such as this will also enable us to develop and test new strategies to search for evidence of life on Enceladus.

  12. Analog storage integrated circuit

    DOEpatents

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  13. A Transiting Jupiter Analog

    NASA Astrophysics Data System (ADS)

    Kipping, D. M.; Torres, G.; Henze, C.; Teachey, A.; Isaacson, H.; Petigura, E.; Marcy, G. W.; Buchhave, L. A.; Chen, J.; Bryson, S. T.; Sandford, E.

    2016-04-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of (0.91+/- 0.02) {R}{{J}}, a low orbital eccentricity ({0.06}-0.04+0.10), and an equilibrium temperature of (131+/- 3) K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target.

  14. The Analogy Theme in Geography.

    ERIC Educational Resources Information Center

    Andrews, Alice C.

    1987-01-01

    Describes ten types of analogies and the role they play in thinking and learning. Devotes specific attention to the use of analogies in geography instruction. Claims that the use of analogies in teaching physical, cultural, and regional geography helps students absorb knowledge quickly and integrate it into their existing frameworks. (JDH)

  15. Analogical scaffolding: Making meaning in physics through representation and analogy

    NASA Astrophysics Data System (ADS)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  16. Neural Analog Information Processing

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1982-07-01

    Neural Analog Information Processing (NAIP) is an effort to develop general purpose pattern classification architectures based upon biological information processing principles. This paper gives an overview of NAIP and its relationship to the previous work in neural modeling from which its fundamental principles are derived. It also presents a theorem concerning the stability of response of a slab (a two dimensional array of identical simple processing units) to time-invariant (spatial) patterns. An experiment (via computer emulation) demonstrating classification of a spatial pattern by a simple, but complete NAIP architecture is described. A concept for hardware implementation of NAIP architectures is briefly discussed.

  17. Antarctic Space Analog Program

    NASA Technical Reports Server (NTRS)

    Palinkas, Lawrence A; Gunderson, E. K. Eric; Johnson, Jeffrey C.; Holland, Albert W.

    1998-01-01

    The primary aim of this project was to examine group dynamics and individual performance in extreme, isolated environments and identify human factors requirements for long-duration space missions using data collected in an analog environment. Specifically, we wished to determine: 1) the characteristics of social relations in small groups of individuals living and working together in extreme, isolated environments, and 2) the environmental, social and psychological determinants of performance effectiveness in such groups. These two issues were examined in six interrelated studies using data collected in small, isolated research stations in Antarctica from 1963 to the present. Results from these six studies indicated that behavior and performance on long-duration space flights is likely to be seasonal or cyclical, situational, social, and salutogenic in nature. The project responded to two NASA program emphases for FY 1997 as described in the NRA: 1) the primary emphasis of the Behavior and Performance Program on determining long-term individual and group performance responses to space, identifying critical factors affecting those responses and understanding underlying mechanisms involved in behavior and performance, and developing and using ground-based models and analogs for studying space-related behavior and performance; and 2) the emphasis of the Data Analysis Program on extended data analysis. Results from the study were used to develop recommendations for the design and development of pre-flight crew training and in-flight psychological countermeasures for long-duration manned space missions.

  18. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

    Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design.

  19. Female analogies to perversion.

    PubMed

    Beier, K M

    2000-01-01

    Unlike the intrapsychic mechanism for self-esteem regulation in males as a basic component of perversion--extrapsychically (compensationally) culminating in an output of sexual impulses--a functional stabilization of the female self-concept seems more likely if conflict drives were to be focused on reproductional aspects and not on sexuality. It therefore seems more suitable to use a new expression in linguistic analogy to perversion: "reproversion." The case history gives an example of a clinical manifestation of "reproverse" symptom formation. The general survey describes the main points of view in regard to clinically oriented differentiation, i.e., intensity, ego-proximity in the personality structure, and one's own self-acceptance within "reproverse" symptom formation. Underlying personality disturbances are also discussed. The significance of reproversion is relevant to many different specialized medical fields. This is explained in conclusion, using the examples of denied pregnancy and infanticide at birth based on initial empirical results.

  20. Mathematical problem solving by analogy.

    PubMed

    Novick, L R; Holyoak, K J

    1991-05-01

    We report the results of 2 experiments and a verbal protocol study examining the component processes of solving mathematical word problems by analogy. College students first studied a problem and its solution, which provided a potential source for analogical transfer. Then they attempted to solve several analogous problems. For some problems, subjects received one of a variety of hints designed to reduce or eliminate the difficulty of some of the major processes hypothesized to be involved in analogical transfer. Our studies yielded 4 major findings. First, the process of mapping the features of the source and target problems and the process of adapting the source solution procedure for use in solving the target problem were clearly distinguished: (a) Successful mapping was found to be insufficient for successful transfer and (b) adaptation was found to be a major source of transfer difficulty. Second, we obtained direct evidence that schema induction is a natural consequence of analogical transfer. The schema was found to co-exist with the problems from which it was induced, and both the schema and the individual problems facilitated later transfer. Third, for our multiple-solution problems, the relation between analogical transfer and solution accuracy was mediated by the degree of time pressure exerted for the test problems. Finally, mathematical expertise was a significant predictor of analogical transfer, but general analogical reasoning ability was not. The implications of the results for models of analogical transfer and for instruction were considered.

  1. Zoledronic acid but not somatostatin analogs exerts anti-tumor effects in a model of murine prostatic neuroendocrine carcinoma of the development of castration-resistant prostate cancer.

    PubMed

    Hashimoto, Kohei; Masumori, Naoya; Tanaka, Toshiaki; Maeda, Toshihiro; Kobayashi, Ko; Kitamura, Hiroshi; Hirata, Koichi; Tsukamoto, Taiji

    2013-04-01

    Since neuroendocrine (NE) cells play an important role in the development of castration-resistant prostate cancer (CRPC), target therapy to NE cells should be considered for treating CRPC. We investigated the effects zoledronic acid (ZOL) and two somatostatin analogs (octreotide: SMS, and pasireotide: SOM) on an NE allograft (NE-10) and its cell line (NE-CS), which were established from the prostate of the LPB-Tag 12T-10 transgenic mouse. We examined the in vivo effects of ZOL, SMS and SOM as single agents and their combinations on subcutaneously inoculated NE-10 allografts and the in vitro effects on NE-CS cells. Apoptosis and cell cycle activity were assessed by immunohistochemistry using TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and a Ki-67 antibody, respectively. In vivo growth of NE-10 tumors treated with ZOL, ZOL plus SMS, or ZOL plus SOM was significantly inhibited compared to the control as a consequence of induction of apoptosis and cell cycle arrest. ZOL induced time- and dose-dependent inhibition of in vitro proliferation of NE-CS cells, but the somatostatin analogs (SMS and SOM) did not. ZOL also inhibited migration of NE-CS cells. These effects were caused by inhibition of Erk1/2 phosphorylation via impairment of prenylation of Ras. ZOL, but not SMS or SOM, induced apoptosis and inhibition of proliferation and migration through impaired prenylation of Ras in NE carcinoma models. Our findings support the possibility that ZOL could be used in the early phase for controlling NE cells, which may trigger progression to CRPC. Copyright © 2012 Wiley Periodicals, Inc.

  2. [Analogies and analogy research in technical biology and bionics].

    PubMed

    Nachtigall, Werner

    2010-01-01

    The procedural approaches of Technical Biology and Bionics are characterized, and analogy research is identified as their common basis. The actual creative aspect in bionical research lies in recognizing and exploiting technically oriented analogies underlying a specific biological prototype to indicate a specific technical application.

  3. Natural analog studies: Licensing perspective

    SciTech Connect

    Bradbury, J.W.

    1995-09-01

    This report describes the licensing perspective of the term {open_quotes}natural analog studies{close_quotes} as used in CFR Part 60. It describes the misunderstandings related to its definition which has become evident during discussions at the U.S Nuclear Regulatory Commission meetings and tries to clarify the appropriate applications of natural analog studies to aspects of repository site characterization.

  4. Drawing Analogies in Environmental Education

    ERIC Educational Resources Information Center

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  5. Analogy, Dialectics and Lifelong Learning.

    ERIC Educational Resources Information Center

    Bailey, Ted

    2003-01-01

    Compares analogies and dialectics, discussing limitations of the Hegelian/Marxian dialectical form in adult education. Proposes the more holistic approach of Vico, a double dialectic that connects social and individual relationships, knowledge, and experience. Demonstrates a dialectical learning exchange that uses an analogy trigger. (SK)

  6. Drawing Analogies in Environmental Education

    ERIC Educational Resources Information Center

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  7. Conjecturing via Reconceived Classical Analogy

    ERIC Educational Resources Information Center

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  8. Conjecturing via Reconceived Classical Analogy

    ERIC Educational Resources Information Center

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  9. Analog pixel array detectors.

    PubMed

    Ercan, A; Tate, M W; Gruner, S M

    2006-03-01

    X-ray pixel array detectors (PADs) are generally thought of as either digital photon counters (DPADs) or X-ray analog-integrating pixel array detectors (APADs). Experiences with APADs, which are especially well suited for X-ray imaging experiments where transient or high instantaneous flux events must be recorded, are reported. The design, characterization and experimental applications of several APAD designs developed at Cornell University are discussed. The simplest design is a ;flash' architecture, wherein successive integrated X-ray images, as short as several hundred nanoseconds in duration, are stored in the detector chips for later off-chip digitization. Radiography experiments using a prototype flash APAD are summarized. Another design has been implemented that combines flash capability with the ability to continuously stream X-ray images at slower (e.g. milliseconds) rates. Progress is described towards radiation-hardened APADs that can be tiled to cover a large area. A mixed-mode PAD, design by combining many of the attractive features of both APADs and DPADs, is also described.

  10. Cannabinoid properties of methylfluorophosphonate analogs.

    PubMed

    Martin, B R; Beletskaya, I; Patrick, G; Jefferson, R; Winckler, R; Deutsch, D G; Di Marzo, V; Dasse, O; Mahadevan, A; Razdan, R K

    2000-09-01

    Methylarachidonylfluorophosphonate (MAFP) and related analogs have been shown to inhibit fatty acid amidohydrolase activity (FAAH), the enzyme responsible for hydrolysis of the endogenous cannabinoid ligand anandamide. To fully characterize this class of compounds, methylfluorophosphonate compounds with saturated alkyl chains ranging from C8 to C20 along with C20 unsaturated derivatives were synthesized and evaluated for their ability to interact with the CB1 receptor, inhibit FAAH, and produce in vivo pharmacological effects. These analogs demonstrated widely varying affinities for the CB1 receptor. Of the saturated compounds, C8:0 was incapable of displacing [(3)H]CP 55,940 binding, whereas C12:0 exhibited high affinity (2.5 nM). The C20:0 saturated analog had low affinity (900 nM), but the introduction of unsaturation into the C20 analogs restored receptor affinity. However, none of the analogs were capable of fully displacing [(3)H]CP 55,940 binding. On the other hand, all compounds were able to completely inhibit FAAH enzyme activity, with the C20:0 analog being the least potent. The most potent FAAH inhibitor was the short-chained saturated C12:0, whereas the other analogs were 15- to 30-fold less potent. In vivo, the C8:0 and C12:0 analogs were highly potent and fully efficacious in producing tetrahydrocannabinol (THC)-like effects, whereas the other analogs were either inactive or acted as partial agonists. None was capable of attenuating the agonist effects of THC. Conversely, the C20:0 analog potentiated the effects of anandamide but not those of 2-arachidonoyl-glycerol and THC. The high in vivo potency of the novel short-chain saturated MAFP derivatives (C8:0 and C12:0) underscores the complexity of manipulating the endogenous cannabinoid system.

  11. Orthographic analogies and developmental dyslexia.

    PubMed

    Hanley, J R; Reynolds, C J; Thornton, A

    1997-08-01

    Goswami (1986, 1988) has demonstrated that children can use orthographic analogies (particularly at the onset-rime level) between the spelling patterns in words to help to decode new words (e.g. using 'beak' to read 'peak'). This strategy has been shown in children as young as six years old. Since it is known that children with developmental dyslexia find it particularly difficult to read words that they have not been specifically taught (Lovett, Warren-Chaplin, Ransby & Borden, 1990), the present study investigated whether dyslexic children might be unable to use analogies. Employing a design similar to that used by Goswami (1988), it was hypothesized that dyslexics would find it difficult to transfer spontaneously knowledge of a 'clue' word to decode new words that could be read by analogy with the clue word. The results of Expt 1 indicated that the dyslexic readers read significantly fewer of the analogous words than a reading age-matched comparison group of younger children. Furthermore, none of the nine dyslexic children read as many of the analogous words as the lowest scoring control child. In a second experiment, a design similar to that of Muter, Snowling & Taylor (1994) was used with a new and larger sample of dyslexic children. In this experiment, all the children were brought to criterion in reading the clue words before the analogous words were presented. Once again, the dyslexic children read significantly fewer words that were analogous with the clue words than did a reading age-matched comparison group. The number of analogous words that the dyslexic children read was significantly correlated with their performance on a test that is sensitive to the ability to detect rhyme. It is argued that a failure to make analogies may be one of the main causes of the reading impairment experienced by children with developmental dyslexia.

  12. Factors Affecting the Difficulty of Verbal Analogies.

    ERIC Educational Resources Information Center

    Roccas, Sonia; Moshinsky, Avital

    2003-01-01

    Examined factors affecting the difficulty of verbal analogies in a psychometric examination by characterizing 104 analogies using 5 defined attributes. Both knowledge and process attributes were found to contribute to the difficulty of verbal analogies assessed by 10 judges. (SLD)

  13. Analog actuator-piston memory

    NASA Technical Reports Server (NTRS)

    Sable, B. A.

    1980-01-01

    Simple analog control system of digitally controlled acuator uses 'stopped' position of actuator as 'memory' and potentiometer as sensing element during power failure to reload drive circuit to value equal to its last position preceding power loss.

  14. Flight Analogs (Bed Rest Research)

    NASA Image and Video Library

    Flight Analogs / Bed Rest Research Projects provide NASA with a ground based research platform to complement space research. By mimicking the conditions of weightlessness in the human body here on ...

  15. Analog device simulates physiological waveforms

    NASA Technical Reports Server (NTRS)

    Hickman, D. M.

    1964-01-01

    An analog physiological simulator generates representative waveforms for a wide range of physiological conditions. Direct comparison of these waveforms with those from telemetric inputs permits quick detection of signal parameter degradation.

  16. Introduction to Analog Field Testing

    NASA Image and Video Library

    NASA tests systems and operational concepts in analog environments, which include locations underwater, in the arctic, on terrestrial impact craters, in the desert, and on the International Space S...

  17. Solving a problem by analogy

    NASA Astrophysics Data System (ADS)

    Easton, Don

    1999-03-01

    This note is a description of a student solution to a problem. I found the solution exciting because it exemplifies the kind of solution by analogy that Feynman describes in The Feynman Lectures on Physics.

  18. Verbal Analogies in the ITPA

    ERIC Educational Resources Information Center

    Levinson, Philip J.; Kunze, Luvern H.

    1973-01-01

    This study examined the extent to which the Auditory Association subtest of the revised Illinois Test of Psycholinguistic Abilities (ITPA) measures the ability of children to complete verbal analogies. (Author)

  19. The Robustness of Acoustic Analogies

    NASA Technical Reports Server (NTRS)

    Freund, J. B.; Lele, S. K.; Wei, M.

    2004-01-01

    Acoustic analogies for the prediction of flow noise are exact rearrangements of the flow equations N(right arrow q) = 0 into a nominal sound source S(right arrow q) and sound propagation operator L such that L(right arrow q) = S(right arrow q). In practice, the sound source is typically modeled and the propagation operator inverted to make predictions. Since the rearrangement is exact, any sufficiently accurate model of the source will yield the correct sound, so other factors must determine the merits of any particular formulation. Using data from a two-dimensional mixing layer direct numerical simulation (DNS), we evaluate the robustness of two analogy formulations to different errors intentionally introduced into the source. The motivation is that since S can not be perfectly modeled, analogies that are less sensitive to errors in S are preferable. Our assessment is made within the framework of Goldstein's generalized acoustic analogy, in which different choices of a base flow used in constructing L give different sources S and thus different analogies. A uniform base flow yields a Lighthill-like analogy, which we evaluate against a formulation in which the base flow is the actual mean flow of the DNS. The more complex mean flow formulation is found to be significantly more robust to errors in the energetic turbulent fluctuations, but its advantage is less pronounced when errors are made in the smaller scales.

  20. Analog approach to mixed analog-digital circuit simulation

    NASA Astrophysics Data System (ADS)

    Ogrodzki, Jan

    2013-10-01

    Logic simulation of digital circuits is a well explored research area. Most up-to-date CAD tools for digital circuits simulation use an event driven, selective trace algorithm and Hardware Description Languages (HDL), e.g. the VHDL. This techniques enable simulation of mixed circuits, as well, where an analog part is connected to the digital one through D/A and A/D converters. The event-driven mixed simulation applies a unified, digital-circuits dedicated method to both digital and analog subsystems. In recent years HDL techniques have been also applied to mixed domains, as e.g. in the VHDL-AMS. This paper presents an approach dual to the event-driven one, where an analog part together with a digital one and with converters is treated as the analog subsystem and is simulated by means of circuit simulation techniques. In our problem an analog solver used yields some numerical problems caused by nonlinearities of digital elements. Efficient methods for overriding these difficulties have been proposed.

  1. Producing and Recognizing Analogical Relations

    PubMed Central

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  2. All-optical analog comparator

    PubMed Central

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

  3. Biomimetic Analogs for Collagen Biomineralization

    PubMed Central

    Gu, L.; Kim, Y.K.; Liu, Y.; Ryou, H.; Wimmer, C.E.; Dai, L.; Arola, D.D.; Looney, S.W.; Pashley, D.H.; Tay, F.R.

    2011-01-01

    Inability of chemical phosphorylation of sodium trimetaphosphate to induce intrafibrillar mineralization of type I collagen may be due to the failure to incorporate a biomimetic analog to stabilize amorphous calcium phosphates (ACP) as nanoprecursors. This study investigated adsorption/desorption characteristics of hydrolyzed and pH-adjusted sodium trimetaphosphate (HPA-Na3P3O9) to collagen. Based on those results, a 5-minute treatment time with 2.8 wt% HPA-Na3P3O9 was used in a single-layer reconstituted collagen model to confirm that both the ACP-stabilization analog and matrix phosphoprotein analog must be present for intrafibrillar mineralization. The results of that model were further validated by complete remineralization of phosphoric-acid-etched dentin treated with the matrix phosphoprotein analog and lined with a remineralizing lining composite, and with the ACP-stabilization analog supplied in simulated body fluid. An understanding of the basic processes involved in intrafibrillar mineralization of reconstituted collagen fibrils facilitates the design of novel tissue engineering materials for hard tissue repair and regeneration. PMID:20940362

  4. All-optical analog comparator.

    PubMed

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-23

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  5. All-optical analog comparator

    NASA Astrophysics Data System (ADS)

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  6. Analogies in Science and Science Teaching

    ERIC Educational Resources Information Center

    Brown, Simon; Salter, Susan

    2010-01-01

    Analogies are often used in science, but students may not appreciate their significance, and so the analogies can be misunderstood or discounted. For this reason, educationalists often express concern about the use of analogies in teaching. Given the important place of analogies in the discourse of science, it is necessary that students are…

  7. Analogies in Science and Science Teaching

    ERIC Educational Resources Information Center

    Brown, Simon; Salter, Susan

    2010-01-01

    Analogies are often used in science, but students may not appreciate their significance, and so the analogies can be misunderstood or discounted. For this reason, educationalists often express concern about the use of analogies in teaching. Given the important place of analogies in the discourse of science, it is necessary that students are…

  8. Teaching Scientific Analogies: A Proposed Model.

    ERIC Educational Resources Information Center

    Zeitoun, Hassan Hussein

    Cognitive psychologists have recently alluded to the role analogies might play in learning unfamiliar topics. However, since the use of analogies in science teaching has not been adequately addressed, analogies mean different things to different people. Therefore, a model for the teaching of scientific analogies is proposed. A theoretical…

  9. Natural analogs for Yucca Mountain

    SciTech Connect

    Murphy, W.M.

    1995-11-01

    High-level radioactive waste in the US, spent fuels from commercial reactors and nuclear materials generated by defense activities, will remain potentially hazardous for thousands of years. Demonstrable long-term stability of certain geologic and geochemical systems motivates and sustains the concept that high-level waste can be safely isolated in geologic repositories for requisite periods of time. Each geologic repository is unique in its properties and performance with reguard to isolation of nuclear wastes. Studies of processes analogous to waste-form alteration and radioelement transport in environments analogous to Yucca Mountain are being conducted at two sites, described in this article to illustrate uses of natural analog data: the Nopal I uranium deposit in the Sierra Pena Blanca, Mexico, and the Akrotiri archaeological site on the island of Santorini, Greece.

  10. Analog enhancement of radiographic images

    NASA Technical Reports Server (NTRS)

    Baily, N. A.; Nachazel, R. J.

    1976-01-01

    The paper shows how analog methods for edge sharpening, contrast enhancement, and expansion of the range of gray levels of particular interest are effective for easy on-line application to video viewing of X-ray roentgenograms or to fluoroscopy. The technique for analog enhancement of radiographic images is a modified version of the system designed by Fuchs et al. (1972), whereby an all directional second derivative signal called detail signal is used to produce both vertical and horizontal enhancement of the image. Particular attention is given to noise filtration and contrast enhancement. Numerous radiographs supplement the text.

  11. Analog circuits for relaxation networks.

    PubMed

    Card, H

    1993-12-01

    Selected examples are presented of recent advances, primarily from the U.S. and Canada, in analog circuits for relaxation networks. Relaxation networks having feedback connections exhibit potentially greater computational power per neuron than feedforward networks. They are also more poorly understood especially with respect to learning algorithms. Examples are described of analog circuits for (i) supervised learning in deterministic Boltzmann machines, (ii) unsupervised competitive learning and feature maps and (iii) networks with resistive grids for vision and audition tasks. We also discuss recent progress on in-circuit learning and synaptic weight storage mechanisms.

  12. Terrestrial analogs for space exploration habitation systems

    NASA Technical Reports Server (NTRS)

    Campbell, Paul D.; Brown, Jeri W.

    1992-01-01

    The Space Exploration Initiative (SEI) can use early earth-based analogs to simulate many aspects of space flight missions and system operation. These analogs can thus provide information supporting future missions to the moon and to Mars. A study was performed to investigate the potential of terrestrial analogs in simulating human space exploration missions. The study resulted in preliminary requirements and concepts for analog habitation systems, and further study in this area is necessary for SEI terrestrial analog development.

  13. Analogies and "Modeling Analogies" in Teaching: Some Examples in Basic Electricity.

    ERIC Educational Resources Information Center

    Dupin, J. J.; Johsua, S.

    1989-01-01

    Investigates the effect of modeling analogy on learning of the concepts of electricity in grade 6, 8, and 10. Describes 2 analogies (train analogy and thermal analogy) with diagrams and examples. Discusses the accessibility, transferability, and difficulty of each analogy. Reports treatment effect and some further implications. (YP)

  14. Algicidal Activity of Stilbene Analogs

    USDA-ARS?s Scientific Manuscript database

    As part of our continuing search for natural product and natural product-based compounds for the control of off-flavor in catfish, a total of twenty nine stilbene analogs were synthesized and evaluated for algicidal activity against the 2-methylisoborneol (MIB)-producing cyanobacterium Oscillatoria ...

  15. Paper Analogies Enhance Biology Teaching.

    ERIC Educational Resources Information Center

    Stencel, John E.

    1997-01-01

    Describes how to use paper analogies as models to illustrate various concepts in biology, human anatomy, and physiology classes. Models include biochemical paper models, protein papergrams, a paper model of early brain development, and a 3-D paper model of a eukaryotic cell. (AIM)

  16. Understanding & Teaching Genetics Using Analogies

    ERIC Educational Resources Information Center

    Woody, Scott; Himelblau, Ed

    2013-01-01

    We present a collection of analogies that are intended to help students better understand the foreign and often nuanced vocabulary of the genetics curriculum. Why is it called the "wild type"? What is the difference between a locus, a gene, and an allele? What is the functional (versus a rule-based) distinction between dominant and…

  17. Electrical analog to projectile motion

    NASA Astrophysics Data System (ADS)

    Vondracek, Mark

    1998-04-01

    This article describes an electrical analog to traditional projectile problems given in high school and introductory college classes. It also discusses the importance of stressing the understanding of physical laws and principles to students, and that the physics behind a problem is more important than being able to memorize and use various equations.

  18. Analog Input Data Acquisition Software

    NASA Technical Reports Server (NTRS)

    Arens, Ellen

    2009-01-01

    DAQ Master Software allows users to easily set up a system to monitor up to five analog input channels and save the data after acquisition. This program was written in LabVIEW 8.0, and requires the LabVIEW runtime engine 8.0 to run the executable.

  19. Analogy of the Cell Project

    ERIC Educational Resources Information Center

    Science Scope, 2005

    2005-01-01

    In this project, students compare the makeup of a cell to an everyday working unit or system. They create a three-dimensional object that represents their analogy. For example, students could create a car motor or manufacturing plant. (Of course, this is totally hand-created by them, so it can be a homemade re-creation of a system, not an actual…

  20. Analogy of the Cell Project

    ERIC Educational Resources Information Center

    Science Scope, 2005

    2005-01-01

    In this project, students compare the makeup of a cell to an everyday working unit or system. They create a three-dimensional object that represents their analogy. For example, students could create a car motor or manufacturing plant. (Of course, this is totally hand-created by them, so it can be a homemade re-creation of a system, not an actual…

  1. Analog Simulation of a Laser.

    ERIC Educational Resources Information Center

    Kessler, Gary

    1982-01-01

    Presents an analog simulation of laser properties (finding time evolution of the intensity of a ruby laser pulse) which serves as the basis of a three-four hour laboratory experiment. Includes programs for solution to rate equations of a three-level laser and production of a giant pulse in a ruby laser. (Author/SK)

  2. Bayesian Analogy with Relational Transformations

    ERIC Educational Resources Information Center

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J.

    2012-01-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy…

  3. Geometrical Analogies in Mathematics Lessons

    ERIC Educational Resources Information Center

    Eid, Wolfram

    2007-01-01

    A typical form of thinking to approach problem solutions humanly is thinking in analogous structures. Therefore school, especially mathematical lessons should help to form and to develop corresponding heuristic abilities of the pupils. In the contribution, a summary of possibilities of mathematics lessons regarding this shall particularly be…

  4. Mathematical Analogy and Metaphorical Insight

    ERIC Educational Resources Information Center

    Zwicky, Jan

    2010-01-01

    How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

  5. Analogy between Thermodynamics and Mechanics.

    ERIC Educational Resources Information Center

    Peterson, Mark A.

    1979-01-01

    Establishes and illustrates a formal analogy between the motion of a particle and the "motion" of the equilibrium state of a homogeneous system in a quasistatic process. The purpose is to show that there is a much larger set of natural coordinate transformations in thermodynamics. (GA)

  6. Understanding & Teaching Genetics Using Analogies

    ERIC Educational Resources Information Center

    Woody, Scott; Himelblau, Ed

    2013-01-01

    We present a collection of analogies that are intended to help students better understand the foreign and often nuanced vocabulary of the genetics curriculum. Why is it called the "wild type"? What is the difference between a locus, a gene, and an allele? What is the functional (versus a rule-based) distinction between dominant and…

  7. Analog Simulation of a Laser.

    ERIC Educational Resources Information Center

    Kessler, Gary

    1982-01-01

    Presents an analog simulation of laser properties (finding time evolution of the intensity of a ruby laser pulse) which serves as the basis of a three-four hour laboratory experiment. Includes programs for solution to rate equations of a three-level laser and production of a giant pulse in a ruby laser. (Author/SK)

  8. Schema Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Robins, Shani; Mayer, Richard E.

    1993-01-01

    In 3 experiments, 93, 97, and 86 college students, respectively, learned how to solve 20 verbal analogy problems and took transfer and memory tests. Results are inconsistent with active responding theory and further indicate that schema induction is maximized when the schemas are made salient and the cognitive system is not overloaded. (SLD)

  9. Processes in Verbal Analogy Solution.

    ERIC Educational Resources Information Center

    Grudin, Jonathan

    1980-01-01

    Verbal analogy solution is more flexible than is suggested by either the standard process theory or Sternberg's theory. It was determined that subjects initially examine terms A and B; if this strategy is not successful, they examine the relationship between A and C. (Author/CP)

  10. Bayesian Analogy with Relational Transformations

    ERIC Educational Resources Information Center

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J.

    2012-01-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy…

  11. International Alligator Rivers Analog Project

    SciTech Connect

    Bichard, G.F.

    1988-01-01

    The Australian Nuclear Science and Technology Organization (ANSTO), the Japan Atomic Energy Research Institute, the Swedish Nuclear Power Inspectorate, the U.K. Department of the Environment, the US Nuclear Regulatory Commission (NRC), and the Power Reactor and Nuclear Fuel Development Corporation of Japan are participating under the aegis of the Nuclear Energy Agency in the International Alligator Rivers Analog Project. The project has a duration of 3 yr, starting in 1988. The project has grown out of a research program on uranium ore bodies as analogs of high-level waste (HLW) repositories undertaken by ANSTO supported by the NRC. A primary objective of the project is to develop an approach to radionuclide transport model validation that may be used by the participants to support assessments of the safety of radioactive waste repositories. The approach involves integrating mathematical and physical modeling with hydrological and geochemical field and laboratory investigations of the analog site. The Koongarra uranium ore body has been chosen as the analog site because it has a secondary ore body that has formed over the past million years as a result of leaching by groundwater flowing through fractures in the primary ore body.

  12. Schema Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Robins, Shani; Mayer, Richard E.

    1993-01-01

    In 3 experiments, 93, 97, and 86 college students, respectively, learned how to solve 20 verbal analogy problems and took transfer and memory tests. Results are inconsistent with active responding theory and further indicate that schema induction is maximized when the schemas are made salient and the cognitive system is not overloaded. (SLD)

  13. Mathematical Analogy and Metaphorical Insight

    ERIC Educational Resources Information Center

    Zwicky, Jan

    2010-01-01

    How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

  14. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Bayesian analogy with relational transformations.

    PubMed

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  16. A CMOS field-programmable analog array

    NASA Astrophysics Data System (ADS)

    Lee, Edward K. F.; Gulak, P. G.

    1991-12-01

    The design details and test results of a field-programmable analog array (FPAA) prototype chip in 1.2-micron CMOS are presented. The analog array is based on subthreshold circuit techniques and consists of a collection of a homogeneous configurable analog blocks (CABs) and an interconnection network. Interconnections between CABs and the analog functions to be implemented in each block are defined by a set of configuration bits loaded serially into an onboard shift register by the user. Macromodels are developed for the analog functions in order to simulate various neural network applications on the field-programmable analog array.

  17. Battery hydrometer with analog output

    SciTech Connect

    Patis, B.L.

    1982-09-21

    There is disclosed a battery hydrometer for providing an analog electrical signal having a magnitude related to the specific gravity of a battery electrolyte. The hydrometer includes a source of radiation for providing a detectable beam of radiation and a piston member arranged to be submerged within the electrolyte and to intercept and modulate the beam of radiation in response to the specific gravity of the electrolyte. The piston member is suspended within the electrolyte by a spring which exerts a compressive force upon the piston member against which the electrolyte must act. The hydrometer further includes a radiation detector aligned with the radiation source for providing an analog electrical signal having a magnitude responsive to the modulated beam of radiation.

  18. Synaptic dynamics in analog VLSI.

    PubMed

    Bartolozzi, Chiara; Indiveri, Giacomo

    2007-10-01

    Synapses are crucial elements for computation and information transfer in both real and artificial neural systems. Recent experimental findings and theoretical models of pulse-based neural networks suggest that synaptic dynamics can play a crucial role for learning neural codes and encoding spatiotemporal spike patterns. Within the context of hardware implementations of pulse-based neural networks, several analog VLSI circuits modeling synaptic functionality have been proposed. We present an overview of previously proposed circuits and describe a novel analog VLSI synaptic circuit suitable for integration in large VLSI spike-based neural systems. The circuit proposed is based on a computational model that fits the real postsynaptic currents with exponentials. We present experimental data showing how the circuit exhibits realistic dynamics and show how it can be connected to additional modules for implementing a wide range of synaptic properties.

  19. Analog Nonvolatile Computer Memory Circuits

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd

    2007-01-01

    In nonvolatile random-access memory (RAM) circuits of a proposed type, digital data would be stored in analog form in ferroelectric field-effect transistors (FFETs). This type of memory circuit would offer advantages over prior volatile and nonvolatile types: In a conventional complementary metal oxide/semiconductor static RAM, six transistors must be used to store one bit, and storage is volatile in that data are lost when power is turned off. In a conventional dynamic RAM, three transistors must be used to store one bit, and the stored bit must be refreshed every few milliseconds. In contrast, in a RAM according to the proposal, data would be retained when power was turned off, each memory cell would contain only two FFETs, and the cell could store multiple bits (the exact number of bits depending on the specific design). Conventional flash memory circuits afford nonvolatile storage, but they operate at reading and writing times of the order of thousands of conventional computer memory reading and writing times and, hence, are suitable for use only as off-line storage devices. In addition, flash memories cease to function after limited numbers of writing cycles. The proposed memory circuits would not be subject to either of these limitations. Prior developmental nonvolatile ferroelectric memories are limited to one bit per cell, whereas, as stated above, the proposed memories would not be so limited. The design of a memory circuit according to the proposal must reflect the fact that FFET storage is only partly nonvolatile, in that the signal stored in an FFET decays gradually over time. (Retention times of some advanced FFETs exceed ten years.) Instead of storing a single bit of data as either a positively or negatively saturated state in a ferroelectric device, each memory cell according to the proposal would store two values. The two FFETs in each cell would be denoted the storage FFET and the control FFET. The storage FFET would store an analog signal value

  20. Classical Analog to Entanglement Reversibility

    NASA Astrophysics Data System (ADS)

    Chitambar, Eric; Fortescue, Ben; Hsieh, Min-Hsiu

    2015-08-01

    In this Letter we study the problem of secrecy reversibility. This asks when two honest parties can distill secret bits from some tripartite distribution pX Y Z and transform secret bits back into pX Y Z at equal rates using local operation and public communication. This is the classical analog to the well-studied problem of reversibly concentrating and diluting entanglement in a quantum state. We identify the structure of distributions possessing reversible secrecy when one of the honest parties holds a binary distribution, and it is possible that all reversible distributions have this form. These distributions are more general than what is obtained by simply constructing a classical analog to the family of quantum states known to have reversible entanglement. An indispensable tool used in our analysis is a conditional form of the Gács-Körner common information.

  1. Superconducting Analog to Digital Converters

    DTIC Science & Technology

    1991-09-01

    superconductivity, Josephson junctions, and superconducting quantum interference devices ( SQUIDs ) are briefly described. Various techniques to perform analog-to...deployment in the 1990s may require a dynamic range in excess of 90 dB (15- bit precision) [3]. However, at the present time, A/D conversion with 16-bit...Interference Devices ( SQUIDs ). JOSEPHSON EFFECTS AND JUNCTIONS Consider a very thin, non-superconducting region separating two superconductors. In 1962

  2. Neurotoxicology of Synthetic Cathinone Analogs.

    PubMed

    Angoa-Pérez, Mariana; Anneken, John H; Kuhn, Donald M

    The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties. Most of the literature on synthetic cathinones has focused on describing their properties as psychostimulants, their behavioral effects on locomotion, memory, and potential for abuse, whereas descriptions of their neurotoxic properties are not abundant. The biochemical gauges of neurotoxicity induced by non-keto analogs are well studied in humans and experimental animals and include their ability to induce neuroinflammation, oxidative stress, excitotoxicity, temperature alterations as well as dysregulation of neurotransmitter systems and induce changes in monoamine transporters and receptors. These neurotoxicity gauges will serve as parameters to discuss the effects of the four previously mentioned synthetic cathinones alone or in combination with either another cathinone or with some of their non-keto analogs. Bath salts are not a defined combination of drugs and may consist of one synthetic cathinone compound or combinations of more cathinones. Furthermore, this review also presents some of the mechanisms that are thought to underlie this toxicity. A better understanding of the cellular and molecular mechanisms involved in the synthetic cathinones-induced neurotoxicity should contribute to generate modern therapeutic approaches to prevent or attenuate the adverse consequences of use of these

  3. Health as an analogical concept.

    PubMed

    Mordacci, R

    1995-10-01

    This article examines the normative structure of the concept of health and tries to suggest an account of it in a phenomenological-hermeneutic framework. It is argued that the concept of health has a logical priority to illness, though the latter has an experiential priority. The fundamental feature of the concept of health as discussed in the literature is initially recognized in the notion of 'norm', in both the bio-statistical and normative-ideal sense. An analysis of this body of literature reveals some weaknesses in bio-statistical definitions of health as well as in those normative ones which endorse a value-relativity thesis. An approach based on the analogical structure of language is then advanced. In this framework, the notion of biological normativeness proposed by G. Canguilhem is connected with an analysis of the language of health through etymologies. It is argued that health can be characterized as an analogy of 'plenitude', which is the common ideal reference of the various health-concepts. The analogical structuring of language allows the recognition of different levels of meaning, and therefore of different kinds of normativeness (biological, mental, social, moral). Some hints of a theory of health deriving from this framework are then given.

  4. Simple Electronic Analog of a Josephson Junction.

    ERIC Educational Resources Information Center

    Henry, R. W.; And Others

    1981-01-01

    Demonstrates that an electronic Josephson junction analog constructed from three integrated circuits plus an external reference oscillator can exhibit many of the circuit phenomena of a real Josephson junction. Includes computer and other applications of the analog. (Author/SK)

  5. Thermal analog device reduces machining errors

    NASA Technical Reports Server (NTRS)

    Mcclure, E. R.

    1972-01-01

    Thermal analog devices predict thermal expansion and contraction of machine structures subjected to various heat inputs. Analog devices correct positioning of machine tools to compensate for distortion of machine frame.

  6. Basic Electricity--a Novel Analogy.

    ERIC Educational Resources Information Center

    Grant, Richard

    1996-01-01

    Uses the analogy of water flow to introduce concepts in basic electricity. Presents a demonstration that uses this analogy to help students grasp the relationship between current, voltage, and resistance. (JRH)

  7. Simple Electronic Analog of a Josephson Junction.

    ERIC Educational Resources Information Center

    Henry, R. W.; And Others

    1981-01-01

    Demonstrates that an electronic Josephson junction analog constructed from three integrated circuits plus an external reference oscillator can exhibit many of the circuit phenomena of a real Josephson junction. Includes computer and other applications of the analog. (Author/SK)

  8. Program Documentation for the Analog Digitization Program,

    DTIC Science & Technology

    COMPUTER PROGRAM DOCUMENTATION, *ANALOG TO DIGITAL CONVERTERS, REAL TIME, COMPUTER LOGIC, INPUT OUTPUT PROCESSING, SAMPLING, INPUT OUTPUT DEVICES...FLOW CHARTING, ANALOG SIGNALS, DISK RECORDING SYSTEMS, DIGITAL RECORDING SYSTEMS, ASSEMBLY LANGUAGES.

  9. Third order digital-to-analog converter

    NASA Technical Reports Server (NTRS)

    Dotson, W. P.

    1972-01-01

    System, consisting of sample and hold digital-to-analog converter, clock circuit, sample delay circuit, initial condition circuit and interpolator circuit, improves accuracy of reconstructed analog signal without increasing sample rates.

  10. Hegel, Analogy, and Extraterrestrial Life

    NASA Astrophysics Data System (ADS)

    Ross, Joseph T.

    Georg Wilhelm Friedrich Hegel rejected the possibility of life outside of the Earth, according to several scholars of extraterrestrial life. Their position is that the solar system and specifically the planet Earth is the unique place in the cosmos where life, intelligence, and rationality can be. The present study offers a very different interpretation of Hegel's statements about the place of life on Earth by suggesting that, although Hegel did not believe that there were other solar systems where rationality is present, he did in fact suggest that planets in general, not the Earth exclusively, have life and possibly also intelligent inhabitants. Analogical syllogisms are superficial, according to Hegel, insofar as they try to conclude that there is life on the Moon even though there is no evidence of water or air on that body. Similar analogical arguments for life on the Sun made by Johann Elert Bode and William Herschel were considered by Hegel to be equally superficial. Analogical arguments were also used by astronomers and philosophers to suggest that life could be found on other planets in our solar system. Hegel offers no critique of analogical arguments for life on other planets, and in fact Hegel believed that life would be found on other planets. Planets, after all, have meteorological processes and therefore are "living" according to his philosophical account, unlike the Moon, Sun, and comets. Whereas William Herschel was already finding great similarities between the Sun and the stars and had extended these similarities to the property of having planets or being themselves inhabitable worlds, Hegel rejected this analogy. The Sun and stars have some properties in common, but for Hegel one cannot conclude from these similarities to the necessity that stars have planets. Hegel's arguments against the presence of life in the solar system were not directed against other planets, but rather against the Sun and Moon, both of which he said have a different

  11. The Micro-Category Account of Analogy

    ERIC Educational Resources Information Center

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  12. Analogical Reasoning: A Review of the Literature.

    ERIC Educational Resources Information Center

    Dawis, Rene V.; Siojo, Luis T.

    The mathematical and philosophical origins of "analogy" are described and their influence on the thinking of intelligence theorists is traced. Theories of intelligence and cognition bearing on analogical reasoning are examined, specifically those of Spearman, Thorndike, Guilford and Piaget. The analogy test item is shown to be a paradigm…

  13. Reasoning by Analogy in Constructing Mathematical Ideas.

    ERIC Educational Resources Information Center

    English, Lyn D.

    A powerful way of understanding something new is by analogy with something already known. An analogy is defined as a mapping from one structure, which is already known (the base or source), to another structure that is to be inferred or discovered (the target). The research community has given considerable attention to analogical reasoning in the…

  14. Are all analogies created equal? Prefrontal cortical functioning may predict types of analogical reasoning.

    PubMed

    Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-06-01

    Abstract The proposed theory can account for analogies based on learned relationships between elements in the source and target domains. However, its explanatory power regarding the discovery of new relationships during analogical reasoning is limited. We offer an alternative perspective for the role of PFC in analogical thought that may better address different types of analogical mappings.

  15. Reliability of analog quantum simulation

    DOE PAGES

    Sarovar, Mohan; Zhang, Jun; Zeng, Lishan

    2017-01-03

    Analog quantum simulators (AQS) will likely be the first nontrivial application of quantum technology for predictive simulation. However, there remain questions regarding the degree of confidence that can be placed in the results of AQS since they do not naturally incorporate error correction. Specifically, how do we know whether an analog simulation of a quantum model will produce predictions that agree with the ideal model in the presence of inevitable imperfections? At the same time there is a widely held expectation that certain quantum simulation questions will be robust to errors and perturbations in the underlying hardware. Resolving these twomore » points of view is a critical step in making the most of this promising technology. In this paper we formalize the notion of AQS reliability by determining sensitivity of AQS outputs to underlying parameters, and formulate conditions for robust simulation. Our approach naturally reveals the importance of model symmetries in dictating the robust properties. Finally, to demonstrate the approach, we characterize the robust features of a variety of quantum many-body models.« less

  16. A precondition prover for analogy.

    PubMed

    Bledsoe, W W

    1995-01-01

    We describe here a prover PC (precondition) that normally acts as an ordinary theorem prover, but which returns a 'precondition' when it is unable to prove the given formula. If F is the formula attempted to be proved and PC returns the precondition Q, then (Q-->F) is a theorem (that PC can prove). This prover, PC, uses a proof-plan. In its simplest mode, when there is no proof-plan, it acts like ordinary abduction. We show here how this method can be used to derive certain proofs by analogy. To do this, it uses a proof-plan from a given guiding proof to help construct the proof of a similar theorem, by 'debugging' (automatically) that proof-plan. We show here the analogy proofs of a few simple example theorems and one hard pair, Ex4 and Ex4L. The given proof-plan for Ex4 is used by the system to prove automatically Ex4; and that same proof-plan is then used to prove Ex4L, during which the proof-plan is 'debugged' (automatically). These two examples are similar to two other, more difficult, theorems from the theory of resolution, namely GCR (the ground completeness of resolution) and GCLR (the ground completeness of lock resolution). GCR and GCLR have also been handled, in essence, by this system but not completed in all their details.

  17. Prostacyclin analogs inhibit fibroblast migration.

    PubMed

    Kohyama, Tadashi; Liu, Xiangde; Kim, Hui Jung; Kobayashi, Tetsu; Ertl, Ronald F; Wen, Fu-Qiang; Takizawa, Hajime; Rennard, Stephen I

    2002-08-01

    The controlled accumulation of fibroblasts to sites of inflammation is crucial to effective tissue repair after injury. Either inadequate or excessive accumulation of fibroblasts could result in abnormal tissue function. Prostacyclin (PGI(2)) is a potent mediator in the coagulation and inflammatory processes. The aim of this study was to investigate the effect of PGI(2) on chemotaxis of human fetal lung fibroblasts (HFL-1). Using the blind well chamber technique, we found that the PGI(2) analog carbaprostacyclin (10(-6) M) inhibited HFL-1 chemotaxis to human plasma fibronectin (20 microg/ml) 58.0 +/- 13.2% (P < 0.05) and to platelet-derived growth factor (PDGF)-BB (10 ng/ml) 48.7 +/- 4.6% (P < 0.05). Checkerboard analysis demonstrated that carbaprostacyclin inhibits both directed and undirected migration. The inhibitory effect of the carbaprostacyclin was concentration dependent and blocked by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, suggesting that a cAMP-PKA pathway may be involved in the process. Two other PGI(2) analogs, ciprostene and dehydro-15-cyclohexyl carbaprostacyclin (both 10(-6) M), significantly inhibited fibroblast migration to fibronectin. In summary, PGI(2) appears to inhibit fibroblast chemotaxis to fibronectin and PDGF-BB. Such an effect may contribute to the regulation of fibroblasts in wound healing and could contribute to the pathogenesis of diseases characterized by abnormal tissue repair remodeling.

  18. Fault diagnosis of analog circuits

    NASA Astrophysics Data System (ADS)

    Bandler, J. W.; Salama, A. E.

    1985-08-01

    Theory and algorithms associated with four main categories of modern techniques used to locate faults in analog circuits are presented. These four general approaches are: the fault dictionary (FDA), the parameter identification (PIA), the fault verification (FVA), and the approximation (AA) approaches. The preliminaries and problems associated with the FDA, such as fault dictionary construction, the methods of optimum measurement selection, fault isolation criteria, and efficient methods of fault simulation, are discussed. The PIA techniques that utilize either linear or nonlinear systems of equations for identification of network elements are examined. Description of the FVA includes node-fault diagnosis, branch-fault diagnosis, subnetwork testability conditions, as well as combinatorial techniques, the failure-bound technique, and the network decomposition technique. In the AA, probabilistic methods and optimization-based methods are considered. In addition, the artificial intelligence technique and the different measures of testability are presented. A series of block diagrams is included.

  19. The Young Solar Analogs Project

    NASA Astrophysics Data System (ADS)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Fuller, V.; Kahvaz, Y.; Lambert, R.; Newsome, I.; Seeds, M.

    2013-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using facilities at the Dark Sky Observatory (DSO - Appalachian State University) and the Vatican Advanced Technology Telescope (VATT). These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in the 6th year of spectroscopic measurements of these stars: these data include Ca II H & K chromospheric flux measurements, and narrow-band measurements in the photospheric G-band, both obtained with the G/M spectrograph on the DSO 32-inch telescope. We will present evidence of activity cycles in a number of our stars, as well as periods determined from rotational modulation of the spectroscopic indices. The relationship between the Ca II activity index and the G-band index will be explored. NSF support for our project has provided funds for the construction of a robotic photometric telescope to monitor the program stars in a 5-passband system (Strömgren-v, Johnson-Cousins B, V, and R, and a 3-nm wide Hα filter). The robotic telescope has been functional since April 2012 and observes the program stars on every clear night; combined with the Piggy-back telescope attached to the DSO 32-inch, we now have photometric observations on over 130 nights stretching over nearly 2 years. We will examine the relationships between variations in the Ca II H & K index, the G-band index and the photometric bands. This project is supported by the National Science Foundation, grant AST-1109158.

  20. The Young Solar Analogs Project

    NASA Astrophysics Data System (ADS)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Seeds, M. F.; Morrison, S. S.

    2012-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using the Dark Sky Observatory (DSO -- Appalachian State University) 32-inch telescope and the G/M spectrograph. These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in our 5th year of obtaining Ca II K & H chromospheric flux measurements, and are beginning to see signs of long-term activity cycles in a number of our stars. In addition, rotational modulation of the chromospheric fluxes is detectable in our data, and we have determined rotational periods for many of our stars. Short timescale increases in the K & H fluxes have been observed in a number of our stars; these events may be related to stellar flares. VATTSpec, a new moderate-resolution spectrograph on the 1.8-m Vatican Telescope in Arizona, has recently become involved with the project. This spectrograph will increase our ability to detect short-term changes in stellar activity on timescales of hours to minutes. We have been monitoring the program stars for one year in a multi-band photometric system consisting of Stromgren-v, and Johnson B, V, and R filters. We will soon add a narrow-band H-alpha filter to the system. Photometry is being carried out with a small piggy-back telescope on the 32-inch, but a robotic photometric telescope is currently being installed at DSO for this purpose. This project is supported by the National Science Foundation.

  1. Priming analogical reasoning with false memories.

    PubMed

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  2. Children's use of analogy during collaborative reasoning.

    PubMed

    Lin, Tzu-Jung; Anderson, Richard C; Hummel, John E; Jadallah, May; Miller, Brian W; Nguyen-Jahiel, Kim; Morris, Joshua A; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age M=10.0, SD=0.6). Use of analogy was found to spread among the children in discussion groups and occur at an accelerating rate, primarily because of the increasing use of novel analogies. Relational analogies with shared surface features triggered purely relational analogies during the next 2 speaking turns, showing a trend of relational shift. These results provide distinctive new evidence for the importance of social interaction in an aspect of cognitive development.

  3. AnalogExplorer2 – Stereochemistry sensitive graphical analysis of large analog series

    PubMed Central

    Hu, Ye; Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2015-01-01

    AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use. PMID:26913194

  4. AnalogExplorer2 - Stereochemistry sensitive graphical analysis of large analog series.

    PubMed

    Hu, Ye; Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2015-01-01

    AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use.

  5. Design and Analysis of Reconfigurable Analog System

    DTIC Science & Technology

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  6. Classical Analogs of a Diatomic Chain

    SciTech Connect

    Gutierrez, L.; Diaz-de-Anda, A.; Mendez-Sanchez, R. A.; Morales, A.; Flores, J.; Monsivais, G.

    2010-12-21

    Using one dimensional rods with different configurations classical analogs of quantum mechanical systems frequently used in solid state physics can be obtained. Among this analogs we have recently discussed locally periodic rods which lead to band spectra; the effect of a topological defect, and the Wannier Stark ladders. In this paper, we present an elastic analog of the diatomic chain and show how the acoustical and optical bands emerge, as well of the nature of the wave amplitudes.

  7. Fermilab accelerator control system: Analog monitoring facilities

    SciTech Connect

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system.

  8. Properties of compressible elastica from relativistic analogy.

    PubMed

    Oshri, Oz; Diamant, Haim

    2016-01-21

    Kirchhoff's kinetic analogy relates the deformation of an incompressible elastic rod to the classical dynamics of rigid body rotation. We extend the analogy to compressible filaments and find that the extension is similar to the introduction of relativistic effects into the dynamical system. The extended analogy reveals a surprising symmetry in the deformations of compressible elastica. In addition, we use known results for the buckling of compressible elastica to derive the explicit solution for the motion of a relativistic nonlinear pendulum. We discuss cases where the extended Kirchhoff analogy may be useful for the study of other soft matter systems.

  9. Robust hyperchaotic synchronization via analog transmission line

    NASA Astrophysics Data System (ADS)

    Sadoudi, S.; Tanougast, C.

    2016-02-01

    In this paper, a novel experimental chaotic synchronization technique via analog transmission is discussed. We demonstrate through Field-Programmable Gate Array (FPGA) implementation design the robust synchronization of two embedded hyperchaotic Lorenz generators interconnected with an analog transmission line. The basic idea of this work consists in combining a numerical generation of chaos and transmitting it with an analog signal. The numerical chaos allows to overcome the callback parameter mismatch problem and the analog transmission offers robust data security. As application, this technique can be applied to all families of chaotic systems including time-delayed chaotic systems.

  10. Real World: Analog Testing in Extreme Environments

    NASA Image and Video Library

    See how NASA uses analog testing to simulate space exploration. Explore extreme environments like the Aquarius underwater laboratory in Key Largo, Florida. Find out how scientists use mathematical ...

  11. Expert analogy use in a naturalistic setting

    PubMed Central

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

    The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance. PMID:25505437

  12. Digital and analog chemical evolution.

    PubMed

    Goodwin, Jay T; Mehta, Anil K; Lynn, David G

    2012-12-18

    Living matter is the most elaborate, elegant, and complex hierarchical material known and is consequently the natural target for an ever-expanding scientific and technological effort to unlock and deconvolute its marvelous forms and functions. Our current understanding suggests that biological materials are derived from a bottom-up process, a spontaneous emergence of molecular networks in the course of chemical evolution. Polymer cooperation, so beautifully manifested in the ribosome, appeared in these dynamic networks, and the special physicochemical properties of the nucleic and amino acid polymers made possible the critical threshold for the emergence of extant cellular life. These properties include the precise and geometrically discrete hydrogen bonding patterns that dominate the complementary interactions of nucleic acid base-pairing that guide replication and ensure replication fidelity. In contrast, complex and highly context-dependent sets of intra- and intermolecular interactions guide protein folding. These diverse interactions allow the more analog environmental chemical potential fluctuations to dictate conformational template-directed propagation. When these two different strategies converged in the remarkable synergistic ribonucleoprotein that is the ribosome, this resulting molecular digital-to-analog converter achieved the capacity for both persistent information storage and adaptive responses to an ever-changing environment. The ancestral chemical networks that preceded the Central Dogma of Earth's biology must reflect the dynamic chemical evolutionary landscapes that allowed for selection, propagation, and diversification and ultimately the demarcation and specialization of function that modern biopolymers manifest. Not only should modern biopolymers contain molecular fossils of this earlier age, but it should be possible to use this information to reinvent these dynamic functional networks. In this Account, we review the first dynamic network

  13. Children's Use of Analogy during Collaborative Reasoning

    ERIC Educational Resources Information Center

    Lin, Tzu-Jung; Anderson, Richard C.; Hummel, John E.; Jadallah, May; Miller, Brian W.; Nguyen-Jahiel, Kim; Morris, Joshua A.; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age…

  14. The Pennies-as-Electrons Analogy

    ERIC Educational Resources Information Center

    Ashmann, Scott

    2009-01-01

    Everyday experiences familiarize students with the ways in which electricity is used, but often the underlying concepts remain a mystery. Teachers often use analogies to help students relate the flow of electrons to other common systems, but many times these analogies are incomplete and lead to more student misconceptions. However, the "pass the…

  15. Piperazine-based nucleic acid analogs

    DOEpatents

    Schmidt, Jurgen; Silks, Louis A.; Michalczyk, Ryszard

    2005-01-11

    A novel nucleoside analog is disclosed which comprises a piperazine ring in the place of the ring ribose or deoxyribose sugar. Monomers utilizing a broad variety of nucleobases are disclosed, as well as oligomers comprising the monomers disclosed herein linked by a variety of linkages, including amide, phosphonamide, and sulfonamide linkages. A method of synthesizing the nucleoside analogs is also disclosed.

  16. Analogical Processes and College Developmental Reading

    ERIC Educational Resources Information Center

    Paulson, Eric J.

    2014-01-01

    Although a solid body of research concerning the role of analogies in reading processes has emerged at a variety of age groups and reading proficiencies, few of those studies have focused on analogy use by readers enrolled in college developmental reading courses. The current study explores whether 232 students enrolled in mandatory (by placement…

  17. Mathematical Analogs and the Teaching of Fractions.

    ERIC Educational Resources Information Center

    Charles, Kathy; Nason, Rod; Cooper, Tom

    The literature has noted that some mathematical analogs are more effective than others for the teaching of fractions. This study aimed to evaluate the efficacy of seven mathematical analogs commonly used in the teaching of the partitive quotient fraction construct. A sample of twelve purposively selected Year Three children were presented with…

  18. Understanding the Development of Analogical Reasoning Ability.

    ERIC Educational Resources Information Center

    Goldman, Susan R.; Bisanz, Jeffrey

    This paper takes the position that theories about individual differences in childhood and theories about cognitive development both would be enhanced if the two lines of research were integrated. The heuristic value of this position is illustrated in the context of analogical reasoning tasks. A general model of analogy solution and potential…

  19. Rotanone analogs: method of preparation and use

    DOEpatents

    VanBrocklin, Henry F; O& #x27; Neil, James P; Gibbs, Andrew R; Erathodiyil, Nandanan

    2013-10-08

    The present invention provides rotenone analogs and methods of making and using them. Labeled with single photon and positron emitting isotopes, the rotenone analogs of the present invention are useful in, for example, clinical imaging applications as tracers to measure cardiac blood flow and detect regions of ischemia.

  20. A Mechanical Analogy for the Photoelectric Effect

    ERIC Educational Resources Information Center

    Kovacevic, Milan S.; Djordjevich, Alexandar

    2006-01-01

    Analogy is a potent tool in the teacher's repertoire. It has been particularly well recognized in the teaching of science. However, careful planning is required for its effective application to prevent documented drawbacks when analogies are stretched too far. Befitting the occasion of the World Year of Physics commemorating Albert Einstein's 1905…

  1. 38 CFR 4.20 - Analogous ratings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Analogous ratings. 4.20 Section 4.20 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES General Policy in Rating § 4.20 Analogous ratings. When an unlisted condition is encountered it...

  2. A Mechanical Analogy for the Photoelectric Effect

    ERIC Educational Resources Information Center

    Kovacevic, Milan S.; Djordjevich, Alexandar

    2006-01-01

    Analogy is a potent tool in the teacher's repertoire. It has been particularly well recognized in the teaching of science. However, careful planning is required for its effective application to prevent documented drawbacks when analogies are stretched too far. Befitting the occasion of the World Year of Physics commemorating Albert Einstein's 1905…

  3. Analogical Reasoning in Restructuring Scientific Knowledge.

    ERIC Educational Resources Information Center

    Mason, Lucia; Sorzio, Paolo

    1996-01-01

    Presents the results of an experiment that evaluated the efficiency of analogy in the conceptual restructuring of a science topic. The experiment involved a fifth-grade class studying water and heat flow. Discovered that analogy can act as an effective trigger for restructuring knowledge. (MJP)

  4. Structure Mapping in Analogy and Similarity.

    ERIC Educational Resources Information Center

    Gentner, Dedre; Markman, Arthur B.

    1997-01-01

    It is suggested that both similarity and analogy involve a process of structural alignment and mapping. The structure mapping process is described as it has been worked out for analogy, and this view is then extended to similarity and used to generate new predictions. (SLD)

  5. The Multidimensionality of Verbal Analogy Items

    ERIC Educational Resources Information Center

    Ullstadius, Eva; Carlstedt, Berit; Gustafsson, Jan-Eric

    2008-01-01

    The influence of general and verbal ability on each of 72 verbal analogy test items were investigated with new factor analytical techniques. The analogy items together with the Computerized Swedish Enlistment Battery (CAT-SEB) were given randomly to two samples of 18-year-old male conscripts (n = 8566 and n = 5289). Thirty-two of the 72 items had…

  6. The Pennies-as-Electrons Analogy

    ERIC Educational Resources Information Center

    Ashmann, Scott

    2009-01-01

    Everyday experiences familiarize students with the ways in which electricity is used, but often the underlying concepts remain a mystery. Teachers often use analogies to help students relate the flow of electrons to other common systems, but many times these analogies are incomplete and lead to more student misconceptions. However, the "pass the…

  7. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

    Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

    2014-01-01

    Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

  8. Use of Analogy in Computer Language Acquisition.

    ERIC Educational Resources Information Center

    Pohl, Heidi L.; Nutter, Jane Terry

    1985-01-01

    Subjects in a study of analogic reasoning use in learning a computer language read text describing an invented LISP dialect and then solved problems and described language constructs. Five of six factors studied indicating use of analogy with a familiar computer language showed statistically significant results, supporting the hypothesis.…

  9. The Multidimensionality of Verbal Analogy Items

    ERIC Educational Resources Information Center

    Ullstadius, Eva; Carlstedt, Berit; Gustafsson, Jan-Eric

    2008-01-01

    The influence of general and verbal ability on each of 72 verbal analogy test items were investigated with new factor analytical techniques. The analogy items together with the Computerized Swedish Enlistment Battery (CAT-SEB) were given randomly to two samples of 18-year-old male conscripts (n = 8566 and n = 5289). Thirty-two of the 72 items had…

  10. Verbal Analogical Reasoning in Children and Adolescents.

    ERIC Educational Resources Information Center

    Nippold, Marilyn A.

    1986-01-01

    Verbal analogical reasoning tasks are described as potentially valuable in the assessment and management of subtle linguistic defects less easily detected by standardized language tests. Semantic and structural factors that should be considered in the development of verbal analogies as test items are cited, as well as adaptations for nonreaders.…

  11. Understanding the Development of Analogical Reasoning Ability.

    ERIC Educational Resources Information Center

    Goldman, Susan R.; Bisanz, Jeffrey

    This paper takes the position that theories about individual differences in childhood and theories about cognitive development both would be enhanced if the two lines of research were integrated. The heuristic value of this position is illustrated in the context of analogical reasoning tasks. A general model of analogy solution and potential…

  12. Response Generation Norms for Verbal Analogies.

    ERIC Educational Resources Information Center

    Ingram, Albert; Pellegrino, James W.

    Normative data were collected for the generation of responses to 150 incomplete verbal analogies. Two types of normative data are provided: (a) the probabilities associated with each response produced for each analogy base and (b) the probabilities that initial responses represented the appropriate semantic relationship, with a division of…

  13. Student-Generated Analogies in Biology.

    ERIC Educational Resources Information Center

    Middleton, James L.

    1991-01-01

    Discusses the advantages of and strategies in having students create analogies to facilitate learning biology. Presents a vocabulary worksheet to facilitate analogy creation and describes its use. The author discusses the use of instructional strategies including forced associations, metaphorical sketches, mnemonics, and association memorization.…

  14. Young Children's Analogical Reasoning in Science Domains

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  15. An Analog Computer for Electronic Engineering Education

    ERIC Educational Resources Information Center

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  16. Young Children's Analogical Reasoning in Science Domains

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  17. An Analog Computer for Electronic Engineering Education

    ERIC Educational Resources Information Center

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  18. Novel Analog For Muscle Deconditioning

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd. Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Ploutz-Snyder, Robert; Bloomberg, Jacob

    2011-01-01

    Existing models (such as bed rest) of muscle deconditioning are cumbersome and expensive. We propose a new model utilizing a weighted suit to manipulate strength, power, or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre-and postflightastronaut performance data for the same tasks. Splineregression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/BW of 79 J/kg, isokineticknee extension (KE)/BW of 6 Nm/kg, and KE torque/BW of 1.9 Nm/kg.Conclusions: Laboratory manipulation of relative strength has promise as an appropriate analog for spaceflight-induced loss of muscle function, for predicting occupational task performance and establishing operationally relevant strength thresholds.

  19. Novel Analog For Muscle Deconditioning

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd, Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Bloomberg, Jacob

    2010-01-01

    Existing models of muscle deconditioning are cumbersome and expensive (ex: bedrest). We propose a new model utilizing a weighted suit to manipulate strength, power or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre- and post-flight astronaut performance data using the same tasks. Spline regression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of: leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/ BW of 79 J/kg, knee extension (KE) isokinetic/BW of 6 Nm/Kg and KE torque/BW of 1.9 Nm/kg. Conclusions: Laboratory manipulation of strength / BW has promise as an appropriate analog for spaceflight-induced loss of muscle function for predicting occupational task performance and establishing operationally relevant exercise targets.

  20. Solar System Analog; WMO Statement

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    Scientists searching for extra-solar planets have discovered the closest known analog to our own Solar System. A planet with a mass about twice that of Jupiter is in a near-circular orbit of the star HD70642, a team of astronomers from Australia, the United Kingdom, and the United States announced on 3 July at a conference in Paris on extra-solar planets.The planet measures about three-fifths the size of Jupiter, circles its star about every six years, and is in an orbit equivalent to being about halfway between Mars and Jupiter if it were located in our Solar System, according to the astronomers. The star is about 90 light years away from Earth in the constellation Puppis.Public concern about a spate of well-publicized, extreme weather events around the world this year has prompted the World Meteorological Organization to issue a statement that, as global temperatures continues to rise due to climate change, the number and intensity of extreme events might increase. The July 2 statement is based on scientific assessments by the Intergovernmental Panel on Climate Change and others, rather than on any new studies, according to Ken Davidson, director orf WMO's World Climate Program Department. The statement cites record high termperatures so far this summer in southern France and in Switzerland, an abnormally high number of tornadoes in the U.S. in May, and particularly heavy rains from tropical cyclones in Sri Lanka.

  1. An Analog Earth Climate Model

    NASA Astrophysics Data System (ADS)

    Varekamp, J. C.

    2010-12-01

    The earth climate is broadly governed by the radiative power of the sun as well as the heat retention and convective cooling of the atmosphere. I have constructed an analog earth model for an undergraduate climate class that simulates mean climate using these three parameters. The ‘earth’ is a hollow, black, bronze sphere (4 cm diameter) mounted on a thin insulated rod, and illuminated by two opposite optic fibers, with light focused on the sphere by a set of lenses. The sphere is encased in a large double-walled aluminum cylinder (34 cm diameter by 26 cm high) with separate water cooling jackets at the top, bottom, and sides. The cylinder can be filled with a gas of choice at a variety of pressures or can be run in vacuum. The exterior is cladded with insulation, and the temperature of the sphere, atmosphere and walls is monitored with thermocouples. The temperature and waterflow of the three cooling jackets can be monitored to establish the energy output of the whole system; the energy input is the energy yield of the two optic fibers. A small IR transmissive lens at the top provides the opportunity to hook up the fiber of a hyper spectrometer to monitor the emission spectrum of the black ‘earth’ sphere. A pressure gauge and gas inlet-outlet system for flushing of the cell completes it. The heat yield of the cooling water at the top is the sum of the radiative and convective components, whereas the bottom jacket only carries off the radiative heat of the sphere. Undergraduate E&ES students at Wesleyan University have run experiments with dry air, pure CO2, N2 and Ar at 1 atmosphere, and a low vacuum run was accomplished to calibrate the energy input. For each experiment, the lights are flipped on, the temperature acquisition routine is activated, and the sphere starts to warm up until an equilibrium temperature has been reached. The lights are then flipped off and the cooling sequence towards ambient is registered. The energy input is constant for a given

  2. Investigation of Celestial Solid Analogs

    NASA Technical Reports Server (NTRS)

    Sievers, A. J.

    2003-01-01

    Our far infrared studies of both hydrophobic and hydrophilic aerogel grains have demonstrated that the mm and sub-mm wave absorption produced by the fundamental two level systems (TLS) mechanism represents a more significant contribution for these open grain structures than for bulk amorphous silicate grains. We found that the region with the anomalous temperature dependence of the spectral index due to the TLS excitations can extend in a fluffy material up to 80 per cm, which is well beyond its typical upper limit for bulk glasses. Currently there is no theoretical explanation for this surprising result. The effects of reduced dimensionality on the optical properties of carbonaceous grains have been studied with a systematic investigation of carbon aerogels. This spectroscopic approach has permitted a more reliable determination of the single grain mass normalized absorption coefficient based on the experimentally determined characteristics of the fluffy material rather than on first principles calculations involving the bulk properties of the substance. Our finding is that the electrical connectivity of the material is the main factor affecting its far infrared absorption coefficient. Another one of the main constituents of the interstellar dust, amorphous ice, has been investigated in the mm-wave region both in the high (HDA) and low (LDA) density amorphous phases and as a function of impurities. We found that doping either phase with ionic (LiCl) or molecular (methanol) impurities decreases the difference in the mm-wave absorption coefficient between the HDA and LDA ice phases so that the HDA spectrum can be used as an analog for impure ice absorption in the far infrared spectral region.

  3. Analog regulation of metabolic demand

    PubMed Central

    2011-01-01

    Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs) from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants), this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN), as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our results show that DNA

  4. Namibian Analogs To Titan Dunes

    NASA Astrophysics Data System (ADS)

    Wall, Stephen D.; Lopes, R.; Kirk, R.; Stofan, E.; Farr, T.; Van der Ploeg, P.; Lorenz, R.; Radebaugh, J.

    2009-09-01

    Titan's equatorial dunes, observed in Cassini SAR, have been described as longitudinal, similar to longitudinal dunes in the Namib sand sea in southern Africa. Their "Y” junctions and the way they divert around topography are used as evidence of equatorial wind flow direction. In two instances of such diversion they exhibit overlying or crosshatched patterns in two distinct directions that have been interpreted as a transition to transverse dunes. Here we describe field observations of the Namibian dunes and these comparisons, we present images of the dunes from terrestrial SAR missions, and we discuss implications to both the Titan dunes and the wind regime that created them. Selected portions of the Namibian dunes resemble Titan's dunes in peak-to-peak distance and length. They are morphologically similar to Titan, and specific superficial analogs are common, but they also differ. For example, when Titan dunes encounter topography they either terminate abruptly, "climb” the upslope, or divert around; only the latter behavior is seen in remote sensing images of Namibia. Namib linear dunes do transition to transverse as they divert, but at considerably smaller wavelength, while at Titan the wavelengths are of the same scale. Crosshatching of similar-wavelength dunes does occur in Namibia, but not near obstacles. Many additional aeolian features that are seen at Namibia such as star dunes, serpentine ridges and scours have not been detected on Titan, although they might be below the Cassini SAR's 300-m resolution. These similarities and differences allow us to explore mechanisms of Titan dune formation, in some cases giving us clues as to what larger scale evidence to look for in SAR images. Viewed at similar resolution, they provide interesting comparisons with the Titan dunes, both in likeness and differences. A part of this work was carried out at JPL under contract with NASA.

  5. Fostering Multilateral Involvement in Analog Research

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2015-01-01

    International collaboration in space flight research is an effective means for conducting investigations and utilizing limited resources to the fullest extent. Through these multilateral collaborations mutual research questions can be investigated and resources contributed by each international partner to maximize the scientific benefits to all parties. Recently the international partners embraced this approach to initiate collaborations in ground-based space flight analog environments. In 2011, the International Analog Research Working Group was established, and later named the International Human Space Flight Analog Research Coordination Group (HANA). Among the goals of this working group are to 1) establish a framework to coordinate research campaigns, as appropriate, to minimize duplication of effort and enhance synergy; 2) define what analogs are best to use for collaborative interests; and 3) facilitate interaction between discipline experts in order to have the full benefit of international expertise. To accomplish these goals, HANA is currently engaged in developing international research campaigns in ground-based analogs. Plans are being made for an international solicitation for proposals to address research of common interest to all international partners. This solicitation with identify an analog environment that will best accommodate the types of investigations requested. Once selected, studies will be integrated into a campaign and implemented at the analog site. Through these combined efforts, research beneficial to all partners will be conducted efficiently to further address human risks of space exploration.

  6. Observed Methods for Generating Analogies in Scientific Problem Solving. Revised.

    ERIC Educational Resources Information Center

    Clement, John

    Evidence from video tapes of experts thinking aloud and using analogies in scientific problem solving is presented. Four processes appear to be important in using an analogy: (1) generating the analogy; (2) establishing confidence in the validity of the analogy relation; (3) understanding the analogous case; and (4) applying findings to the…

  7. Analogies: Explanatory Tools in Web-Based Science Instruction

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Taasoobshirazi, Gita; Fowler, Shawn

    2007-01-01

    This article helps designers of Web-based science instruction construct analogies that are as effective as those used in classrooms by exemplary science teachers. First, the authors explain what analogies are, how analogies foster learning, and what form analogies should take. Second, they discuss science teachers' use of analogies. Third, they…

  8. Analogies: Explanatory Tools in Web-Based Science Instruction

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Taasoobshirazi, Gita; Fowler, Shawn

    2007-01-01

    This article helps designers of Web-based science instruction construct analogies that are as effective as those used in classrooms by exemplary science teachers. First, the authors explain what analogies are, how analogies foster learning, and what form analogies should take. Second, they discuss science teachers' use of analogies. Third, they…

  9. Analog detection for cavity lifetime spectroscopy

    DOEpatents

    Zare, Richard N.; Harb, Charles C.; Paldus, Barbara A.; Spence, Thomas G.

    2001-05-15

    An analog detection system for determining a ring-down rate or decay rate 1/.tau. of an exponentially decaying ring-down beam issuing from a lifetime or ring-down cavity during a ring-down phase. Alternatively, the analog detection system determines a build-up rate of an exponentially growing beam issuing from the cavity during a ring-up phase. The analog system can be employed in continuous wave cavity ring-down spectroscopy (CW CRDS) and pulsed CRDS (P CRDS) arrangements utilizing any type of ring-down cavity including ring-cavities and linear cavities.

  10. Analog detection for cavity lifetime spectroscopy

    DOEpatents

    Zare, Richard N.; Harb, Charles C.; Paldus, Barbara A.; Spence, Thomas G.

    2003-01-01

    An analog detection system for determining a ring-down rate or decay rate 1/.tau. of an exponentially decaying ring-down beam issuing from a lifetime or ring-down cavity during a ring-down phase. Alternatively, the analog detection system determines a build-up rate of an exponentially growing beam issuing from the cavity during a ring-up phase. The analog system can be employed in continuous wave cavity ring-down spectroscopy (CW CRDS) and pulsed CRDS (P CRDS) arrangements utilizing any type of ring-down cavity including ring-cavities and linear cavities.

  11. Programmable Analog-To-Digital Converter

    NASA Technical Reports Server (NTRS)

    Kist, Edward H., Jr.

    1993-01-01

    High-speed analog-to-digital converter with programmable voltage steps that can be changed during operation. Allows concentration of converter resolution over specific portion of waveform. Particularly useful in digitizing wind-shear radar and lidar return signals, in digital oscilloscopes, and other applications in which desirable to increase digital resolution over specific area of waveform while accepting lower resolution over rest of waveform. Effective increase in dynamic range achieved without increase in number of analog-to-digital converter bits. Enabling faster analog-to-digital conversion.

  12. Computer Analogies: Teaching Molecular Biology and Ecology.

    ERIC Educational Resources Information Center

    Rice, Stanley; McArthur, John

    2002-01-01

    Suggests that computer science analogies can aid the understanding of gene expression, including the storage of genetic information on chromosomes. Presents a matrix of biology and computer science concepts. (DDR)

  13. Analog Computer Laboratory with Biological Examples.

    ERIC Educational Resources Information Center

    Strebel, Donald E.

    1979-01-01

    The use of biological examples in teaching applications of the analog computer is discussed and several examples from mathematical ecology, enzyme kinetics, and tracer dynamics are described. (Author/GA)

  14. Review of field-programmable analog arrays

    NASA Astrophysics Data System (ADS)

    Gulak, Glen; D'Mello, Dean R.

    1996-10-01

    The drive towards shorter design cycles for analog integrated circuits has given impetus to several developments in the area of field-programmable analog arrays (FPAAs). Various approaches have been taken in implementing topological and parametric programmability of analog circuits. Recent extensions of this work have married FPAAs to their digital counterparts (FPGAs) along with data conversion interfaces, to form field-programmable mixed signal arrays (FPMAs). This survey paper reviews work to data in the area of programmable analog and mixed signal circuits. The body of work reviewed includes university and industrial research, commercial products and patents. A time-line of important achievements in the area is drawn and the status of various activities is summarized.

  15. An Earth Analog to Mars Yellowknife Bay

    NASA Image and Video Library

    2013-03-12

    A sampling pit exposing clay-bearing lake sediments, deposited in a basaltic basin in southern Australia -- a modern terrestrial analog to the Yellowknife Bay area that NASA Curiosity rover is exploring.

  16. Analog Computer Laboratory with Biological Examples.

    ERIC Educational Resources Information Center

    Strebel, Donald E.

    1979-01-01

    The use of biological examples in teaching applications of the analog computer is discussed and several examples from mathematical ecology, enzyme kinetics, and tracer dynamics are described. (Author/GA)

  17. CMOS analog switches for adaptive filters

    NASA Technical Reports Server (NTRS)

    Dixon, C. E.

    1980-01-01

    Adaptive active low-pass filters incorporate CMOS (Complimentary Metal-Oxide Semiconductor) analog switches (such as 4066 switch) that reduce variation in switch resistance when filter is switched to any selected transfer function.

  18. An Electrical Analog Computer for Poets

    ERIC Educational Resources Information Center

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  19. The Analog (Computer) As a Physiology Adjunct.

    ERIC Educational Resources Information Center

    Stewart, Peter A.

    1979-01-01

    Defines and discusses the analog computer and its use in a physiology laboratory. Includes two examples: (1) The Respiratory Control Function and (2) CO-Two Control in the Respiratory System. Presents diagrams and mathematical models. (MA)

  20. Computer Analogies: Teaching Molecular Biology and Ecology.

    ERIC Educational Resources Information Center

    Rice, Stanley; McArthur, John

    2002-01-01

    Suggests that computer science analogies can aid the understanding of gene expression, including the storage of genetic information on chromosomes. Presents a matrix of biology and computer science concepts. (DDR)

  1. The Analog (Computer) As a Physiology Adjunct.

    ERIC Educational Resources Information Center

    Stewart, Peter A.

    1979-01-01

    Defines and discusses the analog computer and its use in a physiology laboratory. Includes two examples: (1) The Respiratory Control Function and (2) CO-Two Control in the Respiratory System. Presents diagrams and mathematical models. (MA)

  2. NASA Now: Exploring Asteroids: An Analog Mission

    NASA Image and Video Library

    NASA’s Extreme Environment Mission Operations, or NEEMO, project lead Bill Todd describes this analog mission and how aquanauts living and working in an undersea habitat are helping NASA prepare ...

  3. An Electronic Analog of the Diffraction Grating.

    ERIC Educational Resources Information Center

    MacLeod, A. M.

    1978-01-01

    Gives an outline description of electronic circuitry which is analogous to the optical diffraction grating or to crystals used in the Bragg reflection of X-rays or electron waves, and explains how to use it. (Author/GA)

  4. An Analog Computer for Educational Laboratories

    ERIC Educational Resources Information Center

    Hamilton, J. A.

    1975-01-01

    Provides instructions for constructing a desk analog computer which is particularly convenient to the user and has a number of advantages over commercially available models, including lower cost for given computing power. (Author/MLH)

  5. Optical analog-to-digital converter

    DOEpatents

    Vawter, G. Allen; Raring, James; Skogen, Erik J.

    2009-07-21

    An optical analog-to-digital converter (ADC) is disclosed which converts an input optical analog signal to an output optical digital signal at a sampling rate defined by a sampling optical signal. Each bit of the digital representation is separately determined using an optical waveguide interferometer and an optical thresholding element. The interferometer uses the optical analog signal and the sampling optical signal to generate a sinusoidally-varying output signal using cross-phase-modulation (XPM) or a photocurrent generated from the optical analog signal. The sinusoidally-varying output signal is then digitized by the thresholding element, which includes a saturable absorber or at least one semiconductor optical amplifier, to form the optical digital signal which can be output either in parallel or serially.

  6. Use of analogy in learning scientific concepts.

    PubMed

    Donnelly, C M; McDaniel, M A

    1993-07-01

    Four experiments compared learning of scientific concepts as expressed in either traditional literal form or through an analogy. Comprehension of basic-level details and inferential implications was measured through multiple-choice testing. In Experiment 1, literal or analogical renditions were presented in textual form only. In Experiment 2, text was accompanied by a dynamic video. In Experiment 3, the video and text literal rendition was compared with a text-only analogical rendition. In Experiment 4, subjects read only about a familiar domain. Subjects consistently answered basic-level questions most accurately when concepts were expressed literally, but answered inferential questions most accurately when concepts were expressed analogically. Analysis of individual differences (Experiment 2) indicated that this interaction strongly characterized the conceptual learning of science novices. The results are discussed within the framework of schema induction.

  7. An Electronic Analog of the Diffraction Grating.

    ERIC Educational Resources Information Center

    MacLeod, A. M.

    1978-01-01

    Gives an outline description of electronic circuitry which is analogous to the optical diffraction grating or to crystals used in the Bragg reflection of X-rays or electron waves, and explains how to use it. (Author/GA)

  8. An Electrical Analog Computer for Poets

    ERIC Educational Resources Information Center

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  9. Analog hardware for learning neural networks

    NASA Technical Reports Server (NTRS)

    Eberhardt, Silvio P. (Inventor)

    1991-01-01

    This is a recurrent or feedforward analog neural network processor having a multi-level neuron array and a synaptic matrix for storing weighted analog values of synaptic connection strengths which is characterized by temporarily changing one connection strength at a time to determine its effect on system output relative to the desired target. That connection strength is then adjusted based on the effect, whereby the processor is taught the correct response to training examples connection by connection.

  10. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  11. The Structure of Analogical Models in Science.

    DTIC Science & Technology

    1980-07-01

    analogies cannot. 8. A Freudian defense might claim that the theory merely reflects the illogic of the unconscious. But a theory about an unclarified...an initial comparison. To illustrate the points, analogies of historical importance are analyzed. Although the focus is on theory , some empirical...feature-list theory , the structure-mapping approach makes a strong distinction between objects and their attributes, on the one hand, and relationships, on

  12. ANALOG-TO-DIGITAL DATA CONVERTER

    DOEpatents

    Rodgers, G.W.; Althouse, J.E.; Anderson, D.P.; Bussey, G.R.; Minnear, L.H.

    1960-09-01

    Electrical apparatus is described, particularly useful in telemetry work, for converting analog signals into electrical pulses and recording them. An electronic editor commands the taking of signal readings at a frequency which varies according to linearity of the analog signal being converted. Readings of information signals are recorded, along with time base readings and serial numbering, if desired, on magnetic tape and the latter may be used to operate a computer or the like. Magnetic tape data may be transferred to punched cards.

  13. Protein Structure Prediction with Visuospatial Analogy

    NASA Astrophysics Data System (ADS)

    Davies, Jim; Glasgow, Janice; Kuo, Tony

    We show that visuospatial representations and reasoning techniques can be used as a similarity metric for analogical protein structure prediction. Our system retrieves pairs of α-helices based on contact map similarity, then transfers and adapts the structure information to an unknown helix pair, showing that similar protein contact maps predict similar 3D protein structure. The success of this method provides support for the notion that changing representations can enable similarity metrics in analogy.

  14. The analogy between stereo depth and brightness.

    PubMed

    Brookes, A; Stevens, K A

    1989-01-01

    Apparent depth in stereograms exhibits various simultaneous-contrast and induction effects analogous to those reported in the luminance domain. This behavior suggests that stereo depth, like brightness, is reconstructed, ie recovered from higher-order spatial derivatives or differences of the original signal. The extent to which depth is analogous to brightness is examined. There are similarities in terms of contrast effects but dissimilarities in terms of the lateral inhibition effects traditionally attributed to underlying spatial-differentiation operators.

  15. Analog modelling of obduction processes

    NASA Astrophysics Data System (ADS)

    Agard, P.; Zuo, X.; Funiciello, F.; Bellahsen, N.; Faccenna, C.; Savva, D.

    2012-04-01

    Obduction corresponds to one of plate tectonics oddities, whereby dense, oceanic rocks (ophiolites) are presumably 'thrust' on top of light, continental ones, as for the short-lived, almost synchronous Peri-Arabic obduction (which took place along thousands of km from Turkey to Oman in c. 5-10 Ma). Analog modelling experiments were performed to study the mechanisms of obduction initiation and test various triggering hypotheses (i.e., plate acceleration, slab hitting the 660 km discontinuity, ridge subduction; Agard et al., 2007). The experimental setup comprises (1) an upper mantle, modelled as a low-viscosity transparent Newtonian glucose syrup filling a rigid Plexiglas tank and (2) high-viscosity silicone plates (Rhodrosil Gomme with PDMS iron fillers to reproduce densities of continental or oceanic plates), located at the centre of the tank above the syrup to simulate the subducting and the overriding plates - and avoid friction on the sides of the tank. Convergence is simulated by pushing on a piston at one end of the model with velocities comparable to those of plate tectonics (i.e., in the range 1-10 cm/yr). The reference set-up includes, from one end to the other (~60 cm): (i) the piston, (ii) a continental margin containing a transition zone to the adjacent oceanic plate, (iii) a weakness zone with variable resistance and dip (W), (iv) an oceanic plate - with or without a spreading ridge, (v) a subduction zone (S) dipping away from the piston and (vi) an upper, active continental margin, below which the oceanic plate is being subducted at the start of the experiment (as is known to have been the case in Oman). Several configurations were tested and over thirty different parametric tests were performed. Special emphasis was placed on comparing different types of weakness zone (W) and the extent of mechanical coupling across them, particularly when plates were accelerated. Displacements, together with along-strike and across-strike internal deformation in all

  16. Working memory predicts children's analogical reasoning.

    PubMed

    Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

    2017-09-15

    Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. NASA Cribs: Human Exploration Research Analog

    NASA Image and Video Library

    2017-07-20

    Follow along as interns at NASA’s Johnson Space Center show you around the Human Exploration Research Analog (HERA), a mission simulation environment located onsite at the Johnson Space Center in Houston. HERA is a unique three-story habitat designed to serve as an analog for isolation, confinement, and remote conditions in exploration scenarios. This video gives a tour of where crew members live, work, sleep, and eat during the analog missions. Find out more about HERA mission activities: https://www.nasa.gov/analogs/hera Find out how to be a HERA crew member: https://www.nasa.gov/analogs/hera/want-to-participate For more on NASA internships: https://intern.nasa.gov/ For Johnson Space Center specific internships: https://pathways.jsc.nasa.gov/ https://www.nasa.gov/centers/johnson/education/interns/index.html HD download link: https://archive.org/details/jsc2017m000730_NASA-Cribs-Human-Exploration-Research-Analog --------------------------------- FOLLOW JOHNSON SPACE CENTER INTERNS! Facebook: @NASA.JSC.Students https://www.facebook.com/NASA.JSC.Students/ Instagram: @nasajscstudents https://www.instagram.com/nasajscstudents/ Twitter: @NASAJSCStudents https://twitter.com/nasajscstudents

  18. Phonological priming and orthographic analogies in reading.

    PubMed

    Goswami, U

    1990-04-01

    Recent work has demonstrated that children can use orthographic analogies between the spelling patterns in words to help in decoding new words (e.g., using beak to read peak; Goswami, 1986, 1988). However, one objection has been that these analogy effects may be due to phonological priming. Two experiments examined the phonological priming alternative. In Experiment 1, a single word reading task compared the use of analogies to read words that shared both orthography and phonology (e.g., most-post), that shared orthography only (e.g., most-cost), or that shared phonology only (e.g. most-toast--the phonological priming condition). Limited effects of phonological priming were found. Experiment 2 then presented the same words embedded in prose passages--"real reading." While the orthographic analogy effect remained robust, the small phonological priming effect disappeared. It is argued that phonological priming is an insufficient explanation of the analogy effect at the single word level, and plays no role in the use of analogies in story reading.

  19. Students' Pre- and Post-Teaching Analogical Reasoning When They Draw their Analogies

    NASA Astrophysics Data System (ADS)

    Braga Mozzer, Nilmara; Justi, Rosária

    2012-02-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in cognitive science literature about this issue. In this study, we investigated students' analogical reasoning as a creative process where an environment was set up to foster the students' generating and explaining their own analogies. Data were gathered from pre- and post-teaching interviews, in which the 13-14-year-old students were asked to make comparisons that could explain how atoms are bound. Such data supported the discussion about how students reasoned analogically. Our results made it evident that the task aims and the students' salient knowledge exerted a great influence on the drawing of analogies.

  20. Optical domain analog to digital conversion methods and apparatus

    SciTech Connect

    Vawter, Gregory A

    2014-05-13

    Methods and apparatus for optical analog to digital conversion are disclosed. An optical signal is converted by mapping the optical analog signal onto a wavelength modulated optical beam, passing the mapped beam through interferometers to generate analog bit representation signals, and converting the analog bit representation signals into an optical digital signal. A photodiode receives an optical analog signal, a wavelength modulated laser coupled to the photodiode maps the optical analog signal to a wavelength modulated optical beam, interferometers produce an analog bit representation signal from the mapped wavelength modulated optical beam, and sample and threshold circuits corresponding to the interferometers produce a digital bit signal from the analog bit representation signal.

  1. Analog Signal Correlating Using an Analog-Based Signal Conditioning Front End

    NASA Technical Reports Server (NTRS)

    Prokop, Norman; Krasowski, Michael

    2013-01-01

    This innovation is capable of correlating two analog signals by using an analog-based signal conditioning front end to hard-limit the analog signals through adaptive thresholding into a binary bit stream, then performing the correlation using a Hamming "similarity" calculator function embedded in a one-bit digital correlator (OBDC). By converting the analog signal into a bit stream, the calculation of the correlation function is simplified, and less hardware resources are needed. This binary representation allows the hardware to move from a DSP where instructions are performed serially, into digital logic where calculations can be performed in parallel, greatly speeding up calculations.

  2. NaturAnalogs for the Unsaturated Zone

    SciTech Connect

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  3. Magnetic activity of seismic solar analogs

    NASA Astrophysics Data System (ADS)

    Salabert, D.; García, R. A.; Beck, P. G.

    2016-12-01

    We present our latest results on the solar-stellar connection by studying 18 solar analogs that we identified among the Kepler seismic sample tep{salabert16a}. We measured their magnetic activity properties using observations collected by the Kepler satellite and the ground-based, high-resolution HERMES spectrograph. The photospheric (S{_ph}) and chromospheric (S) magnetic activity proxies of these seismic solar analogs are compared in relation to solar activity. We show that the activity of the Sun is actually comparable to the activity of the seismic solar analogs. Furthermore, we report on the discovery of temporal variability in the acoustic frequencies of the young (1 Gyr-old) solar analog KIC 10644253 with a modulation of about 1.5 years, which agrees with the derived photospheric activity tep{salabert16b}. It could actually be the signature of the short-period modulation, or quasi-biennal oscillation, of its magnetic activity as observed in the Sun and the 1-Gyr-old solar analog HD 30495. In addition, the lithium abundance and the chromospheric activity estimated from HERMES confirms that KIC 10644253 is a young and more active star than the Sun.

  4. Analog forecasting with dynamics-adapted kernels

    NASA Astrophysics Data System (ADS)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  5. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    PubMed Central

    Wiese, Maria; D’Agostino, Paul M.; Mihali, Troco K.; Moffitt, Michelle C.; Neilan, Brett A.

    2010-01-01

    Saxitoxin (STX) and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). PSTs are the causative agents of paralytic shellfish poisoning (PSP) and are mostly associated with marine dinoflagellates (eukaryotes) and freshwater cyanobacteria (prokaryotes), which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids. PMID:20714432

  6. Analogy, higher order thinking, and education.

    PubMed

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  7. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

  8. Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage

    ERIC Educational Resources Information Center

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

  9. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

  10. Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage

    ERIC Educational Resources Information Center

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

  11. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    ERIC Educational Resources Information Center

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  12. The Importance of Explicitly Mapping Instructional Analogies in Science Education

    ERIC Educational Resources Information Center

    Asay, Loretta Johnson

    2013-01-01

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With…

  13. Value and Limitations of Analogs in Teaching Mathematics.

    ERIC Educational Resources Information Center

    Halford, Graeme S.; Boulton-Lewis, Gillian M.

    Analogical reasoning is frequently used in acquisition of mathematical concepts. Concrete representations used to teach mathematics are essentially analogs of mathematical concepts, and it is argued that analogies enter into mathematical concept acquisition in numerous other ways as well. According to Gentner's theory, analogies entail a…

  14. The Importance of Explicitly Mapping Instructional Analogies in Science Education

    ERIC Educational Resources Information Center

    Asay, Loretta Johnson

    2013-01-01

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With…

  15. Gravitoelectromagnetic analogy based on tidal tensors

    SciTech Connect

    Costa, L. Filipe O.; Herdeiro, Carlos A. R.

    2008-07-15

    We propose a new approach to a physical analogy between general relativity and electromagnetism, based on tidal tensors of both theories. Using this approach we write a covariant form for the gravitational analogues of the Maxwell equations, which makes transparent both the similarities and key differences between the two interactions. The following realizations of the analogy are given. The first one matches linearized gravitational tidal tensors to exact electromagnetic tidal tensors in Minkowski spacetime. The second one matches exact magnetic gravitational tidal tensors for ultrastationary metrics to exact magnetic tidal tensors of electromagnetism in curved spaces. In the third we show that our approach leads to a two-step exact derivation of Papapetrou's equation describing the force exerted on a spinning test particle. Analogous scalar invariants built from tidal tensors of both theories are also discussed.

  16. Changes in analogical reasoning in adulthood.

    PubMed

    Clark, E; Gardner, M K; Brown, G; Howell, R J

    1990-01-01

    This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).

  17. Polymeric nanogel formulations of nucleoside analogs

    PubMed Central

    Vinogradov, Serguei V

    2008-01-01

    Nanogels are colloidal microgel carriers that have been introduced recently as a prospective drug delivery system for nucleotide therapeutics. The crosslinked protonated polymer network of nanogels binds oppositely charged drug molecules, encapsulating them into submicron particles with a core-shell structure. The nanogel network also provides a suitable template for chemical engineering, surface modification and vectorisation. This review reveals recent attempts to develop novel drug formulations of nanogels with antiviral and antiproliferative nucleoside analogs in the active form of 5′-triphosphates; discusses structural approaches to the optimisation of nanogel properties, and; discusses the development of targeted nanogel drug formulations for systemic administration. Notably, nanogels can improve the CNS penetration of nucleoside analogs that are otherwise restricted from passing across the blood–brain barrier. The latest findings reviewed here demonstrate an efficient intracellular release of nucleoside analogs, encouraging further applications of nanogel carriers for targeted drug delivery. PMID:17184158

  18. Chemical synthesis of dinucleotide cap analogs.

    PubMed

    Kore, Anilkumar R; Shanmugasundaram, Muthian

    2014-12-19

    This unit describes a reliable, efficient and general method for the synthesis of standard cap analog (mCAP), m(7)G[5']ppp[5']G, and anti-reverse cap analog (ARCA), m(7,3')(O)G[5']ppp[5']G. The synthesis of required intermediate m(7)GDP or m(2)(7,3'O)GDP has been achieved through regioselective methylation of the corresponding diphosphate using dimethyl sulfate under aqueous conditions. Then, the coupling reaction of m(7)GDP or m(2)(7,3'O)GDP with ImGMP using ZnCl(2)/DMF system affords the corresponding cap analog in good yields. Copyright © 2014 John Wiley & Sons, Inc.

  19. Interaction of Chloramphenicol Tripeptide Analogs with Ribosomes.

    PubMed

    Tereshchenkov, A G; Shishkina, A V; Tashlitsky, V N; Korshunova, G A; Bogdanov, A A; Sumbatyan, N V

    2016-04-01

    Chloramphenicol amine peptide derivatives containing tripeptide fragments of regulatory "stop peptides" - MRL, IRA, IWP - were synthesized. The ability of the compounds to form ribosomal complexes was studied by displacement of the fluorescent erythromycin analog from its complex with E. coli ribosomes. It was found that peptide chloramphenicol analogs are able to bind to bacterial ribosomes. The dissociation constants were 4.3-10 µM, which is 100-fold lower than the corresponding values for chloramphenicol amine-ribosome complex. Interaction of the chloramphenicol peptide analogs with ribosomes was simulated by molecular docking, and the most probable contacts of "stop peptide" motifs with the elements of nascent peptide exit tunnel were identified.

  20. Mutagenicity of new analogs of 5-nitrofurans

    SciTech Connect

    Hatcher, J.F.; Ichikawa, M.; Bryan, G.T.; Swaminathan, S.

    1986-05-01

    The authors reported earlier the synthesis of methyl 3,4-diphenyl-5-nitro-2-furoate (I) and a number of its reduction products. They extended this synthesis to obtain 3,4-diphenyl substituted analogs of established carcinogenic 5-nitrofuryl thiazoles. They report the mutagenic activities of this new series of furan analogs: methyl 3,4-diphenyl-2-furoate (II), 3,4-diphenyl-5-nitro-2-acetylfuran (III), 3,4-diphenyl-5-nitro-2-bromoacetylfuran (IV), 2-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole (V) and 2-acetylamino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole (VI) using nitroreductase-proficient (TA100 and TA98) and deficient (TA100NR and TA98NR) strains. All the nitro analogs (I, III, IV, V, and VI) were active (114, 31, 70, 3 and 9 rev/nmole) in TA100 while the non-nitro analog (II) was inactive. In TA98, I and III had 15-fold less activity relative to TA100. V and VI were inactive in TA98. Furthermore, I and III were less active in TA100NR and TA98NR compared to the response in the parent strains. In contrast, the bromo analog IV was equally active in TA100, TA98, TA100NR and TA98NR, suggesting alternate pathways of activation of this chemical. V and VI were about 4000-fold less active in TA100 than the carcinogenic analogs lacking the phenyl substituents. These results demonstrate that for mutagenic activity the nitro group is essential and the potency of activity is influenced by the substituents at the 2-position of furan.

  1. Analog graphic display method and apparatus

    DOEpatents

    Kronberg, James W.

    1991-01-01

    An apparatus and method for using an output device such as an LED to show the approximate analog level of a variable electrical signal wherein a modulating AC waveform is superimposed either on the signal or a reference voltage, both of which are then fed to a comparator which drives the output device. Said device flashes at a constant perceptible rate with a duty cycle which varies in response to variations in the level of the input signal. The human eye perceives these variations in duty cycle as analogous to variations in the level of the input signal.

  2. Analog graphic display method and apparatus

    DOEpatents

    Kronberg, J.W.

    1991-08-13

    Disclosed are an apparatus and method for using an output device such as an LED to show the approximate analog level of a variable electrical signal wherein a modulating AC waveform is superimposed either on the signal or a reference voltage, both of which are then fed to a comparator which drives the output device. Said device flashes at a constant perceptible rate with a duty cycle which varies in response to variations in the level of the input signal. The human eye perceives these variations in duty cycle as analogous to variations in the level of the input signal. 21 figures.

  3. Space flight nutrition research: platforms and analogs

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Uchakin, Peter N.; Tobin, Brian W.

    2002-01-01

    Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

  4. Analogies between elastic and capillary interfaces*

    NASA Astrophysics Data System (ADS)

    Snoeijer, Jacco H.

    2016-10-01

    In this paper we exploit some analogies between flows near capillary interfaces and near elastic interfaces. We first consider the elastohydrodynamics of a ball bearing and the motion of a gas bubble inside a thin channel. It is shown that there is a strong analogy between these two lubrication problems, and the respective scaling laws are derived side by side. Subsequently, the paper focuses on the limit where the involved elastic interfaces become extremely soft. It is shown that soft gels and elastomers, like liquids, can be shaped by their surface tension. We highlight some recent advances on this class of elastocapillary phenomena.

  5. Transparent Analogs for Alloy Phase Studies

    NASA Technical Reports Server (NTRS)

    Frazier, D. O.; Smith, James E., Jr.

    1987-01-01

    Report describes experiments to add information to data base supporting use of transparent, partially miscible liquids and solids as analogs in studies of alloy solidification. Behavior of these materials observed directly while they undergo liquid/liquid and liquid/solid phase transformations. Light-scattering techniques used to determine phase boundaries. Transparent analogs allow observation of both solidification patterns and processes leading to those patterns, whereas metal alloys require tedious post-solidification metallographic analyses because processes not generally observed. Experiments with transparent substances safer and cheaper since conducted at much lower temperatures.

  6. Analogy Mapping Development for Learning Programming

    NASA Astrophysics Data System (ADS)

    Sukamto, R. A.; Prabawa, H. W.; Kurniawati, S.

    2017-02-01

    Programming skill is an important skill for computer science students, whereas nowadays, there many computer science students are lack of skills and information technology knowledges in Indonesia. This is contrary with the implementation of the ASEAN Economic Community (AEC) since the end of 2015 which is the qualified worker needed. This study provided an effort for nailing programming skills by mapping program code to visual analogies as learning media. The developed media was based on state machine and compiler principle and was implemented in C programming language. The state of every basic condition in programming were successful determined as analogy visualization.

  7. Electronically scanned analog liquid crystal displays.

    PubMed

    Soref, R A

    1970-06-01

    A new analog display technique for liquid crystal display panels is demonstrated. The size, shape, and location of display patterns can be changed continuously using low power electronic control. The display consists of a thin liquid crystal layer sandwiched between high resistance transparent area electrodes. Transverse voltage gradients on the electrodes actuate the device. The display operates with either dynamic scattering liquids or quiescent scattering liquids. Experimental results are given for three prototype analog displays: a voltmeter, a flying spot scanner, and a null indicator.

  8. A quadratic analog-to-digital converter

    NASA Technical Reports Server (NTRS)

    Harrison, D. C.; Staples, M. H.

    1980-01-01

    An analog-to-digital converter with a square root transfer function has been developed for use with a pair of CCD imaging detectors in the White Light Coronagraph/X-ray XUV Telescope experiment to be flown as part of the Internal Solar Polar Mission. It is shown that in background-noise-limited instrumentation systems a quadratic analog-to-digital converter will allow a maximum dynamic range with a fixed number of data bits. Low power dissipation, moderately fast conversion time, and reliability are achieved in the proposed design using standard components and avoiding nonlinear elements.

  9. Discrete analog computing with rotor-routers.

    PubMed

    Propp, James

    2010-09-01

    Rotor-routing is a procedure for routing tokens through a network that can implement certain kinds of computation. These computations are inherently asynchronous (the order in which tokens are routed makes no difference) and distributed (information is spread throughout the system). It is also possible to efficiently check that a computation has been carried out correctly in less time than the computation itself required, provided one has a certificate that can itself be computed by the rotor-router network. Rotor-router networks can be viewed as both discrete analogs of continuous linear systems and deterministic analogs of stochastic processes.

  10. Fungitoxicity of chemical analogs with heartwood toxins.

    PubMed

    Grohs, B M; Kunz, B

    1998-07-01

    Trans-stilbene and tropolone as chemical analogs with naturally occurring fungitoxic heartwood compounds were studied with respect to their fungitoxic potency. While stilbene showed no fungitoxic activity towards the fungi Aureobasidium pullulans var. melanogenum, Penicillium glabrum, and Trichoderma harzianum in the concentrations tested, the minimal inhibiting concentration of tropolone was 10(-3) M for Penicillium glabrum and Trichoderma harzianum, and 10(-5) M for Aureobasidium pullulans var. melanogenum. In all cases, the effect of tropolone was a fungistatic one. Using chemical analogs for assessing the chemical basis of the fungitoxicity of tropolone, this substance proved to be the only compound tested which possesses fungitoxic properties.

  11. Transparent Analogs for Alloy Phase Studies

    NASA Technical Reports Server (NTRS)

    Frazier, D. O.; Smith, James E., Jr.

    1987-01-01

    Report describes experiments to add information to data base supporting use of transparent, partially miscible liquids and solids as analogs in studies of alloy solidification. Behavior of these materials observed directly while they undergo liquid/liquid and liquid/solid phase transformations. Light-scattering techniques used to determine phase boundaries. Transparent analogs allow observation of both solidification patterns and processes leading to those patterns, whereas metal alloys require tedious post-solidification metallographic analyses because processes not generally observed. Experiments with transparent substances safer and cheaper since conducted at much lower temperatures.

  12. Associative Pattern Recognition In Analog VLSI Circuits

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul

    1995-01-01

    Winner-take-all circuit selects best-match stored pattern. Prototype cascadable very-large-scale integrated (VLSI) circuit chips built and tested to demonstrate concept of electronic associative pattern recognition. Based on low-power, sub-threshold analog complementary oxide/semiconductor (CMOS) VLSI circuitry, each chip can store 128 sets (vectors) of 16 analog values (vector components), vectors representing known patterns as diverse as spectra, histograms, graphs, or brightnesses of pixels in images. Chips exploit parallel nature of vector quantization architecture to implement highly parallel processing in relatively simple computational cells. Through collective action, cells classify input pattern in fraction of microsecond while consuming power of few microwatts.

  13. Synthetic heparin-binding factor analogs

    DOEpatents

    Pena, Louis A [Poquott, NY; Zamora, Paul O [Gaithersburg, MD; Lin, Xinhua [Plainview, NY; Glass, John D [Shoreham, NY

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  14. Binary/Analog CCD Correlator Development.

    DTIC Science & Technology

    1981-07-01

    AD-AI04 438 TEXAS INSTRUMENTS INC DALLAS F/ 9 /5 BINARY/ANALOG CCD COPPEL TOR DE VELOPMEN.(U JUL 81 R A HAKEN F19628-78-C-0122 CLASSIFIED TI -08-79...ANALOG CCD CORRELATOR DEVELOPMENT Texas Instruments Inc. R. A. Hakln APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLMITED DTIC S ELECTE SEP 211981i D...transversal filter with split-electrode weighting is well recogniied as a useful tool liInumher of sampled-data filtering applications.’ However, these

  15. Parallel Analog-to-Digital Image Processor

    NASA Technical Reports Server (NTRS)

    Lokerson, D. C.

    1987-01-01

    Proposed integrated-circuit network of many identical units convert analog outputs of imaging arrays of x-ray or infrared detectors to digital outputs. Converter located near imaging detectors, within cryogenic detector package. Because converter output digital, lends itself well to multiplexing and to postprocessing for correction of gain and offset errors peculiar to each picture element and its sampling and conversion circuits. Analog-to-digital image processor is massively parallel system for processing data from array of photodetectors. System built as compact integrated circuit located near local plane. Buffer amplifier for each picture element has different offset.

  16. Associative Pattern Recognition In Analog VLSI Circuits

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul

    1995-01-01

    Winner-take-all circuit selects best-match stored pattern. Prototype cascadable very-large-scale integrated (VLSI) circuit chips built and tested to demonstrate concept of electronic associative pattern recognition. Based on low-power, sub-threshold analog complementary oxide/semiconductor (CMOS) VLSI circuitry, each chip can store 128 sets (vectors) of 16 analog values (vector components), vectors representing known patterns as diverse as spectra, histograms, graphs, or brightnesses of pixels in images. Chips exploit parallel nature of vector quantization architecture to implement highly parallel processing in relatively simple computational cells. Through collective action, cells classify input pattern in fraction of microsecond while consuming power of few microwatts.

  17. Pseudolog Digital-to-Analog Converter

    NASA Technical Reports Server (NTRS)

    Gooder, S. T.

    1986-01-01

    Sensitivity decreases by 10 at beginning of each input decade. Method conceived to convert binary-coded data to suitable linear form for stripchart recording. Strip-chart recordings obtained from typical pressure readings in a vacuum system during pumpdown. In reading curve, BCD digital vacuum-gage output processed by analog-to-digital converter in such way that only reading digits (but not range) appear in output. In range and reading, range also converted to analog and placed as most significant digit.

  18. A quadratic analog-to-digital converter

    NASA Technical Reports Server (NTRS)

    Harrison, D. C.; Staples, M. H.

    1980-01-01

    An analog-to-digital converter with a square root transfer function has been developed for use with a pair of CCD imaging detectors in the White Light Coronagraph/X-ray XUV Telescope experiment to be flown as part of the Internal Solar Polar Mission. It is shown that in background-noise-limited instrumentation systems a quadratic analog-to-digital converter will allow a maximum dynamic range with a fixed number of data bits. Low power dissipation, moderately fast conversion time, and reliability are achieved in the proposed design using standard components and avoiding nonlinear elements.

  19. Multichannel analog front-end and analog-to-digital converter ICs for silicon photomultipliers

    NASA Astrophysics Data System (ADS)

    Bocharov, Y. I.; Butuzov, V. A.

    2016-10-01

    Integrated circuit (IC) of multichannel analog front-end and a mixed-signal chip of multichannel analog-to-digital converter are presented. A chipset of these two ICs is intended for readout, analog preprocessing and analog to digital conversion of silicon photomultiplier array signals. The number of channels of the analog front-end IC as well as the types of their input stages depends on the application. The current test version of the chip contains three current-input channels and three voltage-input channels. Each of the channels includes a programmable pre-amplifier, integrator with baseline-holder, code-controlled amplifier, amplitude discriminator, two programmable timers, pulse-shaping low-pass filter, peak detector, and an output buffer with baseline tuning circuitry. The analog IC has code-configurable architecture. The mixed-signal IC includes nine main channels and one auxiliary channel, containing 10-bit analog-to-digital converter in each channel. It also has a buffer memory and a voltage reference. The chip features low power consumption, which is less than 0.5 mW per channel at a sampling rate of 100 kHz. Both ICs are implemented in 0.35 μm CMOS technology.

  20. Oseltamivir analog with boron cluster modulator.

    PubMed

    Adamska, Anna; Olejniczak, Agnieszka B; Zwoliński, Krzysztof; Szczepek, Wojciech J; Król, Ewelina; Szewczyk, Bogusław; Grynkiewicz, Grzegorz; Leśnikowski, Zbigniew J

    2012-01-01

    Synthesis of novel neuraminidase inhibitor -- carborane ester of oseltamivir carboxylic acid is described, and its physicochemical and spectral characteristics is provided. Surprisingly, carborane analog of oseltamivir is of an order of magnitude less active than its precursor, the corresponding ethyl ester, which is the active principle of pharmaceutical preparations used in influenza prophylactics and therapy.

  1. Multivariate Analog of Hays Omega-Squared.

    ERIC Educational Resources Information Center

    Sachdeva, Darshan

    The multivariate analog of Hays omega-squared for estimating the strength of the relationship in the multivariate analysis of variance has been proposed in this paper. The multivariate omega-squared is obtained through the use of Wilks' lambda test criterion. Application of multivariate omega-squared to a numerical example has been provided so as…

  2. The GMO-Nanotech (Dis)Analogy?

    ERIC Educational Resources Information Center

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  3. Image Quality in Analog and Digital Microtechniques.

    ERIC Educational Resources Information Center

    White, William

    1991-01-01

    Discusses the basic principles of the application of microfilm (analog) and electronic (digital) technologies for data storage. Image quality is examined, searching and retrieval capabilities are considered, and hardcopy output resolution is described. It is concluded that microfilm is still the preferred archival medium. (5 references) (LRW)

  4. Radiation Behavior of Analog Neural Network Chip

    NASA Technical Reports Server (NTRS)

    Langenbacher, H.; Zee, F.; Daud, T.; Thakoor, A.

    1996-01-01

    A neural network experiment conducted for the Space Technology Research Vehicle (STRV-1) 1-b launched in June 1994. Identical sets of analog feed-forward neural network chips was used to study and compare the effects of space and ground radiation on the chips. Three failure mechanisms are noted.

  5. The Slingshot Effect: Explanation and Analogies.

    ERIC Educational Resources Information Center

    Bartlett, Albert A.; Hord, Charles W.

    1985-01-01

    Scientists often use the "slingshot effect" (also called the "gravity assist") of the gravitational field of a planet to increase or decrease the velocity of a spacecraft. Examples of this effect, puzzling aspects, a qualitative explanation, details of necessary calculations, a thermodynamic analogy, and other topics are discussed. (JN)

  6. A Mechanical Analogy for Ohm's Law.

    ERIC Educational Resources Information Center

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  7. Metaphor, Simile, Analogy and the Brain

    ERIC Educational Resources Information Center

    Riddell, Patricia

    2016-01-01

    Fox argues that the poetic function of language fulfils the human need to symbolise. Metaphor, simile and analogy provide examples of the ways in which symbolic language can be used creatively. The neural representations of these processes therefore provide a means to determine the neurological basis of creative language. Neuro-imaging has…

  8. Resistance Gene Analogs in Cherries (Prunus spp.)

    USDA-ARS?s Scientific Manuscript database

    Genetic studies have shown that NBS-LRR Resistance Gene Analogs (RGAs) tend to occur in clusters and often map to major resistances gene or QTL. The identification and use of specific RGAs as molecular markers among plant material displaying differential resistance phenotypes has the potential to di...

  9. Metaphor, Simile, Analogy and the Brain

    ERIC Educational Resources Information Center

    Riddell, Patricia

    2016-01-01

    Fox argues that the poetic function of language fulfils the human need to symbolise. Metaphor, simile and analogy provide examples of the ways in which symbolic language can be used creatively. The neural representations of these processes therefore provide a means to determine the neurological basis of creative language. Neuro-imaging has…

  10. Analogies and Reconstruction of Mathematical Knowledge.

    ERIC Educational Resources Information Center

    Fast, Gerald R.

    An investigation was conducted to determine the effectiveness of utilizing analogies to effect conceptual change in mathematics. Forty-one high school seniors participated in a knowledge reconstruction process regarding their beliefs about everyday probability situations such as sports events or lotteries. These mathematics students were given…

  11. Reasoning by Analogy in Solving Comparison Problems.

    ERIC Educational Resources Information Center

    English, Lyn D.

    1998-01-01

    Investigates 10-year-old children's abilities to reason by analogy in solving addition and subtraction comparison problems involving unknown compare sets and unknown reference sets. Children responded in a consistent manner to the tasks involving the basic addition problems, indicating substantial relational knowledge of these but responded in an…

  12. Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia.

    PubMed

    Geelhoed, G W; Bass, B L; Mertz, S L; Becker, K L

    1986-12-01

    A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.

  13. Analogy Generation in Scientific Problem Solving.

    ERIC Educational Resources Information Center

    Clement, John

    The spontaneous use of analogies in problem-solving occurs when a subject first spontaneously shifts his attention to a situation (B) which differs in some significant way from an original problem situation (A), and then tries to apply findings from B to A. This paper describes research on the process with 10 scientifically trained subjects…

  14. Aromatic Bagels: An Edible Resonance Analogy

    NASA Astrophysics Data System (ADS)

    Lin, Shirley

    2007-05-01

    A classroom demonstration involving the use of a bagel and cream cheese as an analogy for the two resonance contributors of benzene is described. This method emphasizes the deficiencies of using a single Lewis structure to describe the structure of benzene. Students are also reminded that benzene is a single entity and not a species that oscillates between two resonance contributors.

  15. (-)-Botryodiplodin, A Unique Ribose Analog Toxin

    USDA-ARS?s Scientific Manuscript database

    Many toxins owe their mechanisms of action to being structural analogs of essential metabolites, messengers or structural components. Examples range from tubo-curare to penicillin. Ribose plays a unique role in the metabolism of living organisms, whether prokaryotes or eukaryotes. It and its deri...

  16. Analog Acoustic Expression in Speech Communication

    ERIC Educational Resources Information Center

    Shintel, Hadas; Nusbaum, Howard C.; Okrent, Arika

    2006-01-01

    We present the first experimental evidence of a phenomenon in speech communication we call "analog acoustic expression." Speech is generally thought of as conveying information in two distinct ways: discrete linguistic-symbolic units such as words and sentences represent linguistic meaning, and continuous prosodic forms convey information about…

  17. The GMO-Nanotech (Dis)Analogy?

    ERIC Educational Resources Information Center

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  18. Analogical Transfer from a Simulated Physical System

    ERIC Educational Resources Information Center

    Day, Samuel B.; Goldstone, Robert L.

    2011-01-01

    Previous research has consistently found that spontaneous analogical transfer is strongly tied to concrete and contextual similarities between the cases. However, that work has largely failed to acknowledge that the relevant factor in transfer is the similarity between individuals' mental representations of the situations rather than the overt…

  19. An Analog Processor for Image Compression

    NASA Technical Reports Server (NTRS)

    Tawel, R.

    1992-01-01

    This paper describes a novel analog Vector Array Processor (VAP) that was designed for use in real-time and ultra-low power image compression applications. This custom CMOS processor is based architectually on the Vector Quantization (VQ) algorithm in image coding, and the hardware implementation fully exploits the inherent parallelism built-in the VQ algorithm.

  20. SSERVI Analog Regolith Simulant Testbed Facility

    NASA Astrophysics Data System (ADS)

    Minafra, J.; Schmidt, G. K.

    2016-12-01

    SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers. The SSERVI Analog Regolith Simulant Testbed provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment. The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area. SSERVI provides a bridge between several groups, joining together researchers from: 1) scientific and exploration communities, 2) multiple disciplines across a wide range of planetary sciences, and 3) domestic and international communities and partnerships. This testbed provides a means of consolidating the tasks of acquisition, storage and safety mitigation in handling large quantities of regolith simulant Facility hardware and environment testing scenarios include, but are not limited to the following; Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, and Surface features (i.e. grades and rocks) Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and planetary exploration activities at NASA Research Park, to academia and expanded commercial opportunities in California's Silicon Valley, as well as public outreach and education opportunities.

  1. Presence, Analogy, and "Earth in the Balance."

    ERIC Educational Resources Information Center

    Murphy, John M.

    1994-01-01

    Uses vice president Albert Gore Jr.'s book "Earth in the Balance" as a case study to examine the relationship between analogy and "presence." Argues that presence is a flexible critical construct allowing for examination of the relationship between the style, substance, and structure of arguments. Explores relationships between…

  2. RF digital-to-analog converter

    DOEpatents

    Conway, P.H.; Yu, D.U.L.

    1995-02-28

    A digital-to-analog converter is disclosed for producing an RF output signal proportional to a digital input word of N bits from an RF reference input, N being an integer greater or equal to 2. The converter comprises a plurality of power splitters, power combiners and a plurality of mixers or RF switches connected in a predetermined configuration. 18 figs.

  3. Invention through Form and Function Analogy

    ERIC Educational Resources Information Center

    Rule, Audrey C.

    2015-01-01

    "Invention through Form and Function Analogy" is an invention book for teachers and other leaders working with youth who are involving students in the invention process. The book consists of an introduction and set of nine learning cycle formatted lessons for teaching the principles of invention through the science and engineering design…

  4. A Mechanical Analogy for Ohm's Law.

    ERIC Educational Resources Information Center

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  5. Dopaminergic activity of four analogs of butaclamol.

    PubMed

    Collu, R; Bouvier, C; Basak, A; Dugas, H

    1985-12-01

    The displacing potency of four analogs of the neuroleptic drug butaclamol were evaluated using dog striatal tissue and [3H]-Spiroperidol as ligand. Although significantly less powerful than the parent compound, two of them (N-isobutyl butaclamol equatorial; N-methyl butaclamol equatorial) could be used for dopaminergic receptor studies.

  6. Optical folding-flash analog-to-digital converter with analog encoding.

    PubMed

    Jalali, B; Xie, Y M

    1995-09-15

    We describe an optically assisted folding-flash analog-to-digital converter. The periodic transfer function of the Mach-Zehnder interferometer is used to perform analog folding on the electronic signal to be quantized. A novel analog encoding scheme for efficient generation of gray code digital data is proposed. The new encoding scheme eliminates the requirement for interferometers with ultralow V(pi), which, so far, has hindered the development of such systems. The encoding concept is experimentally demonstrated through the use of LiNbO(3) modulators.

  7. The role of causal models in analogical inference.

    PubMed

    Lee, Hee Seung; Holyoak, Keith J

    2008-09-01

    Computational models of analogy have assumed that the strength of an inductive inference about the target is based directly on similarity of the analogs and in particular on shared higher order relations. In contrast, work in philosophy of science suggests that analogical inference is also guided by causal models of the source and target. In 3 experiments, the authors explored the possibility that people may use causal models to assess the strength of analogical inferences. Experiments 1-2 showed that reducing analogical overlap by eliminating a shared causal relation (a preventive cause present in the source) from the target increased inductive strength even though it decreased similarity of the analogs. These findings were extended in Experiment 3 to cross-domain analogical inferences based on correspondences between higher order causal relations. Analogical inference appears to be mediated by building and then running a causal model. The implications of the present findings for theories of both analogy and causal inference are discussed.

  8. How the creative use of analogies can shape medical practice.

    PubMed

    Prasad, G V Ramesh

    2015-06-01

    Analogical reasoning is central to medical progress, and is either creative or conservative. According to Hofmann et al., conservative analogy relates concepts from old technology to new technologies with emphasis on preservation of comprehension and conduct. Creative analogy however brings new understanding to new technology, brings similarities existing in the source domain to a target domain where they previously had no bearing, and imports something entirely different from the content of the analogy itself. I defend the claim that while conservative analogies are useful by virtue of being comfortable to use from familiarity and experience, and are more easily accepted by society, they only lead to incremental advances in medicine. However, creative analogies are more exciting and productive because they generate previously unexpected associations across widely separated domains, emphasize relations over physical similarities, and structure over superficiality. I use kidney transplantation and anti-rejection medication development as an exemplar of analogical reasoning used to improve medical practice. Anti-rejection medication has not helped highly sensitized patients because of their propensity to rejecting most organs. I outline how conservative analogical reasoning led to anti-rejection medication development, but creative analogical reasoning helped highly sensitized and blood type incompatible patients through domino transplants, by which they obtain a kidney to which they are not sensitized. Creative analogical reasoning is more likely than conservative analogical reasoning to lead to revolutionary progress. While these analogies overlap and creative analogies eventually become conservative, progress is best facilitated by combining conservative and creative analogical reasoning.

  9. The role of analogies in learning to read.

    PubMed

    Kamhi, A G; Laing, S P

    2000-01-01

    A number of factors contribute to proficient word recognition, including phonological awareness and the ability to make orthographic analogies. The present study considered the relative contribution analogy abilities make toward early reading ability. Two analogy tasks and measures of phonological awareness, orthographic knowledge, visual memory, general language ability, and non-verbal intelligence were administered to 20 second grade good readers and 20 third and fourth grade poor readers. The analogy tasks did make a significant contribution to early reading ability; however, the analogy tasks were not very different from the measures of reading they predicted. In other words, it seems difficult to isolate the use of analogies from basic phonological decoding abilities.

  10. Multilateral Research Opportunities in Ground Analogs

    NASA Technical Reports Server (NTRS)

    Corbin, Barbara J.

    2015-01-01

    The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. International collaboration provides an opportunity to leverage other nations' investments to meet common goals. The Humans In Space Community shares a common goal to enable safe, reliable, and productive human space exploration within and beyond Low Earth Orbit. Meeting this goal requires efficient use of limited resources and International capabilities. The International Space Station (ISS) is our primary platform to conduct microgravity research targeted at reducing human health and performance risks for exploration missions. Access to ISS resources, however, is becoming more and more constrained and will only be available through 2020 or 2024. NASA's Human Research Program (HRP) is actively pursuing methods to effectively utilize the ISS and appropriate ground analogs to understand and mitigate human health and performance risks prior to embarking on human exploration of deep space destinations. HRP developed a plan to use ground analogs of increasing fidelity to address questions related to exploration missions and is inviting International participation in these planned campaigns. Using established working groups and multilateral panels, the HRP is working with multiple Space Agencies to invite International participation in a series of 30- day missions that HRP will conduct in the US owned and operated Human Exploration Research Analog (HERA) during 2016. In addition, the HRP is negotiating access to Antarctic stations (both US and non-US), the German :envihab and Russian NEK facilities. These facilities provide unique capabilities to address critical research questions requiring longer duration simulation or isolation. We are negotiating release of international research opportunities to ensure a multilateral approach to future analog research campaigns, hoping to begin multilateral campaigns in the

  11. Not all analogies are created equal: Associative and categorical analogy processing following brain damage

    PubMed Central

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and categorical (dog-cat) relations. To test the hypothesis that analogical mapping of different types of relations would have different neural instantiations, we tested patients with left and right hemisphere lesions on their ability to understand two types of analogies, ones expressing an associative relationship and others expressing a categorical relationship. Voxel-based lesion-symptom mapping (VLSM) and behavioral analyses revealed that associative analogies relied on a large left-lateralized language network while categorical analogies relied on both left and right hemispheres. The verbal nature of the task could account for the left hemisphere findings. We argue that categorical relations additionally rely on the right hemisphere because they are more difficult, abstract, and fragile; and contain more distant relationships. PMID:22402184

  12. Not all analogies are created equal: Associative and categorical analogy processing following brain damage.

    PubMed

    Schmidt, Gwenda L; Cardillo, Eileen R; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-06-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and categorical (dog-cat) relations. To test the hypothesis that analogical mapping of different types of relations would have different neural instantiations, we tested patients with left and right hemisphere lesions on their ability to understand two types of analogies, ones expressing an associative relationship and others expressing a categorical relationship. Voxel-based lesion-symptom mapping (VLSM) and behavioral analyses revealed that associative analogies relied on a large left-lateralized language network while categorical analogies relied on both left and right hemispheres. The verbal nature of the task could account for the left hemisphere findings. We argue that categorical relations additionally rely on the right hemisphere because they are more difficult, abstract, and fragile, and contain more distant relationships. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Playing with a double-edged sword: Analogies in biochemistry

    NASA Astrophysics Data System (ADS)

    Orgill, Marykay

    Analogy pervades our everyday reasoning. No situation we encounter is exactly like a situation we have encountered previously, and our ability to learn and survive in the world is based on our ability to find similarities between past and present situations and use the knowledge we have gained from past situations to manage current situations. Analogies can be powerful teaching tools because they can make new material intelligible to students by comparing it to material that is already familiar. It is clear, though, that not all analogies are good and that not all good analogies are useful to all students. In this study, I have used textbook analysis, classroom observations, student interviews and instructor interviews to determine the role that analogies play in biochemistry learning. Analogies are an important teaching technique in biochemistry classes, being used more often in both biochemistry classes and textbooks than they are in high school chemistry classes and textbooks. Most biochemistry students like, pay particular attention to, and remember the analogies their instructors provide; and they use these analogies to understand, visualize, and recall information from class. Even though students like and use analogies, they do not understand what analogies are or the mechanism by which they improve learning. For the students, analogies are simply any teaching technique that eases understanding, visualization, or recall. Instructors, on the other hand, have a good understanding of what analogies are and of how they should be presented in class; but they do not use analogies as effectively as they should. They do not plan, explain or identify the limitations of the analogies they use in class. However, regardless of how effectively instructors present analogies in class, this study indicates that, in general, analogies are useful in promoting understanding, visualization, recall, and motivation in biochemistry students at all levels. They would be even more

  14. Parabolic flight as a spaceflight analog.

    PubMed

    Shelhamer, Mark

    2016-06-15

    Ground-based analog facilities have had wide use in mimicking some of the features of spaceflight in a more-controlled and less-expensive manner. One such analog is parabolic flight, in which an aircraft flies repeated parabolic trajectories that provide short-duration periods of free fall (0 g) alternating with high-g pullout or recovery phases. Parabolic flight is unique in being able to provide true 0 g in a ground-based facility. Accordingly, it lends itself well to the investigation of specific areas of human spaceflight that can benefit from this capability, which predominantly includes neurovestibular effects, but also others such as human factors, locomotion, and medical procedures. Applications to research in artificial gravity and to effects likely to occur in upcoming commercial suborbital flights are also possible. Copyright © 2016 the American Physiological Society.

  15. Submarine Analogs to Venusian Pancake Domes

    NASA Technical Reports Server (NTRS)

    Bridges, Nathan T.

    1995-01-01

    The morphology and dimensions of the large diameter, steep-sided, flat-topped "pancake domes" on Venus make them unlike any type of terrestrial subaerial volcano. Comparisons between images of Hawaiian seamounts and pancake domes show similarities in shapes and secondary features. The morphometry of pancake domes is closer to that of Pacific seamounts than subaerial lava domes. Considering both morphology and morphometry, seamounts seem a better analog to the pancake domes. The control of volatile exsolution by pressure on Venus and the seafloor can cause lavas to have similar viscosities and densities, although the latter will be counteracted by high buoyancy underwater. However, analogous effects of the Venusian and seafloor alone are probably not sufficient to produce similar volcanoes. Rather, Venusian lavas of various compositions may behave like basalt on the seafloor if appropriate rates and modes of extrusion and planetary thermal structure are also considered.

  16. Terrestrial analogs of the hellespontus dunes, Mars

    USGS Publications Warehouse

    Breed, C.S.

    1977-01-01

    Geomorphic features in the Hellespontus region, Mars, were compared with dunes of the crescentic ridge type in numerous terrestrial sand seas quantitatively by dimensional analysis of dune lengths, widths, and wavelengths. Mean values for the Hellespontus dunes are close to mean values derived from measurements of all sampled terrestrial sand seas. Terrestrial analogs of form and areal distribution of the Hellespontus dunes are shown by comparison of scale ratios derived from the measurements. Dunes of similar form occur in South West Africa, in Pakistan, in the southeastern Arabian peninsula, in the Sahara, in eastern USSR and northern China, and in western North America. Terrestrial analogs closest to form and areal distribution of the Hellespontus dunes are in the Kara Kum Desert, Turkmen SSR, and in the Ala Shan (Gobi) Desert, China. ?? 1977.

  17. The optical analogy for vector fields

    NASA Technical Reports Server (NTRS)

    Parker, E. N. (Editor)

    1991-01-01

    This paper develops the optical analogy for a general vector field. The optical analogy allows the examination of certain aspects of a vector field that are not otherwise readily accessible. In particular, in the cases of a stationary Eulerian flow v of an ideal fluid and a magnetostatic field B, the vectors v and B have surface loci in common with their curls. The intrinsic discontinuities around local maxima in absolute values of v and B take the form of vortex sheets and current sheets, respectively, the former playing a fundamental role in the development of hydrodyamic turbulence and the latter playing a major role in heating the X-ray coronas of stars and galaxies.

  18. Synthesis of tetracycline ring A analogs.

    PubMed

    Moskalyk, R E; Mak, A L; Chatten, L G; Locock, R A

    1981-05-01

    Studies directed at the synthesis of tetracycline ring A analogs are described. 4-Carbethoxycyclohexane-1,3-dione was converted to the ethyl urethan dispiro[1,3-dioxolane-2,2'-cyclohexane-4',2"(1,3)-dioxolane]-1'-carbamic acid ethyl ester via the dispiro[1,3-dioxolane-2,2'-cyclohexane-4'-2"(1,3)-dioxolane]-1'-carboxylic acid hydrazide. An improved synthesis of another cyclohexenone from methyl vinyl ketone and ethyl nitroacetate is reported. Reaction of N-(3-hydroxy-1-oxo-2-cyclohexen-4-yl)benzamide with alpha-chloroacetyl isocyanate afforded a 4(5H)-oxazolone derivative, as did the identical reaction on 5,5-dimethyl-1,3-cyclohexanedione (dimedone). This reaction provides a novel approach to these oxazolones with potential therapeutic importance. Other ring A analogs were synthesized also.

  19. Design of potent, proteolytically stable oxyntomodulin analogs

    PubMed Central

    Muppidi, Avinash; Zou, Huafei; Yang, Peng Yu; Chao, Elizabeth; Sherwood, Lance; Nunez, Vanessa; Woods, Ashley

    2016-01-01

    Incretin-based peptides are effective therapeutics for treating type 2 diabetes mellitus (T2DM). Oxyntomodulin (OXM), a dual agonist of GLP-1R and GCGR, has shown superior weight loss and glucose lowering effects, compared to single GLP-1R agonists. To overcome the short half-life and rapid renal clearance of OXM, which limit its therapeutic potential, both lipid and PEG modified OXM analogs have been reported. However, these approaches often result in reduced potency or PEG-associated toxicity. Herein we report a new class of cross-linked OXM analogs that show increased plasma stability and higher potency in activating both GLP-1R and GCGR. Moreover, the extended in vivo half-life results in superior anti-hyperglycemic activity in mice compared to the wild-type OXM. PMID:26727558

  20. Optimal neural computations require analog processors

    SciTech Connect

    Beiu, V.

    1998-12-31

    This paper discusses some of the limitations of hardware implementations of neural networks. The authors start by presenting neural structures and their biological inspirations, while mentioning the simplifications leading to artificial neural networks. Further, the focus will be on hardware imposed constraints. They will present recent results for three different alternatives of parallel implementations of neural networks: digital circuits, threshold gate circuits, and analog circuits. The area and the delay will be related to the neurons` fan-in and to the precision of their synaptic weights. The main conclusion is that hardware-efficient solutions require analog computations, and suggests the following two alternatives: (i) cope with the limitations imposed by silicon, by speeding up the computation of the elementary silicon neurons; (2) investigate solutions which would allow the use of the third dimension (e.g. using optical interconnections).

  1. Observing spin optodynamical analog of cavity optomechanics

    NASA Astrophysics Data System (ADS)

    Gerber, Justin; Kohler, Jonathan; Spethmann, Nicolas; Schreppler, Sydney; Stamper-Kurn, Dan

    2016-05-01

    Cavity Optomechanics has been realized in many diverse systems and led to many interesting results such as ponderomotive squeezing of light, beyond-SQL measurement sensitivity, and squeezing of mechanical oscillators. Optical cavities also allow sensitive measurements of the spin of an atomic ensemble. It has been proposed to utilize this sensitivity to realize an analog of optomechanics by measuring the precession of small excitations of a spin-oscillator around a transverse magnetic field. I will present our recent work in which we realize optomechanical analogs in our system such as cavity-assisted cooling and amplification and optical spring shifts. In addition, the presence of a high-energy `ground state' of the spin oscillator allows the realization of an effective negative mass oscillator which is demonstrated by an inverted sideband asymmetry. In our ongoing work we attempt to realize coherent quantum noise cancelation by coupling spin oscillation with mechanical oscillation.

  2. The optical analogy for vector fields

    NASA Technical Reports Server (NTRS)

    Parker, E. N. (Editor)

    1991-01-01

    This paper develops the optical analogy for a general vector field. The optical analogy allows the examination of certain aspects of a vector field that are not otherwise readily accessible. In particular, in the cases of a stationary Eulerian flow v of an ideal fluid and a magnetostatic field B, the vectors v and B have surface loci in common with their curls. The intrinsic discontinuities around local maxima in absolute values of v and B take the form of vortex sheets and current sheets, respectively, the former playing a fundamental role in the development of hydrodyamic turbulence and the latter playing a major role in heating the X-ray coronas of stars and galaxies.

  3. Biomedical sensor design using analog compressed sensing

    NASA Astrophysics Data System (ADS)

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2015-05-01

    The main drawback of current healthcare systems is the location-specific nature of the system due to the use of fixed/wired biomedical sensors. Since biomedical sensors are usually driven by a battery, power consumption is the most important factor determining the life of a biomedical sensor. They are also restricted by size, cost, and transmission capacity. Therefore, it is important to reduce the load of sampling by merging the sampling and compression steps to reduce the storage usage, transmission times, and power consumption in order to expand the current healthcare systems to Wireless Healthcare Systems (WHSs). In this work, we present an implementation of a low-power biomedical sensor using analog Compressed Sensing (CS) framework for sparse biomedical signals that addresses both the energy and telemetry bandwidth constraints of wearable and wireless Body-Area Networks (BANs). This architecture enables continuous data acquisition and compression of biomedical signals that are suitable for a variety of diagnostic and treatment purposes. At the transmitter side, an analog-CS framework is applied at the sensing step before Analog to Digital Converter (ADC) in order to generate the compressed version of the input analog bio-signal. At the receiver side, a reconstruction algorithm based on Restricted Isometry Property (RIP) condition is applied in order to reconstruct the original bio-signals form the compressed bio-signals with high probability and enough accuracy. We examine the proposed algorithm with healthy and neuropathy surface Electromyography (sEMG) signals. The proposed algorithm achieves a good level for Average Recognition Rate (ARR) at 93% and reconstruction accuracy at 98.9%. In addition, The proposed architecture reduces total computation time from 32 to 11.5 seconds at sampling-rate=29 % of Nyquist rate, Percentage Residual Difference (PRD)=26 %, Root Mean Squared Error (RMSE)=3 %.

  4. The 2012 Moon and Mars Analog Mission

    NASA Technical Reports Server (NTRS)

    Graham, Lee

    2014-01-01

    The 2012 Moon and Mars Analog Mission Activities (MMAMA) scientific investigations were completed on Mauna Kea volcano in Hawaii in July 2012. The investigations were conducted on the southeast flank of the Mauna Kea volcano at an elevation of approximately 11,500 ft. This area is known as "Apollo Valley" and is in an adjacent valley to the Very Large Baseline Array dish antenna.

  5. Total synthesis of neopeltolide and analogs

    PubMed Central

    Cui, Yubo; Tu, Wangyang; Floreancig, Paul E.

    2010-01-01

    Neopeltolide, a potent cytotoxin from a Carribean sponge, was synthesized through a brief sequence that highlights the use of ethers as oxocarbenium ion precursors. Other key steps include an acid-mediated etherification and sequence that features a Sonogashira reaction, an intramolecular alkyne hydrosilylation reaction, and a Tamao oxidation. The alkene that is required for the oxidative cyclization can be hydrogenated to provide access to the natural product or an epimer, or can be epoxidized or dihydroxylated to form polar analogs. PMID:20697460

  6. Synthesis and biological evaluation of platensimycin analogs

    SciTech Connect

    Shen, Hong C.; Ding, Fa-Xiang; Singh, Sheo B.; Parthasarathy, Gopalakrishnan; Soisson, Stephen M.; Ha, Sookhee N.; Chen, Xun; Kodali, Srinivas; Wang, Jun; Dorso, Karen; Tata, James R.; Hammond, Milton L.; MacCoss, Malcolm; Colletti, Steven L.

    2009-07-23

    Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.

  7. Survey of Evaluated Isobaric Analog States

    SciTech Connect

    MacCormick, M.

    2014-06-15

    Isobaric analog states (IAS) can be used to estimate the masses of members belonging to the same isospin multiplet. Experimental and estimated IAS have been used frequently within the Atomic Mass Evaluation (AME) in the past, but the associated set of evaluated masses have been published for the first time in AME2012 and NUBASE2012. In this paper the current trends of the isobaric multiplet mass equation (IMME) coefficients are shown. The T = 2 multiplet is used as a detailed illustration.

  8. Antimicrobial Activity of Novel Furanonaphthoquinone Analogs

    PubMed Central

    Nagata, Kumiko; Hirai, Kei-Ichi; Koyama, Junko; Wada, Yasunao; Tamura, Toshihide

    1998-01-01

    Analogs of furanonaphthoquinone (FNQ) from Tecoma ipe Mart had MICs ranging from 1.56 to 25 μg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant Staphylococcus aureus than against methicillin-sensitive S. aureus. FNQ inhibited Helicobacter pylori with an MIC of 0.1 μg/ml. Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B. PMID:9517956

  9. Optical Oversampled Analog-to-Digital Conversion

    DTIC Science & Technology

    1992-06-29

    Introduction 1 1.1 Background and Motivation........................... 2 1.1.1 Nyquist Rate Conversion........................ 3 1.1.2 Optical A/ D ...processor [9] was used with the electronic analog input signal driving an optical beam deflector . This method of optical A/ D conversion was limited...implement an optical oversampled A/ D converter. From the theoretical development in Chapter 2 , there are two principal functions which require optical

  10. Magnetic Analog Random-Access Memory

    NASA Technical Reports Server (NTRS)

    Katti, Romney R.; Wu, Jiin-Chuan; Stadler, Henry L.

    1991-01-01

    Proposed integrated, solid-state, analog random-access memory base on principle of magnetic writing and magnetoresistive reading. Current in writing conductor magnetizes storage layer. Remanent magnetization in storage layer penetrates readout layer and detected by magnetoresistive effect or Hall effect. Memory cells are part of integrated circuit including associated reading and writing transistors. Intended to provide high storage density and rapid access, nonvolatile, consumes little power, and relatively invulnerable to ionizing radiation.

  11. Analog Building Blocks for Communications Modems.

    DTIC Science & Technology

    1977-01-01

    Transistors Q2, Q3, Q4 and Q5 provide isolation and power output capa- bilities. Transistor Q5 provides the drive to the programmable counter, Ul...the analog switch, U4. The programmable counter output pulse samples the ramp and charges C6 to its appropriate value. Transistor , Q7, is a source...implemented with low noise, dual gate MOSFET transistors , type RCA 40822. Broadband LC tuning is used to shape the frequency response of the three stage

  12. Analog Fiber Optic Recirculating Delay Line.

    DTIC Science & Technology

    1987-03-31

    signal is input through a BNC type connector and a corresponding optical analog signal is output via a single mode optical fiber. The transmitter...second functional transmitter subdivision. The stripline fix- ture board provides an impedance matching stripline from a BNC input connector to the RF...drive signal input pin of the laser hybrid. Other socket pins on this circuit board provide for the proper routing of sensor outputs to the

  13. Analog measurement of scattered optical fluctuations

    NASA Astrophysics Data System (ADS)

    Smith, P. R.; Green, D. A.

    1995-12-01

    A statistical model that describes the analog measurement of a fluctuating light intensity that arises from a non-Gaussian scattering process is developed. The higher-order statistical moments are derived for a p-i-n diode receiver model and gamma-distributed intensity fluctuations. Criteria for the accurate measurement of the scattering fluctuations are found, and these are used to analyze data derived from an on-line scatterometer system. Implications for future on-line measurement technology are discussed.

  14. Transition State Analog Inhibitors for Esterases.

    DTIC Science & Technology

    1983-06-02

    advanced about 1970, it has led to the synthesis of powerful reversible Inhibitors for a number of enzymes. More recently, transition state analog theory...to inactivate It. Organophosphate anticholinesterases are a classic example; many of the more recent examples allow the enzyme to generate a strong...could be utilized to explore such mechanistic questions. A second more practical goal was to prepare anticholinesterases of novel structure and

  15. On estimation of uncertainties in analog measurements

    SciTech Connect

    Adibi, M.M. ); Stovall, J.P. )

    1990-11-01

    Computer control of power systems require evaluation of uncertainties in analog measurements and their reduction to a level that allows satisfactory control. In this paper a range of measurements is obtained from a substation to span peak- and light-load conditions and to include bus voltages, phase angles and line flows. Then the redundancies in measurements are used to formulate several functions relating these measurements with their attending errors. Minimization of these functions have yielded the required corrective coefficients.

  16. Periglacial and glacial analogs for Martian landforms

    NASA Technical Reports Server (NTRS)

    Rossbacher, Lisa A.

    1992-01-01

    The list of useful terrestrial analogs for Martian landforms has been expanded to include: features developed by desiccation processes; catastrophic flood features associated with boulder-sized materials; and sorted ground developed at a density boundary. Quantitative analytical techniques developed for physical geography have been adapted and applied to planetary studies, including: quantification of the patterns of polygonally fractured ground to describe pattern randomness independent of pattern size, with possible correlation to the mechanism of origin and quantification of the relative area of a geomorphic feature or region in comparison to planetary scale. Information about Martian geomorphology studied in this project was presented at professional meetings world-wide, at seven colleges and universities, in two interactive televised courses, and as part of two books. Overall, this project has expanded the understanding of the range of terrestrial analogs for Martian landforms, including identifying several new analogs. The processes that created these terrestrial features are characterized by both cold temperatures and low humidity, and therefore both freeze-thaw and desiccation processes are important. All these results support the conclusion that water has played a significant role in the geomorphic history of Mars.

  17. Theory of analogous force on number sets

    NASA Astrophysics Data System (ADS)

    Canessa, Enrique

    2003-10-01

    A general statistical thermodynamic theory that considers given sequences of x-integers to play the role of particles of known type in an isolated elastic system is proposed. By also considering some explicit discrete probability distributions px for natural numbers, we claim that they lead to a better understanding of probabilistic laws associated with number theory. Sequences of numbers are treated as the size measure of finite sets. By considering px to describe complex phenomena, the theory leads to derive a distinct analogous force fx on number sets proportional to (∂ px/∂ x) T at an analogous system temperature T. In particular, this leads to an understanding of the uneven distribution of integers of random sets in terms of analogous scale invariance and a screened inverse square force acting on the significant digits. The theory also allows to establish recursion relations to predict sequences of Fibonacci numbers and to give an answer to the interesting theoretical question of the appearance of the Benford's law in Fibonacci numbers. A possible relevance to prime numbers is also analyzed.

  18. Clinical utility of insulin and insulin analogs.

    PubMed

    Sanlioglu, Ahter D; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect--rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes.

  19. Clinical utility of insulin and insulin analogs

    PubMed Central

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  20. Multiphoton excitation of fluorescent DNA base analogs.

    PubMed

    Katilius, Evaldas; Woodbury, Neal W

    2006-01-01

    Multiphoton excitation was used to investigate properties of the fluorescent DNA base analogs, 2-aminopurine (2AP) and 6-methylisoxanthopterin (6MI). 2-aminopurine, a fluorescent analog of adenine, was excited by three-photon absorption. Fluorescence correlation measurements were attempted to evaluate the feasibility of using three-photon excitation of 2AP for DNA-protein interaction studies. However, high excitation power and long integration times needed to acquire high signal-to-noise fluorescence correlation curves render three-photon excitation FCS of 2AP not very useful for studying DNA base dynamics. The fluorescence properties of 6-methylisoxanthopterin, a guanine analog, were investigated using two-photon excitation. The two-photon absorption cross-section of 6MI was estimated to be about 2.5 x 10(-50) cm(4)s (2.5 GM units) at 700 nm. The two-photon excitation spectrum was measured in the spectral region from 700 to 780 nm; in this region the shape of the two-photon excitation spectrum is very similar to the shape of single-photon excitation spectrum in the near-UV spectral region. Two-photon excitation of 6MI is suitable for fluorescence correlation measurements. Such measurements can be used to study DNA base dynamics and DNA-protein interactions over a broad range of time scales.

  1. Synthesis and verification of analog integrated circuits

    NASA Astrophysics Data System (ADS)

    Antao, Brian Anthony Amacio

    This dissertation addresses analog integrated circuit design from a systems perspective. An analog behavioral level is characterized in terms of transfer functions and state-space models; then a behavioral synthesis process defines high-level architectures independent of circuit implementation technologies. The concept of an intermediate architecture is introduced to synthesize the behavioural architectures into technology specific architectures. The two levels provide for system level design and a design space exploration, which allows tradeoffs between various architectures and implementation technologies. A customized behavioral simulation methodology is developed for architectural verification. The behavioral simulator is implemented in a circuit simulation paradigm with time and frequency domain analysis, steady state analysis and sensitivity and distortion analysis. The verification process ensures that the behavioral specifications are met and provides a set of metrics such as sensitivities for design space exploration. The synthesis and verification functionalities are implemented as the two software modules ARCHGEN and ARCHSIM. The two modules are coupled together into an integrated synthesis and verification framework. A C++ based Architecture Specification Language is devised for hardware description. The implementation is open-ended making possible the application of software synthesis techniques to customize the tools to specific classes of analog systems. A constrained nonlinear optimization approach is formulated for circuit-level design of MOS integrated circuits. A C++ based circuit description language is developed for defining the analytical design models, i.e. describing circuit topologies and performance functions for the optimizer.

  2. Targeting thyroid diseases with TSH receptor analogs.

    PubMed

    Galofré, Juan C; Chacón, Ana M; Latif, Rauf

    2013-12-01

    The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  3. Prostaglandin analogs in the treatment of glaucoma.

    PubMed

    Hejkal, T W; Camras, C B

    1999-09-01

    Prostaglandin (PG) analogs are some of the most recent additions to the list of ocular hypotensive medications. Two analogs of naturally occurring PGs are available commercially, isopropyl unoprostone (Rescula [Ciba Vision, Atlanta, GA]) and latanoprost (Xalatan [Pharmacia & Upjohn, Bridgewater, NJ]). Presently, latanoprost 0. 005% is the only PG analog commercially available in the United States. These agents have been shown to be the most effective topical medications for reducing intraocular pressure. They have a different mechanism of action than other ocular hypotensives, and act primarily by increasing uveoscleral outflow. Because of this, PGs have a substantial additive effect when used with agents that reduce aqueous production (eg, beta blockers or carbonic anhydrase inhibitors) or that increase trabecular outflow facility (eg, pilocarpine). Local side effects include mild conjunctival hyperemia and local irritation, darkening of iris color, increased growth of eyelashes, and a possible association with cystoid macular edema or iritis in some patients with other risk factors. No systemic side effects have been proven to be caused by latanoprost. Recommended dosing is once daily at bedtime.

  4. Automated D/3 to Visio Analog Diagrams

    SciTech Connect

    Posey, Stephen B.

    2000-08-10

    ADVAD1 reads an ASCII file containing the D/3 DCS MDL input for analog points for a D/3 continuous database. It uses the information in the files to create a series of Visio files representing the structure of each analog chain, one drawing per Visio file. The actual drawing function is performed by Visio (requires Visio version 4.5+). The user can configure the program to select which fields in the database are shown on the diagram and how the information is to be presented. This gives a visual representation of the structure of the analog chains, showing selected fields in a consistent manner. Updating documentation can be done easily and the automated approach eliminates human error in the cadding process. The program can also create the drawings far faster than a human operator is capable, able to create approximately 270 typical diagrams in about 8 minutes on a Pentium II 400 MHz PC. The program allows for multiple option sets to be saved to provide different settings (i.e., different fields, different field presentations, and /or different diagram layouts) for various scenarios or facilities on one workstation. Option sets may be exported from the Windows registry to allow duplication of settings on another workstation.

  5. Analogical transfer from a simulated physical system.

    PubMed

    Day, Samuel B; Goldstone, Robert L

    2011-05-01

    Previous research has consistently found that spontaneous analogical transfer is strongly tied to concrete and contextual similarities between the cases. However, that work has largely failed to acknowledge that the relevant factor in transfer is the similarity between individuals' mental representations of the situations rather than the overt similarities between the cases themselves. Across several studies, we found that participants were able to transfer strategies learned from a perceptually concrete simulation of a physical system to a task with very dissimilar content and appearance. This transfer was reflected in better performance on the transfer task when its underlying dynamics were consistent rather than inconsistent with the preceding training task. Our data indicate that transfer in these tasks relies on the perceptual and spatial nature of the training task but does not depend on direct interaction with the system, with participants performing equally well after simply observing the concrete simulation. We argue that participants generated a spatial, dynamic, and force-based mental model while interacting with the training simulation and tended to spontaneously interpret the transfer task according to this primed model. Unexpectedly, our data consistently show that transfer was independent of reported recognition of the analogy between tasks: Although such recognition was associated with better overall performance, it was not associated with better transfer (in terms of applying an appropriate strategy). Together, these findings suggest that analogical transfer between overtly dissimilar cases may be much more common--and much more relevant to our cognitive processing--than is generally assumed.

  6. Developmental Patterns in the Solution of Verbal Analogies.

    ERIC Educational Resources Information Center

    Sternberg, Robert J.; Nigro, Georgia

    1980-01-01

    Examines developmental patterns in the solution of verbal analogies. Twenty subjects in each of grades 3, 6, 9, and in college were tested on their relative abilities to solve 180 verbal analogies based on five different verbal relations. (CM)

  7. Solving Verbal Analogies: Some Cognitive Components of Intelligence Test Items

    ERIC Educational Resources Information Center

    Whitely, Susan E.

    1976-01-01

    The results indicate that although relational concepts influence the cognitive aptitudes which are reflected in analogy item performance, success in solving analogies does not depend on individual differences in some major aspects of processing relationships. (Author/DEP)

  8. Using Analogs for Chemistry Problem Solving: Does It Increase Understanding?

    ERIC Educational Resources Information Center

    Friedel, Arthur W.; And Others

    1990-01-01

    Discussed is the effectiveness of using analogies in chemistry instruction. Students' mathematics anxiety, spatial visualization skill, and proportional reasoning ability were found to be important aptitudes for determining chemistry achievement. The relationship between analogs and algorithms is described. (KR)

  9. Scientific Analogies and Their Use in Teaching Science

    NASA Astrophysics Data System (ADS)

    Kipnis, Nahum

    Analogy in science knew its successes and failures, as illustrated by examples from the eighteenth-century physics. At times, some scientists abstained from using a certain analogy on the ground that it had not yet been demonstrated. Several false discoveries in the 18th and early 19th centuries appeared to support their caution. It is now clear that such a position reflected a methodological confusion that resulted from a failure to distinguish between particular and general analogies. Considering analogy as a hierarchical structure provides a new insight into "testing an analogy". While warning science teachers of dangers associated with use of analogy, historical cases and their analysis provided here may encourage them to use analogy more extensively while avoiding misconceptions. An argument is made that the history of science may be a better guide than philosophy of science and cognitive psychology when it concerns the role of analogy in science and in teaching science for understanding.

  10. Using Analogies as an Experiential Learning Technique in Multicultural Education

    ERIC Educational Resources Information Center

    Suthakaran, V.; Filsinger, Keri; White, Brittany

    2013-01-01

    In this article the authors specifically address the use of narratives in the form of analogies as an experiential learning activity. The use of analogies as an experiential learning tool in multicultural education can be helpful in a number of ways. Analogies provide an alternative tool for processing multicultural topics with students who have…

  11. Analogical Instruction in Statistics: Implications for Social Work Educators

    ERIC Educational Resources Information Center

    Thomas, Leela

    2008-01-01

    This paper examines the use of analogies in statistics instruction. Much has been written about the difficulty social work students have with statistics. To address this concern, Glisson and Fischer (1987) called for the use of analogies. Understanding of analogical problem solving has surged in the last few decades with the integration of…

  12. Administration of Biosimilar Insulin Analogs: Role of Devices.

    PubMed

    Heinemann, Lutz; Fritz, Ingo; Khatami, Hootan; Edelman, Steven V

    2017-02-01

    With the expiration of patent protection for several originator insulin analog molecules, the availability of insulin analog copies is set to increase. Many regulatory authorities have developed, and continue to refine, guidelines for the approval of biosimilar insulin analogs. Aspects such as the structure, pharmacokinetics and pharmacodynamics, efficacy, safety, and immunogenicity of biosimilar insulin analogs are extensively addressed in these guidelines, but how the biosimilar insulin analog is administered to people with diabetes is not usually a topic. The aim of this article is to highlight that the delivery device-drug combination is of particular importance. Regulatory, legal, and practical aspects of the delivery device, be it a syringe, pen, or pump, have to be considered in the context of biosimilar insulin analogs. Although the safety and efficacy of biosimilar insulin analogs per se are of primary importance for physicians and people with diabetes, functions and features of the devices used for administration also require attention from a practical point of view. Unfortunately, although there are several clinical studies investigating the technical aspects of and patient preference for the originator insulin analog pens, there are currently very little published data for nonoriginator or biosimilar insulin analog pens. In addition, it is not known if it is safe to assume that a biosimilar insulin analog cartridge is compatible with an existing originator insulin analog pen. We believe that there is a need for more discussion on the role of devices for administration of biosimilar insulin analogs.

  13. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming

    ERIC Educational Resources Information Center

    Pena, Gil Patrus; Andrade-Filho, Jose de Souza

    2010-01-01

    Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to…

  14. When Reasoning Modifies Memory: Schematic Assimilation Triggered by Analogical Mapping

    ERIC Educational Resources Information Center

    Vendetti, Michael S.; Wu, Aaron; Rowshanshad, Ebi; Knowlton, Barbara J.; Holyoak, Keith J.

    2014-01-01

    Analogical mapping highlights shared relations that link 2 situations, potentially at the expense of information that does not fit the dominant pattern of correspondences. To investigate whether analogical mapping can alter subsequent recognition memory for features of a source analog, we performed 2 experiments with 4-term proportional analogies…

  15. Functional DNA: Teaching Infinite Series through Genetic Analogy

    ERIC Educational Resources Information Center

    Kowalski, R. Travis

    2011-01-01

    This article presents an extended analogy that connects infinite sequences and series to the science of genetics, by identifying power series as "DNA for a function." This analogy allows standard topics such as convergence tests or Taylor approximations to be recast in a "forensic" light as mathematical analogs of genetic concepts such as DNA…

  16. Using Analogies as an Experiential Learning Technique in Multicultural Education

    ERIC Educational Resources Information Center

    Suthakaran, V.; Filsinger, Keri; White, Brittany

    2013-01-01

    In this article the authors specifically address the use of narratives in the form of analogies as an experiential learning activity. The use of analogies as an experiential learning tool in multicultural education can be helpful in a number of ways. Analogies provide an alternative tool for processing multicultural topics with students who have…

  17. Language Is Like the Human Body: Teaching Concepts through Analogy.

    ERIC Educational Resources Information Center

    Davis, Patricia M.; Davidson, Gayle V.

    1994-01-01

    Describes 15 types of analogies, their facilitating function in mental processing, the kinds of knowledge for which they are most effectively employed, and their applicability across subject matter. Eight steps for constructing and presenting analogies and types of analogical relationships are included. Prevention of misconceptions is discussed.…

  18. The Role of Causal Models in Analogical Inference

    ERIC Educational Resources Information Center

    Lee, Hee Seung; Holyoak, Keith J.

    2008-01-01

    Computational models of analogy have assumed that the strength of an inductive inference about the target is based directly on similarity of the analogs and in particular on shared higher order relations. In contrast, work in philosophy of science suggests that analogical inference is also guided by causal models of the source and target. In 3…

  19. Investigating and Theorizing Discourse during Analogy Writing in Chemistry

    ERIC Educational Resources Information Center

    Bellocchi, Alberto; Ritchie, Stephen M.

    2011-01-01

    Explanations of the role of analogies in learning science at a cognitive level are made in terms of creating bridges between new information and students' prior knowledge. In this empirical study of learning with analogies in an 11th grade chemistry class, we explore an alternative explanation at the "social" level where analogy shapes…

  20. When Reasoning Modifies Memory: Schematic Assimilation Triggered by Analogical Mapping

    ERIC Educational Resources Information Center

    Vendetti, Michael S.; Wu, Aaron; Rowshanshad, Ebi; Knowlton, Barbara J.; Holyoak, Keith J.

    2014-01-01

    Analogical mapping highlights shared relations that link 2 situations, potentially at the expense of information that does not fit the dominant pattern of correspondences. To investigate whether analogical mapping can alter subsequent recognition memory for features of a source analog, we performed 2 experiments with 4-term proportional analogies…

  1. Functional DNA: Teaching Infinite Series through Genetic Analogy

    ERIC Educational Resources Information Center

    Kowalski, R. Travis

    2011-01-01

    This article presents an extended analogy that connects infinite sequences and series to the science of genetics, by identifying power series as "DNA for a function." This analogy allows standard topics such as convergence tests or Taylor approximations to be recast in a "forensic" light as mathematical analogs of genetic concepts such as DNA…

  2. Modern Communication: Exploring Physiological Transmission through Tech-Savvy Analogies

    ERIC Educational Resources Information Center

    Hollabaugh, Christopher R.; Milanick, Mark A.

    2014-01-01

    Analogies are often helpful for students to grasp key physiological concepts; sometimes the technical jargon makes the concept seem more complex than it actually is. In this article the authors provide several analogies for information transfer processes that sometimes confuse students. For an analogy to be useful, of course, it needs to be…

  3. Analog Microcontroller Model for an Energy Harvesting Round Counter

    DTIC Science & Technology

    2012-07-01

    Technical Report ARWSB-TR-12012 Analog Microcontroller Model for an Energy Harvesting Round Counter Sara...YYYY) 06-06-2012 2. REPORT TYPE FINAL 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Analog Microcontroller Model for an Energy ... Microcontroller The greatest energy requirements of the round counter circuitry are associated with the Microchip PIC12LF1822 microcontroller [4]. An analog

  4. Investigating and Theorizing Discourse during Analogy Writing in Chemistry

    ERIC Educational Resources Information Center

    Bellocchi, Alberto; Ritchie, Stephen M.

    2011-01-01

    Explanations of the role of analogies in learning science at a cognitive level are made in terms of creating bridges between new information and students' prior knowledge. In this empirical study of learning with analogies in an 11th grade chemistry class, we explore an alternative explanation at the "social" level where analogy shapes…

  5. Modern Communication: Exploring Physiological Transmission through Tech-Savvy Analogies

    ERIC Educational Resources Information Center

    Hollabaugh, Christopher R.; Milanick, Mark A.

    2014-01-01

    Analogies are often helpful for students to grasp key physiological concepts; sometimes the technical jargon makes the concept seem more complex than it actually is. In this article the authors provide several analogies for information transfer processes that sometimes confuse students. For an analogy to be useful, of course, it needs to be…

  6. Analogical Instruction in Statistics: Implications for Social Work Educators

    ERIC Educational Resources Information Center

    Thomas, Leela

    2008-01-01

    This paper examines the use of analogies in statistics instruction. Much has been written about the difficulty social work students have with statistics. To address this concern, Glisson and Fischer (1987) called for the use of analogies. Understanding of analogical problem solving has surged in the last few decades with the integration of…

  7. Can Pupils Use Taught Analogies for Electric Current?

    ERIC Educational Resources Information Center

    Black, David; Solomon, Joan

    1987-01-01

    Discusses the use of analogies and models for teaching about electric current. Reports on a study in which one group of students used analogies to learn about electric current and one did not. Results indicate that, in this case, analogies did not play a significant role in student understanding. (TW)

  8. The Role of Schemas in Analogical Problem Solving.

    ERIC Educational Resources Information Center

    Catrambone, Richard; Holyoak, Keith

    In general, people seem to be poor at noticing analogies, especially when they are required to apply an analogy to a domain that is new. It was suspected that schemas influence the noticing and applying of analogies. Schemas are hypothesized to be abstract propositional structures that emphasize relationships among categories of objects rather…

  9. Interactive Optical Disc Systems: Part 1: Analog Storage.

    ERIC Educational Resources Information Center

    Hessler, David W.

    1984-01-01

    Details distinction between digital and analog data, advantages of analog storage, and optical disc use to store analog data. Configuration and potential of three levels of laser disc systems are explained. Selection of display devices for use with laser disc systems and accessing audio data are addressed. (Continued in next issue.) (EJS)

  10. Can Pupils Use Taught Analogies for Electric Current?

    ERIC Educational Resources Information Center

    Black, David; Solomon, Joan

    1987-01-01

    Discusses the use of analogies and models for teaching about electric current. Reports on a study in which one group of students used analogies to learn about electric current and one did not. Results indicate that, in this case, analogies did not play a significant role in student understanding. (TW)

  11. Analogy Use in Eighth-Grade Mathematics Classrooms

    ERIC Educational Resources Information Center

    Richland, Lindsey E.; Holyoak, Keith J.; Stigler, James W.

    2004-01-01

    Analogical reasoning has long been believed to play a central role in mathematics learning and problem solving (see Genter, Holyoak, & Kokinov, 2001); however, little is known about how analogy is used in everyday instructional contexts. This article examines analogies produced in naturally occurring U.S. mathematics lessons to explore…

  12. Comparison of Three Methods for Improving Verbal Analogies Solution.

    ERIC Educational Resources Information Center

    Loewenthal, Gloria G.; Pons, Manuel M.

    1987-01-01

    Investigates the relationship between analogical reasoning and academic learning. Results show that efforts to improve academic achievement through training in analogical thinking are based on the correct assumption that analogical thinking can be trained and that various methods of training are effective in this regard. (MS)

  13. Historical Shifts in the Use of Analogy in Science.

    ERIC Educational Resources Information Center

    Gentner, Dedre; Jeziorski, Michael

    Analogy is widely considered to be an important mechanism of scientific thinking and a source of creative insight in theory development. In this paper the implicit constraints that determine analogical soundness are considered. It first examines the constraints that govern analogical reasoning as it is predicted today. The scientific uses of…

  14. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-05

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.

  15. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming

    ERIC Educational Resources Information Center

    Pena, Gil Patrus; Andrade-Filho, Jose de Souza

    2010-01-01

    Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to…

  16. Inviting Argument by Analogy: Analogical-Mapping-Based Comparison Activities as a Scaffold for Small-Group Argumentation

    ERIC Educational Resources Information Center

    Emig, Brandon R.; McDonald, Scott; Zembal-Saul, Carla; Strauss, Susan G.

    2014-01-01

    This study invited small groups to make several arguments by analogy about simple machines. Groups were first provided training on analogical (structure) mapping and were then invited to use analogical mapping as a scaffold to make arguments. In making these arguments, groups were asked to consider three simple machines: two machines that they had…

  17. Inviting Argument by Analogy: Analogical-Mapping-Based Comparison Activities as a Scaffold for Small-Group Argumentation

    ERIC Educational Resources Information Center

    Emig, Brandon R.; McDonald, Scott; Zembal-Saul, Carla; Strauss, Susan G.

    2014-01-01

    This study invited small groups to make several arguments by analogy about simple machines. Groups were first provided training on analogical (structure) mapping and were then invited to use analogical mapping as a scaffold to make arguments. In making these arguments, groups were asked to consider three simple machines: two machines that they had…

  18. The effectiveness of teaching science with pictorial analogies

    NASA Astrophysics Data System (ADS)

    Lin, Huann-Shyang; Shiau, Bih-Ruh; Lawrenz, Frances

    1996-12-01

    This study used a conceptual problem solving test to investigate the effect of a series of pictorial analogies on the concepts of density, pressure, and atmospheric pressure in Year 8 classrooms. The analogies were taught following Glynn's teaching with analogies model. It was found that the students taught with the pictorial analogies scored significantly higher than their counterparts ( p<01). In addition, the low achievers benefited more from this teaching strategy than did the high achievers. Further, qualitative analysis revealed that most of the students' alternative conceptions were from preexisting naive intuitions rather than arising from analog instruction.

  19. SSERVI Analog Regolith Simulant Testbed Facility

    NASA Astrophysics Data System (ADS)

    Minafra, Joseph; Schmidt, Gregory; Bailey, Brad; Gibbs, Kristina

    2016-10-01

    The Solar System Exploration Research Virtual Institute (SSERVI) at NASA's Ames Research Center in California's Silicon Valley was founded in 2013 to act as a virtual institute that provides interdisciplinary research centered on the goals of its supporting directorates: NASA Science Mission Directorate (SMD) and the Human Exploration & Operations Mission Directorate (HEOMD).Primary research goals of the Institute revolve around the integration of science and exploration to gain knowledge required for the future of human space exploration beyond low Earth orbit. SSERVI intends to leverage existing JSC1A regolith simulant resources into the creation of a regolith simulant testbed facility. The purpose of this testbed concept is to provide the planetary exploration community with a readily available capability to test hardware and conduct research in a large simulant environment.SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers.SSERVI provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment.The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area, including dust mitigation and safety oversight.Facility hardware and environment testing scenarios could include, Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, Surface features (i.e. grades and rocks)Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and

  20. Analog/Digital System for Germanium Thermometer

    NASA Technical Reports Server (NTRS)

    Woodhouse, Christopher

    1988-01-01

    Electronic system containing analog and digital circuits makes high-precision, four-wire measurements of resistance of each germanium resistance thermometer (GRT) in array of devices, using alternating current (ac) of 1 micro-A. At end measurement interval, contents of negative register subtracted from positive one, resulting in very-narrow-band synchronous demodulation of carrier wave and suppression of out-of-band noise. Microprocessor free to perform other duties after measurement complete. Useful in noisy terrestrial environments encountered in factories.

  1. Article for analog vector algebra computation.

    PubMed

    Mills, A P; Yurke, B; Platzman, P M

    1999-10-01

    We introduce the concept of an analog neural network represented by chemical operations performed on strands of DNA. This new type of DNA computing has the advantage that it should be fault tolerant and thus more immune to DNA hybridization errors than a Boolean DNA computer. We describe a particular set of DNA operations to effect the interconversion of electrical and DNA data and to represent the Hopfield associative memory and the feed-forward neural network of Rumelhart et al. We speculate that networks containing as many as 10(9) neurons might be feasible.

  2. Soviet Space Stations as Analogs, Second Edition

    NASA Technical Reports Server (NTRS)

    Bluth, B. J.; Helppie, Martha

    1986-01-01

    The available literature that discusses the various aspects of the Soviet Salyut 6 and Salyut 7 space staions are examined as related to human productivity. The methodology for this analog was a search of unclassified literature. Additional information was obtained in interviews with the cosmonauts and some Soviet space personnel. Topics include: general layout and design of the spacecraft system; cosmonauts role in maintenance and repair; general layout and design of the Mir complex; effects of the environment on personnel; information and computer systems; organization systems; personality systems; and physical conditin of the cosmonaut.

  3. Solid-state-based analog of optomechanics

    DOE PAGES

    Naumann, Nicolas L.; Droenner, Leon; Carmele, Alexander; ...

    2016-09-01

    In this study, we investigate a semiconductor quantum dot as a microscopic analog of a basic optomechanical setup. We show that optomechanical features can be reproduced by the solid-state platform, arising from parallels of the underlying interaction processes, which in the optomechanical case is the radiation pressure coupling and in the semiconductor case the electron–phonon coupling. We discuss bistabilities, lasing, and phonon damping, and recover the same qualitative behaviors for the semiconductor and the optomechanical cases expected for low driving strengths. However, in contrast to the optomechanical case, distinct signatures of higher order processes arise in the semiconductor model.

  4. Tyrphostin analogs are GPR35 agonists.

    PubMed

    Deng, Huayun; Hu, Haibei; Fang, Ye

    2011-06-23

    GPR35 is an orphan G protein-coupled receptor that is not well-characterized. Here we employ dynamic mass redistribution (DMR) assays to discover new GPR35 agonists. DMR assays identified tyrphostin analogs as GPR35 agonists, which were confirmed with receptor internalization, Tango β-arrestin translocation, and extracellular-signal-regulated kinase phosphorylation assays. These agonists provide pharmacological tools to study the biology and function of GPR35. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Synthesis and antioxidant activity of curcumin analogs.

    PubMed

    Zheng, Qu-Tong; Yang, Ze-Hua; Yu, Liu-Ying; Ren, Yu-Yan; Huang, Qiu-Xia; Liu, Qiu; Ma, Xiang-Yu; Chen, Zi-Kang; Wang, Zong-Bao; Zheng, Xing

    2017-05-01

    Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure-activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.

  6. Reconfiguration of Analog Electronics for Extreme Environments

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian; Zebulum, Ricardo; Keymeulen, Didier; Guo, Xin

    2005-01-01

    This paper argues in favor of adaptive reconfiguration as a technique to expand the operational envelope of analog electronics for extreme environments (EE). On a reconfigurable device, although component parameters change in EE, as long as devices still operate, albeit degraded, a new circuit design, suitable for new parameter values, may be mapped into the reconfigurable structure to recover the initial circuit function. Laboratory demonstrations of this technique were performed by JPL in several independent experiments in which bulk CMOS reconfgurable devices were exposed to, and degraded by, high temperatures (approx.300 C) or radiation (300kRad TID), and then recovered by adaptive reconfiguration using evolutionary search algorithms.

  7. CCD Analog Programmable Microprocessor (APUP) Study

    DTIC Science & Technology

    1980-08-01

    chirp filter or CZT at IF. An APUP can function next as a fast read-in/slow read-out analog storage to spread the range data in time to fill the inter...functional partitioning into several distinct candidates primarily on the basis of data storage time and data format. The azimuth- processing function...Simulation of the ISL/MOS Interface 7-53 Circuit for a 20-MHz Clock 7.7-1 Capacitance - Time Curve 7-55 7.7-2 Test Pattern for PCCD, MOS, and ECL 7

  8. Mars-Analog Evaporite Experiment: Initial Results

    NASA Technical Reports Server (NTRS)

    Moore, J. M.; Bullock, M. A.; Sharp, T.G.; Quinn, R.

    2005-01-01

    This research is part of a multiyear experimental investigation to understand the nature and evolution brines and evaporates on Mars. The spectacular discoveries of the MER rovers, particularly those of Opportunity at Meridiani, both illustrate the relevance, as well as guide the future direction, of this work. Here we report the initial results from our just-completed and tested evaporites apparatus, using a synthetic brine analog to our brine experiment simulating a modern Mars environment in which the brine was subjected to rapid evaporation under modern Martian conditions. Additional information is included in the original extended abstract.

  9. Analogy among microfluidics, micromechanics, and microelectronics.

    PubMed

    Li, Sheng-Shian; Cheng, Chao-Min

    2013-10-07

    We wish to illuminate the analogous link between microfluidic-based devices, and the already established pairing of micromechanics and microelectronics to create a triangular/three-way scientific relationship as a means of interlinking familial disciplines and accomplishing two primary goals: (1) to facilitate the modeling of multidisciplinary domains; and, (2) to enable us to co-simulate the entire system within a compact circuit simulator (e.g., Cadence or SPICE). A microfluidic channel-like structure embedded in a micro-electro-mechanical resonator via our proposed CMOS-MEMS technology is used to illustrate the connections among microfluidics, micromechanics, and microelectronics.

  10. A bilateral frontoparietal network underlies visuospatial analogical reasoning.

    PubMed

    Watson, Christine E; Chatterjee, Anjan

    2012-02-01

    Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies.

  11. Analogies as categorization phenomena: Studies from scientific discourse

    NASA Astrophysics Data System (ADS)

    Atkins, Leslie Jill

    Studies on the role of analogies in science classrooms have tended to focus on analogies that come from the teacher or curriculum, and not the analogies that students generate. Such studies are derivative of an educational system that values content knowledge over scientific creativity, and derivative of a model of teaching in which the teacher's role is to convey content knowledge. This dissertation begins with the contention that science classrooms should encourage scientific thinking and one role of the teacher is to model that behavior and identify and encourage it in her students. One element of scientific thinking is analogy. This dissertation focuses on student-generated analogies in science, and offers a model for understanding these. I provide evidence that generated analogies are assertions of categorization, and the base of an analogy is the constructed prototype of an ad hoc category. Drawing from research on categorization, I argue that generated analogies are based in schemas and cognitive models. This model allows for a clear distinction between analogy and literal similarity; prior to this research analogy has been considered to exist on a spectrum of similarity, differing from literal similarity to the degree that structural relations hold but features do not. I argue for a definition in which generated analogies are an assertion of an unexpected categorization: that is, they are asserted as contradictions to an expected schema.

  12. A Bilateral Frontoparietal Network Underlies Visuospatial Analogical Reasoning

    PubMed Central

    Watson, Christine E.; Chatterjee, Anjan

    2011-01-01

    Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies. PMID:21982934

  13. Analogies in medicine: valuable for learning, reasoning, remembering and naming.

    PubMed

    Pena, Gil Patrus; Andrade-Filho, José de Souza

    2010-10-01

    Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to explain a knowledge to be achieved (the target), with pieces of information already familiar to the learner (the source), keeping in mind the constraints of similarity, structure and purpose. The purpose of this essay is to examine the use of analogies in medicine. We provide a brief review of the theoretical basis of analogical reasoning. This theoretical background is discussed in the light of actual examples of analogies retrieved from medical literature. In medicine, analogies have long been used to explain several physiologic and pathologic processes. Besides deeper structural relations, superficial attribute similarity is extensively used in many medical specialties. These attribute similarities are important in naming, categorizing and classifying, and play a role as learning and memorizing tools. Analogies also serve as basis for medical nomenclature. The choice of the source of analogies is highly dependent on cultural background, and may derive from ancient or diverse cultures. Learning by analogies may thus require research on culture diversity in order to establish an adequate justification and to comprehend the purpose of an analogy.

  14. Unconscious violinists and the use of analogies in moral argument.

    PubMed

    Wiland, E

    2000-12-01

    Analogies are the stuff out of which normative moral philosophy is made. Certainly one of the most famous analogies constructed by a philosopher in order to argue for a specific controversial moral conclusion is the one involving Judith Thomson's unconscious violinist. Reflection upon this analogy is meant to show us that abortion is generally not immoral even if the prenatal have the same moral status as the postnatal. This was and still is a controversial conclusion, and yet the analogy does seem to reveal in a very vivid way what makes abortion a reasonable response to a terrible situation. But Thomson's example has frequently been attacked on all sides for not being truly analogous to abortion. Here I develop a brand new analogy that sheds light on the issue with which Thomson was concerned, while at the same time avoiding most of the more serious objections made to her analogy.

  15. The importance of explicitly mapping instructional analogies in science education

    NASA Astrophysics Data System (ADS)

    Asay, Loretta Johnson

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With Analogies (TWA) model (Glynn, 1991) is one of the models frequently cited in the variety of research about analogies. The TWA model outlines steps for instruction, including the step of explicitly mapping the features of the source to the target. An experimental study was conducted to examine the effects of explicitly mapping the features of the source and target in an analogy during computer-based instruction about electrical circuits. Explicit mapping was compared to no mapping and to a control with no analogy. Participants were ninth- and tenth-grade biology students who were each randomly assigned to one of three conditions (no analogy module, analogy module, or explicitly mapped analogy module) for computer-based instruction. Subjects took a pre-test before the instruction, which was used to assign them to a level of previous knowledge about electrical circuits for analysis of any differential effects. After the instruction modules, students took a post-test about electrical circuits. Two weeks later, they took a delayed post-test. No advantage was found for explicitly mapping the analogy. Learning patterns were the same, regardless of the type of instruction. Those who knew the least about electrical circuits, based on the pre-test, made the most gains. After the two-week delay, this group maintained the largest amount of their gain. Implications exist for science education classrooms, as analogy use should be based on research about effective practices. Further studies are suggested to foster the building of research-based models for classroom instruction with analogies.

  16. Analog VLSI for active drag reduction

    NASA Astrophysics Data System (ADS)

    Gupta, Vidyabhusan

    In today's cost-conscious air transportation industry, fuel costs are a substantial economic concern. Drag reduction is an important way to increase fuel efficiency which reduces these costs. Even a 1% reduction in drag can translate into estimated savings of tens of millions of dollars in annual fuel costs. Fluid mechanicists believe that microscopic vortex pairs impinging on the surface play an important role in turbulent transport that may cause large skin friction drag. The microscopic nature and unpredictable appearance of these structures has limited practical approaches to their control. With the advent of micromachining technology providing the ability to build mechanical structures with microscopic dimensions, the tools finally exist with which to detect and control the vortex structures. These sensors and actuators require control circuitry between them in order to build a complete system. We propose an analog VLSI system that can process information along a surface in a moving fluid with the goal of controlling actuators to minimize the surface shear stress. We obtain the information from the surface by using microsensors which measure the surface shear stress. The actuators interact with the fluid by moving up and down in an attempt to diminish the impact of the drag-inducing structures in the fluid. We have designed the fabricated an analog control system. We have tested the system in several different experiments to verify its effectiveness in providing a control signal that energizes an actuator. We also have studied the methodology for a completely integrated wafer-scale system.

  17. Laminate analogy for composites enhanced concrete structures

    SciTech Connect

    Chamis, C.C.; Gotsis, P.K.

    1997-10-01

    A new and effective method is described to design composites to repair damage or enhance the overload strength of concrete infrastructures. The method is based on laminate analogy which is derivable from composite mechanics and available in computer codes. It is used to simulate structural sections made from reinforced concrete which are typical in infrastructures as well as select reinforced concrete structures. The structural sections are represented by a number of layers through the thickness where different layers are used for the concrete, for the reinforcing steel in concrete, and for the composite. The reinforced concrete structures are represented with finite elements where the element stiffness parameters are from the structural sections which are represented by the laminate analogy. The load carrying capability of the structure is determined by progressive structural fracture. Results show up to 40 percent improvements for damage and for overload enhancement with relatively small laminate thickness for the structural sections and up to three times for the composite enhanced select structures (arch and dome).

  18. Digital and analog gene circuits for biotechnology.

    PubMed

    Roquet, Nathaniel; Lu, Timothy K

    2014-05-01

    Biotechnology offers the promise of valuable chemical production via microbial processing of renewable and inexpensive substrates. Thus far, static metabolic engineering strategies have enabled this field to advance industrial applications. However, the industrial scaling of statically engineered microbes inevitably creates inefficiencies due to variable conditions present in large-scale microbial cultures. Synthetic gene circuits that dynamically sense and regulate different molecules can resolve this issue by enabling cells to continuously adapt to variable conditions. These circuits also have the potential to enable next-generation production programs capable of autonomous transitioning between steps in a bioprocess. Here, we review the design and application of two main classes of dynamic gene circuits, digital and analog, for biotechnology. Within the context of these classes, we also discuss the potential benefits of digital-analog interconversion, memory, and multi-signal integration. Though synthetic gene circuits have largely been applied for cellular computation to date, we envision that utilizing them in biotechnology will enhance the efficiency and scope of biochemical production with living cells.

  19. Antarctic Analog for Dilational Bands on Europa

    NASA Technical Reports Server (NTRS)

    Hurford, T. A.; Brunt, K. M.

    2014-01-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  20. The gravitational analog of Faraday's induction law

    NASA Astrophysics Data System (ADS)

    Zile, Daniel; Overduin, James

    2015-04-01

    Michael Faraday, the discoverer of electromagnetic induction, was convinced that there must also be a gravitational analog of this law, and he carried out drop-tower experiments in 1849 to look for the electric current induced in a coil by changes in gravitational flux through the coil. This work, now little remembered, was in some ways the first investigation of what we would now call a unified-field theory. We revisit Faraday's experiments in the light of current knowledge and ask what might be learned if they were to be performed today. We then review the gravitational analog for Faraday's law that arises within the vector (or gravito-electromagnetic) approximation to Einstein's theory of general relativity in the weak-field, low-velocity limit. This law relates spinning masses and induced ``mass currents'' rather than spinning charges and electric currents, but is otherwise remarkably similar to its electromagnetic counterpart. The predicted effects are completely unobservable in everyday settings like those envisioned by Faraday, but are thought to be relevant in astrophysical contexts like the accretion disks around collapsed stars, thus bearing out Faraday's remarkable intuition. Undergraduate student.

  1. Antarctic analog for dilational bands on Europa

    NASA Astrophysics Data System (ADS)

    Hurford, T. A.; Brunt, K. M.

    2014-09-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  2. AFEII Analog Front End Board Design Specifications

    SciTech Connect

    Rubinov, Paul; /Fermilab

    2005-04-01

    This document describes the design of the 2nd iteration of the Analog Front End Board (AFEII), which has the function of receiving charge signals from the Central Fiber Tracker (CFT) and providing digital hit pattern and charge amplitude information from those charge signals. This second iteration is intended to address limitations of the current AFE (referred to as AFEI in this document). These limitations become increasingly deleterious to the performance of the Central Fiber Tracker as instantaneous luminosity increases. The limitations are inherent in the design of the key front end chips on the AFEI board (the SVXIIe and the SIFT) and the architecture of the board itself. The key limitations of the AFEI are: (1) SVX saturation; (2) Discriminator to analog readout cross talk; (3) Tick to tick pedestal variation; and (4) Channel to channel pedestal variation. The new version of the AFE board, AFEII, addresses these limitations by use of a new chip, the TriP-t and by architectural changes, while retaining the well understood and desirable features of the AFEI board.

  3. Menaquinone Analogs Inhibit Growth of Bacterial Pathogens

    PubMed Central

    Merriman, Joseph A.; Salgado-Pabón, Wilmara; Mueller, Elizabeth A.; Spaulding, Adam R.; Vu, Bao G.; Chuang-Smith, Olivia N.; Kohler, Petra L.; Kirby, John R.

    2013-01-01

    Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 μg/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents. PMID:23959313

  4. Metaphor and analogy in everyday problem solving.

    PubMed

    Keefer, Lucas A; Landau, Mark J

    2016-11-01

    Early accounts of problem solving focused on the ways people represent information directly related to target problems and possible solutions. Subsequent theory and research point to the role of peripheral influences such as heuristics and bodily states. We discuss how metaphor and analogy similarly influence stages of everyday problem solving: Both processes mentally map features of a target problem onto the structure of a relatively more familiar concept. When individuals apply this structure, they use a well-known concept as a framework for reasoning about real world problems and candidate solutions. Early studies found that analogy use helped people gain insight into novel problems. More recent research on metaphor goes further to show that activating mappings has subtle, sometimes surprising effects on judgment and reasoning in everyday problem solving. These findings highlight situations in which mappings can help or hinder efforts to solve problems. WIREs Cogn Sci 2016, 7:394-405. doi: 10.1002/wcs.1407 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  5. Photonic analog-to-digital converters

    NASA Astrophysics Data System (ADS)

    Valley, George C.

    2007-03-01

    This paper reviews over 30 years of work on photonic analog-to-digital converters. The review is limited to systems in which the input is a radio-frequency (RF) signal in the electronic domain and the output is a digital version of that signal also in the electronic domain, and thus the review excludes photonic systems directed towards digitizing images or optical communication signals. The state of the art in electronic ADCs, basic properties of ADCs and properties of analog optical links, which are found in many photonic ADCs, are reviewed as background information for understanding photonic ADCs. Then four classes of photonic ADCs are reviewed: 1) photonic assisted ADC in which a photonic device is added to an electronic ADC to improve performance, 2) photonic sampling and electronic quantizing ADC, 3) electronic sampling and photonic quantizing ADC, and 4) photonic sampling and quantizing ADC. It is noted, however, that all 4 classes of “photonic ADC” require some electronic sampling and quantization. After reviewing all known photonic ADCs in the four classes, the review concludes with a discussion of the potential for photonic ADCs in the future.

  6. Martian hillside gullies and icelandic analogs

    NASA Astrophysics Data System (ADS)

    Hartmann, William K.; Thorsteinsson, Thorsteinn; Sigurdsson, Freysteinn

    2003-04-01

    We report observations of Icelandic hillside gully systems that are near duplicates of gullies observed on high-latitude martian hillsides. The best Icelandic analogs involve basaltic talus slopes at the angle of repose, with gully formation by debris flows initiated by ground water saturation, and/or by drainage of water from upslope cliffs. We report not only the existence of Mars analog gullies, but also an erosional sequence of morphologic forms, found both on Mars and in Iceland. The observations support hypotheses calling for creation of martian gullies by aqueous processes. Issues remain whether the water in each case comes only from surficial sources, such as melting of ground ice or snow, or from underground sources such as aquifers that gain surface access in hillsides. Iceland has many examples of the former, but the latter mechanism is not ruled out. Our observations are consistent with the martian debris flow mechanism of F. Costard et al. (2001c, Science295, 110-113), except that classic debris flows begin at midslope more frequently than on Mars. From morphologic observations, we suggest that some martian hillside gully systems not only involve significant evolution by extended erosive activity, but gully formation may occur in episodes, and the time interval since the last episode is considerably less than the time interval needed to erase the gully through normal martian obliteration processes.

  7. Amygdalin analogs for the treatment of psoriasis.

    PubMed

    Perez, Juan J

    2013-05-01

    Psoriasis is one of the most prevalent immune-mediated illness worldwide. The disease can still only be managed rather than cured, so treatments are aimed at clearing skin lesions and preventing their recurrence. Several treatments are available depending on the extent of the psoriatic lesion. Among the topical treatments corticostereoids, vitamin D3 analogs and retinoids are commonly used. However, these treatments may have adverse effects in the long term. Conversely, systemic conventional treatments include immunosuppresors such as cyclosporin or methotrexate associated with high toxicity levels. Biologicals are alternative therapeutical agents introduced in the last 10 years. These include fusion proteins or monoclonal antibodies designed to inhibit the action of specific cytokines or to prevent T-lymphocyte activation. However, due to recent knowledge on the etiology of the disease, diverse new small molecules have appeared as promising alternatives for the treatment of psoriasis. Among them, inhibitors of JAK3, inhibitors of PDE 4 and amygdalin analogs. The latter are promising small molecules presently in preclinical studies which are the object of the present report.

  8. Menaquinone analogs inhibit growth of bacterial pathogens.

    PubMed

    Schlievert, Patrick M; Merriman, Joseph A; Salgado-Pabón, Wilmara; Mueller, Elizabeth A; Spaulding, Adam R; Vu, Bao G; Chuang-Smith, Olivia N; Kohler, Petra L; Kirby, John R

    2013-11-01

    Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 μg/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents.

  9. Digital and Analog Gene Circuits for Biotechnology

    PubMed Central

    Roquet, Nathaniel; Lu, Timothy K.

    2014-01-01

    Biotechnology offers the promise of valuable chemical production via microbial processing of renewable and inexpensive substrates. Thus far, static metabolic engineering strategies have enabled this field to advance industrial applications. However, the industrial scaling of statically engineered microbes inevitably creates inefficiencies due to variable conditions present in large-scale microbial cultures. Synthetic gene circuits that dynamically sense and regulate different molecules can resolve this issue by enabling cells to continuously adapt to variable conditions. These circuits also have the potential to enable next-generation production programs capable of autonomous transitioning between steps in a bioprocess. Here, we review the design and application of two main classes of dynamic gene circuits, digital and analog, for biotechnology. Within the context of these classes, we also discuss the potential benefits of digital-analog interconversion, memory, and multi-signal integration. Though synthetic gene circuits have largely been applied for cellular computation to date, we envision that utilizing them in biotechnology will enhance the efficiency and scope of biochemical production with living cells. PMID:24677719

  10. Operational Lessons Learned from NASA Analog Missions

    NASA Technical Reports Server (NTRS)

    Arnold, Larissa S.

    2010-01-01

    vehicle and system capabilities are required to support the activities? How will the crew and the Earth-based mission control team interact? During the initial phases of manned planetary exploration, one challenge in particular is virtually the same as during the Apollo program: How can scientific return be maximized during a relatively short surface mission? Today, NASA is investigating solutions to these challenges by conducting analog missions. These Earth-based missions possess characteristics that are analogous to missions on the Moon or Mars. These missions are excellent for testing operational concepts, and the design, configuration, and functionality of spacesuits, robots, rovers, and habitats. Analog mission crews test specific techniques and procedures for surface field geology, biological sample collection, and planetary protection. The process of actually working an analog mission reveals a myriad of small details, which either contribute to or impede efficient operations, many of which would never have been thought about otherwise. It also helps to define the suite of tools, containers, and other small equipment that surface explorers will use. This paper focuses on how analog missions have addressed selected operational considerations for future planetary missions.

  11. The ABCs of Analogical Abilities: Evidence for Formal Analogical Reasoning Abilities in 24-Month-Olds

    ERIC Educational Resources Information Center

    Singer-Freeman, Karen E.; Bauer, Patricia J.

    2008-01-01

    Solving formal analogy problems requires the identification of an initial term and the transformation that occurs between the initial two terms as well as the determination of the final term. Experiment 1 tested 24-month-olds' ability to determine final terms when they were shown the initial term and told the transformation that was to occur.…

  12. Synthetic Biology: A Unifying View and Review Using Analog Circuits.

    PubMed

    Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

    2015-08-01

    We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

  13. Experiments on Evolving Software Models of Analog Circuits

    NASA Technical Reports Server (NTRS)

    Lohn, Jason D.

    1999-01-01

    Analog circuits are of great importance in electronic system design since the world is fundamentally analog in nature. While the amount of digital design activity far outpaces that of analog design, most digital systems require analog modules for interfacing with the external world. It was recently estimated that approximately 60% of digital application- specific integrated circuit designs incorporated analog circuits. With challenging analog circuit design problems and few analog design engineers, there are economic reasons for automating the analog design process, especially time-to-market considerations. Techniques for analog circuit design automation began appearing about two decades ago. These methods incorporated heuristics [6], knowledge bases [1], simulated annealing [5], and other algorithms. Efforts using techniques from evolutionary computation began appearing over the last few years. These include the use of genetic algorithms to select electronic component values (for example, the resistance value of a resistor), to select circuit topologies, and to design amplifiers using a limited set of canned topologies [4]. A genetic programming-based analog circuit design system has been demonstrated in which the circuit sizes, component values, and the circuit topologies are determined automatically [3]. The genetic-algorithm systems typically represent circuit structures as vectors of parameters encoded in binary strings, while the genetic programming system manipulates tree data structures.

  14. Experiments on Evolving Software Models of Analog Circuits

    NASA Technical Reports Server (NTRS)

    Lohn, Jason D.

    1999-01-01

    Analog circuits are of great importance in electronic system design since the world is fundamentally analog in nature. While the amount of digital design activity far outpaces that of analog design, most digital systems require analog modules for interfacing with the external world. It was recently estimated that approximately 60% of digital application- specific integrated circuit designs incorporated analog circuits. With challenging analog circuit design problems and few analog design engineers, there are economic reasons for automating the analog design process, especially time-to-market considerations. Techniques for analog circuit design automation began appearing about two decades ago. These methods incorporated heuristics [6], knowledge bases [1], simulated annealing [5], and other algorithms. Efforts using techniques from evolutionary computation began appearing over the last few years. These include the use of genetic algorithms to select electronic component values (for example, the resistance value of a resistor), to select circuit topologies, and to design amplifiers using a limited set of canned topologies [4]. A genetic programming-based analog circuit design system has been demonstrated in which the circuit sizes, component values, and the circuit topologies are determined automatically [3]. The genetic-algorithm systems typically represent circuit structures as vectors of parameters encoded in binary strings, while the genetic programming system manipulates tree data structures.

  15. A Systematic Evaluation of Analogs for the Read-across ...

    EPA Pesticide Factsheets

    Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a target data-poor chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified based on structural similarity. Although much guidance has been published for read-across, practical guiding principles for the identification and evaluation of the scientific validity of source analogs, which is a critical step in deriving a robust read-across prediction, remains largely lacking.This case study explores the extent to which 3 structure descriptor sets (Pubchem, Chemotyper and MoSS) and their combinations are able to identify valid analogs for reading across Estrogen Receptor (ER) activity for a specific class of chemicals: hindered phenols. For each target chemical, two sets of analogs (hindered and non-hindered phenols) were selected using each descriptor set with two cut-offs: (1). Minimum Tanimoto similarity (range 0.1 - 0.9), and (2). Closest N analogs (range 1 - 10). Each target-analog pair was then evaluated for its agreement with measured ER binding and agonism. Subsequently, the analogs were filtered using physchem properties (LogKow & Molecular Volume) and the resultant agreement between each target-analog pair was evaluated. The data set comprised 462 hindered phenols and 296 non-hindered phenols. The results demonstrate that: (1). The concordance in ER activity r

  16. Synthetic analogs of bacterial quorum sensors

    SciTech Connect

    Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

    2013-01-08

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  17. Synthetic analogs of bacterial quorum sensors

    SciTech Connect

    Iyer, Rashi; Ganguly, Kumkum; Silks, Louis A

    2011-12-06

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  18. Automatic digital-analog impedance plethysmograph

    NASA Astrophysics Data System (ADS)

    Goy, C. B.; Mauro, K. A.; Yanicelli, L. M.; Parodi, N. F.; Gómez López, M. A.; Herrera, M. C.

    2016-04-01

    Venous occlusion plethysmography (VOP) is a traditional method widely used to assess limb blood circulation. One common mode to record VOP is by means of evaluating limb volume changes using impedance plethysmography (IP). In this paper the design and implementation of an automatic digital-analog impedance plethysmograph (ADAIP) for VOP is presented. The system is tested using precision resistances in order to calculate its repeatability. Then its global performance is assessed by means of VOP recordings on the upper and me lower limb of a healthy volunteer. The obtained repeatability was very high (95%), and the VOP recordings where the expected ones. It can be concluded that the whole system performs well and that it is suitable for automatic VOP recording.

  19. Analog VLSI neural network integrated circuits

    NASA Technical Reports Server (NTRS)

    Kub, F. J.; Moon, K. K.; Just, E. A.

    1991-01-01

    Two analog very large scale integration (VLSI) vector matrix multiplier integrated circuit chips were designed, fabricated, and partially tested. They can perform both vector-matrix and matrix-matrix multiplication operations at high speeds. The 32 by 32 vector-matrix multiplier chip and the 128 by 64 vector-matrix multiplier chip were designed to perform 300 million and 3 billion multiplications per second, respectively. An additional circuit that has been developed is a continuous-time adaptive learning circuit. The performance achieved thus far for this circuit is an adaptivity of 28 dB at 300 KHz and 11 dB at 15 MHz. This circuit has demonstrated greater than two orders of magnitude higher frequency of operation than any previous adaptive learning circuit.

  20. Analog circuit for controlling acoustic transducer arrays

    DOEpatents

    Drumheller, Douglas S.

    1991-01-01

    A simplified ananlog circuit is presented for controlling electromechanical transducer pairs in an acoustic telemetry system. The analog circuit of this invention comprises a single electrical resistor which replaces all of the digital components in a known digital circuit. In accordance with this invention, a first transducer in a transducer pair of array is driven in series with the resistor. The voltage drop across this resistor is then amplified and used to drive the second transducer. The voltage drop across the resistor is proportional and in phase with the current to the transducer. This current is approximately 90 degrees out of phase with the driving voltage to the transducer. This phase shift replaces the digital delay required by the digital control circuit of the prior art.

  1. ANIMAL ANALOGIES IN FIRST IMPRESSIONS OF FACES

    PubMed Central

    Zebrowitz, Leslie A.; Wadlinger, Heather A.; Luevano, Victor X.; White, Benjamin M.; Xing, Cai; Zhang, Yi

    2013-01-01

    Analogies between humans and animals based on facial resemblance have a long history. We report evidence for reverse anthropomorphism and the extension of facial stereotypes to lions, foxes, and dogs. In the stereotype extension, more positive traits were attributed to animals judged more attractive than con-specifics; more childlike traits were attributed to those judged more babyfaced. In the reverse anthropomorphism, human faces with more resemblance to lions, ascertained by connectionist modeling of facial metrics, were judged more dominant, cold, and shrewd, controlling attractiveness, babyfaceness, and sex. Faces with more resemblance to Labradors were judged warmer and less shrewd. Resemblance to foxes did not predict impressions. Results for lions and dogs were consistent with trait impressions of these animals and support the species overgeneralization hypothesis that evolutionarily adaptive reactions to particular animals are overgeneralized, with people perceived to have traits associated with animals their faces resemble. Other possible explanations are discussed. PMID:25339791

  2. ANIMAL ANALOGIES IN FIRST IMPRESSIONS OF FACES.

    PubMed

    Zebrowitz, Leslie A; Wadlinger, Heather A; Luevano, Victor X; White, Benjamin M; Xing, Cai; Zhang, Yi

    2011-08-01

    Analogies between humans and animals based on facial resemblance have a long history. We report evidence for reverse anthropomorphism and the extension of facial stereotypes to lions, foxes, and dogs. In the stereotype extension, more positive traits were attributed to animals judged more attractive than con-specifics; more childlike traits were attributed to those judged more babyfaced. In the reverse anthropomorphism, human faces with more resemblance to lions, ascertained by connectionist modeling of facial metrics, were judged more dominant, cold, and shrewd, controlling attractiveness, babyfaceness, and sex. Faces with more resemblance to Labradors were judged warmer and less shrewd. Resemblance to foxes did not predict impressions. Results for lions and dogs were consistent with trait impressions of these animals and support the species overgeneralization hypothesis that evolutionarily adaptive reactions to particular animals are overgeneralized, with people perceived to have traits associated with animals their faces resemble. Other possible explanations are discussed.

  3. Scattering by interstellar graphite dust analog

    NASA Astrophysics Data System (ADS)

    Ahmed, Gazi A.; Gogoi, Ankur

    2014-10-01

    The analysis of optical scattering data of interstellar carbonaceous graphite dust analog at 543.5 nm, 594.5 nm and 632.8 nm laser wavelengths by using an original laboratory light scattering setup is presented. The setup primarily consisted of a laser source, optical units, aerosol sprayer, data acquisition system and associated instrumentation. The instrument measured scattered light signals from 10° to 170° in steps of 1°. The results of the measurements of the volume scattering function β(θ) and degree of linear polarization P(θ) of the carbonaceous graphite dust particles that were sprayed in front of the laser beam by using an aerosol sprayer were subsequently compared with theoretically generated Mie plots with estimated parameters.

  4. Cannabinoids, endocannabinoids, and related analogs in inflammation.

    PubMed

    Burstein, Sumner H; Zurier, Robert B

    2009-03-01

    This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.

  5. Four-gate transistor analog multiplier circuit

    NASA Technical Reports Server (NTRS)

    Mojarradi, Mohammad M. (Inventor); Blalock, Benjamin (Inventor); Cristoloveanu, Sorin (Inventor); Chen, Suheng (Inventor); Akarvardar, Kerem (Inventor)

    2011-01-01

    A differential output analog multiplier circuit utilizing four G.sup.4-FETs, each source connected to a current source. The four G.sup.4-FETs may be grouped into two pairs of two G.sup.4-FETs each, where one pair has its drains connected to a load, and the other par has its drains connected to another load. The differential output voltage is taken at the two loads. In one embodiment, for each G.sup.4-FET, the first and second junction gates are each connected together, where a first input voltage is applied to the front gates of each pair, and a second input voltage is applied to the first junction gates of each pair. Other embodiments are described and claimed.

  6. Disease Resistance Gene Analogs (RGAs) in Plants

    PubMed Central

    Sekhwal, Manoj Kumar; Li, Pingchuan; Lam, Irene; Wang, Xiue; Cloutier, Sylvie; You, Frank M.

    2015-01-01

    Plants have developed effective mechanisms to recognize and respond to infections caused by pathogens. Plant resistance gene analogs (RGAs), as resistance (R) gene candidates, have conserved domains and motifs that play specific roles in pathogens’ resistance. Well-known RGAs are nucleotide binding site leucine rich repeats, receptor like kinases, and receptor like proteins. Others include pentatricopeptide repeats and apoplastic peroxidases. RGAs can be detected using bioinformatics tools based on their conserved structural features. Thousands of RGAs have been identified from sequenced plant genomes. High-density genome-wide RGA genetic maps are useful for designing diagnostic markers and identifying quantitative trait loci (QTL) or markers associated with plant disease resistance. This review focuses on recent advances in structures and mechanisms of RGAs, and their identification from sequenced genomes using bioinformatics tools. Applications in enhancing fine mapping and cloning of plant disease resistance genes are also discussed. PMID:26287177

  7. Atwood and Poggendorff: an insightful analogy

    NASA Astrophysics Data System (ADS)

    Coelho, R. L.; Borges, P. F.; Karam, R.

    2016-11-01

    Atwood’s treatise, in which the Atwood machine appears, was published in 1784. About 70 years later, Poggendorff showed experimentally that the weight of an Atwood machine is reduced when it is brought to motion. In the present paper, a twofold connection between this experiment and the Atwood machine is established. Firstly, if the Poggendorff apparatus is taken as an ideal one, the equations of motion of the apparatus coincide with the equations of motion of the compound Atwood machine. Secondly, if the Poggendorff apparatus, which works as a lever, is rebalanced, the equations of this equilibrium provide us with the solution for a compound Atwood machine with the same bodies. This analogy is pedagogically useful because it illustrates a common strategy to transform a dynamic in a static situation improving students’ comprehension of Newton’s laws and equilibrium.

  8. Analogies and metaphors in clinical medicine.

    PubMed

    Masukume, Gwinyai; Zumla, Alimuddin

    2012-02-01

    Medicine is traditionally known as an 'art', and not an exact 'science'. Medical images of clinical signs and pathology were communicated through 'metaphors' in the 19th and early 20th centuries to make recognition easier in anticipation of the clinical counterpart when encountered in medical practice. They have served as teaching aids, enhancing memory retention for medical students, nurses and doctors and have withstood the test of time. Standard medical textbooks contain metaphors that have become entrenched in teaching, learning and examining in medical schools and hospitals worldwide. The continued use of metaphors has given rise to an ongoing debate, particularly in Africa, due to the usage of inappropriate or unfamiliar metaphors which are not locally or culturally relevant. Despite this, medical analogies will no doubt continue to be useful for medical education, clinical practice and 'aide memoirs' for examinations, and bring light humour, for a long time to come.

  9. Analog VLSI system for active drag reduction

    SciTech Connect

    Gupta, B.; Goodman, R.; Jiang, F.; Tai, Y.C.; Tung, S.; Ho, C.M.

    1996-10-01

    In today`s cost-conscious air transportation industry, fuel costs are a substantial economic concern. Drag reduction is an important way to reduce costs. Even a 5% reduction in drag translates into estimated savings of millions of dollars in fuel costs. Drawing inspiration from the structure of shark skin, the authors are building a system to reduce drag along a surface. Our analog VLSI system interfaces with microfabricated, constant-temperature shear stress sensors. It detects regions of high shear stress and outputs a control signal to activate a microactuator. We are in the process of verifying the actual drag reduction by controlling microactuators in wind tunnel experiments. We are encouraged that an approach similar to one that biology employs provides a very useful contribution to the problem of drag reduction. 9 refs., 21 figs.

  10. Cognitive performance in space and analogous environments.

    PubMed

    Casler, J G; Cook, J R

    1999-01-01

    Although human presence in space continues to expand, the literature contains relatively little coverage of human cognitive performance in the space operating environment. This article catalogs and compares the known investigations of human cognitive performance in space and in analogous environments. The methods, sample descriptions and treatments, and the results and limitations of the experiments or observations of 29 studies are compared with respect to 6 cognitive measures: (a) response time, (b) memory, (c) reasoning, (d) pattern recognition, (e) fine motor skills, and (f) dual-task performance. In general, the utility of the data is limited by small sample sizes, short observations periods, and homogeneity of the participant pool. Additionally, the variety of experimental methods used to date often makes generalization of results difficult. Although the combined results of these studies do not suggest a trend toward sustained cognitive performance impairment in the space operating environment, several cognitive performance measures do appear to be affected by an as yet undefined adaptation process.

  11. Analogy between fluid cavitation and fracture mechanics

    NASA Technical Reports Server (NTRS)

    Hendricks, R. C.; Mullen, R. L.; Braun, M. J.

    1983-01-01

    When the stresses imposed on a fluid are sufficiently large, rupture or cavitation can occur. Such conditions can exist in many two-phase flow applications, such as the choked flows, which can occur in seals and bearings. Nonspherical bubbles with large aspect ratios have been observed in fluids under rapid acceleration and high shear fields. These bubbles are geometrically similar to fracture surface patterns (Griffith crack model) existing in solids. Analogies between crack growth in solid and fluid cavitation are proposed and supported by analysis and observation (photographs). Healing phenomena (void condensation), well accepted in fluid mechanics, have been observed in some polymers and hypothesized in solid mechanics. By drawing on the strengths of the theories of solid mechanics and cavitation, a more complete unified theory can be developed.

  12. The Cannabinoid Acids, Analogs and Endogenous Counterparts

    PubMed Central

    Burstein, Sumner H.

    2015-01-01

    The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine (NAgly) that is closely related in structure to the cannabinoid agonist anandamide. The most studied phytocannabinoid is Δ9–THC-11-oic acid, the principal metabolite of Δ9–THC. Both types of acids have in common several biological actions such as low affinity for CB1, anti-inflammatory activity and analgesic properties. This suggests that there may be similarities in their mechanism of action, a point that is discussed in this review. Also presented are reports on analogs of the acids that provide opportunities for the development of novel therapeutic agents, such as ajulemic acid. PMID:24731541

  13. On analog implementations of discrete neural networks

    SciTech Connect

    Beiu, V.; Moore, K.R.

    1998-12-01

    The paper will show that in order to obtain minimum size neural networks (i.e., size-optimal) for implementing any Boolean function, the nonlinear activation function of the neutrons has to be the identity function. The authors shall shortly present many results dealing with the approximation capabilities of neural networks, and detail several bounds on the size of threshold gate circuits. Based on a constructive solution for Kolmogorov`s superpositions they will show that implementing Boolean functions can be done using neurons having an identity nonlinear function. It follows that size-optimal solutions can be obtained only using analog circuitry. Conclusions, and several comments on the required precision are ending the paper.

  14. Disease Resistance Gene Analogs (RGAs) in Plants.

    PubMed

    Sekhwal, Manoj Kumar; Li, Pingchuan; Lam, Irene; Wang, Xiue; Cloutier, Sylvie; You, Frank M

    2015-08-14

    Plants have developed effective mechanisms to recognize and respond to infections caused by pathogens. Plant resistance gene analogs (RGAs), as resistance (R) gene candidates, have conserved domains and motifs that play specific roles in pathogens' resistance. Well-known RGAs are nucleotide binding site leucine rich repeats, receptor like kinases, and receptor like proteins. Others include pentatricopeptide repeats and apoplastic peroxidases. RGAs can be detected using bioinformatics tools based on their conserved structural features. Thousands of RGAs have been identified from sequenced plant genomes. High-density genome-wide RGA genetic maps are useful for designing diagnostic markers and identifying quantitative trait loci (QTL) or markers associated with plant disease resistance. This review focuses on recent advances in structures and mechanisms of RGAs, and their identification from sequenced genomes using bioinformatics tools. Applications in enhancing fine mapping and cloning of plant disease resistance genes are also discussed.

  15. Phase noise performance of analog frequency dividers.

    PubMed

    Driscoll, M M

    1990-01-01

    The phase noise performance obtainable using silicon and GaAs-based TTL (transistor-transistor logic) and ECL (emitter-coupled logic) logic level digital frequency dividers is discussed. Measurement of the spectral performance of two types of analog dividers is reported: a parametric divider using varactor diodes and a regenerative-type divider incorporating a double-balanced mixer in the oscillator feedback circuit. Both dividers were configured for divide-by-two operation at VHF. Evaluation indicates the regenerative divider is capable of providing much lower phase noise than conventional digital logic level devices. The regenerative divider can be successfully operated over bandwidths in excess of an octave, and the design lends itself to small (i.e. TO-8) modular package implementation. Operating frequencies are bounded only by the range of the mixer and RF amplifier utilized and, as such, should extend from HF through microwave.

  16. Synthesis and biodistribution of radioiodinated nicotine analogs

    SciTech Connect

    Chan, S.M.; Basmadjian, G.P.; Marten, D.F.; Sadek, S.; Magarian, R.A.; Grunder, J.R.; Ice, R.D.

    1984-01-01

    The authors reported previously on the synthesis and biodistribution of radioiodinated 5-iodonicotine. In their continuous effort to search for a potential brain as well as adrenal medulla imaging agent, the authors synthesized four radioiodinated nicotine analogs. The labeled compounds were prepared by brominating nicotinic acid, and reacting the acylated product with the appropriate amines to give the respective amides which were then reduced with diborane to the amines. I-125 labeling was done by halogen exchange. Biodistribution studies performed in female Sprague-Dawley rats showed that all these compounds were taken up rapidly by the brain and the adrenal. The highest uptake of all these compounds in both organs occurred at 2 minutes after tail vein injections. The organ:blood ratios at 2 minutes and the T/sub 1/3/ (min.) of radioactivity in these organs were compared.

  17. Analog and digital codes in the brain

    NASA Astrophysics Data System (ADS)

    Mochizuki, Yasuhiro; Shinomoto, Shigeru

    2014-02-01

    It has long been debated whether information in the brain is coded at the rate of neuronal spiking or at the precise timing of single spikes. Although this issue is essential to the understanding of neural signal processing, it is not easily resolved because the two mechanisms are not mutually exclusive. We suggest revising this coding issue so that one hypothesis is uniquely selected for a given spike train. To this end, we decide whether the spike train is likely to transmit a continuously varying analog signal or switching between active and inactive states. The coding hypothesis is selected by comparing the likelihood estimates yielded by empirical Bayes and hidden Markov models on individual data. The analysis method is applicable to generic event sequences, such as earthquakes, machine noises, and human communications, and enhances the gain in decoding signals and infers underlying activities.

  18. X-Rays from Green Pea Analogs

    NASA Astrophysics Data System (ADS)

    Brorby, Matthew

    2014-09-01

    X-rays may have contributed to the heating and reionization of the IGM in the early universe. High mass X-ray binaries (HMXB) within small, low-metallicity galaxies are expected to be the main source of X-rays at this time. Since studying these high-redshift galaxies is currently impossible, we turn to local analogs that have the same properties the galaxies in the early are expected to have. A number of recent studies have shown an enhanced number of HMXBs in nearby low metallicity galaxies. We propose to observe a sample of metal-deficient luminous compact galaxies (LCG) in order to determine if the X-ray luminosity is enhanced relative to SFR, thereby providing further evidence to the importance of X-rays in the early universe.

  19. Automating analog design: Taming the shrew

    NASA Technical Reports Server (NTRS)

    Barlow, A.

    1990-01-01

    The pace of progress in the design of integrated circuits continues to amaze observers inside and outside of the industry. Three decades ago, a 50 transistor chip was a technological wonder. Fifteen year later, a 5000 transistor device would 'wow' the crowds. Today, 50,000 transistor chips will earn a 'not too bad' assessment, but it takes 500,000 to really leave an impression. In 1975 a typical ASIC device had 1000 transistors, took one year to first samples (and two years to production) and sold for about 5 cents per transistor. Today's 50,000 transistor gate array takes about 4 months from spec to silicon, works the first time, and sells for about 0.02 cents per transistor. Fifteen years ago, the single most laborious and error prone step in IC design was the physical layout. Today, most IC's never see the hand of a layout designer: and automatic place and route tool converts the engineer's computer captured schematic to a complete physical design using a gate array or a library of standard cells also created by software rather than by designers. CAD has also been a generous benefactor to the digital design process. The architect of today's digital systems creates the design using an RTL or other high level simulator. Then the designer pushes a button to invoke the logic synthesizer-optimizer tool. A fault analyzer checks the result for testability and suggests where scan based cells will improve test coverage. One obstinate holdout amidst this parade of progress is the automation of analog design and its reduction to semi-custom techniques. This paper investigates the application of CAD techniques to analog design.

  20. Molecular mechanics models for tetracycline analogs.

    PubMed

    Aleksandrov, Alexey; Simonson, Thomas

    2009-01-30

    Tetracyclines (Tcs) are an important family of antibiotics that bind to the ribosome and several proteins. To model Tc interactions with protein and RNA, we have developed a molecular mechanics force field for 12 tetracyclines, consistent with the CHARMM force field. We considered each Tc variant in its zwitterionic tautomer, with and without a bound Mg(2+). We used structures from the Cambridge Crystallographic Data Base to identify the conformations likely to be present in solution and in biomolecular complexes. A conformational search by simulated annealing was undertaken, using the MM3 force field, for tetracycline, anhydrotetracycline, doxycycline, and tigecycline. Resulting, low-energy structures were optimized with an ab initio method. We found that Tc and its analogs all adopt an extended conformation in the zwitterionic tautomer and a twisted one in the neutral tautomer, and the zwitterionic-extended state is the most stable in solution. Intermolecular force field parameters were derived from a standard supermolecule approach: we considered the ab initio energies and geometries of a water molecule interacting with each Tc analog at several different positions. The final, rms deviation between the ab initio and force field energies, averaged over all forms, was 0.35 kcal/mol. Intramolecular parameters were adopted from either the standard CHARMM force field, the ab initio structure, or the earlier, plain Tc force field. The model reproduces the ab initio geometry and flexibility of each Tc. As tests, we describe MD and free energy simulations of a solvated complex between three Tcs and the Tet repressor protein. (c) 2008 Wiley Periodicals, Inc.

  1. [Analogies between the thymus and epidermis].

    PubMed

    De Panfilis, G

    1990-11-01

    In this paper, similarities between epidermis and thymus are reviewed. Both epidermis and thymus deal with an epithelial stroma harbouring dendritic cells, which are bone-marrow derived. Both epithelia are keratinized, and a map can be constructed illustrating histo-topographic and antigenic similarities between thymic epithelial cells distributed in various thymic zones (i.e. subcapsular cortex, outer cortex, inner cortex, medulla, outer layers of Hassall's bodies, inner layers of Hassall's bodies) and keratinocytes of different epidermal layers. By contrast, a possible similarity between thymocytes and Langerhans cells is not so easy to demonstrate, although both cell types are CD1 positive. Rather, in our opinion a comparison is preferable of thymocytes to Thy-1 positive dendritic epidermal cells, due to morphological, antigenic, functional and especially lineage similarities. Similarities between thymus and epidermis are clearly important dealing with analogous molecular interactions, namely, thymic epithelial cells/thymocytes versus keratinocytes/T-lymphocytes. Indeed, our recent investigations demonstrated that a subset of keratinocytes is ICAM-1 positive, and the whole keratinocyte population is LFA-3 positive. Since the interaction thymic epithelial cells (ICAM-1 and LFA-3 positive)/thymocytes (LFA-1 and CD2 positive) has been shown to be necessary for promotion of activation and maturation of thymocytes, the interaction keratinocytes (ICAM-1 and LFA-3 positive, as we demonstrated)/T-lymphocytes (LFA-1 and CD2 positive as well) might be, by analogy, important not only for the "homing" of T-lymphocytes within the epidermis, but also for the epidermis being considered a peripheral inductive site for T-cell activation and maturation.

  2. Parallel analog neural networks for tree searching

    NASA Astrophysics Data System (ADS)

    Saylor, Janet; Stork, David G.

    1986-08-01

    We have modeled parallel analog neural networks designed such that their evolution toward final states is equivalent to finding optimal (or nearly optimal) paths through decision trees. This work extends that done on the Traveling Salesman Problem (TSP)[1] and sheds light on the conditions under which analog neural networks can and cannot find solutions to discrete optimization problems. Neural networks show considerable specificity in finding optimal solutions for tree searches; in the cases when a final state does represent a syntactically correct path, that path will be the best path 70-90% of the time—even for trees with up to two thousand nodes. However, it appears that except for trivial networks lacking the ability to ``think globally,'' there exists no general network architecture that can strictly insure the convergence a state that represents a single, continuous, unambiguous path. In fact, we find that for roughly 15% of trees with six generations, 40% of trees with eight generations, and 70% of trees with ten generations, networks evolve to ``broken paths,'' i.e., combinations of the beginning of one and the end of another path through a tree. Tree searches illustrate well neural dynamics because tree structures make the effects of competition and positive feedback apparent. We have found that 1) convergence times for networks with up to 2000 neurons are very rapid, depend on the gain of neurons and magnitude of neural connections but not on the number of generations or branching factor of a tree, 2) all neurons along a ``winning'' path turn on exponentially with the same exponent, and 3) the general computational mechanism of these networks appears to be the pruning of a tree from the outer branches inward, as chain reactions of neurons being quenched tend to propagate along possible paths.

  3. Automating analog design: Taming the shrew

    NASA Technical Reports Server (NTRS)

    Barlow, A.

    1990-01-01

    The pace of progress in the design of integrated circuits continues to amaze observers inside and outside of the industry. Three decades ago, a 50 transistor chip was a technological wonder. Fifteen year later, a 5000 transistor device would 'wow' the crowds. Today, 50,000 transistor chips will earn a 'not too bad' assessment, but it takes 500,000 to really leave an impression. In 1975 a typical ASIC device had 1000 transistors, took one year to first samples (and two years to production) and sold for about 5 cents per transistor. Today's 50,000 transistor gate array takes about 4 months from spec to silicon, works the first time, and sells for about 0.02 cents per transistor. Fifteen years ago, the single most laborious and error prone step in IC design was the physical layout. Today, most IC's never see the hand of a layout designer: and automatic place and route tool converts the engineer's computer captured schematic to a complete physical design using a gate array or a library of standard cells also created by software rather than by designers. CAD has also been a generous benefactor to the digital design process. The architect of today's digital systems creates the design using an RTL or other high level simulator. Then the designer pushes a button to invoke the logic synthesizer-optimizer tool. A fault analyzer checks the result for testability and suggests where scan based cells will improve test coverage. One obstinate holdout amidst this parade of progress is the automation of analog design and its reduction to semi-custom techniques. This paper investigates the application of CAD techniques to analog design.

  4. Optical analog-to-digital converter

    NASA Technical Reports Server (NTRS)

    Evanchuk, Vincent L. (Inventor)

    1984-01-01

    A method and apparatus for converting the intensity of an unknown optical signal (B) into an electrical signal in digital form utilizes two elongated optical attenuators (11, 13), one for the unknown optical signal from a source (10) and one for a known optical signal (A) from a variable source (12), a plurality of photodetectors (e.g., 17, 18) along each attenuator for detecting the intensity of the optical signals, and a plurality of comparators (e.g., 21) connected to the photodetectors in pairs to determine at what points being compared the attenuated known signal equals the attenuated unknown signal. The intensity of the unknown relative to the known is thus determined by the output of a particular comparator. That output is automatically encoded to a relative intensity value in digital form through a balancing feedback control (24) and encoder (23). The digital value may be converted to analog form in a D-to-A converter (27) and used to vary the source of the known signal so that the attenuated intensity of the known signal at a predetermined point (comparator 16) equals the attenuated intensity of the unknown signal at the predetermined point of comparison. If the known signal is then equal to the unknown, there is verification of the analog-to-digital conversion being complete. Otherwise the output of the comparator indicating equality at some other point along the attenuators will provide an output which is encoded and added, through an accumulator comprised of a register (25) and an adder (26), to a previous relative intensity value thereby to further vary the intensity of the known signal source. The steps are repeated until full conversion is verified.

  5. Four analogies between biological and cultural/linguistic evolution.

    PubMed

    Sereno, M I

    1991-08-21

    The intricate phenomena of biology on the one hand, and language and culture on the other, have inspired many writers to draw analogies between these two evolutionary systems. These analogies can be divided into four principal types: species/language, organism/concept, genes/culture, and cell/person. Here, it is argued that the last analogy--between cells and persons--is the most profound in several respects, and, more importantly, can be used to generate a number of empirical predictions. In the first half of the paper, the four analogies are each evaluated after briefly describing criteria for a good predictive analogy. In the second half of the paper, the cell/person analogy and predictions deriving from it are explored in detail.

  6. Synthesis and biological activity of nifuroxazide and analogs. II.

    PubMed

    Tavares, L C; Chisté, J J; Santos, M G; Penna, T C

    1999-09-01

    Nifuroxazyde and six analogs were synthesized by varying the substitute from the para-position of the benzenic ring and the heteroatom of the heterocyclic ring. The MIC of seven resultant compounds was determined by serial dilutions, testing the ATCC 25923 strain of Staphylococcus aureus. A significant increase in the anti-microbial activity of thyophenic analogs, as compared with furanic and pyrrholic analogs, was observed. In addition, unlike the cyano and hydroxyl groups, the acetyl group promoted anti-microbial activity.

  7. Assembly of a Neural Analog Computer. Phase 2

    DTIC Science & Technology

    1994-02-15

    Neural Computer . Analog VLSI Implementation of Neural Systems, IEEE Carver Mead, Mohammed Ismail, Eds., Kiluwer Academic Publishers, Boston, MA. 1989... Analog Neural Compuer With Modular Architecture for Real-Time Dynamic Computations . IEEE Transactions On Solid State Circuits V 27 82.-92 1992. 9...D FINAL REPORT PHASE II ONR CONTRACT # N00014-91-c-0204 ASSEMBLY OF A NEURAL ANALOG COMPUTER This documen: he- tbeen approved fox public reiease and

  8. Bridging analog and digital video in the surgical setting.

    PubMed

    Miron, Hagai; Blumenthal, Eytan Z

    2003-10-01

    Editing surgical videos requires a basic understanding of key technical issues, especially when transforming from analog to digital media. These issues include an understanding of compression-decompression (eg, MPEGs), generation quality loss, video formats, and compression ratios. We introduce basic terminology and concepts related to analog and digital video, emphasizing the process of converting analog video to digital files. The choice of hardware, software, and formats is discussed, including advantages and drawbacks. Last, we provide an inexpensive hardware-software solution.

  9. Hardware Evolution of Analog Speed Controllers for a DC Motor

    NASA Technical Reports Server (NTRS)

    Gwaltney, David A.; Ferguson, Michael I.

    2003-01-01

    Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a Field Programmable Transistor Array (FPTA). The performance of these evolved controllers is compared to that of a conventional proportional-integral (PI) controller.

  10. Rapid Learning in a Children's Museum via Analogical Comparison.

    PubMed

    Gentner, Dedre; Levine, Susan C; Ping, Raedy; Isaia, Ashley; Dhillon, Sonica; Bradley, Claire; Honke, Garrett

    2016-01-01

    We tested whether analogical training could help children learn a key principle of elementary engineering-namely, the use of a diagonal brace to stabilize a structure. The context for this learning was a construction activity at the Chicago Children's Museum, in which children and their families build a model skyscraper together. The results indicate that even a single brief analogical comparison can confer insight. The results also reveal conditions that support analogical learning.

  11. Hardware Evolution of Analog Speed Controllers for a DC Motor

    NASA Technical Reports Server (NTRS)

    Gwaltney, David A.; Ferguson, Michael I.

    2003-01-01

    Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a Field Programmable Transistor Array (FPTA). The performance of these evolved controllers is compared to that of a conventional proportional-integral (PI) controller.

  12. Analogy use in naturalistic settings: the influence of audience, emotion, and goals.

    PubMed

    Blanchette, I; Dunbar, K

    2001-07-01

    The ways in which analogy was used in a nonexperimental environment-politics-was investigated. We used the framework developed in analogy research to analyze the selection of analogical sources in political discourse. We took all the analogies reported in newspapers during the final week of a referendum campaign in Canada and analyzed the features of the different analogies used. We identified 234 analogies and analyzed the range over which analogies were used, semantic categories of analogies, goals of the analogizer, and emotional connotation of the analogies. Our results reveal that analogy was frequently used, that over two-thirds of the analogical sources were nonpolitical, and that many of the sources had strong emotional connotations. Furthermore, the goal of the analogizer influenced the selection of sources. We conclude that characteristics of the audience and emotionality of the source analog are important features in the selection of source analogs.

  13. CRC handbook of neurohypophyseal hormone analogs. Volume 2

    SciTech Connect

    Jost, K.; Lebl, M.; Brtnik, F.

    1987-01-01

    This book is discussed in two parts. The Part 1 discusses the: Prohormones and Hormonogens of Neuro-hypophyseal Hormones, Analogs with Inhibitory properties. Analogs with Dissociated and/or High activities. Introduction. Uterotonic Activity. Galactogogic Activity. Pressor Activity. Antidiuretic Activity. References. Part 2 discusses the Other Important Activities. CNS Activities. Corticotropin- and ..beta..-Entriuretic Action. Natriferic Action. References. Practical Use in Human and Veterinary Medicine. Introduction. Methyloxytocin. Deamino-Oxytocin. Cargutocin. Glypressin. Octapressin. Desmopressin. Analogs Clinically Tried But Not Introduced into Production and Routine Clinical Practice. References. Tables of Analogs and Index.

  14. Physical analogy between continuum thermodynamics and classical mechanics.

    PubMed

    Umantsev, Alex

    2004-01-01

    The main focus of this paper is the profound physical analogy between a continuum thermodynamical system, which evolves with relaxation under (possibly) nonisothermal conditions, and a classical mechanical system of a few interacting particles moving with dissipation in (possibly), time-dependent nonconservative fields. This analogy is applied to the problem of phase transitions in a one-dimensional thermodynamic system. The thermomechanical analogy stems from the validity of variational methods in mechanics and thermodynamics and allows for a different interpretation of the dynamical selection principle in the theory of pattern formation. This physical analogy is very helpful for understanding different nonlinear thermodynamic phenomena and for developing intuition in numerical simulations.

  15. Analog solar system model relates celestial bodies spatially

    NASA Technical Reports Server (NTRS)

    Baerg, H. R.

    1966-01-01

    Portable analog planetarium indicates the relative time and space angular locations of the sun and planets. Distance measuring scales, angular direction indicators, and typical probe trajectories are included.

  16. ISS Update: ISTAR -- International Space Station Testbed for Analog Research

    NASA Image and Video Library

    NASA Public Affairs Officer Kelly Humphries interviews Sandra Fletcher, EVA Systems Flight Controller. They discuss the International Space Station Testbed for Analog Research (ISTAR) activity that...

  17. Non-analog Monte Carlo estimators for radiation momentum deposition

    SciTech Connect

    Densmore, Jeffery D; Hykes, Joshua M

    2008-01-01

    The standard method for calculating radiation momentum deposition in Monte Carlo simulations is the analog estimator, which tallies the change in a particle's momentum at each interaction with the matter. Unfortunately, the analog estimator can suffer from large amounts of statistical error. In this paper, we present three new non-analog techniques for estimating momentum deposition. Specifically, we use absorption, collision, and track-length estimators to evaluate a simple integral expression for momentum deposition that does not contain terms that can cause large amounts of statistical error in the analog scheme. We compare our new non-analog estimators to the analog estimator with a set of test problems that encompass a wide range of material properties and both isotropic and anisotropic scattering. In nearly all cases, the new non-analog estimators outperform the analog estimator. The track-length estimator consistently yields the highest performance gains, improving upon the analog-estimator figure of merit by factors of up to two orders of magnitude.

  18. Is the link from working memory to analogy causal? No analogy improvements following working memory training gains.

    PubMed

    Richey, J Elizabeth; Phillips, Jeffrey S; Schunn, Christian D; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data, but less work has tested this relationship through experimental manipulation. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants' performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks. Participants' improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning.

  19. Is the Link from Working Memory to Analogy Causal? No Analogy Improvements following Working Memory Training Gains

    PubMed Central

    Richey, J. Elizabeth; Phillips, Jeffrey S.; Schunn, Christian D.; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data [1], but less work has tested this relationship through experimental manipulation [2]. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants’ performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks [3], [4]. Participants’ improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning. PMID:25188356

  20. Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids.

    PubMed

    Zatelli, Maria Chiara; Minoia, Mariella; Martini, Chiara; Tagliati, Federico; Ambrosio, Maria Rosaria; Schiavon, Marco; Buratto, Mattia; Calabrese, Fiorella; Gentilin, Erica; Cavallesco, Giorgio; Berdondini, Lisa; Rea, Federico; degli Uberti, Ettore C

    2010-09-01

    Bronchial carcinoids (BCs) are rare tumors originating from endocrine cells dispersed in the respiratory epithelium. It has been previously demonstrated that everolimus, or RAD001, an mTOR inhibitor, has potent antiproliferative effects in human endocrine tumors. Our aim was to evaluate the possible antiproliferative effects of everolimus in human BCs in primary culture. We collected 24 BCs that were dispersed in primary cultures, treated without or with 1 nM-1 muM everolimus, 10 nM SOM230 (pasireotide, a somatostatin receptor multiligand), and/or 50 nM IGF1. Cell viability was evaluated after 48 h, and chromogranin A (CgA) as well as vascular endothelial growth factor (VEGF) secretion was assessed after 8 h incubation. Somatostatin receptors, mTOR, and AKT expression were investigated by quantitative PCR. We found that in 15 cultures (67.5%), everolimus significantly reduced cell viability (by approximately 30%; P<0.05 versus control), inhibited p70S6K activity (-30%), and blocked IGF1 proliferative effects. Everolimus also significantly reduced CgA (by approximately 20%) and VEGF (by approximately 15%) secretion. Cotreatment with SOM230 did not exert additive effects on cell viability and secretory activity. AKT expression was similar in responder and nonresponder tissues, while mTOR expression was significantly higher in the responder group, which was characterized by higher CgA plasma levels and bigger tumors with higher mitotic index and angiogenesis. Our data demonstrate that everolimus reduces VEGF secretion and cell viability in BCs with a mechanism likely involving IGF1 signaling, suggesting that it might represent a possible medical treatment for BCs.