Variation in temperature tolerance among families of Atlantic salmon (Salmo salar) is associated with hypoxia tolerance, ventricle size and myoglobin level.

PubMed

Anttila, Katja; Dhillon, Rashpal S; Boulding, Elizabeth G; Farrell, Anthony P; Glebe, Brian D; Elliott, Jake A K; Wolters, William R; Schulte, Patricia M

2013-04-01

In fishes, performance failure at high temperature is thought to be due to a limitation on oxygen delivery (the theory of oxygen and capacity limited thermal tolerance, OCLTT), which suggests that thermal tolerance and hypoxia tolerance might be functionally associated. Here we examined variation in temperature and hypoxia tolerance among 41 families of Atlantic salmon (Salmo salar), which allowed us to evaluate the association between these two traits. Both temperature and hypoxia tolerance varied significantly among families and there was a significant positive correlation between critical maximum temperature (CTmax) and hypoxia tolerance, supporting the OCLTT concept. At the organ and cellular levels, we also discovered support for the OCLTT concept as relative ventricle mass (RVM) and cardiac myoglobin (Mb) levels both correlated positively with CTmax (R(2)=0.21, P<0.001 and R(2)=0.17, P=0.003, respectively). A large RVM has previously been shown to be associated with high cardiac output, which might facilitate tissue oxygen supply during elevated oxygen demand at high temperatures, while Mb facilitates the oxygen transfer from the blood to tissues, especially during hypoxia. The data presented here demonstrate for the first time that RVM and Mb are correlated with increased upper temperature tolerance in fish. High phenotypic variation between families and greater similarity among full- and half-siblings suggests that there is substantial standing genetic variation in thermal and hypoxia tolerance, which could respond to selection either in aquaculture or in response to anthropogenic stressors such as global climate change.

UNITED STATES DEPARTMENT OF TRANSPORTATION GLOBAL POSITIONING SYSTEM (GPS) ADJACENT BAND COMPATIBILITY ASSESSMENT

DOT National Transportation Integrated Search

2018-04-01

The goal of the U.S. Department of Transportation (DOT) Global Positioning System (GPS) Adjacent Band Compatibility Assessment is to evaluate the maximum transmitted power levels of adjacent band radiofrequency (RF) systems that can be tolerated by G...

Different cultivation methods to acclimatise ammonia-tolerant methanogenic consortia.

PubMed

Tian, Hailin; Fotidis, Ioannis A; Mancini, Enrico; Angelidaki, Irini

2017-05-01

Bioaugmentation with ammonia tolerant-methanogenic consortia was proposed as a solution to overcome ammonia inhibition during anaerobic digestion process recently. However, appropriate technology to generate ammonia tolerant methanogenic consortia is still lacking. In this study, three basic reactors (i.e. batch, fed-batch and continuous stirred-tank reactors (CSTR)) operated at mesophilic (37°C) and thermophilic (55°C) conditions were assessed, based on methane production efficiency, incubation time, TAN/FAN (total ammonium nitrogen/free ammonia nitrogen) levels and maximum methanogenic activity. Overall, fed-batch cultivation was clearly the most efficient method compared to batch and CSTR. Specifically, by saving incubation time up to 150%, fed-batch reactors were acclimatised to nearly 2-fold higher FAN levels with a 37%-153% methanogenic activity improvement, compared to batch method. Meanwhile, CSTR reactors were inhibited at lower ammonia levels. Finally, specific methanogenic activity test showed that hydrogenotrophic methanogens were more active than aceticlastic methanogens in all FAN levels above 540mgNH 3 -NL -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

A phase I study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed small cell lung cancer: Japan multinational trial organization LC0303.

PubMed

Kawahara, Masaaki; Kubo, Akihito; Komuta, Kiyoshi; Fujita, Yuka; Sasaki, Yoshiaki; Fukushima, Masanori; Daimon, Takashi; Furuse, Kiyoyuki; Mishima, Michiaki; Mio, Tadashi

2012-12-01

To determine the maximum tolerated dose of amrubicin (AMR) with a fixed dose of irinotecan (CPT-11). Patients having pathologically proven small cell lung cancer (SCLC) relapsed after one or two chemotherapies, and Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible for the study. CPT-11 was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80 mg/m2, level 2: 90 mg/m2, and level 3: 100 mg/m2. Dose elevation was determined using the modified continuous reassessment method. Tolerability was assessed after the first cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Eighteen patients (mean age: 66.3 years) were enrolled. A total of 40 courses were conducted. Grade 3/4 toxicities of the first cycle were leukocytopenia: 11 (61%, grade 3/4: 8/3); neutropenia: 15 (83%, grade 3/4: 6/9); and thrombocytopenia: three (17%, grade 3/4: 2/1). Other grade 3 toxicities observed were febrile neutropenia, one; infection, three; diarrhea, one; and dyspnea, one. Dose-limiting toxicity was observed in two of six patients at level 2 (neutropenia and febrile neutropenia) and in one of six at level 3 (thrombocytopenia and infection). The maximum tolerated dose was level 3, and so, the recommended dose for phase II trials was judged to be 90 mg/m2. Objective response was obtained in four of eight patients who were able to evaluate responses. Median survival time was 13 months, with 68% at 1-year survival rate. This combination was well tolerated and showed encouraging activities in SCLC. Randomized phase II trials are being planned in chemonaive SCLC.

(90)Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study.

PubMed

Chevallier, Patrice; Eugene, Thomas; Robillard, Nelly; Isnard, Françoise; Nicolini, Franck; Escoffre-Barbe, Martine; Huguet, Françoise; Hunault, Mathilde; Marcais, Antoine; Gaschet, Joelle; Cherel, Michel; Guillaume, Thierry; Delaunay, Jacques; Peterlin, Pierre; Eveillard, Marion; Thomas, Xavier; Ifrah, Norbert; Lapusan, Simona; Bodet-Milin, Caroline; Barbet, Jacques; Faivre-Chauvet, Alain; Ferrer, Ludovic; Bene, Marie C; Le Houerou, Claire; Goldenberg, David M; Wegener, William A; Kraeber-Bodéré, Françoise

2015-03-01

Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study. Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of (90)Y-DOTA-epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m(2) (92·5 MBq/m(2); level 1), 5·0 mCi/m(2) (185 MBq/m(2); level 2), 7·5 mCi/m(2) (277·5 MBq/m(2); level 3), and 10·0 mCi/m(2) (370 MBq/m(2); level 4). The primary objective was to identify the maximum tolerated dose of (90)Y-DOTA-epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457. Between Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27-77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3-4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4). (90)Y-DOTA-epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m(2) 1 week apart per cycle for phase 2 studies. Immunomedics and Direction de la Recherche Clinique of Nantes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial.

PubMed

Alistar, Angela; Morris, Bonny B; Desnoyer, Rodwige; Klepin, Heidi D; Hosseinzadeh, Keyanoosh; Clark, Clancy; Cameron, Amy; Leyendecker, John; D'Agostino, Ralph; Topaloglu, Umit; Boteju, Lakmal W; Boteju, Asela R; Shorr, Rob; Zachar, Zuzana; Bingham, Paul M; Ahmed, Tamjeed; Crane, Sandrine; Shah, Riddhishkumar; Migliano, John J; Pardee, Timothy S; Miller, Lance; Hawkins, Gregory; Jin, Guangxu; Zhang, Wei; Pasche, Boris

2017-06-01

Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m 2 , leucovorin at 400 mg/m 2 , irinotecan at 140 mg/m 2 , and fluorouracil 400 mg/m 2 bolus followed by 2400 mg/m 2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m 2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m 2 . The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m 2 , and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. A maximum tolerated dose of CPI-613 was established at 500 mg/m 2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. Comprehensive Cancer Center of Wake Forest Baptist Medical Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pesticide tolerant and phosphorus solubilizing Pseudomonas sp. strain SGRAJ09 isolated from pesticides treated Achillea clavennae rhizosphere soil.

PubMed

Rajasankar, R; Manju Gayathry, G; Sathiavelu, A; Ramalingam, C; Saravanan, V S

2013-05-01

In this study, an attempt was made to identify an effective phosphate solubilizing bacteria from pesticide polluted field soil. Based on the formation of solubilization halo on Pikovskaya's agar, six isolates were selected and screened for pesticide tolerance and phosphate (P) solubilization ability through liquid assay. The results showed that only one strain (SGRAJ09) obtained from Achillea clavennae was found to tolerate maximum level of the pesticides tested and it was phylogenetically identified as Pseudomonas sp. It possessed a wide range of pesticide tolerance, ranging from 117 μg mL(-1) for alphamethrin to 2,600 μg mL(-1) for endosulfan. The available P concentrations increased with the maximum and double the maximum dose of monocrotophos and imidacloprid, respectively. On subjected to FT-IR and HPLC analysis, the presence of organic acids functional group in the culture broth and the production of gluconic acid as dominant acid aiding the P solubilization were identified. On comparison with control broth, monocrotophos and imidacloprid added culture broth showed quantitatively high organic acids production. In addition to gluconic acid production, citric and acetic acids were also observed in the pesticide amended broth. Furthermore, the Pseudomonas sp. strain SGRAJ09 possessed all the plant growth promoting traits tested. In presence of monocrotophos and imidacloprid, its plant growth promoting activities were lower than that of the pesticides unamended treatment.

77 FR 48899 - Flutriafol; Pesticide Tolerances for Emergency Exemptions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... cotton, undelinted seed; cotton, meal; cotton, refined oil; and cotton gin byproducts. This action is in..., and Rodenticide Act (FIFRA) authorizing use of the pesticide on cotton. This regulation establishes a maximum permissible level for residues of flutriafol in or on cotton commodities. The time-limited...

Screening of Trichoderma isolates for their potential of biosorption of nickel and cadmium.

PubMed

Nongmaithem, Nabakishor; Roy, Ayon; Bhattacharya, Prateek Madhab

2016-01-01

Fourteen Trichoderma isolates were evaluated for their tolerance to two heavy metals, nickel and cadmium. Three isolates, MT-4, UBT-18, and IBT-I, showed high levels of nickel tolerance, whereas MT-4, UBT-18, and IBT-II showed better tolerance of cadmium than the other isolates. Under nickel stress, biomass production increased up to a Ni concentration of 60ppm in all strains but then decreased as the concentrations of nickel were further increased. Among the nickel-tolerant isolates, UBT-18 produced significantly higher biomass upon exposure to nickel (up to 150ppm); however, the minimum concentration of nickel required to inhibit 50% of growth (MIC50) was highest in IBT-I. Among the cadmium-tolerant isolates, IBT-II showed both maximum biomass production and a maximum MIC50 value in cadmium stress. As the biomass of the Trichoderma isolates increased, a higher percentage of nickel removal was observed up to a concentration of 40ppm, followed by an increase in residual nickel and a decrease in biomass production at higher nickel concentrations in the medium. The increase in cadmium concentrations resulted in a decrease in biomass production and positively correlated with an increase in residual cadmium in the culture broth. Nickel and cadmium stress also influenced the sensitivity of the Trichoderma isolates to soil fungistasis. Isolates IBT-I and UBT-18 were most tolerant to fungistasis under nickel and cadmium stress, respectively. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

[ECS guidelines 2016 - dyslipidaemias].

PubMed

Sinning, D; Landmesser, U

2016-12-01

Dyslipidaemia is a major cause of atherosclerotic cardiovascular disease and its progression towards clinical complications, such as acute coronary syndromes and stroke. In August 2016 the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) issued new joint guidelines for the management of dyslipidaemias. In these new guidelines, the concept of treating patients to a risk-based low-density lipoprotein (LDL) cholesterol target is reinforced. The task force considers LDL cholesterol as the primary target for dyslipidaemia treatment, whereas high-density lipoprotein (HDL) cholesterol is not recommended as a treatment target (based on the failure of HDL cholesterol elevation treatment strategies to reduce cardiovascular risk in recent studies). In patients with a very high risk for cardiovascular events it is recommended to treat to an LDL cholesterol target of less than 70 mg/dl. Moreover, the new guidelines now additionally recommend a > 50% reduction of LDL cholesterol in patients with very high cardiovascular risk patients and baseline levels between 70 and 135 mg/dl as well as in patients with high cardiovascular risk and baseline LDL cholesterol levels between 100 and 200 mg/dl. Statins are recommended as first-line medicinal treatment and the LDL cholesterol goals given imply the more frequent use of maximum tolerated statin therapy, in particular for patients with very high cardiovascular risk. Treatment with ezetimibe in patients with substantially elevated LDL cholesterol levels despite maximum tolerated statin therapy has now received a stronger recommendation (currently IIa recommendation). The guidelines also now include the potential use of the novel proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and a recent ESC/EAS consensus document provides more detailed information on which patients can be considered for treatment with PCSK9 inhibitors, i. e. in particular patients with familial hypercholesterolemia and patients at very high cardiovascular risk who have markedly elevated LDL cholesterol levels despite maximum tolerated statin and ezetimibe therapy.

Deciphering adverse effects of heavy metals on diverse wheat germplasm on irrigation with urban wastewater of mixed municipal-industrial origin.

PubMed

Ali, Zeshan; Mujeeb-Kazi, Abdul; Quraishi, Umar Masood; Malik, Riffat Naseem

2018-04-25

The current study provides one of the first attempts to identify tolerant, moderately sensitive, and highly sensitive wheat genotypes on the basis of heavy metal accumulation, biochemical attributes, and human health risk assessments on urban wastewater (UW) irrigation. Mean heavy metals (Fe, Co, Ni, Cu, Zn, Pb, Cd, Cr, Mn) and macro-nutrients (Na, K, Ca, Mg) levels increased in the roots, stem, and grains of studied genotypes. Except K (stem > root > grain), all metals were accumulated in highest concentrations in roots followed by stem and grains. Principal component analyses (PCA) identified three groups of UW-irrigated genotypes which were confirmed by hierarchical agglomerative cluster analyses (HACA). Wheat genotypes with the lowest metal accumulation were regarded as tolerant, whereas those with maximum accumulation were considered highly sensitive. Tolerant genotypes showed the lowest hazard quotient for heavy metals, i.e., Co, Mn, Cd, Cu, Fe, Pb, and Cr, and hazard index (HI) values (adults, 2.04; children, 2.27) than moderately and highly sensitive genotypes. Higher health risks (HI) associated with moderate (adults 2.26; children 2.53) and highly sensitive (adults 2.52; children 2.82) genotypes revealed maximum uptake of heavy metals. The heatmap showed higher mean biochemical levels of chlorophyll, carotenoids, membrane stability index (MSI%), sugars, proteins, proline, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in tolerant genotypes than remaining genotypes. With the lowest metal accumulation and advanced biochemical mechanisms to cope with the adverse effects of heavy metals in their plant bodies, tolerant genotypes present a better option for cultivation in areas receiving UW or similar type of wastewater.

[Indicators of dynamic work tolerability in healthy subjects].

PubMed

Capodaglio, E M; Capodaglio, P

1997-01-01

This paper reports a study on the dynamics of tolerability in performing dynamic cycling in healthy subjects. Data on individually tolerable levels (power x duration) was obtained from 9 subjects by means of three submaximal tests on an ergometric bicycle lasting < or = 40 minutes, with constant load (50%, 65% and 80% of maximum VO2 reached during a previous test of increasing difficulty within the limits of the symptoms). During performance of the test we monitored heart rate and subjective perception of fatigue (Borg's 10-point scale). We then defined the individual functions of "isoperception", which expressed the individual trend of the product "power x duration" at identical subjective perception score. On the basis of the metabolic parameters monitored, the individual isoperceptive functions at a "moderate" level of fatigue (3 on the Borg scale) were defined as "tolerability) threshold" for prolonged dynamic cycling. The product "power x duration" defined by the isoperceptive curves at a "moderate" level of fatigue does in fact reflect the individual aerobic capacity that can be sustained for prolonged dynamic activity (under 60 minutes). In order to validate the hypothesis of tolerability of the functions identified, three further short tests were performed (duration < or = 8.5 minutes) on an ergometric bicycle, with measurement of ventilatory and metabolic parameters.

Compatibility Flight Profile and Internal Environment Characterization for the RASCAL Pod. Project: Senior RASCAL

DTIC Science & Technology

2008-12-01

pod at increasing angles of attack. An overall vertical acceleration maximum of 7.5 g RMS occurred while in a transonic wind-up turn at 15,000 ft and...landings, level accelerations, and specific maneuver blocks of varying sideslip, load factor, and angle of attack (AOA). The flight conditions...0g 10s maximum Angle of Attack (deg) ±1 ±1 16 Table A1: Data Bands and Tolerances for the Vibroacoustic Tests Table A2 summarizes the conditions

Influence of G-forces and hypodynamia on the portal system of the liver

NASA Technical Reports Server (NTRS)

Drozdova, A. V.

1975-01-01

Longitudinally and transversely applied g-forces as intolerable levels cause damage to the interlobular veins of the liver, with maximum damage caused by dorso-ventral g-force application. The portal vein system is more resilient with respect to g-forces at the limit of tolerance.

Evolution of the climatic tolerance and postglacial range changes of the most primitive orchids (Apostasioideae) within Sundaland, Wallacea and Sahul.

PubMed

Kolanowska, Marta; Mystkowska, Katarzyna; Kras, Marta; Dudek, Magdalena; Konowalik, Kamil

2016-01-01

The location of possible glacial refugia of six Apostasioideae representatives is estimated based on ecological niche modeling analysis. The distribution of their suitable niches during the last glacial maximum (LGM) is compared with their current potential and documented geographical ranges. The climatic factors limiting the studied species occurrences are evaluated and the niche overlap between the studied orchids is assessed and discussed. The predicted niche occupancy profiles and reconstruction of ancestral climatic tolerances suggest high level of phylogenetic niche conservatism within Apostasioideae.

Impact of glyphosate-tolerant soybean and glufosinate-tolerant corn production on herbicide losses in surface runoff.

PubMed

Shipitalo, Martin J; Malone, Robert W; Owens, Lloyd B

2008-01-01

Residual herbicides used in the production of soybean [Glycine max (L.) Merr] and corn (Zea mays L.) are often detected in surface runoff at concentrations exceeding their maximum contaminant levels (MCL) or health advisory levels (HAL). With the advent of transgenic, glyphosate-tolerant soybean and glufosinate-tolerant corn this concern might be reduced by replacing some of the residual herbicides with short half-life, strongly sorbed, contact herbicides. We applied both herbicide types to two chiseled and two no-till watersheds in a 2-yr corn-soybean rotation and at half rates to three disked watersheds in a 3-yr corn/soybean/wheat (Triticum aestivum L.)-red clover (Trifolium pratense L.) rotation and monitored herbicide losses in runoff water for four crop years. In soybean years, average glyphosate loss (0.07%) was approximately 1/7 that of metribuzin (0.48%) and about one-half that of alachlor (0.12%), residual herbicides it can replace. Maximum, annual, flow-weighted concentration of glyphosate (9.2 microg L(-1)) was well below its 700 microg L(-1) MCL and metribuzin (9.5 microg L(-1)) was well below its 200 microg L(-1) HAL, whereas alachlor (44.5 microg L(-1)) was well above its 2 microg L(-1) MCL. In corn years, average glufosinate loss (0.10%) was similar to losses of alachlor (0.07%) and linuron (0.15%), but about one-fourth that of atrazine (0.37%). Maximum, annual, flow-weighted concentration of glufosinate (no MCL) was 3.5 microg L(-1), whereas atrazine (31.5 microg L(-1)) and alachlor (9.8 microg L(-1)) substantially exceeded their MCLs of 3 and 2 microg L(-1), respectively. Regardless of tillage system, flow-weighted atrazine and alachlor concentrations exceeded their MCLs in at least one crop year. Replacing these herbicides with glyphosate and glufosinate can reduce the occurrence of dissolved herbicide concentrations in runoff exceeding drinking water standards.

A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors.

PubMed

Wang-Gillam, Andrea; Arnold, Susanne M; Bukowski, Ronald M; Rothenberg, Mace L; Cooper, Wendy; Wang, Kenneth K; Gauthier, Eric; Lockhart, A Craig

2012-02-01

This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2). Pharmacokinetic studies were performed in patients at all dose levels. Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m(2) was 2,768 ng•h/mL. A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable dose of TTI-237.

Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madani, Indira; Duthoy, Wim; Derie, Cristina R.N.

2007-05-01

Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was appliedmore » for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.« less

Prediction of pain in orthodontic patients based on preoperative pain assessment

PubMed Central

Zheng, Baoyu; Ren, Manman; Lin, Feiou; Yao, Linjie

2016-01-01

Aim To investigate whether pretreatment assessment of experimental pain can predict the level of pain after archwire placement. Methods One hundred and twenty-one general university students seeking orthodontic treatment were enrolled in this study. A cold pressor test was performed to estimate the pain tolerance of subjects before treatment. Self-reported pain intensity was calculated using a 10 cm visual analog scale during the 7 days after treatment. The relationship between pain tolerance and orthodontic pain was analyzed using Spearman’s correlation analysis. Results The maximum mean level of pain intensity occurred at 24 hours after bonding (53.31±16.13) and fell to normal levels at day 7. Spearman’s correlation analysis found a moderate positive association between preoperative pain tolerance and self-reported pain after archwire placement (P<0.01). There was no significant difference in pain intensity between male and female patients at any time point (P>0.05). Conclusion A simple and noninvasive preoperative sensory test (the cold pressor test) was useful in predicting the risk of developing unbearable pain in patients after archwire placement. Self-reported pain after archwire placement decreased as individual pain tolerance increased. PMID:27042019

Prospective, open, multicentre Phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and cisplatin for esophageal carcinoma.

PubMed

Ma, Hong-Bing; Di, Zheng-Li; Wen, Jiao; Ke, Yue; Sun, Xiaodong; Ren, Juan

2015-02-01

Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Overexpression of spinach non-symbiotic hemoglobin in Arabidopsis resulted in decreased NO content and lowered nitrate and other abiotic stresses tolerance

PubMed Central

Bai, Xuegui; Long, Juan; He, Xiaozhao; Yan, Jinping; Chen, Xuanqin; Tan, Yong; Li, Kunzhi; Chen, Limei; Xu, Huini

2016-01-01

A class 1 non-symbiotic hemoglobin family gene, SoHb, was isolated from spinach. qRT-PCR showed that SoHb was induced by excess nitrate, polyethylene glycol, NaCl, H2O2, and salicylic acid. Besides, SoHb was strongly induced by application of nitric oxide (NO) donor, while was suppressed by NO scavenger, nitrate reductase inhibitor, and nitric oxide synthase inhibitor. Overexpression of SoHb in Arabidopsis resulted in decreased NO level and sensitivity to nitrate stress, as shown by reduced root length, fresh weight, the maximum photosystem II quantum ratio of variable to maximum fluorescence (Fv/Fm), and higher malondialdehyde contents. The activities and gene transcription of superoxide dioxidase, and catalase decreased under nitrate stress. Expression levels of RD22, RD29A, DREB2A, and P5CS1 decreased after nitrate treatment in SoHb-overexpressing plants, while increased in the WT plants. Moreover, SoHb-overexpressing plants showed decreased tolerance to NaCl and osmotic stress. In addition, the SoHb-overexpression lines showed earlier flower by regulating the expression of SOC, GI and FLC genes. Our results indicated that the decreasing NO content in Arabidopsis by overexpressing SoHb might be responsible for lowered tolerance to nitrate and other abiotic stresses. PMID:27211528

Proline accumulation and its implication in cold tolerance of regenerable maize callus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duncan, D.R.; Widholm, J.M.

1987-03-01

Embryogenic callus of maize (Zea mays L.) inbreds B37wx, H99, H99/sup 3/H95, Mo17, and Pa91 accumulated proline to levels 2.1 to 2.5 times that of control callus when subjected to mannitol-induced water stress, cool temperatures (19/sup 0/C) and abscisic acid (ABA). A combination of 0.53 molar mannitol plus 0.1 millimolar ABA induced a proline accumulation to about 4.5 times that of control callus, equivalent to approximately 0.18 millimoles proline per gram fresh weight of callus. Proline accumulation was directly related to the level of mannitol in the medium. Levels of ABA greater than 1.0 micromolar were required in the mediummore » to induce proline accumulation comparable to that induced by mannitol. Mannitol and ABA levels that induced maximum accumulation of proline also inhibited callus growth and increased tolerance to cold. Proline (12 millimolar) added to culture media also increased the tolerance of callus to 4/sup 0/C. The increased cold tolerance induced by the combination of mannitol and ABA has permitted the storage of the maize inbreds A632, A634Ht, B37wx, C103DTrf, Fr27rhm, H99, Pa91, Va35, and W117Ht at 4/sup 0/C for 90 days which is more than double the typical survival time of callus. These studies show that proline accumulation increase the cold tolerance of regenerable maize callus.« less

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2016-01-01

We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies. © The Author(s) 2015.

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

Survey of total mercury and methylmercury levels in edible fish from the Adriatic Sea.

PubMed

Storelli, M M; Giacominelli-Stuffler, R; Storelli, A; D'Addabbo, R; Palermo, C; Marcotrigiano, G O

2003-12-01

Total mercury and methylmercury concentrations were measured in the muscle tissue of different fish species from the Adriatic Sea to ascertain whether the concentrations exceeded the maximum level fixed by the European Commission. Large species-dependent variability was observed. The highest total mercury mean concentrations were in benthic (0.20-0.76 microg g(-1) wet wt) and demersal fish (0.22-0.73 microg g(-1) wet wt), while pelagic species showed the lowest levels (0.09-0.23 microg g(-1) wet wt). In 15% of frost fish, in 42% of skate and in 30% of angler fish samples total mercury concentrations exceeded the maximum level fixed by the European Commission (Hg = 1 microg g(-1) wet wt); for the species for which the maximum level was set to 0.5 microg g(-1) wet wt, concentrations exceeding the prescribed legal limit were observed in 6.4% of bokkem, in 6.6% of pandora, in 20% of megrin, in 12.5% of four-spotted megrim, in 16% of striped mullet, in 5.0% of forkbeard and in 5.3% of picarel samples. In all the different species, mercury was present almost completely in the methylated form, with mean percentages between 70 and 100%. Weekly intake was estimated and compared with the provisional tolerable weekly intake recommended by the FAO/WHO Expert Committee on Food Additives. A high exposure was associated with the consumption of only skates, frost fish and angler fish, thought the consumption of the other species, such as, megrim, four spotted megrim, red fish striped mullet and forkbeard, resulted in a weekly intake slightly below the established provisional tolerable weekly intake.

Evolution of the climatic tolerance and postglacial range changes of the most primitive orchids (Apostasioideae) within Sundaland, Wallacea and Sahul

PubMed Central

Mystkowska, Katarzyna; Kras, Marta; Dudek, Magdalena

2016-01-01

The location of possible glacial refugia of six Apostasioideae representatives is estimated based on ecological niche modeling analysis. The distribution of their suitable niches during the last glacial maximum (LGM) is compared with their current potential and documented geographical ranges. The climatic factors limiting the studied species occurrences are evaluated and the niche overlap between the studied orchids is assessed and discussed. The predicted niche occupancy profiles and reconstruction of ancestral climatic tolerances suggest high level of phylogenetic niche conservatism within Apostasioideae. PMID:27635348

The relation between tilt table and acceleration-tolerance and their dependence on stature and physical fitness

NASA Technical Reports Server (NTRS)

Klein, K. E.; Backhausen, F.; Bruner, H.; Eichhorn, J.; Jovy, D.; Schotte, J.; Vogt, L.; Wegman, H. M.

1980-01-01

A group of 12 highly trained athletes and a group of 12untrained students were subjected to passive changes of position on a tilt table and positive accelerations in a centrifuge. During a 20 min tilt, including two additional respiratory maneuvers, the number of faints and average cardiovascular responses did not differ significantly between the groups. During linear increase of acceleration, the average blackout level was almost identical in both groups. Statistically significant coefficients of product-moment correlation for various relations were obtained. The coefficient of multiple determination computed for the dependence of acceleration tolerance on heart-eye distance and systolic blood pressure at rest allows the explanation of almost 50% of the variation of acceleration tolerance. The maximum oxygen uptake showed the expected significant correlation to the heart rate at rest, but not the acceleration tolerance, or to the cardiovascular responses to tilting.

Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less

Phase I study of topical epigallocatechin-3-gallate (EGCG) in patients with breast cancer receiving adjuvant radiotherapy.

PubMed

Zhao, Hanxi; Zhu, Wanqi; Jia, Li; Sun, Xiaorong; Chen, Guanxuan; Zhao, Xianguang; Li, Xiaolin; Meng, Xiangjiao; Kong, Lingling; Xing, Ligang; Yu, Jinming

2016-01-01

The purpose of this study was to investigate the safety, tolerability and preliminary effectiveness of topical epigallocatechin-3-gallate (EGCG) for radiation dermatitis in patients with breast cancer receiving adjuvant radiotherapy. Patients with breast cancer who received radiotherapy to the chest wall after mastectomy were enrolled. EGCG solution was sprayed to the radiation field from the initiation of Grade 1 radiation dermatitis until 2 weeks after completion of radiotherapy. EGCG concentration escalated from 40 to 660 μmol l(-1) in 7 levels with 3-6 patients in each level. EGCG toxicity was graded using the NCI (National Cancer Institute Common Terminology Criteria for Adverse Events) v. 3.0. Any adverse event >Grade 1 attributed to EGCG was considered dose-limiting toxicity. The maximum tolerated dose was defined as the dose level that induced dose-limiting toxicity in more than one-third of patients at a given cohort. Radiation dermatitis was recorded weekly by the Radiation Therapy Oncology Group scoring and patient-reported symptoms. From March 2012 to August 2013, 24 patients were enrolled. Acute skin redness was observed in 1 patient and considered to be associated with the EGCG treatment at 140 μmol l(-1) level. Three more patients were enrolled at this level and did not experience toxicity to EGCG. The dose escalation stopped at 660 μmol l(-1). No other reported acute toxicity was associated with EGCG. Grade 2 radiation dermatitis was observed in eight patients during or after radiotherapy, but all decreased to Grade 1 after EGCG treatments. Patient-reported symptom scores were significantly decreased at 2 weeks after the end of radiotherapy in pain, burning, itching and tenderness, p < 0.05. The topical administration of EGCG was well tolerated and the maximum tolerated dose was not found. EGCG may be effective in treating radiation dermatitis with preliminary investigation. EGCG solution seemed to be feasible for treating radiation dermatitis in patients with breast cancer after mastectomy. It should be tested as a way to reduce radiation-induced normal tissue toxicity and complications in future years.

Establishing the thermal threshold of the tropical mussel Perna viridis in the face of global warming.

PubMed

Goh, B P L; Lai, C H

2014-08-30

With increasing recognition that maximum oxygen demand is the unifying limit in tolerance, the first line of thermal sensitivity is, as a corollary, due to capacity limitations at a high level of organisational complexity before individual, molecular or membrane functions become disturbed. In this study the tropical mussel Perna viridis were subjected to temperature change of 0.4 °C per hour from ambient to 8-36 °C. By comparing thermal mortality against biochemical indices (hsp70, gluthathione), physiological indices (glycogen, FRAP, NRRT) and behavioural indices (clearance rate), a hierarchy of thermal tolerance was therein elucidated, ranging from systemic to cellular to molecular levels. Generally, while biochemical indices indicated a stress signal much earlier than the more integrated behavioural indices, failure of the latter (indicating a tolerance limit and transition to pejus state) occurred much earlier than the other indices tending towards thermal extremities at both ends of the thermal spectrum. Copyright © 2013 Elsevier Ltd. All rights reserved.

Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1more » (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at lethal dose substantially suppresses hepatic Nrf2 pathway.« less

Best of both worlds: simultaneous high-light and shade-tolerance adaptations within individual leaves of the living stone Lithops aucampiae.

PubMed

Field, Katie J; George, Rachel; Fearn, Brian; Quick, W Paul; Davey, Matthew P

2013-01-01

"Living stones" (Lithops spp.) display some of the most extreme morphological and physiological adaptations in the plant kingdom to tolerate the xeric environments in which they grow. The physiological mechanisms that optimise the photosynthetic processes of Lithops spp. while minimising transpirational water loss in both above- and below-ground tissues remain unclear. Our experiments have shown unique simultaneous high-light and shade-tolerant adaptations within individual leaves of Lithops aucampiae. Leaf windows on the upper surfaces of the plant allow sunlight to penetrate to photosynthetic tissues within while sunlight-blocking flavonoid accumulation limits incoming solar radiation and aids screening of harmful UV radiation. Increased concentration of chlorophyll a and greater chlorophyll a:b in above-ground regions of leaves enable maximum photosynthetic use of incoming light, while inverted conical epidermal cells, increased chlorophyll b, and reduced chlorophyll a:b ensure maximum absorption and use of low light levels within the below-ground region of the leaf. High NPQ capacity affords physiological flexibility under variable natural light conditions. Our findings demonstrate unprecedented physiological flexibility in a xerophyte and further our understanding of plant responses and adaptations to extreme environments.

Relaxed selection on the CBF/DREB1 regulatory genes and reduced freezing tolerance in the southern range of Arabidopsis thaliana.

PubMed

Zhen, Ying; Ungerer, Mark C

2008-12-01

Elucidating the molecular basis of adaptive phenotypic variation represents a central aim in evolutionary biology. Traits exhibiting patterns of clinal variation represent excellent models for studies of molecular adaptation, especially when variation in phenotype can be linked to organismal fitness in different environments. Natural accessions of the model plant species Arabidopsis thaliana exhibit clinal variation in freezing tolerance that follows a gradient of temperature variability across the species' native range (Zhen Y, Ungerer MC. 2008. Clinal variation in freezing tolerance among natural accessions of A. thaliana. New Phytol. 177:419-427). Here, we report that this pattern of variation is attributable, at least in part, to relaxed purifying selection on members of a small family of transcriptional activators (the CBF/DREB1s) in the species' southern range. These regulatory genes play a critical role in the ability of A. thaliana plants to undergo cold acclimation and thereby achieve maximum freezing tolerance. Relative to accessions from northern regions, accessions of A. thaliana from the southern part of their geographic range exhibit levels of nonsynonymous nucleotide polymorphism that are approximately 2.8-fold higher across this small gene subfamily. Relaxed selection on the CBF/DREB1s in southern accessions also has resulted in multiple mutations in regulatory regions resulting in abrogated expression of particular subfamily members in particular accessions. These coding-region and regulatory mutations compromise the ability of these genes to act as efficient transcriptional activators during the cold acclimation process, as determined by reductions in rates of induction and maximum levels of expression in the downstream genes they regulate. This study highlights the potential role of regulatory genes in underlying adaptive phenotypic variation in nature.

Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors

PubMed Central

Merchant, Melinda S.; Geller, James I.; Baird, Kristin; Chou, Alexander J.; Galli, Susana; Charles, Ava; Amaoko, Martha; Rhee, Eunice H.; Price, Anita; Wexler, Leonard H.; Meyers, Paul A.; Widemann, Brigitte C.; Tsokos, Maria; Mackall, Crystal L.

2012-01-01

Purpose Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor–related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. Patients and Methods This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age ≤ 21 years with recurrent or progressive solid tumors. Results Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response. Conclusion Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects. PMID:23071222

Level of endogenous formaldehyde in maple syrup as determined by spectrofluorimetry.

PubMed

Lagacé, Luc; Guay, Stéphane; Martin, Nathalie

2003-01-01

The level of endogenous formaldehyde in maple syrup was established from a large number (n = 300) of authentic maple syrup samples collected during 2000 and 2001 in the province of Quebec, Canada. The average level of formaldehyde from these authentic samples was measured at 0.18 mg/kg in 2000 and 0.28 mg/kg in 2001, which is lower than previously published. These average values can be attributed to the improved spectrofluorimetric method used for the determination. However, the formaldehyde values obtained demonstrate a relatively large distribution with maximums observed at 1.04 and 1.54 mg/kg. These values are still under the maximum tolerance level of 2.0 mg/kg paraformaldehyde pesticide residue. Extensive heat treatment of maple syrup samples greatly enhanced the formaldehyde concentration of the samples, suggesting that extensive heat degradation of the sap constituents during evaporation could be responsible for the highest formaldehyde values in maple syrup.

Some physiological aspects of artificial gravity. [gravitational effects on human orthostatic tolerance and physical fitness

NASA Technical Reports Server (NTRS)

Cramer, D. B.; Graybiel, A.

1973-01-01

The effects of increasing artificial gravity exposure on four aspects of physiological fitness are examined in four young men who, prior to exposure, were deconditioned with bed rest and water immersion. The four aspects of physiological fitness are orthostatic tolerance, exercise tolerance, forearm endurance, and maximum strength. Orthostatic tolerance was sharply reduced by deconditioning and was substantially improved by walking in simulated lunar gravity (1/6 g) for 2.5 hours daily for 7 days or by walking in 1/2 g and 1 g for 1 hour daily for 3 days. Exercise tolerance was also sharply reduced by deconditioning but did not significantly improve with increasing g-exposure. Walking in 1 g for 1 hour daily for 3 days raised exercise tolerance only a little above the low produced by deconditioning. Forearm endurance and maximum strength were relatively unaffected by deconditioning and subsequent g-exposure.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

Plant Distribution Data Show Broader Climatic Limits than Expert-Based Climatic Tolerance Estimates

PubMed Central

Curtis, Caroline A.; Bradley, Bethany A.

2016-01-01

Background Although increasingly sophisticated environmental measures are being applied to species distributions models, the focus remains on using climatic data to provide estimates of habitat suitability. Climatic tolerance estimates based on expert knowledge are available for a wide range of plants via the USDA PLANTS database. We aim to test how climatic tolerance inferred from plant distribution records relates to tolerance estimated by experts. Further, we use this information to identify circumstances when species distributions are more likely to approximate climatic tolerance. Methods We compiled expert knowledge estimates of minimum and maximum precipitation and minimum temperature tolerance for over 1800 conservation plant species from the ‘plant characteristics’ information in the USDA PLANTS database. We derived climatic tolerance from distribution data downloaded from the Global Biodiversity and Information Facility (GBIF) and corresponding climate from WorldClim. We compared expert-derived climatic tolerance to empirical estimates to find the difference between their inferred climate niches (ΔCN), and tested whether ΔCN was influenced by growth form or range size. Results Climate niches calculated from distribution data were significantly broader than expert-based tolerance estimates (Mann-Whitney p values << 0.001). The average plant could tolerate 24 mm lower minimum precipitation, 14 mm higher maximum precipitation, and 7° C lower minimum temperatures based on distribution data relative to expert-based tolerance estimates. Species with larger ranges had greater ΔCN for minimum precipitation and minimum temperature. For maximum precipitation and minimum temperature, forbs and grasses tended to have larger ΔCN while grasses and trees had larger ΔCN for minimum precipitation. Conclusion Our results show that distribution data are consistently broader than USDA PLANTS experts’ knowledge and likely provide more robust estimates of climatic tolerance, especially for widespread forbs and grasses. These findings suggest that widely available expert-based climatic tolerance estimates underrepresent species’ fundamental niche and likely fail to capture the realized niche. PMID:27870859

The relationship between maximum tolerated light intensity and photoprotective energy dissipation in the photosynthetic antenna: chloroplast gains and losses

PubMed Central

Ruban, Alexander V.; Belgio, Erica

2014-01-01

The principle of quantifying the efficiency of protection of photosystem II (PSII) reaction centres against photoinhibition by non-photochemical energy dissipation (NPQ) has been recently introduced by Ruban & Murchie (2012 Biochim. Biophys. Acta 1817, 977–982 (doi:10.1016/j.bbabio.2012.03.026)). This is based upon the assessment of two key parameters: (i) the relationship between the PSII yield and NPQ, and (ii) the fraction of intact PSII reaction centres in the dark after illumination. In this paper, we have quantified the relationship between the amplitude of NPQ and the light intensity at which all PSII reaction centres remain intact for plants with different levels of PsbS protein, known to play a key role in the process. It was found that the same, nearly linear, relationship exists between the levels of the protective NPQ component (pNPQ) and the tolerated light intensity in all types of studied plants. This approach allowed for the quantification of the maximum tolerated light intensity, the light intensity at which all plant leaves become photoinhibited, the fraction of (most likely) unnecessary or ‘wasteful’ NPQ, and the fraction of photoinhibited PSII reaction centres under conditions of prolonged illumination by full sunlight. It was concluded that the governing factors in the photoprotection of PSII are the level and rate of protective pNPQ formation, which are often in discord with the amplitude of the conventional measure of photoprotection, the quickly reversible NPQ component, qE. Hence, we recommend pNPQ as a more informative and less ambiguous parameter than qE, as it reflects the effectiveness and limitations of the major photoprotective process of the photosynthetic membrane. PMID:24591709

Low velocity instrumented impact testing of four new damage tolerant carbon/epoxy composite systems

NASA Technical Reports Server (NTRS)

Lance, D. G.; Nettles, A. T.

1990-01-01

Low velocity drop weight instrumented impact testing was utilized to examine the damage resistance of four recently developed carbon fiber/epoxy resin systems. A fifth material, T300/934, for which a large data base exists, was also tested for comparison purposes. A 16-ply quasi-isotropic lay-up configuration was used for all the specimens. Force/absorbed energy-time plots were generated for each impact test. The specimens were cross-sectionally analyzed to record the damage corresponding to each impact energy level. Maximum force of impact versus impact energy plots were constructed to compare the various systems for impact damage resistance. Results show that the four new damage tolerant fiber/resin systems far outclassed the T300/934 material. The most damage tolerant material tested was the IM7/1962 fiber/resin system.

Strategies to reduce exposure of fumonisins from complementary foods in rural Tanzania.

PubMed

Kimanya, Martin E; De Meulenaer, Bruno; Van Camp, John; Baert, Katleen; Kolsteren, Patrick

2012-10-01

Feeding infants with maize can expose them to fumonisin mycotoxins. We assessed fumonisin exposure from complementary foods in rural Tanzania and determined strategies to reduce the exposure. We conducted a cross-sectional study in four villages of Tarakea division, Northern Tanzania. We used a repeat 24-hour dietary recall to collect data of maize consumption as complementary food for 254 infants aged 6-8 months. Fumonisin concentrations in the maize were also estimated. Fumonisin exposure was assessed using @risk analysis software. With the software, several maximum fumonisin contamination and maize consumption patterns were combined in order to determine effective strategies for minimizing fumonisin exposure. Of the infants, 89% consumed maize at amounts up to 158g/person/day (mean; 43g/person/day±28). The maize was contaminated with fumonisins at levels up to 3201µgkg(-1) . Risk of fumonisin intake above the provisional maximum tolerable daily limit of 2µgkg(-1) body weight was 15% (95% confidence interval; 10-19). The risk was minimized when the maximum contamination was set at 150µgkg(-1) . The risk was also minimized when the maximum consumption was set at 20g/child/day while keeping the maximum contamination at the European Union (EU) maximum tolerated limit (MTL) of 1000µgkg(-1) . Considering the economical and technological limitations of adopting good agricultural practices in rural Tanzania, it is practically difficult to reduce contamination in maize to 150µgkg(-1) . We suggest adoption of the EU MTL of 1000µgkg(-1) for fumonisins in maize and reduction, by replacement with another cereal, of the maize component in complementary foods to a maximum intake of 20g/child/day. © 2011 Blackwell Publishing Ltd.

40 CFR 180.505 - Emamectin; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Emamectin; tolerances for residues... § 180.505 Emamectin; tolerances for residues. (a) General. (1) Tolerances are established for combined residues of emamectin (a mixture of a minimum of 90% 4′-epi-methylamino-4′-deoxyavermectin B1a and maximum...

Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in Atlantic salmon (Salmo salar).

PubMed

Lund, Morten; Krudtaa Dahle, Maria; Timmerhaus, Gerrit; Alarcon, Marta; Powell, Mark; Aspehaug, Vidar; Rimstad, Espen; Jørgensen, Sven Martin

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is associated with Piscine orthoreovirus (PRV) infection and is an important disease in Atlantic salmon (Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon frequently experience environmental hypoxia, the current study examined mutual effects of PRV infection and hypoxia on pathogenesis and fish performance. Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance and blood oxygen transport were studied. A cohabitation trial including PRV-infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at 4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic conditions (PRV) was conducted. Periodic hypoxic stress did not influence infection levels or histopathological changes in the heart. Individual incipient lethal oxygen saturation (ILOS) was examined using a standardized hypoxia challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia tolerance was still observed for the PRV group while PRV-H performed equal to non-infected fish, implying a positive effect of the repeated exposure to hypoxic stress. This was in line with maximum heart rate (fHmax) measurements, showing equal performance of PRV-H and non-infected groups, but lower fHmax above 19°C as well as lower temperature optimum (Topt) for aerobic scope for PRV, suggesting reduced cardiac performance and thermal tolerance. In contrast, the PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish. In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance and cardiac performance, which can be improved by preconditioning fish to transient hypoxic stress episodes.

Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in Atlantic salmon (Salmo salar)

PubMed Central

Krudtaa Dahle, Maria; Timmerhaus, Gerrit; Alarcon, Marta; Powell, Mark; Aspehaug, Vidar; Rimstad, Espen; Jørgensen, Sven Martin

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is associated with Piscine orthoreovirus (PRV) infection and is an important disease in Atlantic salmon (Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon frequently experience environmental hypoxia, the current study examined mutual effects of PRV infection and hypoxia on pathogenesis and fish performance. Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance and blood oxygen transport were studied. A cohabitation trial including PRV-infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at 4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic conditions (PRV) was conducted. Periodic hypoxic stress did not influence infection levels or histopathological changes in the heart. Individual incipient lethal oxygen saturation (ILOS) was examined using a standardized hypoxia challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia tolerance was still observed for the PRV group while PRV-H performed equal to non-infected fish, implying a positive effect of the repeated exposure to hypoxic stress. This was in line with maximum heart rate (fHmax) measurements, showing equal performance of PRV-H and non-infected groups, but lower fHmax above 19°C as well as lower temperature optimum (Topt) for aerobic scope for PRV, suggesting reduced cardiac performance and thermal tolerance. In contrast, the PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish. In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance and cardiac performance, which can be improved by preconditioning fish to transient hypoxic stress episodes. PMID:28700748

Impact Damage and Strain Rate Effects for Toughened Epoxy Composite Structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Minnetyan, Levon

2006-01-01

Structural integrity of composite systems under dynamic impact loading is investigated herein. The GENOA virtual testing software environment is used to implement the effects of dynamic loading on fracture progression and damage tolerance. Combinations of graphite and glass fibers with a toughened epoxy matrix are investigated. The effect of a ceramic coating for the absorption of impact energy is also included. Impact and post impact simulations include verification and prediction of (1) Load and Impact Energy, (2) Impact Damage Size, (3) Maximum Impact Peak Load, (4) Residual Strength, (5) Maximum Displacement, (6) Contribution of Failure Modes to Failure Mechanisms, (7) Prediction of Impact Load Versus Time, and (8) Damage, and Fracture Pattern. A computer model is utilized for the assessment of structural response, progressive fracture, and defect/damage tolerance characteristics. Results show the damage progression sequence and the changes in the structural response characteristics due to dynamic impact. The fundamental premise of computational simulation is that the complete evaluation of composite fracture requires an assessment of ply and subply level damage/fracture processes as the structure is subjected to loads. Simulation results for the graphite/epoxy composite were compared with the impact and tension failure test data, correlation and verification was obtained that included: (1) impact energy, (2) damage size, (3) maximum impact peak load, (4) residual strength, (5) maximum displacement, and (6) failure mechanisms of the composite structure.

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Ecological and physiological thermal niches to understand distribution of Chagas disease vectors in Latin America.

PubMed

DE LA Vega, G J; Schilman, P E

2018-03-01

In order to assess how triatomines (Hemiptera, Reduviidae), Chagas disease vectors, are distributed through Latin America, we analysed the relationship between the ecological niche and the limits of the physiological thermal niche in seven species of triatomines. We combined two methodological approaches: species distribution models, and physiological tolerances. First, we modelled the ecological niche and identified the most important abiotic factor for their distribution. Then, thermal tolerance limits were analysed by measuring maximum and minimum critical temperatures, upper lethal temperature, and 'chill-coma recovery time'. Finally, we used phylogenetic independent contrasts to analyse the link between limiting factors and the thermal tolerance range for the assessment of ecological hypotheses that provide a different outlook for the geo-epidemiology of Chagas disease. In triatomines, thermo-tolerance range increases with increasing latitude mainly due to better cold tolerances, suggesting an effect of thermal selection. In turn, physiological analyses show that species reaching southernmost areas have a higher thermo-tolerance than those with tropical distributions, denoting that thermo-tolerance is limiting the southern distribution. Understanding the latitudinal range along its physiological limits of disease vectors may prove useful to test ecological hypotheses and improve strategies and efficiency of vector control at the local and regional levels. © 2017 The Royal Entomological Society.

Response of antioxidant system to drought stress and re-watering in Alfalfa during branching

NASA Astrophysics Data System (ADS)

Tina, R. R.; Shan, X. R.; Wang, Y.; Guo, S. Y.; Mao, B.; Wang, W.; Wu, H. Y.; Zhao, T. H.

2017-11-01

This paper aimed to reveal the response mechanism of active oxygen metabolism and antioxidant enzyme activities in Alfalfa under drought stress and re-watering, and the pot experiment was used, to explore the changes of H2O2, O2·-, electrolyte leakage conductivity and MDA, SOD, POD, CAT activity in Golden Empress (tolerant cultivar) and Sanditi (non-tolerant cultivar) under drought stress and re-watering during branching stage. Three water gradients were set up: CK (Maximum field capacity of 75%±5%), T1 (Maximum field capacity of 45%±5%), T2 (Maximum field capacity of 35%±5%) to compare, and the drought rehydration was also studied. Results: the results indicated that H2O2 content, O2·-production rate, relative conductivity and MDA content were higher than the control, and the increase extent of Golden Empress was higher than the Sanditi under drought stress and after re-watering the recovery capability of Golden Empress was also higher than the Sanditi. After 7 days of re-watering, all indexes were restored to the control level, indicating that the re-watering have compensation effect after drought. After drought stress, to weaken the damage of active oxygen Golden Empress was mainly by increasing the activity of POD and SOD, but Sanditi was mainly through the POD and CAT activity increased to effectively remove ROS. Under drought stress, active oxygen in leaves of Alfalfa increased, and thus the membrane system was damaged which lead to the increase of MDA content and relative electric conductivity. Plants play a defensive role by increasing the activity of antioxidant enzymes and scavenging reactive oxygen species. After re-watering, the stress effect was reduced, and the physiological indexes of plants were restored to the control level. In general, tolerant cultivar has stronger antioxidant properties under drought and re-watering.

40 CFR 180.422 - Tralomethrin; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-handling establishments, including food service, manufacturing, and processing establishments, such as... shall be limited to a maximum of 0.06 percent active ingredient. Contamination of food and food-contact...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

Investigation of arsenic accumulation and biochemical response of in vitro developed Vetiveria zizanoides plants.

PubMed

Singh, Shraddha; Sounderajan, Suvarna; Kumar, Kiran; Fulzele, D P

2017-11-01

Vetiver grass (Vetiveria zizanoides L. Nash) is found to be a suitable candidate for the phytoremediation of heavy metals. An investigation of arsenic (As) accumulation, translocation and tolerance was conducted in V. zizanoides plantlets upon exposure to different concentrations of arsenic (10, 50, 100 and 200µM) for 7 and 14 d. V. zizanoides plants were found effective in remediation of As, maximum being at 200µM after 14 d of exposure. The results of TBARS and photosynthetic pigments demonstrated that plants did not experience significant toxicity at all the concentrations of As after 7 days, however an increase in their level was found after 14 d. The up-regulation of antioxidant enzyme activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and glutathione s-transferase (GST) in a coordinated and complementary manner enhanced tolerance to plants against arsenic induced oxidative stress. Taken together, the results indicated that in vitro developed plants of V. zizanoides have the potential to remediate and tolerate varying levels of As. Copyright © 2017 Elsevier Inc. All rights reserved.

Selection and evaluation of CO2 tolerant indigenous microalga Scenedesmus dimorphus for unsaturated fatty acid rich lipid production under different culture conditions.

PubMed

Vidyashankar, S; Deviprasad, K; Chauhan, V S; Ravishankar, G A; Sarada, R

2013-09-01

Five indigenous microalgal strains of Scenedesmus, Chlorococcum, Coelastrum, and Ankistrodesmus genera, isolated from Indian fresh water habitats, were studied for carbon-dioxide tolerance and its effect on growth, lipid and fatty acid profile. Scenedesmus dimorphus strain showed maximum growth (1.5 g/L) and lipid content (17.83% w/w) under CO2 supplementation, hence selected for detailed evaluation. The selected strain was alkaline adapted but tolerated (i) wide range of pH (5-11); (ii) elevated salinity levels (up to 100 mM, NaCl) with low biomass yields and increased carotenoids (19.34 mg/g biomass); (iii) elevated CO2 levels up to 15% v/v with enhancement in specific growth rate (0.137 d(-1)), biomass yield (1.57 g/L), lipid content (19.6% w/w) and CO2 biofixation rate (0.174 g L(-1) d(-1)). Unsaturated fatty acid content (alpha linolenic acid) increased with CO2 supplementation in the strain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cd tolerance and accumulation in the aquatic macrophyte, Chara australis: potential use for charophytes in phytoremediation.

PubMed

Clabeaux, Bernadette L; Navarro, Divina A G; Aga, Diana S; Bisson, Mary A

2011-06-15

We investigated the potential use of the alga Chara australis (R. Br.) forphytore mediation of Cd-contaminated sediments in aquatic systems. Chara tolerated up to 20 mg added Cd (kg soil)⁻¹ in laboratory culture. Chlorophyll a and b levels were not affected even at Cd concentrations that suppressed growth. Levels of glutathione were suppressed at 2-35 mg added Cd (kg soil)⁻¹ to 200-350 nmol GSH (g DW)⁻¹, while control levels were 660 nmol GSH (g DW)⁻¹). Histochemical studies showed Cd occurred throughout cell walls and cytoplasm in plants grown in 5-20 mg Cd (kg soil)⁻¹. Quantification using ICP-MS showed the maximum concentration in shoots was 72 mg Cd (kg DW)⁻¹ at 35 mg added Cd (kg soil)⁻¹, while the maximum in rhizoids was 116 mg Cd (kg DW)⁻¹ at 25 mg added Cd (kg soil)⁻¹. The bioconcentration factor (BCF, concentration in plant/concentration in soil) exceeded 1.0, the critical value for hyperaccumulators, for shoots exposed to 35 mg Cd (kg soil)⁻¹ and rhizoids exposed to ≥25 mg Cd (kg soil)⁻¹. Translocation factors (TF, shoot concentration/rhizoid concentration) did not exceed 1.0 for any treatment. While Chara cannot be considered a hyperaccumulator, it shows promise for use in phytoremediation efforts.

High-temperature responses of North American cacti

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S.D.; Didden-Zopfy, B.; Nobel, P.S.

1984-04-01

High-temperature tolerances of 14 species of North American cacti were investigated. A reduction in the proportion of chlorenchyma cells taking up a vital stain (neutral red) and reduced nocturnal acid accumulation were used as indicators of high-temperature damage. All species tolerated relatively high tissue temperatures, the mean maximum tolerance being 64/sup 0/C, with an absolute maximum of 69/sup 0/ for two species of ferocactus. Such tissue tolerances to high temperature may be unsurpassed in vascular plants. Morphological features can affect tissue temperatures. Specifically, thin-stemmed species such as the cylindropuntias attain lower maximum temperatures under identical microclimatic conditions than do moremore » massive species; they also tend to be less tolerant of high-temperature stress. Stem diameter changes of three species of columnar ceriod cacti along a Sonoran Desert latitudinal transect were previously attributed to adaptation to progressively colder temperatures northward. Such changes can also be interpreted as a morphological adaptation to high temperatures, particularly in the southern Sonoran Desert. Interspecific differences in high-temperature tolerance may account for distributional differences among other species. Acclimation of high-temperature tolerances in response to increasing day/night air temperatures was observed in all 14 species, especially at higher growh temperatures. From 40/sup 0/ day/30/sup 0/ night to 50/sup 0//40/sup 0/, the tolerable tissue temperatures increased an average of 6/sup 0/. Half-times for the acclimation shifts were 1-3d. Although cacti attain extremely high tissue temperatures in desert habitats, tolerance of high temperatures and pronounced acclimation potential allow them to occur in some of the hottest habitats in North America.« less

Assessment of toxic impact of metals on proline, antioxidant enzymes, and biological characteristics of Pseudomonas aeruginosa inoculated Cicer arietinum grown in chromium and nickel-stressed sandy clay loam soils.

PubMed

Saif, Saima; Khan, Mohammad Saghir

2018-04-17

Considering the heavy metal risk to soil microbiota and agro-ecosystems, the study was designed to determine metal toxicity to bacteria and to find metal tolerant bacteria carrying multifarious plant growth promoting activities and to assess their impact on chickpea cultivated in stressed soils. Metal tolerant strain SFP1 recognized as Pseudomonas aeruginosa employing 16S rRNA gene sequence determination showed maximum tolerance to Cr (400 μg/ml) and Ni (800 μg/ml) and produced variable amounts of indole acetic acid, HCN, NH 3 , and ACC deaminase and could solubilize insoluble phosphates even under Cr (VI) and Ni stress. Metal tolerant P. aeruginosa reduced toxicity of Cr (VI) and Ni and concomitantly enhanced the performance of chickpea grown under stressed and conventional soils. At 144 mg Cr kg -1 , the measured parameters of a bacterial strain was significantly enhanced, but it was lower compared to those recorded at 660 mg Ni kg -1 . The strain SFP1 demonstrated maximum increase in seed yield (81%) and grain protein (16%) at 660 mg Ni kg -1 over uninoculated and untreated control. Stressed plants had more proline, antioxidant enzymes, and metal concentrations in plant tissues. P. aeruginosa, however, remarkably declined the level of stress markers (proline and APX, SOD, CAT, and GR), as well as with Cr (VI) and Ni uptake by chickpea. Conclusively, P. aeruginosa strain SFP1 due to its dual metal tolerant ability, capacity to secrete plant growth promoting regulators even under metal stress and potential to mitigate metal toxicity, could be developed as microbial inoculant for enhancing chickpea production in Cr and Ni contaminated soils.

Supplementation of the diet with the functional fiber PolyGlycoplex is well tolerated by healthy subjects in a clinical trial.

PubMed

Carabin, Ioana G; Lyon, Michael R; Wood, Simon; Pelletier, Xavier; Donazzolo, Yves; Burdock, George A

2009-02-05

The relationship of dietary fiber to overall health is of great importance, as beneficial effects have been demonstrated with the use of fiber from diverse sources, some traditional, other novel. PolyGlycopleX (PGX) is a unique proprietary product composed of three water-soluble polysaccharides, that when processed using novel technology give rise to a final product - a soluble, highly viscous functional fiber. Because of its potential use in food and dietary supplements, a randomized, double-blind, placebo controlled clinical study was conducted to evaluate the tolerance to PGX ingestion for 21 days, to a maximum dose level of 10 g per day, in healthy male and female volunteers. The main objective of the study was to evaluate the overall gastrointestinal (GI) tolerance, while secondary objectives were to evaluate possible changes in hematological, biochemical, urinary and fecal parameters. Results show that PGX is well tolerated as part of a regular diet with only mild to moderate adverse effects, similar to those seen with a moderate intake of dietary fiber in general, and fruits and vegetables. Because PGX is a highly viscous, functional fiber, it also demonstrates several physiological responses including, but not limited to maintaining healthy total and LDL cholesterol and uric acid levels.

Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pugh, Thomas J.; Chen Changhu; Rabinovitch, Rachel

Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, definedmore » as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.« less

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.

PubMed

Vazquez Roque, Maria I; Camilleri, Michael; Stephens, Debra A; Jensen, Michael D; Burton, Duane D; Baxter, Kari L; Zinsmeister, Alan R

2006-12-01

Peptide YY (PYY) levels are reported to be decreased in obesity. The relation between gastric functions, satiation, and gut hormones in obesity is incompletely understood. The aim of this study was to compare gastric volumes, emptying, maximum tolerated volumes, postchallenge symptoms, and selected gut hormones in normal, overweight, or obese healthy volunteers. In 73 nonbulimic normal, overweight, or obese participants weighing less than 137 kg, we measured gastric emptying of solids and liquids by scintigraphy (gastric emptying half-time [GE t(1/2)]); gastric volumes by single-photon emission computed tomography; maximum tolerated volumes and symptoms by satiation test; and plasma leptin, ghrelin, insulin, glucagon-like peptide 1, and PYY levels. Groups were compared using 1-way analysis of covariance adjusted for sex. Univariate associations among measured responses were assessed using Spearman correlations. Multiple linear regression models, adjusting for weight and sex, assessed the independent ability of gastric functions and hormones to predict satiation volume. Obese and overweight subjects had significantly lower postprandial gastric volumes, higher fasting and postprandial insulin and leptin levels, and lower fasting ghrelin and lower postprandial reduction in ghrelin levels. PYY levels were not different in obese or overweight subjects compared with controls. The GE t(1/2) was correlated inversely with postprandial PYY; increased body weight was associated with faster GE t(1/2) of solids (r(s) = 0.33, P = .005) and liquids (r(s) = 0.24, P = .04). Postprandial changes in gastric volume and PYY were independent predictors of satiation (both P = .01). Overweight or obesity are associated with lower postprandial gastric volumes and normal PYY levels. Gastric emptying influences postprandial PYY levels. Postprandial PYY and gastric volume independently predict satiation volume in nonbulimic people across a wide body mass index range.

Heat shock protein expression enhances heat tolerance of reptile embryos

PubMed Central

Gao, Jing; Zhang, Wen; Dang, Wei; Mou, Yi; Gao, Yuan; Sun, Bao-Jun; Du, Wei-Guo

2014-01-01

The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes. PMID:25080340

Update on emergency contraception.

PubMed

Fok, Wing Kay; Blumenthal, Paul D

2016-12-01

Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years. Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers. Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception.

Insulin resistance, β-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

PubMed

Cano Megías, Marta; González Albarrán, Olga; Guisado Vasco, Pablo; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

2015-02-01

diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic mechanism. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

PubMed

Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

2014-03-01

The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

Estimating Long-Term Survival Temperatures at the Assemblage Level in the Marine Environment: Towards Macrophysiology

PubMed Central

Richard, Joëlle; Morley, Simon Anthony; Thorne, Michael A. S.; Peck, Lloyd Samuel

2012-01-01

Defining ecologically relevant upper temperature limits of species is important in the context of environmental change. The approach used in the present paper estimates the relationship between rates of temperature change and upper temperature limits for survival in order to evaluate the maximum long-term survival temperature (Ts). This new approach integrates both the exposure time and the exposure temperature in the evaluation of temperature limits. Using data previously published for different temperate and Antarctic marine environments, we calculated Ts in each environment, which allowed us to calculate a new index: the Warming Allowance (WA). This index is defined as the maximum environmental temperature increase which an ectotherm in a given environment can tolerate, possibly with a decrease in performance but without endangering survival over seasonal or lifetime time-scales. It is calculated as the difference between maximum long-term survival temperature (Ts) and mean maximum habitat temperature. It provides a measure of how close a species, assemblage or fauna are living to their temperature limits for long-term survival and hence their vulnerability to environmental warming. In contrast to data for terrestrial environments showing that warming tolerance increases with latitude, results here for marine environments show a less clear pattern as the smallest WA value was for the Peru upwelling system. The method applied here, relating upper temperature limits to rate of experimental warming, has potential for wide application in the identification of faunas with little capacity to survive environmental warming. PMID:22509340

Noise tolerant dendritic lattice associative memories

NASA Astrophysics Data System (ADS)

Ritter, Gerhard X.; Schmalz, Mark S.; Hayden, Eric; Tucker, Marc

2011-09-01

Linear classifiers based on computation over the real numbers R (e.g., with operations of addition and multiplication) denoted by (R, +, x), have been represented extensively in the literature of pattern recognition. However, a different approach to pattern classification involves the use of addition, maximum, and minimum operations over the reals in the algebra (R, +, maximum, minimum) These pattern classifiers, based on lattice algebra, have been shown to exhibit superior information storage capacity, fast training and short convergence times, high pattern classification accuracy, and low computational cost. Such attributes are not always found, for example, in classical neural nets based on the linear inner product. In a special type of lattice associative memory (LAM), called a dendritic LAM or DLAM, it is possible to achieve noise-tolerant pattern classification by varying the design of noise or error acceptance bounds. This paper presents theory and algorithmic approaches for the computation of noise-tolerant lattice associative memories (LAMs) under a variety of input constraints. Of particular interest are the classification of nonergodic data in noise regimes with time-varying statistics. DLAMs, which are a specialization of LAMs derived from concepts of biological neural networks, have successfully been applied to pattern classification from hyperspectral remote sensing data, as well as spatial object recognition from digital imagery. The authors' recent research in the development of DLAMs is overviewed, with experimental results that show utility for a wide variety of pattern classification applications. Performance results are presented in terms of measured computational cost, noise tolerance, classification accuracy, and throughput for a variety of input data and noise levels.

Climate variations and the physiological basis of temperature dependent biogeography: systemic to molecular hierarchy of thermal tolerance in animals.

PubMed

Pörtner, H O

2002-08-01

The physiological mechanisms limiting and adjusting cold and heat tolerance have regained interest in the light of global warming and associated shifts in the geographical distribution of ectothermic animals. Recent comparative studies, largely carried out on marine ectotherms, indicate that the processes and limits of thermal tolerance are linked with the adjustment of aerobic scope and capacity of the whole animal as a crucial step in thermal adaptation on top of parallel adjustments at the molecular or membrane level. In accordance with Shelford's law of tolerance decreasing whole animal aerobic scope characterises the onset of thermal limitation at low and high pejus thresholds (pejus=getting worse). The drop in aerobic scope of an animal indicated by falling oxygen levels in the body fluids and or the progressively limited capacity of circulatory and ventilatory mechanisms. At high temperatures, excessive oxygen demand causes insufficient oxygen levels in the body fluids, whereas at low temperatures the aerobic capacity of mitochondria may become limiting for ventilation and circulation. Further cooling or warming beyond these limits leads to low or high critical threshold temperatures (T(c)) where aerobic scope disappears and transition to an anaerobic mode of mitochondrial metabolism and progressive insufficiency of cellular energy levels occurs. The adjustments of mitochondrial densities and their functional properties appear as a critical process in defining and shifting thermal tolerance windows. The finding of an oxygen limited thermal tolerance owing to loss of aerobic scope is in line with Taylor's and Weibel's concept of symmorphosis, which implies that excess capacity of any component of the oxygen delivery system is avoided. The present study suggests that the capacity of oxygen delivery is set to a level just sufficient to meet maximum oxygen demand between the average highs and lows of environmental temperatures. At more extreme temperatures only time limited passive survival is supported by anaerobic metabolism or the protection of molecular functions by heat shock proteins and antioxidative defence. As a corollary, the first line of thermal sensitivity is due to capacity limitations at a high level of organisational complexity, i.e. the integrated function of the oxygen delivery system, before individual, molecular or membrane functions become disturbed. These interpretations are in line with the more general consideration that, as a result of the high level of complexity of metazoan organisms compared with simple eukaryotes and then prokaryotes, thermal tolerance is reduced in metazoans. A similar sequence of sensitivities prevails within the metazoan organism, with the highest sensitivity at the organismic level and wider tolerance windows at lower levels of complexity. However, the situation is different in that loss in aerobic scope and progressive hypoxia at the organismic level define the onset of thermal limitation which then transfers to lower hierarchical levels and causes cellular and molecular disturbances. Oxygen limitation contributes to oxidative stress and, finally, denaturation or malfunction of molecular repair, e.g. during suspension of protein synthesis. The sequence of thermal tolerance limits turns into a hierarchy, ranging from systemic to cellular to molecular levels.

Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fouchardiere, Christelle de la, E-mail: delafo@lyon.fnclcc.f; Negrier, Sylvie; Labrosse, Hugues

2010-06-01

Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m{sup 2} per day and then escalated by increments of 2 mg/m{sup 2} every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperabilitymore » was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m{sup 2} to 20 mg/m{sup 2} per day). The maximum tolerated dose was determined to be 18 mg/m{sup 2} per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m{sup 2} per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.« less

Heat shock protein expression enhances heat tolerance of reptile embryos.

PubMed

Gao, Jing; Zhang, Wen; Dang, Wei; Mou, Yi; Gao, Yuan; Sun, Bao-Jun; Du, Wei-Guo

2014-09-22

The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

A safety vs efficiency trade-off identified in the hydraulic pathway of grass leaves is decoupled from photosynthesis, stomatal conductance and precipitation.

PubMed

Ocheltree, Troy W; Nippert, Jesse B; Prasad, P V Vara

2016-04-01

A common theme in plant physiological research is the trade-off between stress tolerance and growth; an example of this trade-off at the tissue level is the safety vs efficiency hypothesis, which suggests that plants with the greatest resistance to hydraulic failure should have low maximum hydraulic conductance. Here, we quantified the leaf-level drought tolerance of nine C4 grasses as the leaf water potential at which plants lost 50% (P50 × RR ) of maximum leaf hydraulic conductance (Ksat ), and compared this trait with other leaf-level and whole-plant functions. We found a clear trade-off between Ksat and P50 × RR when Ksat was normalized by leaf area and mass (P = 0.05 and 0.01, respectively). However, no trade-off existed between P50 × RR and gas-exchange rates; rather, there was a positive relationship between P50 × RR and photosynthesis (P = 0.08). P50 × RR was not correlated with species distributions based on precipitation (P = 0.70), but was correlated with temperature during the wettest quarter of the year (P < 0.01). These results suggest a trade-off between safety and efficiency in the hydraulic system of grass leaves, which can be decoupled from other leaf-level functions. The unique physiology of C4 plants and adaptations to pulse-driven systems may provide mechanisms that could decouple hydraulic conductance from other plant functions. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Nonlinear phase noise tolerance for coherent optical systems using soft-decision-aided ML carrier phase estimation enhanced with constellation partitioning

NASA Astrophysics Data System (ADS)

Li, Yan; Wu, Mingwei; Du, Xinwei; Xu, Zhuoran; Gurusamy, Mohan; Yu, Changyuan; Kam, Pooi-Yuen

2018-02-01

A novel soft-decision-aided maximum likelihood (SDA-ML) carrier phase estimation method and its simplified version, the decision-aided and soft-decision-aided maximum likelihood (DA-SDA-ML) methods are tested in a nonlinear phase noise-dominant channel. The numerical performance results show that both the SDA-ML and DA-SDA-ML methods outperform the conventional DA-ML in systems with constant-amplitude modulation formats. In addition, modified algorithms based on constellation partitioning are proposed. With partitioning, the modified SDA-ML and DA-SDA-ML are shown to be useful for compensating the nonlinear phase noise in multi-level modulation systems.

Postoperative Intensity-Modulated Radiotherapy in Low-Risk Endometrial Cancers: Final Results of a Phase I Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.i; Cilla, Savino M.P.; Ferrandina, Gabriella

2010-04-15

Purpose: To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence. Patients and Methods: A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated bymore » a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity. Results: Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable. Conclusions: The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy.« less

Mycotoxins, pesticides and toxic metals in commercial spices and herbs.

PubMed

Reinholds, Ingars; Pugajeva, Iveta; Bavrins, Konstantins; Kuckovska, Galina; Bartkevics, Vadims

2017-03-01

A total of 300 samples representing six condiments (black pepper, basil, oregano, nutmeg, paprika, and thyme) were analysed for 11 mycotoxins, 134 pesticides and 4 heavy metals by ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry and inductively coupled plasma mass spectrometry. Mycotoxins were detected in 4%, 10% and 30% of all nutmeg, basil and thyme samples, respectively. The residues of 24 pesticides were detected in 59% of the analysed condiments. The maximum residue levels of pesticides were exceeded in 10% of oregano and 46% of thyme samples. A risk assessment of heavy metals was performed, indicating daily intake levels far below the tolerable intake levels.

Growth rates of three geographically separated strains of the ichthyotoxic Prymnesium parvum (Prymnesiophyceae) in response to six different pH levels

NASA Astrophysics Data System (ADS)

Lysgaard, Maria L.; Eckford-Soper, Lisa; Daugbjerg, Niels

2018-05-01

Continued anthropogenic carbon emissions are expected to cause a decline in global average pH of the oceans to a projected value of 7.8 by the end of the century. Understanding how harmful algal bloom (HAB) species will respond to lowered pH levels will be important when predicting future HAB events and their ecological consequences. In this study, we examined how manipulated pH levels affected the growth rate of three strains of Prymnesium parvum from North America, Denmark and Japan. Triplicate strains were grown under pH conditions ranging from 6.6 to 9.1 to simulate plausible future levels. Different tolerances were evident for all strains. Significantly higher growth rates were observed at pH 6.6-8.1 compared to growth rates at pH 8.6-9.1 and a lower pH limit was not observed. The Japanese strain (NIES-1017) had the highest maximum growth rate of 0.39 divisions day-1 at pH 6.6 but a low tolerance (0.22 divisions day-1) to high levels (pH 9.1) with growth declining markedly after pH 7.6. The Danish (SCCAP K-0081) and North American (UTEX LB 2797) strains had maximum growth rates of 0.26 and 0.35 divisions day-1, respectively between pH 6.6-8.1. Compared to the other two strains the Danish strain had a statistically lower growth rate across all pH treatments. Strain differences were either attributed to their provenance or the length of time the strain had been in culture.

A minimally invasive system for glucose area under the curve measurement using interstitial fluid extraction technology: evaluation of the accuracy and usefulness with oral glucose tolerance tests in subjects with and without diabetes.

PubMed

Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Sato, Toshiyuki; Okada, Seiki; Hagino, Kei; Asakura, Yoshihiro; Kikkawa, Yasuo; Kojima, Junko; Maekawa, Yasunori; Nakajima, Hiromu

2012-06-01

Recent studies have highlighted the importance of managing postprandial hyperglycemia, but adequate monitoring of postprandial glucose remains difficult because of wide variations in levels. We have therefore developed a minimally invasive system to monitor postprandial glucose area under the curve (AUC). This system involves no blood sampling and uses interstitial fluid glucose (IG) AUC (IG-AUC) as a surrogate marker of postprandial glucose. This study aimed to evaluate the usefulness of this system by comparing data with the findings of oral glucose tolerance tests (OGTTs) in subjects with and without diabetes. The glucose AUC monitoring system was validated by OGTTs in 37 subjects with and 10 subjects without diabetes. A plastic microneedle array was stamped on the forearm to extract IG. A hydrogel patch was then placed on the pretreated area to accumulate IG. Glucose and sodium ion concentrations in the hydrogel were measured to calculate IG-AUC at 2-h postload glucose. Plasma glucose (PG) levels were measured every 30 min to calculate reference PG-AUC. IG-AUC correlated strongly with reference PG-AUC (r=0.93) over a wide range. The level of correlation between IG-AUC and maximum PG level was also high (r=0.86). The painless nature of the technique was confirmed by the response of patients to questionnaires. The glucose AUC monitoring system using IG provided good estimates of reference PG-AUC and maximum PG level during OGTTs in subjects with and without diabetes. This system provides easy-to-use monitoring of glucose AUC, which is a good indicator of postprandial glucose.

A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tada, Takuhito, E-mail: tada@msic.med.osaka-cu.ac.jp; Department of Radiology, Izumi Municipal Hospital, Izumi; Chiba, Yasutaka

2012-05-01

Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gymore » in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.« less

Thermal adaptation and phosphorus shape thermal performance in an assemblage of rainforest ants.

PubMed

Kaspari, Michael; Clay, Natalie A; Lucas, Jane; Revzen, Shai; Kay, Adam; Yanoviak, Stephen P

2016-04-01

We studied the Thermal Performance Curves (TPCs) of 87 species of rainforest ants and found support for both the Thermal Adaptation and Phosphorus-Tolerance hypotheses. TPCs relate a fitness proxy (here, worker speed) to environmental temperature. Thermal Adaptation posits that thermal generalists (ants with flatter, broader TPCs) are favored in the hotter, more variable tropical canopy compared to the cooler, less variable litter below. As predicted, species nesting in the forest canopy 1) had running speeds less sensitive to temperature; 2) ran over a greater range of temperatures; and 3) ran at lower maximum speeds. Tradeoffs between tolerance and maximum performance are often invoked for constraining the evolution of thermal generalists. There was no evidence that ant species traded off thermal tolerance for maximum speed, however. Phosphorus-Tolerance is a second mechanism for generating ectotherms able to tolerate thermal extremes. It posits that ants active at high temperatures invest in P-rich machinery to buffer their metabolism against thermal extremes. Phosphorus content in ant tissue varied three-fold, and as predicted, temperature sensitivity was lower and thermal range was higher in P-rich species. Combined, we show how the vertical distribution of hot and variable vs. cooler and stable microclimates in a single forest contribute to a diversity of TPCs and suggest that a widely varying P stoichiometry among these ants may drive some of these differences.

Human Tolerance to Rapidly Applied Accelerations: A Summary of the Literature

NASA Technical Reports Server (NTRS)

Eiband, A. Martin

1959-01-01

The literature is surveyed to determine human tolerance to rapidly applied accelerations. Pertinent human and animal experiments applicable to space flight and to crash impact forces are analyzed and discussed. These data are compared and presented on the basis of a trapezoidal pulse. The effects of body restraint and of acceleration direction, onset rate, and plateau duration on the maximum tolerable and survivable rapidly applied accelerations are shown. Results of the survey indicate that adequate torso and extremity restraint is the primary variable in tolerance to rapidly applied accelerations. The harness, or restraint system, must be arranged to transmit the major portion of the accelerating force directly to the pelvic structure and not via the vertebral column. When the conditions of adequate restraint have been met, then the other variables, direction, magnitude, and onset rate of rapidly applied accelerations, govern maximum tolerance and injury limits. The results also indicate that adequately stressed aft-faced passenger seats offer maximum complete body support with minimum objectionable harnessing. Such a seat, whether designed for 20-, 30-, or 40-G dynamic loading, would include lap strap, chest (axillary) strap, and winged-back seat to increase headward and lateral G protection, full-height integral head rest, arm rests (load-bearing) with recessed hand-holds and provisions to prevent arms from slipping either laterally or beyond the seat back, and leg support to keep the legs from being wedged under the seat. For crew members and others whose duties require forward-facing seats, maximum complete body support requires lap, shoulder, and thigh straps, lap-belt tie-down strap, and full-height seat back with integral head support.

Potential for thermal tolerance to mediate climate change effects on three members of a cool temperate lizard genus, Niveoscincus.

PubMed

Caldwell, Amanda J; While, Geoffrey M; Beeton, Nicholas J; Wapstra, Erik

2015-08-01

Climatic changes are predicted to be greater in higher latitude and mountainous regions but species specific impacts are difficult to predict. This is partly due to inter-specific variance in the physiological traits which mediate environmental temperature effects at the organismal level. We examined variation in the critical thermal minimum (CTmin), critical thermal maximum (CTmax) and evaporative water loss rates (EWL) of a widespread lowland (Niveoscincus ocellatus) and two range restricted highland (N. microlepidotus and N. greeni) members of a cool temperate Tasmanian lizard genus. The widespread lowland species had significantly higher CTmin and CTmax and significantly lower EWL than both highland species. Implications of inter-specific variation in thermal tolerance for activity were examined under contemporary and future climate change scenarios. Instances of air temperatures below CTmin were predicted to decline in frequency for the widespread lowland and both highland species. Air temperatures of high altitude sites were not predicted to exceed the CTmax of either highland species throughout the 21st century. In contrast, the widespread lowland species is predicted to experience air temperatures in excess of CTmax on 1 or 2 days by three of six global circulation models from 2068-2096. To estimate climate change effects on activity we reran the thermal tolerance models using minimum and maximum temperatures selected for activity. A net gain in available activity time was predicted under climate change for all three species; while air temperatures were predicted to exceed maximum temperatures selected for activity with increasing frequency, the change was not as great as the predicted decline in air temperatures below minimum temperatures selected for activity. We hypothesise that the major effect of rising air temperatures under climate change is an increase in available activity period for both the widespread lowland and highland species. The consequences of a greater available activity period will depend on the extent to which changes in climate alters other related factors, such as the nature and level of competition between the respective species. Copyright © 2015 Elsevier Ltd. All rights reserved.

A First-Time-In-Human Phase I Clinical Trial of Bispecific Antibody-Targeted, Paclitaxel-Packaged Bacterial Minicells

PubMed Central

Rosenthal, Mark; McArthur, Grant A.; Pattison, Scott T.; Pattison, Stacey L.; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Scott, Andrew M.

2015-01-01

Background We have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics to cancer cells. Preclinical studies showed that epidermal growth factor receptor (EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in xenograft models. To examine the safety of the minicell delivery system, we initiated a first-time-in-human, open-label, phase I clinical study of EGFRminicellsPac in patients with advanced solid tumors. Methodology Patients received 5 weekly infusions followed by a treatment free week. Seven dose levels (1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 dose-escalation design. Primary objectives were safety, tolerability and determination of the maximum tolerated dose. Secondary objectives were assessment of immune/inflammatory responses and antitumor activity. Principal Findings Twenty eight patients were enrolled, 22 patients completed at least one cycle of EGFRminicellsPac; 6 patients did not complete a cycle due to rapidly progressive disease. A total of 236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single patient. Most common treatment-related adverse events were rigors and pyrexia. No deaths resulted from treatment-related adverse events and the maximum tolerated dose was defined as 1x1010 EGFRminicellsPac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNFα and anti-inflammatory IL-10 was observed. Anti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat dosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease as their best response. Conclusions/Significance This is the first study in humans of a novel biological system that can provide targeted delivery of a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted minicells, packaged with the chemotherapeutic paclitaxel, were shown to be safe in patients with advanced solid tumors with modest clinical efficacy observed. Further study in Phase II trials is planned. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000672257 PMID:26659127

Equine goiter associated with excess dietary iodine.

PubMed

Eroksuz, H; Eroksuz, Y; Ozer, H; Ceribasi, A O; Yaman, I; Ilhan, N

2004-06-01

Naturally occurring goiter cases are described in 2 newborn Arabian foals whose mares were supplemented with excess iodine during the final 24 w of the pregnancy. Six nursing foals and 2 mares were also affected clinically with thyroid hypertrophy. At least 12 times the maximum tolerable level of iodine supplementation was given, as the daily iodine intake for each mare was 299 mg. The prevalence of goiter cases was 2 and 9% in the mares and foals, respectively.

S5 Lipase: an organic solvent tolerant enzyme.

PubMed

Rahman, Raja Noor Zaliha Abdul; Baharum, Syarul Nataqain; Salleh, Abu Bakar; Basri, Mahiran

2006-12-01

In this study, an organic solvent tolerant bacterial strain was isolated. This strain was identified as Pseudomonas sp. strain S5, and was shown to degrade BTEX (Benzene, Toluene, Ethyl-Benzene, and Xylene). Strain S5 generates an organic solvent-tolerant lipase in the late logarithmic phase of growth. Maximum lipase production was exhibited when peptone was utilized as the sole nitrogen source. Addition of any of the selected carbon sources to the medium resulted in a significant reduction of enzyme production. Lower lipase generation was noted when an inorganic nitrogen source was used as the sole nitrogen source. This bacterium hydrolyzed all tested triglycerides and the highest levels of production were observed when olive oil was used as a natural triglyceride. Basal medium containing Tween 60 enhanced lipase production to the most significant degree. The absence of magnesium ions (Mg2+) in the basal medium was also shown to stimulate lipase production. Meanwhile, an alkaline earth metal ion, Na+, was found to stimulate the production of S5 lipase.

Comparative of Quercus spp. and Salix spp. for phytoremediation of Pb/Zn mine tailings.

PubMed

Shi, Xiang; Wang, Shufeng; Sun, Haijing; Chen, Yitai; Wang, Dongxue; Pan, Hongwei; Zou, Yazhu; Liu, Jianfeng; Zheng, Linyu; Zhao, Xiulian; Jiang, Zeping

2017-02-01

A pot experiment was conducted to evaluate the feasibility of using tree seedlings for the phytoremediation of lead/zinc (Pb/Zn) mine tailings. Seedlings of three Quercus spp. (Q. shumardii, Q. phellos, and Q. virginiana) and rooted cuttings of two Salix spp. (S. matsudana and S. integra) were transplanted into pots containing 50 and 100 % Pb/Zn mine tailings to evaluate their tolerance of heavy metals. The five species showed different tolerance levels to the Pb/Zn tailings treatments. Q. virginiana was highly tolerant to heavy metals and grew normally in the Pb/Zn tailings. The root systems showed marked differences between the Quercus spp. and Salix spp., indicating that different mechanisms operated to confer tolerance of heavy metals. The maximum efficiency of photosystem II photochemistry value of the five species showed no differences among the treatments, except for Q. shumardii. All species showed low metal translocation factors (TFs). However, S. integra had significantly higher TF values for Zn (1.42-2.18) and cadmium (1.03-1.45) than did the other species. In this respect, Q. virginiana showed the highest tolerance and a low TF, implying that it is a candidate for phytostabilization of mine tailings in southern China. S. integra may be useful for phytoextraction of tailings in temperate regions.

Pesticide Tolerances

EPA Pesticide Factsheets

EPA regulates pesticides used to protect crops and sets limits on the amount of pesticide remaining in or on foods in the U.S. The limits on pesticides on foods are called tolerances in the U.S. (maximum residue limits (MRLs) in many other countries).

Genetic variance of tolerance and the toxicant threshold model.

PubMed

Tanaka, Yoshinari; Mano, Hiroyuki; Tatsuta, Haruki

2012-04-01

A statistical genetics method is presented for estimating the genetic variance (heritability) of tolerance to pollutants on the basis of a standard acute toxicity test conducted on several isofemale lines of cladoceran species. To analyze the genetic variance of tolerance in the case when the response is measured as a few discrete states (quantal endpoints), the authors attempted to apply the threshold character model in quantitative genetics to the threshold model separately developed in ecotoxicology. The integrated threshold model (toxicant threshold model) assumes that the response of a particular individual occurs at a threshold toxicant concentration and that the individual tolerance characterized by the individual's threshold value is determined by genetic and environmental factors. As a case study, the heritability of tolerance to p-nonylphenol in the cladoceran species Daphnia galeata was estimated by using the maximum likelihood method and nested analysis of variance (ANOVA). Broad-sense heritability was estimated to be 0.199 ± 0.112 by the maximum likelihood method and 0.184 ± 0.089 by ANOVA; both results implied that the species examined had the potential to acquire tolerance to this substance by evolutionary change. Copyright © 2012 SETAC.

Level of selected toxic elements in meat, liver, tallow and bone marrow of young semi-domesticated reindeer (Rangifer tarandus tarandus L.) from Northern Norway

PubMed Central

Hassan, Ammar Ali; Rylander, Charlotta; Brustad, Magritt; Sandanger, Torkjel M.

2012-01-01

Objectives To gain knowledge on toxic elements in semi-domesticated reindeer and their distribution in meat, liver, tallow and bone marrow. The correlations between concentrations in meat and liver, as well as the use of the latter as an indicator for toxic elements in meat, were also investigated. Study design Cross-sectional study on population of semi-domesticated reindeer from 2 northern Norwegian counties (Finnmark and Nordland). Methods Semi-domesticated reindeer carcasses (n=31) were randomly selected, from which meat, liver, tallow and bone marrow samples were collected. Selected toxic elements (cadmium, lead, arsenic, nickel and vanadium) were studied. Results Liver was the organ with the highest level of all elements except for nickel, which was highest in bone marrow. Meat had the lowest levels, whereas levels in tallow and bone marrow were between those of meat and liver. Concentrations of cadmium, lead and arsenic were significantly different (p<0.05) between meat and liver, while only arsenic and cadmium were significantly correlated in meat (rs=0.71, p<0.01) and liver (rs=0.72, p<0.01). The cadmium level exceeded the European Commission's (EC) maximum level set for bovine meat and live in 52% of the liver samples (n=29). Nevertheless, the estimated monthly cadmium intake from liver of 2.29 µg/kg body weight was well below the provisional tolerable monthly intake of 25 µg/kg body weight set by the FAO/WHO Joint Expert Committee on Food Additives. Conclusions Based on the measured levels and their relation to the maximum level and to the provisional tolerable weekly/monthly intake limits, it could be inferred that consumption of reindeer meat is not associated with any health risk related to the studied toxic elements for consumers. PMID:22564461

Fumonisins B₁ and B₂ in maize harvested in Hebei province, China, during 2011-2013.

PubMed

Li, Renjie; Guo, Congcong; Zhang, Quanguo; Pang, Minhao; Liu, Yingchao; Dong, Jingao

2015-01-01

A total of 125 maize kernel samples were collected from Hebei province in China during 2011-2013 and were analysed for incidence and contamination levels of fumonisins (FB₁ + FB₂) by HPLC with fluorescence detection. The incidence of FBs for all samples was 46.4%. The mean contamination level of FBs for the samples collected in 2013 was 706 μg kg⁻¹, which was higher than the levels in 2012 (429 μg kg⁻¹) and 2011 (250 μg kg⁻¹). All samples, except five, exhibited total FB levels below 4000 μg kg⁻¹, which is the maximum limit as set by the European Commission. The probable daily intakes of FBs (0.04 in 2011; 0.07 in 2012; 0.12 in 2013, expressed as μg kg⁻¹ body weight/day) were all within the provisional maximum tolerable daily intake of 2.0 μg kg⁻¹ of body weight/day as set by the Joint FAO/WHO Expert Committee on Food Additives. Nevertheless, monitoring is needed to prevent and control the potential risk of FB exposure to the consumers.

Phase I/II clinical trial of 2-Difluoromethylornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma

PubMed Central

Skorupski, Katherine A.; O'Brien, Thomas G.; Guerrero, Teri; Rodriguez, Carlos O.; Burns, Mark R.

2011-01-01

Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumor regression in mouse models of SCC. The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase inhibitor, DFMO, and to determine whether this therapy results in reduction in tumor polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumor biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose of MQT 1426 when combined with DFMO was determined. Dose limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, 2 cats experienced objective tumor regression, and 6 cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted. PMID:22077408

Health and Risk Assessment by ICP-OES of Heavy Metals and Trace Minerals in Commercial Mushrooms Marketed in China.

PubMed

Huang, Mengyi; Zeng, Huansong; Xu, Baojun

2017-01-01

The objectives of this study were to investigate mineral profiles of 35 species of edible mushrooms collected in China; we compared nutritional values and tolerable values with the official recommended daily intakes (RDIs), maximum intake limits, and provisional tolerable weekly intakes. A total of 19 minerals were detected in edible mushrooms by inductively coupled plasma optical emission spectrometry. The results showed that the mushroom samples had a low percentage of RDI for the minerals calcium, iron, magnesium, manganese, zinc, potassium, and sodium and a relatively higher percentage of RDI for copper and molybdenum. The samples also had a very high percentage of RDI for chromium and selenium. The level of heavy metals in a majority of the mushrooms was above the limited level, and only concentrations of copper and zinc were safe in all mushrooms. In conclusion, the mushrooms collected in China are a good source of minerals such as molybdenum and selenium but are badly contaminated with aluminum, arsenic, cadmium, chromium, and lead.

Defect Tolerant Semiconductors for Solar Energy Conversion.

PubMed

Zakutayev, Andriy; Caskey, Christopher M; Fioretti, Angela N; Ginley, David S; Vidal, Julien; Stevanovic, Vladan; Tea, Eric; Lany, Stephan

2014-04-03

Defect tolerance is the tendency of a semiconductor to keep its properties despite the presence of crystallographic defects. Scientific understanding of the origin of defect tolerance is currently missing. Here we show that semiconductors with antibonding states at the top of the valence band are likely to be tolerant to defects. Theoretical calculations demonstrate that Cu3N with antibonding valence band maximum has shallow intrinsic defects and no surface states, in contrast to GaN with bonding valence band maximum. Experimental measurements indicate shallow native donors and acceptors in Cu3N thin films, leading to 10(16)-10(17) cm(-3) doping with either electrons or holes depending on the growth conditions. The experimentally measured bipolar doping and the solar-matched optical absorption onset (1.4 eV) make Cu3N a promising candidate absorber for photovoltaic and photoelectrochemical solar cells, despite the calculated indirect fundamental band gap (1.0 eV). These conclusions can be extended to other materials with antibonding character of the valence band, defining a class of defect-tolerant semiconductors for solar energy conversion applications.

Temperature-stress resistance and tolerance along a latitudinal cline in North American Arabidopsis lyrata.

PubMed

Wos, Guillaume; Willi, Yvonne

2015-01-01

The study of latitudinal gradients can yield important insights into adaptation to temperature stress. Two strategies are available: resistance by limiting damage, or tolerance by reducing the fitness consequences of damage. Here we studied latitudinal variation in resistance and tolerance to frost and heat and tested the prediction of a trade-off between the two strategies and their costliness. We raised plants of replicate maternal seed families from eight populations of North American Arabidopsis lyrata collected along a latitudinal gradient in climate chambers and exposed them repeatedly to either frost or heat stress, while a set of control plants grew under standard conditions. When control plants reached maximum rosette size, leaf samples were exposed to frost and heat stress, and electrolyte leakage (PEL) was measured and treated as an estimate of resistance. Difference in maximum rosette size between stressed and control plants was used as an estimate of tolerance. Northern populations were more frost resistant, and less heat resistant and less heat tolerant, but-unexpectedly-they were also less frost tolerant. Negative genetic correlations between resistance and tolerance to the same and different thermal stress were generally not significant, indicating only weak trade-offs. However, tolerance to frost was consistently accompanied by small size under control conditions, which may explain the non-adaptive latitudinal pattern for frost tolerance. Our results suggest that adaptation to frost and heat is not constrained by trade-offs between them. But the cost of frost tolerance in terms of plant size reduction may be important for the limits of species distributions and climate niches.

Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: a pediatric oncology group study.

PubMed

Horton, Terzah M; Blaney, Susan M; Langevin, Anne-Marie; Kuhn, John; Kamen, Barton; Berg, Stacey L; Bernstein, Mark; Weitman, Steven

2005-03-01

To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia. Raltitrexed was administered as a 15-minute infusion for 3 consecutive weeks every 5 weeks, at doses ranging from 1.3 to 2.8 mg/m(2). The first course was used to determine the dose-limiting toxicities and maximum tolerated dose. Correlative studies included an assessment of raltitrexed pharmacokinetics and measurement of plasma 2'-deoxyuridine concentrations, a surrogate measure of thymidylate synthase inhibition. Twenty-one children (18 evaluable) with refractory leukemia received 25 courses of raltitrexed. The dose-limiting toxicity was reversible elevation in liver transaminases at the 2.8-mg/m(2) dose level and the maximum tolerated dose was 2.1 mg/m(2) per dose. Pharmacokinetics were best characterized by a two-compartment model with a clearance of 139 mL/min/m(2) (8.3 L/h/m(2)), a 2.4-L volume of distribution, an initial half-life (t(1/2alpha)) of 6 minutes, and a terminal half-life (t(1/2beta)) of 45 minutes. There were three objective responses. Raltitrexed was well tolerated when administered as a single agent to children with recurrent or refractory leukemia. We observed preliminary evidence of antileukemia activity using this weekly dosing schedule and these observations support further evaluation of raltitrexed in this population.

Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): results of a phase 1/2 trial.

PubMed

Mulder, Gerit; Tallis, Arthur J; Marshall, V Tracy; Mozingo, David; Phillips, Laurie; Pierce, Glenn F; Chandler, Lois A; Sosnowski, Barbara K

2009-01-01

The results from a Phase 1/2 study of a replication-defective adenovirus encoding human platelet-derived growth factor (PDGF)-B formulated in a bovine collagen (Ad-5PDGF-B; 2.6% collagen; GAM501) gel for nonhealing neuropathic diabetic foot ulcers is reported. The primary objectives of the study were to evaluate the safety, maximum-tolerated dose, and preliminary biological activity of GAM501. Fifteen patients enrolled into the study with chronic, nonhealing ulcers received either a single administration of GAM501 at one of three dose levels, or up to four administrations of GAM501 at 1-week intervals. All patients received standard of care treatment including debridement and were required to wear an off-loading shoe. GAM501 was found to be safe and well tolerated with no evidence of systemic or local toxicity at all doses so no maximum-tolerated dose was reached. Serum antibody titers to platelet-derived growth factor-B homodimer and collagen were negative and adenoviral DNA was not detected in the blood. In the 12 patients that completed the study, ulcer closure was observed by Month 3 in 10 patients, seven of whom received a single application of GAM501. In conclusion, GAM501 did not appear to have any toxicity at doses that showed biological activity. GAM501 holds promise as a potentially effective treatment for nonhealing diabetic foot ulcers.

A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer.

PubMed

Fakih, Marwan G; Pendyala, Lakshmi; Fetterly, Gerald; Toth, Karoli; Zwiebel, James A; Espinoza-Delgado, Igor; Litwin, Alan; Rustum, Youcef M; Ross, Mary Ellen; Holleran, Julianne L; Egorin, Merrill J

2009-05-01

We conducted a phase I study to determine the maximum tolerated dose of vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin, and oxaliplatin (FOLFOX). Vorinostat was given orally twice daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg twice daily. Escalation occurred in cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and oxaliplatin were studied. Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable patients at dose level 4 (vorinostat 400 mg orally twice daily) developed dose-limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and the area under the curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with day 1. The median C(max) of FU at each dose level increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was not consistent; only two of six patients had a decrease in intratumoral TS expression by reverse transcription-PCR. The maximum tolerated dose of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of TS expression.

Comparative Performance of Multivariable Agro-Physiological Parameters for Detecting Salt Tolerance of Wheat Cultivars under Simulated Saline Field Growing Conditions

PubMed Central

El-Hendawy, Salah E.; Hassan, Wael M.; Al-Suhaibani, Nasser A.; Refay, Yahya; Abdella, Kamel A.

2017-01-01

Field-based trials are crucial for successfully achieving the goals of plant breeding programs aiming to screen and improve the salt tolerance of crop genotypes. In this study, simulated saline field growing conditions were designed using the subsurface water retention technique (SWRT) and three saline irrigation levels (control, 60, and 120 mM NaCl) to accurately appraise the suitability of a set of agro-physiological parameters including shoot biomass, grain yield, leaf water relations, gas exchange, chlorophyll fluorescence, and ion accumulation as screening criteria to establish the salt tolerance of the salt-tolerant (Sakha 93) and salt-sensitive (Sakha 61) wheat cultivars. Shoot dry weight and grain yield per hectare were substantially reduced by salinity, but the reduction was more pronounced in Sakha 61 than in Sakha 93. Increasing salinity stress caused a significant decrease in the net photosynthesis rate and stomatal conductance of both cultivars, although their leaf turgor pressure increased. The accumulation of toxic ions (Na+ and Cl-) was higher in Sakha 61, but the accumulation of essential cations (K+ and Ca2+) was higher in Sakha 93, which could be the reason for the observed maintenance of the higher leaf turgor of both cultivars in the salt treatments. The maximum quantum PSII photochemical efficiency (Fv/Fm) and the PSII quantum yield (ΦPSII) decreased with increasing salinity levels in Sakha 61, but they only started to decline at the moderate salinity condition in Sakha 93. The principle component analysis successfully identified the interrelationships between all parameters. The parameters of leaf water relations and toxic ion concentrations were significantly related to each other and could identify Sakha 61 at mild and moderate salinity levels, and, to a lesser extent, Sakha 93 at the moderate salinity level. Both cultivars under the control treatment and Sakha 93 at the mild salinity level were identified by most of the other parameters. The variability in the angle between the vectors of parameters explained which parameters could be used as individual, interchangeable, or supplementary screening criteria for evaluating wheat salt tolerance under simulated field conditions. PMID:28424718

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom.

PubMed

Lye, Jessica; Kenny, John; Lehmann, Joerg; Dunn, Leon; Kron, Tomas; Alves, Andrew; Cole, Andrew; Williams, Ivan

2014-10-01

The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantoms are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%-8%. The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.

Intervarietal variations in various oxidative stress markers and antioxidant potential of finger millet (Eleusine coracana) subjected to drought stress.

PubMed

Bartwal, Arti; Pande, Anjali; Sharma, Priyadarshini; Arora, Sandeep

2016-07-01

Drought is a major form of abiotic stress leading to lower crop productivity. Experiment was carried out for selecting the most tolerant genotype among six different genotypes of finger millet under drought stress. Seeds of six finger millet genotypes were sown in pots and grown for 35 days. After this period, drought was induced by withholding watering for stressed plants while control plants were watered regularly for comparison. Among all six different varieties of finger millet screened (PR202, PES400, PRM6107, VL283, VL328 and VL149) under varying intensities of drought stress,PRM6107 and PR202 showed highest stress tolerance by limiting excessive accumulation of reactive oxygen species (ROS) through activation of ROS scavenging antioxidative enzymes. A 200% increase in ascorbate content was recorded in PRM6107 and PR202, while in other varieties limited increase in ascorbate content was observed. Maximum decrease in chlorophyll content was observed in VL328 (83%) while least drop was observed in VL149 (65%). Relative water content indicated that PR202 was able to retain maximum water content under stress, as it recorded least drop in relative water content (55%), contributing to its better survival under stress. In conclusion finger millet genotypes PRM6107 and PR202 possessed maximum drought tolerance potential and thus may be used for allele mining of drought tolerant genes, which can further be employed for the development of more drought stress tolerant staple crops using biotechnological approach.

Monitoring of environmental parameters for CO2 sequestration: a case study of Nagpur City, India.

PubMed

Chaudhari, P R; Gajghate, D G; Dhadse, Sharda; Suple, Sonali; Satapathy, D R; Wate, S R

2007-12-01

Carbon dioxide concentration is an index of total amount of combustion and natural ventilation in an urban environment and therefore required more careful attention for assessment of CO(2) level in air environment. An attempt was made to monitor CO(2) levels in ambient air of Nagpur city at industrial, commercial and residential sites. In addition to this a remote sensing studies and biotic survey for floral biodiversity were carried out to study the green cover at respective sampling locations. The observations showed that the largest amount of CO(2) occurred at night due to absence of photosynthesis and lowest concentration of CO(2) was observed in the afternoon due to photosynthesis at its maximum level. The most pollution tolerant species found in Nagpur city are having higher Air Pollution Tolerance Index (APTI) value, which acts as a natural sink for CO(2) sequestration. In case of commercial site the CO(2) level is highest (366 ppm) because of lowest vegetation and vehicular pollution. The generation of database of CO(2) concentration and floral biodiversity along with percentage of green cover helps to formulate the strategy for prevention of global worming phenomenon.

Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

NASA Astrophysics Data System (ADS)

Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

2016-08-01

We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

Evaluation of Pyrolysis Oil as Carbon Source for Fungal Fermentation

PubMed Central

Dörsam, Stefan; Kirchhoff, Jennifer; Bigalke, Michael; Dahmen, Nicolaus; Syldatk, Christoph; Ochsenreither, Katrin

2016-01-01

Pyrolysis oil, a complex mixture of several organic compounds, produced during flash pyrolysis of organic lignocellulosic material was evaluated for its suitability as alternative carbon source for fungal growth and fermentation processes. Therefore several fungi from all phyla were screened for their tolerance toward pyrolysis oil. Additionally Aspergillus oryzae and Rhizopus delemar, both established organic acid producers, were chosen as model organisms to investigate the suitability of pyrolysis oil as carbon source in fungal production processes. It was observed that A. oryzae tolerates pyrolysis oil concentrations between 1 and 2% depending on growth phase or stationary production phase, respectively. To investigate possible reasons for the low tolerance level, eleven substances from pyrolysis oil including aldehydes, organic acids, small organic compounds and phenolic substances were selected and maximum concentrations still allowing growth and organic acid production were determined. Furthermore, effects of substances to malic acid production were analyzed and compounds were categorized regarding their properties in three groups of toxicity. To validate the results, further tests were also performed with R. delemar. For the first time it could be shown that small amounts of phenolic substances are beneficial for organic acid production and A. oryzae might be able to degrade isoeugenol. Regarding pyrolysis oil toxicity, 2-cyclopenten-1-on was identified as the most toxic compound for filamentous fungi; a substance never described for anti-fungal or any other toxic properties before and possibly responsible for the low fungal tolerance levels toward pyrolysis oil. PMID:28066378

Evaluation of Pyrolysis Oil as Carbon Source for Fungal Fermentation.

PubMed

Dörsam, Stefan; Kirchhoff, Jennifer; Bigalke, Michael; Dahmen, Nicolaus; Syldatk, Christoph; Ochsenreither, Katrin

2016-01-01

Pyrolysis oil, a complex mixture of several organic compounds, produced during flash pyrolysis of organic lignocellulosic material was evaluated for its suitability as alternative carbon source for fungal growth and fermentation processes. Therefore several fungi from all phyla were screened for their tolerance toward pyrolysis oil. Additionally Aspergillus oryzae and Rhizopus delemar , both established organic acid producers, were chosen as model organisms to investigate the suitability of pyrolysis oil as carbon source in fungal production processes. It was observed that A. oryzae tolerates pyrolysis oil concentrations between 1 and 2% depending on growth phase or stationary production phase, respectively. To investigate possible reasons for the low tolerance level, eleven substances from pyrolysis oil including aldehydes, organic acids, small organic compounds and phenolic substances were selected and maximum concentrations still allowing growth and organic acid production were determined. Furthermore, effects of substances to malic acid production were analyzed and compounds were categorized regarding their properties in three groups of toxicity. To validate the results, further tests were also performed with R. delemar . For the first time it could be shown that small amounts of phenolic substances are beneficial for organic acid production and A. oryzae might be able to degrade isoeugenol. Regarding pyrolysis oil toxicity, 2-cyclopenten-1-on was identified as the most toxic compound for filamentous fungi; a substance never described for anti-fungal or any other toxic properties before and possibly responsible for the low fungal tolerance levels toward pyrolysis oil.

Seasonal and geographical variation in heat tolerance and evaporative cooling capacity in a passerine bird.

PubMed

Noakes, Matthew J; Wolf, Blair O; McKechnie, Andrew E

2016-03-01

Intraspecific variation in avian thermoregulatory responses to heat stress has received little attention, despite increasing evidence that endothermic animals show considerable physiological variation among populations. We investigated seasonal (summer versus winter) variation in heat tolerance and evaporative cooling in an Afrotropical ploceid passerine, the white-browed sparrow-weaver (Plocepasser mahali; ∼ 47 g) at three sites along a climatic gradient with more than 10 °C variation in mid-summer maximum air temperature (Ta). We measured resting metabolic rate (RMR) and total evaporative water loss (TEWL) using open flow-through respirometry, and core body temperature (Tb) using passive integrated transponder tags. Sparrow-weavers were exposed to a ramped profile of progressively higher Ta between 30 and 52 °C to elicit maximum evaporative cooling capacity (N=10 per site per season); the maximum Ta birds tolerated before the onset of severe hyperthermia (Tb ≈ 44 °C) was considered to be their hyperthermia threshold Ta (Ta,HT). Our data reveal significant seasonal acclimatisation of heat tolerance, with a desert population of sparrow-weavers reaching significantly higher Ta in summer (49.5 ± 1.4 °C, i.e. higher Ta,HT) than in winter (46.8 ± 0.9 °C), reflecting enhanced evaporative cooling during summer. Moreover, desert sparrow-weavers had significantly higher heat tolerance and evaporative cooling capacity during summer compared with populations from more mesic sites (Ta,HT=47.3 ± 1.5 and 47.6 ± 1.3 °C). A better understanding of the contributions of local adaptation versus phenotypic plasticity to intraspecific variation in avian heat tolerance and evaporative cooling capacity is needed for modelling species' responses to changing climates. © 2016. Published by The Company of Biologists Ltd.

Rapid change in the thermal tolerance of a tropical lizard.

PubMed

Leal, Manuel; Gunderson, Alex R

2012-12-01

The predominant view is that the thermal physiology of tropical ectotherms, including lizards, is not labile over ecological timescales. We used the recent introduction (∼35 years ago) of the Puerto Rican lizard Anolis cristatellus to Miami, Florida, to test this thermal rigidity hypothesis. We measured lower (critical thermal minimum [CT(min)]) and upper (critical thermal maximum [CT(max)]) thermal tolerances and found that the introduced population tolerates significantly colder temperatures (by ∼3°C) than does the Puerto Rican source population; however, CT(max) did not differ. These results mirror the thermal regimes experienced by each population: Miami reaches colder ambient temperatures than Puerto Rico, but maximum ambient temperatures are similar. The differences in CT(min) were observed even though lizards from both sites experienced nearly identical conditions for 49 days before CT(min) measurement. Our results demonstrate that changes in thermal tolerance occurred relatively rapidly (∼35 generations), which strongly suggests that the thermal physiology of tropical lizards is more labile than previously proposed.

Pilot Study on the Safety and Tolerability of Extended Release Niacin for HIV-infected Patients with Hypertriglyceridemia

PubMed Central

Souza, Scott A; Walsh, Erica J; Shippey, Ford; Shikuma, Cecilia

2010-01-01

Background To determine the safety and tolerability of extended release niacin (ERN) in HIV-infected patients. Methods This was a pilot, open-label, 36 week study evaluating the safety and tolerability of ERN in HIV-infected patients with hypertriglyceridemia. Subjects with cardiovascular disease, diabetes or liver disease were excluded. Subjects with persistent elevation of triglyceride (TG) >200 after 8 weeks on American Heart Association Step One and Two Diets were started on ERN 500mg once daily, with continuation of the diet and exercise recommendations until the end of the study. ERN was increased by 500mg every 4 weeks, to a maximum of 1500mg/day, depending on subject tolerability. Safety and tolerability of ERN were assessed. Results Ten subjects enrolled received ERN. Dose titration and maintenance to 1500mg/day were achieved in all 10 subjects. No subject required dose adjustment. Mild flushing was experienced in 8 subjects. Asymptomatic hypophosphotemia was noted in 4 subjects; all resolved with oral phosphate supplementation. Median TG was reduced by 254 mg/dL (p<0.05). Non-significant changes were noted in liver enzymes, HDL, LDL, and total cholesterol. Fasting insulin and glucose levels did not change with treatment. Conclusion In this pilot study, ERN was well-tolerated and resulted in reduction of TG. Although the results of this study are promising, the study is limited in the small number of subjects. Further investigation is warranted. PMID:20533755

An increased rectal maximum tolerable volume and long anal canal are associated with poor short-term response to biofeedback therapy for patients with anismus with decreased bowel frequency and normal colonic transit time.

PubMed

Rhee, P L; Choi, M S; Kim, Y H; Son, H J; Kim, J J; Koh, K C; Paik, S W; Rhee, J C; Choi, K W

2000-10-01

Biofeedback is an effective therapy for a majority of patients with anismus. However, a significant proportion of patients still failed to respond to biofeedback, and little has been known about the factors that predict response to biofeedback. We evaluated the factors associated with poor response to biofeedback. Biofeedback therapy was offered to 45 patients with anismus with decreased bowel frequency (less than three times per week) and normal colonic transit time. Any differences in demographics, symptoms, and parameters of anorectal physiologic tests were sought between responders (in whom bowel frequency increased up to three times or more per week after biofeedback) and nonresponders (in whom bowel frequency remained less than three times per week). Thirty-one patients (68.9 percent) responded to biofeedback and 14 patients (31.1 percent) did not. Anal canal length was longer in nonresponders than in responders (4.53 +/- 0.5 vs. 4.08 +/- 0.56 cm; P = 0.02), and rectal maximum tolerable volume was larger in nonresponders than in responders. (361 +/- 87 vs. 302 +/- 69 ml; P = 0.02). Anal canal length and rectal maximum tolerable volume showed significant differences between responders and nonresponders on multivariate analysis (P = 0.027 and P = 0.034, respectively). This study showed that a long anal canal and increased rectal maximum tolerable volume are associated with poor short-term response to biofeedback for patients with anismus with decreased bowel frequency and normal colonic transit time.

Developmental Hypoxia Has Negligible Effects on Long-Term Hypoxia Tolerance and Aerobic Metabolism of Atlantic Salmon (Salmo salar).

PubMed

Wood, Andrew T; Clark, Timothy D; Andrewartha, Sarah J; Elliott, Nicholas G; Frappell, Peter B

Exposure to developmental hypoxia can have long-term impacts on the physiological performance of fish because of irreversible plasticity. Wild and captive-reared Atlantic salmon (Salmo salar) can be exposed to hypoxic conditions during development and continue to experience fluctuating oxygen levels as juveniles and adults. Here, we examine whether developmental hypoxia impacts subsequent hypoxia tolerance and aerobic performance of Atlantic salmon. Individuals at 8°C were exposed to 50% (hypoxia) or 100% (normoxia) dissolved oxygen (DO) saturation (as percent of air saturation) from fertilization for ∼100 d (800 degree days) and then raised in normoxic conditions for a further 15 mo. At 18 mo after fertilization, aerobic scope was calculated in normoxia (100% DO) and acute (18 h) hypoxia (50% DO) from the difference between the minimum and maximum oxygen consumption rates ([Formula: see text] and [Formula: see text], respectively) at 10°C. Hypoxia tolerance was determined as the DO at which loss of equilibrium (LOE) occurred in a constantly decreasing DO environment. There was no difference in [Formula: see text], [Formula: see text], or aerobic scope between fish raised in hypoxia or normoxia. There was some evidence that hypoxia tolerance was lower (higher DO at LOE) in hypoxia-raised fish compared with those raised in normoxia, but the magnitude of the effect was small (12.52% DO vs. 11.73% DO at LOE). Acute hypoxia significantly reduced aerobic scope by reducing [Formula: see text], while [Formula: see text] remained unchanged. Interestingly, acute hypoxia uncovered individual-level relationships between DO at LOE and [Formula: see text], [Formula: see text], and aerobic scope. We discuss our findings in the context of developmental trajectories and the role of aerobic performance in hypoxia tolerance.

The Research on the Loan-to-Value of Inventory Pledge Loan Based Upon the Unified Credit Mode

NASA Astrophysics Data System (ADS)

Peng, Yang

This paper focus on loan limit indicator of seasonal inventory financing in supply chain financial innovation based on the logistics features of unified credit mode. According to the "corporate and debt" method in trade credit, this paper analyzes the cash flow properties of borrowing firm and the profit level of logistics enterprise, then it assumes downside-risk-averse logistics enterprise instead of risk-neutral logistics enterprise and takes the method of VaR to figure out the maximum loan-to-value ratio of inventory which is in accord with the risk tolerance level of logistics enterprise in seasonal inventory impawn financing.

A new chlorophycean nickel hyperaccumulator.

PubMed

Harish; Sundaramoorthy, S; Kumar, Devendra; Vaijapurkar, S G

2008-06-01

Bioremediation of nickel by chlorophycean bioremediator, Chlorococcum hemicolum was investigated. The growth rates at various concentrations of Ni2+ were assessed in terms of protein level and 12 mg L(-1) of the Ni2+ is the tolerance limit (46.76% level of growth kinetics). Absorption/adsorption kinetics was estimated after 240 h of Ni2+ treatments. Absorptions were higher than adsorption with maximum accumulation factor (AF) of 1.37. Ni2+ concentration and absorption were linearly related (r=0.98; p>0.01). Other biochemical parameters like total sugar, chlorophyll and carotenoids were also quantified to correlate the state of metabolism and these exhibited reduction due to heavy metal stress.

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

PubMed Central

Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

2015-01-01

Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

The linear sizes tolerances and fits system modernization

NASA Astrophysics Data System (ADS)

Glukhov, V. I.; Grinevich, V. A.; Shalay, V. V.

2018-04-01

The study is carried out on the urgent topic for technical products quality providing in the tolerancing process of the component parts. The aim of the paper is to develop alternatives for improving the system linear sizes tolerances and dimensional fits in the international standard ISO 286-1. The tasks of the work are, firstly, to classify as linear sizes the elements additionally linear coordinating sizes that determine the detail elements location and, secondly, to justify the basic deviation of the tolerance interval for the element's linear size. The geometrical modeling method of real details elements, the analytical and experimental methods are used in the research. It is shown that the linear coordinates are the dimensional basis of the elements linear sizes. To standardize the accuracy of linear coordinating sizes in all accuracy classes, it is sufficient to select in the standardized tolerance system only one tolerance interval with symmetrical deviations: Js for internal dimensional elements (holes) and js for external elements (shafts). The main deviation of this coordinating tolerance is the average zero deviation, which coincides with the nominal value of the coordinating size. Other intervals of the tolerance system are remained for normalizing the accuracy of the elements linear sizes with a fundamental change in the basic deviation of all tolerance intervals is the maximum deviation corresponding to the limit of the element material: EI is the lower tolerance for the of the internal elements (holes) sizes and es is the upper tolerance deviation for the outer elements (shafts) sizes. It is the sizes of the material maximum that are involved in the of the dimensional elements mating of the shafts and holes and determine the fits type.

Accumulation of 19-kDa plasma membrane polypeptide during induction of freezing tolerance in wheat suspension-cultured cells by abscisic acid.

PubMed

Koike, M; Takezawa, D; Arakawa, K; Yoshida, S

1997-06-01

Suspension-cultured cells derived from immature embryos of winter wheat (Triticum aestivum L. cv. Chihoku) were used in experiments designed to obtain clues to the mechanism of the ABA-induced development of freezing tolerance. Cultured cells treated with 50 microM ABA for 5 d at 23 degrees C acquired the maximum level of freezing tolerance (LT50; -21.6 degrees C). The increased freezing tolerance of ABA-treated cells was closely associated with the remarkable accumulation of 19-kDa polypeptides in the plasma membrane. The 19-kDa polypeptide components were isolated by preparative gel electrophoresis and were further separated into one major (AWPM-19) and other minor polypeptide components by Tricine-SDS-PAGE. N-terminal amino acid sequence of AWPM-19 was determined, and a cDNA clone encoding AWPM-19 was isolated by PCR from the library prepared from the ABA-treated cultured cells. The cDNA clone (WPM-1) encoded a 18.9 kDa hydrophobic polypeptide with four putative membrane spanning domains and with a high pI value (10.2). Expression of WPM-1 mRNA was dramatically induced by 50 microM ABA within a few hours. These results suggest that the AWPM-19 might be closely associated with the ABA-induced increase in freezing tolerance in wheat cultured cells.

Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression.

PubMed

Serebrovska, Tetiana V; Portnychenko, Alla G; Drevytska, Tetiana I; Portnichenko, Vladimir I; Xi, Lei; Egorov, Egor; Gavalko, Anna V; Naskalova, Svitlana; Chizhova, Valentina; Shatylo, Valeriy B

2017-09-01

The present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1α (HIF-1α) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1α mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1α target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1α was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes. Impact statement The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1α mRNA expressions as well as its target genes, which were positively correlated with higher tolerance to acute hypoxia and better glucose homeostasis in both middle-aged healthy and prediabetic subjects. This small clinical trial has provided new data suggesting a potential utility of IHT for management of prediabetes patients.

Thermal Tolerance in Anuran Embryos with Different Reproductive Modes: Relationship to Altitude

PubMed Central

Lynch, John D.

2013-01-01

Anurans are ectothermic animals very sensitive to temperature, mainly during the embryonic stage. In addition, environmental temperature decreases with altitude, and the amphibian fauna changes. Therefore, we studied the relationship between the embryonic thermal tolerances of twelve species of anurans and the temperatures of their microhabitat along an altitudinal gradient from 430 m to 2600 m. We hypothesized that there is a strong thermal adjustment of embryos to their microhabitat and, consequently, that temperature could be a limiting factor of altitudinal distribution of the anurans. We also compared the embryonic thermal tolerances according to six postulated reproductive modes of the study species. We found a significant relationship between the maximum and minimum thermal tolerances of the anuran embryos and the maximum and minimum temperatures of their microhabitat and altitudinal distribution. We also found a wide range of embryonic thermal tolerances for aquatic breeding species and a narrower range for terrestrial breeding species. Particularly, embryos of direct development species were the most sensitive to temperature. These results show the strong thermal adjustment of anuran embryos to their microhabitat and elevation and do not reject the hypothesis that temperature can be a limiting factor of their altitudinal distribution. PMID:23766678

Lambda network having 2.sup.m-1 nodes in each of m stages with each node coupled to four other nodes for bidirectional routing of data packets between nodes

DOEpatents

Napolitano, Jr., Leonard M.

1995-01-01

The Lambda network is a single stage, packet-switched interprocessor communication network for a distributed memory, parallel processor computer. Its design arises from the desired network characteristics of minimizing mean and maximum packet transfer time, local routing, expandability, deadlock avoidance, and fault tolerance. The network is based on fixed degree nodes and has mean and maximum packet transfer distances where n is the number of processors. The routing method is detailed, as are methods for expandability, deadlock avoidance, and fault tolerance.

Gyro-based Maximum-Likelihood Thruster Fault Detection and Identification

NASA Technical Reports Server (NTRS)

Wilson, Edward; Lages, Chris; Mah, Robert; Clancy, Daniel (Technical Monitor)

2002-01-01

When building smaller, less expensive spacecraft, there is a need for intelligent fault tolerance vs. increased hardware redundancy. If fault tolerance can be achieved using existing navigation sensors, cost and vehicle complexity can be reduced. A maximum likelihood-based approach to thruster fault detection and identification (FDI) for spacecraft is developed here and applied in simulation to the X-38 space vehicle. The system uses only gyro signals to detect and identify hard, abrupt, single and multiple jet on- and off-failures. Faults are detected within one second and identified within one to five accords,

14 CFR 27.571 - Fatigue evaluation of flight structure.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 27.309, except that maneuvering load factors need not exceed the maximum values expected in operation... paragraph (a)(3) of this section. (b) Fatigue tolerance evaluation. It must be shown that the fatigue tolerance of the structure ensures that the probability of catastrophic fatigue failure is extremely remote...

Ammonia tolerant inocula provide a good base for anaerobic digestion of microalgae in third generation biogas process.

PubMed

Mahdy, Ahmed; Fotidis, Ioannis A; Mancini, Enrico; Ballesteros, Mercedes; González-Fernández, Cristina; Angelidaki, Irini

2017-02-01

This study investigated the ability of an ammonia-acclimatized inoculum to digest efficiently protein-rich microalgae for continuous 3rd generation biogas production. Moreover, we investigated whether increased C/N ratio could alleviate ammonia toxicity. The biochemical methane potential (BMP) of five different algae (Chlorella vulgaris)/manure (cattle) mixtures showed that the mixture of 80/20 (on VS basis) resulted in the highest BMP value (431mLCH 4 gVS -1 ), while the BMP of microalgae alone (100/0) was 415mLCH 4 gVS -1 . Subsequently, anaerobic digestion of those two substrates was tested in continuous stirred tank reactors (CSTR). Despite of the high ammonium levels (3.7-4.2g NH 4 + -NL -1 ), CSTR reactors using ammonia tolerant inoculum resulted in relatively high methane yields (i.e. 77.5% and 84% of the maximum expected, respectively). These results demonstrated that ammonia tolerant inocula could be a promising approach to successfully digest protein-rich microalgae and achieve a 3rd generation biogas production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of long-term self-massage at the musculotendinous junction on hamstring extensibility, stiffness, stretch tolerance, and structural indices: A randomized controlled trial.

PubMed

Akazawa, Naoki; Okawa, Naomi; Kishi, Masaki; Nakatani, Kiyoshi; Nishikawa, Katsuya; Tokumura, Daichi; Matsui, Yuji; Moriyama, Hideki

2016-09-01

The purpose of this study was to examine the effect of long-term self-massage at the musculotendinous junction on hamstring extensibility, stiffness, stretch tolerance, and structural indices. Single-blind, randomized, controlled trial. Laboratory. Thirty-seven healthy men. The right or left leg of each participant was randomly assigned to the massage group, and the other leg was assigned to the control group. The participants conducted self-massage at the musculotendinous junction for 3 min daily, five times per week, for 12 weeks. Hamstring extensibility, stiffness, stretch tolerance, and structural indices were measured by a blinded examiner prior to the massage intervention and after 6 and 12 weeks of intervention. The maximum hip flexion angle (HFA) and the maximum passive pressure after 6 and 12 weeks of intervention in the massage group were significantly higher than prior to intervention. The visual analog scale (for pain perception) at maximum HFA, the stiffness of the hamstring, and the structural indices did not differ in either group over the 12 week period. Our results suggest that long-term self-massage at the musculotendinous junction increases hamstring extensibility by improving stretch tolerance. However, this intervention does not change hamstring stiffness. University Hospital Medical Information Network registration number UMIN000011233. Copyright © 2016 Elsevier Ltd. All rights reserved.

A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients.

PubMed

Schneider, Lynda C; Rachid, Rima; LeBovidge, Jennifer; Blood, Emily; Mittal, Mudita; Umetsu, Dale T

2013-12-01

Peanut allergy is a major public health problem that affects 1% of the population and has no effective therapy. To examine the safety and efficacy of oral desensitization in peanut-allergic children in combination with a brief course of anti-IgE mAb (omalizumab [Xolair]). We performed oral peanut desensitization in peanut-allergic children at high risk for developing significant peanut-induced allergic reactions. Omalizumab was administered before and during oral peanut desensitization. We enrolled 13 children (median age, 10 years), with a median peanut-specific IgE level of 229 kU(A)/L and a median total serum IgE level of 621 kU/L, who failed an initial double-blind placebo-controlled food challenge at peanut flour doses of 100 mg or less. After pretreatment with omalizumab, all 13 subjects tolerated the initial 11 desensitization doses given on the first day, including the maximum dose of 500 mg peanut flour (cumulative dose, 992 mg, equivalent to >2 peanuts), requiring minimal or no rescue therapy. Twelve subjects then reached the maximum maintenance dose of 4000 mg peanut flour per day in a median time of 8 weeks, at which point omalizumab was discontinued. All 12 subjects continued on 4000 mg peanut flour per day and subsequently tolerated a challenge with 8000 mg peanut flour (equivalent to about 20 peanuts), or 160 to 400 times the dose tolerated before desensitization. During the study, 6 of the 13 subjects experienced mild or no allergic reactions, 5 subjects had grade 2 reactions, and 2 subjects had grade 3 reactions, all of which responded rapidly to treatment. Among children with high-risk peanut allergy, treatment with omalizumab may facilitate rapid oral desensitization and qualitatively improve the desensitization process. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Food Safety Legislation Regarding Of Aflatoxins Contamination

NASA Astrophysics Data System (ADS)

Ketney, Otto

2015-09-01

The main objective of the European Union (EU) is to reduce certain contaminants in foodstuffs to acceptable levels. The occurrence of aflatoxin B1 in food was considered to be one of the most important issues of global food security to protect the health of humans and animals, over 100 nations have established maximum tolerable levels for aflatoxin in food. Although EU legislation covers many aspects of food safety was not legally establish an integrated framework that could effectively combat and cover all sectors of the food chain. Monitoring and reporting levels of aflatoxins after controls are essential actions that assist to identify potential risks to human health. The review process for aflatoxin regulations is a complex activity involving many factors and stakeholders.

Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study.

PubMed

Atkins, Michael B; Hodi, F Stephen; Thompson, John A; McDermott, David F; Hwu, Wen-Jen; Lawrence, Donald P; Dawson, Nancy A; Wong, Deborah J; Bhatia, Shailender; James, Marihella; Jain, Lokesh; Robey, Seth; Shu, Xinxin; Homet Moreno, Blanca; Perini, Rodolfo F; Choueiri, Toni K; Ribas, Antoni

2018-04-15

Purpose: Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. Experimental Design: The phase Ib KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6 of 18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review. Results: The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3 to 4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17 (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2 of 12 (17%) patients with RCC. Conclusions: Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population. Clin Cancer Res; 24(8); 1805-15. ©2018 AACR . ©2018 American Association for Cancer Research.

Gross mismatch between thermal tolerances and environmental temperatures in a tropical freshwater snail: climate warming and evolutionary implications.

PubMed

Polgar, Gianluca; Khang, Tsung Fei; Chua, Teddy; Marshall, David J

2015-01-01

The relationship between acute thermal tolerance and habitat temperature in ectotherm animals informs about their thermal adaptation and is used to assess thermal safety margins and sensitivity to climate warming. We studied this relationship in an equatorial freshwater snail (Clea nigricans), belonging to a predominantly marine gastropod lineage (Neogastropoda, Buccinidae). We found that tolerance of heating and cooling exceeded average daily maximum and minimum temperatures, by roughly 20°C in each case. Because habitat temperature is generally assumed to be the main selective factor acting on the fundamental thermal niche, the discordance between thermal tolerance and environmental temperature implies trait conservation following 'in situ' environmental change, or following novel colonisation of a thermally less-variable habitat. Whereas heat tolerance could relate to an historical association with the thermally variable and extreme marine intertidal fringe zone, cold tolerance could associate with either an ancestral life at higher latitudes, or represent adaptation to cooler, higher-altitudinal, tropical lotic systems. The broad upper thermal safety margin (difference between heat tolerance and maximum environmental temperature) observed in this snail is grossly incompatible with the very narrow safety margins typically found in most terrestrial tropical ectotherms (insects and lizards), and hence with the emerging prediction that tropical ectotherms, are especially vulnerable to environmental warming. A more comprehensive understanding of climatic vulnerability of animal ectotherms thus requires greater consideration of taxonomic diversity, ecological transition and evolutionary history. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose

PubMed Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer.

PubMed

Dy, Grace K; Bruzek, Laura M; Croghan, Gary A; Mandrekar, Sumithra; Erlichman, Charles; Peethambaram, Prema; Pitot, Henry C; Hanson, Lorelei J; Reid, Joel M; Furth, Alfred; Cheng, Shinta; Martell, Robert E; Kaufmann, Scott H; Adjei, Alex A

2005-03-01

This phase I study was conducted to determine the toxicities, pharmacokinetics, and pharmacodynamics of BMS-214662, a farnesyl transferase inhibitor, in combination with paclitaxel and carboplatin, in patients with advanced solid tumors. Patients with solid tumors received one of six escalating dose levels of BMS-214662 infused over 1 hour given following paclitaxel and carboplatin on the first day of a 21-day cycle. Toxicities were graded by the National Cancer Institute common toxicity criteria and recorded as maximum grade per patient for each treatment cycle. Inhibition of farnesyl transferase activity in peripheral blood mononuclear cells (PBMCs) was evaluated. Accumulation of unfarnesylated HDJ-2 in PBMCs of patients was evaluated as a marker of farnesyl transferase inhibition by BMS-214662. Thirty patients received 141 cycles of treatment through six dose levels. Dose-limiting toxicities were neutropenia, thrombocytopenia, nausea, and vomiting. There was no pharmacokinetic interaction between BMS-214662 and paclitaxel. The maximum tolerated dose was established as BMS-214662 (160 mg/m(2)), paclitaxel (225 mg/m(2)) and carboplatin (area under the curve = 6 on day 1), every 21 days. Inhibition of HDJ-2 farnesylation in PBMCs of patients was shown. One measurable partial response was observed in a patient with taxane-resistant esophageal cancer. There was partial regression of evaluable disease in two other patients (endometrial and ovarian cancer). Stable disease (> 4 cycles) occurred in eight other patients. The combination of BMS-214662 with paclitaxel and carboplatin was well tolerated, with broad activity in solid tumors. There was no correlation between dose level and accumulation of unfarnesylated HDJ-2 in PBMCs nor tumor response.

Reconfigurable fault tolerant avionics system

NASA Astrophysics Data System (ADS)

Ibrahim, M. M.; Asami, K.; Cho, Mengu

This paper presents the design of a reconfigurable avionics system based on modern Static Random Access Memory (SRAM)-based Field Programmable Gate Array (FPGA) to be used in future generations of nano satellites. A major concern in satellite systems and especially nano satellites is to build robust systems with low-power consumption profiles. The system is designed to be flexible by providing the capability of reconfiguring itself based on its orbital position. As Single Event Upsets (SEU) do not have the same severity and intensity in all orbital locations, having the maximum at the South Atlantic Anomaly (SAA) and the polar cusps, the system does not have to be fully protected all the time in its orbit. An acceptable level of protection against high-energy cosmic rays and charged particles roaming in space is provided within the majority of the orbit through software fault tolerance. Check pointing and roll back, besides control flow assertions, is used for that level of protection. In the minority part of the orbit where severe SEUs are expected to exist, a reconfiguration for the system FPGA is initiated where the processor systems are triplicated and protection through Triple Modular Redundancy (TMR) with feedback is provided. This technique of reconfiguring the system as per the level of the threat expected from SEU-induced faults helps in reducing the average dynamic power consumption of the system to one-third of its maximum. This technique can be viewed as a smart protection through system reconfiguration. The system is built on the commercial version of the (XC5VLX50) Xilinx Virtex5 FPGA on bulk silicon with 324 IO. Simulations of orbit SEU rates were carried out using the SPENVIS web-based software package.

First-in-man-proof of concept study with molidustat: a novel selective oral HIF-prolyl hydroxylase inhibitor for the treatment of renal anaemia.

PubMed

Böttcher, M; Lentini, S; Arens, E R; Kaiser, A; van der Mey, D; Thuss, U; Kubitza, D; Wensing, G

2018-07-01

Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO levels dose dependently in preclinical models. We examined the pharmacokinetics, safety, tolerability and effect on EPO levels of single oral doses of molidustat in healthy male volunteers. This was a single-centre, randomized, single-blind, placebo-controlled, group-comparison, dose-escalation study. Molidustat was administered at doses of 5, 12.5, 25, 37.5 or 50 mg as a polyethylene glycol-based solution. In total, 45 volunteers received molidustat and 14 received placebo. Molidustat was absorbed rapidly, and the mean maximum plasma concentration and area under the concentration-time curve increased dose dependently. The mean terminal half-life was 4.64-10.40 h. A significant increase in endogenous EPO was observed following single oral doses of molidustat of 12.5 mg and above. Geometric mean peak EPO levels were 14.8 IU l -1 (90% confidence interval 13.0, 16.9) for volunteers who received placebo and 39.8 IU l -1 (90% confidence interval: 29.4, 53.8) for those who received molidustat 50 mg. The time course of EPO levels resembled the normal diurnal variation in EPO. Maximum EPO levels were observed approximately 12 h postdose and returned to baseline after approximately 24-48 h. All doses of molidustat were well tolerated and there were no significant changes in vital signs or laboratory safety parameters. Oral administration of molidustat to healthy volunteers elicited a dose-dependent increase in endogenous EPO. These results support the ongoing development of molidustat as a potential new treatment for patients with renal anaemia. © 2018 The British Pharmacological Society.

An analysis of the development of cauliflower seed as a model to improve the molecular mechanism of abiotic stress tolerance in cauliflower artificial seeds.

PubMed

Rihan, Hail Z; Al-Issawi, Mohammed; Fuller, Michael P

2017-07-01

The development stages of conventional cauliflower seeds were studied and the accumulation of dehydrin proteins through the maturation stages was investigated with the aim of identifying methods to improve the viability of artificial seeds of cauliflower. While carbohydrate, ash and lipids increased throughout the development of cauliflower traditional seeds, proteins increased with the development of seed and reached the maximum level after 75 days of pollination, however, the level of protein started to decrease after that. A significant increase in the accumulation of small size dehydrin proteins (12, 17, 26 KDa) was observed during the development of cauliflower seeds. Several experiments were conducted in order to increase the accumulation of important dehydrin proteins in cauliflower microshoots (artificial seeds). Mannitol and ABA (Absisic acid) increased the accumulation of dehydrins in cauliflower microshoots while cold acclimation did not have a significant impact on the accumulation of these proteins. Molybdenum treatments had a negative impact on dehydrin accumulation. Dehydrins have an important role in the drought tolerance of seeds and, therefore, the current research helps to improve the accumulation of these proteins in cauliflower artificial seeds. This in turns improves the quality of these artificial seeds. The current results suggest that dehydrins do not play an important role in cold tolerance of cauliflower artificial seeds. This study could have an important role in improving the understanding of the molecular mechanism of abiotic stress tolerance in plants. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Potato Annexin STANN1 Promotes Drought Tolerance and Mitigates Light Stress in Transgenic Solanum tuberosum L. Plants.

PubMed

Szalonek, Michal; Sierpien, Barbara; Rymaszewski, Wojciech; Gieczewska, Katarzyna; Garstka, Maciej; Lichocka, Malgorzata; Sass, Laszlo; Paul, Kenny; Vass, Imre; Vankova, Radomira; Dobrev, Peter; Szczesny, Pawel; Marczewski, Waldemar; Krusiewicz, Dominika; Strzelczyk-Zyta, Danuta; Hennig, Jacek; Konopka-Postupolska, Dorota

2015-01-01

Annexins are a family of calcium- and membrane-binding proteins that are important for plant tolerance to adverse environmental conditions. Annexins function to counteract oxidative stress, maintain cell redox homeostasis, and enhance drought tolerance. In the present study, an endogenous annexin, STANN1, was overexpressed to determine whether crop yields could be improved in potato (Solanum tuberosum L.) during drought. Nine potential potato annexins were identified and their expression characterized in response to drought treatment. STANN1 mRNA was constitutively expressed at a high level and drought treatment strongly increased transcription levels. Therefore, STANN1 was selected for overexpression analysis. Under drought conditions, transgenic potato plants ectopically expressing STANN1 were more tolerant to water deficit in the root zone, preserved more water in green tissues, maintained chloroplast functions, and had higher accumulation of chlorophyll b and xanthophylls (especially zeaxanthin) than wild type (WT). Drought-induced reductions in the maximum efficiency and the electron transport rate of photosystem II (PSII), as well as the quantum yield of photosynthesis, were less pronounced in transgenic plants overexpressing STANN1 than in the WT. This conferred more efficient non-photochemical energy dissipation in the outer antennae of PSII and probably more efficient protection of reaction centers against photooxidative damage in transgenic plants under drought conditions. Consequently, these plants were able to maintain effective photosynthesis during drought, which resulted in greater productivity than WT plants despite water scarcity. Although the mechanisms underlying this stress protection are not yet clear, annexin-mediated photoprotection is probably linked to protection against light-induced oxidative stress.

Potato Annexin STANN1 Promotes Drought Tolerance and Mitigates Light Stress in Transgenic Solanum tuberosum L. Plants

PubMed Central

Szalonek, Michal; Sierpien, Barbara; Rymaszewski, Wojciech; Gieczewska, Katarzyna; Garstka, Maciej; Lichocka, Malgorzata; Sass, Laszlo; Paul, Kenny; Vass, Imre; Vankova, Radomira; Dobrev, Peter; Szczesny, Pawel; Marczewski, Waldemar; Krusiewicz, Dominika; Strzelczyk-Zyta, Danuta; Hennig, Jacek; Konopka-Postupolska, Dorota

2015-01-01

Annexins are a family of calcium- and membrane-binding proteins that are important for plant tolerance to adverse environmental conditions. Annexins function to counteract oxidative stress, maintain cell redox homeostasis, and enhance drought tolerance. In the present study, an endogenous annexin, STANN1, was overexpressed to determine whether crop yields could be improved in potato (Solanum tuberosum L.) during drought. Nine potential potato annexins were identified and their expression characterized in response to drought treatment. STANN1 mRNA was constitutively expressed at a high level and drought treatment strongly increased transcription levels. Therefore, STANN1 was selected for overexpression analysis. Under drought conditions, transgenic potato plants ectopically expressing STANN1 were more tolerant to water deficit in the root zone, preserved more water in green tissues, maintained chloroplast functions, and had higher accumulation of chlorophyll b and xanthophylls (especially zeaxanthin) than wild type (WT). Drought-induced reductions in the maximum efficiency and the electron transport rate of photosystem II (PSII), as well as the quantum yield of photosynthesis, were less pronounced in transgenic plants overexpressing STANN1 than in the WT. This conferred more efficient non-photochemical energy dissipation in the outer antennae of PSII and probably more efficient protection of reaction centers against photooxidative damage in transgenic plants under drought conditions. Consequently, these plants were able to maintain effective photosynthesis during drought, which resulted in greater productivity than WT plants despite water scarcity. Although the mechanisms underlying this stress protection are not yet clear, annexin-mediated photoprotection is probably linked to protection against light-induced oxidative stress. PMID:26172952

Pupillography as a sensitive, noninvasive biomarker in healthy volunteers: first-in-man study of BAY 63-9044, a new 5-HT1A-receptor agonist with dopamine agonistic properties.

PubMed

Wensing, Georg; Haase, Claus; Brendel, Erich; Böttcher, Michael Friedrich

2007-12-01

BAY 63-9044 is a new full 5-HT(1A)-agonist with functional dopamine agonist properties aimed for the treatment of Parkinson's disease. This first-in-man study investigated the pharmacodynamics, safety and tolerability as well as the pharmacokinetics of BAY 63-9044 in a randomized, single-blind, placebo-controlled group-comparison dose escalation study. 45 healthy men received BAY 63-9044 as an oral solution in single doses of 0.25 mg, 0.5 mg, 1.2 mg, 2.5 mg and 5.0 mg. Pupil reaction (baseline pupil diameter (DIAM), constriction amplitude (CA)), body temperature, electroencephalography (EEG) and prolactin, cortisol and adrenocorticotrophic hormone (ACTH) served as pharmacodynamic measures and were monitored up to 24 h after drug intake. Safety, tolerability and plasma samples for determination of BAY 63-9044 were followed up to 72 h. Up to a dose of 2.5 mg, BAY 63-9044 was safe and well tolerated. Dose-limiting adverse events (nausea, vomiting, and dizziness) occurred in 5 out of 6 volunteers at the 5 mg dose. Adverse events resolved spontaneously in all but one volunteers who was treated with an antihistaminergic for vomiting. Dose-dependent changes of DIAM and CA were observed at doses higher than 0.5 mg and 1.2 mg, respectively. Body temperature showed a trend for reduction starting at C(max) in the highest two doses only. No clear effect was found on prolactin, cortisol and ACTH levels. The pharmacokinetics of BAY 63-9044 showed a dose-dependent increase with maximum plasma concentrations reached within 1 h. Plasma concentrations declined in a bi-phased manner with an apparent terminal half-life of 5.2-8.1 h. Up to the maximum tolerated dose (MTD) of 2.5 mg BAY 63-9044 was safe and well tolerated and showed predictable linear pharmacokinetics. Pupil reaction may serve as a non-invasive biomarker for pharmacodynamic effects of 5-HT(1A)-compounds with DIAM being the most sensitive parameter.

Level-tolerant duration selectivity in the auditory cortex of the velvety free-tailed bat Molossus molossus.

PubMed

Macías, Silvio; Hernández-Abad, Annette; Hechavarría, Julio C; Kössl, Manfred; Mora, Emanuel C

2015-05-01

It has been reported previously that in the inferior colliculus of the bat Molossus molossus, neuronal duration tuning is ambiguous because the tuning type of the neurons dramatically changes with the sound level. In the present study, duration tuning was examined in the auditory cortex of M. molossus to describe if it is as ambiguous as the collicular tuning. From a population of 174 cortical 104 (60 %) neurons did not show duration selectivity (all-pass). Around 5 % (9 units) responded preferentially to stimuli having longer durations showing long-pass duration response functions, 35 (20 %) responded to a narrow range of stimulus durations showing band-pass duration response functions, 24 (14 %) responded most strongly to short stimulus durations showing short-pass duration response functions and two neurons (1 %) responded best to two different stimulus durations showing a two-peaked duration-response function. The majority of neurons showing short- (16 out of 24) and band-pass (24 out 35) selectivity displayed "O-shaped" duration response areas. In contrast to the inferior colliculus, duration tuning in the auditory cortex of M. molossus appears level tolerant. That is, the type of duration selectivity and the stimulus duration eliciting the maximum response were unaffected by changing sound level.

Recommended energy and nutrients intakes in the European Union: 2008-2016

PubMed

García Gabarra, Antoni; Castellà Soley, Marta; Calleja Fernández, Alicia

2017-03-30

The aim of this document is to refl ect the changes happened in the European Union legislation and the opinions of the European Food Safety Authority in relation to the nutritional labeling on food, the reference values for energy, macronutrients and micronutrients, and the tolerable upper safe levels. The European legislation in force uses the labeling reference values established by the Scientific Committee on Food in 2003. There would be advisable an update of them from the reference values for vitamins and minerals established by the European Food Safety Authority. Equally, there would be good to include reference labeling values for polyunsaturated fatty acids, dietary fiber and choline, and specific reference labeling values for children from 6 to 36 months. For vitamins and minerals there would be desirable the revision of tolerable upper safe levels and the establishment of maximum amounts allowed in fortified food and food supplements in the European Union; its absence might represent a risk in some population groups for an excessive and unsafe intake of certain minerals and vitamins.

46 CFR 162.018-5 - Blow-down adjustment and popping tolerance.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Safety Relief Valves, Liquefied Compressed Gas § 162.018-5 Blow-down adjustment and popping tolerance. (a) Safety relief valves shall be so.... Safety relief valves shall be designed to open sharply and reach full lift and capacity at the maximum...

46 CFR 162.018-5 - Blow-down adjustment and popping tolerance.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Safety Relief Valves, Liquefied Compressed Gas § 162.018-5 Blow-down adjustment and popping tolerance. (a) Safety relief valves shall be so.... Safety relief valves shall be designed to open sharply and reach full lift and capacity at the maximum...

46 CFR 162.018-5 - Blow-down adjustment and popping tolerance.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Safety Relief Valves, Liquefied Compressed Gas § 162.018-5 Blow-down adjustment and popping tolerance. (a) Safety relief valves shall be so.... Safety relief valves shall be designed to open sharply and reach full lift and capacity at the maximum...

46 CFR 162.018-5 - Blow-down adjustment and popping tolerance.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Safety Relief Valves, Liquefied Compressed Gas § 162.018-5 Blow-down adjustment and popping tolerance. (a) Safety relief valves shall be so.... Safety relief valves shall be designed to open sharply and reach full lift and capacity at the maximum...

46 CFR 162.018-5 - Blow-down adjustment and popping tolerance.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Safety Relief Valves, Liquefied Compressed Gas § 162.018-5 Blow-down adjustment and popping tolerance. (a) Safety relief valves shall be so.... Safety relief valves shall be designed to open sharply and reach full lift and capacity at the maximum...

77 FR 66721 - Metconazole; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... information in support of this action. EPA has sufficient data to assess the hazards of and to make a... tolerance shows that there will be no increase in the maximum reasonably balanced dietary burden for beef cattle, swine, or poultry but a small increase for diary cattle. There is no increase for beef cattle...

76 FR 82152 - Cyhalofop-butyl; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... original long-term studies were approaching a maximum tolerated dose. In addition, there were no positive....regulations.gov , or, if only available in hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One..., identified by docket ID number EPA-HQ-OPP-2011-0283, by one of the following methods: Federal eRulemaking...

Isolation and expression profiling of GhNAC transcription factor genes in cotton (Gossypium hirsutum L.) during leaf senescence and in response to stresses.

PubMed

Shah, Syed Tariq; Pang, Chaoyou; Fan, Shuli; Song, Meizhen; Arain, Saima; Yu, Shuxun

2013-12-01

NAC (NAM, ATAF, and CUC) is a plant-specific transcription factor family with diverse roles in plant development and stress regulation. In this report, stress-responsive NAC genes (GhNAC8-GhNAC17) isolated from cotton (Gossypium hirsutum L.) were characterised in the context of leaf senescence and stress tolerance. The characterisation of NAC genes during leaf senescence has not yet been reported for cotton. Based on the sequence characterisation, these GhNACs could be classified into three groups belonging to three known NAC sub-families. Their predicted amino acid sequences exhibited similarities to NAC genes from other plant species. Senescent leaves were the sites of maximum expression for all GhNAC genes except GhNAC10 and GhNAC13, which showed maximum expression in fibres, collected from 25 days post anthesis (DPA) plants. The ten GhNAC genes displayed differential expression patterns and levels during natural and induced leaf senescence. Quantitative RT-PCR and promoter analyses suggest that these genes are induced by ABA, ethylene, drought, salinity, cold, heat, and other hormonal treatments. These results support a role for cotton GhNAC genes in transcriptional regulation of leaf senescence, stress tolerance and other developmental stages of cotton. © 2013.

The SRS-Viewer: A Software Tool for Displaying and Evaluation of Pyroshock Data

NASA Astrophysics Data System (ADS)

Eberl, Stefan

2014-06-01

For the evaluation of the success of a pyroshock, the time domain and the corresponding Shock-Response- Spectra (SRS) have to be considered. The SRS-Viewer is an IABG developed software tool [1] to read data in Universal File format (*.unv) and either display or plot for each accelerometer the time domain, corresponding SRS and the specified Reference-SRS with tolerances in the background.The software calculates the "Average (AVG)", "Maximum (MAX)" and "Minimum (MIN)" SRS of any selection of accelerometers. A statistical analysis calculates the percentages of measured SRS above the specified Reference-SRS level and the percentage within the tolerance bands for comparison with the specified success criteria.Overlay plots of single accelerometers of different test runs enable to monitor the repeatability of the shock input and the integrity of the specimen. Furthermore the difference between the shock on a mass-dummy and the real test unit can be examined.

Role of glycemic elements of Cynodon dactylon and Musa paradisiaca in diabetes management.

PubMed

Rai, Prashant Kumar; Jaiswal, Dolly; Rai, Nilesh K; Pandhija, Shiwani; Rai, A K; Watal, Geeta

2009-09-01

The study defined the scientific evaluation of glycemic elements of extracts of Cynodon dactylon and Musa paradisiaca. A dose of 500 mg/kg body weight (bw) of C. dactylon produced maximum falls of 23.2% and 22.8% in blood glucose levels of normoglycemic rats during studies of fasting blood glucose and glucose tolerance, respectively, whereas the same dose of M. paradisiaca produced a rise of 34.9% and 18.4%. In diabetic rats during glucose tolerance tests, a fall of 27.8% and a rise of 17.5% were observed with the same dose of C. dactylon and M. paradisiaca, respectively. Laser-induced breakdown spectroscopy used for detection of glycemic elements present in both the extracts indicated that C. dactylon was rich in magnesium (Mg), whereas M. paradisiaca was rich in potassium (K) and sodium (Na), comparatively, suggesting thereby the defined roles of these elements in diabetes management.

Evaluation of a hydrological model based on Bidirectional Reach (BReach)

NASA Astrophysics Data System (ADS)

Van Eerdenbrugh, Katrien; Van Hoey, Stijn; Verhoest, Niko E. C.

2016-04-01

Evaluation and discrimination of model structures is crucial to ensure an appropriate use of hydrological models. When evaluating model results by aggregating their quality in (a subset of) individual observations, overall results of this analysis sometimes conceal important detailed information about model structural deficiencies. Analyzing model results within their local (time) context can uncover this detailed information. In this research, a methodology called Bidirectional Reach (BReach) is proposed to evaluate and analyze results of a hydrological model by assessing the maximum left and right reach in each observation point that is used for model evaluation. These maximum reaches express the capability of the model to describe a subset of the evaluation data both in the direction of the previous (left) and of the following data (right). This capability is evaluated on two levels. First, on the level of individual observations, the combination of a parameter set and an observation is classified as non-acceptable if the deviation between the accompanying model result and the measurement exceeds observational uncertainty. Second, the behavior in a sequence of observations is evaluated by means of a tolerance degree. This tolerance degree expresses the condition for satisfactory model behavior in a data series and is defined by the percentage of observations within this series that can have non-acceptable model results. Based on both criteria, the maximum left and right reaches of a model in an observation represent the data points in the direction of the previous respectively the following observations beyond which none of the sampled parameter sets both are satisfactory and result in an acceptable deviation. After assessing these reaches for a variety of tolerance degrees, results can be plotted in a combined BReach plot that show temporal changes in the behavior of model results. The methodology is applied on a Probability Distributed Model (PDM) of the river Grote Nete upstream of Geel-Zammel with 1 106 randomly sampled parameter sets for three separate years. Acceptable model results must fit in the 95 % uncertainty bounds of observed discharges and tolerance degrees of 0 %, 5 %, 10 %, 20 % and 40 % are applied. An evaluation of BReach results with regard to other variables, such as the magnitude and the rate of change of the observed discharges enables to detect recurring patterns in model errors. This results in an augmented understanding of the model's structural deficiencies, revealing the incapability of the PDM model to simulate both high and low flow simulations with a single parameter set for this catchment. As the methodology can be applied for different hydrological model structures, it is a useful tool to gain understanding of the difference in behavior of competing models.

Evaluation of Saccharomyces cerevisiae GAS1 with respect to its involvement in tolerance to low pH and salt stress.

PubMed

Matsushika, Akinori; Suzuki, Toshihiro; Goshima, Tetsuya; Hoshino, Tamotsu

2017-08-01

We previously showed that overexpression of IoGAS1, which was isolated from the multiple stress-tolerant yeast Issatchenkia orientalis, endows Saccharomyces cerevisiae cells with the ability to grow and ferment under acidic and high-salt conditions. The deduced amino acid sequence of the IoGAS1 gene product exhibits 60% identity with the S. cerevisiae Gas1 protein, a glycosylphosphatidylinositol-anchored protein essential for maintaining cell wall integrity. However, the functional roles of ScGAS1 in stress tolerance and pH regulation remain unclear. In the present study, we characterized ScGAS1 regarding its roles in tolerance to low pH and high salt concentrations. Transcriptional analysis indicated that, as for the IoGAS1 gene, ScGAS1 expression was pH dependent, with maximum expression at pH 3.0; the presence of salt increased endogenous expression of both GAS1 genes at almost all pH levels. These results suggested that ScGAS1, like IoGAS1, is involved in a novel acid- and salt-stress adaptation mechanism in S. cerevisiae. Overexpression of ScGAS1 in S. cerevisiae improved growth and ethanol production from glucose under acid stress without added salt, although the stress tolerance of the ScGAS1-overexpressing strain was inferior to that of the IoGAS1-overexpressing strain. However, overexpression of ScGAS1 did not result in increased tolerance of S. cerevisiae to combined acid and salt stress, even though ScGAS1 appears to be a salt-responsive gene. Thus, ScGAS1 is directly implicated in tolerance to low pH but does not confer salinity tolerance, supporting the view that ScGAS1 and IoGAS1 have overlapping yet distinct roles in stress tolerance in yeast. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Lambda network having 2{sup m{minus}1} nodes in each of m stages with each node coupled to four other nodes for bidirectional routing of data packets between nodes

DOEpatents

Napolitano, L.M. Jr.

1995-11-28

The Lambda network is a single stage, packet-switched interprocessor communication network for a distributed memory, parallel processor computer. Its design arises from the desired network characteristics of minimizing mean and maximum packet transfer time, local routing, expandability, deadlock avoidance, and fault tolerance. The network is based on fixed degree nodes and has mean and maximum packet transfer distances where n is the number of processors. The routing method is detailed, as are methods for expandability, deadlock avoidance, and fault tolerance. 14 figs.

Cardiovascular responses of semi-arboreal snakes to chronic, intermittent hypergravity

NASA Technical Reports Server (NTRS)

Lillywhite, H. B.; Ballard, R. E.; Hargens, A. R.

1996-01-01

Cardiovascular functions were studied in semi-arboreal rat snakes (Elaphe obsoleta) following long-term, intermittent exposure to +1.5 Gz (head-to-tail acceleration) on a centrifuge. Snakes were held in a nearly straight position within horizontal plastic tubes during periods of centrifugation. Centrifugal acceleration, therefore, subjected snakes to a linear force gradient with the maximal force being experienced at the tail. Compared to non-centrifuged controls, Gz-acclimated snakes showed greater increases of heart rate during head-up tilt or acceleration, greater sensitivity of arterial pressure to circulating catecholamines, higher blood levels of corticosterone, and higher blood ratios of prostaglandin F 2 alpha/prostaglandin E2. Cardiovascular tolerance to increased gravity during graded Gz acceleration was measured as the maximum (caudal) acceleration force at which carotid arterial blood flow became null. When such tolerances were adjusted for effects of body size and other continuous variables incorporated into an analysis of covariance, the difference between the adjusted mean values of control and acclimated snakes (2.37 and 2.84 Gz, respectively) corresponded closely to the 0.5 G difference between the acclimation G (1.5) and Earth gravity (1.0). As in other vertebrates, cardiovascular tolerance to Gz stress tended to be increased by acclimation, short body length, high arterial pressure, and comparatively large blood volume. Voluntary body movements were important for promoting carotid blood flow at the higher levels of Gz stress.

The provision of clearances accuracy in piston - cylinder mating

NASA Astrophysics Data System (ADS)

Glukhov, V. I.; Shalay, V. V.

2017-08-01

The paper is aimed at increasing the quality of the pumping equipment in oil and gas industry. The main purpose of the study is to stabilize maximum values of productivity and durability of the pumping equipment based on the selective assembly of the cylinder-piston kinematic mating by optimization criterion. It is shown that the minimum clearance in the piston-cylinder mating is formed by maximum material dimensions. It is proved that maximum material dimensions are characterized by their own laws of distribution within the tolerance limits for the diameters of the cylinder internal mirror and the outer cylindrical surface of the piston. At that, their dispersion zones should be divided into size groups with a group tolerance equal to half the tolerance for the minimum clearance. The techniques for measuring the material dimensions - the smallest cylinder diameter and the largest piston diameter according to the envelope condition - are developed for sorting them into size groups. Reliable control of the dimensions precision ensures optimal minimum clearances of the piston-cylinder mating in all the size groups of the pumping equipment, necessary for increasing the equipment productivity and durability during the production, operation and repair processes.

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer

PubMed Central

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang

2016-01-01

Lessons Learned This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity. These findings provide clinicians with evidence for application of higher-dose icotinib. Background. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100–200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Methods. Twenty-six patients with advanced NSCLC were treated at doses of 250–625 mg three times daily The EGFR mutation test was not mandatory in this study. Results. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (Tmax) ranged from 1 to 3 hours (1.5–4 hours) after multiple doses. The t1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. Conclusion. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. PMID:27789778

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

PubMed

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

2016-11-01

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Postprandial glucose response to selected tropical fruits in normal glucose-tolerant Nigerians.

PubMed

Edo, A; Eregie, A; Adediran, O; Ohwovoriole, A; Ebengho, S

2011-01-01

The glycemic response to commonly eaten fruits in Nigeria has not been reported. Therefore, this study assessed the plasma glucose response to selected fruits in Nigeria. Ten normal glucose-tolerant subjects randomly consumed 50 g carbohydrate portions of three fruits: banana (Musa paradisiaca), pineapple (Ananus comosus), and pawpaw (Carica papaya), and a 50-g glucose load at 1-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2-h period post-ingestion of the fruits or glucose. The samples were analyzed for plasma glucose concentrations. Plasma glucose responses were assessed by the peak plasma glucose concentration, maximum increase in plasma glucose, 2-h postprandial plasma glucose level, and incremental area under the glucose curve and glycemic index (GI). The results showed that the blood glucose response to these three fruits was similar in terms of their incremental areas under the glucose curve, maximum increase in plasma glucose, and glycemic indices (GIs). The 2-h postprandial plasma glucose level of banana was significantly higher than that of pineapple, P < 0.025. The mean ± SEM GI values were as follows: pawpaw; 86 ± 26.8%; banana, 75.1 ± 21.8%; pineapple, 64.5 ± 11.3%. The GI of glucose is taken as 100. The GI of pineapple was significantly lower than that of glucose (P < 0.05). Banana, pawpaw, and pineapple produced a similar postprandial glucose response. Measured portions of these fruits may be used as fruit exchanges with pineapple having the most favorable glycemic response.

[Comfort and noise level in infants with helmet interface].

PubMed

Medina, A; Alvarez Fernández, P; Rey Galán, C; Álvarez Mendiola, P; Álvarez Blanco, S; Vivanco Allende, A

2015-10-01

To evaluate comfort and noise intensity using the COMFORT scale in infants who receive respiratory support with a helmet interface. An observational descriptive study was conducted on all infants (1 to 12 months of age) admitted to a PICU from November 1st 2013 to March 31st 2014 and who received non-invasive ventilation with a helmet interface. Tolerance to the interface was assessed by use of the COMFORT scale. The intensity of the noise to which the infants were exposed was measured with a TES1350A HIBOK 412 sound-level meter. Three measurements were made every day. Twenty seven patients with bronchiolitis (median age: 54 days; range: 10 to 256) were included. Median COMFORT score in the first day was 21 points (14 - 28). An increase in patient comfort was found with a gradual decrease in the scores, with a maximum reduction of 22% from the first hours (score of 22) to the fifth day (score of 18). The minimum sound intensity registered was 42dB, and the maximum was 78dB. Background noise intensity was associated with noise intensity in the helmet. No differences were observed in COMFORT score and noise intensity between ventilator devices. Helmet interface was well tolerated by infants. COMFORT score results are an indicator that infants were comfortable or very comfortable. The measured noise intensity was in the safe range permitted by World Health Organization. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

A 2D ion chamber array audit of wedged and asymmetric fields in an inhomogeneous lung phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lye, Jessica; Dunn, Leon, E-mail: leon.dunn@arpansa.gov.au; Alves, Andrew

Purpose: The Australian Clinical Dosimetry Service (ACDS) has implemented a new method of a nonreference condition Level II type dosimetric audit of radiotherapy services to increase measurement accuracy and patient safety within Australia. The aim of this work is to describe the methodology, tolerances, and outcomes from the new audit. Methods: The ACDS Level II audit measures the dose delivered in 2D planes using an ionization chamber based array positioned at multiple depths. Measurements are made in rectilinear homogeneous and inhomogeneous phantoms composed of slabs of solid water and lung. Computer generated computed tomography data sets of the rectilinear phantomsmore » are supplied to the facility prior to audit for planning of a range of cases including reference fields, asymmetric fields, and wedged fields. The audit assesses 3D planning with 6 MV photons with a static (zero degree) gantry. Scoring is performed using local dose differences between the planned and measured dose within 80% of the field width. The overall audit result is determined by the maximum dose difference over all scoring points, cases, and planes. Pass (Optimal Level) is defined as maximum dose difference ≤3.3%, Pass (Action Level) is ≤5.0%, and Fail (Out of Tolerance) is >5.0%. Results: At close of 2013, the ACDS had performed 24 Level II audits. 63% of the audits passed, 33% failed, and the remaining audit was not assessable. Of the 15 audits that passed, 3 were at Pass (Action Level). The high fail rate is largely due to a systemic issue with modeling asymmetric 60° wedges which caused a delivered overdose of 5%–8%. Conclusions: The ACDS has implemented a nonreference condition Level II type audit, based on ion chamber 2D array measurements in an inhomogeneous slab phantom. The powerful diagnostic ability of this audit has allowed the ACDS to rigorously test the treatment planning systems implemented in Australian radiotherapy facilities. Recommendations from audits have led to facilities modifying clinical practice and changing planning protocols.« less

Can chilling tolerance of C4 photosynthesis in Miscanthus be transferred to sugarcane?

USDA-ARS?s Scientific Manuscript database

The goal of this study was to investigate if chilling tolerance of C4 photosynthesis in Miscanthus can be transferred to sugarcane. Net leaf CO2 uptake (Asat) and the maximum operating efficiency of photosystem II ('PSII) were measured in warm conditions (25 °C/20 °C), and then during and following ...

A Dose Escalation and Pharmacodynamic Study of Triapine and Radiation in Patients With Locally Advanced Pancreas Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Ludmila Katherine; Grecula, John; Jia, Guang

2012-11-15

Purpose: Triapine, a novel inhibitor of the M2 subunit of ribonucleotide reductase (RR), is a potent radiosensitizer. This phase 1 study, sponsored by the National Cancer Institute Cancer Therapy Evaluation Program, assessed the safety and tolerability of triapine in combination with radiation (RT) in patients with locally advanced pancreas cancer (LAPCA). Methods and Materials: We evaluated 3 dosage levels of triapine (24 mg/m{sup 2}, 48 mg/m{sup 2}, 72 mg/m{sup 2}) administered with 50.4 Gy of RT in 28 fractions. Patients with LAPCA received triapine thrice weekly, every other week during the course of RT. Dose-limiting toxicity (DLT) was assessed duringmore » RT and for 4 weeks after its completion. Dynamic contrast-enhanced magnetic resonance imaging and serum RR levels were evaluated as potential predictors for early response. Results: Twelve patients were treated. Four patients (1 nonevaluable) were enrolled at dosage level 1 (DL1), 3 patients at DL2, and 5 patients (2 nonevaluable) at DL3. No DLTs were observed, and the maximum tolerated dose was not reached. Two patients (17%) achieved partial response, and 6 patients (50%) had stable disease. One patient underwent R0 resection after therapy. Ninety-two percent of patients (100% at DL3) experienced freedom from local tumor progression. In 75% of patients who eventually experienced progression, metastases developed without local progression. RR levels did not seem to predict outcome. In 4 patients with available data, dynamic contrast-enhanced magnetic resonance imaging may predict early response or resistance to therapy. Conclusion: The combination of triapine at 72 mg/m{sup 2} 3 times weekly every other week and standard RT is tolerable with interesting activity in patients with LAPCA.« less

Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: A phase I study.

PubMed

Kato, Ken; Ura, Takashi; Koizumi, Wasaburo; Iwasa, Satoru; Katada, Chikatoshi; Azuma, Mizutomo; Ishikura, Satoshi; Nakao, Yoshinori; Onuma, Hiroshi; Muro, Kei

2018-03-01

Nimotuzumab is a humanized anti-epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 on days 1-4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose-limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum-tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment-related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression-free survival was 13.9 months. One- and 3-year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study.

PubMed

Schulz, Craig A; Mehta, Minesh P; Badie, Benham; McGinn, Cornelius J; Robins, H Ian; Hayes, Lori; Chappell, Rick; Volkman, Jen; Binger, Kim; Arzoomanian, Rhoda; Simon, Kris; Alberti, Dona; Feierabend, Christine; Tutsch, Kendra D; Kunugi, Keith A; Wilding, George; Kinsella, Timothy J

2004-07-15

To investigate the maximal tolerated dose of a continuous 28-day iododeoxyuridine (IUdr) infusion combined with hyperfractionated accelerated radiotherapy (HART); to analyze the percentage of IUdr-thymidine replacement in peripheral granulocytes as a surrogate marker for IUdr incorporation into tumor cells; to measure the steady-state serum IUdr levels; and to assess the feasibility of continuous IUdr infusion and HART in the management of malignant glioma. Patients were required to have biopsy-proven malignant glioma. Patients received 100 (n = 4), 200 (n = 3), 300 (n = 3), 400 (n = 6), 500 (n = 4), 625 (n = 5), or 781 (n = 6) mg/m(2)/d of IUdr by continuous infusion for 28 days. HART was started 7 days after IUdr initiation. The total dose was 70 Gy (1.2 Gy b.i.d. for 25 days with a 10-Gy boost [2.0 Gy for 5 Saturdays]). Weekly assays were performed to determine the percentage of IUdr-DNA replacement in granulocytes and serum IUdr levels using standard high performance liquid chromatography methods. Standard Phase I toxicity methods were used. Between June 1994 and August 1999, 31 patients were enrolled. No patient had Grade 3 or worse HART toxicity. Grade 3 or greater IUdr toxicity predominantly included neutropenia (n = 3), thrombocytopenia (n = 3), and elevated liver function studies (n = 3). The maximal tolerated dose was 625 mg/m(2)/d. Thymidine replacement in the peripheral granulocytes peaked at 3 weeks and increased with the dose (maximal thymidine replacement 4.9%). The steady-state plasma IUdr level increased with the dose (maximum, 1.5 microM). In our study, continuous long-term IUdr i.v. infusion had a maximal tolerated dose of 625 mg/m(2)/d. Granulocyte incorporation data verified the concept that prolonged IUdr infusion results in IUdr-DNA replacement that corresponds to a high degree of cell labeling. IUdr steady-state plasma levels increased with increasing dose and attained levels needed for clinical radiosensitization. Continuous IUdr infusion and HART were both feasible and well tolerated.

Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer.

PubMed

Fidias, Panos; Pennell, Nathan A; Boral, Anthony L; Shapiro, Geoffrey I; Skarin, Arthur T; Eder, Joseph P; Kwoh, T Jesse; Geary, Richard S; Johnson, Bruce E; Lynch, Thomas J; Supko, Jeffrey G

2009-09-01

A phase I trial was performed to evaluate the administration of carboplatin/paclitaxel in combination with ISIS-5132, a phosphorothioate antisense oligodeoxynucleotide inhibitor of c-raf-1 kinase expression, in patients with advanced non-small cell lung cancer (NSCLC). Previously untreated patients with stage IIIB/IV NSCLC received ISIS 5132 by continuous intravenous infusion at 2.0 mg/kg/d for 14 days. Starting doses were paclitaxel 175 mg/m(2) and carboplatin targeting an area under the free platinum plasma concentration-time curve (AUC(fp)) of 5 mg . min/ml (dose level 1). The carboplatin dose was then increased to AUC(fp) 6 mg . min/ml (dose level 2) after which the paclitaxel dose was increased to 200 mg/m(2) (dose level 3). The maximum tolerated dose was established by toxicity during the first two 21-day cycles of therapy. The pharmacokinetics of all three agents was determined before and during the ISIS 5132 infusion. Thirteen patients were treated with the carboplatin/paclitaxel/ISIS 5132 combination. Dose-limiting neutropenia occurred in two patients at dose level 3. Grade 3 and 4 nonhematologic toxicities were infrequent and limited to nausea and constipation. The maximum tolerated doses were carboplatin AUC(fp) 6 mg . min/ml, paclitaxel 175 mg/m(2), and ISIS 5132 2.0 mg/kg/d for 14 days. There were no objective responses and the concurrent infusion of ISIS 5132 did not alter the plasma pharmacokinetics of paclitaxel or total platinum. ISIS 5132 can be safely combined with standard doses of carboplatin and paclitaxel. Combining cytotoxic chemotherapeutic agents with inhibitors of aberrant signal transduction mediated by Raf proteins produced no objective responses in the dose and schedule administered in this study.

Ethanol Production and Maximum Cell Growth Are Highly Correlated with Membrane Lipid Composition during Fermentation as Determined by Lipidomic Analysis of 22 Saccharomyces cerevisiae Strains

PubMed Central

Henderson, Clark M.; Lozada-Contreras, Michelle; Jiranek, Vladimir; Longo, Marjorie L.

2013-01-01

Optimizing ethanol yield during fermentation is important for efficient production of fuel alcohol, as well as wine and other alcoholic beverages. However, increasing ethanol concentrations during fermentation can create problems that result in arrested or sluggish sugar-to-ethanol conversion. The fundamental cellular basis for these problem fermentations, however, is not well understood. Small-scale fermentations were performed in a synthetic grape must using 22 industrial Saccharomyces cerevisiae strains (primarily wine strains) with various degrees of ethanol tolerance to assess the correlation between lipid composition and fermentation kinetic parameters. Lipids were extracted at several fermentation time points representing different growth phases of the yeast to quantitatively analyze phospholipids and ergosterol utilizing atmospheric pressure ionization-mass spectrometry methods. Lipid profiling of individual fermentations indicated that yeast lipid class profiles do not shift dramatically in composition over the course of fermentation. Multivariate statistical analysis of the data was performed using partial least-squares linear regression modeling to correlate lipid composition data with fermentation kinetic data. The results indicate a strong correlation (R2 = 0.91) between the overall lipid composition and the final ethanol concentration (wt/wt), an indicator of strain ethanol tolerance. One potential component of ethanol tolerance, the maximum yeast cell concentration, was also found to be a strong function of lipid composition (R2 = 0.97). Specifically, strains unable to complete fermentation were associated with high phosphatidylinositol levels early in fermentation. Yeast strains that achieved the highest cell densities and ethanol concentrations were positively correlated with phosphatidylcholine species similar to those known to decrease the perturbing effects of ethanol in model membrane systems. PMID:23064336

Ethanol production and maximum cell growth are highly correlated with membrane lipid composition during fermentation as determined by lipidomic analysis of 22 Saccharomyces cerevisiae strains.

PubMed

Henderson, Clark M; Lozada-Contreras, Michelle; Jiranek, Vladimir; Longo, Marjorie L; Block, David E

2013-01-01

Optimizing ethanol yield during fermentation is important for efficient production of fuel alcohol, as well as wine and other alcoholic beverages. However, increasing ethanol concentrations during fermentation can create problems that result in arrested or sluggish sugar-to-ethanol conversion. The fundamental cellular basis for these problem fermentations, however, is not well understood. Small-scale fermentations were performed in a synthetic grape must using 22 industrial Saccharomyces cerevisiae strains (primarily wine strains) with various degrees of ethanol tolerance to assess the correlation between lipid composition and fermentation kinetic parameters. Lipids were extracted at several fermentation time points representing different growth phases of the yeast to quantitatively analyze phospholipids and ergosterol utilizing atmospheric pressure ionization-mass spectrometry methods. Lipid profiling of individual fermentations indicated that yeast lipid class profiles do not shift dramatically in composition over the course of fermentation. Multivariate statistical analysis of the data was performed using partial least-squares linear regression modeling to correlate lipid composition data with fermentation kinetic data. The results indicate a strong correlation (R(2) = 0.91) between the overall lipid composition and the final ethanol concentration (wt/wt), an indicator of strain ethanol tolerance. One potential component of ethanol tolerance, the maximum yeast cell concentration, was also found to be a strong function of lipid composition (R(2) = 0.97). Specifically, strains unable to complete fermentation were associated with high phosphatidylinositol levels early in fermentation. Yeast strains that achieved the highest cell densities and ethanol concentrations were positively correlated with phosphatidylcholine species similar to those known to decrease the perturbing effects of ethanol in model membrane systems.

A phase I trial of bortezomib and interferon-α-2b in metastatic melanoma.

PubMed

Markowitz, Joseph; Luedke, Eric A; Grignol, Valerie P; Hade, Erinn M; Paul, Bonnie K; Mundy-Bosse, Bethany L; Brooks, Taylor R; Dao, Thao-Vi; Kondalasula, Sri V; Lesinski, Gregory B; Olencki, Thomas; Kendra, Kari L; Carson, William E

2014-01-01

The possibility that cytokine administration could enhance the antitumor effects of proteasome inhibition was explored. It was found that coadministration of bortezomib and interferon-α (IFN-α) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. A phase I study was conducted to determine the tolerability and the maximum tolerated dose of bortezomib when administered in combination with IFN-α-2b to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-α subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-α thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-α. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men; median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3), and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1). The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a partial response, and 7 had stable disease. Progression-free survival was 2.5 months, and overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-α to induce phosphorylation of STAT1 in circulating immune cells; however, it did lead to reduced plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-α can be safely administered to melanoma patients.

Temperature tolerance of young-of-the-year cisco, Coregonus artedii

USGS Publications Warehouse

Edsall, Thomas A.; Colby, Peter J.

1970-01-01

Young-of-the-year ciscoes (Coregonus artedii) acclimated to 2, 5, 10, 20 and 25 C and tested for tolerance to high and low temperatures provide the first detailed description of the thermal tolerance of coregonids in North America. The upper ultimate lethal temperature of the young ciscoes was 26 C (6 C higher than the maximum sustained temperature tolerated by adult ciscoes in nature) and the ultimate lower lethal temperature approached 0 C (near that commonly tolerated in nature by adult ciscoes). The temperature of 26 C is slightly higher than the lowest ultimate upper lethal temperature recorded for North American freshwater fishes; however, published information on the depth distributions of fishes in the Great Lakes suggests that some of the other coregonids may be less tolerant of high temperatures than the cisco.

Trace Metal Levels in Rainbow Trout (Oncorhynchus mykiss) Cultured in Net Cages in a Reservoir and Evaluation of Human Health Risks from Consumption.

PubMed

Varol, Memet; Kaya, Gülderen Kurt; Alp, Sumru Anık; Sünbül, Muhammet Raşit

2017-09-19

Although fish consumption has positive health effects, metals accumulated in fish can cause human health risks. In this study, the levels of ten metals in rainbow trout (Oncorhynchus mykiss) farmed in the Keban Dam Reservoir, which has the biggest rainbow trout production capacity in Turkey, were determined and compared with the maximum permissible levels (MPLs). Also, human health risks associated with rainbow trout consumption were assessed. The metal concentrations in rainbow trout were found below the MPLs. The estimated daily intake of each metal was much lower than the respective tolerable daily intake. The target hazard quotient (THQ) for individual metal and total THQ for combined metals did not exceed 1, indicating no health risk for consumers. The cancer risk (CR) value for inorganic arsenic was within the acceptable lifetime risk range of 10 -6 and 10 -4 . For carcinogenic and non-carcinogenic effects, the maximum allowable fish consumption rates were high enough to ensure the human health. According to these results, the consumption of rainbow trout farmed in the Keban Dam Reservoir does not pose a risk on human health.

Interspecific variation in thermoregulation among three sympatric bats inhabiting a hot, semi-arid environment.

PubMed

Cory Toussaint, Dawn; McKechnie, Andrew E

2012-12-01

Bats in hot roosts experience some of the most thermally challenging environments of any endotherms, but little is known about how heat tolerance and evaporative cooling capacity vary among species. We investigated thermoregulation in three sympatric species (Nycteris thebaica, Taphozous mauritianus and Sauromys petrophilus) in a hot, semi-arid environment by measuring body temperature (T(b)), metabolic rate and evaporative water loss (EWL) at air temperatures (T(a)) of 10-42 °C. S. petrophilus was highly heterothermic with no clear thermoneutral zone, and exhibited rapid increases in EWL at high T(a) to a maximum of 23.7 ± 7.4 mg g⁻¹ h⁻¹ at T(a) ≈ 42 °C, with a concomitant maximum T(b) of 43.7 ± 1.0 °C. T. mauritianus remained largely normothermic at T(a)s below thermoneutrality and increased EWL to 14.7 ± 1.3 mg g⁻¹ h⁻¹ at T(a) ≈ 42 °C, with a maximum T(b) of 42.9 ± 1.6 °C. In N. thebaica, EWL began increasing at lower T (a) than in either of the other species and reached a maximum of 18.6 ± 2.1 mg g⁻¹ h⁻¹ at T(a) = 39.4 °C, with comparatively high maximum T(b) values of 45.0 ± 0.9 °C. Under the conditions of our study, N. thebaica was considerably less heat tolerant than the other two species. Among seven species of bats for which data on T(b) as well as roost temperatures in comparison to outside T(a) are available, we found limited evidence for a correlation between overall heat tolerance and the extent to which roosts are buffered from high T(a).

Identification of two metallothionein genes and their roles in stress responses of Musca domestica toward hyperthermy and cadmium tolerance.

PubMed

Tang, Ting; Huang, Da-wei; Zhang, Di; Wu, Yin-jian; Murphy, Robert W; Liu, Feng-song

2011-10-01

Stress proteins such as metallothioneins (MTs) play a key role in cellular protection against environmental stressors. In nature, insects such as houseflies (Musca domestica) are commonly exposed to multiple stressors including heavy metals (e.g. Cadmium, Cd) and high temperatures. In this paper, we identify two novel MT genes from the cDNAs of M. domestica, MdMT1 and MdMT2, which putatively encode 40 and 42 amino acid residues respectively. Expression of the two MTs' mRNAs, which are examined in the fat body, gut, hemocyte, and the epidermis. From our study, we saw that the expression of MdMT1 and MdMT2 are enhanced by Cd and thermal stress. Levels of expression are highest at 10 mM Cd(2+) within a 24-h period, and expressions increase significantly with exposure to 10 mM Cd for 12h. Levels of the mRNAs are up-regulated after heat shock and that of MdMT2 reaches its maximum peak faster than MdMT1. Both of the MT genes might be involved in a transient systemic tolerance response to stressors and they may play important roles in heavy metal and high temperature tolerance in the housefly. To detect whether or not the MTs bind heavy metals, the target genes are cloned into the prokaryotic expression vector pET-DsbA to obtain fusion protein expressed in Escherichia coli BL21 (DE3). Recombinant DsbA-MdMT1 significantly increases tolerance of the host bacteria to Cd(2+), but DsbA-MdMT2 is absent. These differential characteristics will facilitate future investigations into the physiological functions of MTs. Copyright © 2011 Elsevier Inc. All rights reserved.

C-reactive protein and cold-pressor tolerance in the general population: the Tromsø Study.

PubMed

Schistad, Elina Iordanova; Stubhaug, Audun; Furberg, Anne-Sofie; Engdahl, Bo Lars; Nielsen, Christopher Sivert

2017-07-01

The aim of this study was to examine whether increases in severity of subclinical inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased experimental pain sensitivity, measured by cold-pressor tolerance, and to test whether this relationship is independent of chronic pain. A large population-based study from 2007 to 2008, the sixth Tromsø Study, provided data from 12,981 participants. For the present analysis, complete data for 10,274 participants (age: median 58 years) were available. The main outcome measure was cold-pressor tolerance, tested by placing the dominant hand in circulating cold water (3°C) for a maximum of 106 seconds. Cox proportional hazard models, treating hand withdrawal during the cold-pressor test as the event and enduring the full test time as censored data, were used to investigate the relationship between hs-CRP levels (≤3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model was controlled for age, sex, education, body mass index, smoking status, alcohol consumption, emotional distress, statin usage, and self-reported presence of chronic pain. Additional analysis was performed in participants without chronic pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance (hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001), adjusted for age and sex. This relationship remained essentially unaltered after controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001), as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001). The present data show that subclinical inflammation is related to increased pain sensitivity, suggesting a potential role of inflammation in experimental pain which may be of importance for the development of clinical pain.

23 CFR 658.17 - Weight.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... derived from the Bridge Formula, up to a maximum of 80,000 pounds, including all enforcement tolerances...

23 CFR 658.17 - Weight.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the bridge formula. (c) The maximum gross weight upon any one axle, including any one axle of a group... following formula, referred to as the Bridge Gross Weight Formula: EC14OC91.012 except that two consecutive... derived from the Bridge Formula, up to a maximum of 80,000 pounds, including all enforcement tolerances...

Effects of Fuel Composition on EGR Dilution Tolerance in Spark Ignited Engines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szybist, James P

2016-01-01

Fuel-specific differences in exhaust gas recirculation (EGR) dilution tolerance are studied in a modern, direct-injection single-cylinder research engine. A total of 6 model fuel blends are examined at a constant research octane number (RON) of 95 using n-heptane, iso-octane, toluene, and ethanol. Laminar flame speeds for these mixtures, which were calculated two different methods (an energy fraction mixing rule and a detailed kinetic simulation), spanned a range of about 6 cm/s. A constant fueling nominal load of 350 kPa IMEPg at 2000 rpm was operated with varying CA50 from 8-20 CAD aTDCf, and with EGR increasing until a COV ofmore » IMEP of 5% is reached. The results illustrate that flame speed affects EGR dilution tolerance; fuels with increased flame speeds increase EGR tolerance. Specifically, flame speed correlates most closely to the initial flame kernel growth, measured as the time of ignition to 5% mass fraction burned. The effect of the latent heat of vaporization on the flame speed is taken into account for the ethanol-containing fuels. At a 30 vol% blend level, the increased enthalpy of vaporization of ethanol compared to conventional hydrocarbons can decrease the temperature at the time of ignition by a maximum of 15 C, which can account for up to a 3.5 cm/s decrease in flame speed. The ethanol-containing fuels, however, still exhibit a flame speed advantage, and a dilution tolerance advantage over the slower flame-speed fuels. The fuel-specific differences in dilution tolerance are significant at the condition examined, allowing for a 50% relative increase in EGR (4% absolute difference in EGR) at a constant COV of IMEP of 3%.« less

On the monitoring and implications of growing damages caused by manufacturing defects in composite structures

NASA Astrophysics Data System (ADS)

Schagerl, M.; Viechtbauer, C.; Hörrmann, S.

2015-07-01

Damage tolerance is a classical safety concept for the design of aircraft structures. Basically, this approach considers possible damages in the structure, predicts the damage growth under applied loading conditions and predicts the following decrease of the structural strength. As a fundamental result the damage tolerance approach yields the maximum inspection interval, which is the time a damage grows from a detectable to a critical level. The above formulation of the damage tolerance safety concept targets on metallic structures where the damage is typically a simple fatigue crack. Fiber-reinforced polymers show a much more complex damage behavior, such as delaminationsin laminated composites. Moreover, progressive damage in composites is often initiated by manufacturing defects. The complex manufacturing processes for composite structures almost certainly yield parts with defects, e.g. pores in the matrix or undulations of fibers. From such defects growing damages may start after a certain time of operation. The demand to simplify or even avoid the inspection of composite structures has therefore led to a comeback of the traditional safe-life safety concept. The aim of the so-called safe-life flaw tolerance concept is a structure that is capable of carrying the static loads during operation, despite significant damages and after a representative fatigue load spectrum. A structure with this property does not need to be inspected, respectively monitored at all during its service life. However, its load carrying capability is thereby not fully utilized. This article presents the possible refinement of the state-of-the-art safe-life flaw tolerance concept for composite structures towards a damage tolerance approach considering also the influence of manufacturing defects on damage initiation and growth. Based on fundamental physical relations and experimental observations the challenges when developing damage growth and residual strength curves are discussed.

Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

PubMed Central

Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

2012-01-01

Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization. PMID:22915658

Pilot-scale verification of maximum tolerable hydrodynamic stress for mammalian cell culture.

PubMed

Neunstoecklin, Benjamin; Villiger, Thomas K; Lucas, Eric; Stettler, Matthieu; Broly, Hervé; Morbidelli, Massimo; Soos, Miroslav

2016-04-01

Although several scaling bioreactor models of mammalian cell cultures are suggested and described in the literature, they mostly lack a significant validation at pilot or manufacturing scale. The aim of this study is to validate an oscillating hydrodynamic stress loop system developed earlier by our group for the evaluation of the maximum operating range for stirring, based on a maximum tolerable hydrodynamic stress. A 300-L pilot-scale bioreactor for cultivation of a Sp2/0 cell line was used for this purpose. Prior to cultivations, a stress-sensitive particulate system was applied to determine the stress values generated by stirring and sparging. Pilot-scale data, collected from 7- to 28-Pa maximum stress conditions, were compared with data from classical 3-L cultivations and cultivations from the oscillating stress loop system. Results for the growth behavior, analyzed metabolites, productivity, and product quality showed a dependency on the different environmental stress conditions but not on reactor size. Pilot-scale conditions were very similar to those generated in the oscillating stress loop model confirming its predictive capability, including conditions at the edge of failure.

Phase I Study of Oral S-1 Plus Cisplatin With Concurrent Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaira, Kyoichi; Sunaga, Noriaki; Yanagitani, Noriko

Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m{sup -2}/day{sup -1}]/cisplatin [mg/m{sup -2}/day{sup -1}]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to amore » total dose of 60 Gy. Results: Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed {>=}Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients. Conclusions: The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.« less

Water activity and the challenge for life on early Mars.

PubMed

Tosca, Nicholas J; Knoll, Andrew H; McLennan, Scott M

2008-05-30

In situ and orbital exploration of the martian surface has shown that acidic, saline liquid water was intermittently available on ancient Mars. The habitability of these waters depends critically on water activity (aH2O), a thermodynamic measure of salinity, which, for terrestrial organisms, has sharply defined limits. Using constraints on fluid chemistry and saline mineralogy based on martian data, we calculated the maximum aH2O for Meridiani Planum and other environments where salts precipitated from martian brines. Our calculations indicate that the salinity of well-documented surface waters often exceeded levels tolerated by known terrestrial organisms.

Estimated exposure to zearalenone, ochratoxin A and aflatoxin B1 through the consume of bakery products and pasta considering effects of food processing.

PubMed

Bol, Emilli Keller; Araujo, Letícia; Veras, Flávio Fonseca; Welke, Juliane Elisa

2016-03-01

The objective of this research was to estimate the processing effect on mycotoxins levels and the exposure to zearalenone (ZEA), ochratoxin (OTA) and aflatoxin B1 (AFB1) through the consumption of pasta and bakery products. The higher reduction percentage of mycotoxins was observed in cake production (95, 90 and 70% for ZEA, OTA and AFB1, respectively). Bread and biscuit showed similar reduction in mycotoxins levels (89 and 90% for ZEA; 80 and 85% for OTA; 36 and 40% for AFB1, respectively). The lower reduction in the levels of mycotoxins has been observed for pasta (75, 65 and 10% for ZEA, OTA and AFB1, respectively). The consumption of these products could represent 12.6% of the maximum tolerable daily intake of ZEA and 30.5% of the tolerable weekly intake of OTA. The margin of exposure value related to the exposure to AFB1 was 24.6. The exposure to ZEA and OTA through the consumption of bakery products and pasta would not represent risk for consumer health, (although conjugated forms were not determined). However, the exposure to AFB1 represents a risk (even without considering the AFB1-conjugated forms). Copyright © 2016 Elsevier Ltd. All rights reserved.

Alterations in heat loss and heat production mechanisms in rat exposed to hypergravic fields

NASA Technical Reports Server (NTRS)

Horowitz, J. M.; Horwitz, B. A.; Oyama, J.

1982-01-01

A review of studies investigating the thermal response of rats exposed to hypergravic fields well below maximum tolerance levels is presented. It is concluded that several lines of evidence indicate that the neural switching network for temperature regulation and cardiovascular channeling of blood flow is transiently affected during the first hour a rat is exposed to hypergravity. Moreover, even after one hour of exposure, when the core temperature has fallen several degrees, shivering and nonshivering thermogenesis are not fully activated. Only after prolonged exposure to hypergravic fields do heat production mechanisms recover sufficiently to bring the core temperature back to a normal level. Thus, the data indicate a more rapid recovery of effector mechanisms for heat loss than for heat production.

Effect of Cinnamon Tea on Postprandial Glucose Concentration.

PubMed

Bernardo, Maria Alexandra; Silva, Maria Leonor; Santos, Elisabeth; Moncada, Margarida Maria; Brito, José; Proença, Luis; Singh, Jaipaul; de Mesquita, Maria Fernanda

2015-01-01

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p < 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained from C. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period.

Arsenic processing of yeast isolates IIB-As1 & IIB-As2 and production of glutathione under stress conditions.

PubMed

Muneer, Bushra; Lali, Tayyaba; Iqbal, Muhammad J; Shakoori, Farah R; Shakoori, Abdul R

2016-10-01

Four arsenic resistant yeast were isolated from the industrial wastewater. Two strains IIB-As1 and IIB-As2 identified as Candida tropicalis and Saccharomyces cerevisiae, respectively. IIB-As1 and IIB-As2 showed maximum arsenic resistance. IIB-As1 showed maximum growth at 35 °C whereas it was 30 °C for IIB-As2. The yeast isolate showed typical growth curves, but arsenic extended the lag phase. Glutathione plays an important role in metal tolerance. In the present study, As increased the level glutathione and non-protein thiols in yeast isolates. Removal of As from supernatant was analyzed using the atomic absorption spectrophotometer. They removed arsenic from the medium after 72 h of incubation. Both yeast strains efficiently removed arsenic from the industrial effluent when used individually or in consortia. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Response of an algal consortium to diesel under varying culture conditions.

PubMed

Chavan, Anal; Mukherji, Suparna

2010-03-01

A diesel-tolerant sessile freshwater algal consortium obtained from the vicinity of Powai Lake (Mumbai, India) was cultured in the laboratory. The presence of diesel in batch cultures enhanced the maximum specific growth rate of the algal consortium. With decrease in light-dark (L:D) cycle from 20:4 to 4:20 h, the chlorophyll-a levels decreased; however, the removal of diesel was found to be maximum at L:D of 18:6 h with 37.6% degradation over and above controls. In addition to growth in the form of green clumps, white floating biomass was found surrounding the diesel droplets on the surface. This culture predominated at the least L:D ratio of 4:20 h. Studies confirmed the ability of the floating organisms to grow heterotrophically in the dark utilizing diesel as carbon source and also in the presence of light in a medium devoid of organic carbon sources.

Validation of the BetaStar® Advanced for Tetracyclines Test Kit for the Screening of Bulk Tank and Tanker Truck Milks for the Presence of Tetracycline Drug Residues.

PubMed

Ankrapp, David; Schaus, Benjamin; Clements, Lauren; Klein, Frank; Rice, Jennifer; Rejman, John

2018-05-09

A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Tetracyclines) for detection of tetracycline antibiotic residues in raw, commingled bovine milk. The assay was demonstrated to detect tetracycline, chlortetracycline, and oxytetracycline at levels below the FDA tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. Results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. All three drugs at the approximate 90/95% sensitivity levels were detected in milk collected from cows that had been treated with the specific drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 881 control milk samples. Testing the estimated 90/95 sensitivity level for tetracycline (213 ppb), chlortetracycline (272 ppb), and oxytetracycline (180 ppb) and at 1000 ppb for each antibiotic resulted in 100% positive tests for each tetracycline. Results of ruggedness experiments established the operating parameter tolerances for the test. Results of cross-reactivity testing established that the assay detects certain other tetracycline drugs but does not cross-react with any of 32 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts (SCC) in raw milk produced no assay interference.

Progesterone bioavailability with a progesterone-releasing silicone vaginal ring in IVF candidates.

PubMed

Dragonas, C; Maltaris, T; Binder, H; Kat, M; Mueller, A; Cupisti, S; Hoffmann, I; Beckmann, M W; Dittrich, Ralf

2007-06-27

A vaginal ring made of silicone polymers and barium sulfate, and containing 1 g of pure micronized progesterone, was developed for luteal supplementation in women undergoing cycles of in vitro fertilization (IVF). The ring, modeled on the Estring, was designed as a means of providing continuous intravaginal delivery of progesterone. Bioavailability of progesterone in the blood was demonstrated for 24 hours in IVF candidates who had an endogenous progesterone deficiency after treatment with gonadotropin-releasing hormone (GnRH) analogues. After the first 4 h of increasing release of progesterone from the ring (with mean serum levels of 1.39 +/- 0.8 ng/ml after 4 h), only a slight increase in serum progesterone levels (with a mean peak of 1.5 +/- 0.45 ng/ml after 24 h) was observed during the rest of the test period. Gonadotropin levels were not affected after insertion of the ring. The ring was well tolerated by the patients. The maximum serum progesterone level was lower in comparison with other forms of progesterone application, but it should be sufficiently high, due to the uterine first-pass effect. This study demonstrated that progesterone administration through a silicone ring for luteal support is feasible in IVF treatment. As the vaginal ring is very well tolerated by the patients, these findings may encourage the pharmaceutical industry to design an appropriate progesterone ring for luteal support.

A verified design of a fault-tolerant clock synchronization circuit: Preliminary investigations

NASA Technical Reports Server (NTRS)

Miner, Paul S.

1992-01-01

Schneider demonstrates that many fault tolerant clock synchronization algorithms can be represented as refinements of a single proven correct paradigm. Shankar provides mechanical proof that Schneider's schema achieves Byzantine fault tolerant clock synchronization provided that 11 constraints are satisfied. Some of the constraints are assumptions about physical properties of the system and cannot be established formally. Proofs are given that the fault tolerant midpoint convergence function satisfies three of the constraints. A hardware design is presented, implementing the fault tolerant midpoint function, which is shown to satisfy the remaining constraints. The synchronization circuit will recover completely from transient faults provided the maximum fault assumption is not violated. The initialization protocol for the circuit also provides a recovery mechanism from total system failure caused by correlated transient faults.

Pharmacokinetic/pharmacodynamic modeling of psychomotor impairment induced by oral clonazepam in healthy volunteers.

PubMed

dos Santos, Fábio Monteiro; Gonçalves, José Carlos Saraiva; Caminha, Ricardo; da Silveira, Gabriel Estolano; Neves, Claúdia Silvana de Miranda; Gram, Karla Regina da Silva; Ferreira, Carla Teixeira; Jacqmin, Philippe; Noël, François

2009-10-01

This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacodynamic (PK/PD) study is important to interpret properly the consequences of determined levels of plasma concentrations of psychoactive therapeutic drugs reported to be involved in road-traffic accidents. Twenty-three male subjects received a single oral dose of 4 mg clonazepam. Plasma concentration, determined by on-line solid phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry, and psychomotor performance, quantified through the Digit Symbol Substitution Test, were monitored for 72 hours. A 2-compartment open model with first order absorption and lag-time better fitted the plasma clonazepam concentrations. Clonazepam decreased the psychomotor performance by 72 +/- 3.7% (observed maximum effect), 1.5 to 4 hours (25th-75th percentile) after drug administration. A simultaneous population PK/PD model based on a sigmoid Emax model with time-dependent tolerance described well the time course of effect. Such acute tolerance could minimize the risk of accident as a result of impairment of motor skill after a single dose of clonazepam. However, an individual analysis of the data revealed a great interindividual variation in the relationship between clonazepam effect and plasma concentration, indicating that the phenomenon of acute tolerance can be predicted at a population, but not individual, level.

Metals in agricultural produce associated with acid-mine drainage in Mount Morgan (Queensland, Australia).

PubMed

Vicente-Beckett, Victoria A; McCauley, Gaylene J Taylor; Duivenvoorden, Leo J

2016-01-01

Acid-mine drainage (AMD) into the Dee River from the historic gold and copper mine in Mount Morgan, Queensland (Australia) has been of concern to farmers in the area since 1925. This study sought to determine the levels of AMD-related metals and sulfur in agricultural produce grown near the mine-impacted Dee River, compare these with similar produce grown in reference fields (which had no known AMD influence), and assess any potential health risk using relevant Australian or US guidelines. Analyses of lucerne (Medicago sativa; also known as alfalfa) from five Dee fields showed the following average concentrations (mg/kg dry basis): Cd < 1, Cu 11, Fe 106, Mn 52, Pb < 5, Zn 25 and S 3934; similar levels were found in lucerne hay (used as cattle feed) from two Dee fields. All lucerne and lucerne hay data were generally comparable with levels found in the lucerne reference fields, suggesting no AMD influence; the levels were within the US National Research Council (US NRC) guidelines for maximum tolerable cattle dietary intake. Pasture grass (also cattle feed) from two fields in the Dee River floodplains gave mean concentrations (mg/kg dry) of Cd 0.14, Cu 12, Fe 313, Mn 111, Pb 1.4, Zn 86 and S 2450. All metal levels from the Dee and from reference sites were below the US NRC guidelines for maximum tolerable cattle dietary intake; however, the average Cd, Cu and Fe levels in Dee samples were significantly greater than the corresponding levels in the pasture grass reference sites, suggesting AMD influence in the Dee samples. The average levels in the edible portions of mandarin oranges (Citrus reticulata) from Dee sites (mg/kg wet weight) were Cd 0.011, Cu 0.59, Fe 2.2, Mn 0.56, Pb 0.18, S 91 and Zn 0.96. Cd and Zn were less than or close to, average Fe and Mn levels were at most twice, Cd 1.8 or 6.5 times, and Pb 8.5 or 72 times the maximum levels in raw oranges reported in the US total diet study (TDS) or the Australian TDS, respectively. Average Cd, Fe, Mn, Pb and Zn levels in the citrus reference samples were found to exceed the maximum reported in one or both TDS surveys. Cu, Fe, Mn, Pb and Zn plant-soil transfer factor (TF) values were < 1 for all agricultural samples from both Dee and reference sites, suggesting relatively poor transfer of these metals from soil to plant. In the case of Cd, TF values for Dee pasture grass and citrus fruit samples were 0.14 and 0.73, respectively; lucerne and lucerne hay from both Dee and reference sites gave TF = 10, suggesting some potential risk to cattle, although this conclusion is tentative because Cd levels were close to or less than the detection limit. TF values for S in lucerne, lucerne hay, pasture grass and mandarin oranges from Dee sites were 18, 14, 3 and 3.6, respectively, indicating that S in soil was readily available to plant or fruit. Sulfur in pasture grass and citrus fruit (TF = 11 for both) was apparently more bioavailable at the reference sites than at the Dee sites (TF = 3.0 for pasture grass; TF = 3.6 for citrus fruit).

Characterization of boron tolerant bacteria isolated from a fly ash dumping site for bacterial boron remediation.

PubMed

Edward Raja, Chellaiah; Omine, Kiyoshi

2013-08-01

Boron is an essential micronutrient for plants, but can above certain concentrations be toxic to living organisms. A major environmental concern is the removal of boron from contaminated water and fly ash. For this purpose, the samples were collected from a fly ash dumping site, Nagasaki prefecture, Japan. The chemical characteristics and heavy metal concentration of the samples were performed by X-ray fluorescent analysis and leaching test. For bacterial analysis, samples were collected in sterile plastic sheets and isolation was carried out by serial dilution method. The boron tolerant isolates that showed values of maximum inhibitory concentration toward boron ranging from 100 to 260 mM level were screened. Based on 16S rRNA sequencing and phylogenetic analysis, the isolates were most closely related to the genera Bacillus, Lysinibacillus, Microbacterium and Ralstonia. The boron tolerance of these strains was also associated with resistant to several heavy metals, such as As (III), Cr (VI), Cd, Cu, Pb, Ni, Se (III) and Zn. Indeed, these strains were arsenic oxidizing bacteria confirmed by silver nitrate test. These strains exhibited their salt resistances ranging from 4 to 15 % were determined in Trypticase soy agar medium. The boron tolerant strains were capable of removing 0.1-2.0 and 2.7-3.7 mg l(-1) boron from the medium and fly ash at 168 h. Thus, we have successfully identified the boron tolerant and removal bacteria from a fly ash dumping site for boron remediation.

Cadmium accumulation and tolerance of Macleaya cordata: a newly potential plant for sustainable phytoremediation in Cd-contaminated soil.

PubMed

Nie, Jian; Liu, Yunguo; Zeng, Guangming; Zheng, Bohong; Tan, Xiaofei; Liu, Huan; Xie, Jieli; Gan, Chao; Liu, Wei

2016-05-01

Heavy metal pollution is a major concern of the public due to their threats to the safety of food chains. A 60-day pot experiment was conducted using Macleaya cordata as plant material to investigate the phytoremediation potential and anti-oxidative responses of M. cordata under different Cd stress. Significant growth inhibition phenomenon and toxic symptoms were not detected in the experiment. The high biomass of the plant provided high accumulation capacity for Cd with an average dry weight of 3.6 g. The maximum extraction amount of Cd was 393 μg·plant(-1), suggesting that this species had potential for phytoremediation of Cd-contaminated soil. A slight increase of chlorophyll (CHL) content was observed in Cd10 treatment. The plant was confirmed to have relatively high tolerance to the Cd stress on the basis of tolerance indexes (TI), relative water content, and CHLa/CHLb ratio. M. cordata could maintain high level of superoxide dismutase (SOD) activity under Cd stress, indicating strong tolerance capacity for reactive oxygen species (ROS) in plant cells. Catalase (CAT) activity show a certain range of decline in the experiment compare to the control. And peroxidase (POD) activity in leaves changed irregularly when compared to the control. The malondialdehyde (MDA) content increased as Cd concentration elevated compared to the control. In addition, as an inedible crop with relatively high economic value, M. cordata have shown the advantage of high biomass and high tolerance under Cd stress, which can provide a new plant resource for sustainable phytoremediation.

Impact of fresh and saline water flooding on leaf gas exchange in two Italian provenances of Tamarix africana Poiret.

PubMed

Abou Jaoudé, R; de Dato, G; Palmegiani, M; De Angelis, P

2013-01-01

In Mediterranean coastal areas, changes in precipitation patterns and seawater levels are leading to increased frequency of flooding and to salinization of estuaries and freshwater systems. Tamarix spp. are often the only woody species growing in such environments. These species are known for their tolerance to moderate salinity; however, contrasting information exists regarding their tolerance to flooding, and the combination of the two stresses has never been studied in Tamarix spp. Here, we analyse the photosynthetic responses of T. africana Poiret to temporary flooding (45 days) with fresh or saline water (200 mm) in two Italian provenances (Simeto and Baratz). The measurements were conducted before and after the onset of flooding, to test the possible cumulative effects of the treatments and effects on twig aging, and to analyse the responses of twigs formed during the experimental period. Full tolerance was evident in T. africana with respect to flooding with fresh water, which did not affect photosynthetic performances in either provenance. Saline flooding was differently tolerated by the two provenances. Moreover, salinity tolerance differently affected the two twig generations. In particular, a reduction in net assimilation rate (-48.8%) was only observed in Baratz twigs formed during the experimental period, compared to pre-existing twigs. This reduction was a consequence of non-stomatal limitations (maximum carboxylation rate and electron transport), probably as a result of higher Na transport to the twigs, coupled with reduced Na storage in the roots. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Flaw tolerance promoted by dissipative deformation mechanisms between material building blocks

NASA Astrophysics Data System (ADS)

Verho, Tuukka; Buehler, Markus J.

2014-09-01

Novel high-performance composite materials often draw inspiration from natural materials such as bone or mollusc shells. A prime feature of such composites is that they are, like their natural counterparts, quasibrittle. They are tolerant to material flaws up to a certain characteristic flaw-tolerant size scale, exhibiting high strength and toughness, but start to behave in a brittle manner when sufficiently large flaws are present. Here, we establish that better flaw tolerance can be achieved by maximizing fracture toughness relative to the maximum elastic energy available in the material, and we demonstrate this concept with simple two-dimensional coarse-grained simulations where the transition from brittle to quasibrittle behaviour is examined.

Impact of industrial dry-milling on fumonisin redistribution in non-transgenic corn in Brazil.

PubMed

Bordini, Jaqueline Gozzi; Ono, Mario Augusto; Garcia, Glauco Tironi; Fazani, Victor Hugo Meconi; Vizoni, Édio; Rodrigues, Karem Caroline Bonacin; Hirooka, Elisa Yoko; Ono, Elisabete Yurie Sataque

2017-04-01

The aim of this study was to evaluate the fate of fumonisins B 1 (FB 1 ) and B 2 (FB 2 ) during industrial dry-milling in two lots from 2014 (n=120) and 2015 (n=120) of non-transgenic corn and their fractions (germ, pericarp, endosperm, cornmeal and grits), collected from one of the major Brazilian milling industries. Fumonisins were concentrated in the germ and pericarp at a rate of 322% and 188% (lot 1) and 311% and 263% (lot 2), respectively. In the endosperm, cornmeal and grits fumonisin levels decreased from 60 to 95%. Fumonisin levels in cornmeal and grits were below the maximum limit tolerated by the European Commission. Therefore, corn industrial dry-milling can contribute to reducing fumonisin levels in corn products intended for human consumption. Copyright © 2016 Elsevier Ltd. All rights reserved.

40 CFR 180.1052 - 2,2,5-trimethyl-3-dichloro-acetyl-1,3-oxazolidine; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false 2,2,5-trimethyl-3-dichloro-acetyl-1,3... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR... diisobutylthiocarbamate applied to corn fields before the corn plants emerge from the soil with a maximum of 0.5 pound of...

Isolation of a lead tolerant novel bacterial species, Achromobacter sp. TL-3: assessment of bioflocculant activity.

PubMed

Batta, Neha; Subudhi, Sanjukta; Lal, Banwari; Devi, Arundhuti

2013-11-01

Lead is one of the four heavy metals that has a profound damaging effects on human health. In the recent past there has been an increasing global concern for development of sustainable bioremediation technologies for detoxification of lead contaminant. Present investigation highlights for lead biosorption by a newly isolated novel bacterial species; Achromobacter sp. TL-3 strain, isolated from activated sludge samples contaminated with heavy metals (collected from oil refinery, Assam, North-East India). For isolation of lead tolerant bacteria, sludge samples were enriched into Luria Broth medium supplemented separately with a range of lead nitrate; 250, 500, 750, 1000, 1250 and 1500 ppm respectively. The bacterial consortium that could tolerate 1500 ppm of lead nitrate was selected further for purification of lead tolerant bacterial isolates. Purified lead tolerant bacterial isolates were then eventually inoculated into production medium supplemented with ethanol and glycerol as carbon and energy source to investigate for bioflocculant production. Bioflocculant production was estimated by monitoring the potential of lead tolerant bacterial isolate to flocculate Kaolin clay in presence of 1% CaCl2. Compared to other isolates, TL-3 isolate demonstrated for maximum bioflocculant activity of 95% and thus was identified based on 16S rRNA gene sequence analysis. TL3 isolate revealed maximum homology (98%) with Achromobacter sp. and thus designated as Achromobacter sp. TL-3. Bioflocculant activity of TL-3 isolate was correlated with the change in pH and growth. Achromobacter sp. TL-3 has significant potential for lead biosorption and can be effectively employed for detoxification of lead contaminated waste effluents/waste waters.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Impacts of rising tropospheric ozone on photosynthesis and metabolite levels on field grown soybean.

PubMed

Sun, Jindong; Feng, Zhaozhong; Ort, Donald R

2014-09-01

The response of leaf photosynthesis and metabolite profiles to ozone (O3) exposure ranging from 37 to 116 ppb was investigated in two soybean cultivars Dwight and IA3010 in the field under fully open-air conditions. Leaf photosynthesis, total non-structural carbohydrates (TNC) and total free amino acids (TAA) decreased linearly with increasing O3 levels in both cultivars with average decrease of 7% for an increase in O3 levels by 10 ppb. Ozone interacted with developmental stages and leaf ages, and caused higher damage at later reproductive stages and in older leaves. Ozone affected yield mainly via reduction of maximum rate of Rubisco carboxylation (Vcmax) and maximum rates of electron transport (Jmax) as well as a shorter growing season due to earlier onset of canopy senescence. For all parameters investigated the critical O3 levels (∼50 ppb) for detectable damage fell within O3 levels that occur routinely in soybean fields across the US and elsewhere in the world. Strong correlations were observed in O3-induced changes among yield, photosynthesis, TNC, TAA and many metabolites. The broad range of metabolites that showed O3 dose dependent effect is consistent with multiple interaction loci and thus multiple targets for improving the tolerance of soybean to O3. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Resilience of rice (Oryza spp.) pollen germination and tube growth to temperature stress.

PubMed

Coast, Onoriode; Murdoch, Alistair J; Ellis, Richard H; Hay, Fiona R; Jagadish, Krishna S V

2016-01-01

Resilience of rice cropping systems to potential global climate change will partly depend on the temperature tolerance of pollen germination (PG) and tube growth (PTG). Pollen germination of high temperature-susceptible Oryza glaberrima Steud. (cv. CG14) and Oryza sativa L. ssp. indica (cv. IR64) and high temperature-tolerant O. sativa ssp. aus (cv. N22), was assessed on a 5.6-45.4 °C temperature gradient system. Mean maximum PG was 85% at 27 °C with 1488 μm PTG at 25 °C. The hypothesis that in each pollen grain, the minimum temperature requirements (Tn ) and maximum temperature limits (Tx ) for germination operate independently was accepted by comparing multiplicative and subtractive probability models. The maximum temperature limit for PG in 50% of grains (Tx(50) ) was the lowest (29.8 °C) in IR64 compared with CG14 (34.3 °C) and N22 (35.6 °C). Standard deviation (sx ) of Tx was also low in IR64 (2.3 °C) suggesting that the mechanism of IR64's susceptibility to high temperatures may relate to PG. Optimum germination temperatures and thermal times for 1 mm PTG were not linked to tolerating high temperatures at anthesis. However, the parameters Tx(50) and sx in the germination model define new pragmatic criteria for successful and resilient PG, preferable to the more traditional cardinal (maximum and minimum) temperatures. © 2014 John Wiley & Sons Ltd.

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

PubMed

Robinson, Jennifer G; Farnier, Michel; Krempf, Michel; Bergeron, Jean; Luc, Gérald; Averna, Maurizio; Stroes, Erik S; Langslet, Gisle; Raal, Frederick J; El Shahawy, Mahfouz; Koren, Michael J; Lepor, Norman E; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Kastelein, John J P

2015-04-16

Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02). Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).

Effect of Surgical Curve Correction on Exercise Tolerance and Physical Capacities in Patients of Severe Spinal Deformity.

PubMed

Patil, Prateek C; Rathod, Ashok K; Borde, Mandar; Singh, Vishwajeet; Singh, Hemant U

2016-12-01

Traditionally, surgical intervention for patients with a spinal deformity has been considered for cosmetic benefits, but surgical intervention can alter the lung physiology or volumes and in turn leads to increase in physical capacity and exercise tolerance. Therefore, we conducted this to determine whether a surgical correction would restore the lung physiology, physical capacity and exercise tolerance in patients with kyphoscoliosis. To evaluate the usage of six-minute walk test scores and modified Borg scores as tools/measures for exercise tolerance in patients with spinal deformity and to study the effects of surgical correction of spinal deformity on exercise tolerance with above parameters as the measures. Thirty patients with spinal deformity, who had undergone surgery for deformity correction, were evaluated. All patients were investigated pre-operatively with x-rays of the spine (anteroposterior and lateral views). Clinical tests like breath holding time (after full inspiration) in number of seconds, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked); were recorded as measures of exercise tolerance. The patients were followed up on the first, third, sixth and twelfth month post-operatively and tested clinically for breath holding time, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked) and x-rays of the spine (anteroposterior and lateral views). In our study, breath holding time (p-value = 0.001) and modified Borg scores (p-value = 0.012) showed a significant improvement at 12 months post-operatively. We noted similar findings with heart rate, respiratory rate and maximum distance walked after a six-minute walk test. Improvements were noted in all the parameters, especially in the group of patients with greater than 60 degrees of cobb angle. However, the differences between the two groups (pre-operative cobb angle less than 60 degrees and pre-operative cobb angle more than 60 degrees) were not significant. The results were analysed and tested for significance using Student's t-test (paired and unpaired as appropriate) and Wilcoxon signed rank test. Surgical correction in cases of spinal deformity improves the cosmetic appearance and balance in the patients. Favourable results of surgical intervention were found in exercise tolerance with improvements in modified Borg scores, six-minute walk test results and breath holding time. The above parameters appear to be good tools for the assessment of physical capacity and exercise tolerance in patients with spinal deformity.

Larval connectivity across temperature gradients and its potential effect on heat tolerance in coral populations.

PubMed

Kleypas, Joan A; Thompson, Diane M; Castruccio, Frederic S; Curchitser, Enrique N; Pinsky, Malin; Watson, James R

2016-11-01

Coral reefs are increasingly exposed to elevated temperatures that can cause coral bleaching and high levels of mortality of corals and associated organisms. The temperature threshold for coral bleaching depends on the acclimation and adaptation of corals to the local maximum temperature regime. However, because of larval dispersal, coral populations can receive larvae from corals that are adapted to very different temperature regimes. We combine an offline particle tracking routine with output from a high-resolution physical oceanographic model to investigate whether connectivity of coral larvae between reefs of different thermal regimes could alter the thermal stress threshold of corals. Our results suggest that larval transport between reefs of widely varying temperatures is likely in the Coral Triangle and that accounting for this connectivity may be important in bleaching predictions. This has important implications in conservation planning, because connectivity may allow some reefs to have an inherited heat tolerance that is higher or lower than predicted based on local conditions alone. © 2016 John Wiley & Sons Ltd.

Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

PubMed

Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

2012-09-01

A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study design and data interpretation challenges.

Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules

PubMed Central

Sutiman, Natalia; Zhang, Zhenxian; Tan, Eng Huat; Ang, Mei Kim; Tan, Shao-Weng Daniel; Toh, Chee Keong; Ng, Quan Sing; Chowbay, Balram; Lim, Wan-Teck

2016-01-01

Purpose This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC). Methods This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16) and at 100 mg/week in the MSV group (N = 14). Erlotinib was administered orally daily. Results The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13%) and hyponatremia (N = 1; 6%) in the CSV group, and neutropenia (N = 5; 36%) in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group. Conclusions Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups. Trial Registration ClinicalTrials.gov NCT00702182 PMID:27135612

Impact of Threat Level, Task Instruction, and Individual Characteristics on Cold Pressor Pain and Fear among Children and Their Parents.

PubMed

Boerner, Katelynn E; Noel, Melanie; Birnie, Kathryn A; Caes, Line; Petter, Mark; Chambers, Christine T

2016-07-01

The cold pressor task (CPT) is increasingly used to induce experimental pain in children, but the specific methodology of the CPT is quite variable across pediatric studies. This study examined how subtle variations in CPT methodology (eg. provision of low- or high-threat information regarding the task; provision or omission of maximum immersion time) may influence children's and parents' perceptions of the pain experience. Forty-eight children (8 to 14 years) and their parents were randomly assigned to receive information about the CPT that varied on 2 dimensions, prior to completing the task: (i) threat level: high-threat (task described as very painful, high pain expressions depicted) or low-threat (standard CPT instructions provided, low pain expressions depicted); (ii) ceiling: informed (provided maximum immersion time) or uninformed (information about maximum immersion time omitted). Parents and children in the high-threat condition expected greater child pain, and these children reported higher perceived threat of pain and state pain catastrophizing. For children in the low-threat condition, an informed ceiling was associated with less state pain catastrophizing during the CPT. Pain intensity, tolerance, and fear during the CPT did not differ by experimental group, but were predicted by child characteristics. Findings suggest that provision of threatening information may impact anticipatory outcomes, but experienced pain was better explained by individual child variables. © 2015 World Institute of Pain.

The Effects of Metabolic Work Rate and Ambient Environment on Physiological Tolerance Times While Wearing Explosive and Chemical Personal Protective Equipment

PubMed Central

Costello, Joseph T.; Stewart, Kelly L.; Stewart, Ian B.

2015-01-01

This study evaluated the physiological tolerance times when wearing explosive and chemical (>35 kg) personal protective equipment (PPE) in simulated environmental extremes across a range of differing work intensities. Twelve healthy males undertook nine trials which involved walking on a treadmill at 2.5, 4, and 5.5 km·h−1 in the following environmental conditions, 21, 30, and 37°C wet bulb globe temperature (WBGT). Participants exercised for 60 min or until volitional fatigue, core temperature reached 39°C, or heart rate exceeded 90% of maximum. Tolerance time, core temperature, skin temperature, mean body temperature, heart rate, and body mass loss were measured. Exercise time was reduced in the higher WBGT environments (WBGT37 < WBGT30 < WBGT21; P < 0.05) and work intensities (5.5 < 4 < 2.5 km·h−1; P < 0.001). The majority of trials (85/108; 78.7%) were terminated due to participant's heart rate exceeding 90% of their maximum. A total of eight trials (7.4%) lasted the full duration. Only nine (8.3%) trials were terminated due to volitional fatigue and six (5.6%) due to core temperatures in excess of 39°C. These results demonstrate that physiological tolerance times are influenced by the external environment and workload and that cardiovascular strain is the limiting factor to work tolerance when wearing this heavy multilayered PPE. PMID:25866818

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

PubMed

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

High lenticular tolerance to ultraviolet radiation-B by pigmented guinea-pig; application of a safety limit strategy for UVR-induced cataract.

PubMed

Mody, Vino C; Kakar, Manoj; Söderberg, Per G; Löfgren, Stefan

2012-05-01

The purpose of this study was to determine a threshold measure, maximum tolerable dose (MTD), for avoidance of UVR-B-induced cataract in the pigmented guinea-pig. Thirty pupil-dilated anesthetized young female guinea-pigs, divided into five equal groups, received between 0 and 84.9 kJ/m(2) unilateral UVR-B. Lens extraction and in vitro lens photography occurred 24 hr after exposure. Measurement of intensity of lens light scattering served as quantifying tool for the degree of cataract. Data analysis included regression, using a second order polynomial model. The applied MTD concept was based on the UVR-B dose-response curve obtained for the pigmented guinea-pig. A smaller number of pigmented guinea-pigs, pigmented rats and albino rats underwent morphometric analysis of the anterior segment geometry. All eyes exposed to UVR-B developed cataract in the anterior subcapsular region. MTD for avoidance of UVR-B-induced cataract was 69.0 kJ/m(2) in the pigmented guinea-pig. Iris was considerably thicker in the guinea-pig than in the rats. Lens blockage by the dilated iris was lowest in the guinea-pig. Maximum tolerable dose for avoidance of UVR-B-induced cataract in the pigmented guinea-pig was 69.0 kJ/m(2), over 10-fold higher than the threshold 5 kJ/m(2) obtained by Pitts et al. in the pigmented rabbit. Maximum tolerable dose is an appropriate method for estimation of toxicity for UVR-B-induced cataract in the guinea-pig. The pigmented guinea-pig is significantly less sensitive to UVR-B exposure than the pigmented rabbit and pigmented rat. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose.

PubMed

Doyle, G; Furey, S; Berlin, R; Cooper, S; Jayawardena, S; Ashraf, E; Baird, L

1999-07-01

Delineation of non-steroidal anti-inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non-prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare. This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non-prescription dose and duration of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by >/= 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. When used as directed to treat episodic pain, non-prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

36 CFR 1192.4 - Miscellaneous instructions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... General § 1192.4 Miscellaneous instructions. (a) Dimensional conventions. Dimensions that are not noted as minimum or maximum are absolute. (b) Dimensional tolerances. All dimensions are subject to conventional...

36 CFR 1192.4 - Miscellaneous instructions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... General § 1192.4 Miscellaneous instructions. (a) Dimensional conventions. Dimensions that are not noted as minimum or maximum are absolute. (b) Dimensional tolerances. All dimensions are subject to conventional...

36 CFR 1192.4 - Miscellaneous instructions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... General § 1192.4 Miscellaneous instructions. (a) Dimensional conventions. Dimensions that are not noted as minimum or maximum are absolute. (b) Dimensional tolerances. All dimensions are subject to conventional...

Higher hdl levels are a preventive factor for metabolic syndrome in obese Turkish children.

PubMed

Özer, Samet; Yılmaz, Resul; Özlem Kazanci, Nafia; Sönmezgöz, Ergün; Karaaslan, Erhan; Altuntaş, Buket; Emre Kuyucu, Yunus

2014-10-03

The definition of childhood metabolic syndrome has not been described clearly. Childhood obesity is increasing gradually, and the incidence of childhood metabolic syndrome is also rising. We aimed to show metabolic syndrome components and preventive factors for metabolic syndrome in obese children Methods: In the present study, 187 obese children and adolescents 5-18 years old were investigated retrospectively. Demographic data, anthropometric measurements, body mass index, blood pressure values, insulin levels, oral glucose tolerance test results, total cholesterol, high density lipoprotein, and triglyceride levels were obtained from hospital records. A body mass index > 95th percentile was considered obese. Insulin resistance was calculated according to the oral glucose tolerance test with 1.75 g/kg glucose maximum 75 g glucose. The insulin sensitivity index and homeostatic model assessment-insulin resistance (HOMA IR) were calculated and compared. Metabolic syndrome was diagnosed according to the modified WHO criteria adapted for metabolic syndrome in children. Abnormal glucose homeostasis was detected in 53% of subjects. Dyslipidaemia was present in 45.7% and hypertension in 16.6% of the patients. Metabolic syndrome was identified in 24.6% of obese children and adolescents. High HOMA-IR values and fasting glucose levels, elevated triglycerides and lower HDL levels were an indication of metabolic syndrome. Obesity and insulin resistance are significant factors for the development of metabolic syndrome in children and adolescents. In obese children higher HDL levels are preventive factor for metabolic syndrome. Preventing obesity and insulin resistance may decrease the prevalence of metabolic syndrome. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

CORSSTOL: Cylinder Optimization of Rings, Skin, and Stringers with Tolerance sensitivity

NASA Technical Reports Server (NTRS)

Finckenor, J.; Bevill, M.

1995-01-01

Cylinder Optimization of Rings, Skin, and Stringers with Tolerance (CORSSTOL) sensitivity is a design optimization program incorporating a method to examine the effects of user-provided manufacturing tolerances on weight and failure. CORSSTOL gives designers a tool to determine tolerances based on need. This is a decisive way to choose the best design among several manufacturing methods with differing capabilities and costs. CORSSTOL initially optimizes a stringer-stiffened cylinder for weight without tolerances. The skin and stringer geometry are varied, subject to stress and buckling constraints. Then the same analysis and optimization routines are used to minimize the maximum material condition weight subject to the least favorable combination of tolerances. The adjusted optimum dimensions are provided with the weight and constraint sensitivities of each design variable. The designer can immediately identify critical tolerances. The safety of parts made out of tolerance can also be determined. During design and development of weight-critical systems, design/analysis tools that provide product-oriented results are of vital significance. The development of this program and methodology provides designers with an effective cost- and weight-saving design tool. The tolerance sensitivity method can be applied to any system defined by a set of deterministic equations.

Assessment of potential probiotic properties of Lactobacillus spp., Lactococcus spp., and Pediococcus spp. strains isolated from kefir.

PubMed

Sabir, Firat; Beyatli, Yavuz; Cokmus, Cumhur; Onal-Darilmaz, Derya

2010-01-01

In this study, the metabolic activities (in terms of quantities of the produced lactic acid, hydrogen peroxide, and exopolysaccharides) of 8 strains of Lactobacillus spp., Lactococcus spp., and Pediococcus spp., were determined. Lactic acid levels produced by strains were 8.1 to 17.4 mg/L. The L. acidophilus Z1L strain produced the maximum amount (3.18 μg/mL) of hydrogen peroxide. The exopolysaccharides (EPS) production by the strains was ranged between 173 and 378 mg/L. The susceptibility of 7 different antibiotics against these strains was also tested. All strains were found to be sensitive to ampicillin. The tolerance of the strains to low pH, their resistance to bile salts of strains, and their abilities to autoaggregate and coaggregate with Escherichia coli ATCC 11229 were also evaluated. High EPS-producing strains showed significant autoaggregation and coaggregation ability with test bacteria (P < 0.01). A correlation also was determined between EPS production and acid-bile tolerance (P < 0.05). EPS production possibly affects or is involved in acid-bile tolerance and aggregation of Lactobacillus spp., Lactococcus spp., and Pediococcus spp. strains and supports the potential of L. acidophilus Z1L strain as new probiotic. © 2010 Institute of Food Technologists®

Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

PubMed

Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

2013-01-01

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

Thermal tolerances of fishes occupying groundwater and surface-water dominated streams

USGS Publications Warehouse

Farless, Nicole; Brewer, Shannon K.

2017-01-01

A thermal tolerance study mimicking different stream environments could improve our ecological understanding of how increasing water temperatures affect stream ectotherms and improve our ability to predict organism responses based on river classification schemes. Our objective was to compare the thermal tolerances of stream fishes of different habitat guilds among 3 exposure periods: critical thermal maximum (CTmax, increase of 2°C/h until loss of equilibrium [LOE] and death [D]), and 2 longer-term treatments (net daily increase of 1°C) that mimicked spring-fed (SF; 4°C daily increase) and non-spring-fed (NSF; 8°C daily increase) conditions. Fishes in the pelagic habitat guild had a 1°C higher average CTmax than benthic fishes. Thermal responses of species depended on exposure period with higher and increased variation in tolerances associated with the SF and NSF exposure periods. Logperch, Orangebelly Darter, Orangethroat Darter, and Southern Redbelly Dace were more sensitive to thermal increases regardless of SF or NSF treatment than were the 3 remaining species (Brook Silverside, Central Stoneroller, and Redspot Chub), which represented average thermal responses among the species tested. The 3 species that had a higher thermal response to CTmax-D (lethal endpoint of death) also were able to increase their tolerances more than other species in both SF and NSF treatments. Our data indicate finer guild designations may be useful for predicting thermal-response patterns. A diel thermal refuge increases the thermal responses of ectotherms to daily maxima, but the patterns across our SF and NSF treatments were similar suggesting minimum refuge temperatures may be more important than maximums. Nonetheless, stream temperature cooling over a 24-h period is important to ectotherm thermal tolerances, a result suggesting that sources of cooler water to streams might benefit from protection.

Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

PubMed

Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

2016-10-25

To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

Deconstructing tolerance with clobazam

PubMed Central

Wechsler, Robert T.; Sankar, Raman; Montouris, Georgia D.; White, H. Steve; Cloyd, James C.; Kane, Mary Clare; Peng, Guangbin; Tworek, David M.; Shen, Vivienne; Isojarvi, Jouko

2016-01-01

Objective: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Methods: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg−1·d−1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg−1·d−1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Results: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Conclusions: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. ClinicalTrials.gov identifier: NCT00518713 and NCT01160770. Classification of evidence: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID:27683846

Identifying a maximum tolerated contour in two-dimensional dose-finding

PubMed Central

Wages, Nolan A.

2016-01-01

The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.

PubMed

Hu, Wei; Wang, Wei; Yang, Peinong; Zhou, Chao; Yang, Weifang; Wu, Bo; Lu, Hongsheng; Yang, Haihua

2015-01-01

Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC. Eligible patients with NPC received escalating doses of icotinib during IMRT. We treated six patients at a particular dose level until the maximum tolerated dose (MTD) was determined. The starting dose was 125 mg, once-daily and the dose was escalated to another level 125 mg, twice- and thrice- daily, until dose-limiting toxicity (DLT) occurred in two or more patients at a dose level. Expression and mutation analysis of EGFR were performed in all cases. A total of twelve patients were enrolled. Three patients experienced DLT (250 mg/day cohort) and MTD was 125 mg/day. Mucositis toxicity appears to be the major DLT. While EGFR expression in tumor tissue was detected in 75% (9/12) patients, EGFR mutation was detected in 16.67% (1/6) patients in 125 mg/day cohort, and 50% (3/6) in 250 mg/day cohort. The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiCostanzo, D; Ayan, A; Woollard, J

Purpose: To automate the daily verification of each patient’s treatment by utilizing the trajectory log files (TLs) written by the Varian TrueBeam linear accelerator while reducing the number of false positives including jaw and gantry positioning errors, that are displayed in the Treatment History tab of Varian’s Chart QA module. Methods: Small deviations in treatment parameters are difficult to detect in weekly chart checks, but may be significant in reducing delivery errors, and would be critical if detected daily. Software was developed in house to read TLs. Multiple functions were implemented within the software that allow it to operate viamore » a GUI to analyze TLs, or as a script to run on a regular basis. In order to determine tolerance levels for the scripted analysis, 15,241 TLs from seven TrueBeams were analyzed. The maximum error of each axis for each TL was written to a CSV file and statistically analyzed to determine the tolerance for each axis accessible in the TLs to flag for manual review. The software/scripts developed were tested by varying the tolerance values to ensure veracity. After tolerances were determined, multiple weeks of manual chart checks were performed simultaneously with the automated analysis to ensure validity. Results: The tolerance values for the major axis were determined to be, 0.025 degrees for the collimator, 1.0 degree for the gantry, 0.002cm for the y-jaws, 0.01cm for the x-jaws, and 0.5MU for the MU. The automated verification of treatment parameters has been in clinical use for 4 months. During that time, no errors in machine delivery of the patient treatments were found. Conclusion: The process detailed here is a viable and effective alternative to manually checking treatment parameters during weekly chart checks.« less

40 CFR 180.33 - Fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (b) Each petition for the establishment of a tolerance at a lower numerical level or levels than a... additional raw agricultural commodities at the same numerical level as a tolerance already established for... has a tolerance for other uses at the same numerical level or a higher numerical level shall be...

Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

DTIC Science & Technology

2012-10-01

ABSTRACT: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous...Surgical Technique) will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Aim 2 (Graft...connected to a rigid needle of the same gauge as the floating cannula one – Figure 7) using the maximum volume/number of injections could result in

46 CFR 154.448 - Calculations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... similar vessel. (d) A tank buckling analysis considering the maximum construction tolerance. (e) A finite element analysis using the loads determined under § 154.406. (f) A fracture mechanics analysis using the...

46 CFR 154.448 - Calculations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... similar vessel. (d) A tank buckling analysis considering the maximum construction tolerance. (e) A finite element analysis using the loads determined under § 154.406. (f) A fracture mechanics analysis using the...

46 CFR 154.448 - Calculations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... similar vessel. (d) A tank buckling analysis considering the maximum construction tolerance. (e) A finite element analysis using the loads determined under § 154.406. (f) A fracture mechanics analysis using the...

46 CFR 154.448 - Calculations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... similar vessel. (d) A tank buckling analysis considering the maximum construction tolerance. (e) A finite element analysis using the loads determined under § 154.406. (f) A fracture mechanics analysis using the...

46 CFR 154.448 - Calculations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... similar vessel. (d) A tank buckling analysis considering the maximum construction tolerance. (e) A finite element analysis using the loads determined under § 154.406. (f) A fracture mechanics analysis using the...

36 CFR § 1192.4 - Miscellaneous instructions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... General § 1192.4 Miscellaneous instructions. (a) Dimensional conventions. Dimensions that are not noted as minimum or maximum are absolute. (b) Dimensional tolerances. All dimensions are subject to conventional...

Avian thermoregulation in the heat: resting metabolism, evaporative cooling and heat tolerance in Sonoran Desert songbirds.

PubMed

Smith, Eric Krabbe; O'Neill, Jacqueline J; Gerson, Alexander R; McKechnie, Andrew E; Wolf, Blair O

2017-09-15

We examined thermoregulatory performance in seven Sonoran Desert passerine bird species varying in body mass from 10 to 70 g - lesser goldfinch, house finch, pyrrhuloxia, cactus wren, northern cardinal, Abert's towhee and curve-billed thrasher. Using flow-through respirometry, we measured daytime resting metabolism, evaporative water loss and body temperature at air temperatures ( T air ) between 30 and 52°C. We found marked increases in resting metabolism above the upper critical temperature ( T uc ), which for six of the seven species fell within a relatively narrow range (36.2-39.7°C), but which was considerably higher in the largest species, the curve-billed thrasher (42.6°C). Resting metabolism and evaporative water loss were minimal below the T uc and increased with T air and body mass to maximum values among species of 0.38-1.62 W and 0.87-4.02 g H 2 O h -1 , respectively. Body temperature reached maximum values ranging from 43.5 to 45.3°C. Evaporative cooling capacity, the ratio of evaporative heat loss to metabolic heat production, reached maximum values ranging from 1.39 to 2.06, consistent with known values for passeriforms and much lower than values in taxa such as columbiforms and caprimulgiforms. These maximum values occurred at heat tolerance limits that did not scale with body mass among species, but were ∼50°C for all species except the pyrrhuloxia and Abert's towhee (48°C). High metabolic costs associated with respiratory evaporation appeared to drive the limited heat tolerance in these desert passeriforms, compared with larger desert columbiforms and galliforms that use metabolically more efficient mechanisms of evaporative heat loss. © 2017. Published by The Company of Biologists Ltd.

Fungal Traits That Drive Ecosystem Dynamics on Land

PubMed Central

Lennon, Jay T.

2015-01-01

SUMMARY Fungi contribute extensively to a wide range of ecosystem processes, including decomposition of organic carbon, deposition of recalcitrant carbon, and transformations of nitrogen and phosphorus. In this review, we discuss the current knowledge about physiological and morphological traits of fungi that directly influence these processes, and we describe the functional genes that encode these traits. In addition, we synthesize information from 157 whole fungal genomes in order to determine relationships among selected functional genes within fungal taxa. Ecosystem-related traits varied most at relatively coarse taxonomic levels. For example, we found that the maximum amount of variance for traits associated with carbon mineralization, nitrogen and phosphorus cycling, and stress tolerance could be explained at the levels of order to phylum. Moreover, suites of traits tended to co-occur within taxa. Specifically, the genetic capacities for traits that improve stress tolerance—β-glucan synthesis, trehalose production, and cold-induced RNA helicases—were positively related to one another, and they were more evident in yeasts. Traits that regulate the decomposition of complex organic matter—lignin peroxidases, cellobiohydrolases, and crystalline cellulases—were also positively related, but they were more strongly associated with free-living filamentous fungi. Altogether, these relationships provide evidence for two functional groups: stress tolerators, which may contribute to soil carbon accumulation via the production of recalcitrant compounds; and decomposers, which may reduce soil carbon stocks. It is possible that ecosystem functions, such as soil carbon storage, may be mediated by shifts in the fungal community between stress tolerators and decomposers in response to environmental changes, such as drought and warming. PMID:25971588

Energy attenuation performance of impact protection worn by motorcyclists in real-world crashes.

PubMed

Albanese, Bianca; Gibson, Tom; Whyte, Tom; Meredith, Lauren; Savino, Giovanni; de Rome, Liz; Baldock, Matthew; Fitzharris, Michael; Brown, Julie

2017-05-29

Laboratory studies have demonstrated that impact protectors (IP) used in motorcycle clothing can reduce fracture severities. While crash studies have reported IP are associated with reduced likelihood of soft tissue injury, there is little evidence of their effectiveness in reducing fracture likelihood. This discrepancy might be related to IP quality. There are mandatory requirements for IP supplied with protective clothing in Europe, but not elsewhere. This study examines the energy attenuation performance of IP used by Australian riders. IP were harvested from clothing worn by crashed riders admitted to hospital. The IP were examined and energy attenuation properties were determined using EN 1621-1 test procedures. Impact injury was identified from medical records and defined as fractures, dislocations, and avulsions that occurred following impact to the rider's shoulders, elbows, hips, and/or knees. Fisher's exact test was used to examine the relationship between meeting the EN 1621-1 energy attenuation requirements and impact injury. The association between the average and maximum transmitted force, and impact injury was examined using generalized estimating equations. Motorcycle riders were recruited as part of an in-depth crash study through three hospitals in New South Wales, Australia, between 2012 and 2014. Riders were interviewed, and engineers conducted site, vehicle, and clothing inspections. Clothing was collected, or identical garments were purchased. Clothing was inspected for 62 riders. Of these, 19 wore clothing incorporating 76 IP. Twenty-six of these were impacted in the crash event. Almost all impacted IP (96%) were CE marked, and most (83%) met Level 1 energy attenuation requirements of EN 1621-1 when tested. Of the 26 impacted IP, four were associated with impact injuries, including midshaft and distal clavicle fractures and a scapula and olecranon fracture. No associations between meeting EN 1621-1 requirements and impact injury were found (p = 0.5). There was no association between average force transmitted and impact injury (95% CI: 0.91-1.24); however, as maximum force transmitted increased, the odds of impact injury increased (95% CI: 1.01-1.2). These results indicate a high probability of impact injury at 50 kN, the limit of maximum transmitted force specified in EN 1621-1. The allowable transmitted force of EN 1621-1 may be too high to effectively reduce the probability of impact injury. This is not surprising, given human tolerance levels that are reported in literature. Reducing the force limit below the reported fracture tolerance limits might be difficult with current technology. However, there is scope to reduce the EN 1621-1 maximum limit of 50 kN transmitted force. A reduction in the maximum force limit would improve rider protection and appears feasible, as 77% of tested IP recorded a maximum force <35 kN. This level of transmitted force is estimated to be associated with <20% probability of impact injury. While the performance of IP available to Australian riders is not regulated, most IP was CE marked. The results indicate a significant association between maximum transmitted force, tested according to EN 1621-1 procedures, and impact injury. Further investigation of the EN 1621-1 requirements may be warranted. This work will interest those targeting protective equipment for motorcyclists as a mechanism for reducing injury to these vulnerable road users.

+Gz tolerance after 14 days bed rest and the effects of rehydration.

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Van Beaumont, W.; Bernauer, E. M.; Haines, R. F.; Sandler, H.; Young, H. L.; Yusken, J. W.

1972-01-01

Measurement of the reduction in centrifugation tolerance after two weeks of bedrest with moderate daily exercise, with an attempt to determine if rehydration improves +Gz tolerance. There were significant reductions in +Gz tolerance during bedrest periods at three acceleration levels. Rehydration resulted in a significant increase in tolerance at 2.1G but it did not restore tolerance to control levels. Rehydration did not affect tolerance at 3.2G and 3.8G.

Reaction time in pilots during intervals of high sustained g.

PubMed

Truszczynski, Olaf; Lewkowicz, Rafal; Wojtkowiak, Mieczyslaw; Biernacki, Marcin P

2014-11-01

An important problem for pilots is visual disturbances occurring under +Gz acceleration. Assessment of the degree of intensification of these disturbances is generally accepted as the acceleration tolerance level (ATL) criterion determined in human centrifuges. The aim of this research was to evaluate the visual-motor responses of pilots during rapidly increasing acceleration contained in cyclic intervals of +6 Gz to the maximum ATL. The study involved 40 male pilots ages 32-41 yr. The task was a quick and faultless response to the light stimuli presented on a light bar during exposure to acceleration until reaching the ATL. Simple response time (SRT) measurements were performed using a visual-motor analysis system throughout the exposures which allowed assessment of a pilot's ATL. There were 29 pilots who tolerated the initial phase of interval acceleration and achieved +6 Gz, completing the test at ATL. Relative to the control measurements, the obtained results indicate a significant effect of the applied acceleration on response time. SRT during +6 Gz exposure was not significantly longer compared with the reaction time between each of the intervals. SRT and erroneous reactions indicated no statistically significant differences between the "lower" and "higher" ATL groups. SRT measurements over the +6-Gz exposure intervals did not vary between "lower" and "higher" ATL groups and, therefore, are not useful in predicting pilot performance. The gradual exposure to the maximum value of +6 Gz with exposure to the first three intervals on the +6-Gz plateau effectively differentiated pilots.

Production of an extracellular thermohalophilic lipase from a moderately halophilic bacterium, Salinivibrio sp. strain SA-2.

PubMed

Amoozegar, Mohammad Ali; Salehghamari, Ensieh; Khajeh, Khosro; Kabiri, Mahbube; Naddaf, Saied

2008-06-01

Fifty strains of moderately halophilic bacteria were isolated from various salty environments in Iran. A strain designated as SA-2 was shown to be the best producer of extracellular lipase and was selected for further studies. Biochemical and physiological characterization along with 16S rDNA sequence analysis placed SA-2 in the genus Salinivibrio. The optimum salt, pH, temperature and aeration for enzyme production were 0.1 M KCl, pH 8, 35 degrees C and 150 rpm, respectively. The enzyme production was synchronized bacterial growth and reached a maximum level during the early-stationary phase in the basal medium containing 1 M NaCl. Triacylglycerols enhanced lipase production, while carbohydrates had inhibitory effects on it. The maximum lipase activity was obtained at pH 7.5, 50 degrees C and CaCl(2) concentration of 0.01 M. The enzyme was stable at pH range of 7.5-8 and retained 90% of its activity at 80 degrees C for 30 min. Different concentrations of NaNO(3), Na(2)SO(4), KCl and NaCl had no affect on lipase stability for 3 h. These results suggest that the lipase secreted by Salinivibrio sp. strain SA-2 is industrially important from the perspective of its tolerance to a broad temperature range, its moderate thermoactivity and its high tolerance to a wide range of salt concentrations (0-3 M NaCl).

Relationship between fish size and upper thermal tolerance

USGS Publications Warehouse

Recsetar, Matthew S.; Zeigler, Matthew P.; Ward, David L.; Bonar, Scott A.; Caldwell, Colleen A.

2012-01-01

Using critical thermal maximum (CTMax) tests, we examined the relationship between upper temperature tolerances and fish size (fry-adult or subadult lengths) of rainbow trout Oncorhynchus mykiss (41-200-mm TL), Apache trout O. gilae apache (40-220-mm TL), largemouth bass Micropterus salmoides (72-266-mm TL), Nile tilapia Oreochromis niloticus (35-206-mm TL), channel catfish Ictalurus punctatus (62-264 mm-TL), and Rio Grande cutthroat trout O. clarkii virginalis (36-181-mm TL). Rainbow trout and Apache trout were acclimated at 18°C, Rio Grande cutthroat trout were acclimated at 14°C, and Nile tilapia, largemouth bass, and channel catfish were acclimated at 25°C, all for 14 d. Critical thermal maximum temperatures were estimated and data were analyzed using simple linear regression. There was no significant relationship (P > 0.05) between thermal tolerance and length for Nile tilapia (P = 0.33), channel catfish (P = 0.55), rainbow trout (P = 0.76), or largemouth bass (P = 0.93) for the length ranges we tested. There was a significant negative relationship between thermal tolerance and length for Rio Grande cutthroat trout (R2 = 0.412, P 2 = 0.1374, P = 0.028); however, the difference was less than 1°C across all lengths of Apache trout tested and about 1.3°C across all lengths of Rio Grande cutthroat trout tested. Because there was either no or at most a slight relationship between upper thermal tolerance and size, management and research decisions based on upper thermal tolerance should be similar for the range of sizes within each species we tested. However, the different sizes we tested only encompassed life stages ranging from fry to adult/subadult, so thermal tolerance of eggs, alevins, and larger adults should also be considered before making management decisions affecting an entire species.

Seasonal variation in thermal tolerance, oxygen consumption, antioxidative enzymes and non-specific immune indices of Indian hill trout, Barilius bendelisis (Hamilton, 1807) from central Himalaya, India.

PubMed

Sharma, Neeraj Kumar; Akhtar, M S; Pandey, Nityanand; Singh, Ravindra; Singh, Atul Kumar

2015-08-01

We studied the season dependent thermal tolerance, oxygen consumption, respiratory burst response and antioxidative enzyme activities in juveniles of Barilius bendelisis. The critical thermal maximum (CTmax), lethal thermal maximum (LTmax), critical thermal minimum (CTmin) and lethal thermal minimum (LTmin) were significantly different at five different seasons viz. winter (10.64°C), spring (16.25°C), summer (22.11°C), rainy (20.87°C) and autumn (17.77°C). The highest CTmax was registered in summer (36.02°C), and lowest CTmin was recorded during winter (2.77°C). Water temperature, dissolved oxygen and pH were strongly related to CTmax, LTmax, CTmin and LTmin suggesting seasonal acclimatization of B. bendelisis. The thermal tolerance polygon area of the B. bendelisis juveniles within the range of seasonal temperature (10.64-22.11°C) was calculated as 470.92°C(2). Oxygen consumption rate was significantly different (p<0.05) between seasons with maximum value during summer (57.66mgO2/kg/h) and lowest in winter (32.60mgO2/kg/h). Total white blood cell count including neutrophil and monocytes also showed significant difference (p<0.05) between seasons with maximum value during summer and minimum number in winter and were found correlated to temperature, dissolved oxygen, pH and respiratory burst activity. Respiratory burst activity of blood phagocytes significantly differed (p<0.05) among seasons with higher value during summer (0.163 OD540nm) and minimum in winter season (0.054 OD540nm). The activity of superoxide dismutase, catalase and glutathione-s-transferase both in liver and gill, also varied significantly (p<0.05) during different seasons. Overall results of this study suggest that multiple environmental factors play a role in seasonal acclimation in B. bendelisis, which modulate the thermal tolerance, oxygen consumption, respiratory burst activity and status of anti-oxidative potential in wild environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Insulin and glucose responses during bed rest with isotonic and isometric exercise

NASA Technical Reports Server (NTRS)

Dolkas, C. B.; Greenleaf, J. E.

1977-01-01

The effects of daily intensive isotonic (68% maximum oxygen uptake) and isometric (21% maximum extension force) leg exercise on plasma insulin and glucose responses to an oral glucose tolerance test (OGTT) during 14-day bed-rest (BR) periods were investigated in seven young healthy men. The OGTT was given during ambulatory control and on day 10 of the no-exercise, isotonic, and isometric exercise BR periods during the 15-wk study. The subjects were placed on a controlled diet starting 10 days before each BR period. During BR, basal plasma glucose concentration remained unchanged with no exercise, but increased (P less 0.05) to 87-89 mg/100 ml with both exercise regimens on day 2, and then fell slightly below control levels on day 13. The fall in glucose content during BR was independent of the exercise regimen and was an adjustment for the loss of plasma volume. The intensity of the responses of insulin and glucose to the OGTT was inversely proportional to the total daily energy expenditure during BR. It was estimated that at least 1020 kcal/day must be provided by supplemental exercise to restore the hyperinsulinemia to control levels.

Health risk assessment of trace elements via dietary intake of 'non-piscine protein source' foodstuffs (meat, milk and egg) in Bangladesh.

PubMed

Shaheen, Nazma; Ahmed, Md Kawser; Islam, Md Saiful; Habibullah-Al-Mamun, Md; Tukun, Avonti Basak; Islam, Saiful; M A Rahim, Abu Torab

2016-04-01

Concentrations of six trace elements [chromium (Cr), nickel (Ni), copper (Cu), cadmium (Cd), lead (Pb) and arsenic (As)] were assessed in 'non-piscine protein source' foodstuffs (meat, milk and eggs) to evaluate contamination level and human health risks in Bangladesh. The range of Cr, Ni, Cu, Cd, Pb and As in the investigated foodstuffs was 1.24-2.17, 1.29-2.56, 0.92-2.31, 0.12-0.44, 0.15-0.48 and 0.14-0.57 mg kg fresh weight(-1), respectively. The estimated mean levels of most of the elements were higher than the maximum allowable concentration (MAC) for dietary foods. The estimated daily intakes (EDIs) of Cr and Cd were higher than the maximum tolerable daily intake (MTDI) for children, indicating that they are more susceptible to toxic elements through food consumption. The target hazard quotients (THQs) and target carcinogenic risk (TCR) of As (THQ > 1 and TCR > 10(-4)) for both the adults and children suggest that the consumers of non-piscine foodstuffs (especially cow milk and chicken meat) are exposed chronically to metal pollution with carcinogenic and non-carcinogenic health consequences.

[Determination of insulin in saliva and its correlation with plasma insulin. Assessment of the possible participation++ of the salivary glands in the production of the hormone].

PubMed

Sánchez García, P; de Portugal Alvarez, J; Alonso Gutiérrez, D; Cruz Hernández, J J

1989-01-01

The finding of immunoreactive insulin (IRI) in saliva and an insulin-like protein, similar to pancreatic insulin and with the same biological activities, suggest that both products are pancreatic insulin stored and/or eliminated in the salival manner or an extrapancreatic hormone synthesis, bearing in mind the features which both glands share. The aim of this study is to ascertain whether the amount of insulin from saliva depends on plasmatic insulin and, if so, whether this is a form of elimination. Our results pointed out that the amount of insulin in saliva is similar to the plasmatic insulin in those patients with normal pancreatic function. The oral glucose tolerance test was carried out on 20 patients. The maximum insulin level was produced at the same time as maximum serum glucose level, taking place 60 minutes later. These data, support the concept that salival insulin is a product of the elimination more than synthesis by salival glands, however we can not exclude the possibility of synthesis by the salival gland without direct studies, the ideal test being the immunocytochemist.

Brushed permanent magnet DC MLC motor operation in an external magnetic field.

PubMed

Yun, J; St Aubin, J; Rathee, S; Fallone, B G

2010-05-01

Linac-MR systems for real-time image-guided radiotherapy will utilize the multileaf collimators (MLCs) to perform conformal radiotherapy and tumor tracking. The MLCs would be exposed to the external fringe magnetic fields of the linac-MR hybrid systems. Therefore, an experimental investigation of the effect of an external magnetic field on the brushed permanent magnet DC motors used in some MLC systems was performed. The changes in motor speed and current were measured for varying external magnetic field strengths up to 2000 G generated by an EEV electromagnet. These changes in motor characteristics were measured for three orientations of the motor in the external magnetic field, mimicking changes in motor orientations due to installation and/or collimator rotations. In addition, the functionality of the associated magnetic motor encoder was tested. The tested motors are used with the Varian 120 leaf Millennium MLC (Maxon Motor half leaf and full leaf motors) and the Varian 52 leaf MKII MLC (MicroMo Electronics leaf motor) including a carriage motor (MicroMo Electronics). In most cases, the magnetic encoder of the motors failed prior to any damage to the gearbox or the permanent magnet motor itself. This sets an upper limit of the external magnetic field strength on the motor function. The measured limits of the external magnetic fields were found to vary by the motor type. The leaf motor used with a Varian 52 leaf MKII MLC system tolerated up to 450 +/- 10 G. The carriage motor tolerated up to 2000 +/- 10 G field. The motors used with the Varian 120 leaf Millennium MLC system were found to tolerate a maximum of 600 +/- 10 G. The current Varian MLC system motors can be used for real-time image-guided radiotherapy coupled to a linac-MR system, provided the fringe magnetic fields at their locations are below the determined tolerance levels. With the fringe magnetic fields of linac-MR systems expected to be larger than the tolerance levels determined, some form of magnetic shielding would be required.

Calcium homeostasis during oral glucose load in healthy women.

PubMed

D'Erasmo, E; Pisani, D; Ragno, A; Raejntroph, N; Vecci, E; Acca, M

1999-04-01

It has been demonstrated that in healthy subjects during oral glucose tolerance test, serum calcium declines, while urinary calcium excretion increases, even if there is not a general agreement in this regard. The study was carried out in order to evaluate the effects of glucose oral load on calcium homeostasis in eight healthy adult women, also considering ionized calcium, plasma insulin and parathyroid hormone changes. The results showed a decline of total and ionized serum calcium (p < 0.05 and p < 0.01, respectively; maximum of the decrease at time 120'), in parallel with the increase of urinary calcium/ creatinine ratio (p < 0.05). Serum glucose and insulin increase (p < 0.0001 and p < 0.0005 respectively; maximum value at time 60'), while the parathyroid hormone level decreases (maximum decline at time 120', p < 0.01). No changes were observed in fasting control subjects for all parameters considered. The changes of these parameters with time suggest that the effects of glucose oral load on calcium metabolism in healthy adult women may be the consequence of parathyroid hormone suppression induced by acute hyperglycemia/hyperinsulinemia. The results confirm in vivo the PTH behaviour in vitro, on cultured bovine parathyroid cells, with high glucose concentration.

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

PubMed

Takeoka, Hiroaki; Yamada, Kazuhiko; Azuma, Koichi; Zaizen, Yoshiaki; Yamashita, Fumie; Yoshida, Tsukasa; Naito, Yoshiko; Okayama, Yusuke; Miyamoto, Maki; Hoshino, Tomoaki

2014-05-01

The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Molecular evolution of globin genes in Gymnotiform electric fishes: relation to hypoxia tolerance.

PubMed

Tian, Ran; Losilla, Mauricio; Lu, Ying; Yang, Guang; Zakon, Harold

2017-02-13

Nocturnally active gymnotiform weakly electric fish generate electric signals for communication and navigation, which can be energetically taxing. These fish mainly inhabit the Amazon basin, where some species prefer well-oxygenated waters and others live in oxygen-poor, stagnant habitats. The latter species show morphological, physiological, and behavioral adaptations for hypoxia-tolerance. However, there have been no studies of hypoxia tolerance on the molecular level. Globins are classic respiratory proteins. They function principally in oxygen-binding and -delivery in various tissues and organs. Here, we investigate the molecular evolution of alpha and beta hemoglobins, myoglobin, and neuroglobin in 12 gymnotiforms compared with other teleost fish. The present study identified positively selected sites (PSS) on hemoglobin (Hb) and myoglobin (Mb) genes using different maximum likelihood (ML) methods; some PSS fall in structurally important protein regions. This evidence for the positive selection of globin genes suggests that the adaptive evolution of these genes has helped to enhance the capacity for oxygen storage and transport. Interestingly, a substitution of a Cys at a key site in the obligate air-breathing electric eel (Electrophorus electricus) is predicted to enhance oxygen storage of Mb and contribute to NO delivery during hypoxia. A parallel Cys substitution was also noted in an air-breathing African electric fish (Gymnarchus niloticus). Moreover, the expected pattern under normoxic conditions of high expression of myoglobin in heart and neuroglobin in the brain in two hypoxia-tolerant species suggests that the main effect of selection on these globin genes is on their sequence rather than their basal expression patterns. Results indicate a clear signature of positive selection in the globin genes of most hypoxia-tolerant gymnotiform fishes, which are obligate or facultative air breathers. These findings highlight the critical role of globin genes in hypoxia tolerance evolution of Gymnotiform electric fishes.

The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H₃ receptor antagonist in patients with mild to moderate Alzheimer's disease: a preliminary investigation.

PubMed

Nathan, Pradeep J; Boardley, Rebecca; Scott, Nicola; Berges, Alienor; Maruff, Paul; Sivananthan, Tharani; Upton, Neil; Lowy, Martin T; Nestor, Peter J; Lai, Robert

2013-03-01

The histamine H3 receptor plays a critical role in the negative neuromodulation of neurotransmitters involved in cognitive function. H3 receptor antagonists/inverse agonists have been shown to exert pro-cognitive effects in pre-clinical models. GSK239512 is a potent and selective H₃ receptor antagonist developed for the treatment of cognitive dysfunction in neurodegenerative disorders. In this study we examined the safety, tolerability, pharmacokinetics and pro-cognitive effects of GSK239512 (oral) in patients with mild to moderate Alzheimer's disease using ascending dose titration regimens. The study was conducted in two parts. Part A was a single-blind, placebo run-in, flexible dose titration over 9 days in two cohorts, each consisting of two patients. Part B was a double-blind, randomised, placebo controlled, parallel group, which investigated 3 flexible dose titration regimens over 4 weeks in 3 cohorts, each consisting of eight patients. Overall, the 5/10/20/40 μg and 10/20/40/80 μg regimens were well-tolerated. The regimen of 20/40/80/150 μg showed the poorest tolerability likely due to the higher starting dose. There were no clinically significant abnormalities in haematology, clinical chemistry, urinalysis parameters and cardiovascular parameters. GSK239512 had positive effects on tasks of attention and memory with effect sizes between 0.56 and 1.37. GSK239512 displayed asatisfactory level of tolerability in patients with Alzheimer's disease with evidence for positive effects on attention and memory. The findings suggest that a titration regimen with a starting dose of 5-10 μg and a maximum dose of 80 μg is likely to be a well-tolerated and potentially efficacious regimen for future clinical trials in patients with Alzheimer's disease. These findings await replication in a larger study.

An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder.

PubMed

Takahashi, Michihiro; Takita, Yasushi; Goto, Taro; Ichikawa, Hironobu; Saito, Kazuhiko; Matsumoto, Hideo; Tanaka, Yasuo

2011-02-01

The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001). This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Modafinil in the treatment of excessive sleepiness

PubMed Central

Schwartz, Jonathan RL

2008-01-01

The wake-promoting agent modafinil is approved for the treatment of excessive sleepiness associated with obstructive sleep apnea (OSA), shift work disorder (SWD), and narcolepsy. In OSA, modafinil is recommended for use as an adjunct to standard therapies that treat the underlying airway obstruction. This article reviews the literature on modafinil (pharmacology, pharmacokinetics, efficacy, tolerability, and abuse potential), with emphasis on use of modafinil in the treatment of excessive sleepiness in patients with OSA, SWD, and narcolepsy. In large-scale, double-blind, placebo-controlled studies, modafinil improved objectively determined sleep latency, improved overall clinical condition related to severity of sleepiness, and reduced patient-reported sleepiness. Improvements in wakefulness were accompanied by improvements in behavioral alertness, functional status, and health-related quality of life. In patients with SWD, diary data showed modafinil reduced the maximum level of sleepiness during night shift work, level of sleepiness during the commute home, and incidence of accidents or near-accidents during the commute home when compared with placebo. Modafinil was well tolerated, without adversely affecting cardiovascular parameters or scheduled sleep. These findings and those of extension studies which reported improvements were maintained suggest modafinil has a beneficial effect on daily life and well-being in patients with excessive sleepiness associated with OSA, SWD, or narcolepsy. PMID:19920895

Cadmium, lead, tin, total mercury, and methylmercury in canned tuna commercialised in São Paulo, Brazil.

PubMed

de Paiva, Esther Lima; Morgano, Marcelo Antonio; Milani, Raquel Fernanda

2017-09-01

The objective of this work was to determine levels of inorganic contaminants in 30 samples of five commercial brands of canned tuna, acquired on the local market in Campinas, São Paulo, Brazil, in the year of 2015. Total mercury and methylmercury (MeHg+) were determined by atomic absorption with thermal decomposition and amalgamation; and cadmium, lead, and tin were determined by inductively coupled plasma optical emission spectrometry. Results indicated that 20% of the tuna samples surpassed limits determined by the Brazilian and European Commission legislation for cadmium; for lead, the maximum value found was 59 µg kg -1 and tin was not detected in any samples. The maximum values found for total Hg and MeHg+ were 261 and 258 µg kg -1 , respectively. As from the results obtained, it was estimated that the consumption of four cans per week (540 g) of tuna canned in water could surpass the provisional tolerable monthly intake for MeHg + by 100%.

Physiological Effects of Acceleration Observed During a Centrifuge Study of Pilot Performance

NASA Technical Reports Server (NTRS)

Smedal, Harald A.; Creer, Brent Y.; Wingrove, Rodney C.

1960-01-01

An investigation was conducted by the National Aeronautics and Space Administration, Ames Research Center, and the Naval Air Development Center, Aviation Medical Acceleration Laboratory, to study the effects of acceleration on pilot performance and to obtain some meaningful data for use in establishing tolerance to acceleration levels. The flight simulator used in the study was the Johnsville centrifuge operated as a closed loop system. The pilot was required to perform a control task in various sustained acceleration fields typical of those that Might be encountered by a pilot flying an entry vehicle in which he is seated in a forward-facing position. A special restraint system was developed and designed to increase the pilot's tolerance to these accelerations. The results of this study demonstrated that a well-trained subject, such as a test pilot, can adequately carry out a control task during moderately high accelerations for prolonged periods of time. The maximum levels of acceleration tolerated were approximately 6 times that of gravity for approximately 6 minutes, and varied slightly with the acceleration direction. The tolerance runs were in each case terminated by the subject. In all but two instances, the cause was extreme fatigue. On two occasions the subject terminated the run when he "grayed out." Although there were subjective and objective findings involving the visual and cardiovascular systems, the respiratory system yielded the more critical limiting factors. It would appear that these limiting factors were less severe during the "eyeballs-out" accelerations when compared with the "eyeballs-in" accelerations. These findings are explained on the basis of the influence that the inertial forces of acceleration have on the mechanics of respiration. A condensed version of this report was presented at the Annual Meeting of the Aerospace Medical Association, Miami Beach, May 5-11, 1960, in a paper entitled "Ability of Pilots to Perform a Control Task in Various Sustained Acceleration Fields."

Change in the Content of Immunoproteasomes and Macrophages in Rat Liver At the Induction of Donor-Specific Tolerance.

PubMed

Karpova, Ya D; Ustichenko, V D; Alabedal'karim, N M; Stepanova, A A; Lyupina, Yu V; Boguslavski, K I; Bozhok, G A; Sharova, N P

2017-01-01

Induction of donor specific tolerance (DST) by the introduction of donor cells into a recipient's portal vein is one of the approaches used to solve the problem of transplant engraftment. However, the mechanism of DST development remains unclear to this moment. In the present work, we first studied the change in the content of immunoproteasomes and macrophages of the liver at early stages of the development of allospecific portal tolerance in rats by Western blotting and flow cytofluorimetry. On the basis of the data obtained, we can conclude that the induction of DST is an active process characterized by two phases during which the level of the proteasome immune subunits LMP2 and LMP7 in liver mononuclear cells, including Kupffer cells, and the number of Kupffer cells change. The first phase lasts up to 5 days after the beginning of DST induction; the second phase - from 5 to 14 days. In both phases, the level of the subunits LMP2 and LMP7 in the total pool of mononuclear cells and Kupffer cells increases, with maximum values on days 1 and 7. In addition, the total number of Kupffer cells increases in both phases with a shift in several days. The most noticeable changes take place in the second phase. The third day is characterized by a lower content of mononuclear cells expressing immunoproteasomes compared to the control value in native animals. Presumably, at this time point a "window of opportunity" appears for subsequent filling of an empty niche with cells of different subpopulations and, depending on this fact, the development of tolerance or rejection. The results obtained raise the new tasks of finding ways to influence the cellular composition in the liver and the expression of immunoproteasomes on the third day after the beginning of DST induction to block the development of rejection.

SU-E-T-179: Clinical Impact of IMRT Failure Modes at Or Near TG-142 Tolerance Criteria Levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faught, J Tonigan; Balter, P; Johnson, J

2015-06-15

Purpose: Quantitatively assess the clinical impact of 11 critical IMRT dose delivery failure modes. Methods: Eleven step-and-shoot IMRT failure modes (FMs) were introduced into twelve Pinnacle v9.8 treatment plans. One standard and one highly modulated plan on the IROC IMRT phantom and ten previous H&N patient treatment plans were used. FMs included physics components covered by basic QA near tolerance criteria levels (TG-142) such as beam energy, MLC positioning, and MLC modeling. Resultant DVHs were compared to those of failure-free plans and the severity of plan degradation was assessed considering PTV coverage and OAR and normal tissue tolerances and usedmore » for FMEA severity scoring. Six of these FMs were physically simulated and phantom irradiations performed. TLD and radiochromic film results are used for comparison to treatment planning studies. Results: Based on treatment planning studies, the largest clinical impact from the phantom cases was induced by 2 mm systematic MLC shift in one bank with the combination of a D95% target under dose near 16% and OAR overdose near 8%. Cord overdoses of 5%–11% occurred with gantry angle, collimator angle, couch angle, MLC leaf end modeling, and MLC transmission and leakage modeling FMs. PTV coverage and/or OAR sparing was compromised in all FMs introduced in phantom plans with the exception of CT number to electron density tables, MU linearity, and MLC tongue-and-groove modeling. Physical measurements did not entirely agree with treatment planning results. For example, symmetry errors resulted in the largest physically measured discrepancies of up to 3% in the PTVs while a maximum of 0.5% deviation was seen in the treatment planning studies. Patient treatment plan study results are under analysis. Conclusion: Even in the simplistic anatomy of the IROC phantom, some basic physics FMs, just outside of TG-142 tolerance criteria, appear to have the potential for large clinical implications.« less

Can chilling tolerance of C 4 photosynthesis in Miscanthus be transferred to sugarcane?

DOE PAGES

Glowacka, Katarzyna; Ahmed, Aasifuddin; Sharma, Shailendra; ...

2015-07-29

Our goal is to investigate whether chilling tolerance of C 4 photosynthesis in Miscanthus can be transferred to sugarcane by hybridization. Net leaf CO 2 uptake (A sat) and we measured the maximum operating efficiency of photosystem II (Ф PSII) in warm conditions (25 °C/20 °C), and then during and following a chilling treatment of 10 °C/5 °C for 11 day in controlled environment chambers.

High Efficiency, Low EMI and Positioning Tolerant Wireless Charging of EVs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chabaan, Rakan

The objective of this project is to develop, implement, and demonstrate a wireless power transfer (WPT) system that is capable of the following metrics: Total system efficiencies of more than 85 percent with minimum 20 cm coil-to-coil gap; System output power at least 6.6 kW; but design system up to 19.2 kW for future higher power study; Maximum lateral positioning tolerance achievable while meeting regulatory emission guidelines.

The neotropical shrub Lupinus elegans, fromtemperate forests, may not adapt to climate change.

PubMed

Soto-Correa, J C; Sáenz-Romero, C; Lindig-Cisneros, R; de la Barrera, E

2013-05-01

Considering that their distribution is limited to altitudinal gradients along mountains that are likely to become warmer and drier, climate change poses an increased threat to temperate forest species from tropical regions. We studied whether the understorey shrub Lupinus elegans, endemic to temperate forests of west-central Mexico, will be able to withstand the projected temperature increase under seven climate change scenarios. Seeds were collected along an altitudinal gradient and grown in a shade-house over 7 months before determining their temperature tolerance as electrolyte leakage. The plants from colder sites tolerated lower temperatures, i.e. the temperature at which half of the maximum electrolyte leakage occurred (LT50), ranged from −6.4 ± 0.7 to −2.4 ± 0.3 °C. In contrast, no pattern was found for tolerance to high temperature (LT50 average 42.8 ± 0.3 °C). The climate change scenarios considered here consistently estimated an increase in air temperature during the present century that was higher for the maximum air temperature than for the mean or minimum. In particular, the anomaly from the normal maximum air temperature at the study region ranged from 2.8 °C by 2030 to 5.8 °C by 2090. In this respect, the inability of L. elegans to adapt to increasingly higher temperatures found here, in addition to a possible inhibition of reproduction caused by warmer winters, may limit its future distribution.

A two-dimensional biased coin design for dual-agent dose-finding trials.

PubMed

Sun, Zhichao; Braun, Thomas M

2015-12-01

Given the limited efficacy observed with single agents, there is growing interest in Phase I clinical trial designs that allow for identification of the maximum tolerated combination of two agents. Existing parametric designs may suffer from over- or under-parameterization. Thus, we have designed a nonparametric approach that can be easily understood and implemented for combination trials. We propose a two-stage adaptive biased coin design that extends existing methods for single-agent trials to dual-agent dose-finding trials. The basic idea of our design is to divide the entire trial into two stages and apply the biased coin design, with modification, in each stage. We compare the operating characteristics of our design to four competing parametric approaches via simulation in several numerical examples. Under all simulation scenarios we have examined, our method performs well in terms of identification of the maximum tolerated combination and allocation of patients relative to the performance of its competitors. In our design, stopping rule criteria and the distribution of the total sample size among the two stages are context-dependent, and both need careful consideration before adopting our design in practice. Efficacy is not a part of the dose-assignment algorithm, nor used to define the maximum tolerated combination. Our design inherits the favorable statistical properties of the biased coin design, is competitive with existing designs, and promotes patient safety by limiting patient exposure to toxic combinations whenever possible. © The Author(s) 2015.

Further evidence that a terminal drought tolerance QTL of pearl millet is associated with reduced salt uptake

PubMed Central

Sharma, Parbodh C.; Singh, Dhananjay; Sehgal, Deepmala; Singh, Gurbachan; Hash, C.T.; Yadav, Rattan S.

2014-01-01

Earlier, we established that a major drought tolerance QTL on linkage group 2 of pearl millet is also associated with reduced salt uptake and enhanced growth under salt stress. Present study was undertaken to re-assess the performance of drought tolerant (PRLT 2/89-33) and drought sensitive (H 77/833-2) parents along with two QTL-NILs (ICMR 01029 and ICMR 01040), under salinity stress specifically imposed during post-flowering growth stages when plants had developed their ion sinks in full. Time course changes in ionic accumulation and their compartmentalization in different plant parts was studied, specifically to monitor and capture changes conferred by the two alleles at this QTL, at small intervals. Amongst different plant parts, higher accumulation of toxic ion Na+ was recorded in roots. Further, the Na+ concentration in roots of the testcross hybrid of the drought-sensitive parent (H 77/833-2) reached its maximum at ECiw 15 dS m−1 within 24 h after salinity imposition, whereas it continued to increase with time in the testcross hybrids of the drought tolerant parent PRLT 2/89-33 as well as those of its QTL-NILs (ICMR 01029 and ICMR 01004) and reached at its maximum at 120 h stage. Comparison of differential distribution of toxic ions in individual leaves revealed that Na+ ions were not uniformly distributed in the leaves of the drought-tolerant parent and drought-tolerant QTL-NILs; but accumulated preferentially in the older leaves, whereas the hybrid of the drought-sensitive parent showed significantly higher Na+ concentration in all main stem leaves irrespective of their age. Dynamics of chlorophyll and proline concentration variation studied under salt stress at late flowering stages revealed a greater reduction, almost twice, in both leaf chlorophyll and proline concentrations in younger leaves in the hybrids of the sensitive parent as compared to the tolerant parent and QTL NILs. Imposition of salinity stress even at flowering stage affected the yield performance in pearl millet, wherein higher yield was recorded in drought tolerant parent and the two QTL-NILs compared to drought sensitive parent. PMID:24895469

Cloning of organic solvent tolerance gene ostA that determines n-hexane tolerance level in Escherichia coli.

PubMed Central

Aono, R; Negishi, T; Nakajima, H

1994-01-01

A variety of genes are involved in determining the level of organic solvent tolerance of Escherichia coli K-12. Gene ostA is one of the genes contributing to the level of organic solvent tolerance. This gene was cloned from an n-hexane-tolerant strain of E. coli, JA300. A JA300-based n-hexane-sensitive strain, OST4251, was converted to the n-hexane-tolerant phenotype by transformation with DNA containing the ostA gene derived from JA300. Thus, the cloned ostA gene complemented the n-hexane-sensitive phenotype of OST4251. Images PMID:7811102

Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial.

PubMed

Ghofrani, Hossein A; Reichenberger, Frank; Kohstall, Markus G; Mrosek, Eike H; Seeger, Timon; Olschewski, Horst; Seeger, Werner; Grimminger, Friedrich

2004-08-03

Alveolar hypoxia causes pulmonary hypertension and enhanced right ventricular afterload, which may impair exercise tolerance. The phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. To investigate the effects of sildenafil on exercise capacity under conditions of hypoxic pulmonary hypertension. Randomized, double-blind, placebo-controlled crossover study. University Hospital Giessen, Giessen, Germany, and the base camp on Mount Everest. 14 healthy mountaineers and trekkers. Systolic pulmonary artery pressure, cardiac output, and peripheral arterial oxygen saturation at rest and during assessment of maximum exercise capacity on cycle ergometry 1) while breathing a hypoxic gas mixture with 10% fraction of inspired oxygen at low altitude (Giessen) and 2) at high altitude (the Mount Everest base camp). Oral sildenafil, 50 mg, or placebo. At low altitude, acute hypoxia reduced arterial oxygen saturation to 72.0% (95% CI, 66.5% to 77.5%) at rest and 60.8% (CI, 56.0% to 64.5%) at maximum exercise capacity. Systolic pulmonary artery pressure increased from 30.5 mm Hg (CI, 26.0 to 35.0 mm Hg) at rest to 42.9 mm Hg (CI, 35.6 to 53.5 mm Hg) during exercise in participants taking placebo. Sildenafil, 50 mg, significantly increased arterial oxygen saturation during exercise (P = 0.005) and reduced systolic pulmonary artery pressure at rest (P < 0.001) and during exercise (P = 0.031). Of note, sildenafil increased maximum workload (172.5 W [CI, 147.5 to 200.0 W]) vs. 130.6 W [CI, 108.8 to 150.0 W]); P < 0.001) and maximum cardiac output (P < 0.001) compared with placebo. At high altitude, sildenafil had no effect on arterial oxygen saturation at rest and during exercise compared with placebo. However, sildenafil reduced systolic pulmonary artery pressure at rest (P = 0.003) and during exercise (P = 0.021) and increased maximum workload (P = 0.002) and cardiac output (P = 0.015). At high altitude, sildenafil exacerbated existing headache in 2 participants. The study did not examine the effects of sildenafil on normoxic exercise tolerance. Sildenafil reduces hypoxic pulmonary hypertension at rest and during exercise while maintaining gas exchange and systemic blood pressure. To the authors' knowledge, sildenafil is the first drug shown to increase exercise capacity during severe hypoxia both at sea level and at high altitude.

Investigations of suprathreshold color-difference tolerances with different visual scales and different perceptual correlates using CRT colors.

PubMed

Wang, Zhehong; Xu, Haisong

2008-12-01

In order to investigate the performance of suprathreshold color-difference tolerances with different visual scales and different perceptual correlates, a psychophysical experiment was carried out by the method of constant stimuli using CRT colors. Five hue circles at three lightness (L*=30, 50, and 70) and chroma (C*ab=10, 20, and 30) levels were selected to ensure that the color-difference tolerances did not exceed the color gamut of the CRT display. Twelve color centers distributed evenly every 30 degrees along each hue circle were assessed by a panel of eight observers, and the corresponding color-difference tolerances were obtained. The hue circle with L*=50 and C*ab=20 was assessed with three different visual scales (DeltaV=3.06, 5.92, and 8.87 CIELAB units), which ranged from small to large visual scales, while the remaining hue circles were observed only with the small visual scale. The lightness tolerances had no significant correlation with the hue angles, while chroma and hue tolerances showed considerable hue angle dependences. The color-difference tolerances were linearly proportional to the visual scales but with different slopes. The lightness tolerances with different lightness levels but the same chroma showed the crispening effect to some extent, while the chroma and hue tolerances decreased with the increment of the lightness. For the color-difference tolerances with different chroma levels but the same lightness, there was no correlation between the lightness tolerances and the chroma levels, while the chroma and hue tolerances were nearly linearly proportional to the chroma levels.

Immunologic changes in children with egg allergy ingesting extensively heated egg.

PubMed

Lemon-Mulé, Heather; Sampson, Hugh A; Sicherer, Scott H; Shreffler, Wayne G; Noone, Sally; Nowak-Wegrzyn, Anna

2008-11-01

Prior studies have suggested that heated egg might be tolerated by some children with egg allergy. We sought to confirm tolerance of heated egg in a subset of children with egg allergy, to evaluate clinical and immunologic predictors of heated egg tolerance, to characterize immunologic changes associated with continued ingestion of heated egg, and to determine whether a diet incorporating heated egg is well tolerated. Subjects with documented IgE-mediated egg allergy underwent physician-supervised oral food challenges to extensively heated egg (in the form of a muffin and a waffle), with tolerant subjects also undergoing regular egg challenges (in a form of scrambled egg or French toast). Heated egg-tolerant subjects incorporated heated egg into their diets. Skin prick test wheal diameters and egg white, ovalbumin, and ovomucoid IgE levels, as well as ovalbumin and ovomucoid IgG4 levels, were measured at baseline for all subjects and at 3, 6, and 12 months for those tolerant of heated egg. Sixty-four of 117 subjects tolerated heated egg, 23 tolerated regular egg, and 27 reacted to heated egg. Heated egg-reactive subjects had larger skin test wheals and greater egg white-specific, ovalbumin-specific, and ovomucoid-specific IgE levels compared with heated egg- and egg-tolerant subjects. Continued ingestion of heated egg was associated with decreased skin test wheal diameters and ovalbumin-specific IgE levels and increased ovalbumin-specific and ovomucoid-specific IgG4 levels. The majority of subjects with egg allergy were tolerant of heated egg. Continued ingestion of heated egg was well tolerated and associated with immunologic changes that paralleled the changes observed with the development of clinical tolerance to regular egg.

Water- and wastewater-related disease and infection risks: what is an appropriate value for the maximum tolerable additional burden of disease?

PubMed

Mara, Duncan

2011-06-01

The maximum additional burden of water- and wastewater-related disease of 10-6 disability-adjusted life year (DALY) loss per person per year (pppy), used in the WHO Drinking-water Quality Guidelines and the WHO Guidelines for Wastewater Use in Agriculture, is based on US EPA'S acceptance of a 70-year lifetime waterborne cancer risk of 10(-5) per person, equivalent to an annual risk of 1.4x10(-7) per person which is four orders of magnitude lower than the actual all-cancer incidence in the USA in 2009 of 1.8x10(-3) pppy. A maximum additional burden of 10(-4) DALY loss pppy would reduce this risk to a more cost-effective, but still low, risk of 1.4x10(-5) pppy. It would increase the DALY loss pppy in low- and middle-income countries due to diarrhoeal diseases from the current level of 0.0119 pppy to 0.0120 pppy, and that due to ascariasis from 0.0026 pppy to 0.0027 pppy, but neither increase is of public-health significance. It is therefore recommended that the maximum additional burden of disease from these activities be increased to a DALY loss of 10(-4) pppy as this provides an adequate margin of public-health safety in relation to waterborne-cancer deaths, diarrhoeal disease and ascariasis in all countries.

NaCl-induced physiological and biochemical changes in two cyanobacteria Nostoc muscorum and Phormidium foveolarum acclimatized to different photosynthetically active radiation.

PubMed

Kumar, Jitendra; Singh, Vijay Pratap; Prasad, Sheo Mohan

2015-10-01

The present study is aimed at investigating physiological and biochemical behavior of two cyanobacteria Nostoc muscorum and Phormidium foveolarum acclimatized to different levels (sub-optimum; 25 ± 0.5, optimum; 75 ± 2.5 and supra-optimum; 225 ± 3.5 μmol photons m(-2) s(-1)) of photosynthetic active radiation (PAR), and subsequently treated with two doses (30 and 90 mM) of NaCl. PAR influences growth in tested cyanobacteria being maximum in supra-optimum PAR acclimatized cells. NaCl-induced maximum percent decline in growth was observed in sub-optimum PAR acclimatized cells, which was in consonance with a decrease in chlorophyll content. Sub-optimum PAR acclimatization stimulated phycocyanin content in control cells, whereas maximum carotenoids content was observed in supra-optimum PAR acclimatized cells. Photosystem II photochemistry viz. Fv/F0, Fv/Fm, Ψ0, ϕE0, PIABS, ABS/RC, TR0/RC, ET0/RC and DI0/RC was also influenced by PAR and NaCl. Maximum percent rise in superoxide radical (SOR), hydrogen peroxide (H2O2) and lipid peroxidation was observed in sub-optimum PAR acclimatized cells exposed to NaCl, which could be correlated with lower values of enzymatic (superoxide dismutase, catalase, peroxidase and glutathione-S-transferase) and non-enzymatic (NP-SH and cysteine) antioxidants. In supra-optimum PAR acclimatized cells level of oxidative stress markers was in parallel with enhanced antioxidants. The results suggest that PAR significantly changes physiological and biochemical responses of studied cyanobacteria under NaCl stress. Besides this, this study also shows that P. foveolarum is more tolerant than N. muscorum under test conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Biodegradation of propargite by Pseudomonas putida, isolated from tea rhizosphere.

PubMed

Sarkar, Soumik; Seenivasan, Subbiah; Asir, Robert Premkumar Samuel

2010-02-15

Biodegradation of miticide propargite was carried out in vitro by selected Pseudomonas strains isolated from tea rhizosphere. A total number of 13 strains were isolated and further screened based on their tolerance level to different concentrations of propargite. Five best strains were selected and further tested for their nutritional requirements. Among the different carbon sources tested glucose exhibited the highest growth promoting capacity and among nitrogen sources ammonium nitrate supported the growth to the maximum. The five selected Pseudomonas strain exhibited a range of degradation capabilities. Mineral salts medium (MSM) amended with glucose provided better environment for degradation with the highest degradation potential in strain SPR 13 followed by SPR 8 (71.9% and 69.0% respectively).

Optimization of composite sandwich cover panels subjected to compressive loadings

NASA Technical Reports Server (NTRS)

Cruz, Juan R.

1991-01-01

An analysis and design method is presented for the design of composite sandwich cover panels that include the transverse shear effects and damage tolerance considerations. This method is incorporated into a sandwich optimization computer program entitled SANDOP. As a demonstration of its capabilities, SANDOP is used in the present study to design optimized composite sandwich cover panels for for transport aircraft wing applications. The results of this design study indicate that optimized composite sandwich cover panels have approximately the same structural efficiency as stiffened composite cover panels designed to satisfy individual constraints. The results also indicate that inplane stiffness requirements have a large effect on the weight of these composite sandwich cover panels at higher load levels. Increasing the maximum allowable strain and the upper percentage limit of the 0 degree and +/- 45 degree plies can yield significant weight savings. The results show that the structural efficiency of these optimized composite sandwich cover panels is relatively insensitive to changes in core density. Thus, core density should be chosen by criteria other than minimum weight (e.g., damage tolerance, ease of manufacture, etc.).

The Impact of Truth Surrogate Variance on Quality Assessment/Assurance in Wind Tunnel Testing

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2016-01-01

Minimum data volume requirements for wind tunnel testing are reviewed and shown to depend on error tolerance, response model complexity, random error variance in the measurement environment, and maximum acceptable levels of inference error risk. Distinctions are made between such related concepts as quality assurance and quality assessment in response surface modeling, as well as between precision and accuracy. Earlier research on the scaling of wind tunnel tests is extended to account for variance in the truth surrogates used at confirmation sites in the design space to validate proposed response models. A model adequacy metric is presented that represents the fraction of the design space within which model predictions can be expected to satisfy prescribed quality specifications. The impact of inference error on the assessment of response model residuals is reviewed. The number of sites where reasonably well-fitted response models actually predict inadequately is shown to be considerably less than the number of sites where residuals are out of tolerance. The significance of such inference error effects on common response model assessment strategies is examined.

Isothermal pumping analysis for high-altitude tethered balloons

PubMed Central

Kuo, Kirsty A.; Hunt, Hugh E. M.

2015-01-01

High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe. PMID:26543573

Isothermal pumping analysis for high-altitude tethered balloons.

PubMed

Kuo, Kirsty A; Hunt, Hugh E M

2015-06-01

High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe.

Effect of metal tolerant plant growth promoting bacteria on growth and metal accumulation in Zea mays plants grown in fly ash amended soil.

PubMed

Kumar, Kalpna V; Patra, D D

2013-01-01

The present study was undertaken to examine the effect of the application of fly ash (FA) into Garden soil (GS), with and without inoculation of plant growth promoting bacteria (PGPB), on the growth and metal uptake by Zea mays plants. Three FA tolerant PGPB strains, Pseudomonas sp. PS5, PS14, and Bacillus sp. BC29 were isolated from FA contaminated soils and assessed for their plant growth promoting features on the Z. mays plants. All three strains were also examined for their ability to solubilize phosphate and to produce Indole Acetic Acid (IAA), siderophores, and hydrogencynide acid (HCN) production. Although inoculation of all strains significantly enhanced the growth of plants at both the concentration of FA but maximum growth was observed in plants inoculated with BC29 and PS14 at low level (25%) of FA concentration. The experimental results explored the plant growth promoting features of selected strains which not only enhanced growth and biomass of plants but also protected them from toxicity of FA.

Evaluation of indigenous fresh water microalga Scenedesmus obtusus for feed and fuel applications: Effect of carbon dioxide, light and nutrient sources on growth and biochemical characteristics.

PubMed

Sarat Chandra, T; Deepak, R S; Maneesh Kumar, M; Mukherji, S; Chauhan, V S; Sarada, R; Mudliar, S N

2016-05-01

Scenedesmus obtusus, a freshwater microalga, was evaluated for its growth and biochemical characteristics under various culture conditions. S. obtusus was tolerant at all tested CO2 concentrations up to 20%. Among the different nitrogen sources, urea showed enhanced biomass productivities up to 2-fold compared to control, where the nitrogen source was sodium nitrate. Light intensity and photoperiod had a significant effect on growth rate and biomass productivity. The growth rate was observed maximum under continuous light exposure at the light intensities, 30μmolm(-2)sec(-1) and 60μmolm(-2)sec(-1) The species was able to tolerate the salinity levels up to 25mM NaCl, where, the increase in the concentration of NaCl suppressed the growth. Ammonium acetate and glycine showed better growth rate and biomass productivity indicating mixotrophic ability of S. obtusus. Supplementation of acetate and bicarbonate significantly enhanced the biomass productivity. Biodiesel properties of S. obtusus cultivated at various culture conditions were estimated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alternatives to Weight Tolerance Permits

DOT National Transportation Integrated Search

2000-10-01

A complex web of government regulations in the United States establishes maximum weights for vehicles on public roads. The primary purpose is to ensure compatibility of roadway design and operations with vehicle weight and dimensions. Of particular c...

Aerothermal performance and damage tolerance of a Rene 41 metallic standoff thermal protection system at Mach 6.7

NASA Technical Reports Server (NTRS)

Avery, D. E.

1984-01-01

A flight-weight, metallic thermal protection system (TPS) model applicable to Earth-entry and hypersonic-cruise vehicles was subjected to multiple cycles of both radiant and aerothermal heating in order to evaluate its aerothermal performance, structural integrity, and damage tolerance. The TPS was designed for a maximum operating temperature of 2060 R and featured a shingled, corrugation-stiffened corrugated-skin heat shield of Rene 41, a nickel-base alloy. The model was subjected to 10 radiant heating tests and to 3 radiant preheat/aerothermal tests. Under radiant-heating conditions with a maximum surface temperature of 2050 R, the TPS performed as designed and limited the primary structure away from the support ribs to temperatures below 780 R. During the first attempt at aerothermal exposure, a failure in the panel-holder test fixture severely damaged the model. However, two radiant preheat/aerothermal tests were made with the damaged model to test its damage tolerance. During these tests, the damaged area did not enlarge; however, the rapidly increasing structural temperature measuring during these tests indicates that had the damaged area been exposed to aerodynamic heating for the entire trajectory, an aluminum burn-through would have occurred.

A fault-tolerant intelligent robotic control system

NASA Technical Reports Server (NTRS)

Marzwell, Neville I.; Tso, Kam Sing

1993-01-01

This paper describes the concept, design, and features of a fault-tolerant intelligent robotic control system being developed for space and commercial applications that require high dependability. The comprehensive strategy integrates system level hardware/software fault tolerance with task level handling of uncertainties and unexpected events for robotic control. The underlying architecture for system level fault tolerance is the distributed recovery block which protects against application software, system software, hardware, and network failures. Task level fault tolerance provisions are implemented in a knowledge-based system which utilizes advanced automation techniques such as rule-based and model-based reasoning to monitor, diagnose, and recover from unexpected events. The two level design provides tolerance of two or more faults occurring serially at any level of command, control, sensing, or actuation. The potential benefits of such a fault tolerant robotic control system include: (1) a minimized potential for damage to humans, the work site, and the robot itself; (2) continuous operation with a minimum of uncommanded motion in the presence of failures; and (3) more reliable autonomous operation providing increased efficiency in the execution of robotic tasks and decreased demand on human operators for controlling and monitoring the robotic servicing routines.

SlCOR413IM1: A novel cold-regulation gene from tomato, enhances drought stress tolerance in tobacco.

PubMed

Ma, Xiaocui; Wang, Guodong; Zhao, Weiyang; Yang, Minmin; Ma, Nana; Kong, Fanying; Dong, Xinchun; Meng, Qingwei

2017-09-01

Drought stress adversely affects plant growth, development, and productivity. Genes functioning in plant response to drought stress are essential for drought tolerance. In this study, SlCOR413IM1, a cold-regulated gene isolated from Solanum lycopersium, was transferred to Nicotiana tabacum to investigate its function under drought stress. The subcellular localisation of SlCOR413IM1-GFP fusion protein in Arabidopsis protoplasts suggested that SlCOR413IM1 is a chloroplast protein. Expression analyses revealed that SlCOR413IM1 responded to drought and cold stresses. Under drought stress, transgenic plants maintained the high maximum photochemical efficiency, net photosynthetic rate (Pn) and D1 protein content of photosystem II (PSII). Compared with wild-type (WT) plants, transgenic plants showed higher superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities and proline and soluble sugar content, which reduced reactive oxygen species (ROS) generation. However, the high SOD and APX activities in transgenic plants were independent of their transcription levels. Moreover, the transgenic plants exhibited better seed germination, water status and survival, as well as lower malondialdehyde (MDA) content and relative electrical conductivity (REC) than WT plants under drought stress. Taken together, these data demonstrated that overexpression of SlCOR413IM1 enhanced drought stress tolerance in transgenic tobacco. Copyright © 2017. Published by Elsevier GmbH.

[Selection of acetate-tolerant mutants from Escherichia coli DH5alpha and the metabolic properties of mutant DA19].

PubMed

Zhu, Caiqing; Ye, Qin

2003-08-01

Esherichia coli DH5alpha is one of the widely used host strains in genetic engineering. However, foreign gene expression level in this strain is seriously inhibited due to its great sensitivity to the accumulated metabolite, acetate. This study aimed at improving the tolerance of this strain against acetate. Cells of E. coli DH5alpha were irradiated with 60Co, and subsequently continuous culture of the irradiated cells was conducted with gradual increase in the dilution rate and the selective pressure, acetate concentration in the medium. The mutants were picked up on MA plates which contained 5g/L sodium acetate. 5 strains with great improvement in acetate tolerance were obtained, among which DA19 was the best. In cultivation of DA19 in complex media YPS and YPS2G, the cell density, maximum specific growth rate and acetate produced were respectively 1.17 and 1.05, 1.08 and 1.27, and 0.06 and 0.59 times of those of DH5alpha. In a chemically defined medium, the cell density of DA19 was 3.4-fold of that of DH5alpha. The cell density of DA19 in a medium containing 10g/L sodium acetate was comparable to that of DH5alpha in the same medium without the addition of acetate.

Conserved effects of salinity acclimation on thermal tolerance and hsp70 expression in divergent populations of threespine stickleback (Gasterosteus aculeatus).

PubMed

Metzger, David C H; Healy, Timothy M; Schulte, Patricia M

2016-10-01

In natural environments, organisms must cope with complex combinations of abiotic stressors. Here, we use threespine stickleback (Gasterosteus aculeatus) to examine how changes in salinity affect tolerance of high temperatures. Threespine stickleback inhabit a range of environments that vary in both salinity and thermal stability making this species an excellent system for investigating interacting stressors. We examined the effects of environmental salinity on maximum thermal tolerance (CTMax) and 70 kDa heat shock protein (hsp70) gene expression using divergent stickleback ecotypes from marine and freshwater habitats. In both ecotypes, the CTMax of fish acclimated to 20 ppt was significantly higher compared to fish acclimated to 2 ppt. The effect of salinity acclimation on the expression of hsp70-1 and hsp70-2 was similar in both the marine and freshwater stickleback ecotype. There were differences in the expression profiles of hsp70-1 and hsp70-2 during heat shock, with hsp70-2 being induced earlier and to a higher level compared to hsp70-1. These data suggest that the two hsp70 isoforms may have functionally different roles in the heat shock response. Lastly, acute salinity challenge coupled with heat shock revealed that the osmoregulatory demands experienced during the heat shock response have a larger effect on the hsp70 expression profile than does the acclimation salinity.

Temperature and Leaf Osmotic Potential as Factors in the Acclimation of Photosynthesis to High Temperature in Desert Plants 1

PubMed Central

Seemann, Jeffrey R.; Downton, W. John S.; Berry, Joseph A.

1986-01-01

Seasonal changes in the high temperature limit for photosynthesis of desert winter annuals growing under natural conditions in Death Valley, California were studied using an assay based upon chlorophyll fluorescence. All species of this group were 6 to 9°C more tolerant of high temperature at the end of the growing season (May) than at its beginning (February). Over this same time period, the mean daily maximum air temperatures increased by 12°C. Laboratory studies have demonstrated that increases in thermal tolerance could be induced by increasing growth temperature alone. For plants growing under field conditions there was also a good correlation between the thermal tolerance of leaves and the osmotic potential of leaf water, indicating that increases in the concentrations of some small molecules might also confer increased thermal tolerance. Isolated chloroplast thylakoids subjected to increasing concentrations of sorbitol could be demonstrated to have increased thermal tolerance. PMID:16664743

Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients

PubMed Central

Grosbois, JM; Riquier, C; Chehere, B; Coquart, J; Béhal, H; Bart, F; Wallaert, B; Chenivesse, C

2016-01-01

Introduction Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. Objective The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. Methods Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. Results The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03). Conclusion The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR. PMID:27099483

An Empirical Comparison of Discrete Choice Experiment and Best-Worst Scaling to Estimate Stakeholders' Risk Tolerance for Hip Replacement Surgery.

PubMed

van Dijk, Joris D; Groothuis-Oudshoorn, Catharina G M; Marshall, Deborah A; IJzerman, Maarten J

2016-06-01

Previous studies have been inconclusive regarding the validity and reliability of preference elicitation methods. The aim of this study was to compare the metrics obtained from a discrete choice experiment (DCE) and profile-case best-worst scaling (BWS) with respect to hip replacement. We surveyed the general US population of men aged 45 to 65 years, and potentially eligible for hip replacement surgery. The survey included sociodemographic questions, eight DCE questions, and twelve BWS questions. Attributes were the probability of a first and second revision, pain relief, ability to participate in sports and perform daily activities, and length of hospital stay. Conditional logit analysis was used to estimate attribute weights, level preferences, and the maximum acceptable risk (MAR) for undergoing revision surgery in six hypothetical treatment scenarios with different attribute levels. A total of 429 (96%) respondents were included. Comparable attribute weights and level preferences were found for both BWS and DCE. Preferences were greatest for hip replacement surgery with high pain relief and the ability to participate in sports and perform daily activities. Although the estimated MARs for revision surgery followed the same trend, the MARs were systematically higher in five of the six scenarios using DCE. This study confirms previous findings that BWS or DCEs are comparable in estimating attribute weights and level preferences. However, the risk tolerance threshold based on the estimation of MAR differs between these methods, possibly leading to inconsistency in comparing treatment scenarios. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Phase I trial of combination chemotherapy with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer.

PubMed

Tahara, M; Araki, K; Okano, S; Kiyota, N; Fuse, N; Minashi, K; Yoshino, T; Doi, T; Zenda, S; Kawashima, M; Ogino, T; Hayashi, R; Minami, H; Ohtsu, A

2011-01-01

we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC). treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks. forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%. TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

Validation of the BetaStar® Advanced for Beta-lactams Test Kit for the Screening of Bulk Tank and Tanker Truck Milks for the Presence of Beta-lactam Drug Residues.

PubMed

Denhartigh, Andrew; Reynolds, Lindsay; Palmer, Katherine; Klein, Frank; Rice, Jennifer; Rejman, John J

2018-05-18

A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Beta-lactams) for the detection of beta-lactam residues in raw, commingled bovine milk. The assay detected amoxicillin, ampicillin, cloxacillin, penicillin, cephapirin, and ceftiofur below the U.S. Food and Drug Administration tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. The results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. The test detected all six drugs at the approximate 90/95% sensitivity levels in milk from cows treated with each drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 1148 control milk samples. Testing the estimated 90/95% sensitivity level for amoxicillin (8.5 ppb), ampicillin (6.9 ppb), cloxacillin (8.9 ppb), penicillin (4.2 ppb), and cephapirin (17.6 ppb), and at 100 ppb for each antibiotic, resulted in 94-100% positive tests for each of the beta-lactam drugs. The results of ruggedness experiments established the operating parameter tolerances for the assay. Cross-reactivity testing established that the assay detects other certain beta-lactam drugs, but it does not cross-react with any of 30 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts in raw milk produced no assay interference.

Efficacy and safety of disodium ascorbyl phytostanol phosphates in men with moderate dyslipidemia

PubMed Central

Trip, Mieke D.; Pritchard, P. Haydn; Tam, Patrick; Lukic, Tatjana; de Sain-van der Velden, Monique G.; de Barse, Martina; Kastelein, John J. P.

2008-01-01

Objective This study investigated the efficacy, safety, tolerability, and pharmacokinetics of a novel cholesterol absorption inhibitor, FM-VP4, comprising disodium ascorbyl sitostanol phosphate (DASP) and disodium ascorbyl campestanol phosphate (DACP). Methods In phase 1, 30 men received a single dose of 100, 200, 400, 800, 1,600, or 2,000 mg FM-VP4 or placebo. In phase 2, 100 men were treated with 100, 200, 400, or 800 mg/day of FM-VP4 or placebo for 4 weeks. Results The drug was well tolerated at each single or multiple dose level. After 4 weeks of treatment, low-density lipoprotein cholesterol (LDL-C) levels changed by 2.7% in the placebo group and by 2.9%, −4.2%, and −4.6% in the 100, 200, and 800 mg/day groups, respectively, which was not statistically significant. However, 400 mg/day of FM-VP4 significantly decreased LDL-C by 6.5% (p=0.02). Phase 1 showed that DACP and DASP were absorbed into plasma with a median tmax of 12 h for both components, and clearance was slow with a mean t1/2λ of 57 h. During 4 weeks of treatment, steady state was reached by approximately 8 days. Conclusion This study demonstrated that up to 800 mg/day of FM-VP4 is safe and well tolerated for at least 4 weeks. Furthermore, the higher doses significantly reduced LDL-C by 7% compared with baseline or by 10% compared with placebo, with the maximum effect reached at 400 mg/day. PMID:18320185

The Effects of Promethazine on Human Performance, Mood States, and Motion Sickness Tolerance

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Stout, Cynthia; Toscano, William B.; Reynoso, Samuel; DeRoshia, Charles

1996-01-01

Intramuscular (IM) injections of promethazine in 25 mg or 50 mg dosages are commonly used to treat space motion sickness in astronauts. The present study examined the effects of IM injections of promethazine on neuropsy-chological performance, mood states, and motion sickness tolerance in humans. Twelve men, mean age 36 plus or minus 3.1 participated in one training (no injections) and three treatment conditions: a 25 mg injection of promethazine, a 50 mg injection of promethazine, and a placebo injection of sterile saline. Each condition, spaced at 7 day intervals, required an 8-10 hr session in which subjects were given four repetitions of 12 performance tasks, and one rotating chair motion sickness test. On the training day subjects were trained on each task to establish stability and proficiency. On treatment days, the order in which the drug or placebo was assigned to subjects was counter-balanced and a double-blind technique was used. Statistically significant decrements in performance were observed on 10 of 12 tasks when subjects were given 25 mg or 50 mg of promethazine as compared to the placebo. Performance decrements were associated with mean blood alcohol dose equivalency levels of 0.085% for 25 mg and 0. 1 37% for 50 mg dosages. The mood scale results showed significant changes in individual subjective experiences with maximum deterioration in the arousal state and fatigue level. When compared to placebo significant increases in motion sickness tolerance were found for both dosages of promethazine. These data suggest that effective dosages of promethazine currently used to counteract motion sickness in astronauts may significantly impair task components of their operational performance.

A Study of the Focal Adhesion Kinase Inhibitor GSK2256098 in Patients with Recurrent Glioblastoma with Evaluation of Tumor Penetration of [11C]GSK2256098.

PubMed

Brown, Nicholas F; Williams, Matthew; Arkenau, Hendrik-Tobias; Fleming, Ronald A; Tolson, Jerry; Yan, Li; Zhang, Jianping; Swartz, Lisa; Singh, Rajendra; Auger, Kurt R; Lenox, Laurie; Cox, David; Lewis, Yvonne; Plisson, Christophe; Searle, Graham; Saleem, Azeem; Blagden, Sarah; Mulholland, Paul

2018-05-17

GSK2256098 is a novel oral focal adhesion kinase inhibitor. Preclinical studies demonstrate growth inhibition in glioblastoma cell lines. However, rodent studies indicate limited blood-brain barrier penetration. In this expansion cohort within a phase I study, the safety, tolerability, pharmacokinetics and clinical activity of GSK2256098 were evaluated in patients with recurrent glioblastoma. Biodistribution and kinetics of [11C]GSK2256098 were assessed in a sub-study using positron-emission tomography (PET). Patients were treated with GSK2256098 until disease progression or withdrawal due to adverse events (AEs). Serial pharmacokinetic samples were collected on Day 1. On a single day between Days 9-20, patients received a microdose of intravenous [11C]GSK2256098 and scanned with PET over 90 minutes with parallel PK sample collection. Response was assessed by MRI every six weeks. Thirteen patients were treated in three dose cohorts (1000 mg, 750 mg, 500 mg; all dosed twice-daily). The maximum tolerated dose was 1000 mg twice-daily. Dose-limiting toxicities were related to cerebral edema. Treatment-related AEs (>25%) were diarrhea, fatigue and nausea. Eight patients participated in the PET sub-study, with [11C]GSK2256098 VT estimates of 0.9 in tumor tissue, 0.5 in surrounding T2 enhancing areas, and 0.4 in normal brain,. Best response of stable disease was observed in three patients, including one patient on treatment for 11.3 months. GSK2256098 was tolerable in patients with relapsed glioblastoma. GSK2256098 crossed the blood-brain barrier at low levels into normal brain, but at markedly higher levels into tumor, consistent with tumor-associated blood-brain barrier disruption. Additional clinical trials of GSK2256098 are ongoing.

Comparison of heavy metal levels of farmed and escaped farmed rainbow trout and health risk assessment associated with their consumption.

PubMed

Varol, Memet; Sünbül, Muhammet Raşit

2017-10-01

In this study, levels of ten metals (arsenic, cadmium, cobalt, chromium, copper, iron, manganese, nickel, lead, and zinc) in muscles of farmed and escaped farmed rainbow trout (Oncorhynchus mykiss) in the Keban Dam Reservoir (Turkey) were determined. Also, human health risks associated with their consumption were assessed. Of ten metals, only Co and Fe levels in escaped rainbow trout were significantly higher than those in farmed rainbow trout. The metal levels in farmed and escaped rainbow trout were below the maximum permissible limits. The estimated daily intake (EDI) of each metal in both farmed and escaped farmed rainbow trout was much lower than the respective tolerable daily intake (TDI). The target hazard quotient (THQ) values for individual metal and the total THQ values for combined metals were lower than 1 in both farmed and escaped rainbow trout, indicating no health risk for humans. The cancer risk (CR) values estimated for inorganic As in both farmed and escaped rainbow trout indicated low carcinogenic risk to the consumers. According to the maximum allowable monthly consumption limits (CR mm) , adults may safely consume 24 meals of farmed rainbow trout per month or 39 meals of escaped rainbow trout per month, with minimal adverse carcinogenic and non-carcinogenic health effects. This study revealed that the risk from consuming farmed and escaped farmed rainbow trout in the Keban Dam Reservoir due to these trace elements is minimal.

Perimeter Barrier Selection Guide

DOT National Transportation Integrated Search

1989-05-01

This document provides a methodology to determine the magnitude of the threat from attack vehicles to the perimeter of a facility. The threat is determined by the penetration tolerance and the maximum speed attainable. After the threat is defined thi...

An examination of the damage tolerance enhancement of carbon/epoxy using an outer lamina of spectra (R)

NASA Technical Reports Server (NTRS)

Lance, D. G.; Nettles, A. T.

1991-01-01

Low velocity instrumented impact testing was utilized to examine the effects of an outer lamina of ultra-high molecular weight polyethylene (Spectra) on the damage tolerance of carbon epoxy composites. Four types of 16-ply quasi-isotropic panels (0, +45, 90, -45) were tested. Some panels contained no Spectra, while others had a lamina of Spectra bonded to the top (impacted side), bottom, or both sides of the composite plates. The specimens were impacted with energies up to 8.5 J. Force time plots and maximum force versus impact energy graphs were generated for comparison purposes. Specimens were also subjected to cross-sectional analysis and compression after impact tests. The results show that while the Spectra improved the maximum load that the panels could withstand before fiber breakage, the Spectra seemingly reduced the residual strength of the composites.

Heavy metals in aromatic spices by inductively coupled plasma-mass spectrometry.

PubMed

Bua, Daniel Giuseppe; Annuario, Giovanni; Albergamo, Ambrogina; Cicero, Nicola; Dugo, Giacomo

2016-09-01

Objective of this study was to determine the content of Cd, Hg, As and Pb in common spices traded in the Italian market, using inductively coupled plasma-mass spectrometry (ICP-MS). The results were compared with the maximum limits established by the national Legislative Decree (LD) no. 107 implementing the Council Directive 88/388/EEC and by international organisations, such as Food and Agriculture Organization (FAO) and World Health Organization (WHO). Food safety for spices was assessed considering the tolerable weekly intake (TWI) and the provisional tolerable weekly intake (PTWI), respectively, for Cd and Hg and the 95% lower confidence limit of the benchmark dose of 1% extra risk (BMDL01) for As and Pb. Investigated elements in all samples were within the maximum limits as set by the national and international normative institutions. Nevertheless, the heavy metal content of some spices exceeded the PTWI, TWI and BMDL01, which needs attention when considering consumer's health.

Impact of Expiratory Strength Training in Amyotrophic Lateral Sclerosis

PubMed Central

Plowman, Emily K.; Watts, Stephanie A.; Tabor, Lauren; Robison, Raele; Gaziano, Joy; Domer, Amanda S.; Richter, Joel; Vu, Tuan; Gooch, Clifton

2016-01-01

Introduction We evaluated the feasibility and impact of Expiratory Muscle Strength Training (EMST) on respiratory and bulbar function in persons with amyotrophic lateral sclerosis (ALS). Methods 25 ALS patients participated in this delayed intervention open-label clinical trial. Following a lead-in period, patients completed a 5-week EMST protocol. Outcome measures included: maximum expiratory pressure (MEP), physiologic measures of swallow and cough, and Penetration-Aspiration Scale (PAS) scores. Results Of those participants who entered the active phase of the study (n=15), EMST was well tolerated and led to significant increases in MEPs and maximum hyoid displacement during swallowing post-EMST (P<0.05). No significant differences were observed for PAS scores or cough spirometry measures. Discussion EMST was feasible and well tolerated in this small cohort of ALS patients and led to improvements in expiratory force-generating pressures and swallow kinematics. Further investigation is warranted to confirm these preliminary findings. PMID:26599236

The effects of in-flight treadmill exercise on postflight orthostatic tolerance

NASA Technical Reports Server (NTRS)

Siconolfi, Steven F.; Charles, John B.

1992-01-01

In-flight aerobic exercise is thought to decrease the deconditioning effects of microgravity. Two deconditioning characteristics are the decreases in aerobic capacity (maximum O2 uptake) and an increased cardiovascular response to orthostatic stress (supine to standing). Changes in both parameters were examined after Shuttle flights of 8 to 11 days in astronauts who performed no in-flight exercise, a lower than normal volume of exercise, and a near-normal volume of exercise. The exercise regimen was a traditional continuous protocol. Maximum O2 uptake was maintained in astronauts who completed a near-normal exercise volume of in-flight exercise. Cardiovascular responses to stand test were equivocal among the groups. The use of the traditional exercise regimen as a means to maintain adequate orthostatic responses produced equivocal responses. A different exercise prescription may be more effective in maintaining both exercise capacity and orthostatic tolerance.

Phototrophic cultivation of NaCl-tolerant mutant of Spirulina platensis for enhanced C-phycocyanin production under optimized culture conditions and its dynamic modeling.

PubMed

Gupta, Apurva; Mohan, Devendra; Saxena, Rishi Kumar; Singh, Surendra

2018-02-01

Commercial cultivation of Spirulina sp. is highly popular due to the presence of high amount of C-phycocyanin (C-PC) and other valuable chemicals like carotenoids and γ-linolenic acid. In this study, the pH and the concentrations of nitrogen and carbon source were manipulated to achieve improved cell growth and C-PC production in NaCl-tolerant mutant of Spirulina platensis. In this study, highest C-PC (147 mg · L -1 ) and biomass (2.83 g · L -1 ) production was achieved when a NaCl-tolerant mutant of S. platensis was cultivated in a nitrate and bicarbonate sufficient medium (40 and 60 mM, respectively) at pH 9.0 under phototrophic conditions. Kinetic study of wildtype S. platensis and its NaCl-tolerant mutant was also done to determine optimum nitrate concentrations for maximum growth and C-PC production. Kinetic parameter of inhibition (Haldane model) was fitted to the relationship between specific growth rate and substrate concentration obtained from the growth curves. Results showed that the maximum specific growth rate (μ max ) for NaCl-tolerant mutant increased by 17.94% as compared to its wildtype counterpart, with a slight increase in half-saturation constant (K s ), indicating that this strain could grow well at high concentration of NaNO 3 . C-PC production rate (C max ) in mutant cells increased by 12.2% at almost half the value of K s as compared to its wildtype counterpart. Moreover, the inhibition constant (K i ) value was 207.85% higher in NaCl-tolerant mutant as compared to its wildtype strain, suggesting its ability to produce C-PC even at high concentrations of NaNO 3 . © 2017 Phycological Society of America.

Psychological Stability of a Personality and Capability of Tolerant Interaction as Diverse Manifestations of Tolerance

ERIC Educational Resources Information Center

Belasheva, Irina Valeryevna; Petrova, Nina Fedorovna

2016-01-01

Present article addresses studying tolerance as a factor of personality stability, which manifests on the level of interpersonal relationships and on the level of intra-personal system of stressors resistance. The article includes theoretical analysis of the tolerance construct as an integrative personality formation. It explores the question of…

Cadmium-induced stress response of Phanerochaete chrysosporium during the biodegradation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47).

PubMed

Feng, Mi; Yin, Hua; Cao, Yajuan; Peng, Hui; Lu, Guining; Liu, Zehua; Dang, Zhi

2018-06-15

Cd-induced stress response of Phanerochaete chrysosporium during the biodegradation of BDE-47 was investigated in this study, with the goal of elucidating the tolerance behavior and the detoxification mechanisms of P. chrysosporium to resist the Cd stress in the course of BDE-47 biodegradation, which has implications for expanding the application of P. chrysosporium in the bioremediation of Cd and BDE-47 combined pollution. The results suggested that single BDE-47 exposure did not induce obvious oxidative stress in P. chrysosporium, but coexistent Cd significantly triggered ROS generation, both intracellular ROS level and H 2 O 2 content showed positive correlation with Cd concentration. The activities of SOD and CAT were enhanced by low level of Cd (≤ 1 mg/L), but Cd of higher doses (＞1 mg/L) depressed the expression of these two antioxidant enzymes at the later exposure period (3-5 days). The intracellular content of GSH along with GSH/GSSG ratio also exhibited a bell-shaped response with a maximum value at Cd of 1 mg/L. Furthermore, Cd-induced ROS generation resulted in the lipid peroxidation, as indicated by a noticeable increment of MDA content found after 3 days. Moreover, the study also indicated that Cd less than 1 mg/L promoted the production of extracellular protein and quickened the decrease of pH value in the medium, while excessive Cd (＞1 mg/L) would lead to inhibition. These findings obtained demonstrated that P. chrysosporium had a certain degree of tolerance to Cd within a specific concentration range via regulating the antioxidant levels, inducing the synthesis of extracellular protein as well as stimulating the production of organic acids, and 1 mg/L is suggested to be the tolerance threshold of this strains under Cd stress during BDE-47 biodegradation. Copyright © 2018 Elsevier Inc. All rights reserved.

Aboriginal Consumption of Estuarine Food Resources and Potential Implications for Health through Trace Metal Exposure; A Study in Gumbaynggirr Country, Australia.

PubMed

Russell, Shaina; Sullivan, Caroline A; Reichelt-Brushett, Amanda J

2015-01-01

Fishing and resource use continues to be an essential aspect of life for many Aboriginal communities throughout Australia. It is important for dietary sustenance, and also retains deep social, cultural and economic significance, playing a fundamental role in maintaining group cohesion, transferring cultural knowledge and affirming Indigenous identities. We surveyed approximately 20% of the Gumbaynggirr Aboriginal community of Nambucca Heads, New South Wales, Australia. This paper explores Gumbaynggirr Connection to Country and engagement in cultural practice. It quantifies fishing efforts and consumption of seafood within the community. We found 95% of the sample group fish, with the highest rate of fishing being 2-3 times a week (27%). Furthermore, 98% of participants eat seafood weekly or more frequently, up to more than once a day (24%). Survey results revealed that Myxus elongatus (Sand mullet) and naturally recruited Saccostrea glomerata (Sydney rock oysters) continue to be important wild resources to the Gumbaynggirr community. Trace metals were measured in M. elongatus and S. glomerata samples collected by community participants in this study. Maximum levels prescribed in the Australia New Zealand Food Standards Code were not exceeded in the edible tissue for either species, however both species exceeded the generally expected levels for zinc and copper and S. glomerata samples exceeded the generally expected level for selenium. Furthermore the average dietary exposure to trace metals from consuming seafood was calculated for the surveyed population. Trace metal intake was then compared to the provisional tolerable weekly intake prescribed by the Joint Expert Committee on Food Additives. This process revealed that copper and selenium intake were both within the provisional tolerable weekly intake, while there is no guideline for zinc. Furthermore, participants relying heavily on wild resources from the Nambucca River estuary may exceed the provisional tolerable weekly intake for cadmium. This suggests the need for further investigation of this issue to minimize any possible health risk.

Aboriginal Consumption of Estuarine Food Resources and Potential Implications for Health through Trace Metal Exposure; A Study in Gumbaynggirr Country, Australia

PubMed Central

Russell, Shaina; Sullivan, Caroline A.; Reichelt-Brushett, Amanda J.

2015-01-01

Fishing and resource use continues to be an essential aspect of life for many Aboriginal communities throughout Australia. It is important for dietary sustenance, and also retains deep social, cultural and economic significance, playing a fundamental role in maintaining group cohesion, transferring cultural knowledge and affirming Indigenous identities. We surveyed approximately 20% of the Gumbaynggirr Aboriginal community of Nambucca Heads, New South Wales, Australia. This paper explores Gumbaynggirr Connection to Country and engagement in cultural practice. It quantifies fishing efforts and consumption of seafood within the community. We found 95% of the sample group fish, with the highest rate of fishing being 2-3 times a week (27%). Furthermore, 98% of participants eat seafood weekly or more frequently, up to more than once a day (24%). Survey results revealed that Myxus elongatus (Sand mullet) and naturally recruited Saccostrea glomerata (Sydney rock oysters) continue to be important wild resources to the Gumbaynggirr community. Trace metals were measured in M. elongatus and S. glomerata samples collected by community participants in this study. Maximum levels prescribed in the Australia New Zealand Food Standards Code were not exceeded in the edible tissue for either species, however both species exceeded the generally expected levels for zinc and copper and S. glomerata samples exceeded the generally expected level for selenium. Furthermore the average dietary exposure to trace metals from consuming seafood was calculated for the surveyed population. Trace metal intake was then compared to the provisional tolerable weekly intake prescribed by the Joint Expert Committee on Food Additives. This process revealed that copper and selenium intake were both within the provisional tolerable weekly intake, while there is no guideline for zinc. Furthermore, participants relying heavily on wild resources from the Nambucca River estuary may exceed the provisional tolerable weekly intake for cadmium. This suggests the need for further investigation of this issue to minimize any possible health risk. PMID:26098897

Differential responses of double petal and multi petal jasmine to shading: I. Photosynthetic characteristics and chloroplast ultrastructure.

PubMed

Deng, Yanming; Li, Congcong; Shao, Qingsong; Ye, Xiaoqing; She, Jianming

2012-06-01

A double petal (DP) and a multi petal (MP) type jasmine (Jasminum sambac Ait.) growth and flowering was known largely affected by different levels of irradiance. Here, our objective was to determine the effects of shade on photosynthesis related characteristics and chloroplast ultrastructure of these two types. In both types, net photosynthetic rate (Pn), stomatal conductance (g(s)) and transpiration rate increased with decreasing irradiance from 100% to 20%, while both maximum and variable fluorescence showed a steady increase, and photochemical and nonphotochemical quenching indexes declined. At each conducted time, chlorophyll a, b and carotenoids contents in DP type shaded leaves increased whereas those in MP type decreased at 5% irradiance (considered as extreme shade). The maximum photochemical efficiency of photosystem II of DP plants showed subtle changes but that of MP plants declined by shading thereafter 21 days of treatment. Observation of chloroplast ultrastructure showed its best development in the leaves of DP and MP types mostly from 50% to 20% irradiance (considered as weak and moderate shade, respectively). At each shade treatment, Pn, g(s) and water use efficiency of DP-jasmine were always higher than those of MP-jasmine, thus the shade tolerance ability of the former was higher than that of the latter. The results showed that full sunlight and 5% natural irradiance caused photoinhibition and light deficiency of jasmine plants respectively, and modulating chloroplast development by the more numbers of thylakoids and grana to contain more photosynthetic pigments is an important shade tolerance mechanism of DP type. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours.

PubMed

Venugopal, B; Awada, A; Evans, T R J; Dueland, S; Hendlisz, A; Rasch, W; Hernes, K; Hagen, S; Aamdal, S

2015-10-01

CP-4126 (gemcitabine elaidate, previously CO-101) is a lipid-drug conjugate of gemcitabine designed to circumvent human equilibrative nucleoside transporter1-related resistance to gemcitabine. The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of CP-4126, and to describe its pharmacokinetic profile. Eligible patients with advanced refractory solid tumours, and adequate performance status, haematological, renal and hepatic function, were treated with one of escalating doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and 15 of a 28-day cycle. Blood and urine samples were collected to determine the pharmacokinetics (PKs) of CP-4126. Forty-three patients, median age 59 years (range 18-76; male = 27, female = 16), received one of ten dose levels (30-1600 mg/m(2)). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m(2) on basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven patients achieved stable disease sustained for ≥3 months, including two patients with pancreatic cancer who had progressed on or after gemcitabine exposure. CP-4126 was well tolerated with comparable toxicity profile to gemcitabine. Future studies are required to determine its anti-tumour efficacy, either alone or in combination with other cytotoxic chemotherapy regimens.

Oxygen dependence of upper thermal limits in fishes.

PubMed

Ern, Rasmus; Norin, Tommy; Gamperl, A Kurt; Esbaugh, Andrew J

2016-11-01

Temperature-induced limitations on the capacity of the cardiorespiratory system to transport oxygen from the environment to the tissues, manifested as a reduced aerobic scope (maximum minus standard metabolic rate), have been proposed as the principal determinant of the upper thermal limits of fishes and other water-breathing ectotherms. Consequently, the upper thermal niche boundaries of these animals are expected to be highly sensitive to aquatic hypoxia and other environmental stressors that constrain their cardiorespiratory performance. However, the generality of this dogma has recently been questioned, as some species have been shown to maintain aerobic scope at thermal extremes. Here, we experimentally tested whether reduced oxygen availability due to aquatic hypoxia would decrease the upper thermal limits (i.e. the critical thermal maximum, CT max ) of the estuarine red drum (Sciaenops ocellatus) and the marine lumpfish (Cyclopterus lumpus). In both species, CT max was independent of oxygen availability over a wide range of oxygen levels despite substantial (>72%) reductions in aerobic scope. These data show that the upper thermal limits of water-breathing ectotherms are not always linked to the capacity for oxygen transport. Consequently, we propose a novel metric for classifying the oxygen dependence of thermal tolerance; the oxygen limit for thermal tolerance (P CT max ), which is the water oxygen tension (Pw O 2 ) where an organism's CT max starts to decline. We suggest that this metric can be used for assessing the oxygen sensitivity of upper thermal limits in water-breathing ectotherms, and the susceptibility of their upper thermal niche boundaries to environmental hypoxia. © 2016. Published by The Company of Biologists Ltd.

Ethanol adaptation induces direct protection and cross-protection against freezing stress in Salmonella enterica serovar Enteritidis.

PubMed

He, S; Zhou, X; Shi, C; Shi, X

2016-03-01

Salmonella enterica serovar Enteritidis (Salm. Enteritidis) encounters mild ethanol stress during its life cycle. However, adaptation to a stressful condition may affect bacterial resistance to subsequent stresses. Hence, this work was undertaken to investigate the influences of ethanol adaptation on stress tolerance of Salm. Enteritidis. Salmonella Enteritidis was subjected to different ethanol adaptation treatments (2·5-10% ethanol for 1 h). Cellular morphology and tolerance to subsequent environmental stresses (15% ethanol, -20°C, 4°C, 50°C and 10% NaCl) were evaluated. It was found that 10% was the maximum ethanol concentration that allowed growth of the target bacteria. Ethanol adaptation did not cause cell-surface damage in Salm. Enteritidis as revealed by membrane permeability measurements and electron micrograph analysis. Salmonella Enteritidis adapted with 2·5-10% ethanol displayed an enhanced resistance to a 15%-ethanol challenge compared with an unchallenged control. The maximum ethanol resistance was observed when ethanol concentration used for ethanol adaptation was increased to 5·0%. Additionally, pre-adaptation to 5·0% ethanol cross-protected Salm. Enteritidis against -20°C, but not against 4°C, 50°C or 10% NaCl. Ethanol adaptation provided Salm. Enteritidis direct protection from a high level ethanol challenge and cross-protection from freezing, but not other stresses tested (low temperature, high salinity or high temperature). The results are valuable in developing adequate and efficient control measures for Salm. Enteritidis in foods. © 2016 The Society for Applied Microbiology.

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension - study protocol for a randomized controlled trial.

PubMed

Cestário, Elizabeth do Espirito Santo; Fernandes, Letícia Aparecida Barufi; Giollo-Júnior, Luiz Tadeu; Uyemura, Jéssica Rodrigues Roma; Matarucco, Camila Suemi Sato; Landim, Manoel Idelfonso Paz; Cosenso-Martin, Luciana Neves; Tácito, Lúcia Helena Bonalume; Moreno, Heitor; Vilela-Martin, José Fernando; Yugar-Toledo, Juan Carlos

2018-02-12

Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney. This is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride. On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group. In recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney. Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973 . Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.

Effects of oxygen on responses to heating in two lizard species sampled along an elevational gradient.

PubMed

DuBois, P Mason; Shea, Tanner K; Claunch, Natalie M; Taylor, Emily N

2017-08-01

Thermal tolerance is an important variable in predictive models about the effects of global climate change on species distributions, yet the physiological mechanisms responsible for reduced performance at high temperatures in air-breathing vertebrates are not clear. We conducted an experiment to examine how oxygen affects three variables exhibited by ectotherms as they heat-gaping threshold, panting threshold, and loss of righting response (the latter indicating the critical thermal maximum)-in two lizard species along an elevational (and therefore environmental oxygen partial pressure) gradient. Oxygen partial pressure did not impact these variables in either species. We also exposed lizards at each elevation to severely hypoxic gas to evaluate their responses to hypoxia. Severely low oxygen partial pressure treatments significantly reduced the gaping threshold, panting threshold, and critical thermal maximum. Further, under these extreme hypoxic conditions, these variables were strongly and positively related to partial pressure of oxygen. In an elevation where both species overlapped, the thermal tolerance of the high elevation species was less affected by hypoxia than that of the low elevation species, suggesting the high elevation species may be adapted to lower oxygen partial pressures. In the high elevation species, female lizards had higher thermal tolerance than males. Our data suggest that oxygen impacts the thermal tolerance of lizards, but only under severely hypoxic conditions, possibly as a result of hypoxia-induced anapyrexia. Copyright © 2017. Published by Elsevier Ltd.

Worldwide Mycotoxins Exposure in Pig and Poultry Feed Formulations

PubMed Central

Guerre, Philippe

2016-01-01

The purpose of this review is to present information about raw materials that can be used in pig and poultry diets and the factors responsible for variations in their mycotoxin contents. The levels of mycotoxins in pig and poultry feeds are calculated based on mycotoxin contamination levels of the raw materials with different diet formulations, to highlight the important role the stage of production and the raw materials used can have on mycotoxins levels in diets. Our analysis focuses on mycotoxins for which maximum tolerated levels or regulatory guidelines exist, and for which sufficient contamination data are available. Raw materials used in feed formulation vary considerably depending on the species of animal, and the stage of production. Mycotoxins are secondary fungal metabolites whose frequency and levels also vary considerably depending on the raw materials used and on the geographic location where they were produced. Although several reviews of existing data and of the literature on worldwide mycotoxin contamination of food and feed are available, the impact of the different raw materials used on feed formulation has not been widely studied. PMID:27886128

Interdependency of Reactive Oxygen Species generating and scavenging system in salt sensitive and salt tolerant cultivars of rice.

PubMed

Kaur, Navdeep; Dhawan, Manish; Sharma, Isha; Pati, Pratap Kumar

2016-06-10

Salinity stress is a major constrain in the global rice production and hence serious efforts are being undertaken towards deciphering its remedial strategies. The comparative analysis of differential response of salt sensitive and salt tolerant lines is a judicious approach to obtain essential clues towards understanding the acquisition of salinity tolerance in rice plants. However, adaptation to salt stress is a fairly complex process and operates through different mechanisms. Among various mechanisms involved, the reactive oxygen species mediated salinity tolerance is believed to be critical as it evokes cascade of responses related to stress tolerance. In this background, the present paper for the first time evaluates the ROS generating and the scavenging system in tandem in both salt sensitive and salt tolerant cultivars of rice for getting better insight into salinity stress adaptation. Comparative analysis of ROS indicates the higher level of hydrogen peroxide (H2O2) and lower level of superoxide ions (O(2-)) in the salt tolerant as compared to salt sensitive cultivars. Specific activity of ROS generating enzyme, NADPH oxidase was also found to be more in the tolerant cultivars. Further, activities of various enzymes involved in enzymatic and non enzymatic antioxidant defence system were mostly higher in tolerant cultivars. The transcript level analysis of antioxidant enzymes were in alignment with the enzymatic activity. Other stress markers like proline were observed to be higher in tolerant varieties whereas, the level of malondialdehyde (MDA) equivalents and chlorophyll content were estimated to be more in sensitive. The present study showed significant differences in the level of ROS production and antioxidant enzymes activities among sensitive and tolerant cultivars, suggesting their possible role in providing natural salt tolerance to selected cultivars of rice. Our study demonstrates that the cellular machinery for ROS production and scavenging system works in an interdependent manner to offer better salt stress adaptation in rice. The present work further highlights that the elevated level of H2O2 which is considered as a key determinant for conferring salt stress tolerance to rice might have originated through an alternative route of photocatalytic activity of chlorophyll.

Salinity and temperature tolerance of brown-marbled grouper Epinephelus fuscoguttatus.

PubMed

Cheng, Sha-Yen; Chen, Chih-Sung; Chen, Jiann-Chu

2013-04-01

Grouper have to face varied environmental stressors as a result of drastic changes to water conditions during the storm season. We aimed to test the response of brown-marbled grouper to drastic and gradual changes in temperature and salinity to understand the grouper's basic stress response. The results can improve the culture of grouper. Brown-marbled grouper, Epinephelus fuscoguttatus (6.2 ± 0.8 g) were examined for temperature and salinity tolerances at nine different environmental regimes (10, 20, and 33 ‰ combined with 20, 26 and 32 °C), in which the fish were subjected to both gradual and sudden changes in temperature and salinity. The critical thermal maximum (50 % CTMAX) and the upper incipient lethal temperature (UILT) were in the ranges of 35.9-38.3 and 32.7-36.5 °C, respectively. The critical thermal minimum (50 % CTMIN) and the lower incipient lethal temperature (LILT) were in the ranges of 9.8-12.2 and 14.9-22.3 °C, respectively. The critical salinity maximum (50 % CSMAX) and the upper incipient lethal salinity (UILS) were in the ranges of 67.0-75.5 and 54.2-64.8 ‰, respectively. Fish at temperature of 20 °C and a salinity of 33 ‰ tolerated temperatures as low as 10 °C when the temperature was gradually decreased. Fish acclimated at salinities of 10-33 ‰ and a temperature of 32 °C tolerated salinities of as high as 75-79 ‰. All fish survived from accumulating salinity after acute transfer to 20, 10, 5, and 3 ‰. But all fish died while transferred to 0 ‰. Relationships among the UILT, LILT, 50 % CTMAX, 50 % CTMIN, UILS, 50 % CSMAX, salinity, and temperature were examined. The grouper's temperature and salinity tolerance elevated by increasing acclimation temperature and salinity. On the contrary, the grouper's temperature and salinity tolerance degraded by decreasing acclimation temperature and salinity. The tolerance of temperature and salinity on grouper in gradual changes were higher than in drastic changes.

SU-F-J-25: Position Monitoring for Intracranial SRS Using BrainLAB ExacTrac Snap Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, S; McCaw, T; Huq, M

2016-06-15

Purpose: To determine the accuracy of position monitoring with BrainLAB ExacTrac snap verification following couch rotations during intracranial SRS. Methods: A CT scan of an anthropomorphic head phantom was acquired using 1.25mm slices. The isocenter was positioned near the centroid of the frontal lobe. The head phantom was initially aligned on the treatment couch using cone-beam CT, then repositioned using ExacTrac x-ray verification with residual errors less than 0.2mm and 0.2°. Snap verification was performed over the full range of couch angles in 15° increments with known positioning offsets of 0–3mm applied to the phantom along each axis. At eachmore » couch angle, the smallest tolerance was determined for which no positioning deviation was detected. Results: For couch angles 30°–60° from the center position, where the longitudinal axis of the phantom is approximately aligned with the beam axis of one x-ray tube, snap verification consistently detected positioning errors exceeding the maximum 8mm tolerance. Defining localization error as the difference between the known offset and the minimum tolerance for which no deviation was detected, the RMS error is mostly less than 1mm outside of couch angles 30°–60° from the central couch position. Given separate measurements of patient position from the two imagers, whether to proceed with treatment can be determined by the criterion of a reading within tolerance from just one (OR criterion) or both (AND criterion) imagers. Using a positioning tolerance of 1.5mm, snap verification has sensitivity and specificity of 94% and 75%, respectively, with the AND criterion, and 67% and 93%, respectively, with the OR criterion. If readings exceeding maximum tolerance are excluded, the sensitivity and specificity are 88% and 86%, respectively, with the AND criterion. Conclusion: With a positioning tolerance of 1.5mm, ExacTrac snap verification can be used during intracranial SRS with sensitivity and specificity between 85% and 90%.« less

The safety and pharmacokinetics of rapid iloprost aerosol delivery via the BREELIB nebulizer in pulmonary arterial hypertension

PubMed Central

Gessler, Tobias; Ghofrani, Hossein-Ardeschir; Held, Matthias; Klose, Hans; Leuchte, Hanno; Olschewski, Horst; Rosenkranz, Stephan; Fels, Lueder; Li, Na; Ren, Dawn; Kaiser, Andreas; Schultze-Mosgau, Marcus-Hillert; Müllinger, Bernhard; Rohde, Beate; Seeger, Werner

2017-01-01

The BREELIB nebulizer was developed for iloprost to reduce inhalation times for patients with pulmonary arterial hypertension (PAH). This multicenter, randomized, unblinded, four-part study compared inhalation time, pharmacokinetics, and acute tolerability of iloprost 5 µg at mouthpiece delivered via BREELIB versus the standard I-Neb nebulizer in 27 patients with PAH. The primary safety outcome was the proportion of patients with a maximum increase in heart rate (HR) ≥ 25% and/or a maximum decrease in systolic blood pressure ≥ 20% within 30 min after inhalation. Other safety outcomes included systolic, diastolic, and mean blood pressure, HR, oxygen saturation, and adverse events (AEs). Median inhalation times were considerably shorter with BREELIB versus I-Neb (2.6 versus 10.9 min; n = 24). Maximum iloprost plasma concentration and systemic exposure (area under the plasma concentration–time curve) were 77% and 42% higher, respectively, with BREELIB versus I-Neb. Five patients experienced a maximum systolic blood pressure decrease ≥ 20%, four with BREELIB (one mildly and transiently symptomatic), and one with I-Neb; none required medical intervention. AEs reported during the study were consistent with the known safety profile of iloprost. The BREELIB nebulizer offers reduced inhalation time, good tolerability, and may improve iloprost aerosol therapy convenience and thus compliance for patients with PAH. PMID:28597762

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

2016-08-01

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

Strong environmental tolerance of moss Venturiella under very high pressure

NASA Astrophysics Data System (ADS)

Ono, F.; Mori, Y.; Takarabe, K.; Nishihira, N.; Shindo, A.; Saigusa, M.; Matsushima, Y.; Saini, N. L.; Yamashita, M.

2010-03-01

It was shown by the present authors group that tardigrade can survive under high pressure of 7.5 GPa. In the case of land plants, however, no result of such experiment has been reported. We have extended our experiments to moss searching for lives under very high pressure. Spore placentas of moss Venturiella were sealed in a small Teflon capsule together with a liquid pressure medium. The capsule was put in the center of a pyrophillite cube, and the maximum pressure of 7.5 GPa was applied using a two-stage cubic anvil press. The pressure was kept constant at the maximum pressure for12, 24, 72 and 144 hours. After the pressure was released, the spores were seeded on a ager medium, and incubated for one week and more longer at 25°C with white light of 2000 lux. It was proved that 70-90% of the spores were alive and germinated after exposed to the maximum pressure of 7.5 GPa for up to 72 hours. However, after exposed to 7.5 GPa for 6 days, only 4 individuals in a hundred were germinated. The pressure tolerance of moss Venturiella is found to be stronger than a small animal, tardigrade.

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

Concentration of Mercury in Cockles (Anadara granosa and A. antiquata) Harvested from Estuaries of Western Lombok, Indonesia, and Potential Risks to Human Health.

PubMed

Rahayu, Rachmawati Noviana; Irawan, Bambang; Soegianto, Agoes

2016-01-01

This study measured the levels of total mercury (tHg) in the whole tissues of cockles (Anadara granosa and A. antiquata) harvested from three estuaries of Western Lombok Island (WLI), Indonesia. This paper also evaluated the hazard level posed by the mercury in relation to the maximum residual limit for human consumption and to estimate the weekly intake and compare it with the provisional tolerable weekly intake (PTWI). The tHg concentrations in A. granosa ranged from 0.020 to 0.070 mg kg(-1), and those in A. antiquata were between 0.032 and 0.077 mg kg(-1) at all locations. All samples of cockles harvested from WLI contain tHg below the permissible limit for human consumption. The maximum weekly intakes for total mercury by coastal people range from 0.28 to 1.08 µg kg(-1) b.w., and they are below the recommended values of PTWI (5.6 µg kg(-1) b.w.). If it is assumed that 100% of the Hg in cockles is methyl mercury (MeHg), consumption of the indicated amounts at the measured values wouldn't exceed the MeHg PTWI (1.6 µg kg(-1) b.w.).

Copper tolerance in clones of Agrostis gigantea from a mine waste site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, G.D.; Courtin, G.M.; Rauser, W.E.

1977-04-15

A mine waste site from Sudbury, Ontario, contaminated with heavy metals is described. The dominant vegetative cover was formed by two grasses: Agrostis gigantea Roth. and Agrostis scabra Willd. Testing of 10 clones of A. gigantea from the roast bed and an adjoining area for copper tolerance showed that two clones collected from the roast bed were tolerant to increased copper levels. Copper tolerance was found in clones growing on soils with high copper contents and low pHs. The combination of high copper content and low pH brought about a high level of extractable copper within the soil. Soils withmore » equally high copper levels but higher pHs and therefore low extractable-copper levels did not support copper-tolerant clones.« less

Assessing variation in tolerance in 23 Muslim-majority and Western countries.

PubMed

Milligan, Scott; Andersen, Robert; Brym, Robert

2014-08-01

Scholars disagree over whether Islam hinders the development of liberal democracy in Muslim-majority countries. We contribute to this debate by assessing the influence of Islam at the individual and national levels on ethnic, racial, and religious tolerance in 23 countries. Our analyses are based on a set of multilevel models fitted to World Values Survey data and national-level contextual information from various sources. Our findings suggest that people living in Muslim-majority countries tend to be less tolerant than are those living in Western countries. Although a significant part of this difference is attributable to variation in level of economic development and income inequality, Muslim countries remain less tolerant even after controlling for these factors. On the other hand, controlling for other individual-level factors, nonpracticing Muslims in Western countries are more tolerant than are all others in both Muslim-majority and Western countries. This finding challenges common claims about the effects of Islam as a religion on tolerance, suggesting that it is Islamic political regimes--not Islam itself--that pose problems for social tolerance.

Antimicrobial resistant coliform bacteria in the Gomti river water and determination of their tolerance level.

PubMed

Akhter, Asma; Imran, Mohd; Akhter, Firoz

2014-01-01

The distribution of resistance to ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin among coliform in the Gomti river water samples was investigated. The coliform populations were isolated on Mac Conky and eosin methylene blue (EMB) agar plates supplemented with antibiotics. The incidence of resistance among the coliform population varied considerably in different drug and water sampling sites. Coliform bacteria showed lower drug resistant viable count in sampling site-III (receiving treated wastewater) as compared to more polluted site-I and site-II. Viable count of coliform population obtained on both medium was recorded higher against erythromycin from sampling site-III. Lower viable count of coliforms was recorded against tetracycline in site-II and III. Similar resistance pattern was obtained in the frequency of E. coli and Enterobacter species from all the three sampling sites. Percentage of antibiotic resistant E. coli was observed higher than Enterobacter spp among the total coliforms against all antibiotics tested without Erythromycin and penicillin in site-I and II respectively. Isolates of E. coli and Enterobacter spp. showed their tolerance level (MIC) in the range of 2-100 against the antibiotics tested. Maximum number of isolates of both genus exhibited their MICs at lower concentration range 2-5µg/ml against ciprofloxacin, tetracyclin and amoxycillin. EMB - Eosin methylene blue, IMViC tests - Indole, Methyl Red, Voges Proskauer and Citrate Utilization Tests, MIC - Minimum inhibitory concentration.

Antimicrobial resistant coliform bacteria in the Gomti river water and determination of their tolerance level

PubMed Central

Akhter, Asma; Imran, Mohd; Akhter, Firoz

2014-01-01

The distribution of resistance to ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin among coliform in the Gomti river water samples was investigated. The coliform populations were isolated on Mac Conky and eosin methylene blue (EMB) agar plates supplemented with antibiotics. The incidence of resistance among the coliform population varied considerably in different drug and water sampling sites. Coliform bacteria showed lower drug resistant viable count in sampling site-III (receiving treated wastewater) as compared to more polluted site-I and site-II. Viable count of coliform population obtained on both medium was recorded higher against erythromycin from sampling site-III. Lower viable count of coliforms was recorded against tetracycline in site-II and III. Similar resistance pattern was obtained in the frequency of E. coli and Enterobacter species from all the three sampling sites. Percentage of antibiotic resistant E. coli was observed higher than Enterobacter spp among the total coliforms against all antibiotics tested without Erythromycin and penicillin in site-I and II respectively. Isolates of E. coli and Enterobacter spp. showed their tolerance level (MIC) in the range of 2-100 against the antibiotics tested. Maximum number of isolates of both genus exhibited their MICs at lower concentration range 2-5µg/ml against ciprofloxacin, tetracyclin and amoxycillin. Abbreviations EMB - Eosin methylene blue, IMViC tests - Indole, Methyl Red, Voges Proskauer and Citrate Utilization Tests, MIC - Minimum inhibitory concentration. PMID:24966515

Factors driving public tolerance levels and information‐seeking behaviour concerning insects in the household environment

PubMed Central

Poortvliet, P Marijn; Takken, Willem

2018-01-01

Abstract BACKGROUND The public's negative attitudes towards household insects drive tolerance for these insects and their control. Tolerance levels are important in integrated pest management (IPM), as are pest knowledge and information. The risk information seeking and processing (RISP) model describes the relationships between personal factors and information‐seeking behaviour. We combined IPM and RISP to determine important relationships between factors driving insect tolerance levels and information‐seeking behaviour through an online survey and tested whether this model is valid and generally applicable. RESULTS Relationships between variables from both IPM and RISP models were tested for seven insect species. Tolerance levels were measured with two factors: willingness to pay for pest control and whether insects are tolerated. Willingness to pay for control was positively affected by age, experience, risk perception, insect characteristics, and negative emotions and affected behavioural intention, by influencing information sufficiency and information‐seeking behaviour. Tolerability was influenced by perception of insect characteristics and determines whether control measures are taken. CONCLUSION It was possible to combine the RISP and IPM models. Relevant driving factors were a person's age, experience, risk perception, negative affective responses, tolerance levels, relevant channel beliefs about online forums, information sufficiency and information‐seeking behaviour. There was, however, variation in important factors between different insects. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:29274106

Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

PubMed

Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

2016-05-01

SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

Development of a neuromuscular electrical stimulation protocol for sprint training.

PubMed

Russ, David W; Clark, Brian C; Krause, Jodi; Hagerman, Fredrick C

2012-09-01

Sprint training is associated with several beneficial adaptations in skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca(2+) release. Unfortunately, several patient populations (e.g., the elderly, those with cardiac dysfunction) that might derive great benefit from sprint exercise are unlikely to tolerate it. The purpose of this report was to describe the development of a tolerable neuromuscular electrical stimulation (NMES) protocol that induces skeletal muscle adaptations similar to those observed with sprint training. Our NMES protocol was modeled after a published sprint exercise protocol and used a novel electrode configuration and stimulation sequence to provide adequate training stimulus while maintaining subject tolerance. Nine young, healthy subjects (four men) began and completed the training protocol of the knee extensor muscles. All subjects completed the protocol, with ratings of discomfort far less than those reported in studies of traditional NMES. Training induced significant increases in SR Ca(2+) release and citrate synthase activity (~16% and 32%, respectively), but SR Ca(2+) uptake did not change. The percentage of myosin heavy chain IIx isoform was decreased significantly after training. At the whole muscle level, neither central activation nor maximum voluntary isometric contraction force were significantly altered, although isometric force did exhibit a trend toward an increase (~3%, P = 0.055). Surprisingly, the NMES training produced a significant increase in muscle cross-sectional area (~3%, P = 0.04). It seems that an appropriately designed NMES protocol can mimic many of the benefits of sprint exercise training, with a low overall time commitment and training volume. These findings suggest that NMES has the potential to bring the benefits of sprint exercise to individuals who are unable to tolerate traditional sprint training.

Do mitochondrial properties explain intraspecific variation in thermal tolerance?

PubMed

Fangue, Nann A; Richards, Jeffrey G; Schulte, Patricia M

2009-02-01

As global temperatures rise, there is a growing need to understand the physiological mechanisms that determine an organism's thermal niche. Here, we test the hypothesis that increases in mitochondrial capacity with cold acclimation and adaptation are associated with decreases in thermal tolerance using two subspecies of killifish (Fundulus heteroclitus) that differ in thermal niche. We assessed whole-organism metabolic rate, mitochondrial amount and mitochondrial function in killifish acclimated to several temperatures. Mitochondrial enzyme activities and mRNA levels were greater in fish from the northern subspecies, particularly in cold-acclimated fish, suggesting that the putatively cold-adapted northern subspecies has a greater capacity for increases in mitochondrial amount in response to cold acclimation. When tested at the fish's acclimation temperature, maximum ADP-stimulated (State III) rates of mitochondrial oxygen consumption in vitro were greater in cold-acclimated northern fish than in southern fish but did not differ between subspecies at higher acclimation temperatures. Whole-organism metabolic rate was greater in fish of the northern subspecies at all acclimation temperatures. Cold acclimation also changed the response of mitochondrial respiration to acute temperature challenge. Mitochondrial oxygen consumption was greater in cold-acclimated northern fish than in southern fish at low test temperatures, but the opposite was true at high test temperatures. These differences were reflected in whole-organism oxygen consumption. Our data indicate that the plasticity of mitochondrial function and amount differs between killifish subspecies, with the less high-temperature tolerant, and putatively cold adapted, northern subspecies having greater ability to increase mitochondrial capacity in the cold. However, there were few differences in mitochondrial properties between subspecies at warm acclimation temperatures, despite differences in both whole-organism oxygen consumption and thermal tolerance at these temperatures.

Lack of Physiological Depth Patterns in Conspecifics of Endemic Antarctic Brown Algae: A Trade-Off between UV Stress Tolerance and Shade Adaptation?

PubMed Central

Gómez, Iván; Huovinen, Pirjo

2015-01-01

A striking characteristic of endemic Antarctic brown algae is their broad vertical distribution. This feature is largely determined by the shade adaptation in order to cope with the seasonal variation in light availability. However, during spring-summer months, when light penetrates deep in the water column these organisms have to withstand high levels of solar radiation, including UV. In the present study we examine the light use characteristics in parallel to a potential for UV tolerance (measured as content of phenolic compounds, antioxidant activity and maximum quantum yield of fluorescence) in conspecific populations of four Antarctic brown algae (Ascoseira mirabilis, Desmarestia menziesii, D. anceps and Himantothallus grandifolius) distributed over a depth gradient between 5 and 30 m. The main results indicated that a) photosynthetic efficiency was uniform along the depth gradient in all the studied species, and b) short-term (6 h) exposure to UV radiation revealed a high tolerance measured as chlorophyll fluorescence, phlorotannin content and antioxidant capacity. Multivariate analysis of similarity indicated that light requirements for photosynthesis, soluble phlorotannins and antioxidant capacity are the variables determining the responses along the depth gradient in all the studied species. The suite of physiological responses of algae with a shallower distribution (A. mirabilis and D. menziesii) differed from those with deeper vertical range (D. anceps and H. grandifolius). These patterns are consistent with the underwater light penetration that defines two zones: 0–15 m, with influence of UV radiation (1% of UV-B and UV-A at 9 m and 15 m respectively) and a zone below 15 m marked by PAR incidence (1% up to 30 m). These results support the prediction that algae show a UV stress tolerance capacity along a broad depth range according to their marked shade adaptation. The high contents of phlorotannins and antioxidant potential appear to be strongly responsible for the lack of clear depth patterns in light demand characteristics and UV tolerance. PMID:26252953

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a κ-Opioid Agonist in THC-Treated Mice.

PubMed

Chopda, Girish R; Parge, Viraj; Thakur, Ganesh A; Gatley, S John; Makriyannis, Alexandros; Paronis, Carol A

2016-08-01

Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to >90% of maximal possible effect. Treatment with THC produced 9- and 7-fold rightward shifts of the diuresis and antinociception dose-response curves for THC and, respectively, 7- and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to >35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the Bmax value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis dose-effect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

[High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure].

PubMed

Tauchert, M; Gildor, A; Lipinski, J

1999-10-01

The efficacy and tolerance of the standardized hawthorn (crataegus) extract WS 1442 were tested in a multicenter utilization observational study. We monitored 1,011 patients with cardiac insufficiency stage NYHA II, treated with this extract (Crataegutt novo 450, 1 tablet b.i.d.) over a period of 24 weeks. During and at the end of the observation period a significant improvement in clinical symptoms (reduced performance in the exercise tolerance test, fatigue, palpitation and exercise dyspnea) was observed. Ankle edema and nocturia disappeared by 83%, and by half of the patients respectively manifesting these symptoms before treatment. The improvement and economization of cardiac performance were additionally shown by a reduction in blood pressure, an increased maximal exercise tolerance and a reduction in the difference in the pressure/heart rate product (PHRP). The positive effects of WS 1442 were further demonstrated by an improved ejection fraction and an increased percentile shortening fraction measured using M-mode echocardiography. The stabilizing effect of the hawthorn extract on the heart rate was shown by a slower rest pulse, as well as by an increase in the number of day and night normorhythmic patients, as documented by long-term ECG. The reduction in the number of patients showing ST depressions, arrhythmias and ventricular extrasystoles at the maximum exercise level is regarded as an indication for an improved myocardial perfusion. Fourteen side effects were noted. In two cases (abdominal discomfort and facial pains accompanied by tachycardia) a possible relationship with the hawthorn therapy, was postulated which however was considered unlikely by the treating physicians. Almost 2/3 of the patients felt better or much better following the 24 weeks of treatment. More than 3/4 of the participating physicians noted a good or a very good efficacy, and 98.7% noted a good or a very good tolerance. High-dose hawthorn therapy is an efficient, well-tolerated and easily regulated therapeutic alternative for patients suffering from cardiac insufficiency stage NYHA II.

40 CFR 86.000-8 - Emission standards for 2000 and later model year light-duty vehicles.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Fueled, Natural Gas-Fueled, Liquefied Petroleum Gas-Fueled and Methanol-Fueled Heavy-Duty Vehicles § 86... mixture required to obtain maximum torque (lean best torque), plus a tolerance of six (6) percent. The...

40 CFR 86.000-8 - Emission standards for 2000 and later model year light-duty vehicles.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Fueled, Natural Gas-Fueled, Liquefied Petroleum Gas-Fueled and Methanol-Fueled Heavy-Duty Vehicles § 86... mixture required to obtain maximum torque (lean best torque), plus a tolerance of six (6) percent. The...

Multiple Heavy Metal Tolerance of Soil Bacterial Communities and Its Measurement by a Thymidine Incorporation Technique

PubMed Central

Díaz-Raviña, Montserrat; Bååth, Erland; Frostegård, Åsa

1994-01-01

A thymidine incorporation technique was used to determine the tolerance of a soil bacterial community to Cu, Cd, Zn, Ni, and Pb. An agricultural soil was artificially contaminated in our laboratory with individual metals at three different concentrations, and the results were compared with the results obtained by using the plate count technique. Thymidine incorporation was found to be a simple and rapid method for measuring tolerance. Data obtained by this technique were very reproducible. A linear relationship was found between changes in community tolerance levels obtained by the thymidine incorporation and plate count techniques (r = 0.732, P < 0.001). An increase in tolerance to the metal added to soil was observed for the bacterial community obtained from each polluted soil compared with the community obtained from unpolluted soil. The only exception was when Pb was added; no indication of Pb tolerance was found. An increase in the tolerance to metals other than the metal originally added to soil was also observed, indicating that there was multiple heavy metal tolerance at the community level. Thus, Cu pollution, in addition to increasing tolerance to Cu, also induced tolerance to Zn, Cd, and Ni. Zn and Cd pollution increased community tolerance to all five metals. Ni amendment increased tolerance to Ni the most but also increased community tolerance to Zn and, to lesser degrees, increased community tolerance to Pb and Cd. In soils polluted with Pb increased tolerance to other metals was found in the following order: Ni > Cd > Zn > Cu. We found significant positive relationships between changes in Cd, Zn, and Pb tolerance and, to a lesser degree, between changes in Pb and Ni tolerance when all metals and amendment levels were compared. The magnitude of the increase in heavy metal tolerance was found to be linearly related to the logarithm of the metal concentration added to the soil. Threshold tolerance concentrations were estimated from these linear relationships, and changes in tolerance could be detected at levels of soil contamination similar to those reported previously to result in changes in the phospholipid fatty acid pattern (Å. Frostegård, A. Tunlid, and E. Bååth, Appl. Environ. Microbiol. 59: 3605-3617, 1993). PMID:16349314

Heavy metals in rice samples on the Torbat-Heidarieh market, Iran.

PubMed

Roya, Amiri Qandashtani; Ali, Mohamadi Sani

2017-03-01

Levels of the heavy metals arsenic (As), cadmium (Cd) and lead (Pb) were determined in rice samples imported from India and Pakistan and marketed in Torbat-Heidarieh, Iran. To assess the safety of dietary intake of these metals by rice, the estimated weekly intake (EWI) was calculated and compared with the provisional tolerable weekly intake (PTWI). The results indicated that mean values for Pb and cadmium in imported rice were considerably higher than the safe limit as set by FAO/WHO. EWI for cadmium and As among the consumed types of imported rice was lower than the PTWI. The results also revealed that the weekly intake of Pb was higher than the maximum weekly intake recommended by WHO/FAO.

Dissipation of excess photosynthetic energy contributes to salinity tolerance: a comparative study of salt-tolerant Ricinus communis and salt-sensitive Jatropha curcas.

PubMed

Lima Neto, Milton C; Lobo, Ana K M; Martins, Marcio O; Fontenele, Adilton V; Silveira, Joaquim Albenisio G

2014-01-01

The relationships between salt tolerance and photosynthetic mechanisms of excess energy dissipation were assessed using two species that exhibit contrasting responses to salinity, Ricinus communis (tolerant) and Jatropha curcas (sensitive). The salt tolerance of R. communis was indicated by unchanged electrolyte leakage (cellular integrity) and dry weight in leaves, whereas these parameters were greatly affected in J. curcas. The leaf Na+ content was similar in both species. Photosynthesis was intensely decreased in both species, but the reduction was more pronounced in J. curcas. In this species biochemical limitations in photosynthesis were more prominent, as indicated by increased C(i) values and decreased Rubisco activity. Salinity decreased both the V(cmax) (in vivo Rubisco activity) and J(max) (maximum electron transport rate) more significantly in J. curcas. The higher tolerance in R. communis was positively associated with higher photorespiratory activity, nitrate assimilation and higher cyclic electron flow. The high activity of these alternative electron sinks in R. communis was closely associated with a more efficient photoprotection mechanism. In conclusion, salt tolerance in R. communis, compared with J. curcas, is related to higher electron partitioning from the photosynthetic electron transport chain to alternative sinks. Copyright © 2013 Elsevier GmbH. All rights reserved.

Chlorophyll fluorescence emission as a reporter on cold tolerance in Arabidopsis thaliana accessions

PubMed Central

Mishra, Anamika; Höermiller, Imke I; Heyer, Arnd G; Nedbal, Ladislav

2011-01-01

Non-invasive, high-throughput screening methods are valuable tools in breeding for abiotic stress tolerance in plants. Optical signals such as chlorophyll fluorescence emission can be instrumental in developing new screening techniques. In order to examine the potential of chlorophyll fluorescence to reveal plant tolerance to low temperatures, we used a collection of nine Arabidopsis thaliana accessions and compared their fluorescence features with cold tolerance quantified by the well established electrolyte leakage method on detached leaves. We found that, during progressive cooling, the minimal chlorophyll fluorescence emission rose strongly and that this rise was highly dependent on the cold tolerance of the accessions. Maximum quantum yield of PSII photochemistry and steady state fluorescence normalized to minimal fluorescence were also highly correlated to the cold tolerance measured by the electrolyte leakage method. In order to further increase the capacity of the fluorescence detection to reveal the low temperature tolerance, we applied combinatorial imaging that employs plant classification based on multiple fluorescence features. We found that this method, by including the resolving power of several fluorescence features, can be well employed to detect cold tolerance already at mild sub-zero temperatures. Therefore, there is no need to freeze the screened plants to the largely damaging temperatures of around −15°C. This, together with the method's easy applicability, represents a major advantage of the fluorescence technique over the conventional electrolyte leakage method. PMID:21427532

Evidence for a freezing tolerance-growth rate trade-off in the live oaks (Quercus series Virentes) across the tropical-temperate divide.

PubMed

Koehler, Kari; Center, Alyson; Cavender-Bares, Jeannine

2012-02-01

• It has long been hypothesized that species are limited to the north by minimum temperature and to the south by competition, resulting in a trade-off between freezing tolerance and growth rate. We investigated the extent to which the climatic origins of populations from four live oak species (Quercus series Virentes) were associated with freezing tolerance and growth rate, and whether species fitted a model of locally adapted populations, each with narrow climatic tolerances, or of broadly adapted populations with wide climatic tolerances. • Acorns from populations of four species across a tropical-temperate gradient were grown under common tropical and temperate conditions. Growth rate, seed mass, and leaf and stem freezing traits were compared with source minimum temperatures. • Maximum growth rates under tropical conditions were negatively correlated with freezing tolerance under temperate conditions. The minimum source temperature predicted the freezing tolerance of populations under temperate conditions. The tropical species Q. oleoides was differentiated from the three temperate species, and variation among species was greater than among populations. • The trade-off between freezing tolerance and growth rate supports the range limit hypothesis. Limited variation within species indicates that the distributions of species may be driven more strongly by broad climatic factors than by highly local conditions. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

Hydraulics and life history of tropical dry forest tree species: coordination of species' drought and shade tolerance.

PubMed

Markesteijn, Lars; Poorter, Lourens; Bongers, Frans; Paz, Horacio; Sack, Lawren

2011-07-01

Plant hydraulic architecture has been studied extensively, yet we know little about how hydraulic properties relate to species' life history strategies, such as drought and shade tolerance. The prevailing theories seem contradictory. We measured the sapwood (K(s) ) and leaf (K(l) ) hydraulic conductivities of 40 coexisting tree species in a Bolivian dry forest, and examined associations with functional stem and leaf traits and indices of species' drought (dry-season leaf water potential) and shade (juvenile crown exposure) tolerance. Hydraulic properties varied across species and between life-history groups (pioneers vs shade-tolerant, and deciduous vs evergreen species). In addition to the expected negative correlation of K(l) with drought tolerance, we found a strong, negative correlation between K(l) and species' shade tolerance. Across species, K(s) and K(l) were negatively correlated with wood density and positively with maximum vessel length. Consequently, drought and shade tolerance scaled similarly with hydraulic properties, wood density and leaf dry matter content. We found that deciduous species also had traits conferring efficient water transport relative to evergreen species. Hydraulic properties varied across species, corresponding to the classical trade-off between hydraulic efficiency and safety, which for these dry forest trees resulted in coordinated drought and shade tolerance across species rather than the frequently hypothesized trade-off. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

Mercury concentrations in lean fish from the Western Mediterranean Sea: Dietary exposure and risk assessment in the population of the Balearic Islands.

PubMed

Llull, Rosa Maria; Garí, Mercè; Canals, Miquel; Rey-Maquieira, Teresa; Grimalt, Joan O

2017-10-01

The present study reports total mercury (THg) and methylmercury (MeHg) concentrations in 32 different lean fish species from the Western Mediterranean Sea, with a special focus on the Balearic Islands. The concentrations of THg ranged between 0.05mg/kg ww and 3.1mg/kg ww (mean 0.41mg/kg ww). A considerable number of the most frequently fish species consumed by the Spanish population exceed the maximum levels proposed by the European legislation when they originate from the Mediterranean Sea, such as dusky grouper (100% of the examined specimens), common dentex (65%), conger (45%), common sole (38%), hake (26%) and angler (15%), among others. The estimated weekly intakes (EWI) in children (7-12 years of age) and adults from the Spanish population (2.7µg/kg bw and 2.1µg/kg bw, respectively) for population only consuming Mediterranean fish were below the provisional tolerable weekly intake (PTWI) of THg established by EFSA in 2012, 4µg/kg bw. However, the equivalent estimations for methylmercury, involving PTWI of 1.3µg/kg bw, were two times higher in children and above 50% in adults. For hake, sole, angler and dusky grouper, the most frequently consumed fish, the estimated weekly intakes in both children and adults were below the maximum levels accepted. These intakes correspond to maximum potential estimations because fish from non-Mediterranean origin is often consumed by the Spanish population including the one from the Balearic Islands. Copyright © 2017 Elsevier Inc. All rights reserved.

Do fattening process and biological parameters affect the accumulation of metals in Atlantic bluefin tuna?

PubMed

Milatou, Niki; Dassenakis, Manos; Megalofonou, Persefoni

2015-01-01

The objective of this study was to determine the current levels of heavy metals and trace elements in Atlantic bluefin tuna muscle tissues and how they are influenced by the fattening process and various life history parameters to ascertain whether the concentrations in muscle tissue exceed the maximum levels defined by the European Commission Decision and to evaluate the health risk posed by fish consumption. A total of 20 bluefin tuna reared in sea cages, ranging from 160 to 295 cm in length and from 80 to 540 kg in weight, were sampled from a bluefin tuna farm in the Ionian Sea. The condition factor K of each specimen was calculated and their age was estimated. Heavy metal and trace element (Hg, Zn, Fe and Cu) contents were determined in muscle tissue using cold vapour atomic absorption spectrometry and flame and graphite furnace atomic absorption spectrometry. The total Hg concentrations ranged from 0.28 to 1.28 mg kg(-1) w/w, Zn from 5.81 to 76.37 mg kg(-1) w/w, Fe from 12.14 to 39.58 mg kg(-1) w/w, and Cu from 0.36 to 0.94 mg kg(-1) w/w. Only 5% of the muscle samples of tuna contained Hg above the maximum level laid down by the European Commission Decision. Moreover, 15% of the muscle samples contained Zn above the maximum level, while Fe and Cu concentrations were within the acceptable tolerable guideline values. The reared bluefin tuna had lower concentrations of Hg than the wild ones from the Mediterranean Sea. Hg and Fe concentrations showed a positive relationship with size and age of bluefin tuna, whereas negative relationships were found for the concentrations of Zn and Cu. The estimated dietary intake values of the analysed metals were mostly below the derived guidelines.

Production of xylanase from an alkali tolerant Streptomyces sp. 7b under solid-state fermentation, its purification, and characterization.

PubMed

Bajaj, Bijender Kumar; Singh, Narendera Pratap

2010-11-01

Streptomyces sp. 7b showed highest xylanase activity among 41 bacterial isolates screened under submerged fermentation. The organism grew over broad pH (5-11) and temperatures range (25-55 degrees C) and displayed maximum xylanase production on wheat bran (1230 U/g) under solid-state fermentation. Xylanase production was enhanced substantially (76%-77%) by inclusion of trypton (2180 U/g) or beef extract (2170 U/g) and moderately (36%-46%) by yeast extract (1800 U/g) or soybean meal (1670 U/g). Inclusion of readily utilizable sugars such as glucose, maltose, fructose, lactose or xylose in the substrate repressed the xylanase production. The optimum initial pH of the medium for maximum enzyme production was 7 to 8; however, appreciable level of activity was obtained at pH 6 (1,680 U/g) and 9 (1,900 U/g). Most appropriate solid to liquid ratio for maximum xylanase production in solid-state fermentation was found to be 1:2.5. The organism produced a single xylanase of molecular weight of approximately 30 kDa as analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis after purification with ammonium sulfate precipitation, and carboxy methyl sephadex chromatography. The enzyme was purified to the extent of 5.68-fold by salt precipitation and ion-exchange chromatography. Optimum temperature and pH for maximum xylanase activity were 50 degrees C and 6, respectively.

Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

PubMed

Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

1998-06-01

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.

Comparing salt tolerance of beet cultivars and their halophytic ancestor: consequences of domestication and breeding programmes

PubMed Central

Rozema, Jelte; Cornelisse, Danny; Zhang, Yuancheng; Li, Hongxiu; Bruning, Bas; Katschnig, Diana; Broekman, Rob; Ji, Bin; van Bodegom, Peter

2015-01-01

Salt tolerance of higher plants is determined by a complex set of traits, the timing and rate of evolution of which are largely unknown. We compared the salt tolerance of cultivars of sugar beet and their ancestor, sea beet, in hydroponic studies and evaluated whether traditional domestication and more recent breeding have changed salt tolerance of the cultivars relative to their ancestor. Our comparison of salt tolerance of crop cultivars is based on values of the relative growth rate (RGR) of the entire plant at various salinity levels. We found considerable salt tolerance of the sea beet and slightly, but significantly, reduced salt tolerance of the sugar beet cultivars. This indicates that traditional domestication by selection for morphological traits such as leaf size, beet shape and size, enhanced productivity, sugar content and palatability slightly affected salt tolerance of sugar beet cultivars. Salt tolerance among four sugar beet cultivars, three of which have been claimed to be salt tolerant, did not differ. We analysed the components of RGR to understand the mechanism of salt tolerance at the whole-plant level. The growth rate reduction at higher salinity was linked with reduced leaf area at the whole-plant level (leaf area ratio) and at the individual leaf level (specific leaf area). The leaf weight fraction was not affected by increased salinity. On the other hand, succulence and leaf thickness and the net assimilation per unit of leaf area (unit leaf rate) increased in response to salt treatment, thus partially counteracting reduced capture of light by lower leaf area. This compensatory mechanism may form part of the salt tolerance mechanism of sea beet and the four studied sugar beet cultivars. Together, our results indicate that domestication of the halophytic ancestor sea beet slightly reduced salt tolerance and that breeding for improved salt tolerance of sugar beet cultivars has not been effective. PMID:25492122

A new concept of feature-based gauge for coordinate measuring arm evaluation

NASA Astrophysics Data System (ADS)

Cuesta, E.; González-Madruga, D.; Alvarez, B. J.; Barreiro, J.

2014-06-01

Articulated arm coordinate measuring machines (AACMM or CMA) have conquered a market share in the actual dimensional metrology field, overall when their role implies the inspection of geometrical and dimensional tolerances in an accurate 3D environment for medium-size parts. However, the unavoidable fact of AACMM manual operation constrains its reliability to a great extent, avoiding rigorous evaluation and casting doubt upon the usefulness of external calibration. In this research, a dimensional gauge especially aimed at AACMM evaluation has been developed. Furthermore, the operator skill will be revealed through the use of this gauge. A set of geometrical features, some of them oriented to evaluate the operator and others the equipment, have been collected for the gauge. The proposed evaluation methodology clearly distinguishes between dimensional and geometrical tolerances (with or without datum references), whereas actual verification standards only consider the former. Next, quality indicators deduced from the measurement results are proposed in order to compare AACMM versus coordinate measuring machine (CMM) performance, assuming that CMM possess the maximum accuracy that AACMM could reach, because CMM combines maximum contact accuracy with minimum operator influence. As a result, AACMM evaluation time could be significantly reduced since this gauge allows us to perform a customized evaluation of only those specific tolerances of interest to the user.

High tolerance of and removal of cefazolin sodium in single-chamber microbial fuel cells operation.

PubMed

Zhang, Enren; Yu, Qingling; Zhai, Wenjing; Wang, Feng; Scott, Keith

2018-02-01

Single-chamber microbial fuel cells (MFCs) have been shown to be a promising approach for cefazolin sodium (CFZS)-contaminated wastewater treatment, in terms of electricity production, high CFZS tolerance and effective CFZS removal. MFCs exposed to CFZS loadings up to 100 mg L -1 , produced stable power of 18.2 ± 1.1 W m -3 and a maximum power of 30.4 ± 2.1 W m -3 , similar to that of CFZS-free MFCs (stable power 19.4 ± 0.8 W m -3 and maximum power 32.5 ± 1.6 W m -3 ), notwithstanding a longer acclimitisation MFC activation. More anodophilic genera (i.e. Acinetobacter, Stenotrophomonas, Lysinibacillus) and antibiotic-resisting genera (i.e. Dysgonomonas) were enriched in CFZS acclimitised anodes. Both the thickness of biofilms and the duration of CFZS acclimitisation were essential for the development of high CFZS tolerance (e.g. 450 mg L -1 ). The inhibition of MFCs by CFZS was reversible. The present MFCs generated a CFZS removal rate of 1.2-6.8 mg L -1  h -1 without any apparent inhibition of electricity production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Non-destructive Determination of Shikimic Acid Concentration in Transgenic Maize Exhibiting Glyphosate Tolerance Using Chlorophyll Fluorescence and Hyperspectral Imaging

PubMed Central

Feng, Xuping; Yu, Chenliang; Chen, Yue; Peng, Jiyun; Ye, Lanhan; Shen, Tingting; Wen, Haiyong; He, Yong

2018-01-01

The development of transgenic glyphosate-tolerant crops has revolutionized weed control in crops in many regions of the world. The early, non-destructive identification of superior plant phenotypes is an important stage in plant breeding programs. Here, glyphosate-tolerant transgenic maize and its parental wild-type control were studied at 2, 4, 6, and 8 days after glyphosate treatment. Visible and near-infrared hyperspectral imaging and chlorophyll fluorescence imaging techniques were applied to monitor the performance of plants. In our research, transgenic maize, which was highly tolerant to glyphosate, was phenotyped using these high-throughput non-destructive methods to validate low levels of shikimic acid accumulation and high photochemical efficiency of photosystem II as reflected by maximum quantum yield and non-photochemical quenching in response to glyphosate. For hyperspectral imaging analysis, the combination of spectroscopy and chemometric methods was used to predict shikimic acid concentration. Our results indicated that a partial least-squares regression model, built on optimal wavelengths, effectively predicted shikimic acid concentrations, with a coefficient of determination value of 0.79 for the calibration set, and 0.82 for the prediction set. Moreover, shikimic acid concentration estimates from hyperspectral images were visualized on the prediction maps by spectral features, which could help in developing a simple multispectral imaging instrument for non-destructive phenotyping. Specific physiological effects of glyphosate affected the photochemical processes of maize, which induced substantial changes in chlorophyll fluorescence characteristics. A new data-driven method, combining mean fluorescence parameters and featuring a screening approach, provided a satisfactory relationship between fluorescence parameters and shikimic acid content. The glyphosate-tolerant transgenic plants can be identified with the developed discrimination model established on important wavelengths or sensitive fluorescence parameters 6 days after glyphosate treatment. The overall results indicated that both hyperspectral imaging and chlorophyll fluorescence imaging techniques could provide useful tools for stress phenotyping in maize breeding programs and could enable the detection and evaluation of superior genotypes, such as glyphosate tolerance, with a non-destructive high-throughput technique. PMID:29686693

Non-destructive Determination of Shikimic Acid Concentration in Transgenic Maize Exhibiting Glyphosate Tolerance Using Chlorophyll Fluorescence and Hyperspectral Imaging.

PubMed

Feng, Xuping; Yu, Chenliang; Chen, Yue; Peng, Jiyun; Ye, Lanhan; Shen, Tingting; Wen, Haiyong; He, Yong

2018-01-01

The development of transgenic glyphosate-tolerant crops has revolutionized weed control in crops in many regions of the world. The early, non-destructive identification of superior plant phenotypes is an important stage in plant breeding programs. Here, glyphosate-tolerant transgenic maize and its parental wild-type control were studied at 2, 4, 6, and 8 days after glyphosate treatment. Visible and near-infrared hyperspectral imaging and chlorophyll fluorescence imaging techniques were applied to monitor the performance of plants. In our research, transgenic maize, which was highly tolerant to glyphosate, was phenotyped using these high-throughput non-destructive methods to validate low levels of shikimic acid accumulation and high photochemical efficiency of photosystem II as reflected by maximum quantum yield and non-photochemical quenching in response to glyphosate. For hyperspectral imaging analysis, the combination of spectroscopy and chemometric methods was used to predict shikimic acid concentration. Our results indicated that a partial least-squares regression model, built on optimal wavelengths, effectively predicted shikimic acid concentrations, with a coefficient of determination value of 0.79 for the calibration set, and 0.82 for the prediction set. Moreover, shikimic acid concentration estimates from hyperspectral images were visualized on the prediction maps by spectral features, which could help in developing a simple multispectral imaging instrument for non-destructive phenotyping. Specific physiological effects of glyphosate affected the photochemical processes of maize, which induced substantial changes in chlorophyll fluorescence characteristics. A new data-driven method, combining mean fluorescence parameters and featuring a screening approach, provided a satisfactory relationship between fluorescence parameters and shikimic acid content. The glyphosate-tolerant transgenic plants can be identified with the developed discrimination model established on important wavelengths or sensitive fluorescence parameters 6 days after glyphosate treatment. The overall results indicated that both hyperspectral imaging and chlorophyll fluorescence imaging techniques could provide useful tools for stress phenotyping in maize breeding programs and could enable the detection and evaluation of superior genotypes, such as glyphosate tolerance, with a non-destructive high-throughput technique.

Reinforcement of thermoplastic chitosan hydrogel using chitin whiskers optimized with response surface methodology.

PubMed

Sun, Guohui; Zhang, Xin; Bao, Zixian; Lang, Xuqian; Zhou, Zhongzheng; Li, Yang; Feng, Chao; Chen, Xiguang

2018-06-01

To strengthen the mechanical strength of thermo-sensitive hydroxybutyl chitosan (HBC) hydrogel, chitin whiskers were used as sticker to fabricate reinforced HBC (HBCW) hydrogel by using response surface methodology. Unlike the intrinsic network of HBC hydrogel, HBCW hydrogel showed a laminar shape with firm structure. The preparation condition was optimized by three-factor-three-level Box-Behnken design. The maximum mechanical strength (1011.11 Pa) was achieved at 50 °C, when the concentrations of HBC and chitin whiskers were 5.1 wt% and 2.0 wt%, respectively. The effects of temperature, pH value and NaCl concentration on mechanical strength of HBCW hydrogels were investigated via the oscillatory stress sweeps. The results showed that HBCW hydrogel could reach the maximum stiffness (∼1126 Pa) at 37 °C pH 12.0. Low pH and high salty ions could decrease the stability of hydrogel, while chitin whiskers could increase the stress tolerance and related ruptured strain of HBCW hydrogels. Copyright © 2018. Published by Elsevier Ltd.

Growth and heavy metal removal by Klebsiella aerogenes at different pH and temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Shahwani, M.F.; Jazrawi, S.F.; Al-Rawi, E.H.

1984-01-01

A strain of Klebsiella aerogenes isolated from Rustamiyah Station for treatment of wastewater was examined for its ability to grow in a media supplemented with maximum tolerance concentrations of Pb/sup + +/, Zn/sup + +/, Ni/sup + +/, and Cd/sup + +/, separately, at different temperatures and initial pH. The results indicated that at 28/sup 0/C during the first 24 hr, Pb/sup + +/ and Ni/sup + +/ had no effect on the growth of the bacteria, while the presence of Zn/sup + +/ and Cd/sup + +/ decreased the cell count. The growth reached a maximum level after themore » second day and started to decrease gradually. The bacterial count at 37/sup 0/C was less than that at 28/sup 0/C. No bacterial multiplication occurred at 44/sup 0/C. There was little difference between heavy metal removal at 28 and 37/sup 0/C. At 44/sup 0/C, little removal took place. In general, slightly acidic or neutral medium was better for both bacterial growth and metal removal.« less

Modeling and analysis of energy quantization effects on single electron inverter performance

NASA Astrophysics Data System (ADS)

Dan, Surya Shankar; Mahapatra, Santanu

2009-08-01

In this paper, for the first time, the effects of energy quantization on single electron transistor (SET) inverter performance are analyzed through analytical modeling and Monte Carlo simulations. It is shown that energy quantization mainly changes the Coulomb blockade region and drain current of SET devices and thus affects the noise margin, power dissipation, and the propagation delay of SET inverter. A new analytical model for the noise margin of SET inverter is proposed which includes the energy quantization effects. Using the noise margin as a metric, the robustness of SET inverter is studied against the effects of energy quantization. A compact expression is developed for a novel parameter quantization threshold which is introduced for the first time in this paper. Quantization threshold explicitly defines the maximum energy quantization that an SET inverter logic circuit can withstand before its noise margin falls below a specified tolerance level. It is found that SET inverter designed with CT:CG=1/3 (where CT and CG are tunnel junction and gate capacitances, respectively) offers maximum robustness against energy quantization.

Liver size, bodyweight, and tolerance to acute complete occlusion of congenital extrahepatic portosystemic shunts in dogs.

PubMed

Doran, Ivan P; Barr, Frances J; Hotston Moore, Alasdair; Knowles, Toby G; Holt, Peter E

2008-10-01

To investigate the relationship between preoperative liver size, bodyweight, and tolerance to shunt occlusion in dogs with congenital extrahepatic portosystemic shunt(s) (CPSS). Longitudinal cohort study. Dogs with CPSS (n=35). Ultrasonography was used to measure preoperative maximum transverse dimension of the liver (TS) of each dog. Intraoperative portal pressures were measured, before and after CPSS occlusion, via a jejunal vein catheter. Tolerance to shunt occlusion was judged on gross visceral observations, and on changes in portal pressure, central venous and mean arterial pressures. TS was significantly related to bodyweight (P<.05). Mean ratios for TS/bodyweight were calculated for dogs tolerant and intolerant of acute complete shunt occlusion. Dogs tolerant to occlusion had significantly higher TS/bodyweight ratios than dogs intolerant to occlusion (P=.025). Dogs with a TS/bodyweight ratio of >7 were more likely to tolerate CPSS occlusion than dogs with a TS/bodyweight ratio of <5 (P=.036). A model was generated to predict portal pressure rise after shunt occlusion, based on liver dimensions and bodyweight (R=0.668). Intestinal oxygenation did not correlate significantly with tolerance to CPSS occlusion (P=.29). In dogs with CPSS, liver size (relative to bodyweight) is significantly greater (P=.025) in dogs that are tolerant of full ligation than intolerant of occlusion. Preoperative measurement of bodyweight and liver size help indicate the likelihood of tolerance to acute complete occlusion of CPSS in dogs.

Identification and characterization of an expansin gene AsEXP1 associated with heat tolerance in C3 Agrostis grass species.

PubMed

Xu, Jichen; Tian, Jiang; Belanger, Faith C; Huang, Bingru

2007-01-01

Plant tolerance of heat stress involves various changes at physiological and molecular levels. The objective of this study was to examine the expression of a gene encoding expansin protein in relation to heat tolerance in two C(3) grass species and genotypes differing in heat tolerance. Heat-tolerant, thermal Agrostis scabra, adapted to high temperatures in geothermal areas in Yellowstone National Park, was subjected to 20 degrees C (control) or 40 degrees C (heat stress) for 7 d in a growth chamber. Differential display analysis identified that a gene, AsEXP1, encoding an expansin protein, was strongly up-regulated in leaves exposed to heat stress in thermal A. scabra. Virtual northern hybridization and RT-PCR confirmed that AsEXP1 was a heat-inducible gene in leaves. The expression of AsEXP1 was induced at 1 h of plant exposure to heat stress and reached the highest level of expression at 4 h of treatment. A 1.3 kb full-length cDNA of AsEXP1 was isolated, which encodes a 251 amino acid protein. Two ecotypes of thermal A. scabra and 10 genotypes of Agrostis stolonifera (creeping bentgrass), a widely used turfgrass species in cool climatic regions, varying in the level of heat tolerance, were exposed to 40 degrees C for 7 d to examine the level of AsEXP1 expression in relation to heat tolerance. Genetic variation in heat tolerance was evaluated by measuring cell membrane stability, photochemical efficiency, and leaf growth. RT-PCR analysis revealed that the level of AsEXP1 in different genotypes was positively correlated with the level of heat tolerance in both grass species. The results first identified a heat-related expansin gene in grass species and suggest that AsEXP1 may be useful as a molecular marker to select for heat-tolerant grass germplasm.

Stress-gradient hypothesis explains susceptibility to Bromus tectorum invasion and community stability in North America's semi-arid Artemisia tridentata wyomingensis ecosystems

USGS Publications Warehouse

Reisner, Michael D.; Doescher, Paul S.; Pyke, David A.

2015-01-01

Results/Conclusions: Cattle herbivory, a novel disturbance and selective force, was a significant component of two overlapping stress gradients most strongly associated with observed shifts in interactions. Facilitation and competition were strongest and most frequent at the highest and lowest stress levels along both gradients, respectively. Contrasting ecological optima among native and non-native beneficiaries led to strikingly different patterns of interactions. The four native bunchgrasses with the strongest competitive response abilities exhibited the strongest facilitation at their upper limits of stress tolerance, while the two non-natives exhibited the strongest competition at the highest stress levels, which coincided with their maximum abundance. Artemisia facilitation enhanced stability at intermediate stress levels by providing a refuge for native bunchgrasses, which in turn reduced the magnitude of B. tectorum invasion. However, facilitation was a destabilizing force at the highest stress levels when native bunchgrasses became obligate beneficiaries dependent on facilitation for their persistence. B. tectorum dominated these communities, and the next fire may convert them to annual grasslands.

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke.

PubMed

Nagpal, Anjali; Kremer, Karlea L; Hamilton-Bruce, Monica A; Kaidonis, Xenia; Milton, Austin G; Levi, Christopher; Shi, Songtao; Carey, Leeanne; Hillier, Susan; Rose, Miranda; Zacest, Andrew; Takhar, Parabjit; Koblar, Simon A

2016-07-01

Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Globally, cell-based therapy in stroke is at the stage of clinical translation and may improve neurological function through various mechanisms such as neural replacement, neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity. Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke as reported in four independent studies indicates improvement in neurobehavioral function with adult human dental pulp stem cell therapy. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. TOOTH is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design that comprises three stages: Stage 1 will involve the selection of 27 participants with middle cerebral artery ischemic stroke and the commencement of autologous dental pulp stem cell isolation, growth, and testing in sequential cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem cell in each cohort of participants with an ascending dose and subsequent observation for a 6-month period for any dental pulp stem cell-related adverse events. Stage 3 will investigate the neurosurgical intervention of the maximum tolerable dose of autologous dental pulp stem cell followed by 9 weeks of intensive task-specific rehabilitation. Advanced magnetic resonance and positron emission tomography neuro-imaging, and clinical assessment will be employed to probe any change afforded by stem cell therapy in combination with rehabilitation. Nine participants will step-wise progress in Stage 2 to a dose of up to 10 million dental pulp stem cell, employing a cumulative 3 + 3 statistical design with low starting stem cell dose and subsequent dose escalation, assuming that an acceptable probability of dose-limiting complications is between 1 in 6 (17%) and 1 in 3 (33%) of patients. In Stage 3, another 18 participants will receive an intracranial injection with the maximum tolerable dose of dental pulp stem cell. The primary outcomes to be measured are safety and feasibility of intracranial administration of autologous human adult DPSC in patients with chronic stroke and determination of the maximum tolerable dose in human subjects. Secondary outcomes include estimation of the measures of effectiveness required to design a future Phase 2/3 clinical trial. © 2016 World Stroke Organization.

Tolerance of snakes to hypergravity

NASA Technical Reports Server (NTRS)

Lillywhite, H. B.; Ballard, R. E.; Hargens, A. R.

1996-01-01

Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.

21 CFR 526.313 - Ceftiofur.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Related tolerances. See § 556.113 of this chapter. (d) Conditions of use in cattle—(1) Lactating cows—(i... lactating dairy cattle associated with coagulase-negative staphylococci, Streptococcus dysgalactiae, and Escherichia coli. (iii) Limitations. Milk taken from cows during treatment (a maximum of eight daily infusions...

Functional traits and plasticity in response to light in seedlings of four Iberian forest tree species.

PubMed

Sánchez-Gómez, David; Valladares, Fernando; Zavala, Miguel A

2006-11-01

We investigated the differential roles of physiological and morphological features on seedling survivorship along an experimental irradiance gradient in four dominant species of cool temperate-Mediterranean forests (Quercus robur L., Quercus pyrenaica Willd., Pinus sylvestris L. and Pinus pinaster Ait.). The lowest photochemical efficiency (F(v)/F(m) in dark-adapted leaves) was reached in deep shade (1% of full sunlight) in all species except Q. robur, which had the lowest photochemical efficiency in both deep shade and 100% of full sunlight. Species differed significantly in their survival in 1% of full sunlight but exhibited similar survivorship in 6, 20 and 100% of full sunlight. Shade-tolerant oaks had lower leaf area ratios, shoot to root ratios, foliage allocation ratios and higher rates of allocation to structural biomass (stem plus thick roots) than shade-intolerant pines. Overall phenotypic plasticity for each species, estimated as the difference between the minimum and the maximum mean values of the ecophysiological variables studied at the various irradiances divided by the maximum mean value of those variables, was inversely correlated with shade tolerance. Observed morphology, allocation and plasticity conformed to a conservative resource-use strategy, although observed differences in specific leaf area, which was higher in shade-tolerant species, supported a carbon gain maximization strategy. Lack of a congruent suite of traits underlying shade tolerance in the studied species provides evidence of adaptation to multiple selective forces. Although the study was based on only four species, the importance of ecophysiological variables as determinants of interspecific differences in survival in limiting light was demonstrated.

Sequential Oral Hydroxyurea and Intravenous Cytosine Arabinoside in Refractory Childhood Acute Leukemia: A Pediatric Oncology Group Phase I Study

PubMed Central

Dubowy, Ronald; Graham, Michael; Hakami, Nasrollah; Kletzel, Morris; Mahoney, Donald; Newman, Edward; Ravindranath, Yaddanapudi; Camitta, Bruce

2015-01-01

Summary At concentrations >0.1 mM, Hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU, 1200 mg/m2 was followed 2 hours later by ara-C, 250-3100 mg/m2 intravenously in 15 minutes. The combination was given on days 1,2,3 and 8,9,10. Thirty-three children (26 ALL, 7 ANLL) were treated; 29 received at least one full course. All patients developed grade 4 cytopenias. Other grade 3-4 toxicities included: hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9) and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1-3 months). 20/26 patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range 0.21-0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism. PMID:18458568

Sequential oral hydroxyurea and intravenous cytosine arabinoside in refractory childhood acute leukemia: a pediatric oncology group phase 1 study.

PubMed

Dubowy, Ronald; Graham, Michael; Hakami, Nasrollah; Kletzel, Morris; Mahoney, Donald; Newman, Edward; Ravindranath, Yaddanapudi; Camitta, Bruce

2008-05-01

At concentrations >0.1 mM, hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU (1200 mg/m2) was followed 2 hours later by ara-C (250-3100 mg/m2) intravenously in 15 minutes. The combination was given on days 1, 2, 3 and 8, 9, 10. Thirty-three children [26 acute lymphocytic leukemia (ALL), 7 acute nonlymphocytic leukemia] were treated; 29 received at least 1 full course. All patients developed grade 4 cytopenias. Other grade 3 to 4 toxicities included hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9), and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5 ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1 to 3 mo). Twenty of twenty-six patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range: 0.21 to 0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism.

Factors driving public tolerance levels and information-seeking behaviour concerning insects in the household environment.

PubMed

Schoelitsz, Bruce; Poortvliet, P Marijn; Takken, Willem

2018-06-01

The public's negative attitudes towards household insects drive tolerance for these insects and their control. Tolerance levels are important in integrated pest management (IPM), as are pest knowledge and information. The risk information seeking and processing (RISP) model describes the relationships between personal factors and information-seeking behaviour. We combined IPM and RISP to determine important relationships between factors driving insect tolerance levels and information-seeking behaviour through an online survey and tested whether this model is valid and generally applicable. Relationships between variables from both IPM and RISP models were tested for seven insect species. Tolerance levels were measured with two factors: willingness to pay for pest control and whether insects are tolerated. Willingness to pay for control was positively affected by age, experience, risk perception, insect characteristics, and negative emotions and affected behavioural intention, by influencing information sufficiency and information-seeking behaviour. Tolerability was influenced by perception of insect characteristics and determines whether control measures are taken. It was possible to combine the RISP and IPM models. Relevant driving factors were a person's age, experience, risk perception, negative affective responses, tolerance levels, relevant channel beliefs about online forums, information sufficiency and information-seeking behaviour. There was, however, variation in important factors between different insects. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Elasticity in portion selection is predicted by severity of anorexia and food type in adolescents.

PubMed

Herzog, M; Douglas, C R; Kissileff, H R; Brunstrom, J M; Halmi, K A

2016-08-01

The size of portions that people select is an indicator of underlying mechanisms controlling food intake. Fears of eating excessive portions drive down the sizes of portions patients with anorexia nervosa (AN) can tolerate eating significantly below those of healthy controls (HC) (Kissileff et al., 2016). To determine whether patients with AN will also reduce the sizes of typical or ideal portions below those of controls, ANOVA was used to compare maximum tolerable, typical, and ideal portions of four foods (potatoes, rice, pizza, and M&M's) in the same group of 24 adolescent AN patients and 10 healthy adolescent controls (HC), on which only the maximal portion data were previously reported. Typical and ideal portion sizes did not differ on any food for AN, but for HC, typical portions sizes (kcals) became larger than ideal as the energy density of the food increased, and were significant for the most energy dense food. Ideal portions of low energy dense foods were the same for AN as for in HC. There was a significant 3-way (group × food × portion type) interaction, such that HC selected larger maximum than typical portions only for pizza. We therefore proposed that individuals of certain groups, depending on the food, can be flexible in the amounts of food chosen to be eaten. We call this difference between maximum-tolerable, and typical portion sizes selected "elasticity." Elasticity was significantly smaller for AN patients compared to HC for pizza and was significantly inversely correlated with severity of illness. This index could be useful for clinical assessment of AN patients, and those with eating problems such as in obesity and bulimia nervosa and tracking their response to treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

77 FR 32400 - Fenamidone; Pesticide Tolerance; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

...., of the preamble, the text correctly listed the tolerance level for the commodity ``strawberry'' at 0... the tolerance level for ``strawberry'' at 0.15. This technical amendment corrects that error. III. Why... revising the entry for ``Strawberry'' in paragraph (d) to read as follows: Sec. [emsp14]180.579 Fenamidone...

Prenatal tolerance induction: relationship between cell dose, marrow T-cells, chimerism, and tolerance.

PubMed

Chen, Jeng-Chang; Chang, Ming-Ling; Huang, Shiu-Feng; Chang, Pei-Yeh; Muench, Marcus O; Fu, Ren-Huei; Ou, Liang-Shiou; Kuo, Ming-Ling

2008-01-01

It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2K(q)) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2K(b)) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 x 10(6) and host leukocytes could be nearly replaced at a dose of 7.5-10.0 x 10(6). High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft-versus-host disease. Depletion of marrow T cells lessened graft-versus-host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of > or = 2% chimerism at 1 month of age and predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%) only caused hyporesponsiveness to the donor. Tolerance induction did not succeed without peripheral chimerism even if a large amount of injected donor cells persisted in the peritoneum. Neither did an increase in cell doses or donor T-cell contents benefit skin graft survivals unless it had substantially improved peripheral chimerism. Thus, peripheral chimerism level can be a simple and straightforward test to predict the degree of prenatal immune tolerance.

[The antigravity suit, chamberless type, as a means of increasing orthostatic tolerance after water immersion hypokinesis and acceleration].

PubMed

Shul'zhenko, E B; Kozlova, V G; Kurdin, K A; Iarov, A S; Plokhova, V G

1983-01-01

Orthostatic tolerance after 7-day dry immersion and head-to-feet acceleration was investigated on test subjects with and without an antigravity suit of bladderless type. With the suit on, the 20 min tilt test at 70 degrees prior to immersion induced less marked changes than without the suit. When the suit was on, cardiovascular reactions to tilt tests after immersion and acceleration improved. The maximum heart rate decreased from 135 +/- 4 to 101 +/- 5 beats/min (p less than 0.01), minimum stroke volume increased from 29 +/- 2 to 41 +/- 3 ml (p less than 0.05), and pulse pressure grew. Thus, an antigravity suit may help increase initial orthostatic tolerance and maintain it after the combined effect of simulated hypogravity and acceleration.

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

PubMed

Gavin, Paul D; Simon, Lee S; Schlagheck, Thomas; Smith, Alisha J; Shakib, Sepehr

2017-07-01

To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM). Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h. Oxycodone was detected 8.0 ± 2.7-h postpatch administration, reaching a mean maximum plasma concentration of 3.41 ± 1.34 ng/ml at 49.3 ± 21.2 h. The safety profile was consistent with the application method and known side-effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation was observed. A 3-day application of the TPM/oxycodone patch demonstrated an acceptable safety profile and was well tolerated by healthy subjects, with limited dermal irritation following application.

Non-linear effects of drought under shade: reconciling physiological and ecological models in plant communities.

PubMed

Holmgren, Milena; Gómez-Aparicio, Lorena; Quero, José Luis; Valladares, Fernando

2012-06-01

The combined effects of shade and drought on plant performance and the implications for species interactions are highly debated in plant ecology. Empirical evidence for positive and negative effects of shade on the performance of plants under dry conditions supports two contrasting theoretical models about the role of shade under dry conditions: the trade-off and the facilitation hypotheses. We performed a meta-analysis of field and greenhouse studies evaluating the effects of drought at two or more irradiance levels on nine response variables describing plant physiological condition, growth, and survival. We explored differences in plant response across plant functional types, ecosystem types and methodological approaches. The data were best fit using quadratic models indicating a humped-back shape response to drought along an irradiance gradient for survival, whole plant biomass, maximum photosynthetic capacity, stomatal conductance and maximal photochemical efficiency. Drought effects were ameliorated at intermediate irradiance, becoming more severe at higher or lower light levels. This general pattern was maintained when controlling for potential variations in the strength of the drought treatment among light levels. Our quantitative meta-analysis indicates that dense shade ameliorates drought especially among drought-intolerant and shade-tolerant species. Wet tropical species showed larger negative effects of drought with increasing irradiance than semiarid and cold temperate species. Non-linear responses to irradiance were stronger under field conditions than under controlled greenhouse conditions. Non-linear responses to drought along the irradiance gradient reconciliate opposing views in plant ecology, indicating that facilitation is more likely within certain range of environmental conditions, fading under deep shade, especially for drought-tolerant species.

Wavefront error budget and optical manufacturing tolerance analysis for 1.8m telescope system

NASA Astrophysics Data System (ADS)

Wei, Kai; Zhang, Xuejun; Xian, Hao; Rao, Changhui; Zhang, Yudong

2010-05-01

We present the wavefront error budget and optical manufacturing tolerance analysis for 1.8m telescope. The error budget accounts for aberrations induced by optical design residual, manufacturing error, mounting effects, and misalignments. The initial error budget has been generated from the top-down. There will also be an ongoing effort to track the errors from the bottom-up. This will aid in identifying critical areas of concern. The resolution of conflicts will involve a continual process of review and comparison of the top-down and bottom-up approaches, modifying both as needed to meet the top level requirements in the end. As we all know, the adaptive optical system will correct for some of the telescope system imperfections but it cannot be assumed that all errors will be corrected. Therefore, two kinds of error budgets will be presented, one is non-AO top-down error budget and the other is with-AO system error budget. The main advantage of the method is that at the same time it describes the final performance of the telescope, and gives to the optical manufacturer the maximum freedom to define and possibly modify its own manufacturing error budget.

Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Volunteers Treated With GDC-0853, a Selective Reversible Bruton's Tyrosine Kinase Inhibitor.

PubMed

Herman, Ann E; Chinn, Leslie W; Kotwal, Shweta G; Murray, Elaine R; Zhao, Rui; Florero, Marilyn; Lin, Alyse; Moein, Anita; Wang, Rena; Bremer, Meire; Kokubu, Serika; Serone, Adrian P; Hanze, Eva L; Viberg, Anders; Morimoto, Alyssa M; Winter, Helen R; Katsumoto, Tamiko R

2018-06-01

GDC-0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that is highly selective and noncovalent, leading to reversible binding. In double-blind, randomized, and placebo-controlled phase I healthy volunteer studies, GDC-0853 was well tolerated, with no dose-limiting adverse events (AEs) or serious AEs. The maximum tolerated dose was not reached during dose escalation (≤600 mg, single ascending dose (SAD) study; ≤250 mg twice daily (b.i.d.) and ≤500 mg once daily, 14-day multiple ascending dose (MAD) study). Plasma concentrations peaked 1-3 hours after oral administration and declined thereafter, with a steady-state half-life ranging from 4.2-9.9 hours. Independent assays demonstrated dose-dependent BTK target engagement. Based on pharmacokinetic/pharmacodynamic (PK/PD) simulations, a once-daily dosing regimen (e.g., 100 mg, q.d.) is expected to maintain a high level of BTK inhibition over the dosing interval. Taken together, the safety and PK/PD data support GDC-0853 evaluation in rheumatoid arthritis, lupus, and other autoimmune or inflammatory indications. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Damage Tolerance of Pre-Stressed Composite Panels Under Impact Loads

NASA Astrophysics Data System (ADS)

Johnson, Alastair F.; Toso-Pentecôte, Nathalie; Schueler, Dominik

2014-02-01

An experimental test campaign studied the structural integrity of carbon fibre/epoxy panels preloaded in tension or compression then subjected to gas gun impact tests causing significant damage. The test programme used representative composite aircraft fuselage panels composed of aerospace carbon fibre toughened epoxy prepreg laminates. Preload levels in tension were representative of design limit loads for fuselage panels of this size, and maximum compression preloads were in the post-buckle region. Two main impact scenarios were considered: notch damage from a 12 mm steel cube projectile, at velocities in the range 93-136 m/s; blunt impact damage from 25 mm diameter glass balls, at velocities 64-86 m/s. The combined influence of preload and impact damage on panel residual strengths was measured and results analysed in the context of damage tolerance requirements for composite aircraft panels. The tests showed structural integrity well above design limit loads for composite panels preloaded in tension and compression with visible notch impact damage from hard body impact tests. However, blunt impact tests on buckled compression loaded panels caused large delamination damage regions which lowered plate bending stiffness and reduced significantly compression strengths in buckling.

Integration of a vision-based tracking platform, visual instruction, and error analysis models for an efficient billiard training system

NASA Astrophysics Data System (ADS)

Shih, Chihhsiong; Hsiung, Pao-Ann; Wan, Chieh-Hao; Koong, Chorng-Shiuh; Liu, Tang-Kun; Yang, Yuanfan; Lin, Chu-Hsing; Chu, William Cheng-Chung

2009-02-01

A billiard ball tracking system is designed to combine with a visual guide interface to instruct users for a reliable strike. The integrated system runs on a PC platform. The system makes use of a vision system for cue ball, object ball and cue stick tracking. A least-squares error calibration process correlates the real-world and the virtual-world pool ball coordinates for a precise guidance line calculation. Users are able to adjust the cue stick on the pool table according to a visual guidance line instruction displayed on a PC monitor. The ideal visual guidance line extended from the cue ball is calculated based on a collision motion analysis. In addition to calculating the ideal visual guide, the factors influencing selection of the best shot among different object balls and pockets are explored. It is found that a tolerance angle around the ideal line for the object ball to roll into a pocket determines the difficulty of a strike. This angle depends in turn on the distance from the pocket to the object, the distance from the object to the cue ball, and the angle between these two vectors. Simulation results for tolerance angles as a function of these quantities are given. A selected object ball was tested extensively with respect to various geometrical parameters with and without using our integrated system. Players with different proficiency levels were selected for the experiment. The results indicate that all players benefit from our proposed visual guidance system in enhancing their skills, while low-skill players show the maximum enhancement in skill with the help of our system. All exhibit enhanced maximum and average hit-in rates. Experimental results on hit-in rates have shown a pattern consistent with that of the analysis. The hit-in rate is thus tightly connected with the analyzed tolerance angles for sinking object balls into a target pocket. These results prove the efficiency of our system, and the analysis results can be used to attain an efficient game-playing strategy.

Triglycerides and carotid intima-media thickness in ischemic stroke patients.

PubMed

Batluk, Jana; Leonards, Christopher O; Grittner, Ulrike; Lange, Kristin Sophie; Schreiber, Stephan J; Endres, Matthias; Ebinger, Martin

2015-11-01

Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charité Virchow and Charité Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3-7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism-namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and clinicaltrials.gov (NCT 01378468). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Tympanic temperature in confined beef cattle exposed to excessive heat load

NASA Astrophysics Data System (ADS)

Mader, T. L.; Gaughan, J. B.; Johnson, L. J.; Hahn, G. L.

2010-11-01

Angus crossbred yearling steers ( n = 168) were used to evaluate effects on performance and tympanic temperature (TT) of feeding additional potassium and sodium to steers exposed to excessive heat load (maximum daily ambient temperature exceeded 32°C for three consecutive days) during seasonal summer conditions. Steers were assigned one of four treatments: (1) control; (2) potassium supplemented (diet containing 2.10% KHCO3); (3) sodium supplemented (diet containing 1.10% NaCl); or (4) potassium and sodium supplemented (diet containing 2.10% KHCO3 and 1.10% NaCl). Overall, additional KHCO3 at the 2% level or NaCl at the 1% level did not improve performance or heat stress tolerance with these diet formulations. However, the addition of KHCO3 did enhance water intake. Independent of treatment effects, TT of cattle displaying high, moderate, or low levels of stress suggest that cattle that do not adequately cool down at night are prone to achieving greater body temperatures during a subsequent hot day. Cattle that are prone to get hot but can cool at night can keep average tympanic temperatures at or near those of cattle that tend to consistently maintain lower peak and mean body temperatures. In addition, during cooler and moderately hot periods, cattle change TT in a stair-step or incremental pattern, while under hot conditions, average TT of group-fed cattle moves in conjunction with ambient conditions, indicating that thermoregulatory mechanisms are at or near maximum physiological capacity.

The rehydration transcriptome of the desiccation-tolerant bryophyte Tortula ruralis: transcript classification and analysis

PubMed Central

Oliver, Melvin J; Dowd, Scot E; Zaragoza, Joaquin; Mauget, Steven A; Payton, Paxton R

2004-01-01

Background The cellular response of plants to water-deficits has both economic and evolutionary importance directly affecting plant productivity in agriculture and plant survival in the natural environment. Genes induced by water-deficit stress have been successfully enumerated in plants that are relatively sensitive to cellular dehydration, however we have little knowledge as to the adaptive role of these genes in establishing tolerance to water loss at the cellular level. Our approach to address this problem has been to investigate the genetic responses of plants that are capable of tolerating extremes of dehydration, in particular the desiccation-tolerant bryophyte, Tortula ruralis. To establish a sound basis for characterizing the Tortula genome in regards to desiccation tolerance, we analyzed 10,368 expressed sequence tags (ESTs) from rehydrated rapid-dried Tortula gametophytes, a stage previously determined to exhibit the maximum stress induced change in gene expression. Results The 10, 368 ESTs formed 5,563 EST clusters (contig groups representing individual genes) of which 3,321 (59.7%) exhibited similarity to genes present in the public databases and 2,242 were categorized as unknowns based on protein homology scores. The 3,321 clusters were classified by function using the Gene Ontology (GO) hierarchy and the KEGG database. The results indicate that the transcriptome contains a diverse population of transcripts that reflects, as expected, a period of metabolic upheaval in the gametophyte cells. Much of the emphasis within the transcriptome is centered on the protein synthetic machinery, ion and metabolite transport, and membrane biosynthesis and repair. Rehydrating gametophytes also have an abundance of transcripts that code for enzymes involved in oxidative stress metabolism and phosphorylating activities. The functional classifications reflect a remarkable consistency with what we have previously established with regards to the metabolic activities that are important in the recovery of the gametophytes from desiccation. A comparison of the GO distribution of Tortula clusters with an identical analysis of 9,981 clusters from the desiccation sensitive bryophyte species Physcomitrella patens, revealed, and accentuated, the differences between stressed and unstressed transcriptomes. Cross species sequence comparisons indicated that on the whole the Tortula clusters were more closely related to those from Physcomitrella than Arabidopsis (complete genome BLASTx comparison) although because of the differences in the databases there were more high scoring matches to the Arabidopsis sequences. The most abundant transcripts contained within the Tortula ESTs encode Late Embryogenesis Abundant (LEA) proteins that are normally associated with drying plant tissues. This suggests that LEAs may also play a role in recovery from desiccation when water is reintroduced into a dried tissue. Conclusion The establishment of a rehydration EST collection for Tortula ruralis, an important plant model for plant stress responses and vegetative desiccation tolerance, is an important step in understanding the genome level response to cellular dehydration. The type of transcript analysis performed here has laid the foundation for more detailed functional and genome level analyses of the genes involved in desiccation tolerance in plants. PMID:15546486

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program..., contract loading tolerance and, if necessary, a request for CCC to reserve coverage up to the maximum...

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program..., contract loading tolerance and, if necessary, a request for CCC to reserve coverage up to the maximum...

Clinical impact of dosimetric changes for volumetric modulated arc therapy in log file-based patient dose calculations.

PubMed

Katsuta, Yoshiyuki; Kadoya, Noriyuki; Fujita, Yukio; Shimizu, Eiji; Matsunaga, Kenichi; Matsushita, Haruo; Majima, Kazuhiro; Jingu, Keiichi

2017-10-01

A log file-based method cannot detect dosimetric changes due to linac component miscalibration because log files are insensitive to miscalibration. Herein, clinical impacts of dosimetric changes on a log file-based method were determined. Five head-and-neck and five prostate plans were applied. Miscalibration-simulated log files were generated by inducing a linac component miscalibration into the log file. Miscalibration magnitudes for leaf, gantry, and collimator at the general tolerance level were ±0.5mm, ±1°, and ±1°, respectively, and at a tighter tolerance level achievable on current linac were ±0.3mm, ±0.5°, and ±0.5°, respectively. Re-calculations were performed on patient anatomy using log file data. Changes in tumor control probability/normal tissue complication probability from treatment planning system dose to re-calculated dose at the general tolerance level was 1.8% on planning target volume (PTV) and 2.4% on organs at risk (OARs) in both plans. These changes at the tighter tolerance level were improved to 1.0% on PTV and to 1.5% on OARs, with a statistically significant difference. We determined the clinical impacts of dosimetric changes on a log file-based method using a general tolerance level and a tighter tolerance level for linac miscalibration and found that a tighter tolerance level significantly improved the accuracy of the log file-based method. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Tolerance analyses of a quadrupole magnet for advanced photon source upgrade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, J., E-mail: Jieliu@aps.anl.gov; Jaski, M., E-mail: jaski@aps.anl.gov; Borland, M., E-mail: borland@aps.anl.gov

2016-07-27

Given physics requirements, the mechanical fabrication and assembly tolerances for storage ring magnets can be calculated using analytical methods [1, 2]. However, this method is not easy for complicated magnet designs [1]. In this paper, a novel method is proposed to determine fabrication and assembly tolerances consistent with physics requirements, through a combination of magnetic and mechanical tolerance analyses. In this study, finite element analysis using OPERA is conducted to estimate the effect of fabrication and assembly errors on the magnetic field of a quadrupole magnet and to determine the allowable tolerances to achieve the specified magnetic performances. Based onmore » the study, allowable fabrication and assembly tolerances for the quadrupole assembly are specified for the mechanical design of the quadrupole magnet. Next, to achieve the required assembly level tolerances, mechanical tolerance stackup analyses using a 3D tolerance analysis package are carried out to determine the part and subassembly level fabrication tolerances. This method can be used to determine the tolerances for design of other individual magnets and of magnet strings.« less

Noise tolerance in optical waveguide circuits for recognition of optical 16 quadrature amplitude modulation codes

NASA Astrophysics Data System (ADS)

Inoshita, Kensuke; Hama, Yoshimitsu; Kishikawa, Hiroki; Goto, Nobuo

2016-12-01

In photonic label routers, various optical signal processing functions are required; these include optical label extraction, recognition of the label, optical switching and buffering controlled by signals based on the label information and network routing tables, and label rewriting. Among these functions, we focus on photonic label recognition. We have proposed two kinds of optical waveguide circuits to recognize 16 quadrature amplitude modulation codes, i.e., recognition from the minimum output port and from the maximum output port. The recognition function was theoretically analyzed and numerically simulated by finite-difference beam-propagation method. We discuss noise tolerance in the circuit and show numerically simulated results to evaluate bit-error-rate (BER) characteristics against optical signal-to-noise ratio (OSNR). The OSNR required to obtain a BER less than 1.0×10-3 for the symbol rate of 2.5 GBaud was 14.5 and 27.0 dB for recognition from the minimum and maximum output, respectively.

The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia.

PubMed

Stein, Eytan M; Garcia-Manero, Guillermo; Rizzieri, David A; Tibes, Raoul; Berdeja, Jesus G; Savona, Michael R; Jongen-Lavrenic, Mojca; Altman, Jessica K; Thomson, Blythe; Blakemore, Stephen J; Daigle, Scott R; Waters, Nigel J; Suttle, A Benjamin; Clawson, Alicia; Pollock, Roy; Krivtsov, Andrei; Armstrong, Scott A; DiMartino, Jorge; Hedrick, Eric; Löwenberg, Bob; Tallman, Martin S

2018-05-03

Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m 2 /day by continuous intravenous infusion in 28-day cycles. As a maximum tolerated dose was not established in the dose escalation phase, the expansion doses were selected based upon safety and clinical response data combined with pharmacodynamic evidence of reduction in H3K79 methylation during dose escalation. Across all dose levels, plasma pinometostat concentrations increased in an approximately dose-proportional fashion, reaching an apparent steady state by 4-8 hours after infusion, and rapidly decreased following treatment cessation. The most common adverse events, of any cause, were fatigue (39%), nausea (39%), constipation (35%), and febrile neutropenia (35%). Overall, 2 patients, both with t(11;19), experienced complete remissions at 54 mg/m 2 /day by continuous intravenous infusion, demonstrating proof of concept for delivering clinically meaningful responses through targeting DOT1L using single agent pinometostat in MLL-r leukemia patients. Administration of pinometostat was generally safe with the maximum tolerated dose not being reached, although efficacy as a single agent was modest. This study demonstrates the therapeutic potential for targeting DOT1L in MLL-r leukemia and lays the groundwork for future combination approaches in this patient population. This clinical trial is registered at www.clinicaltrials.gov as no. NCT01684150. Copyright © 2018 American Society of Hematology.

Aerobic scope does not predict the performance of a tropical eurythermal fish at elevated temperatures.

PubMed

Norin, Tommy; Malte, Hans; Clark, Timothy D

2014-01-15

Climate warming is predicted to negatively impact fish populations through impairment of oxygen transport systems when temperatures exceed those which are optimal for aerobic scope (AS). This concept of oxygen- and capacity-limited thermal tolerance (OCLTT) is rapidly gaining popularity within climate change research and has been applied to several fish species. Here, we evaluated the relevance of aerobic performance of juvenile barramundi (Lates calcarifer) in the context of thermal preference and tolerance by (1) measuring standard and maximum metabolic rates (SMR and MMR, respectively) and AS of fish acclimated to 29°C and acutely exposed to temperatures from 23 to 38°C, (2) allowing the fish to behaviourally select a preferred temperature between 29 and 38°C, and (3) quantifying alterations to AS after 5 weeks of acclimation to 29 and 38°C. SMR and MMR both increased continuously with temperature in acutely exposed fish, but the increase was greater for MMR such that AS was highest at 38°C, a temperature approaching the upper lethal limit (40-41°C). Despite 38°C eliciting maximum AS, when given the opportunity the fish selected a median temperature of 31.7 ± 0.5°C and spent only 10 ± 3% of their time at temperatures >36°C. Following acclimation to 38°C, AS measured at 38°C was decreased to the same level as 29°C-acclimated fish measured at 29°C, suggesting that AS may be dynamically modulated independent of temperature to accommodate the requirements of daily life. Together, these results reveal limited power of the OCLTT hypothesis in predicting optimal temperatures and effects of climate warming on juvenile barramundi.

Physiological plasticity of cardiorespiratory function in a eurythermal marine teleost, the longjaw mudsucker, Gillichthys mirabilis.

PubMed

Jayasundara, Nishad; Somero, George N

2013-06-01

An insufficient supply of oxygen under thermal stress is thought to define thermal optima and tolerance limits in teleost fish. When under thermal stress, cardiac function plays a crucial role in sustaining adequate oxygen supply for respiring tissues. Thus, adaptive phenotypic plasticity of cardiac performance may be critical for modifying thermal limits during temperature acclimation. Here we investigated effects of temperature acclimation on oxygen consumption, cardiac function and blood oxygen carrying capacity of a eurythermal goby fish, Gillichthys mirabilis, acclimated to 9, 19 and 26°C for 4 weeks. Acclimation did not alter resting metabolic rates or heart rates; no compensation of rates was observed at acclimation temperatures. However, under an acute heat ramp, warm-acclimated fish exhibited greater heat tolerance (CTmax=33.3, 37.1 and 38.9°C for 9°C-, 19°C- and 26°C-acclimated fish, respectively) and higher cardiac arrhythmia temperatures compared with 9°C-acclimated fish. Heart rates measured under an acute heat stress every week during 28 days of acclimation suggested that both maximum heart rates and temperature at onset of maximum heart rates changed over time with acclimation. Hemoglobin levels increased with acclimation temperature, from 35 g l(-1) in 9°C-acclimated fish to 60-80 g l(-1) in 19°C- and 26°C-acclimated fish. Oxygen consumption rates during recovery from acute heat stress showed post-stress elevation in 26°C-acclimated fish. These data, coupled with elevated resting metabolic rates and heart rates at warm temperatures, suggest a high energetic cost associated with warm acclimation in G. mirabilis. Furthermore, acclimatory capacity appears to be optimized at 19°C, a temperature shown by behavioral studies to be close to the species' preferred temperature.

Acute and repeated dose (28 days) toxicity studies in rats and dogs of recombinant batroxobin, a snake venom thrombin-like enzyme expressed from Pichia pastoris.

PubMed

Kim, Ok Hwan; Cho, Kil-Sang; Seomun, Young; Kim, Jong-Tak; Chung, Kwang-Hoe

2017-04-01

Recombinant batroxobin is a thrombin-like enzyme of Bothrops atrox moojeni venom. To evaluate its toxicological effect, it was highly expressed in Pichia pastorisand successfully purified to homogeneity from culture broth supernatant following Good Manufacturing Practice (GMP). The maximum tolerated dose of the recombinant batroxobin was examined in Sprague-Dawley (SD) rat and Beagle dogs following Good Laboratory Practice (GLP) regulations. The approximate lethal dose of recombinant batroxobin was 10 National Institute of Health (NIH) u/kg in male and female rats. Slight test substance-related effects were clearly in male and female dogs at more than 10 NIH u/kg. The maximum tolerated dose (MTD) was considered to be greater than 30 NIH u/kg in dogs. To investigate the repeated dose toxicity of batroxobin, the test item was intravenously administered to groups of SD rat and Beagle dog every day for 4 weeks. We observed that all animals survived the duration of the study without any effects on their mortality. There were no effects in both rats and dogs regarding their clinical signs, body weight, food consumption, ophthalmological examination, urinalysis, hematology, clinical chemistry, organ weightand gross post mortem examinations. The no adverse effect level (NOAEL) of recombinant batroxobin for both males and females is considered to be greater than 2.5 NIH u/kgin rats and 1 NIH u/kg in dogs, respectively. No toxic effects were noted in target organs. In conclusion, these results show a favorable preclinical profile and may contribute clinical development of recombinant batroxobin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

PubMed

Norris, David C

2017-01-01

Background . Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA) -finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to cytotoxic chemotherapy, the DTAT principle appears similarly applicable to Phase I studies of cancer immunotherapy and molecularly targeted agents.

Antimicrobial Tolerance of Pseudomonas aeruginosa Biofilms Is Activated during an Early Developmental Stage and Requires the Two-Component Hybrid SagS

PubMed Central

Gupta, Kajal; Marques, Cláudia N. H.; Petrova, Olga E.

2013-01-01

A hallmark characteristic of biofilms is their extraordinary tolerance to antimicrobial agents. While multiple factors are thought to contribute to the high level of antimicrobial tolerance of biofilms, little is known about the timing of induction of biofilm tolerance. Here, we asked when over the course of their development do biofilms gain their tolerance to antimicrobial agents? We demonstrate that in Pseudomonas aeruginosa, biofilm tolerance is linked to biofilm development, with transition to the irreversible attachment stage regulated by the two-component hybrid SagS, marking the timing when biofilms switch to the high-level tolerance phenotype. Inactivation of sagS rendered biofilms but not planktonic cells more susceptible to tobramycin, norfloxacin, and hydrogen peroxide. Moreover, inactivation of sagS also eliminated the recalcitrance of biofilms to killing by bactericidal antimicrobial agents, a phenotype comparable to that observed upon inactivation of brlR, which encodes a MerR-like transcriptional regulator required for biofilm tolerance. Multicopy expression of brlR in a ΔsagS mutant restored biofilm resistance and recalcitrance to killing by bactericidal antibiotics to wild-type levels. In contrast, expression of sagS did not restore the susceptibility phenotype of ΔbrlR mutant biofilms to wild-type levels, indicating that BrlR functions downstream of SagS. Inactivation of sagS correlated with reduced BrlR levels in biofilms, with the produced BrlR being impaired in binding to the previously described BrlR-activated promoters of the two multidrug efflux pump operons mexAB-oprM and mexEF-oprN. Our findings demonstrate that biofilm tolerance is linked to early biofilm development and SagS, with SagS contributing indirectly to BrlR activation. PMID:23995639

40 CFR 180.505 - Emamectin; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Emamectin; tolerances for residues... § 180.505 Emamectin; tolerances for residues. (a) General. (1) Tolerances are established for emamectin... tolerance levels specified below is to be determined by measuring only the sum of emamectin (a mixture of a...

40 CFR 180.505 - Emamectin; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Emamectin; tolerances for residues... § 180.505 Emamectin; tolerances for residues. (a) General. (1) Tolerances are established for emamectin... tolerance levels specified below is to be determined by measuring only the sum of emamectin (a mixture of a...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2011 CFR

2011-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

College Students' Intercultural Competence and Interethnic Tolerance

ERIC Educational Resources Information Center

Karnyshev, A. D.; Karnysheva, O. A.; Ivanova, E. A.

2014-01-01

Data from studies of interethnic tolerance among college students in Russia show that positive or negative attitudes toward other ethnic groups is a factor of both personal characteristics and experience of and access to other groups. Levels of tolerance in turn are associated with different levels of interest in other groups and in building…

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2014 CFR

2014-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2013 CFR

2013-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2012 CFR

2012-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

Long-term safety, tolerability, and efficacy of α1-adrenergic blocker in young men with primary bladder neck obstruction: results from a single centre in China.

PubMed

Li, Bing; Gao, Wansheng; Dong, Chuanjiang; Han, Xiaomin; Li, Shuqiang; Jia, Renfeng; Xiao, Chuanguo

2012-06-01

Primary bladder neck obstruction (PBNO) is a nonneurogenic voiding disorder and frequently overlooked in young men. Prior studies have reported the efficacy of α-blockers only in the short-term for male patients with PBNO. We hereby report our long-term results using α1-blocker therapy in young men with PBNO. Between January 2005 and December 2009, PBNO was diagnosed in 30 young men (mean age 27.3 years, range 18-35) at our institution. Doxazosin 4 mg once daily was administered for at least 12 months. Safety and tolerability were assessed, and efficacy was evaluated from International Prostate Symptom Score (I-PSS), Quality of Life (QOL), uroflowmetry, and post-void residual following 3- and 12-month treatment. Successful treatment was defined as at least 3 ml per second increase in the maximum flow rate and more than a 40% decrease in I-PSS. In all 30 patients, Mean symptom duration was 26.4 (3-65) months. The most common symptoms were hesitancy (93.3%), weak stream (76.7%), and frequency (66.7%). A total of 24 patients (80%, 24/30) successfully completed the 12 month of treatment. The medication period was 15.2 months, and follow-up duration was 16.3 months. Doxazosin was safe and well tolerated. The efficacy of doxazosin was maintained over the 12-month treatment period. Relative to baseline, there were reductions in the number of mean I-PSS (from 17.7 ± 4.2 to 10.4 ± 4.8), mean QOL (from 4.2 ± 1.1 to 2.4 ± 1.3), and mean post-void residual urine (from 79.3 ± 33.4 to 47.1 ± 21.3), and an increase in mean maximum flow rate (from 11.4 ± 2.9 to 15.1 ± 3.2 ml) after 12-month treatment. Treatment was successful in 16 patients (66.7%, 16/24) according to the improvement in both symptoms and maximum urine flow. α1-blocker therapy displayed a favorable safety, tolerability, and efficacy profile during 12-month treatment in young male patients with PBNO.

Effect of photoperiod prior to cold acclimation on freezing tolerance and carbohydrate metabolism in alfalfa (Medicago sativa L.).

PubMed

Bertrand, Annick; Bipfubusa, Marie; Claessens, Annie; Rocher, Solen; Castonguay, Yves

2017-11-01

Cold acclimation proceeds sequentially in response to decreases in photoperiod and temperature. This study aimed at assessing the impact of photoperiod prior to cold acclimation on freezing tolerance and related biochemical and molecular responses in two alfalfa cultivars. The fall dormant cultivar Evolution and semi-dormant cultivar 6010 were grown in growth chambers under different photoperiods (8, 10, 12, 14 or 16h) prior to cold acclimation. Freezing tolerance was evaluated as well as carbohydrate concentrations, levels of transcripts encoding enzymes of carbohydrate metabolism as well as a K-3dehydrin, before and after cold acclimation. The fall dormant cultivar Evolution had a better freezing tolerance than the semi-dormant cultivar 6010. The effect of photoperiod prior to cold acclimation on the level of freezing tolerance differed between the two cultivars: an 8h-photoperiod induced the highest level of freezing tolerance in Evolution and the lowest in 6010. In Evolution, the 8h-induced superior freezing tolerance was associated with higher concentration of raffinose-family oligosaccharides (RFO). The transcript levels of sucrose synthase (SuSy) decreased whereas those of sucrose phosphatase synthase (SPS) and galactinol synthase (GaS) increased in response to cold acclimation in both cultivars. Our results indicate that RFO metabolism could be involved in short photoperiod-induced freezing tolerance in dormant alfalfa cultivars. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Acetone, butanol, and ethanol production from gelatinized cassava flour by a new isolates with high butanol tolerance.

PubMed

Li, Han-Guang; Ofosu, Fred Kwame; Li, Kun-Tai; Gu, Qiu-Ya; Wang, Qiang; Yu, Xiao-Bin

2014-11-01

To obtain native strains resistant to butanol toxicity, a new isolating method and serial enrichment was used in this study. With this effort, mutant strain SE36 was obtained, which could withstand 35g/L (compared to 20g/L of the wild-type strain) butanol challenge. Based on 16s rDNA comparison, the mutant strain was identified as Clostridium acetobutylicum. Under the optimized condition, the phase shift was smoothly triggered and fermentation performances were consequently enhanced. The maximum total solvent and butanol concentration were 23.6% and 24.3%, respectively higher than that of the wild-type strain. Furthermore, the correlation between butanol produced and the butanol tolerance was investigated, suggesting that enhancing butanol tolerance could improve butanol production. These results indicate that the simple but effective isolation method and acclimatization process are a promising technique for isolation and improvement of butanol tolerance and production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress response in medically important Mucorales.

PubMed

Singh, Pankaj; Paul, Saikat; Shivaprakash, M Rudramurthy; Chakrabarti, Arunaloke; Ghosh, Anup K

2016-10-01

Mucorales are saprobes, ubiquitously distributed and able to infect a heterogeneous population of human hosts. The fungi require robust stress responses to survive in human host. We tested the growth of Mucorales in the presence of different abiotic stress. Eight pathogenic species of Mucorales, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Apophysomyces elegans, Licthemia corymbifera, Cunninghamella bertholletiae, Syncephalastrum racemosum and Mucor racemosus, were exposed to different stress inducers: osmotic (sodium chloride and d-sorbitol), oxidative (hydrogen peroxide and menadione), pH, cell wall and metal ions (Cu, Zn, Fe and Mg). Wide variation in stress responses was noted: R. arrhizus showed maximum resistance to both osmotic and oxidative stresses, whereas R. pusillus and M. indicus were relatively sensitive. Rhizopus arrhizus and R. microsporus showed maximum resistance to alkaline pH, whereas C. bertholletiae, L. corymbifera, M. racemosus and A. elegans were resistant to acidic pH. Maximum tolerance was noted in R. microsporus to Cu, R. microsporus and R. arrhizus to Fe and C. bertholletiae to Zn. In contrast, L. corymbifera, A. elegans and M. indicus were sensitive to Cu, Zn and Fe respectively. In conclusion, R. arrhizus showed high stress tolerance in comparison to other species of Mucorales, and this could be the possible reason for high pathogenic potential of this fungi. © 2016 Blackwell Verlag GmbH.

Image fusion using sparse overcomplete feature dictionaries

DOEpatents

Brumby, Steven P.; Bettencourt, Luis; Kenyon, Garrett T.; Chartrand, Rick; Wohlberg, Brendt

2015-10-06

Approaches for deciding what individuals in a population of visual system "neurons" are looking for using sparse overcomplete feature dictionaries are provided. A sparse overcomplete feature dictionary may be learned for an image dataset and a local sparse representation of the image dataset may be built using the learned feature dictionary. A local maximum pooling operation may be applied on the local sparse representation to produce a translation-tolerant representation of the image dataset. An object may then be classified and/or clustered within the translation-tolerant representation of the image dataset using a supervised classification algorithm and/or an unsupervised clustering algorithm.

DIETARY BAKED EGG ACCELERATES RESOLUTION OF EGG ALLERGY IN CHILDREN

PubMed Central

Leonard, Stephanie A.; Sampson, Hugh A.; Sicherer, Scott H.; Noone, Sally; Moshier, Erin L.; Godbold, James; Nowak-Wȩgrzyn, Anna

2012-01-01

Background Baked egg is tolerated by a majority of egg-allergic children. Objective To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets plays in the development of tolerance to regular egg. Methods Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. Results Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initial baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kUA/L) than those who subsequently tolerated baked egg (4.4 kUA/L; P=0.04) and regular egg (3.1 kUA/L, P=0.05). In subjects ingesting baked egg, EW-induced SPT wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG4 levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely to develop regular egg tolerance than subjects in the comparison group (P < 0.0001), and they developed tolerance earlier (median 50.0 versus 78.7 months; P<0.0001). Conclusion Initiation of a baked egg diet accelerates the development of regular egg tolerance compared to strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not. PMID:22846751

Dietary baked egg accelerates resolution of egg allergy in children.

PubMed

Leonard, Stephanie A; Sampson, Hugh A; Sicherer, Scott H; Noone, Sally; Moshier, Erin L; Godbold, James; Nowak-Węgrzyn, Anna

2012-08-01

Baked egg is tolerated by a majority of egg-allergic children. To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg. Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001). Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Adding Fault Tolerance to NPB Benchmarks Using ULFM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parchman, Zachary W; Vallee, Geoffroy R; Naughton III, Thomas J

2016-01-01

In the world of high-performance computing, fault tolerance and application resilience are becoming some of the primary concerns because of increasing hardware failures and memory corruptions. While the research community has been investigating various options, from system-level solutions to application-level solutions, standards such as the Message Passing Interface (MPI) are also starting to include such capabilities. The current proposal for MPI fault tolerant is centered around the User-Level Failure Mitigation (ULFM) concept, which provides means for fault detection and recovery of the MPI layer. This approach does not address application-level recovery, which is currently left to application developers. In thismore » work, we present a mod- ification of some of the benchmarks of the NAS parallel benchmark (NPB) to include support of the ULFM capabilities as well as application-level strategies and mechanisms for application-level failure recovery. As such, we present: (i) an application-level library to checkpoint and restore data, (ii) extensions of NPB benchmarks for fault tolerance based on different strategies, (iii) a fault injection tool, and (iv) some preliminary results that show the impact of such fault tolerant strategies on the application execution.« less

[Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

PubMed

Liu, Zhi-Juan; Liu, Guo-Sheng; Chen, Yong-Ge; Zhang, Hui-Li; Wu, Xue-Fen

2015-01-01

To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05). Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

The relationship between education and levels of trust and tolerance in Europe.

PubMed

Borgonovi, Francesca

2012-03-01

In this article we explore the relationship between education and levels of trust and tolerance in Europe. More specifically we assess whether the relationship between years of schooling and the extent to which individuals trust others in their communities and are tolerant towards immigrants varies across European countries and attempt to identify possible sources of these variations. Findings based on data from the first three rounds of the European Social Survey indicate that the association between education and levels of trust and tolerance varies significantly across countries and that a major source of this variation lies in the way in which individuals react to the level of diversity in the country where they live. © London School of Economics and Political Science 2012.

Potential for the development of tolerance by Aspergillus amstelodami, A. repens and A. ruber after repeated exposure to potassium sorbate.

PubMed

Viñas, I; Morlans, I; Sanchis, V

1990-01-01

Three strains of A. amstelodami, A. repens and A. ruber were exposed to various levels of potassium sorbate, and the MICs were determined. Selected strains of the molds were then repeatedly exposed to subinhibitory levels of the compound to determine whether increased tolerance might develop. The MIC of sorbate (pH 5.5 or 6.5) for 3 species of Aspergillus was 0.07%. Increasing levels of sorbate resulted in increasing growth suppression of the molds. The 3 Aspergillus species were tested for increased tolerance to potassium sorbate, and none was found. They developed a slight increase in tolerance dependent upon pH and the mold strain by subculturing at low levels of sorbate.

Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis

PubMed Central

Jolley, Caroline J.; Elston, Caroline; Moxham, John; Rafferty, Gerrard F.

2016-01-01

The electromyogram recorded from the diaphragm (EMGdi) and parasternal intercostal muscle using surface electrodes (sEMGpara) provides a measure of neural respiratory drive (NRD), the magnitude of which reflects lung disease severity in stable cystic fibrosis. The aim of this study was to explore perception of NRD and breathlessness in both healthy individuals and patients with cystic fibrosis. Given chronic respiratory loading and increased NRD in cystic fibrosis, often in the absence of breathlessness at rest, we hypothesised that patients with cystic fibrosis would be able to tolerate higher levels of NRD for a given level of breathlessness compared to healthy individuals during exercise. 15 cystic fibrosis patients (mean forced expiratory volume in 1 s (FEV1) 53.5% predicted) and 15 age-matched, healthy controls were studied. Spirometry was measured in all subjects and lung volumes measured in the cystic fibrosis patients. EMGdi and sEMGpara were recorded at rest and during incremental cycle exercise to exhaustion and expressed as a percentage of maximum (% max) obtained from maximum respiratory manoeuvres. Borg breathlessness scores were recorded at rest and during each minute of exercise. EMGdi % max and sEMGpara % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMGdi % max and sEMGpara % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMGdi % max and sEMGpara % max the cystic fibrosis patients reported significantly lower Borg breathlessness scores compared to the healthy individuals. At Borg score 1 (clinically significant increase in breathlessness from baseline) corresponding levels of EMGdi % max (20.2±12% versus 32.15±15%, p=0.02) and sEMGpara % max (18.9±8% versus 29.2±15%, p=0.04) were lower in the healthy individuals compared to the cystic fibrosis patients. In the cystic fibrosis patients EMGdi % max at Borg score 1 was related to the degree of airways obstruction (FEV1) (r=−0.664, p=0.007) and hyperinflation (residual volume/total lung capacity) (r=0.710, p=0.03). This relationship was not observed for sEMGpara % max. These data suggest that compared to healthy individuals, patients with cystic fibrosis can tolerate much higher levels of NRD before increases in breathlessness from baseline become clinically significant. EMGdi % max and sEMGpara % max provide physiological tools with which to elucidate factors underlying inter-individual differences in breathlessness perception. PMID:27730171

Automatic, nondestructive test monitors in-process weld quality

NASA Technical Reports Server (NTRS)

Deal, F. C.

1968-01-01

Instrument automatically and nondestructively monitors the quality of welds produced in microresistance welding. It measures the infrared energy generated in the weld as the weld is made and compares this energy with maximum and minimum limits of infrared energy values previously correlated with acceptable weld-strength tolerances.

7 CFR 1493.430 - Application for a payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.430 Application for a payment guarantee... request for CCC to reserve coverage up to the maximum quantity permitted by the contract loading tolerance...

7 CFR 1493.430 - Application for a payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.430 Application for a payment guarantee... request for CCC to reserve coverage up to the maximum quantity permitted by the contract loading tolerance...

Variation of plantar pressure in Chinese diabetes mellitus.

PubMed

Yang, Chuan; Xiao, Huisheng; Wang, Chuan; Mai, LiFang; Liu, Dan; Qi, Yiqing; Ren, Meng; Yan, Li

2015-01-01

To investigate dynamic changes in plantar pressure in Chinese diabetes mellitus patients and to provide a basis for further preventing diabetic foot. This is a cross-sectional investigation including 649 Chinese diabetes mellitus patients (diabetes group) and 808 "normal" Chinese persons (nondiabetes group) with normal blood glucose levels. All the subjects provided a complete medical history and underwent a physical examination and a 75-g oral glucose tolerance test. All subjects walked barefoot with their usual gait, and their dynamic plantar forces were measured using the one-step method with a plantar pressure measurement instrument; 5 measurements were performed for each foot. No significant differences were found in age, height, body weight, or body mass index between the two groups. The fasting blood glucose levels, plantar contact time, maximum force, pressure-time integrals and force-time integrals in the diabetes group were significantly higher than those in the nondiabetes group (p < 0.05). However, the maximum pressure was significantly higher in the nondiabetes group than in the diabetes group (p < 0.05). No difference was found in the contact areas between the two groups (p > 0.05). The maximum plantar force distributions were essentially the same, with the highest force found for the medial heel, followed by the medial forefoot and the first toe. The peak plantar pressure was located at the medial forefoot for the nondiabetes group and at the hallucis for the diabetes group. In the diabetes group, the momentum in each plantar region was higher than that in the nondiabetes group; this difference was especially apparent in the heel, the lateral forefoot and the hallucis. The dynamic plantar pressures in diabetic patients differ from those in nondiabetic people with increased maximum force and pressure, a different distribution pattern and significantly increased momentum, which may lead to the formation of foot ulcers. © 2015 by the Wound Healing Society.

Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension.

PubMed

Bellofiore, Alessandro; Dinges, Eric; Naeije, Robert; Mkrdichian, Hamorabi; Beussink-Nelson, Lauren; Bailey, Melissa; Cuttica, Michael J; Sweis, Ranya; Runo, James R; Keevil, Jon G; Francois, Christopher J; Shah, Sanjiv J; Chesler, Naomi C

2017-03-01

Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z 0 ), characteristic impedance (Z C , a measure of proximal PA stiffness) and proximal and distal PA compliance (C PA ). In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m 2 at rest; p=0.003) and PA compliance was decreased (C PA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m 2 at rest; p=0.0002). Z 0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10 -6 ). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z 0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Electronic modification of Pt via Ti and Se as tolerant cathodes in air-breathing methanol microfluidic fuel cells.

PubMed

Ma, Jiwei; Habrioux, Aurélien; Morais, Cláudia; Alonso-Vante, Nicolas

2014-07-21

We reported herein on the use of tolerant cathode catalysts such as carbon supported Pt(x)Ti(y) and/or Pt(x)Se(y) nanomaterials in an air-breathing methanol microfluidic fuel cell. In order to show the improvement of mixed-reactant fuel cell (MRFC) performances obtained with the developed tolerant catalysts, a classical Pt/C nanomaterial was used for comparison. Using 5 M methanol concentration in a situation where the fuel crossover is 100% (MRFC-mixed reactant fuel cell application), the maximum power density of the fuel cell with a Pt/C cathodic catalyst decreased by 80% in comparison with what is observed in the laminar flow fuel cell (LFFC) configuration. With Pt(x)Ti(y)/C and Pt(x)Se(y)/C cathode nanomaterials, the performance loss was only 55% and 20%, respectively. The evaluation of the tolerant cathode catalysts in an air-breathing microfluidic fuel cell suggests the development of a novel nanometric system that will not be size restricted. These interesting results are the consequence of the high methanol tolerance of these advanced electrocatalysts via surface electronic modification of Pt. Herein we used X-ray photoelectron and in situ FTIR spectroscopies to investigate the origin of the high methanol tolerance on modified Pt catalysts.

Heavy metal tolerance and accumulation of Triarrhena sacchariflora, a large amphibious ornamental grass.

PubMed

Tian, R N; Yu, S; Wang, S G; Zhang, Y; Tang, J Y; Liu, Y L; Nie, Y H

2013-01-01

In this study, we report the tolerance and accumulation of Triarrhena sacchariflora to copper (Cu) and cadmium (Cd). The results show that T. sacchariflora had strong tolerance to Cu and Cd stress. The tolerance indexes (TI) were greater than 0.5 for all treatments. The bioconcentration factors (BCFs) to Cu and Cd were both above 1.0. The accumulation ability of roots was stronger than that of shoots, and ranges of BCF to Cu and Cd in roots were 37.89-79.08 and 83.96-300.57, respectively. However, the translocation ability to Cu and Cd was weak, with more than 86% of Cu or Cd accumulated in roots, suggesting an exclusion strategy for heavy metal tolerance. The uptake efficiency (UE) and translocation efficiency (TE) to Cu and Cd increased linearly as the Cu and Cd concentration in the substrate increased. UE was higher than TE, with a maximum of 2,118.90 μg g(-1) root dry weight (DW) (50 mg L(-1) Cu) and 1,847.51 μg g(-1) root DW (20 mg L(-1)Cd), respectively. The results indicate that T. sacchariflora is a Cu- and Cd-tolerant non-hyperaccumulator plant, suggesting that T. sacchariflora could play an important role in phytoremediation in areas contaminated with Cu and Cd.

Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.

PubMed

He, Xiao-Tao; Zhou, Kai-Xiang; Zhao, Wen-Jun; Zhang, Chen; Deng, Jian-Ping; Chen, Fa-Ming; Gu, Ze-Xu; Li, Yun-Qing; Dong, Yu-Lin

2018-01-01

The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in the pathogenesis of BCP is still unknown. In the current study, we explored the possible engagement of HDACs in morphine tolerance during the pathogenesis of BCP. After intra-tibia tumor cell inoculation (TCI), we found that the increased expression of HDACs was negatively correlated with the decreased expression of MOR in the DRG following TCI. The paw withdrawal threshold (PWT) and percentage maximum possible effects (MPEs) decreased rapidly in TCI rats when morphine was used alone. In contrast, the concomitant use of SAHA and morphine significantly elevated the PWT and MPEs of TCI rats compared to morphine alone. Additionally, we found that SAHA administration significantly elevated MOR expression in the DRG of TCI rats with or without morphine treatment. Moreover, the TCI-induced increase in the co-expression of MOR and HDAC1 in neurons was significantly decreased after SAHA administration. These results suggest that HDACs are correlated with the downregulation of MOR in the DRG during the pathogenesis of BCP. Inhibition of HDACs using SAHA can be used to attenuate morphine tolerance in BCP.

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

PubMed

Kimura, Tomoki; Nagata, Yasushi; Harada, Hideyuki; Hayashi, Shinya; Matsuo, Yukinori; Takanaka, Tsuyoshi; Kokubo, Masaki; Takayama, Kenji; Onishi, Hiroshi; Hirakawa, Koichi; Shioyama, Yoshiyuki; Ehara, Takeshi

2017-10-01

To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Development of Communicative Tolerance among Teachers of Primary and Senior Level of the General Education School

ERIC Educational Resources Information Center

Povarenkov, Yury P.; Baranova, Nataly A.; Sidorova, Anna D.; Mitiukov, Nicholas W.

2018-01-01

The article is devoted to the study of the influence of the level of development of communicative tolerance on the effectiveness of the teaching and educational activity of primary and senior schoolteachers. In the article the concepts of psychophysiological and communicative tolerance are separated. The psychological content of communicative…

A study on the tolerance level of farmers toward human-wildlife conflict in the forest buffer zones of Tamil Nadu

PubMed Central

Senthilkumar, K.; Mathialagan, P.; Manivannan, C.; Jayathangaraj, M. G.; Gomathinayagam, S.

2016-01-01

Aim: The aim of this work was to study the tolerance level of farmers toward different human-wildlife conflict (HWC) situations. Materials and Methods: This study was conducted in 24 villages of nine blocks from Kancheepuram, Coimbatore, Erode, and Krishnagiri districts of Tamil Nadu by personally interviewing 240 farmers affected with four different HWC situations such as human-elephant conflict (HEC), human-wild pig conflict (HPC), human-gaur conflict (HGC), and human-monkey conflict (HMC). A scale developed for this purpose was used to find out the tolerance level of the farmers. Results: In general, the majority (61.70%) of the farmers had medium level of tolerance toward HWC, whereas 25.40% and 12.90% belonged to a high and low category, respectively. The mean tolerance level of the farmer’s encountering HMC is low (8.77) among the other three wild animal conflicts. In tackling HWC, the majority (55.00%) of the HEC farmers drove the elephant once it entered into their farmland. In the HPC, more than three-fourths of the respondents drove away the wild pig once they were found in farmlands. With regard to the HMC, a less number of them (1.70%) drove the monkey away if monkeys were spotted in their village. With regard to HGC, 95.00% of the respondents frightened the gaurs if their family members were threatened by gaurs. Conclusion: The present study suggests that that majority of the farmers had medium level of tolerance toward HWC. The tolerance level of the HMC farmers was lower than other three HWC affected farmers. This study emphasizes the need for necessary training to tackle the problem in an effective manner for wild animal conservation. PMID:27536037

A study on the tolerance level of farmers toward human-wildlife conflict in the forest buffer zones of Tamil Nadu.

PubMed

Senthilkumar, K; Mathialagan, P; Manivannan, C; Jayathangaraj, M G; Gomathinayagam, S

2016-07-01

The aim of this work was to study the tolerance level of farmers toward different human-wildlife conflict (HWC) situations. This study was conducted in 24 villages of nine blocks from Kancheepuram, Coimbatore, Erode, and Krishnagiri districts of Tamil Nadu by personally interviewing 240 farmers affected with four different HWC situations such as human-elephant conflict (HEC), human-wild pig conflict (HPC), human-gaur conflict (HGC), and human-monkey conflict (HMC). A scale developed for this purpose was used to find out the tolerance level of the farmers. In general, the majority (61.70%) of the farmers had medium level of tolerance toward HWC, whereas 25.40% and 12.90% belonged to a high and low category, respectively. The mean tolerance level of the farmer's encountering HMC is low (8.77) among the other three wild animal conflicts. In tackling HWC, the majority (55.00%) of the HEC farmers drove the elephant once it entered into their farmland. In the HPC, more than three-fourths of the respondents drove away the wild pig once they were found in farmlands. With regard to the HMC, a less number of them (1.70%) drove the monkey away if monkeys were spotted in their village. With regard to HGC, 95.00% of the respondents frightened the gaurs if their family members were threatened by gaurs. The present study suggests that that majority of the farmers had medium level of tolerance toward HWC. The tolerance level of the HMC farmers was lower than other three HWC affected farmers. This study emphasizes the need for necessary training to tackle the problem in an effective manner for wild animal conservation.

Incorporation of Bacterial Blight Resistance Genes Into Lowland Rice Cultivar Through Marker-Assisted Backcross Breeding.

PubMed

Pradhan, Sharat Kumar; Nayak, Deepak Kumar; Pandit, Elssa; Behera, Lambodar; Anandan, Annamalai; Mukherjee, Arup Kumar; Lenka, Srikanta; Barik, Durga Prasad

2016-07-01

Bacterial blight (BB) of rice caused by Xanthomonas oryzae pv. oryzae is a major disease of rice in many rice growing countries. Pyramided lines carrying two BB resistance gene combinations (Xa21+xa13 and Xa21+xa5) were developed in a lowland cultivar Jalmagna background through backcross breeding by integrating molecular markers. In each backcross generation, markers closely linked to the disease resistance genes were used to select plants possessing the target genes. Background selection was continued in those plants carrying resistant genes until BC(3) generation. Plants having the maximum contribution from the recurrent parent genome were selected in each generation and hybridized with the recipient parent. The BB-pyramided line having the maximum recipient parent genome recovery of 95% was selected among BC3F1 plants and selfed to isolate homozygous BC(3)F(2) plants with different combinations of BB resistance genes. Twenty pyramided lines with two resistance gene combinations exhibited high levels of tolerance against the BB pathogen. In order to confirm the resistance, the pyramided lines were inoculated with different X. oryzae pv. oryzae strains of Odisha for bioassay. The genotypes with combination of two BB resistance genes conferred high levels of resistance to the predominant X. oryzae pv. oryzae isolates prevalent in the region. The pyramided lines showed similarity with the recipient parent with respect to major agro-morphologic traits.

Infants’ Exposure to Aflatoxin M1 from Mother’s Breast Milk in Iran

PubMed Central

Ghiasian, SA; Maghsood, AH

2012-01-01

Background The occurrence of aflatoxin M1 (AFM1) in milk, especially breast milk, is a valuable biomarker for exposure determination to aflatoxin B1 (AFB1). In the present study, the risk of exposure to AFM1 in infants fed breast milk was investigated. Methods: An enzyme-linked immunosorbent assay (ELISA) was used for the analysis of AFM1 in breast milk samples from 132 lactating mothers referred to four urban Mothers and Babies Care Unit of Hamadan, western Iran. Results: AFM1 was detected in eight samples (6.06%) at mean concentration of 9.45 ng/L. The minimum and maximum of concentration was 7.1 to 10.8 ng/L, respectively. Although the concentration of AFM1 in none of the samples was higher than the maximum tolerance limit accepted by USA and European Union (25 ng/kg) however, 25% had a level of AFM1 above the allowable level of Australia and Switzerland legal limit (10 ng/L). Conclusions: Lactating mothers and infants in western parts of Iran could be at risk for AFB1 and AFM1 exposure, respectively. Considering all this information, the investigation of AFM1 in lactating mothers as a biomarker for post-natal exposure of infants to this carcinogen deserves further studies in various seasons and different parts of Iran. PMID:23113156

Change in blood coagulation indices as a function of the incubation period of plasma in a constant magnetic field. [considering heparin tolerance and recalcification

NASA Technical Reports Server (NTRS)

Yepishina, S. G.

1974-01-01

The influence of a constant magnetic field (CMF) with a strength of 250 and 2500 oersteds on the recalcification reaction and the tolerance of plasma to heparin was studied as a function of the exposure time of the plasma to the CMF. The maximum and reliable change in the activation of the coagulatory system of the blood was observed after a 20-hour incubation of the plasma in a CMF. As the exposure time increased, the recalcification reaction changed insigificantly; the difference between the mean arithmetic of the experiment and control values was not statistically reliable. The tolerance of the plasma to heparin as a function of the exposure time to the CMF of the plasma was considerably modified, an was statistically reliable.

Intraspecific variability of Steinernema feltiae strains from Cemoro Lawang, eastern Java, Indonesia.

PubMed

Addis, T; Mulawarman, M; Waeyenberge, L; Moens, M; Viaene, N; Ehlers, R U

2010-01-01

Four strains of Steinernema feltiae from Eastern Java, Indonesia were characterized based on morphometric, morphological and molecular data. In addition, their virulence against last instar Tenebrio molitor and heat tolerance was tested. Infective juvenile have a mean body length ranging from 749 to 792 microm. The maximum sequence difference among the four strains was 7 bp (8.8%) in the ITS and 2 bp (0.3%) in D2D3 regions of the rDNA. All the strains are not reproductively isolated and can reproduce with European strain S. feltiae Owiplant. The lowest LC50 was observed for strain SCM (373) and the highest for S. feltiae strain Owiplant (458) IJs/40 T. molitor. All four strains showed relatively better mean heat tolerance when compared with S. feltiae Owiplant, both in adapted and non-adapted heat tolerance experiments.

B Cell Receptor Signaling-Based Index as a Biomarker for the Loss of Peripheral Immune Tolerance in Autoreactive B Cells in Rheumatoid Arthritis

PubMed Central

Lyubchenko, Taras; Zerbe, Gary O.

2014-01-01

This study examines the loss of peripherally induced B cell immune tolerance in Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of activation in a subset of autoreactive B cells - the Induced tolerance status index (ITSI). Naturally occurring naïve autoreactive B cells can escape the “classical” tolerogenic mechanisms of clonal deletion and receptor editing, but remain peripherally tolerized through B cell receptor (BCR) signaling inhibition (postdevelopmental “receptor tuning” or anergy). ITSI is a statistical index that numerically determines the level of homology between activation patterns of BCR signaling intermediaries in B cells that are either tolerized or activated by auto antigen exposure, and thus quantifies the level of peripheral immune tolerance. The index is based on the logistic regression analysis of phosphorylation levels in a panel of BCR signaling proteins. Our results demonstrate a new approach to identifying autoreactive B cells based on their BCR signaling features. PMID:25057856

Studying DDT Susceptibility at Discriminating Time Intervals Focusing on Maximum Limit of Exposure Time Survived by DDT Resistant Phlebotomus argentipes (Diptera: Psychodidae): an Investigative Report.

PubMed

Rama, Aarti; Kesari, Shreekant; Das, Pradeep; Kumar, Vijay

2017-07-24

Extensive application of routine insecticide i.e., dichlorodiphenyltrichloroethane (DDT) to control Phlebotomus argentipes (Diptera: Psychodidae), the proven vector of visceral leishmaniasis in India, had evoked the problem of resistance/tolerance against DDT, eventually nullifying the DDT dependent strategies to control this vector. Because tolerating an hour-long exposure to DDT is not challenging enough for the resistant P. argentipes, estimating susceptibility by exposing sand flies to insecticide for just an hour becomes a trivial and futile task.Therefore, this bioassay study was carried out to investigate the maximum limit of exposure time to which DDT resistant P. argentipes can endure the effect of DDT for their survival. The mortality rate of laboratory-reared DDT resistant strain P. argentipes exposed to DDT was studied at discriminating time intervals of 60 min and it was concluded that highly resistant sand flies could withstand up to 420 min of exposure to this insecticide. Additionally, the lethal time for female P. argentipes was observed to be higher than for males suggesting that they are highly resistant to DDT's toxicity. Our results support the monitoring of tolerance limit with respect to time and hence points towards an urgent need to change the World Health Organization's protocol for susceptibility identification in resistant P. argentipes.

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

[The impaired glucose tolerance in the pathogenesis of dyslipidemia].

PubMed

Ikoue, I; Takahashi, K; Katayama, S

1996-10-01

It is well known that hyperlipidemia is often present in patient with impaired glucose tolerance, obesity and/or hypertension. All of these are risk factors for coronary artery disease (CAD). The coexistence of these risk factors markedly increase the likelihood of CAD. Recently, it has been reported that the impaired glucose tolerance and insulin resistence are associated with the increased proinsulin, which is linked to the risk of CAD. We review that the impaired glucose tolerance is an important factor causing dyslipidemia. The characteristic of dyslipidemia associated with the impaired glucose tolerance include hypertriglyceridemia, high level of VLDL and low level of HDL cholesterol. They also associate with accumulation of remnant lipoproteins and appearance of small dense LDL. In addition, we pointed out that the increased number of risk factors is associated with elevated insulin and proinsulin level.

Covariance Based Pre-Filters and Screening Criteria for Conjunction Analysis

NASA Astrophysics Data System (ADS)

George, E., Chan, K.

2012-09-01

Several relationships are developed relating object size, initial covariance and range at closest approach to probability of collision. These relationships address the following questions: - Given the objects' initial covariance and combined hard body size, what is the maximum possible value of the probability of collision (Pc)? - Given the objects' initial covariance, what is the maximum combined hard body radius for which the probability of collision does not exceed the tolerance limit? - Given the objects' initial covariance and the combined hard body radius, what is the minimum miss distance for which the probability of collision does not exceed the tolerance limit? - Given the objects' initial covariance and the miss distance, what is the maximum combined hard body radius for which the probability of collision does not exceed the tolerance limit? The first relationship above allows the elimination of object pairs from conjunction analysis (CA) on the basis of the initial covariance and hard-body sizes of the objects. The application of this pre-filter to present day catalogs with estimated covariance results in the elimination of approximately 35% of object pairs as unable to ever conjunct with a probability of collision exceeding 1x10-6. Because Pc is directly proportional to object size and inversely proportional to covariance size, this pre-filter will have a significantly larger impact on future catalogs, which are expected to contain a much larger fraction of small debris tracked only by a limited subset of available sensors. This relationship also provides a mathematically rigorous basis for eliminating objects from analysis entirely based on element set age or quality - a practice commonly done by rough rules of thumb today. Further, these relations can be used to determine the required geometric screening radius for all objects. This analysis reveals the screening volumes for small objects are much larger than needed, while the screening volumes for pairs of large objects may be inadequate. These relationships may also form the basis of an important metric for catalog maintenance by defining the maximum allowable covariance size for effective conjunction analysis. The application of these techniques promises to greatly improve the efficiency and completeness of conjunction analysis.

Scaling laws for oxygen transport across the space-filling system of respiratory membranes in the human lung

NASA Astrophysics Data System (ADS)

Hou, Chen

Space-filling fractal surfaces play a fundamental role in how organisms function at various levels and in how structure determines function at different levels. In this thesis, we develop a quantitative theory of oxygen transport to and across the surface of the highly branched, space-filling system of alveoli, the fundamental gas exchange unit (acinar airways), in the human lung. Oxygen transport in the acinar airways is by diffusion, and we treat the two steps---diffusion through the branched airways, and transfer across the alveolar membranes---as a stationary diffusion-reaction problem, taking into account that there may be steep concentration gradients between the entrance and remote alveoli (screening). We develop a renormalization treatment of this screening effect and derive an analytic formula for the oxygen current across the cumulative alveolar membrane surface, modeled as a fractal, space-filling surface. The formula predicts the current from a minimum of morphological data of the acinus and appropriate values of the transport parameters, through a number of power laws (scaling laws). We find that the lung at rest operates near the borderline between partial screening and no screening; that it switches to no screening under exercise; and that the computed currents agree with measured values within experimental uncertainties. From an analysis of the computed current as a function of membrane permeability, we find that the space-filling structure of the gas exchanger is simultaneously optimal with respect to five criteria. The exchanger (i) generates a maximum oxygen current at minimum permeability; (ii) 'wastes' a minimum of surface area; (iii) maintains a minimum residence time of oxygen in the acinar airways; (iv) has a maximum fault tolerance to loss of permeability; and (v) generates a maximum current increase when switching from rest to exercise.

[Gradation in the level of vitamin consumption: possible risk of excessive consumption].

PubMed

Kodentsova, V M

2014-01-01

The ratio between the levels of consumption of certain vitamins and minerals [recommended daily allowance for labelling purposes < maximum supplement levels < tolerable upper intake level (UL) < safe level (limit) of consumption < or = therapeutic dose has been characterized. Vitamin A and beta-carotene maximum supplement levels coincides with UL, and recommended daily allowance for these micronutrients coincides with the maximal level of consumption through dietary supplements and/or multivitamins. Except for vitamin A and beta-carotene recommended daily allowance for other vitamins adopted in Russia are considerably lower than the upper safe level of consumption. For vitamin A and beta-carotene there is a potential risk for excess consumption. According to the literature data (meta-analysis) prolonged intake of high doses of antioxidant vitamins (above the RDA) both alone and in combination with two other vitamins or vitamin C [> 800 microg (R.E.) of vitamin A, > 9.6 mg of beta-carotene, > 15 mg (T.E.) of vitamin E] do not possess preventive effects and may be harmful with unwanted consequences to health, especially in well-nourished populations, persons having risk of lung cancer (smokers, workers exposed to asbestos), in certain conditions (in the atmosphere with high oxygen content, hyperoxia, oxygen therapy). Proposed mechanisms of such action may be due to the manifestation of prooxidant action when taken in high doses, shifting balance with other important natural antioxidants, their displacement (substitution), interference with the natural defense mechanisms. Athletes are the population group that requires attention as used antioxidant vitamins A, C, E, both individually and in combination in extremely high doses. In summary, it should be noted that intake of physiological doses which are equivalent to the needs of the human organism, as well as diet inclusion of fortified foods not only pose no threat to health, but will bring undoubted benefits, filling the existing lack of vitamins in the ration.

Three approaches to define desired soil organic matter contents.

PubMed

Sparling, G; Parfitt, R L; Hewitt, A E; Schipper, L A

2003-01-01

Soil organic C is often suggested as an indicator of soil quality, but desirable targets are rarely specified. We tested three approaches to define maximum and lowest desirable soil C contents for four New Zealand soil orders. Approach 1 used the New Zealand National Soils Database (NSD). The maximum C content was defined as the median value of long-term pastures, and the lower quartile defined the lowest desirable soil C content. Approach 2 used the CENTURY model to predict maximum C contents of long-term pasture. Lowest desirable content was defined by the level that still allowed recovery to 80% of the maximum C content over 25 yr. Approach 3 used an expert panel to define desirable C contents based on production and environmental criteria. Median C contents (0-20 cm) for the Recent, Granular, Melanic, and Allophanic orders were 72, 88, 98, 132 Mg ha(-1), and similar to contents predicted by the CENTURY model (78, 93, 102, and 134 Mg ha(-1), respectively). Lower quartile values (54, 78, 73, and 103 Mg ha(-1), respectively) were similar to the lowest desirable C contents calculated by CENTURY (55, 54, 67, and 104 Mg ha(-1), respectively). Expert opinion was that C contents could be depleted below these values with tolerable effects on production but less so for the environment. The CENTURY model is our preferred approach for setting soil organic C targets, but the model needs calibrating for other soils and land uses. The statistical and expert opinion approaches are less defensible in setting lower limits for desirable C contents.

Glucose in vaginal secretions before and after oral glucose tolerance testing in women with and without recurrent vulvovaginal candidiasis.

PubMed

Ehrström, Sophia; Yu, Anna; Rylander, Eva

2006-12-01

To measure the change of glucose in vaginal secretions during glucose tolerance testing in women with recurrent vulvovaginal candidiasis and in healthy control subjects. Thirty-eight women with recurrent vulvovaginal candidiasis and 45 healthy, age-matched controls completed a health questionnaire regarding general and gynecologic health and food and alcohol habits. They all underwent an oral glucose tolerance test and a vaginal examination. Vaginal secretion was collected from the proximal part of the vagina. Glucose in plasma and in vaginal secretions were measured at fasting and after 2 hours and analyzed with the hexokinase method. A sample size analysis showed that the number of subjects included in the study was sufficient for a beta value of 0.80, at the significance level of alpha=.05, at a difference in glucose in vaginal secretions of 30% after oral glucose tolerance test. In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. No significant difference was seen regarding change of glucose level in vaginal secretions and plasma glucose after testing, compared with before oral glucose tolerance testing. There were no differences between women with recurrent vulvovaginal candidiasis and control subjects regarding change in glucose level in vaginal secretions or in plasma during oral glucose tolerance test. II-2.

LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.

PubMed

Takahashi, Shunji; Kobayashi, Takayuki; Tomomatsu, Junichi; Ito, Yoshinori; Oda, Hisanobu; Kajitani, Tatsuhiro; Kakizume, Tomoyuki; Tajima, Takeshi; Takeuchi, Hiromi; Maacke, Heiko; Esaki, Taito

2017-01-01

Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients. LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status. The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11-14 days. No anti-LJM716 antibodies were detected. LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed. ClinicalTrials.gov NCT01911936.

Finger cold-induced vasodilation of older Korean female divers, haenyeo: effects of chronic cold exposure and aging

NASA Astrophysics Data System (ADS)

Lee, Joo-Young; Park, Joonhee; Koh, Eunsook; Cha, Seongwon

2017-07-01

The aim of the present study was to evaluate the local cold tolerance of older Korean female divers, haenyeo ( N = 22) in terms of cold acclimatization and ageing. As control groups, older non-diving females ( N = 25) and young females from a rural area ( N = 15) and an urban area ( N = 51) participated in this study. To evaluate local cold tolerance, finger cold-induced vasodilation (CIVD) during finger immersion of 4 °C water was examined. As a result, older haenyeos showed greater minimum finger temperature and recovery finger temperature than older non-diving females ( P < 0.05), but similar responses in onset time, peak time, maximum finger temperature, frequency of CIVD, heart rate, blood pressure, and thermal and pain sensations as those of older non-diving females. Another novel finding was that young urban females showed more vulnerable responses to local cold in CIVD variables and subjective sensations when compared to older females, whereas young rural females had the most excellent cold tolerance in terms of maximum temperature and frequency of CIVD among the four groups ( P < 0.05). The present results imply that older haenyeos still retain cold acclimatized features on the periphery even though they changed their cotton diving suits to wet suits in the early 1980s. However, cardiovascular responses and subjective sensations to cold reflect aging effects. In addition, we suggest that young people who have been adapted to highly insulated clothing and indoor heating systems in winter should be distinguished from young people who were exposed to less modern conveniences when compared to the aged in terms of cold tolerance.

A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

PubMed

Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

2017-06-01

Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis ▿ §

PubMed Central

Cornely, O. A.; Vehreschild, J. J.; Vehreschild, M. J. G. T.; Würthwein, G.; Arenz, D.; Schwartz, S.; Heussel, C. P.; Silling, G.; Mahne, M.; Franklin, J.; Harnischmacher, U.; Wilkens, A.; Farowski, F.; Karthaus, M.; Lehrnbecher, T.; Ullmann, A. J.; Hallek, M.; Groll, A. H.

2011-01-01

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin. PMID:21911573

Finger cold-induced vasodilation of older Korean female divers, haenyeo: effects of chronic cold exposure and aging.

PubMed

Lee, Joo-Young; Park, Joonhee; Koh, Eunsook; Cha, Seongwon

2017-07-01

The aim of the present study was to evaluate the local cold tolerance of older Korean female divers, haenyeo (N = 22) in terms of cold acclimatization and ageing. As control groups, older non-diving females (N = 25) and young females from a rural area (N = 15) and an urban area (N = 51) participated in this study. To evaluate local cold tolerance, finger cold-induced vasodilation (CIVD) during finger immersion of 4 °C water was examined. As a result, older haenyeos showed greater minimum finger temperature and recovery finger temperature than older non-diving females (P < 0.05), but similar responses in onset time, peak time, maximum finger temperature, frequency of CIVD, heart rate, blood pressure, and thermal and pain sensations as those of older non-diving females. Another novel finding was that young urban females showed more vulnerable responses to local cold in CIVD variables and subjective sensations when compared to older females, whereas young rural females had the most excellent cold tolerance in terms of maximum temperature and frequency of CIVD among the four groups (P < 0.05). The present results imply that older haenyeos still retain cold acclimatized features on the periphery even though they changed their cotton diving suits to wet suits in the early 1980s. However, cardiovascular responses and subjective sensations to cold reflect aging effects. In addition, we suggest that young people who have been adapted to highly insulated clothing and indoor heating systems in winter should be distinguished from young people who were exposed to less modern conveniences when compared to the aged in terms of cold tolerance.

Alcohol levels do not accurately predict physical or mental impairment in ethanol-tolerant subjects: relevance to emergency medicine and dram shop laws.

PubMed

Roberts, James R; Dollard, Denis

2010-12-01

The human body and the central nervous system can develop tremendous tolerance to ethanol. Mental and physical dysfunctions from ethanol, in an alcohol-tolerant individual, do not consistently correlate with ethanol levels traditionally used to define intoxication, or even lethality, in a nontolerant subject. Attempting to relate observed signs of alcohol intoxication or impairment, or to evaluate sobriety, by quantifying blood alcohol levels can be misleading, if not impossible. We report a case demonstrating the disconnect between alcohol levels and generally assigned parameters of intoxication and impairment. In this case, an alcohol-tolerant man, with a serum ethanol level of 515 mg/dl, appeared neurologically intact and cognitively normal. This individual was without objective signs of impairment or intoxication by repeated evaluations by experienced emergency physicians. In alcohol-tolerant individuals, blood alcohol levels cannot always be predicted by and do not necessarily correlate with outward appearance, overt signs of intoxication, or physical examination. This phenomenon must be acknowledged when analyzing medical decision making in the emergency department or when evaluating the ability of bartenders and party hosts to identify intoxication in dram shop cases.

40 CFR 1042.840 - Application requirements for remanufactured engines.

Code of Federal Regulations, 2013 CFR

2013-07-01

... other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel). List each distinguishable... and the range of values for maximum engine power resulting from production tolerances, as described in...

40 CFR 1042.840 - Application requirements for remanufactured engines.

Code of Federal Regulations, 2012 CFR

2012-07-01

... other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel). List each distinguishable... and the range of values for maximum engine power resulting from production tolerances, as described in...

7 CFR 201.55 - Retests.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Germination Tests in the Administration of the Act § 201.55 Retests. Retests shall be made as follows: (a) When the range of 100-seed replicates of a given test exceeds the maximum tolerated range in the table...

7 CFR 201.55 - Retests.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Germination Tests in the Administration of the Act § 201.55 Retests. Retests shall be made as follows: (a) When the range of 100-seed replicates of a given test exceeds the maximum tolerated range in the table...

75 FR 28155 - Acephate, Cacodylic acid, Dicamba, Dicloran et al.; Proposed Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... (NAICS code 112). Food manufacturing (NAICS code 311). Pesticide manufacturing (NAICS code 32532). This..., including food service, manufacturing and processing establishments, such as restaurants, cafeterias... concentration shall be limited to a maximum of 1.0 percent active ingredient. Contamination of food or food...

Variation in temperature tolerance among families of Atlantic salmon (Salmo salar L.) is associated with hypoxia tolerance, ventricle size and myoglobin level

USDA-ARS?s Scientific Manuscript database

In fishes, performance failure at high temperature is thought to be due to a limitation on oxygen delivery (the theory of oxygen and capacity limited thermal tolerance, OCLTT), which suggests that thermal tolerance and hypoxia tolerance might be functionally associated. Here we examined variation in...

The metal tolerance profile of Thlaspi goesingense is mimicked in Arabidopsis thaliana heterologously expressing serine acetyl-transferase.

PubMed

Freeman, John L; Salt, David E

2007-11-28

The Ni hyperaccumulator Thlaspi goesingense is tolerant to Ni congruent with Zn, congruent with Co and slightly resistant to > Cd. We previously observed that elevated glutathione, driven by constitutive activation of serine acetyltransferase (SAT), plays a role in the Ni tolerance of T. goesingense. Here we show that the elevated shoot concentration of glutathione, previously shown to cause elevated Ni tolerance in Arabidopsis thaliana heterologously expressing T. goesingense mitochondrial serine acetyltransferase (SATm), also causes tolerance to Co and Zn while slightly enhancing resistance to Cd. The level of tolerance afforded to each metal is ranked Ni congruent with Co, > Zn > Cd. The Ni congruent with Co, > Zn tolerances are positively correlated with both the accumulation of glutathione (GSH) and the ability to resist the oxidative damage induced by these different metals. Based on the relative concentrations of each metal used a relatively low level of resistance to Cd was observed in both T. goesingense and TgSATm expressing lines and Cd resistance was least correlated to GSH accumulation. Such data supports the conclusion that elevated glutathione levels, driven by constitutively enhanced SAT activity in the hyperaccumulator T. goesingense, plays an important role in the Ni, Co and Zn tolerance of this and other Thlaspi species. The hyper-activation of S assimilation through SAT is an excellent strategy for engineering enhanced metal tolerance in transgenic plants potentially used for phytoremediation.

The metal tolerance profile of Thlaspi goesingense is mimicked in Arabidopsis thaliana heterologously expressing serine acetyl-transferase

PubMed Central

Freeman, John L; Salt, David E

2007-01-01

Background The Ni hyperaccumulator Thlaspi goesingense is tolerant to Ni ≅ Zn, ≅ Co and slightly resistant to > Cd. We previously observed that elevated glutathione, driven by constitutive activation of serine acetyltransferase (SAT), plays a role in the Ni tolerance of T. goesingense. Results Here we show that the elevated shoot concentration of glutathione, previously shown to cause elevated Ni tolerance in Arabidopsis thaliana heterologously expressing T. goesingense mitochondrial serine acetyltransferase (SATm), also causes tolerance to Co and Zn while slightly enhancing resistance to Cd. The level of tolerance afforded to each metal is ranked Ni ≅ Co, > Zn > Cd. The Ni ≅ Co, > Zn tolerances are positively correlated with both the accumulation of glutathione (GSH) and the ability to resist the oxidative damage induced by these different metals. Based on the relative concentrations of each metal used a relatively low level of resistance to Cd was observed in both T. goesingense and TgSATm expressing lines and Cd resistance was least correlated to GSH accumulation. Conclusion Such data supports the conclusion that elevated glutathione levels, driven by constitutively enhanced SAT activity in the hyperaccumulator T. goesingense, plays an important role in the Ni, Co and Zn tolerance of this and other Thlaspi species. The hyper-activation of S assimilation through SAT is an excellent strategy for engineering enhanced metal tolerance in transgenic plants potentially used for phytoremediation. PMID:18045473

Urinary analysis reveals high deoxynivalenol exposure in pregnant women from Croatia.

PubMed

Sarkanj, Bojan; Warth, Benedikt; Uhlig, Silvio; Abia, Wilfred A; Sulyok, Michael; Klapec, Tomislav; Krska, Rudolf; Banjari, Ines

2013-12-01

In this pilot survey the levels of various mycotoxin biomarkers were determined in third trimester pregnant women from eastern Croatia. First void urine samples were collected and analysed using a "dilute and shoot" LC-ESI-MS/MS multi biomarker method. Deoxynivalenol (DON) and its metabolites: deoxynivalenol-15-glucuronide and deoxynivalenol-3-glucuronide were detected in 97.5% of the studied samples, partly at exceptionally high levels, while ochratoxin A was found in 10% of the samples. DON exposure was primarily reflected by the presence of deoxynivalenol-15-glucuronide with a mean concentration of 120 μg L(-1), while free DON was detected with a mean concentration of 18.3 μg L(-1). Several highly contaminated urine samples contained a third DON conjugate, tentatively identified as deoxynivalenol-7-glucuronide by MS/MS scans. The levels of urinary DON and its metabolites measured in this study are the highest ever reported, and 48% of subjects were estimated to exceed the provisional maximum tolerable daily intake (1 μg kg(-1) b.w.). Copyright © 2013 Elsevier Ltd. All rights reserved.

Polycyclic aromatic hydrocarbons in Italian preserved food products in oil.

PubMed

Sannino, Anna

2016-06-01

A method based on gas chromatography/ tandem mass spectrometry was used to assess levels of 16 EU priority polycyclic aromatic hydrocarbons (PAHs) in 48 preserved food products in oil including foods such as vegetables in oil, fish in oil and oil-based sauces obtained from the Italian market. The benzo[a]pyrene concentrations ranged from <0.04 to 0.40 µg kg(-1), and 72.9% of the samples showed detectable levels of this compound. The highest contamination level was observed for chrysene with three additional PAHs (benzo[a]anthracene, benzo[b]fluoranthene and benzo[c]fluorene) giving mean values higher than the mean value for benzo[a]pyrene. Chrysene was detected in all the samples at concentrations ranging from 0.07 to 1.80 µg kg(-1) (median 0.31 µg kg(-1)). The contamination expressed as PAH4 (sum of benzo(a)pyrene, chrysene, benzo(a)anthracene and benzo(b)fluoranthene), for which the maximum tolerable limit has been set by Commission Regulation (EU) No. 835/2011, varied between 0.10 and 2.94 µg kg(-1).

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II.

PubMed

Degenring, F H; Suter, A; Weber, M; Saller, R

2003-01-01

A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator. In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.

40 CFR 141.66 - Maximum contaminant levels for radionuclides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Maximum contaminant levels for... Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.66 Maximum contaminant levels for radionuclides. (a) [Reserved] (b) MCL for combined radium-226 and -228. The maximum...

40 CFR 141.66 - Maximum contaminant levels for radionuclides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Maximum contaminant levels for... Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.66 Maximum contaminant levels for radionuclides. (a) [Reserved] (b) MCL for combined radium-226 and -228. The maximum...

40 CFR 141.66 - Maximum contaminant levels for radionuclides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Maximum contaminant levels for... Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.66 Maximum contaminant levels for radionuclides. (a) [Reserved] (b) MCL for combined radium-226 and -228. The maximum...

40 CFR 141.66 - Maximum contaminant levels for radionuclides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Maximum contaminant levels for... Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.66 Maximum contaminant levels for radionuclides. (a) [Reserved] (b) MCL for combined radium-226 and -228. The maximum...

Safety assessment of medium- and long-chain triacylglycerols containing 30% (w/w) medium-chain fatty acids in mice and rats.

PubMed

Zhou, Shengmin; Wang, Yueqiang; Jiang, Yuanrong; Yu, Liangli Lucy

2017-06-01

A novel medium- and long-chain triacylglycerols (MLCT), with 30% (w/w) medium-chain fatty acids (MCFA) was evaluated for its safety as a dietary fat in mice and rats. The subacute oral toxicity study showed that the maximum tolerated dose exceeded 54.33 g/kg body weight (kg bw)/day. In the 90-day feeding study, no dose-related adverse effects were observed in rats administered diets formulated with different levels of MLCT (2.0, 4.0, and 8.0 g/kg bw/day) as compared to the rapeseed oil control diet. Further safety assessment in pregnant rats did not reveal any significant difference relative to the control at a treatment level up to 8.0 g MLCT/kg bw/day. The results from this study indicated the safe use of MLCT with high contents of MCFA in food products for improving human health. Copyright © 2017 Elsevier Inc. All rights reserved.

Patulin in apple leather in Iran.

PubMed

Montaseri, H; Eskandari, M H; Yeganeh, A T; Karami, S; Javidnia, K; Dehghanzadeh, G R; Mesbahi, G R; Niakousari, M

2014-01-01

Apple leather is made by dehydration of cooked fruit into leathery sheets. Mould growth and patulin production can occur in damaged apples or when fallen fruit is collected for apple leather processing. A survey was conducted to determine levels and dietary intake of patulin from apple leather marketed in Iran. Patulin was detected in all samples at concentrations ranging from <10 to 2559 µg/kg. Mean patulin concentration was 620 µg/kg and 91.4% of the samples had levels higher than 50 µg/kg. Estimated daily intake (EDI) of patulin for adults and children considering the mean concentration of patulin obtained in this study (620 µg/kg) were higher than the provisional maximum tolerable daily intake (PMTDI) of 0.4 µg/kg bw/day for patulin that has been established by the Joint FAO/WHO Expert Committee on Food Additives. This indicated the need for stricter control and improvement in processing techniques to reduce the incidence of patulin in apple leather.

[Significance of extruded feeds for trout nutrition and water protection].

PubMed

Steffens, W

1993-01-01

Extruded feeds exhibit an improved starch digestibility and are more firmly bound due to the almost complete gelatinization of the starch. This results in fewer fines and longer water stability than pelleted feeds. Extruded pellets also have the advantage that they can soak up more oil than a conventional pellet. It is therefore possible to increase the maximum oil content to more than 20%. On the other hand extruding feeds is more expensive than steam pelleting. Gelatinized starch is a useful energy source in trout diets helping to reduce feed conversion ratios. Proportions up to 35-40% in the diet are tolerable. Using high dietary levels of both gelatinized starch and oil the non-protein energy of feed may be increased and thus a protein-sparing effect results. High-energy diets enable to reduce excretion of faeces and of nitrogen via gills. In addition a decrease of phosphorus level in feeds and thus of phosphorus excretion by fish is possible. Extruded high-energy diets therefore make a contribution to improve water quality.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

PubMed

Hammana, I; Malet, A; Costa, M; Brochiero, E; Berthiaume, Y; Potvin, S; Chiasson, J-L; Coderre, L; Rabasa-Lhoret, R

2007-06-01

Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic Treatment.

PubMed

Tarcan, Tufan; Akbal, Cem; Sekerci, Cağri A; Top, Tuncay; Simşek, Ferruh

2014-04-01

This was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization. The study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia. Thirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated. Onabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.

Metabolomics analysis of rice responses to salinity stress revealed elevation of serotonin, and gentisic acid levels in leaves of tolerant varieties.

PubMed

Gupta, Poulami; De, Bratati

2017-07-03

A GC-MS based analytical approach was undertaken to understand the metabolomic responses of seedlings of 2 salt sensitive (Sujala and MTU 7029) and 2 tolerant varieties (Bhutnath, and Nonabokra) of indica rice (Oryza sativa L.) to NaCl induced stress. The 4 varieties responded differently to NaCl treatment with respect to the conserved primary metabolites (sugars, polyols, amino acids, organic acids and certain purine derivatives) of the leaf of rice seedlings. However, there were significant differences in salt induced production of chorismic acid derivatives. Serotonin level was increased in both the salt tolerant varieties in response to NaCl induced stress. In both the salt tolerant varieties, increased production of the signaling molecule gentisic acid in response to NaCl treatment was noticed. Salt tolerant varieties also produced increased level of ferulic acid and vanillic acid. In the salt sensitive varieties, cinnamic acid derivatives, 4-hydroxycinnamic acid (in Sujala) and 4-hydroxybenzoic acid (in MTU 7029), were elevated in the leaves. So increased production of the 2 signaling molecules serotonin and gentisic acid may be considered as 2 important biomarker compounds produced in tolerant varieties contributing toward NaCl tolerance.

The Role of the Environment in the Evolution of Tolerance and Resistance to a Pathogen.

PubMed

Zeller, Michael; Koella, Jacob C

2017-09-01

Defense against parasites can be divided into resistance, which limits parasite burden, and tolerance, which reduces pathogenesis at a given parasite burden. Distinguishing between the two and understanding which defense is favored by evolution in different ecological settings are important, as they lead to fundamentally different evolutionary trajectories of host-parasite interactions. We let the mosquito Aedes aegypti evolve under different food levels and with either no parasite, a constant parasite, or a coevolving parasite (the microsporidian Vavraia culicis). We then tested tolerance and resistance of the evolved lines on a population level at the two food levels. Exposure to parasites during evolution increased resistance and tolerance, but there were no differences between the lines evolved with coevolving or constant parasites. Mosquitoes that had evolved with food restriction had higher resistance than those evolved with high food but similar tolerance. The mosquitoes that had restricted food when being tested had lower tolerance than those with normal food, but there was no difference in resistance. Our results emphasize the complexity and dependence on environmental conditions of the evolution and expression of resistance and tolerance and help to evaluate some of the predictions about the evolution of host defense against parasites.

40 CFR 180.498 - Sulfentrazone; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances... Parts per million Asparagus 0.15 Bean, lima, succulent 0.15 Brassica, head and stem, subgroup 5A 0.20... pesticide under section 18 emergency exemptions granted by EPA. Compliance with the tolerance levels...

Analyses of flooding tolerance of soybean varieties at emergence and varietal differences in their proteomes.

PubMed

Nanjo, Yohei; Jang, Hee-Young; Kim, Hong-Sig; Hiraga, Susumu; Woo, Sun-Hee; Komatsu, Setsuko

2014-10-01

Flooding of fields due to heavy and/or continuous rainfall influences soybean production. To identify soybean varieties with flooding tolerance at the seedling emergence stage, 128 soybean varieties were evaluated using a flooding tolerance index, which is based on plant survival rates, the lack of apparent damage and lateral root development, and post-flooding radicle elongation rate. The soybean varieties were ranked according to their flooding tolerance index, and it was found that the tolerance levels of soybean varieties exhibit a continuum of differences between varieties. Subsequently, tolerant, moderately tolerant and sensitive varieties were selected and subjected to comparative proteomic analysis to clarify the tolerance mechanism. Proteomic analysis of the radicles, combined with correlation analysis, showed that the ratios of RNA binding/processing related proteins and flooding stress indicator proteins were significantly correlated with flooding tolerance index. The RNA binding/processing related proteins were positively correlated in untreated soybeans, whereas flooding stress indicator proteins were negatively correlated in flooded soybeans. These results suggest that flooding tolerance is regulated by mechanisms through multiple factors and is associated with abundance levels of the identified proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of air pollution tolerance index and anticipated performance index of plants and their application in development of green space along the urban areas.

PubMed

Kaur, Mandeep; Nagpal, Avinash Kaur

2017-08-01

Air pollution due to vehicular emissions has become one of the most serious problems in the whole world and has resulted in huge threat to both the environment and the health of living organisms (plants, humans, animals, microorganisms). Plants growing along the roadsides get affected at the maximum as they are the primary recipients to different air pollutants and show varied levels of tolerance and sensitivity. Taking this into account, the present work was based on assessment of seasonal variation in air pollution tolerance index (APTI) and anticipated performance index (API) of four roadside plants, namely, Alstonia scholaris, Nerium oleander, Tabernaemontana coronaria, and Thevetia peruviana belonging to family Apocynaceae. APTI was calculated by the determination of four important biochemical parameters, viz., pH, relative water content (RWC), total chlorophyll (TChl), and ascorbic acid (AsA) content of leaves. The leaf samples were collected from plants growing at seven different sites of Amritsar (Punjab), India, for pre-monsoon and post-monsoon seasons. Highest APTI (82.14) was reported in N. oleander during the pre-monsoon season while the lowest was recorded in T. coronaria (18.59) in the post-monsoon season. On the basis of API score, A. scholaris was anticipated to be an excellent performer during the pre-monsoon and post-monsoon seasons followed by N. oleander, T. coronaria, and T. peruviana. Linear regression analysis and Pearson's correlation coefficient depicted significant positive correlation between APTI and ascorbic acid content during the pre-monsoon and post-monsoon seasons.

Pregabalin role in inhibition of morphine analgesic tolerance and physical dependency in rats.

PubMed

Hasanein, Parisa; Shakeri, Saeed

2014-11-05

Pregabalin is recently proposed as analgesic or adjuvant in pain management. While previous preclinical investigations have evaluated pregabalin-opioid interactions, the effect of pregabalin on opioid tolerance and dependency has not yet been studied. Here we evaluated the effects of different doses of pregabalin (50, 100 and 200mg/kg, s.c.) on morphine-induced tolerance and dependency in rats. Adult male Wistar rats were rendered tolerant to analgesic effect of morphine by injection of morphine (10mg/kg, s.c.) twice daily for 7 days. To develop morphine dependence, rats were given escalating doses of morphine. To determine the effect of pregabalin on the development of morphine tolerance and dependence, different doses of pregabalin were administrated before morphine. The tail-flick and naloxone precipitation withdrawal tests were used to evaluate the degree of tolerance and dependence, respectively. Chronic morphine-injected rats showed significant decrements in the percentage maximum possible effect (%MPE) of morphine on the days 5 and 7 (32.5%±3.5, 21.5%±4, respectively) compared to the first day (100%) which showed morphine tolerance. Pregabalin 200mg/kg completely prevented the development of morphine tolerance. In addition, concomitant treatment of morphine with pregabalin attenuated almost all of the naloxone-induced withdrawal signs which include weight loss, jumping, penis licking, teeth chattering, wet dog shakes, rearing, standing, sniffing, face grooming and paw tremor. These data show that pregabaline has a potential anti-tolerant/anti-dependence property against chronic usage of morphine. Therefore, pregabalin appears to be a promising candidate for the treatment of opioid addiction after confirming by future clinical studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of the Winter Wheat Cheyenne 5A Substituted Chromosome on Dynamics of Abscisic Acid and Cytokinins in Freezing-Sensitive Chinese Spring Genetic Background

PubMed Central

Kalapos, Balázs; Novák, Aliz; Dobrev, Petre; Vítámvás, Pavel; Marincs, Ferenc; Galiba, Gábor; Vanková, Radomira

2017-01-01

The effect of short- and long-term cold treatment on the abscisic acid (ABA) and cytokinin (CK) metabolism, and their main biosynthesis- and signaling-related genes were investigated in freezing-sensitive and freezing-tolerant wheat genotypes. Varieties Cheyenne and Chinese Spring substituted with the 5A Cheyenne chromosome, which represented freezing-tolerant genotypes, were compared with the freezing-sensitive Chinese Spring. Hormone levels and gene expression data indicated that the short- and long-term cold treatments are associated with specific regulation of the accumulation of cold-protective proteins and phytohormone levels, as well as the expression profiles of the hormone-related genes. The significant differences were observed between the genotypes, and between their leaf and crown tissues, too. The level of dehydrins, including WCS120 protein, and expression of WCS120 gene were considerably higher in the freezing-tolerant genotypes after 21 days of cold treatment. Expression of Cor14b and CBF14, cold-responsive regulator genes, was increased by cold treatment in all genotypes, to higher extent in freezing-tolerant genotypes. Cluster analysis revealed that the tolerant genotypes had a similar response to cold treatment, regarding expression of the ABA and CK metabolic genes, as well as hormone levels in leaves. As far as hormone levels in crowns are concerned, however, the strongly freezing-tolerant Cheyenne variety clustered separately from the Chinese Spring and the substitution line, which were more similar to each other after both 1 and 21 days of cold treatment than to Cheyenne. Based on these results we concluded that the 5A chromosome of wheat might have both a direct and an indirect impact on the phytohormone-dependent cold-induced freezing tolerance. Based on the gene expression data, novel genetic markers could be developed, which may be used to determine the freezing tolerance level in a wide range of wheat varieties. PMID:29238355

Adaptation to metals in widespread and endemic plants.

PubMed Central

Shaw, A J

1994-01-01

Bryophytes, including the mosses, liverworts, and hornworts, occur in a variety of habitats with high concentrations of metals and have other characteristics that are advantageous for studies of metal tolerance. Mosses may evolve genetically specialized, metal-tolerant races less frequently than flowering plants. Some species of mosses appear to have inherently high levels of metal tolerance even in individuals that have not been subjected to natural selection in contaminated environments. Scopelophila cataractae, one of the so-called copper mosses, not only tolerates extremely high concentrations of metals in its substrates, but requires these substrates for optimum growth. This species should be included in mechanistic studies of tolerance at the cellular and molecular levels. PMID:7713025

RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org; Won, Minhee; Wen, Patrick Y.

Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established dailymore » dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.« less

A phase I, pharmacokinetic, and pharmacodynamic study of two schedules of vorinostat in combination with 5-fluorouracil and leucovorin in patients with refractory solid tumors.

PubMed

Fakih, Marwan G; Fetterly, Gerald; Egorin, Merrill J; Muindi, Josephia R; Espinoza-Delgado, Igor; Zwiebel, James A; Litwin, Alan; Holleran, Julianne L; Wang, Kangsheng; Diasio, Robert B

2010-07-15

We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat x 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Vorinostat doses were escalated in a standard 3 x 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m(2) i.v. over 2 hours followed by FU 400 mg/m(2) i.v. bolus and 2,400 mg/m(2) over 46 hours (sLV5FU2). Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU. The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily x 3 or 600 mg orally twice daily x 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. Copyrighth 2010 AACR.

A Phase I, Pharmacokinetic, and Pharmacodynamic Study of Two Schedules of Vorinostat in Combination with 5-Fluorouracil and Leucovorin in Patients with Refractory Solid Tumors

PubMed Central

Fakih, Marwan G.; Fetterly, Gerald; Egorin, Merrill J.; Muindi, Josephia R.; Espinoza-Delgado, Igor; Zwiebel, James A.; Litwin, Alan; Holleran, Julianne L.; Wang, Kangsheng; Diasio, Robert B.

2010-01-01

Purpose We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat × 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Experimental Design Vorinostat doses were escalated in a standard 3 × 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m2 i.v. over 2 hours followed by FU 400 mg/m2 i.v. bolus and 2,400 mg/m2 over 46 hours (sLV5FU2). Results Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU. Conclusions The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily × 3 or 600 mg orally twice daily × 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. PMID:20463088

A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas.

PubMed

Hong, David S; Kurzrock, Razelle; Supko, Jeffrey G; He, Xiaoying; Naing, Aung; Wheler, Jennifer; Lawrence, Donald; Eder, Joseph Paul; Meyer, Colin J; Ferguson, Deborah A; Mier, James; Konopleva, Marina; Konoplev, Sergej; Andreeff, Michael; Kufe, Donald; Lazarus, Hillard; Shapiro, Geoffrey I; Dezube, Bruce J

2012-06-15

Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity. Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2-related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies. The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-κB and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased. Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. ©2012 AACR.

A Phase I First-in-Human Trial of Bardoxolone Methyl in Patients with Advanced Solid Tumors and Lymphomas

PubMed Central

Hong, David S.; Kurzrock, Razelle; Supko, Jeffrey G.; He, Xiaoying; Naing, Aung; Wheler, Jennifer; Lawrence, Donald; Eder, Joseph Paul; Meyer, Colin J.; Ferguson, Deborah A.; Mier, James; Konopleva, Marina; Konoplev, Sergej; Andreeff, Michael; Kufe, Donald; Lazarus, Hillard; Shapiro, Geoffrey I.; Dezube, Bruce J.

2015-01-01

Purpose Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant inflammation modulator, potently induces Nrf2 and inhibits NF-κB and Janus-activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and appropriate dose for phase II studies; characterize pharmacokinetic and pharmacodynamic parameters; and assess antitumor activity. Experimental Design Bardoxolone methyl was administered orally once daily for 21 days of a 28-day cycle. An accelerated titration design was employed until a grade 2–related adverse event occurred. A standard 3 + 3 dose escalation was then employed until the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the drug were characterized. Assessment of Nrf2 activation was examined in peripheral blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1) mRNA levels. Immunohistochemical assessment of markers of inflammation, cell cycle, and apoptosis was carried out on tumor biopsies. Results The DLTs were grade 3 reversible liver transaminase elevations. The MTD was established as 900 mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a partial response was observed in an anaplastic thyroid carcinoma patient. NQO1 mRNA levels increased in PBMCs, and NF-κB and cyclin D1 levels decreased in tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased. Conclusions Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic kidney disease. Objective tumor responses and pharmacodynamic effects were observed, supporting continued development of other synthetic triterpenoids in cancer. PMID:22634319

Evaluation of hypoglycemic and anti-hyperglycemic potential of Tridax procumbens (Linn.).

PubMed

Pareek, Hemant; Sharma, Sameer; Khajja, Balvant S; Jain, Kusum; Jain, G C

2009-11-29

Diabetes is a metabolic disorder affecting carbohydrate, fat and protein metabolism. Tridax procumbens Linn. (Family-Asteraceae; common name-Dhaman grass) is common herb found in India. Traditionally, the tribal inhabitants of Udaipur district in Rajasthan (India) uses the leaf powder (along with other herb) orally to treat diabetes. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's application in traditional medicine system. Extraction of whole plant of T. procumbens using 50%methanol. The extract was tested for acute and sub-chronic anti-hyperglycemic activity in alloxan induced diabetic rats and for acute toxicity test among normal rats. Observations on body weight as well as on the oral glucose tolerance levels were also recorded. Oral administration of acute and sub chronic doses (250 and 500 mg/kg b.wt.) of T. procumbens extract showed a significant (p < 0.05) reduction in fasting blood glucose levels in diabetic rats, however the decline in blood sugar levels in normal rats was not observed. In acute study the maximum percent blood glucose reduction (68.26% at 250 mg/kg and 71.03% at 500 mg/kg body weight) in diabetic rats was observed at 6 h. The anti-hyperglycemic effects were not dependent of dose and the OGTT and Body weight supported the antihyperglycemic action of the drug. The results of anti-diabetic effect of T. procumbens were compared with the reference standard drug Glibenclamide (10 mg/kg b.wt.). These test results support traditional medicinal use of, T. procumbens for the treatment of diabetes mellitus with corrections in body weight and oral glucose tolerance and no visible signs or symptoms of toxicity in normal rats indicating a high margin of safety. These results warrant follow-up through bioassay-directed isolation of the active principles.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

PubMed

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions undermore » the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.« less

Oxidative stress and antioxidant responses to increasing concentrations of trivalent chromium in the Andean crop species Chenopodium quinoa Willd.

PubMed

Scoccianti, Valeria; Bucchini, Anahi E; Iacobucci, Marta; Ruiz, Karina B; Biondi, Stefania

2016-11-01

Quinoa (Chenopodium quinoa Willd), an ancient Andean seed crop, exhibits exceptional nutritional properties and resistance to abiotic stress. The species' tolerance to heavy metals has, however, not yet been investigated nor its ability to take up and translocate chromium (Cr). This study aimed to investigate the metabolic adjustments occurring upon exposure of quinoa to several concentrations (0.01-5mM) of CrCl3. Young hydroponically grown plants were used to evaluate Cr uptake, growth, oxidative stress, and other biochemical parameters three and/or seven days after treatment. Leaves accumulated the lowest amounts of Cr, while roots and stems accumulated the most at low and at high metal concentrations, respectively. Fresh weight and photosynthetic pigments were reduced only by the higher Cr(III) doses. Substantially increased lipid peroxidation, hydrogen peroxide, and proline levels were observed only with 5mM Cr(III). Except for a significant decrease at day 7 with 5mM Cr(III), total polyphenols and flavonoids maintained control levels in Cr(III)-treated plants, whereas antioxidant activity increased in a dose-dependent manner. Maximum polyamine accumulation was observed in 1mM CrCl3-treated plants. Even though α- and γ-tocopherols also showed enhanced levels only with the 1mM concentration, tyrosine aminotransferase (TAT, EC 2.6.1.5) activity increased under Cr(III) treatment in a dose- and time-dependent manner. Taken together, results suggest that polyamines, tocopherols, and TAT activity could contribute to tolerance to 1mM Cr(III), but not to the highest concentration that, instead, generated oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy - results of an exploratory phase I study.

PubMed

Pappot, H; von der Maase, H; Ullén, A; Agerbæk, M

2017-10-28

Vinflunine is to date the only registered agent for second-line treatment of metastatic urothelial cell carcinoma (UCC) in Europe. However, the effect is modest. Pemetrexed has demonstrated some single-agent activity in this disease entity. In order to improve treatment possibilities for UCC patients, a phase I trial (VINTREX) was undertaken to assess the safety of vinflunine and pemetrexed in metastatic UCC patients. A dose escalation design was planned to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a vinflunine/pemetrexed combination. Pemetrexed was added to vinflunine dosed at 280 mg/m2 on day 1 of a 21-day cycle. Three levels of pemetrexed were planned starting at 400 mg/m2. Four patients were enrolled with a mean age of 66 years and with a mean number of prior GC-cycles of 6,8. Two DLT's were observed at the lowest dose-level in cohort 1. One patient experienced grade 4 thrombocytopenia and a second demonstrated hepatobiliary toxicity grade 3 with an increase in alanine aminotransaminase. Most common grade 3 and 4 adverse events were anemia, thrombocytopenia and neutropenia. Three out of four patients received 3 cycles of pemetrexed and vinflunine, all had progressive disease. Based on these observations and due to protocol design, the study was interrupted at dose level 1 for safety reasons. The combined therapy of vinflunine (Javlor®, Pierre Fabre Pharma) and pemetrexed (Alimta®, Eli Lilly) is poorly tolerated in metastatic UCC patients. The combination cannot be recommended for further investigations in metastatic UCC.

Compensation and resistance to herbivory in seagrasses: induced responses to simulated consumption by fish.

PubMed

Vergés, Adriana; Pérez, Marta; Alcoverro, Teresa; Romero, Javier

2008-04-01

Herbivory can induce changes in plant traits that may involve both tolerance mechanisms that compensate for biomass loss and resistance traits that reduce herbivore preference. Seagrasses are marine vascular plants that possess many attributes that may favour tolerance and compensatory growth, and they are also defended with mechanisms of resistance such as toughness and secondary metabolites. We quantified phenotypic changes induced by herbivore damage on the temperate seagrass Posidonia oceanica in order to identify specific compensatory and resistance mechanisms in this plant, and to assess any potential trade-offs between these two strategies of defence. We simulated three natural levels of fish herbivory by repeatedly clipping seagrass leaves during the summer period of maximum herbivory. Compensatory responses were determined by measuring shoot-specific growth, photosynthetic rate, and the concentration of nitrogen and carbon resources in leaves and rhizomes. Induced resistance was determined by measuring the concentration of phenolic secondary metabolites and by assessing the long-term effects of continued clipping on herbivore feeding preferences using bioassays. Plants showed a significant ability to compensate for low and moderate losses of leaf biomass by increasing aboveground growth of damaged shoots, but this was not supported by an increase in photosynthetic capacity. Low levels of herbivory induced compensatory growth without any measurable effects on stored resources. In contrast, nitrogen reserves in the rhizomes played a crucial role in the plant's ability to compensate and survive herbivore damage under moderate and high levels of herbivory, respectively. We found no evidence of inducibility of long-term resistance traits in response to herbivory. The concentration of phenolics decreased with increasing compensatory growth despite all treatments having similar carbon leaf content, suggesting reallocation of these compounds towards primary functions such as cell-wall construction.

On the Compliance of Simbol-X Mirror Roughness with its Effective Area Requirements

NASA Astrophysics Data System (ADS)

Spiga, D.; Basso, S.; Cotroneo, V.; Pareschi, G.; Tagliaferri, G.

2009-05-01

Surface microroughness of X-ray mirrors is a key issue for the angular resolution of Simbol-X to comply with the required one (<20 arcsec at 30 keV). The maximum tolerable microroughness for Simbol-X mirrors, in order to satisfy the required imaging capability, has already been derived in terms of its PSD (Power Spectral Density). However, also the Effective Area of the telescope is affected by the mirror roughness. In this work we will show how the expected effective area of the Simbol-X mirror module can be computed from the roughness PSD tolerance, checking its compliance with the requirements.

Successful pod infections by Moniliophthora roreri result in differential Theobroma cacao gene expression depending on the clone's level of tolerance.

PubMed

Ali, Shahin S; Melnick, Rachel L; Crozier, Jayne; Phillips-Mora, Wilberth; Strem, Mary D; Shao, Jonathan; Zhang, Dapeng; Sicher, Richard; Meinhardt, Lyndel; Bailey, Bryan A

2014-09-01

An understanding of the tolerance mechanisms of Theobroma cacao used against Moniliophthora roreri, the causal agent of frosty pod rot, is important for the generation of stable disease-tolerant clones. A comparative view was obtained of transcript populations of infected pods from two susceptible and two tolerant clones using RNA sequence (RNA-Seq) analysis. A total of 3009 transcripts showed differential expression among clones. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of differentially expressed genes indicated shifts in 152 different metabolic pathways between the tolerant and susceptible clones. Real-time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR) analyses of 36 genes verified the differential expression. Regression analysis validated a uniform progression in gene expression in association with infection levels and fungal loads in the susceptible clones. Expression patterns observed in the susceptible clones diverged in tolerant clones, with many genes showing higher expression at a low level of infection and fungal load. Principal coordinate analyses of real-time qRT-PCR data separated the gene expression patterns between susceptible and tolerant clones for pods showing malformation. Although some genes were constitutively differentially expressed between clones, most results suggested that defence responses were induced at low fungal load in the tolerant clones. Several elicitor-responsive genes were highly expressed in tolerant clones, suggesting rapid recognition of the pathogen and induction of defence genes. Expression patterns suggested that the jasmonic acid-ethylene- and/or salicylic acid-mediated defence pathways were activated in the tolerant clones, being enhanced by reduced brassinosteroid (BR) biosynthesis and catabolic inactivation of both BR and abscisic acids. Finally, several genes associated with hypersensitive response-like cell death were also induced in tolerant clones. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Zinc, nickel and cadmium in carambolas marketed in Guangzhou and Hong Kong, China: implication for human health.

PubMed

Li, J T; Liao, B; Lan, C Y; Qiu, J W; Shu, W S

2007-12-15

Carambola (Averrhoa carambola L.) is a popular juicy fruit throughout the tropical and subtropical world. This study was designed to quantify the levels of zinc (Zn), nickel (Ni) and cadmium (Cd) in carambolas marketed in southern China, and further to evaluate the potential health risk of human consumption of carambola. Zinc concentrations, ranging from 1.471 to 2.875 mg/kg (on fresh weight basis), were below the maximum permissible concentration for Zn in fruit of China (5 mg/kg). However, Ni concentrations (0.134-0.676 mg/kg) were considerably higher than the related recommendation values. Furthermore, Cd concentrations in 51% of the carambolas purchased from Guangzhou exceeded the maximum permissible concentration for Cd in fruit of China (0.03 mg/kg). Our results implicated that the consumption of 0.385 kg carambola contaminated by Cd per day would cause the tolerable daily intake (TDI) of Cd by the consumer to be exceeded. In addition, the remarkably high Ni concentrations in carambolas should also be of concern. The status of heavy metal contamination of carambola products marketed in the other regions and their implications for human health should be identified urgently by in-depth studies.

n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

PubMed

Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

2015-09-01

This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pyrrolizidine alkaloids in food: a spectrum of potential health consequences.

PubMed

Edgar, J A; Colegate, S M; Boppré, M; Molyneux, R J

2011-03-01

Contamination of grain with 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs) and their N-oxides is responsible for large incidents of acute and subacute food poisoning, with high morbidity and mortality, in Africa and in central and south Asia. Herbal medicines and teas containing dehydroPAs have also caused fatalities in both developed and developing countries. There is now increasing recognition that some staple and widely consumed foods are sometimes contaminated by dehydroPAs and their N-oxides at levels that, while insufficient to cause acute poisoning, greatly exceed maximum tolerable daily intakes and/or maximum levels determined by a number of independent risk assessment authorities. This suggests that there may have been cases of disease in the past not recognised as resulting from dietary exposure to dehydroPAs. A review of the literature shows that there are a number of reports of liver disease where either exposure to dehydroPAs was suspected but no source was identified or a dehydroPA-aetiology was not considered but the symptoms and pathology suggests their involvement. DehydroPAs also cause progressive, chronic diseases such as cancer and pulmonary arterial hypertension but proof of their involvement in human cases of these chronic diseases, including sources of exposure to dehydroPAs, has generally been lacking. Growing recognition of hazardous levels of dehydroPAs in a range of common foods suggests that physicians and clinicians need to be alert to the possibility that these contaminants may, in some cases, be a possible cause of chronic diseases such as cirrhosis, pulmonary hypertension and cancer in humans.

Toxicokinetics of fumonisin B1 in turkey poults and tissue persistence after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

PubMed

Tardieu, Didier; Bailly, Jean-Denis; Skiba, Fabien; Grosjean, François; Guerre, Philippe

2008-09-01

The kinetic of fumonisin B1 (FB1) after a single IV and oral dose, and FB1 persistence in tissue were investigated in turkey poults by HPLC after purification of samples on columns. After IV administration (single-dose: 10mg FB1/kg bw), serum concentration-time curves were best described by a three-compartment open model. Elimination half-life and mean residence time of FB1 were 85 and 52min, respectively. After oral administration (single-dose: 100mg FB1/kg bw) bioavailability was 3.2%; elimination half-life and mean residence time were 214 and 408min, respectively. Clearance of FB1 was 7.6 and 7.5ml/min/kg for IV and oral administration, respectively. Twenty-four hours after the administration of FB1 by the intravenous route, liver and kidney contained the highest levels of FB1 in tissues, level in muscle was low or below the limit of detection (LD, 13microg/kg). The persistence of FB1 in tissue was also studied after administration for 9 weeks of a feed that contained 5, 10 and 20mg FB1+FB2/kg diet. Eight hours after the last intake of 20mg FB1+FB2/kg feed (maximum recommended concentration of fumonisins established by the EU for avian feed), hepatic and renal FB1 concentrations were 119 and 22microg/kg, level in muscles was below the LD.

Difference in oxidative stress tolerance between rice cultivars estimated with chlorophyll fluorescence analysis.

PubMed

Kasajima, Ichiro

2017-04-26

Oxidative stress is considered to be involved in growth retardation of plants when they are exposed to a variety of biotic and abiotic stresses. Despite its potential importance in improving crop production, comparative studies on oxidative stress tolerance between rice (Oryza sativa L.) cultivars are limited. This work describes the difference in term of oxidative stress tolerance between 72 rice cultivars. 72 rice cultivars grown under naturally lit greenhouse were used in this study. Excised leaf discs were subjected to a low concentration of methyl viologen (paraquat), a chemical reagent known to generate reactive oxygen species in chloroplast. Chlorophyll fluorescence analysis using a two-dimensional fluorescence meter, ion leakage analysis as well as the measurement of chlorophyll contents were used to evaluate the oxidative stress tolerance of leaf discs. Furthermore, fluorescence intensities were finely analyzed based on new fluorescence theories that we have optimized. Treatment of leaf discs with methyl viologen caused differential decrease of maximum quantum yield of photosystem II (Fv/Fm) between cultivars. Decrease of Fv/Fm was also closely correlated with increase of ion leakage and decrease of chlorophyll a/b ratio. Fv/Fm was factorized into photochemical and non-photochemical parameters to classify rice cultivars into sensitive and tolerant ones. Among the 72 compared rice cultivars, the traditional cultivar Co13 was identified as the most tolerant to oxidative stress. Koshihikari, a dominant modern Japonica cultivar in Japan as well as IR58, one of the modern Indica breeding lines exhibited a strong tolerance to oxidative stress. Close correlation between Fv/Fm and chlorophyll a/b ratio provides a simple method to estimate oxidative stress tolerance, without measurement of chlorophyll fluorescence with special equipment. The fact that modern cultivars, especially major cultivars possessed tolerance to oxidative stress suggests that oxidative stress tolerance is one of the agricultural traits prerequisite for improvement of modern rice cultivars. Data presented in this study would enable breeding of rice cultivars having strong tolerance to oxidative stress.

Improved training tolerance by supplementation with α-Keto acids in untrained young adults: a randomized, double blind, placebo-controlled trial

PubMed Central

2012-01-01

Background Exercise causes a variety of physiological and metabolic changes that can in turn reduce exercise tolerance. One of the potential mechanisms responsible for fatigue is “exercise-induced hyperammonemia”. Previous studies have shown that supplementation with amino acids can increase training tolerance. The α-keto acids are biochemical analogs of amino acids and can be converted to amino acids through transamination, thus reducing the cellular ammonia level. This double blind, placebo-controlled study was designed to investigate the effects of α-keto acid supplementation (KAS) on training tolerance, training effect, and stress-recovery state. Methods Thirty-three untrained young male adults underwent four weeks of training (5 sessions/week; 30 minutes running at the individual anaerobic threshold followed by 3 x 3 minute sprints/each session). Throughout the 4 weeks of training and one week of recovery, subjects took α-ketoglutarate (AKG group, 0.2 g/kg/d, n = 9), branched-chain keto acids (BCKA group, 0.2 g/kg/d, n = 12) or isocaloric placebo (control group, n = 12) daily. Results The 4th week training volume, maximum power output and muscle torque were higher in the AKG group (175 ± 42 min, 412 ± 49 Watts and 293 ± 58 Newton meters, respectively, P<0.05) and the BCKA group (158 ± 35, 390 ± 29 and 273 ± 47, P<0.05) than in the control group (92 ± 70, 381 ± 67 and 233 ± 43). The general stress and emotional exhaustion as assessed by the rest-stress-questionnaire-sport after the 3rd week of training increased significantly in the control group (P<0.05), but not in the KAS groups. Conclusions Under KAS, subjects could bear a higher training volume and reach a higher power output and peak muscle torque, accompanied by a better stress-recovery-state. Thus, KAS improves exercise tolerance and training effects along with a better stress-recovery state. Whether the improved training tolerance by KAS is associated with effects on ammonia homeostasis requires further observation. PMID:22857787

Management of Hypercholesterolemia, Appropriateness of Therapeutic Approaches and New Drugs in Patients with High Cardiovascular Risk.

PubMed

Agabiti Rosei, Enrico; Salvetti, Massimo

2016-09-01

Control of lipid levels is one of the most effective strategies for cardiovascular (CV) event prevention. In fact, many clinical trials have clearly demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, primarily with statins, reduces major CV events and mortality. The evidence from these trials has been useful in designing the cholesterol treatment guidelines, which are mainly aimed at preventing and managing cardiovascular disease (CVD). However, available data indicate that a large proportion of patients fail to achieve lipid goals, and this is particularly frequent in patients at high or very high CV risk. Furthermore, owing to side effects, a significant percentage of patients cannot tolerate statin treatment. Hence, researchers have focused their attention on novel LDL-C-lowering agents that act via mechanisms distinct from that of statins. Among the new compounds under investigation, the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) seem particularly promising, having recently been shown to be well tolerated and highly effective at lowering LDL-C, with a possible effect on the occurrence of CV events. Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non-familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated. Evolocumab is approved by the FDA as an adjunct to diet and maximally tolerated statins for adults with hetero- and homozygous FH and those with atherosclerotic CV disease who require additional lowering of LDL-C, and by the EMA in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet, in combination with a statin or a statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; alone or in combination with other lipid lowering therapies in patients who are statin-intolerant, or those for whom a statin is contraindicated. Evolocumab is also indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.

Association of metal tolerance with multiple antibiotic resistance of bacteria isolated from drinking water.

PubMed

Calomiris, J J; Armstrong, J L; Seidler, R J

1984-06-01

Bacterial isolates from the drinking water system of an Oregon coastal community were examined to assess the association of metal tolerance with multiple antibiotic resistance. Positive correlations between tolerance to high levels of Cu2+, Pb2+, and Zn2+ and multiple antibiotic resistance were noted among bacteria from distribution waters but not among bacteria from raw waters. Tolerances to higher levels of Al3+ and Sn2+ were demonstrated more often by raw water isolates which were not typically multiple antibiotic resistant. A similar incidence of tolerance to Cd2+ was demonstrated by isolates of both water types and was not associated with multiple antibiotic resistance. These results suggest that simultaneous selection phenomena occurred in distribution water for bacteria which exhibited unique patterns of tolerance to Cu2+, Pb2+, and Zn2+ and antibiotic resistance.

Guiding principle for crystalline Si photovoltaic modules with high tolerance to acetic acid

NASA Astrophysics Data System (ADS)

Masuda, Atsushi; Hara, Yukiko

2018-04-01

A guiding principle for highly reliable crystalline Si photovoltaic modules, especially those with high tolerance to acetic acid generated by hydrolysis reaction between water vapor and an ethylene-vinyl acetate (EVA) encapsulant, is proposed. Degradation behavior evaluated by the damp heat test strongly depends on Ag finger electrodes and also EVA encapsulants. The acetic acid concentration in EVA on the glass side directly determines the degradation behavior. The most important factor for high tolerance is the type of Ag finger electrode materials when using an EVA encapsulant. Photovoltaic modules using newly developed crystalline Si cells with improved Ag finger electrode materials keep their maximum power of 80% of the initial value even after the damp heat test at 85 °C and 85% relative humidity for 10000 h. The pattern of dark regions in electroluminescence images is also discussed on the basis of the dynamics of acetic acid in the modules.

Fault-tolerant clock synchronization validation methodology. [in computer systems

NASA Technical Reports Server (NTRS)

Butler, Ricky W.; Palumbo, Daniel L.; Johnson, Sally C.

1987-01-01

A validation method for the synchronization subsystem of a fault-tolerant computer system is presented. The high reliability requirement of flight-crucial systems precludes the use of most traditional validation methods. The method presented utilizes formal design proof to uncover design and coding errors and experimentation to validate the assumptions of the design proof. The experimental method is described and illustrated by validating the clock synchronization system of the Software Implemented Fault Tolerance computer. The design proof of the algorithm includes a theorem that defines the maximum skew between any two nonfaulty clocks in the system in terms of specific system parameters. Most of these parameters are deterministic. One crucial parameter is the upper bound on the clock read error, which is stochastic. The probability that this upper bound is exceeded is calculated from data obtained by the measurement of system parameters. This probability is then included in a detailed reliability analysis of the system.

Coordinated Changes in Antioxidative Enzymes Protect the Photosynthetic Machinery from Salinity Induced Oxidative Damage and Confer Salt Tolerance in an Extreme Halophyte Salvadora persica L.

PubMed Central

Rangani, Jaykumar; Parida, Asish K.; Panda, Ashok; Kumari, Asha

2016-01-01

Salinity-induced modulations in growth, photosynthetic pigments, relative water content (RWC), lipid peroxidation, photosynthesis, photosystem II efficiency, and changes in activity of various antioxidative enzymes were studied in the halophyte Salvadora persica treated with various levels of salinity (0, 250, 500, 750, and 1000 mM NaCl) to obtain an insight into the salt tolerance ability of this halophyte. Both fresh and dry biomass as well as leaf area (LA) declined at all levels of salinity whereas salinity caused an increase in leaf succulence. A gradual increase was observed in the Na+ content of leaf with increasing salt concentration up to 750 mM NaCl, but at higher salt concentration (1000 mM NaCl), the Na+ content surprisingly dropped down to the level of 250 mM NaCl. The chlorophyll and carotenoid contents of the leaf remained unaffected by salinity. The photosynthetic rate (PN), stomatal conductance (gs), the transpiration rate (E), quantum yield of PSII (ΦPSII), photochemical quenching (qP), and electron transport rate remained unchanged at low salinity (250 to 500 mM NaCl) whereas, significant reduction in these parameters were observed at high salinity (750 to 1000 mM NaCl). The RWC% and water use efficiency (WUE) of leaf remained unaffected by salinity. The salinity had no effect on maximum quantum efficiency of PS II (Fv/Fm) which indicates that PS II is not perturbed by salinity-induced oxidative damage. Analysis of the isoforms of antioxidative enzymes revealed that the leaves of S. persica have two isoforms each of Mn-SOD and Fe-SOD and one isoform of Cu-Zn SOD, three isoforms of POX, two isoforms of APX and one isoform of CAT. There was differential responses in activity and expression of different isoforms of various antioxidative enzymes. The malondialdehyde (MDA) content (a product of lipid peroxidation) of leaf remained unchanged in S. persica treated with various levels of salinity. Our results suggest that the absence of pigment degradation, the reduction of water loss, and the maintenance of WUE and protection of PSII from salinity-induced oxidative damage by the coordinated changes in antioxidative enzymes are important factors responsible for salt tolerance of S. persica. PMID:26904037

Stem carbohydrate dynamics and expression of genes involved in fructan accumulation and remobilization during grain growth in wheat (Triticum aestivum L.) genotypes with contrasting tolerance to water stress.

PubMed

Yáñez, Alejandra; Tapia, Gerardo; Guerra, Fernando; Del Pozo, Alejandro

2017-01-01

The genetic and physiological mechanisms underlying the relationship between water-soluble carbohydrates (WSC) and water stress tolerance are scarcely known. This study aimed to evaluate the main WSC in stems, and the expression of genes involved in fructan metabolism in wheat genotypes growing in a glasshouse with water stress (WS; 50% field capacity from heading) and full irrigation (FI; 100% field capacity). Eight wheat genotypes (five tolerant and three susceptible to water stress) were evaluated initially (experiment 1) and the two most contrasting genotypes in terms of WSC accumulation were evaluated in a subsequent experiment (experiment 2). Maximum accumulation of WSC occurred 10-20 days after anthesis. Under WS, the stress-tolerant genotype exhibited higher concentrations of WSC, glucose, fructose and fructan in the stems, compared to FI. In addition, the stress-tolerant genotype exhibited higher up-regulation of the fructan 1-fructosyltransferase B (1-FFTB) and fructan 1-exohydrolase w2 (1-FEHw2) genes, whereas the susceptible cultivar presented an up-regulation of the fructan 6-fructosyltransferase (6-SFT) and fructan 1-exohydrolase w3 (1-FEHw3) genes. Our results indicated clear differences in the pattern of WSC accumulation and the expression of genes regulating fructan metabolism between the tolerant and susceptible genotypes under WS.

Stem carbohydrate dynamics and expression of genes involved in fructan accumulation and remobilization during grain growth in wheat (Triticum aestivum L.) genotypes with contrasting tolerance to water stress

PubMed Central

Yáñez, Alejandra; Tapia, Gerardo; Guerra, Fernando

2017-01-01

The genetic and physiological mechanisms underlying the relationship between water-soluble carbohydrates (WSC) and water stress tolerance are scarcely known. This study aimed to evaluate the main WSC in stems, and the expression of genes involved in fructan metabolism in wheat genotypes growing in a glasshouse with water stress (WS; 50% field capacity from heading) and full irrigation (FI; 100% field capacity). Eight wheat genotypes (five tolerant and three susceptible to water stress) were evaluated initially (experiment 1) and the two most contrasting genotypes in terms of WSC accumulation were evaluated in a subsequent experiment (experiment 2). Maximum accumulation of WSC occurred 10–20 days after anthesis. Under WS, the stress-tolerant genotype exhibited higher concentrations of WSC, glucose, fructose and fructan in the stems, compared to FI. In addition, the stress-tolerant genotype exhibited higher up-regulation of the fructan 1-fructosyltransferase B (1-FFTB) and fructan 1-exohydrolase w2 (1-FEHw2) genes, whereas the susceptible cultivar presented an up-regulation of the fructan 6-fructosyltransferase (6-SFT) and fructan 1-exohydrolase w3 (1-FEHw3) genes. Our results indicated clear differences in the pattern of WSC accumulation and the expression of genes regulating fructan metabolism between the tolerant and susceptible genotypes under WS. PMID:28552955

Production, purification and characterization of halophilic organic solvent tolerant protease from marine crustacean shell wastes and its efficacy on deproteinization.

PubMed

Maruthiah, Thirumalai; Somanath, Beena; Jasmin, Jebamonydhas Vijila; Immanuel, Grasian; Palavesam, Arunachalam

2016-12-01

The quantum of marine fish wastes produced by fish processing industries has necessitated to search new methods for its disposal. Hence, this study is focused on production and purification of halophilic organic solvent tolerant protease (HOSP) from marine Alcaligenes faecalis APCMST-MKW6 using marine shell wastes as substrate. The candidate bacterium was isolated from the marine sediment of Manakudi coast and identified as A. faecalis APCMST-MKW6. The purified protease showed 16.39-fold purity, 70.34 U/mg specific activity with 21.67 % yield. The molecular weight of the purified alkaline protease was 49 kDa. This purified protease registered maximum activity at pH 9 and it was stable between pH 8-9 after 1.30 h of incubation. The optimum temperature registered was 60 °C and it was stable between 50 and 60 °C even after 1.30 h of incubation. This enzyme also showed maximum activity at 20 % NaCl concentration. Further, manganese chloride, magnesium chloride, calcium chloride and barium chloride influenced this enzyme activity remarkably and it was also found to be enhanced by many of the tested surfactants and solvents. The candidate bacterium effectively deproteinized the shrimp shell waste compared to the other tested crustaceans shell wastes and also attained maximum antioxidant activity.

Effect of salt-tolerant plant growth-promoting rhizobacteria on wheat plants and soil health in a saline environment.

PubMed

Upadhyay, S K; Singh, D P

2015-01-01

Salt-tolerant plant growth-promoting rhizobacteria (ST-PGPR) significantly influence the growth and yield of wheat crops in saline soil. Wheat growth improved in pots with inoculation of all nine ST-PGPR (ECe = 4.3 dS·m(-1) ; greenhouse experiment), while maximum growth and dry biomass was observed in isolate SU18 Arthrobacter sp.; simultaneously, all ST-PGPR improved soil health in treated pot soil over controls. In the field experiment, maximum wheat root dry weight and shoot biomass was observed after inoculation with SU44 B. aquimaris, and SU8 B. aquimaris, respectively, after 60 and 90 days. Isolate SU8 B. aquimaris, induced significantly higher proline and total soluble sugar accumulation in wheat, while isolate SU44 B. aquimaris, resulted in higher accumulation of reducing sugars after 60 days. Percentage nitrogen (N), potassium (K) and phosphorus (P) in leaves of wheat increased significantly after inoculation with ST-PGPR, as compared to un-inoculated plants. Isolate SU47 B. subtilis showed maximum reduction of sodium (Na) content in wheat leaves of about 23% at both 60 and 90 days after sowing, and produced the best yield of around 17.8% more than the control. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Tannic acid degradation by Klebsiella strains isolated from goat feces

PubMed Central

Tahmourespour, Arezoo; Tabatabaee, Nooroldin; Khalkhali, Hossein; Amini, Imane

2016-01-01

Background and Objectives: Tannins are toxic polyphenols that either bind and precipitate or condense proteins. The high tannin content of some plants is the preliminary limitation of using them as a ruminant feed. So, the aim of this study was the isolation and characterization of tannic acid degrading bacterial strains from goat feces before and after feeding on Pistachio-Soft Hulls as tannin rich diet (TRD). Materials and Methods: Bacterial strains capable of utilizing tannic acid as sole carbon and energy source were isolated and characterized from goat feces before and after feeding on TRD. Tannase activity, maximum tolerable concentration and biodegradation potential were assessed. Results: Four tannase positive isolates were identified as Klebsiella pneumoniae. Isolated strains showed the maximum tolerable concentration of 64g/L of tannin. The tannic acid degradation percentage at a concentration of 15.0 g/L reached a maximum of 68% after 24 h incubation, and more than 98% after 72 h incubation. The pH of the medium also decreased along with tannic acid utilization. Conclusions: It is obvious that TRD induced adaptive responses. Thus, while the bacteria were able to degrade and detoxify the tannic acids, they had to adapt in the presence of high concentrations of tannic acid. So, these isolates have an amazing potential for application in bioremediation, waste water treatment, also reduction of tannins antinutritional effects in animal feeds. PMID:27092220

40 CFR 141.55 - Maximum contaminant level goals for radionuclides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Maximum contaminant level goals for... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Maximum Contaminant Level Goals and Maximum Residual Disinfectant Level Goals § 141.55 Maximum contaminant level goals for radionuclides...