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Sample records for biphasic myopathic phenotype

  1. RNA interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1).

    PubMed

    Wallace, Lindsay M; Garwick-Coppens, Sara E; Tupler, Rossella; Harper, Scott Q

    2011-11-01

    Muscular dystrophies, and other diseases of muscle, arise from recessive and dominant gene mutations. Gene replacement strategies may be beneficial for the former, while gene silencing approaches may provide treatment for the latter. In the last two decades, muscle-directed gene therapies were primarily focused on treating recessive disorders. This disparity at least partly arose because feasible mechanisms to silence dominant disease genes lagged behind gene replacement strategies. With the discovery of RNA interference (RNAi) and its subsequent development as a promising new gene silencing tool, the landscape has changed. In this study, our objective was to demonstrate proof-of-principle for RNAi therapy of a dominant myopathy in vivo. We tested the potential of adeno-associated viral (AAV)-delivered therapeutic microRNAs, targeting the human Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1), to correct myopathic features in mice expressing toxic levels of human FRG1 (FRG1(-high) mice). We found that FRG1 gene silencing improved muscle mass, strength, and histopathological abnormalities associated with muscular dystrophy in FRG1(-high) mice, thereby demonstrating therapeutic promise for treatment of dominantly inherited myopathies using RNAi. This approach potentially applies to as many as 29 different gene mutations responsible for myopathies inherited as dominant disorders.

  2. Expanding the Phenotype Associated With the NEFL Mutation Neuromuscular Disease in a Family with Overlapping Myopathic and Neurogenic Findings

    PubMed Central

    Agrawal, Pankaj B.; Joshi, Mugdha; Marinakis, Nicholas S.; Schmitz-Abe, Klaus; Ciarlini, Pedro D. S. C.; Sargent, Jane C.; Markianos, Kyriacos; De Girolami, Umberto; Chad, David A.; Beggs, Alan H.

    2014-01-01

    Importance Newer sequencing technologies in combination with traditional gene mapping techniques, such as linkage analysis, can help identify the genetic basis of disease for patients with rare disorders of uncertain etiology. This approach may expand the phenotypic spectrum of disease associated with those genetic mutations. Objective To elucidate the molecular cause of a neuromuscular disease among a family in which 4 members, a mother and her 3 sons, were affected. Design, Setting, and Participants Two of 4 affected members manifested nemaline myopathy, a common subtype of congenital myopathy, while the other 2 had a nonspecific myopathy. Single-nucleotide polymorphism–based linkage analysis was performed on DNA samples from the 4 affected family members, and whole-genome sequencing was performed in the proband. Real-time quantitative reverse transcription–polymerase chain reaction, immunofluorescence, and Western blot analysis were performed on muscle biopsy specimens. Main outcomes and Measures Whole-genome sequencing and linkage analysis identified a variant in a gene that explains the phenotype. Results We identified a novel neurofilament light polypeptide (NEFL) nonsense mutation in all affected members. NEFL mutations have been previously linked to Charcot-Marie-Tooth disease in humans. This led us to reevaluate the diagnosis, and we recognized that several of the findings, especially those related to the muscle biopsy specimens and electromyography, were consistent with a neurogenic disease. Conclusions and Relevance NEFL mutations are known to cause Charcot-Marie-Tooth disease in humans and motor neuron disease in mice. We report the identification of an NEFL mutation in a family clinically manifesting congenital myopathy. We also describe potential overlap between myopathic and neurogenic findings in this family. These findings expand the phenotypic spectrum of diseases associated with NEFL mutations. This study is an example of the power of genomic

  3. Decitabine has a biphasic effect on natural killer cell viability, phenotype, and function under proliferative conditions.

    PubMed

    Kopp, Lisa M; Ray, Anish; Denman, Cecele J; Senyukov, Vladimir S; Somanchi, Srinivas S; Zhu, Shiguo; Lee, Dean A

    2013-07-01

    DNA hypermethylation resulting in aberrant epigenetic silencing plays an important role in the oncogenesis of many cancer types, including acute myelogenous leukemia (AML).(4) The modulation of NK cell receptors and their cognate ligands is a known mechanism of immune escape in AML, and some membrane proteins, such as killer immunoglobulin-like receptors (KIR), are known to be transcriptionally regulated by DNA methylation of their promoter regions. Thus, restoring proper expression of immunoreceptors or their ligands with immunosensitizing drugs is an attractive approach to improving cancer immunotherapy. The cytidine analog 5-aza-2'-deoxycytidine (decitabine, DAC) has both a hypomethylating effect at low doses when incorporated into DNA and a cytotoxic effect at higher doses as a result of interfering with translation when incorporated into RNA. Thus, decitabine has been used at higher doses for its direct anti-leukemic effect, and is being tested at low doses for its ability to correct the malignant gene expression phenotype. A known benefit of hypomethylating agents is their ability to sensitize AML blasts to lysis by NK cells. However, there is little information on the direct effect of hypomethylating agents on NK cell phenotype, proliferation, survival, or function. We recently described a method for inducing robust proliferation of NK cells, enabling us to study the hypomethylating effects of decitabine. To distinguish direct toxicity of the decitabine from its hypomethylating effect, and promote hypomethylation during proliferation, decitabine was added to human peripheral blood NK cells at concentrations from 0.02 to 5μM under either static or proliferation-inducing culture conditions. After 5 days, NK cells were assessed for viability, proliferation, cytotoxicity, expression of major activating and inhibitory receptors, and global DNA methylation. Increasing concentrations of decitabine not only causes increased expression of KIR and the activating

  4. Myopathic mtDNA Depletion Syndrome Due to Mutation in TK2 Gene.

    PubMed

    Martín-Hernández, Elena; García-Silva, María Teresa; Quijada-Fraile, Pilar; Rodríguez-García, María Elena; Rivera, Henry; Hernández-Laín, Aurelio; Coca-Robinot, David; Fernández-Toral, Joaquín; Arenas, Joaquín; Martín, Miguel A; Martínez-Azorín, Francisco

    2017-01-01

    Whole-exome sequencing was used to identify the disease gene(s) in a Spanish girl with failure to thrive, muscle weakness, mild facial weakness, elevated creatine kinase, deficiency of mitochondrial complex III and depletion of mtDNA. With whole-exome sequencing data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The analysis of whole exome uncovered a homozygous pathogenic mutation in thymidine kinase 2 gene ( TK2; NM_004614.4:c.323 C>T, p.T108M). TK2 mutations have been identified mainly in patients with the myopathic form of mtDNA depletion syndromes. This patient presents an atypical TK2-related myopathic form of mtDNA depletion syndromes, because despite having a very low content of mtDNA (<20%), she presents a slower and less severe evolution of the disease. In conclusion, our data confirm the role of TK2 gene in mtDNA depletion syndromes and expanded the phenotypic spectrum.

  5. Limb girdle muscular dystrophy type 2G with myopathic-neurogenic motor unit potentials and a novel muscle image pattern

    PubMed Central

    2014-01-01

    Background Limb girdle muscular dystrophy type 2G (LGMD2G) is a subtype of autosomal recessive muscular dystrophy caused by mutations in the telethonin gene. There are few LGMD2G patients worldwide reported, and this is the first description associated with early tibialis anterior sparing on muscle image and myopathic-neurogenic motor unit potentials. Case presentation Here we report a 31 years old caucasian male patient with progressive gait disturbance, and severe lower limb proximal weakness since the age of 20 years, associated with subtle facial muscle weakness. Computed tomography demonstrated soleus, medial gastrocnemius, and diffuse thigh muscles involvement with tibialis anterior sparing. Electromyography disclosed both neurogenic and myopathic motor unit potentials. Muscle biopsy demonstrated large groups of atrophic and hypertrophic fibers, frequent fibers with intracytoplasmic rimmed vacuoles full of autophagic membrane and sarcoplasmic debris, and a total deficiency of telethonin. Molecular investigation identified the common homozygous c.157C > T in the TCAP gene. Conclusion This report expands the phenotypic variability of telethoninopathy/ LGMD2G, including: 1) mixed neurogenic and myopathic motor unit potentials, 2) facial weakness, and 3) tibialis anterior sparing. Appropriate diagnosis in these cases is important for genetic counseling and prognosis. PMID:25298746

  6. Levator resection in the management of myopathic ptosis.

    PubMed

    Buttanri, Ibrahim Bulent; Serin, Didem

    2014-12-01

    To evaluate the results of levator resection in patients with myopathic ptosis. The medical records of consecutive patients who underwent levator resection surgery performed for myopathic ptosis between October 2009 and March 2013 were reviewed. Indications for surgery were ptosis obscuring the visual axis and margin-reflex distance ≤ 2 mm. Surgical success was defined as clear pupillary axis when the patient voluntarily opened his eye and margin-reflex distance ≥ 3 mm. We analyzed the effect of levator function and Bell's phenomenon on the rates of success and corneal complication. This series included six male and six female patients. Levator function was between 4 and 12 mm. We performed bilateral levator resection surgery in all patients. The mean follow-up time was 14.8 months (range, 6 to 36 months). No patient was overcorrected. Adequate lid elevation was achieved after the operation in 20 eyes. Ptosis recurred in three out of 20 eyes after adequate lid elevation was achieved. Our overall success rate was 70.8%. In three eyes with poor Bell's phenomenon, corneal irritation and punctate epitheliopathy that required artificial eye drops and ointments developed in the early postoperative period, although symptoms resolved completely within 2 months of the resection surgery. No patients required levator recession or any other revision surgery for lagophthalmos or corneal exposure after levator resection. Levator resection seems to be a safe and effective procedure in myopathic patients with moderate or good Bell's phenomenon and levator function greater than 5 mm.

  7. Genetic ablation of cyclophilin D rescues mitochondrial defects and prevents muscle apoptosis in collagen VI myopathic mice.

    PubMed

    Palma, Elena; Tiepolo, Tania; Angelin, Alessia; Sabatelli, Patrizia; Maraldi, Nadir M; Basso, Emy; Forte, Michael A; Bernardi, Paolo; Bonaldo, Paolo

    2009-06-01

    Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy are inherited muscle disorders caused by mutations of genes encoding the extracellular matrix protein collagen VI (ColVI). Mice lacking ColVI (Col6a1(-/-)) display a myopathic phenotype associated with ultrastructural alterations of mitochondria and sarcoplasmic reticulum, mitochondrial dysfunction with abnormal opening of the permeability transition pore (PTP) and increased apoptosis of muscle fibers. Treatment with cyclosporin (Cs) A, a drug that desensitizes the PTP by binding to cyclophilin (Cyp)-D, was shown to rescue myofiber alterations in Col6a1(-/-) mice and in UCMD patients, suggesting a correlation between PTP opening and pathogenesis of ColVI muscular dystrophies. Here, we show that inactivation of the gene encoding for Cyp-D rescues the disease phenotype of ColVI deficiency. In the absence of Cyp-D, Col6a1(-/-) mice show negligible myofiber degeneration, rescue from mitochondrial dysfunction and ultrastructural defects, and normalized incidence of apoptosis. These findings (i) demonstrate that lack of Cyp-D is equivalent to its inhibition with CsA at curing the mouse dystrophic phenotype; (ii) establish a cause-effect relationship between Cyp-D-dependent PTP regulation and pathogenesis of the ColVI muscular dystrophy and (iii) validate Cyp-D and the PTP as pharmacological targets for the therapy of human ColVI myopathies.

  8. The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene.

    PubMed

    Gempel, Klaus; Topaloglu, Haluk; Talim, Beril; Schneiderat, Peter; Schoser, Benedikt G H; Hans, Volkmar H; Pálmafy, Beatrix; Kale, Gulsev; Tokatli, Aysegul; Quinzii, Catarina; Hirano, Michio; Naini, Ali; DiMauro, Salvatore; Prokisch, Holger; Lochmüller, Hanns; Horvath, Rita

    2007-08-01

    Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II + III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients. Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type II (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment.

  9. Paraneoplastic Dermatomyositis with Cutaneous and Myopathic Disease Responsive to Adrenocorticotropic Hormone Therapy

    PubMed Central

    Mancuso, Christopher; Lal, Karan; Dicostanzo, Damian; Gropper, Charles

    2017-01-01

    Dermatomyositis is a myopathic or amyopathic autoimmune connective tissue disease that presents with classic dermatologic findings ranging from: poikilodermatous photosensitivity (shawl sign), eyelid edema and violaceous-pigmentation (heliotrope sign), lichenoid eruptions on the knuckles and elbows (Gottron’s sign), periungual telangiectasias, and ragged cuticles (Samitz sign). Up to 30 percent of adult-onset cases of dermatomyositis may represent a paraneoplastic syndrome warranting a thorough work-up for malignancy. The authors present a case report of paraneoplastic dermatomyositis associated with triple negative, BRCA-1 positive, invasive intraductal carcinoma of the breast, whose myopathic and cuteanous symptoms were recalcitrant to high-dose corticosteroid therapy. Herein, the authors describe the first reported case of the use of an injectable adrenocorticotropic hormone agonist gel in a patient with myopathic paraneoplastic disease that achieved clinical resolution of both myopathic and cutaneous symptoms, but subseuqently developed significant hyperpigmentation of her face suspected to be secondary to a chemotherapeutic-induced pigmentary change which was augmented by adrenocorticotropic hormone therapy. PMID:28210382

  10. Biphasic anaphylaxis to gemifloxacin.

    PubMed

    Yilmaz, Insu; Doğan, Serkan; Tutar, Nuri; Kanbay, Asiye; Büyükoğlan, Hakan; Demir, Ramazan

    2012-10-01

    Anaphylaxis have been documented as adverse effects of ciprofloxacin, ofloxacin, norfloxacin, levofloxacin, and moxifloxacin. However resistant and biphasic anaphlylactic reactions to gemifloxacin have not been reported to date. Management of severe anaphylaxis in the elderly can be complicated by concurrent medications such as beta (β) adrenergic, alpha (α) adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors. We report here in the case of a 60-year-old male who was taking on ACE inhibitor, α and β blockers and experienced a severe, resistant and biphasic anaphlylactic reaction to gemifloxacin mesylate.

  11. [A two-year-old infant with a myopathic form of very-long-chain Acyl-CoA dehydrogenase deficiency].

    PubMed

    Ito, Yasushi; Nakano, Kazutoshi; Shishikura, Keiko; Suzuki, Haruko; Iida, Norihisa; Sasaki, Nobutaka; Kimura, Masahiko; Hasegawa, Yuki; Yamaguchi, Seiji; Osawa, Makiko

    2003-11-01

    A two-year-three-month old girl was hospitalized for detailed examination following repeated hyper-creatine kinasemia and cervical muscle cramps induced by pyrexia and persistent hypertonicity of the cervical muscles. Physical examination showed mild hypotonia but no muscle weakness. Induction of symptoms by continuous cervical muscular exercise and the appearance of dicarboxylic aciduria during the fasting test indicated a disorder of fatty acid oxidation. Free fatty acid and acyl carnitine analyses using dried blood spots, and acyl-CoA dehydrogenase activity assays using cultured skin fibroblasts established a diagnosis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Currently VLCAD deficiency has been divided into three phenotypes; a severe childhood form, a milder childhood form, and an adult form. However, we suggest that the severe and milder childhood forms would be better described as a systemic form, and the adult form and our infant case as a myopathic form. An early onset of the myopathic form within the first year of life, as well as its diagnosis in early infancy, has never been described in the literature.

  12. Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

    PubMed Central

    Kho, Alvin T; Kang, Peter B; Kohane, Isaac S; Kunkel, Louis M

    2006-01-01

    Background Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. Methods Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx5cv); (H1) biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2) four different control human muscle types obtained at autopsy; and (H3) 12 different control human tissues (ten non-muscle). Results Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy). Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3), indicating this finding to be muscle specific. Conclusion This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled. PMID:16522209

  13. Myopathic changes detected by quantitative electromyography in patients with MuSK and AChR positive myasthenia gravis.

    PubMed

    Nikolic, Ana; Basta, Ivana; Stojanovic, Vidosava Rakocevic; Stevic, Zorica; Peric, Stojan; Lavrnic, Dragana

    2016-05-01

    Myopathic changes are frequent a electrophysiological finding in patients with muscle specific tyrosine kinase (MuSK) positive myasthenia gravis (MG). The aim of this study was to explore the importance of quantitative electromyography (EMG) in the detection of myopathic changes in MuSK MG patients. Classical and quantitative EMG were performed in 31 MuSK and 28 acetylcholine receptor (AChR) positive MG patients, matched by sex, age, disease duration and severity. Classical EMG revealed the presence of myopathic changes more frequently in MuSK MG compared to AChR MG patients, especially in the facial muscles. Quantitative EMG registered myopathic lesions more frequently than classical EMG, but the frequency was similar between MuSK and AChR MG patients. Quantitative EMG revealed myopathic changes in the majority of both MuSK and AChR positive MG patients. This examination is sensitive, but it cannot be used to differentiate between MG patients belonging to the different disease groups. It should not be used in isolation. Rather, it should complement classical EMG in the detection of myopathic changes.

  14. Myopathic changes in murine skeletal muscle lacking synemin

    PubMed Central

    García-Pelagio, Karla P.; Muriel, Joaquin; O'Neill, Andrea; Desmond, Patrick F.; Lovering, Richard M.; Lund, Linda; Bond, Meredith

    2015-01-01

    Diseases of striated muscle linked to intermediate filament (IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. PMID:25567810

  15. Aqueous biphasic extraction

    SciTech Connect

    Chaiko, D.J.

    1994-02-01

    The aqueous biphasic separation (ABS) process, which involves the selective partitioning of ultrafine particles or solutes between two immiscible aqueous phases, is being evaluated for removing uranium from contaminated clay soils. Goal is to remove ultrafine U from the soil, leaving residues below regulatory cleanup limits. Tests were made using U-contaminated soil near the Fernald waste incinerator; over 80% of the soil is <45 {mu}m. All the biphasic systems used polyethylene glycol in combination with inorganic salt phase. Results: U was reduced from 500--600 mg/kg to about 90 mg/kg, and in some cases even down to 15 mg/kg. However, a soil sample from the Fernald storage pad area did not give encouraging results. Selective flocculation of soil particles and dissolution of U in the salt phase occurred but were not troublesome. Scaleup tests using uncontaminated clay mineral feed were successful. Operating costs for soil remediation using ABS is estimated to be $25--50 per ton. A pilot-scale column is being installed at ANL.

  16. Subcutaneous immunoglobulin therapy in a patient with myopathic dropped head syndrome and common variable immunodeficiency.

    PubMed

    Rosato, E; Molinaro, I; Pisarri, S; Salsano, F

    2011-01-01

    Prominent neck extension weakness is an uncommon clinical entity, also termed dropped-head syndrome, that may be part of a generalized neuromuscular disorder. We report here the case of a woman with dropped-head syndrome and pulmonary arterial hypertension secondary to systemic sclerosis. Subsequently, she developed common variable immunodeficiency and subcutaneous immunoglobulin therapy was started. After two months from the start of therapy we did not observe any improvement in the degree of flexion of the head, although the clinical examination shows an improvement in neck extensor muscle strength. Subcutaneous immunoglobulin therapy could be a possible therapeutic option for the treatment of myopathic neck extensor weakness.

  17. Biphasic nanofibrous constructs with seeded cell layers for osteochondral repair.

    PubMed

    Jin, Guang-Zhen; Kim, Jung-Ju; Park, Jeong-Hui; Seo, Seog-Jin; Kim, Joong-Hyun; Lee, Eun-Jung; Kim, Hae-Won

    2014-11-01

    Biphasic scaffolds have gained increasing attention for the regeneration of osteochondral interfacial tissue because they are expected to effectively define the interfacial structure of tissue that comprises stratified cartilage with a degree of calcification. Here, we propose a biphasic nanofiber construct made of poly(lactide-co-caprolactone) (PLCL) and its mineralized form (mPLCL) populated with cells. Primary rat articular chondrocytes (ACs) and bone marrow-derived mesenchymal stem cells (MSCs) were cultured on the layers of bare PLCL and mPLCL nanofibers, respectively, for 7 days, and the biphasic cell-nanofiber construct was investigated at 4 weeks after implantation into nude mice. Before implantation, the ACs and MSCs grown on each layer of PLCL and mPLCL nanofibers exhibited phenotypes typical of chondrocytes and osteoblasts, respectively, under proper culture conditions, as analyzed by electron microscopy, histological staining, cell growth kinetics, and real-time polymerase chain reaction. The biphasic constructs also showed the development of a possible formation of cartilage and bone tissue in vivo. Results demonstrated that the cell-laden biphasic nanofiber constructs may be useful for the repair of osteochondral interfacial tissue structure.

  18. [Educational and Professional Qualifications of Adults With Myotonic Dystrophies - A Misleading Perception by the Myopathic Face?].

    PubMed

    Stahl, K; Wenninger, S; Schüller, A; Montagnese, F; Schoser, B

    2016-04-01

    Myotonic dystrophies types 1 and 2 (DM1 / DM2) are the most frequent inherited progressive, segmental progeroid, multisystemic neuromuscular diseases in adulthood. The executive impairment is one of the key disease features. The myopathic face triggers the general perception of DM1 patients being associated with a low educational level. We used a standardized questionnaire to evaluate educational levels in adults with genetically confirmed DM1 and DM2 in comparison to data of the general population. Investigated topics included the level of education, e. g. the highest university degree aquired. Out of a total cohort of 546 DM patients, 125 DM1 and 156 DM2 patients (51 %) participated in this study. There was no statistically significant difference between the two collectives as far as high school levels are concerned. 50.4 % of DM1 and 48.3 % of DM2 patients obtained the higher education entrance qualification compared to 29.6 % of the normal German population. However, there were significant differences between the two collectives in "spelling problems" (DM1 cohort: p = 0.039), "difficulty in mental arithmetic" (p = 0.043), and classification of patients "with learning difficulties" (p = 0.012). Misled by a myopathic face, many physicians associate myotonic dystrophy with cognitive deficiency. Based on our study, the minimal deviation between DM1 and DM2 and the normal German population indicates that the multisystemic disease does not significantly influence the maximum attainable level of education in adults with DM1. In summary, physicians should be aware that the general educational levels are rather normal in patients with myotonic dystrophy type 1 and rethink their perception of DM1 patients. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Correction of myopathic blepharoptosis by check ligament suspension: clinical evaluation of 89 eyelids.

    PubMed

    Santanelli, Fabio; Paolini, Guido; Renzi, Luca Francesco; Longo, Benedetto; Pagnoni, Marco; Holmström, Hans

    2011-09-01

    Myopathic blepharoptosis is a congenital anomaly of the eyelid. The levator muscle does not function because of primary myogenic atrophy. Different procedures based on eyelid suspension, or the simple or combined resection of the eyelid have been described. A simple dynamic suspension of the tarsus to the check ligament of the superior fornix, neither sacrificing nor adding any tissue was used for 89 procedures on 71 consecutive patients with primary myopathic blepharoptosis. Their mean age at operation was 16 years (range 2-58) and the follow up ranged from 2 months to 12 years. Ptosis was unilateral in 53 patients (33 left, 20 right) and bilateral in 18. Preoperatively 27 had mild ptosis (1-2 mm), 33 moderate (3-4 mm), and 29 severe (>4 mm). The patients were divided into two groups: not previously operated on (50 patients/63 eyelids) and previously operated on by other techniques (21 patients/26 eyelids); both groups were compared for duration of procedure, normalisation rate, and number of revisions. In the unoperated group the normalisation rate was 81% (51 eyelids), and to achieve a good final result nine eyelids were revised once, while just three were reoperated on twice (19%). In the group previously operated on the normalisation rate was 69% (18 eyelids), while 3 eyelids needed one revision (12%). In unilateral cases the normalisation rate was 79% (42 eyelids) and in bilateral 75% (27 eyelids). In unilateral blepharoptosis there were 13% of revisions (7 eyelids) while bilaterally there were 22% (8 eyelids). Despite a previous operation, the operating time of a unilateral correction was similar in both groups, while the number of revisions needed to achieve the final result was low for unilateral ptosis, but higher for bilateral ones. This simple atraumatic suspension technique produced an improvement in all cases and it seemed useful in both primary and secondary cases.

  20. Aging Effects of Caenorhabditis elegans Ryanodine Receptor Variants Corresponding to Human Myopathic Mutations

    PubMed Central

    Baines, Katie Nicoll; Ferreira, Célia; Hopkins, Philip M.; Shaw, Marie-Anne; Hope, Ian A.

    2017-01-01

    Delaying the decline in skeletal muscle function will be critical to better maintenance of an active lifestyle in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance and is hypothesized to be a significant factor for age-related decline in muscle function. The nematode Caenorhabditis elegans is a key model system for the study of human aging, and strains were generated with modified C. elegans ryanodine receptors corresponding to human myopathic variants linked with malignant hyperthermia and related conditions. The altered response of these strains to pharmacological agents reflected results of human diagnostic tests for individuals with these pathogenic variants. Involvement of nerve cells in the C. elegans responses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications in C. elegans also conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging. PMID:28325813

  1. Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

    PubMed

    Caso, Giuseppe; Kelly, Patricia; McNurlan, Margaret A; Lawson, William E

    2007-05-15

    Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p <0.001) and pain interference with daily activities decreased by 38% (p <0.02) in the group treated with coenzyme Q10. In contrast, no changes in pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

  2. Variable Myopathic Presentation in a Single Family with Novel Skeletal RYR1 Mutation

    PubMed Central

    Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

    2013-01-01

    We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca2+ stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient’s muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies. PMID:23894444

  3. Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.

    PubMed

    Attali, Ruben; Aharoni, Sharon; Treves, Susan; Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

    2013-01-01

    We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+) stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.

  4. Analysis, design and development of a carbon fibre reinforced plastic knee-ankle-foot orthosis prototype for myopathic patients.

    PubMed

    Granata, C; De Lollis, A; Campo, G; Piancastelli, L; Merlini, L

    1990-01-01

    A traditional knee-ankle-foot orthosis (KAFO) for myopathic patients has been studied for the assessment of loads and fatigue resistance. Starting from this basis a thermoplastic matrix carbon fibre reinforced plastic composite (CFRP) KAFO has been developed in order to reduce the weight. A finite-element simulation programme for deformation analysis was used to compare the behaviour of conventional and CFRP orthosis. There were no breakages either of the prototype or of its parts. The CFRP orthosis allows a weight reduction of more than 40 per cent.

  5. Biphasic water splitting by osmocene

    PubMed Central

    Ge, Peiyu; Todorova, Tanya K.; Patir, Imren Hatay; Olaya, Astrid J.; Vrubel, Heron; Mendez, Manuel; Hu, Xile; Corminboeuf, Clémence; Girault, Hubert H.

    2012-01-01

    The photochemical reactivity of osmocene in a biphasic water-organic solvent system has been investigated to probe its water splitting properties. The photoreduction of aqueous protons to hydrogen under anaerobic conditions induced by osmocene dissolved in 1,2-dichloroethane and the subsequent water splitting by the osmocenium metal-metal dimer formed during H2 production were studied by electrochemical methods, UV-visible spectrometry, gas chromatography, and nuclear magnetic resonance spectroscopy. Density functional theory computations were used to validate the reaction pathways. PMID:22665787

  6. Biphasic nature of gastric emptying.

    PubMed Central

    Siegel, J A; Urbain, J L; Adler, L P; Charkes, N D; Maurer, A H; Krevsky, B; Knight, L C; Fisher, R S; Malmud, L S

    1988-01-01

    The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min-1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic

  7. Acute Biphasic Effects of Ayahuasca

    PubMed Central

    Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D.; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A.; da Silveira, Dartiu Xavier

    2015-01-01

    Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered. PMID:26421727

  8. Acute Biphasic Effects of Ayahuasca.

    PubMed

    Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A; da Silveira, Dartiu Xavier

    2015-01-01

    Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered.

  9. Biodesulfurization in Biphasic Systems Containing Organic Solvents†

    PubMed Central

    Tao, Fei; Yu, Bo; Xu, Ping; Ma, Cui Qing

    2006-01-01

    Biphasic systems can overcome the problem of low productivity in conventional media and have been exploited for biocatalysis. Solvent-tolerant microorganisms are useful in biotransformation with whole cells in biphasic reactions. A solvent-tolerant desulfurizing bacterium, Pseudomonas putida A4, was constructed by introducing the biodesulfurizing gene cluster dszABCD, which was from Rhodococcus erythropolis XP, into the solvent-tolerant strain P. putida Idaho. Biphasic reactions were performed to investigate the desulfurization of various sulfur-containing heterocyclic compounds in the presence of various organic solvents. P. putida A4 had the same substrate range as R. erythropolis XP and could degrade dibenzothiophene at a specific rate of 1.29 mM g (dry weight) of cells−1 h−1 for the first 2 h in the presence of 10% (vol/vol) p-xylene. P. putida A4 was also able to degrade dibenzothiophene in the presence of many other organic solvents at a concentration of 10% (vol/vol). This study is a significant step in the exploration of the biotechnological potential of novel biocatalysts for developing an efficient biodesulfurization process in biphasic reaction mixtures containing toxic organic solvents. PMID:16820450

  10. A comparison of biphasic and monophasic shocks for external defibrillation. Physio-Control Biphasic Investigators.

    PubMed

    Higgins, S L; Herre, J M; Epstein, A E; Greer, G S; Friedman, P L; Gleva, M L; Porterfield, J G; Chapman, F W; Finkel, E S; Schmitt, P W; Nova, R C; Greene, H L

    2000-01-01

    The ability of a shock to defibrillate the heart depends on its waveform and energy. Past studies of biphasic truncated exponential (BTE) shocks for external defibrillation focused on low energy levels. This prospective, randomized, double-blind clinical trial compared the first-shock efficacies of 200-joule (J) BTE, 130-J BTE, and 200-J monophasic damped sine wave shocks. Ventricular fibrillation (VF) was induced in 115 patients during evaluation of implantable cardioverter-defibrillator function and 39 patients during electrophysiologic evaluation of ventricular arrhythmias. After 19 +/- 10 seconds of VF, a randomized transthoracic shock was administered. Mean first-shock success rates of the three groups were compared using a "Tukey-like" statistical test, adjusting for multiple comparisons. Blood pressures and arterial oxygen saturations were measured before VF induction and 30, 90, and 150 seconds after successful defibrillation. First-shock success rates were 61/68 (90%) for 200-J monophasic, 39/39 (100%) for 200-J biphasic, and 39/47 (83%) for 130-J biphasic shocks. The 200-J biphasic shocks were simultaneously superior in first-shock efficacy to both 200-J monophasic and 130-J biphasic shocks (experimentwise error rate, alpha < 0.01). There was no significant difference between the efficacies of 200-J monophasic and 130-J biphasic shocks, nor was there any significant difference between the three groups in hemodynamic parameters after successful shocks. Biphasic shocks of 200 J provide better first-shock defibrillation efficacy for short-duration VF than 200-J monophasic and 130-J biphasic shocks and thus may allow earlier termination of VF in cardiac arrest patients.

  11. Metal separations using aqueous biphasic partitioning systems

    SciTech Connect

    Chaiko, D.J.; Zaslavsky, B.; Rollins, A.N.; Vojta, Y.; Gartelmann, J.; Mego, W.

    1996-05-01

    Aqueous biphasic extraction (ABE) processes offer the potential for low-cost, highly selective separations. This countercurrent extraction technique involves selective partitioning of either dissolved solutes or ultrafine particulates between two immiscible aqueous phases. The extraction systems that the authors have studied are generated by combining an aqueous salt solution with an aqueous polymer solution. They have examined a wide range of applications for ABE, including the treatment of solid and liquid nuclear wastes, decontamination of soils, and processing of mineral ores. They have also conducted fundamental studies of solution microstructure using small angle neutron scattering (SANS). In this report they review the physicochemical fundamentals of aqueous biphase formation and discuss the development and scaleup of ABE processes for environmental remediation.

  12. Biomimetic biphasic scaffolds for osteochondral defect repair

    PubMed Central

    Li, Xuezhou; Ding, Jianxun; Wang, Jincheng; Zhuang, Xiuli; Chen, Xuesi

    2015-01-01

    The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed. Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues. For osteochondral reconstruction, one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone. Therefore, the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm. A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers, or the ones loading with growth factors, cells, or both of them make great progresses in osteochondral defect repair. In this review, the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed, as well as the prospect is predicted. PMID:26816644

  13. Coxsackievirus B1-induced chronic inflammatory myopathy: differences in induction of autoantibodies to muscle and nuclear antigens by cloned myopathic and amyopathic viruses.

    PubMed

    Tam, Patricia E; Fontana, Donna R; Messner, Ronald P

    2003-09-01

    Infection of susceptible strains of mice with the myopathic Tucson strain of coxsackievirus B1 (CVB1(T)) leads to the development of chronic inflammatory myopathy (CIM). The underlying mechanism of CIM appears to be immunopathic, but it is not known whether autoimmunity is involved. The objectives of this study were to determine whether autoantibodies are produced and whether they correlate with the pathology of CIM. Mice were infected with either a myopathic (MP1.23 or MP1.24) or an amyopathic (AMP2.17) CVB1(T) cloned virus. The two myopathic (MP) viruses cause CIM, whereas the amyopathic (AMP) virus, derived from a variant of the same parent, causes the same acute disease but does not cause CIM. Antimuscle IgG was found in 51% of MP1.23-infected and 58% of MP1.24-infected mice but in just 18% of mice infected with AMP2.17 and in 10% of controls (MP vs AMP: chi(2), P < or =.006). Several staining patterns were observed, indicating that autoantibodies of multiple specificities were produced. Antinuclear antibodies were found in 57% of MP1.23-infected and 27% of MP1.24-infected mice but were rare in mice infected with AMP2.17 (0%) or in controls (4%) (MP vs AMP: chi(2), P < or =.01). Antiviral-antibody titers were higher with MP virus than with AMP virus (ANOVA, P <.001). A trend toward an association between antiviral antibody or autoantibodies and the presence or severity of clinical measures of CIM was noted but was not significant. These data suggest that the autoantibodies do not mediate muscle disease but are an independent manifestation of an immunopathic response induced by infection with MP but not AMP CVB1(T).

  14. The cyclophilin inhibitor Debio 025 normalizes mitochondrial function, muscle apoptosis and ultrastructural defects in Col6a1−/− myopathic mice

    PubMed Central

    Tiepolo, T; Angelin, A; Palma, E; Sabatelli, P; Merlini, L; Nicolosi, L; Finetti, F; Braghetta, P; Vuagniaux, G; Dumont, J-M; Baldari, CT; Bonaldo, P; Bernardi, P

    2009-01-01

    Background and purpose: We have investigated the therapeutic effects of the selective cyclophilin inhibitor D-MeAla3-EtVal4-cyclosporin (Debio 025) in myopathic Col6a1−/− mice, a model of muscular dystrophies due to defects of collagen VI. Experimental approach: We studied calcineurin activity based on NFAT translocation; T cell activation based on expression of CD69 and CD25; propensity to open the permeability transition pore in mitochondria and skeletal muscle fibres based on the ability to retain Ca2+ and on membrane potential, respectively; muscle ultrastructure by electronmicroscopy; and apoptotic rates by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assays in Col6a1−/− mice before after treatment with Debio 025. Key results: Debio 025 did not inhibit calcineurin activity, yet it desensitizes the mitochondrial permeability transition pore in vivo. Treatment with Debio 025 prevented the mitochondrial dysfunction and normalized the apoptotic rates and ultrastructural lesions of myopathic Col6a1−/− mice. Conclusions and implications: Desensitization of the mitochondrial permeability transition pore can be achieved by selective inhibition of matrix cyclophilin D without inhibition of calcineurin, resulting in an effective therapy of Col6a1−/− myopathic mice. These findings provide an important proof of principle that collagen VI muscular dystrophies can be treated with Debio 025. They represent an essential step towards an effective therapy for Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy, because Debio 025 does not expose patients to the potentially harmful effects of immunosuppression. PMID:19519726

  15. Truncated biphasic pulses for transthoracic defibrillation.

    PubMed

    Bardy, G H; Gliner, B E; Kudenchuk, P J; Poole, J E; Dolack, G L; Jones, G K; Anderson, J; Troutman, C; Johnson, G

    1995-03-15

    Early defibrillation is the single most important factor for improving out-of-hospital ventricular fibrillation resuscitation rates. To achieve the earlier response times required for survival, typically < 6 minutes from time of collapse, it will be necessary to equip a far wider network of first responders (firefighters, police, and other individuals with responsibility for public safety) with small, lightweight, and inexpensive automatic external defibrillators (AEDs). An important step in reducing the size and cost of AEDs will be to improve defibrillation efficacy. Because biphasic waveform defibrillation has had a favorable impact on implantable cardioverter-defibrillators (ICDs), there are reasons to believe that biphasic waveforms would also improve transthoracic defibrillators. Our purpose, therefore, was to examine the efficacy of two different low-energy biphasic truncated waveforms referenced to a standard damped sine waveform for transthoracic defibrillation in humans. We prospectively and randomly compared the transthoracic defibrillation efficacy of two different truncated biphasic waveforms, 115 J (70 microF) and 130 J (105 microF), with that of a standard 200-J (36-microF, 28-mH) damped sine wave pulse using right anterior and left lateral thoracic pads (R2 Medical Systems) in 30 cardiac arrest survivors during transvenous ICD surgery. The right anterior patch electrode was used as the cathode and the left lateral thoracic pad as the anode. Transthoracic ventricular defibrillation rescue shocks were tested after a failed transvenous defibrillation shock delivered in the course of ICD testing. Each of the three different rescue shocks was tested in random order in each patient. All shocks were delivered at end expiration. The investigators responsible for determining transthoracic shock efficacy were blinded throughout the study to the transthoracic rescue waveform used. A total of 33 patients were considered for study, but three patients failed to

  16. Comparison of single-biphasic versus sequential-biphasic shocks on defibrillation threshold in pigs.

    PubMed

    Csanadi, Z; Jones, D L; Wood, G K; Klein, G J

    1997-06-01

    Current generation implantable cardioverter defibrillators use monophasic, biphasic, or sequential pulse shocks, most of which truncate after a given time, dumping the remaining charge on the capacitor through an internal resistor. We hypothesized that having an additional current pathway, and delivering the majority of the remaining charge on a single capacitor to the two pathways using additional shock phases, would improve defibrillation efficacy. This hypothesis was tested by comparing DFTs using a simulated single capacitor, single-biphasic shock (two 5-ms pulses separated by 0.2 ms), delivered to coupled pairs of electrodes, to those using a sequential-biphasic shock (four 5-ms pulses separated by 0.2 ms) delivered to separate opposing electrodes, delivered from the same electrodes for both waveforms. In eight open-chest anesthetized pigs, four mesh electrodes (Medtronic TX-7, 6.5 cm2), were sutured on the epicardium of the anterior and posterior surfaces of each ventricle. Shocks were delivered from a 200-microF capacitor bank. Triplicate DFTs were obtained using each waveform in a randomized crossover design. Initial leading edge voltage (mean +/- SEM: 420 +/- 33 V vs 497 +/- 34 V; P < 0.05), initial peak current (4.8 +/- 0.4 A vs 13 +/- 1.1 A; P < 0.001), and delivered energy (16.9 +/- 2.6 J vs 30.4 +/- 5.3 J; P < 0.05) at the DFT were all significantly lower using sequential-biphasic shocks than those using single-biphasic shocks, respectively. We conclude that for direct heart defibrillation, it is worthwhile to combine sequential capability to biphasic shocks and deliver the remaining charge on the capacitor to the two different pathways.

  17. Soil decontamination using aqueous biphasic separation

    SciTech Connect

    Chaiko, D.J.; Mensah-Biney, R.; Gupta, D.

    1994-02-01

    This paper summarizes efforts to develop a biphasic extraction process for separating ultrafine particulate contaminants from soils having high amounts of silt and clay. This work has thus far dealt with the removal of refractory uranium particles from the soils at Fernald, Ohio. The separation process involves the selective partitioning of ultra-fine particles between two immiscible aqueous phases. The authors have conducted batch extraction studies and are now beginning to scaleup the process for pilot-plant testing at Argonne National Laboratory (ANL). The results of these extraction studies are discussed.

  18. Biphasic cell responses on laterally mobile films

    NASA Astrophysics Data System (ADS)

    Kourouklis, Andreas; Lerum, Ronald; Bermudez, Harry

    2013-03-01

    The engineering of polymer surfaces or matrices that are capable of controlling cell adhesion has been widely explored. In nearly all of these works, the polymer chains (and ligands) are chemically attached to the underlying substrate, and therefore these systems are inherently static. By contrast, cellular environments such as the extracellular matrix (ECM) are dynamic and remodeled by biochemical reactions and biophysical forces. Borrowing this concept from Nature, we created polymer films by an interfacial self-assembly process, whereby individual chains can exhibit lateral mobility (in-plane diffusive motion). NIH 3T3 fibroblasts seeded on such RGD-presenting polymer films show biphasic responses in spreading and adhesion strength to lateral mobility, with a minimal response for intermediate mobility values. Futhermore, preliminary immuno-staining experiments reveal that the total area of focal adhesions demonstrates a similar biphasic trend to the cellular-scale behaviors. In contrast, actin filaments or stress fibers appear to be unaffected by the substrate lateral mobility. These results show that lateral mobility is an important, although not fully explored aspect of mechano-sensing by cells, and can potentially give new perspectives on cell-ECM interactions. National Science Foundation

  19. Biphasic microtiter method for campylobacter recovery and enumeration

    USDA-ARS?s Scientific Manuscript database

    We developed a biphasic method for recovery and enumeration of campylobacters. The biphasic system was composed of 96-well microtiter plates containing Campy-Line Agar (CLA) prepared 2X for all ingredients except for 1X agar (0.1 ml per well). Samples of pure Campylobacter spp. isolates, post-chi...

  20. AQUEOUS BIPHASE EXTRACTION FOR PROCESSING OF FINE COAL

    SciTech Connect

    K. Osseo-Asare; X. Zeng

    2002-01-01

    The objective of this research project is to develop an aqueous biphase extraction process for the treatment of fine coals. Aqueous biphase extraction is an advanced separation technology that relies on the ability of an aqueous system consisting of a water-soluble polymer and another component, e.g., another polymer, an inorganic salt, or a nonionic surfactant, to separate into two immiscible aqueous phases. The principle behind the partition of solid particles in aqueous biphase systems is the physicochemical interaction between the solid surface and the surrounding liquid solution. In order to remove sulfur and mineral matter from fine coal with aqueous biphasic extraction, it is necessary to know the partitioning behavior of coal, as well as the inorganic mineral components. Therefore, in this research emphasis was placed on the partitioning behavior of fine coal particles as well as model fine inorganic particles in aqueous biphase systems.

  1. Biphasic versus monophasic shock waveform for conversion of atrial fibrillation.

    PubMed

    Rho, Robert W; Page, Richard L

    2003-09-01

    Cardioversion of atrial fibrillation (AF) using traditional monophasic shock waveform is unsuccessful in up to 20% of cases, and often requires several shocks of up to 360 J. Based on the success with biphasic shock waveform in converting ventricular fibrillation, it was postulated that biphasic shocks would allow cardioversion with lower energy. In a international multicenter, double-blind, randomized trial of 203 patients, damped sine wave monophasic shocks were compared with impedance-compensated truncated exponential biphasic waveform shocks. Patients received up to five shocks: 100 J, 150 J, 200 J, a fourth shock at maximum output for the initial waveform (200 J biphasic, 360 J monophasic) and a final cross-over shock at maximum output of the alternate waveform. For each energy level, the biphasic waveform compared favorably to the monophasic waveform in successful cardioversion (100 J: 60% versus 22%, P < 0.0001; 150 J: 77% versus 44%, p < 0.0001; 200 J: 90% versus 53%, p < 0.0001). Success with 200 J biphasic was equivalent to 360 J monophasic shock (91% versus 85%, p = 0.29). Patients randomized to biphasic waveform required fewer shocks and lower total energy delivered; in addition, this waveform was associated with less dermal injury and no blistering. Biphasic shocks converted AF present for less than 48 hours with 80% efficacy, but conversion of AF present for more than 48 hours and more than 1 year the success rate was only 63 and 20%, respectively. The results of this study is similar to other investigations comparing biphasic and monophasic shock waveforms for conversion of atrial fibrillation. We recommend starting with biphasic energy of 100 J for atrial fibrillation of less than 48 hours duration, but using higher energies (150 J, 200 J or greater) when AF has been present for longer periods.

  2. Biphasic synovial sarcoma of the abdominal wall.

    PubMed

    Vera, Jesús; García, María-Dolores; Marigil, Miguel; Abascal, Manuel; Lopez, Jose-Ignacio; Ligorred, Luis

    2006-09-01

    Synovial sarcoma arising in the abdominal wall is a rare tumor. We report a case of a 38-year-old man who complained of abdominal pain. Physical examination revealed a firm mobile mass, 25 cm in diameter, in the left lower abdominal wall. The tumor was first thought to be a sarcoma arising from the omentum or mesentery. During surgery, a large tumor was found attached to the inner surface of the abdominal wall and compressing the gastrointestinal tract. On microscopic examination the tumor corresponded to a biphasic synovial sarcoma immunoreactive for cytokeratins (AE1/AE3, 7 and 19), epithelial membrane antigen and carcinoembryonic antigen in the epithelial tumor cells, for E-cadherin especially in their glandular structure, vimentin, CD99, and CD56 in the spindle cell component and for bcl-2 protein. The tumor recurred at the same site, and clinical course progressed to death 3 months after the initial diagnosis.

  3. Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury.

    PubMed

    Roy, Edwige; Seppanen, Elke; Ellis, Rebecca; Lee, Eddy S; Khosrotehrani, Kiarash; Khosroterani, Kiarash; Fisk, Nicholas M; Bou-Gharios, George

    2014-03-01

    Fetal microchimeric cells (FMCs) enter the maternal circulation and persist in tissue for decades. They have capacity to home to injured maternal tissue and differentiate along that tissue's lineage. This raises the question of the origin(s) of cells transferred to the mother during pregnancy. FMCs with a mesenchymal phenotype have been documented in several studies, which makes mesenchymal stem cells an attractive explanation for their broad plasticity. Here we assessed the recruitment and mesenchymal lineage contribution of FMCs in response to acute kidney fibrosis induced by aristolochic acid injection. Serial in vivo bioluminescence imaging revealed a biphasic recruitment of active collagen-producing FMCs during the repair process of injured kidney in post-partum wild-type mothers that had delivered transgenic pups expressing luciferase under the collagen type I-promoter. The presence of FMCs long-term post injury (day 60) was associated with profibrotic molecules (TGF-β/CTGF), serum urea levels, and collagen deposition. Immunostaining confirmed FMCs at short term (day 15) using post-partum wild-type mothers that had delivered green fluorescent protein-positive pups and suggested a mainly hematopoietic phenotype. We conclude that there is biphasic recruitment to, and activity of, FMCs at the injury site. Moreover, we identified five types of FMC, implicating them all in the reparative process at different stages of induced renal interstitial fibrosis.

  4. Acute encephalopathy with biphasic seizures and late reduced diffusion

    PubMed Central

    Yadav, Saroj S.; Lawande, Malini A.; Kulkarni, Shilpa D.; Patkar, Deepak A.

    2013-01-01

    Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is a syndrome of encephalopathy characterized by biphasic seizures and altered consciousness in the acute stage followed in the subacute stage by restricted diffusion in the subcortical white matter on magnetic resonance imaging. The etiology of AESD has been attributed to viral infection like influenza A and human herpes virus 6. The exact pathogenesis of AESD is uncertain. Here we report a case of AESD, diagnosed based on clinicoradiological correlation. PMID:23772250

  5. Vorticity banding in biphasic polymer blends.

    PubMed

    Caserta, Sergio; Guido, Stefano

    2012-11-27

    Pattern formation under the action of flow is a subject of considerable scientific interest with applications going from microfluidics to granular materials. Here, we present a systematic investigation of shear-induced banding in confined biphasic liquid-liquid systems, i.e., formation of alternating regions of high and low volume fraction of droplets in a continuous phase (shear bands). This phenomenon is investigated in immiscible polymer blends sheared in a sliding parallel plate flow cell. Starting from a spatially uniform distribution of droplets, the formation of bands aligned along the flow direction is observed, eventually leading to an almost complete separation between droplet-rich and continuous phase regions. The initial band size is related to the gap dimension; the merging of bands and consequent spacing reduction has also been observed for long times. Shear banding is only observed when the viscosity of the dispersed phase is lower as compared to the continuous phase and in a limited range of the applied shear rate. Rheological measurements show that band formation is associated with a viscosity decrease with respect to the homogeneous case, thus implying that system microstructure is somehow evolving toward reduced viscous dissipation under flow.

  6. Purification of Helicobacter suis Strains From Biphasic Cultures by Single Colony Isolation: Influence on Strain Characteristics.

    PubMed

    Liang, Jungang; De Bruyne, Ellen; Ducatelle, Richard; Smet, Annemieke; Haesebrouck, Freddy; Flahou, Bram

    2015-06-01

    Helicobacter (H.) suis causes gastritis and decreased weight gain in pigs. It is also the most prevalent non-Helicobacter pylori Helicobacter species in humans with gastric disease. H. suis is extremely fastidious, and so far, biphasic culture conditions were essential for isolation and culture, making it impossible to obtain single colonies. Hence, cultures obtained from an individual animal may contain multiple H. suis strains, which is undesirable for experiments aiming for instance at investigating H. suis strain differences. Pure cultures of H. suis were established by growing bacteria as colonies on 1% brucella agar plates, followed by purification and enrichment by biphasic subculture. Characteristics of these single colony-derived strains were compared with those of their parent strains using multilocus sequence typing (MLST) and by studying bacterium-host interactions using a gastric epithelial cell line and Mongolian gerbil model. The purification/enrichment procedure required a nonstop culture of several weeks. For 4 of 17 H. suis strains, MLST revealed differences between parental and single colony-derived strains. For three of four single colony-derived strains tested, the cell death-inducing capacity was higher than for the parental strain. One single colony-derived strain lost its capacity to colonize Mongolian gerbils. For the four other strains tested, colonization capacity and histopathologic changes were similar to what has been described when using strains with only a history of limited biphasic culture. A method was developed to obtain single colony-derived H. suis strains, but this procedure may affect the bacterial genotype and phenotype. © 2015 John Wiley & Sons Ltd.

  7. Assessment of balanced biphasic defibrillation waveforms in transthoracic atrial cardioversion.

    PubMed

    Krasteva, V; Trendafilova, E; Cansell, A; Daskalov, I

    2001-01-01

    Various electrical pulses have been used for defibrillation. The monophasic damped sinusoid waveform, initiated in 60 s, was adopted in virtually all defibrillators. Biphasic pulses were introduced recently, achieving success with less energy. A biphasic exponential waveform was modelled with 4 ms duration per phase with a balanced 3:1 ratio of the first to second phase peak voltages and implemented in a defibrillator. A version obtained by chopping the pulses with a 5 kHz frequency was also used. It was hypothesized that the modelled transmembrane voltage decay time is a parameter that could be associated with successful defibrillation. The results of cardioversion for two groups of patients with the 'classic' monophasic waveform and with the biphasic pulses were compared. The mean efficient energy with the damped sinusoid was 205 +/- 85 J, versus 88 +/- 43 J with the biphasic pulses, yielding a ratio of 2.32 (1.92 to 3.2 for fibrillation and flutter, respectively). An acceptable agreement between model data and clinical results was found. The transmembrane voltage decay time ratios for monophasic versus biphasic pulses was in the approximate range of 2.5 to 3.5.

  8. Biphasic catalysis in water/carbon dioxide micellar systems

    DOEpatents

    Jacobson, Gunilla B.; Tumas, William; Johnston, Keith P.

    2002-01-01

    A process is provided for catalyzing an organic reaction to form a reaction product by placing reactants and a catalyst for the organic reaction, the catalyst of a metal complex and at least one ligand soluble within one of the phases of said aqueous biphasic system, within an aqueous biphasic system including a water phase, a dense phase fluid, and a surfactant adapted for forming an emulsion or microemulsion within the aqueous biphasic system, the reactants soluble within one of the phases of the aqueous biphasic system and convertible in the presence of the catalyst to a product having low solubility in the phase in which the catalyst is soluble; and, maintaining the aqueous biphasic system under pressures, at temperatures, and for a period of time sufficient for the organic reaction to occur and form the reaction product and to maintain sufficient density on the dense phase fluid, the reaction product characterized as having low solubility in the phase in which the catalyst is soluble.

  9. Biphasic nanoparticles made by electrified jetting

    NASA Astrophysics Data System (ADS)

    Lahann, Joerg

    2005-03-01

    Nano-colloids have recently attracted intense attention due to unique properties that are distinctly different from bulk solid-state materials; including unique magnetic, electronic, optical, chemical, and biological characteristics. The vision that these nano-objects could essentially act as functional components in novel device generations, which ``magically'' assemble following a master blueprint void any human manipulation, has resulted in a new ``gold rush'' in materials science. These concepts have results in the synthesis of a multitude of nano-objects, such as nano-wires, nano-rods, nano-disks, or nano-prisms.^ Recently, nano-particles with anisotropic materials distributions (biphasic nano-particles) moved in the focus of research. Our approach differs fundamentally from the above-mentioned methods in that it takes advantage of electrified polymer jets to create anisotropic materials distributions in nano-objects. jetting is a process to generate liquid jets by use of electrostatic forces. It is well-known that high electrical potentials (typically several thousand volts) applied between the jetting liquids that are fed through a capillary and a collecting substrate will induce jetting of a charged liquid. The differences in the final morphologies from similar processes are mainly determined by the properties of the jetting liquids and the process parameters. transmission electron microscopy, scanning electron microscopy, and scanning laser confocal microscopy, we demonstrate the applicability of the process to control size, shape, and materials distribution at the nanoscale. The resulting anisotropic nanoparticles may have potential applications for targeted drug delivery or as electro-rehological fluids. a) F. M. Van der Kooij, K. Kassapidou and H. N. W. Lekkerkerker, Liquid crystal phase transitions in suspensions of polydisperse plate-like particles, Nature 406, 868 (2000); b) C. A. Mirkin, R. L. Letsinger, R. C. Mucic and J. J. Storhoff, A DNA

  10. Progress on the biphase turbine at Cerro Prieto

    SciTech Connect

    Cerini, D.; Hays, L.; Studhalter, W.

    1997-12-31

    The status of a Biphase turbine power plant being installed at the Cerro Prieto geothermal field is presented. The major modules for the power plant are completed except for a back pressure steam turbine. The power plant will be started in April 1997 with the Biphase turbine alone followed by the addition of the steam turbine module two months later. The current power plant performance level is 2780 kWe due to a decline in the well. An increase in power output to 4060 kWe by adding the flow from another well is planned. The addition of five Biphase power plants with a total power output of 21.2 megawatts is described.

  11. Biphasic materials for bone grafting and hyperthermia treatment of cancer.

    PubMed

    Arcos, D; del Real, R P; Vallet-Regí, M

    2003-04-01

    Three biphasic materials have been synthesized from a magnetic glass-ceramic (Si-Ca-Fe) and a bioactive sol-gel glass (Si-P-Ca). The ratios of glass-ceramic:sol-gel glass used in this work were 1:1, 2:1, and 5:1. These materials show bioactive and magnetic properties and can be used as thermoseeds for hyperthermia treatment of bone tumors. The sol-gel glass content affects the textural properties of the glass-ceramic, giving rise to porosity, which plays a fundamental role in the formation of an apatite-like layer on the surface. On the other hand, as the sol-gel glass content increases, the magnetic properties change due to the diffusion of Fe ions to the glassy phases of the biphasic materials. The biphasic nature of these materials allows the changing of both properties, depending on the requirements of the patient.

  12. Microfluidic electrospinning of biphasic nanofibers with Janus morphology

    PubMed Central

    Srivastava, Yasmin; Marquez, Manuel; Thorsen, Todd

    2009-01-01

    In this paper a method of electrospinning conducting and nonconducting biphasic Janus nanofibers using microfluidic polydimethylsiloxane (PDMS)-based manifolds is described. Key benefits of using microfluidic devices for nanofiber synthesis include rapid prototyping, ease of fabrication, and the ability to spin multiple Janus fibers in parallel through arrays of individual microchannels. Biphasic Janus nanofibers of polyvinylpyrrolidone (PVP)+polypyrrole (PPy)∕PVP nanofibers with an average diameter of 250 nm were successfully fabricated using elastomeric microfluidic devices. Fiber characterization and confirmation of the Janus morphology was subsequently carried out using a combination of scanning electron microscopy, energy dispersion spectroscopy, and transmission electron microscopy. PMID:19693390

  13. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    PubMed Central

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

  14. Bi-phase transition diagrams of metallic thin multilayers

    SciTech Connect

    Li, J.C.; Liu, W.; Jiang, Q. . E-mail: jiangq@jlu.edu.cn

    2005-02-01

    Phase transitions of metallic multilayers induced by differences in interface energy are considered thermodynamically, based on a thermodynamic model for interface energy and the Goldschmidt premise for lattice contraction. Bi-phase transition diagrams of Co/Cr, Zr/Nb, Ti/Nb and Ti/Al multilayers are constructed, which are in agreement with experimental results.

  15. TREATMENT OF TYPE 2 DIABETES WITH BIPHASIC INSULIN ANALOGUES

    PubMed Central

    Rizvi, Ali A.

    2016-01-01

    The majority of patients with Type 2 diabetes require insulin therapy for treating hyperglycaemia. There are several regimens available for insulin initiation and maintenance. Insulin analogues have been developed to mimic normal physiology as closely as possible. Biphasic analogues can target both fasting and postprandial hyperglycaemia, with the added advantage of being premixed and thus convenient for the patient. A practical and feasible option is to initiate insulin with one or more biphasic preparations at mealtimes, thus providing both basal and prandial coverage. Individual titration of dose and frequency of daily injections with biphasic insulin preparations has the potential for improving glycaemic control with a high degree of patient acceptance. Drawbacks include a more rigid regimen, a relative lack of flexibility, and a somewhat higher degree of glycaemic variability and hypoglycaemia when compared to multiple daily basal-bolus injections. Awareness of the advantages and limitations of biphasic insulin analogues can assist clinicians in their appropriate use for the treatment of patients with Type 2 diabetes. PMID:27918600

  16. Biphasic dose response in low level light therapy - an update.

    PubMed

    Huang, Ying-Ying; Sharma, Sulbha K; Carroll, James; Hamblin, Michael R

    2011-01-01

    Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.

  17. A biphasic basal body temperature record during pregnancy.

    PubMed

    Urman, B C; McComb, P F

    1989-01-01

    A case of biphasic temperature record is reported during the course of an ectopic pregnancy. Possible implications of this phenomenon may improve our understanding of the role of ovum transmigration and the endocrinological interaction of pregnancy with hormonal control of ovulation.

  18. Biphasic surface amorphous layer lubrication of articular cartilage.

    PubMed

    Graindorge, Simon; Ferrandez, Wendy; Jin, Zhongmin; Ingham, Eileen; Grant, Colin; Twigg, Peter; Fisher, John

    2005-12-01

    The biphasic nature of articular cartilage has been acknowledged for some time and is known to play an important role in many of the biomechanical functions performed by this unique tissue. From the lubrication point of view however, a simple biphasic model is unable to account for the extremely low friction coefficients that have been recorded experimentally, particularly during start-up. In addition, research over the last decade has indicated the presence of a surface amorphous layer on top of articular cartilage. Here, we present results from a finite element model of articular cartilage that includes a thin, soft, biphasic surface amorphous layer (BSAL). The results of this study show that a thin BSAL, with lower elastic modulus, dramatically altered the load sharing between the solid and liquid phases of articular cartilage, particularly in the near-surface regions of the underlying bulk cartilage and within the surface amorphous layer itself where the fluid load support exceeded 85%. By transferring the load from the solid phase to the fluid phase, the biphasic surface layer improves lubrication and reduces friction, whilst also protecting the underlying cartilage surface by 'shielding' the solid phase from elevated stresses. The increase in lubrication effectiveness is shown to be greatest during short duration loading scenarios, such as shock loads.

  19. The biphasic nature of nitric oxide responses in tumor biology.

    PubMed

    Ridnour, Lisa A; Thomas, Douglas D; Donzelli, Sonia; Espey, Michael G; Roberts, David D; Wink, David A; Isenberg, Jeffrey S

    2006-01-01

    The dual or biphasic responses of cancer to nitric oxide (NO) arise from its concentration dependent ability to regulate tumor growth, migration, invasion, survival, angiogenesis, and metastasis. The outcome of these various NO-dependent processes is dictated by several factors including NO flux, the chemical redox environment, and the duration of NO exposure. Further, it was recently discovered that an NO-induced redox flux in vascular endothelial cells hypersensitizes these cells to the antiangiogenic effects of thrombospondin-1. This suggests a novel treatment paradigm for targeting tumor-driven angiogenesis that combines redox modulation with mimetic derivatives of thrombospondin-1. This article discusses the biphasic nature of NO in cancer biology and the implications of NO-driven redox flux for modulation of tumor-stimulated angiogenesis, growth, and metastasis.

  20. Thermoreversible (Ionic-Liquid-Based) Aqueous Biphasic Systems

    PubMed Central

    Passos, Helena; Luís, Andreia; Coutinho, João A. P.; Freire, Mara G.

    2016-01-01

    The ability to induce reversible phase transitions between homogeneous solutions and biphasic liquid-liquid systems, at pre-defined and suitable operating temperatures, is of crucial relevance in the design of separation processes. Ionic-liquid-based aqueous biphasic systems (IL-based ABS) have demonstrated superior performance as alternative extraction platforms, and their thermoreversible behaviour is here disclosed by the use of protic ILs. The applicability of the temperature-induced phase switching is further demonstrated with the complete extraction of two value-added proteins, achieved in a single-step. It is shown that these temperature-induced mono(bi)phasic systems are significantly more versatile than classical liquid-liquid systems which are constrained by their critical temperatures. IL-based ABS allow to work in a wide range of temperatures and compositions which can be tailored to fit the requirements of a given separation process. PMID:26843320

  1. Time-engineeringed biphasic drug release by electrospun nanofiber meshes.

    PubMed

    Huang, Li-Ya; Branford-White, Christopher; Shen, Xia-Xia; Yu, Deng-Guang; Zhu, Li-Min

    2012-10-15

    A drug-loaded nanofiber mesh which could achieve time-engineeringed biphasic release was fabricated through sequential electrospinning. The drug to polymer ratio of each single mesh was allocated and designed before the tri-layered meshes were created. The resultant meshes had the following construction: (i) the first drug-loaded mesh (top side), (ii) the second drug-loaded mesh (second side), and (iii) the third drug-loaded mesh (bottom side). The drug release speed and duration were controlled by designing morphological features of the electrospun meshes such as the fiber diameter and mesh thickness. An in vitro release experiment revealed that the tri-layered construction with distinct morphological features of each component mesh can provide biphasic drug release. The time-engineeringed dual release system using the multilayered electrospun nanofiber meshes was proved to be a useful formulation when achieving controlled drug release at different times. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Thermoreversible (Ionic-Liquid-Based) Aqueous Biphasic Systems.

    PubMed

    Passos, Helena; Luís, Andreia; Coutinho, João A P; Freire, Mara G

    2016-02-04

    The ability to induce reversible phase transitions between homogeneous solutions and biphasic liquid-liquid systems, at pre-defined and suitable operating temperatures, is of crucial relevance in the design of separation processes. Ionic-liquid-based aqueous biphasic systems (IL-based ABS) have demonstrated superior performance as alternative extraction platforms, and their thermoreversible behaviour is here disclosed by the use of protic ILs. The applicability of the temperature-induced phase switching is further demonstrated with the complete extraction of two value-added proteins, achieved in a single-step. It is shown that these temperature-induced mono(bi)phasic systems are significantly more versatile than classical liquid-liquid systems which are constrained by their critical temperatures. IL-based ABS allow to work in a wide range of temperatures and compositions which can be tailored to fit the requirements of a given separation process.

  3. Thermoreversible (Ionic-Liquid-Based) Aqueous Biphasic Systems

    NASA Astrophysics Data System (ADS)

    Passos, Helena; Luís, Andreia; Coutinho, João A. P.; Freire, Mara G.

    2016-02-01

    The ability to induce reversible phase transitions between homogeneous solutions and biphasic liquid-liquid systems, at pre-defined and suitable operating temperatures, is of crucial relevance in the design of separation processes. Ionic-liquid-based aqueous biphasic systems (IL-based ABS) have demonstrated superior performance as alternative extraction platforms, and their thermoreversible behaviour is here disclosed by the use of protic ILs. The applicability of the temperature-induced phase switching is further demonstrated with the complete extraction of two value-added proteins, achieved in a single-step. It is shown that these temperature-induced mono(bi)phasic systems are significantly more versatile than classical liquid-liquid systems which are constrained by their critical temperatures. IL-based ABS allow to work in a wide range of temperatures and compositions which can be tailored to fit the requirements of a given separation process.

  4. Biophysical shunt theory for neuropsychopathology: biphasal homeostatic dysregulation.

    PubMed

    Naisberg, Y; Weizman, A

    1999-03-01

    We challenge Freud's psychodynamic theory using a systematic modus operandi which has been outlined in detail in a succession of articles. Here, we deal with Freud's first assumption of human psychological primacy in forming goal-directed behavior. According to our theory, biphasal homeostatic dysregulation is the underlying mechanism of clinical phenomenology. Evolutionary neurobiology has provided humans with a precise technical solution for optimal organismic survival. Humans are armed with an accurate negative feedback mechanism that operates within the alternating upper and lower thresholds of biphasal homeostatic maintenance and is coupled with a basal indicator of individual sensation of the degree of the given organismic well-being in any unit of time. This originates the organismic pleasure principle (OPP). The latter is achieved by a straightforward quantal injection of endorphins according to one of eight possible body operational regimens. Thanks to the essential duality of the dynamic interactions, stipulated by the complex harmonics of term-dependent and event-dependent adaptation when one or more of the essential elements for homeostasis goes above or below its predetermined threshold, certain branches of the organismic defense system (ODS) are 'turned on' in the second phase of homeostasis. The individual then adapts behavioral modifications directed toward a long-lasting search for the optimal resources needed for normal survival. This evolutionary biphasal homeostatic design has an intrinsic, methodical expression that confirms changes and correctly informs the individual about them, further imposing behavioral modifications, when necessary. In cases of a homeostatic derangement, the OPP is replaced by an erratic inclusion of pain, tension or depression, all components of the alarm system of the ODS, which may lead to disordered behavioral patterns. The underlying biological mechanism of goal-directed assignments for biphasal homeostatic

  5. Biphasic dose response in low level light therapy.

    PubMed

    Huang, Ying-Ying; Chen, Aaron C-H; Carroll, James D; Hamblin, Michael R

    2009-09-01

    The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.

  6. Actinide recovery using aqueous biphasic extraction: Initial developmental studies

    SciTech Connect

    Chaiko, D.J.; Mensah-Biney, R.; Mertz, C.J.; Rollins, A.N.

    1992-08-01

    Aqueous biphasic extraction systems are being developed to treat radioactive wastes. The separation technique involves the selective partitioning of either solutes or colloid-size particles between two scible aqueous phases. Wet grinding of plutonium residues to an average particle size of one micron will be used to liberate the plutonium from the bulk of the particle matrix. The goal is to produce a plutonium concentrate that will integrate with existing and developing chemical recovery processes. Ideally, the process would produce a nonTRU waste stream. Coupling physical beneficiation with chemical processing will result in a substantial reduction in the volume of mixed wastes generated from dissolution recovery processes. As part of this program, we will also explore applications of aqueous biphasic extraction that include the separation and recovery of dissolved species such as metal ions and water-soluble organics. The expertise and data generated in this work will form the basis for developing more cost-effective processes for handling waste streams from environmental restoration and waste management activities within the DOE community. This report summarizes the experimental results obtained during the first year of this effort. Experimental efforts were focused on elucidating the surface and solution chemistry variables which govern partitioning behavior of plutonium and silica in aqueous biphasic extraction systems. Additional efforts were directed toward the development of wet grinding methods for producing ultrafine particles with diameters of one micron or less.

  7. Actinide recovery using aqueous biphasic extraction: Initial developmental studies

    SciTech Connect

    Chaiko, D.J.; Mensah-Biney, R.; Mertz, C.J.; Rollins, A.N.

    1992-08-01

    Aqueous biphasic extraction systems are being developed to treat radioactive wastes. The separation technique involves the selective partitioning of either solutes or colloid-size particles between two scible aqueous phases. Wet grinding of plutonium residues to an average particle size of one micron will be used to liberate the plutonium from the bulk of the particle matrix. The goal is to produce a plutonium concentrate that will integrate with existing and developing chemical recovery processes. Ideally, the process would produce a nonTRU waste stream. Coupling physical beneficiation with chemical processing will result in a substantial reduction in the volume of mixed wastes generated from dissolution recovery processes. As part of this program, we will also explore applications of aqueous biphasic extraction that include the separation and recovery of dissolved species such as metal ions and water-soluble organics. The expertise and data generated in this work will form the basis for developing more cost-effective processes for handling waste streams from environmental restoration and waste management activities within the DOE community. This report summarizes the experimental results obtained during the first year of this effort. Experimental efforts were focused on elucidating the surface and solution chemistry variables which govern partitioning behavior of plutonium and silica in aqueous biphasic extraction systems. Additional efforts were directed toward the development of wet grinding methods for producing ultrafine particles with diameters of one micron or less.

  8. Biphasic interaction of Triton detergents with the erythrocyte membrane.

    PubMed Central

    Trägner, D; Csordas, A

    1987-01-01

    Octylphenoxy polyoxyethylene ethers (Triton detergents) interact with the erythrocyte membrane in a biphasic manner, i.e. they stabilize erythrocytes against hypo-osmotic haemolysis at low concentrations (0.0001-0.01%, v/v), but become haemolytic at higher concentrations. This biphasic behaviour was demonstrated with Triton X-114, Triton X-100 and Triton X-102. However, a critical chain length is a prerequisite for the haemolytic effect, because Triton X-45, which differs from the other Tritons only by the shorter chain of the polyoxyethylene residue, does not exhibit this biphasic behaviour, but goes on protecting against osmotic rupture up to saturating concentrations. Even a 1% solution of Triton X-45 does not cause haemolysis. This structural specificity of Triton X-45, namely the lack of haemolysis and efficient stabilization against osmolysis even at higher concentrations of the detergent, is exhibited at 0 degree and 37 degrees C as well as at room temperature. Three conclusions are reached: (i) a critical chain length of the octylphenoxy polyoxyethylene ethers is required for the haemolytic effect; (ii) the different structural requirements would suggest that different mechanisms are responsible for the haemolytic and the stabilizing effect of amphiphilic substances; (iii) the results suggest that haemolysis is not caused simply by dissolution of the membrane by the detergent but is a rather more specific process. PMID:3446180

  9. Biphasic Dose Response in Low Level Light Therapy

    PubMed Central

    Huang, Ying-Ying; Chen, Aaron C.-H.; Carroll, James D.; Hamblin, Michael R.

    2009-01-01

    The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response. PMID:20011653

  10. Biphasic NF-kappaB activation in the excitotoxic hippocampus.

    PubMed

    Caba, Ebru; Bahr, Ben A

    2004-09-01

    Excitotoxic stimulation of NMDA receptors results in the activation of a variety of cellular responses. The inducible transcription factor NF-kappaB is known to be involved in excitotoxic responses by neurons. Here, we show that NF-kappaB activation occurs in a biphasic manner in hippocampal slices following a 20-min N-methyl- d-aspartate (NMDA) exposure. The biphasic activation profile consists of an early, rapid phase at 0.5-1 h post-insult, and a delayed phase evident 10-24 h post-insult. Endogenous inhibitors of NF-kappaB, IkappaBs, were examined for their involvement in the biphasic activation. IkappaBbeta exhibited marked degradation in response to the excitotoxity, while changes in the levels of IkappaBalpha and p105 isoforms were not detected. The initial decline in IkappaBbeta occurred in as little as 30 min post-NMDA exposure, coinciding with early NF-kappaB activity. A second, more gradual phase of IkappaBbeta degradation was also evident, possibly giving rise to the delayed activation of the transcription factor. While both phases of NF-kappaB activation were disrupted by the NMDA receptor antagonist AP5, they were distinct with regard to the composition of activated complexes and their responsiveness to altered culture conditions. The two phases of NF-kappaB activity also were associated with distinct gene regulation events. Up-regulation of bcl-2 message occurred early after the excitotoxic insult and remained up-regulated for an extended period. In contrast, bax message initially remained unchanged after the insult, but then exhibited an increase 24 h later, corresponding with the second phase of the NF-kappaB response. These results indicate that distinct phases of NF-kappaB activation are generated in the excitotoxic hippocampus, and that the phases may be involved in opposing cellular responses.

  11. Biphasic enantioselective olefin epoxidation using Tropos dibenzoazepinium catalysts.

    PubMed

    Vachon, Jérôme; Pérollier, Céline; Monchaud, David; Marsol, Claire; Ditrich, Klaus; Lacour, Jérôme

    2005-07-22

    Several novel chiral iminium TRISPHAT [tris(tetrachlorobenzenediolato)phosphate(V)] salts combining a diphenylazepinium core, chiral exocyclic appendages, and lipophilic counterions have been prepared and tested in biphasic enantioselective olefin epoxidation conditions. Interestingly, the iminium salts derived from commercially available (S)- or (R)-1,2,2-trimethylpropylamine can display efficiency similar to those made from L-acetonamine. Variable-temperature NMR spectroscopy (VT-NMR) and circular dichroism (CD) experiments were performed in search of a correlation between good enantioselectivity in the products and high diastereomeric control of the biphenyl axial chirality of the catalysts.

  12. Cell–material interactions on biphasic polyurethane matrix

    PubMed Central

    Dicesare, Patrick; Fox, Wade M.; Hill, Michael J.; Krishnan, G. Rajesh; Yang, Shuying; Sarkar, Debanjan

    2013-01-01

    Cell–matrix interaction is a key regulator for controlling stem cell fate in regenerative tissue engineering. These interactions are induced and controlled by the nanoscale features of extracellular matrix and are mimicked on synthetic matrices to control cell structure and functions. Recent studies have shown that nanostructured matrices can modulate stem cell behavior and exert specific role in tissue regeneration. In this study, we have demonstrated that nanostructured phase morphology of synthetic matrix can control adhesion, proliferation, organization and migration of human mesenchymal stem cells (MSCs). Nanostructured biodegradable polyurethanes (PU) with segmental composition exhibit biphasic morphology at nanoscale dimensions and can control cellular features of MSCs. Biodegradable PU with polyester soft segment and hard segment composed of aliphatic diisocyanates and dipeptide chain extender were designed to examine the effect polyurethane phase morphology. By altering the polyurethane composition, morphological architecture of PU was modulated and its effect was examined on MSC. Results show that MSCs can sense the nanoscale morphology of biphasic polyurethane matrix to exhibit distinct cellular features and, thus, signifies the relevance of matrix phase morphology. The role of nanostructured phases of a synthetic matrix in controlling cell–matrix interaction provides important insights for regulation of cell behavior on synthetic matrix and, therefore, is an important tool for engineering tissue regeneration. PMID:23255285

  13. Biphasic behavior of energy in a stepped chain

    NASA Astrophysics Data System (ADS)

    Ping-Jian, Wang; Ai-Xiang, He; Zhong-Hai, Lin; Guang-Fen, Wei; Yan-Li, Liu

    2016-06-01

    The impact energy decay in a step-up chain containing two sections is numerically studied. There is a marked biphasic behavior of energy decay in the first section. Two sections close to the interface are in compression state. The degree of compression of the first section first decreases and becomes weakest at “crossing” time of biphasic behavior of energy, then increases. The further calculations provide the dependence of the character time on mass ratio (m 1/m 2), where m 1 and m 2 are the particle mass in the first and second section respectively. The bigger the α (α = [(Ωm 1 - m 2)/(Ωm 1 + m 2)]2 with Ω = 1.345), the bigger the energy ratio is. The multipulse structure restricts the transport of energy. Project supported by the National Natural Science Foundation of China (Grant Nos. 61174007 and 61307041) and the Natural Science Foundation of Shandong Province, China (Grant No. ZR2013AL014).

  14. Biphasic patterns of diversification and the emergence of modules

    PubMed Central

    Mittenthal, Jay; Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

    2012-01-01

    The intricate molecular and cellular structure of organisms converts energy to work, which builds and maintains structure. Evolving structure implements modules, in which parts are tightly linked. Each module performs characteristic functions. In this work we propose that a module can emerge through two phases of diversification of parts. Early in the first phase of this biphasic pattern, the parts have weak linkage—they interact weakly and associate variously. The parts diversify and compete. Under selection for performance, interactions among the parts increasingly constrain their structure and associations. As many variants are eliminated, parts self-organize into modules with tight linkage. Linkage may increase in response to exogenous stresses as well as endogenous processes. In the second phase of diversification, variants of the module and its functions evolve and become new parts for a new cycle of generation of higher-level modules. This linkage hypothesis can interpret biphasic patterns in the diversification of protein domain structure, RNA and protein shapes, and networks in metabolism, codes, and embryos, and can explain hierarchical levels of structural organization that are widespread in biology. PMID:22891076

  15. A New Biphasic Dicalcium Silicate Bone Cement Implant

    PubMed Central

    Murciano, Angel; Maté-Sánchez de Val, José E.

    2017-01-01

    This study aimed to investigate the processing parameters and biocompatibility of a novel biphasic dicalcium silicate (C2S) cement. Biphasic α´L + β-C2Sss was synthesized by solid-state processing, and was used as a raw material to prepare the cement. In vitro bioactivity and biocompatibility studies were assessed by soaking the cement samples in simulated body fluid (SBF) and human adipose stem cell cultures. Two critical-sized defects of 6 mm Ø were created in 15 NZ tibias. A porous cement made of the high temperature forms of C2S, with a low phosphorous substitution level, was produced. An apatite-like layer covered the cement’s surface after soaking in SBF. The cell attachment test showed that α´L + β-C2Sss supported cells sticking and spreading after 24 h of culture. The cement paste (55.86 ± 0.23) obtained higher bone-to-implant contact (BIC) percentage values (better quality, closer contact) in the histomorphometric analysis, and defect closure was significant compared to the control group (plastic). The residual material volume of the porous cement was 35.42 ± 2.08% of the initial value. The highest BIC and bone formation percentages were obtained on day 60. These results suggest that the cement paste is advantageous for initial bone regeneration. PMID:28773119

  16. A New Biphasic Dicalcium Silicate Bone Cement Implant.

    PubMed

    Zuleta, Fausto; Murciano, Angel; Gehrke, Sergio A; Maté-Sánchez de Val, José E; Calvo-Guirado, José L; De Aza, Piedad N

    2017-07-06

    This study aimed to investigate the processing parameters and biocompatibility of a novel biphasic dicalcium silicate (C₂S) cement. Biphasic α´L + β-C₂Sss was synthesized by solid-state processing, and was used as a raw material to prepare the cement. In vitro bioactivity and biocompatibility studies were assessed by soaking the cement samples in simulated body fluid (SBF) and human adipose stem cell cultures. Two critical-sized defects of 6 mm Ø were created in 15 NZ tibias. A porous cement made of the high temperature forms of C₂S, with a low phosphorous substitution level, was produced. An apatite-like layer covered the cement's surface after soaking in SBF. The cell attachment test showed that α´L + β-C₂Sss supported cells sticking and spreading after 24 h of culture. The cement paste (55.86 ± 0.23) obtained higher bone-to-implant contact (BIC) percentage values (better quality, closer contact) in the histomorphometric analysis, and defect closure was significant compared to the control group (plastic). The residual material volume of the porous cement was 35.42 ± 2.08% of the initial value. The highest BIC and bone formation percentages were obtained on day 60. These results suggest that the cement paste is advantageous for initial bone regeneration.

  17. Biphasic cardiovascular and respiratory effects induced by β-citronellol.

    PubMed

    Ribeiro-Filho, Helder Veras; de Souza Silva, Camila Meirelles; de Siqueira, Rodrigo JoséBezerra; Lahlou, Saad; dos Santos, Armênio Aguiar; Magalhães, Pedro Jorge Caldas

    2016-03-15

    β-Citronellol is a monoterpene found in the essential oil of various plants with antihypertensive properties. In fact, β-citronellol possesses hypotensive actions due to its vasodilator abilities. Here we aimed to show that β-citronellol recruits airway sensory neural circuitry to evoke cardiorespiratory effects. In anesthetized rats, intravenous injection of β-citronellol caused biphasic hypotension, bradycardia and apnea. Bilateral vagotomy, perivagal capsaicin treatment or injection into the left ventricle abolished first rapid phase (named P1) but not delayed phase P2 of the β-citronellol effects. P1 persisted after pretreatment with capsazepine, ondansetron, HC-030031 or suramin. Suramin abolished P2 of apnea. In awake rats, β-citronellol induced biphasic hypotension and bradycardia being P1 abolished by methylatropine. In vitro, β-citronellol inhibited spontaneous or electrically-evoked contractions of rat isolated right or left atrium, respectively, and fully relaxed sustained contractions of phenylephrine in mesenteric artery rings. In conclusion, chemosensitive pulmonary vagal afferent fibers appear to mediate the cardiovascular and respiratory effects of β-citronellol. The transduction mechanism in P1 seems not to involve the activation of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential ankyrin subtype 1 (TRPA1), purinergic (P2X) or 5-HT3 receptors located on airways sensory nerves. P2 of hypotension and bradycardia seems resulting from a cardioinhibitory and vasodilatory effect of β-citronellol and the apnea from a purinergic signaling.

  18. Biphasic Affinity Chromatographic Approach for Deep Tyrosine Phosphoproteome Analysis.

    PubMed

    Deng, Zhenzhen; Dong, Mingming; Wang, Yan; Dong, Jing; Li, Shawn S-C; Zou, Hanfa; Ye, Mingliang

    2017-02-21

    Tyrosine phosphorylation (pTyr) is important for normal physiology and implicated in many human diseases, particularly cancer. Identification of pTyr sites is critical to dissecting signaling pathways and understanding disease pathologies. However, compared with serine/threonine phosphorylation (pSer/pThr), the analysis of pTyr at the proteome level is more challenging due to its low abundance. Here, we developed a biphasic affinity chromatographic approach where Src SH2 superbinder was coupled with NeutrAvidin affinity chromatography, for tyrosine phosphoproteome analysis. With the use of competitive elution agent biotin-pYEEI, this strategy can distinguish high-affinity phosphotyrosyl peptides from low-affinity ones, while the excess competitive agent is readily removed by using NeutrAvidin agarose resin in an integrated tip system. The excellent performance of this system was demonstrated by analyzing tyrosine phosphoproteome of Jurkat cells from which 3,480 unique pTyr sites were identified. The biphasic affinity chromatography method for deep Tyr phosphoproteome analysis is rapid, sensitive, robust, and cost-effective. It is widely applicable to the global analysis of the tyrosine phosphoproteome associated with tyrosine kinase signal transduction.

  19. Development and Characterization of Biphasic Hydroxyapatite/β-TCP Cements.

    PubMed

    Gallinetti, Sara; Canal, Cristina; Ginebra, Maria-Pau; Ferreira, J

    2014-04-01

    Biphasic calcium phosphate bioceramics composed of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) have relevant properties as synthetic bone grafts, such as tunable resorption, bioactivity, and intrinsic osteoinduction. However, they have some limitations associated to their condition of high-temperature ceramics. In this work self-setting Biphasic Calcium Phosphate Cements (BCPCs) with different HA/β-TCP ratios were obtained from self-setting α-TCP/β-TCP pastes. The strategy used allowed synthesizing BCPCs with modulated composition, compressive strength, and specific surface area. Due to its higher solubility, α-TCP was fully hydrolyzed to a calcium-deficient HA (CDHA), whereas β-TCP remained unreacted and completely embedded in the CDHA matrix. Increasing amounts of the non-reacting β-TCP phase resulted in a linear decrease of the compressive strength, in association to the decreasing amount of precipitated HA crystals, which are responsible for the mechanical consolidation of apatitic cements. Ca(2+) release and degradation in acidic medium was similar in all the BCPCs within the timeframe studied, although differences might be expected in longer term studies once β-TCP, the more soluble phase was exposed to the surrounding media.

  20. Cell-material interactions on biphasic polyurethane matrix.

    PubMed

    Dicesare, Patrick; Fox, Wade M; Hill, Michael J; Krishnan, G Rajesh; Yang, Shuying; Sarkar, Debanjan

    2013-08-01

    Cell-matrix interaction is a key regulator for controlling stem cell fate in regenerative tissue engineering. These interactions are induced and controlled by the nanoscale features of extracellular matrix and are mimicked on synthetic matrices to control cell structure and functions. Recent studies have shown that nanostructured matrices can modulate stem cell behavior and exert specific role in tissue regeneration. In this study, we have demonstrated that nanostructured phase morphology of synthetic matrix can control adhesion, proliferation, organization and migration of human mesenchymal stem cells (MSCs). Nanostructured biodegradable polyurethanes (PU) with segmental composition exhibit biphasic morphology at nanoscale dimensions and can control cellular features of MSCs. Biodegradable PU with polyester soft segment and hard segment composed of aliphatic diisocyanates and dipeptide chain extender were designed to examine the effect polyurethane phase morphology. By altering the polyurethane composition, morphological architecture of PU was modulated and its effect was examined on MSC. Results show that MSCs can sense the nanoscale morphology of biphasic polyurethane matrix to exhibit distinct cellular features and, thus, signifies the relevance of matrix phase morphology. The role of nanostructured phases of a synthetic matrix in controlling cell-matrix interaction provides important insights for regulation of cell behavior on synthetic matrix and, therefore, is an important tool for engineering tissue regeneration. Copyright © 2012 Wiley Periodicals, Inc.

  1. A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae

    PubMed Central

    Atack, John M.; Srikhanta, Yogitha N.; Fox, Kate L.; Jurcisek, Joseph A.; Brockman, Kenneth L.; Clark, Tyson A.; Boitano, Matthew; Power, Peter M.; Jen, Freda E.-C.; McEwan, Alastair G.; Grimmond, Sean M.; Smith, Arnold L.; Barenkamp, Stephen J.; Korlach, Jonas; Bakaletz, Lauren O.; Jennings, Michael P.

    2015-01-01

    Non-typeable Haemophilus influenzae contains an N6-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system. PMID:26215614

  2. A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.

    PubMed

    Atack, John M; Srikhanta, Yogitha N; Fox, Kate L; Jurcisek, Joseph A; Brockman, Kenneth L; Clark, Tyson A; Boitano, Matthew; Power, Peter M; Jen, Freda E-C; McEwan, Alastair G; Grimmond, Sean M; Smith, Arnold L; Barenkamp, Stephen J; Korlach, Jonas; Bakaletz, Lauren O; Jennings, Michael P

    2015-07-28

    Non-typeable Haemophilus influenzae contains an N(6)-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

  3. An augmented Lagrangian finite element formulation for 3D contact of biphasic tissues.

    PubMed

    Guo, Hongqiang; Spilker, Robert L

    2014-01-01

    Biphasic contact analysis is essential to obtain a complete understanding of soft tissue biomechanics, and the importance of physiological structure on the joint biomechanics has long been recognised; however, up to date, there are no successful developments of biphasic finite element contact analysis for three-dimensional (3D) geometries of physiological joints. The aim of this study was to develop a finite element formulation for biphasic contact of 3D physiological joints. The augmented Lagrangian method was used to enforce the continuity of contact traction and fluid pressure across the contact interface. The biphasic contact method was implemented in the commercial software COMSOL Multiphysics 4.2(®) (COMSOL, Inc., Burlington, MA). The accuracy of the implementation was verified using 3D biphasic contact problems, including indentation with a flat-ended indenter and contact of glenohumeral cartilage layers. The ability of the method to model multibody biphasic contact of physiological joints was proved by a 3D knee model. The 3D biphasic finite element contact method developed in this study can be used to study the biphasic behaviours of the physiological joints.

  4. Biphasic reactions in patients with anaphylaxis treated with corticosteroids.

    PubMed

    Ko, Byuk Sung; Kim, Won Young; Ryoo, Seung Mok; Ahn, Shin; Sohn, Chang Hwan; Seo, Dong-Woo; Lee, Yoon-Seon; Lim, Kyoung Soo; Kim, Tae-Bum

    2015-10-01

    Although the incidence of anaphylaxis is rapidly increasing, the clinical characteristics and associated factors of a biphasic reaction are unclear. To determine the incidence and clinical characteristics of biphasic reactions in patients with anaphylaxis treated with corticosteroids. A total of 655 patients with anaphylaxis visiting the emergency department of a tertiary teaching hospital from January 2007 through December 2014 were analyzed. Patient characteristics, triggers, symptoms and signs, in-hospital management, and disposition were recorded. A biphasic reaction was defined as the development of anaphylaxis after complete resolution of the initial reaction without further exposure to the offending agent within 7 days. Univariate and multivariate analyses on the predictors of the biphasic reaction were performed. Of the 415 patients with anaphylaxis treated with corticosteroids, 9 patients (2.2%) developed a biphasic reaction. The mean age was 48.4 years, and 221 patients (54.4%) were women. The median time from complete resolution of initial clinical symptoms to occurrence of the biphasic reaction was 15 hours (range 1-45). History of drug anaphylaxis (odds ratio 14.3, 95% confidence interval 2.4-85.8) was a contributing factor to the development of the biphasic reaction. The incidence of biphasic reactions was 2.2% in patients treated with corticosteroids and those with a history of drug anaphylaxis were at greater risk. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. miRNA profiling of high, low and non-producing CHO cells during biphasic fed-batch cultivation reveals process relevant targets for host cell engineering.

    PubMed

    Stiefel, Fabian; Fischer, Simon; Sczyrba, Alexander; Otte, Kerstin; Hesse, Friedemann

    2016-05-10

    Fed-batch cultivation of recombinant Chinese hamster ovary (CHO) cell lines is one of the most widely used production modes for commercial manufacturing of recombinant protein therapeutics. Furthermore, fed-batch cultivations are often conducted as biphasic processes where the culture temperature is decreased to maximize volumetric product yields. However, it remains to be elucidated which intracellular regulatory elements actually control the observed pro-productive phenotypes. Recently, several studies have revealed microRNAs (miRNAs) to be important molecular switches of cell phenotypes. In this study, we analyzed miRNA profiles of two different recombinant CHO cell lines (high and low producer), and compared them to a non-producing CHO DG44 host cell line during fed-batch cultivation at 37°C versus a temperature shift to 30°C. Taking advantage of next-generation sequencing combined with cluster, correlation and differential expression analyses, we could identify 89 different miRNAs, which were differentially expressed in the different cell lines and cultivation phases. Functional validation experiments using 19 validated target miRNAs confirmed that these miRNAs indeed induced changes in process relevant phenotypes. Furthermore, computational miRNA target prediction combined with functional clustering identified putative target genes and cellular pathways, which might be regulated by these miRNAs. This study systematically identified novel target miRNAs during different phases and conditions of a biphasic fed-batch production process and functionally evaluated their potential for host cell engineering.

  6. Evaluation of liquid biphasic Granada medium and instant liquid biphasic Granada medium for group B streptococcus detection.

    PubMed

    Martinho, Filipa; Prieto, Emília; Pinto, Dulce; Castro, Rita Maria; Morais, Ana Maria; Salgado, Luísa; Exposto, Filomena da Luz

    2008-02-01

    Group B streptococci (GBS) are transmitted from the mother to the newborn. Prevention of neonatal infection is achieved by intrapartum prophylaxis given to mothers colonized with GBS at 35 to 37 weeks of pregnancy. Liquid biphasic Granada medium (LB) and instant liquid biphasic Granada medium (ILB) were evaluated for GBS detection. Vaginal swabs obtained from 300 women were inoculated onto LB or ILB, or onto Todd-Hewitt broth and analyzed with the ATB system (comparison method). Prevalence of GBS was 20% (61/300). LB and Todd-Hewitt with ATB detected GBS in 20% of women, and ILB in 19% of women. No growth was observed at four hours in any of the media studied. At 10 h and 14 h, identification of GBS was possible in 43/300 (14%) and 53/300 (18%) of ILB cultures, respectively, and in 32/300 (11%) and 46/300 (15%) of LB cultures. All the media used are suitable for GBS detection. The majority of GBS were identified in ILB and LB cultures at 10 h and 14 h.

  7. Oscillatory Motion of a Bi-Phasic Slug in a Teflon Reactor

    NASA Astrophysics Data System (ADS)

    Abolhasani, Milad; Jensen, Klavs

    2015-11-01

    Bi-phasic physical/chemical processes require transfer of solute/reagent molecules across the interface. Continuous multi-phase flow approaches (using gas as the continuous phase), usually fail in providing sufficient interfacial area for transfer of molecules between the aqueous and organic phases. In continuous segmented flow platforms (with a fluorinated polymer-based reactor), the higher surface tension of the aqueous phase compared to the organic phase of a bi-phasic slug, in combination with the low surface energy of the reactor wall result in a more facile motion of the aqueous phase. Thus, upon applying a pressure gradient across the bi-phasic slug, the aqueous phase of the slug moves through the organic phase and leads the bi-phasic slug, thereby limiting the available interfacial area for the bi-phasic mass transfer only to the semi-spherical interface between the two phases. Disrupting the quasi-equilibrium state of the bi-phasic slug through reversing the pressure gradient across the bi-phasic slug causes the aqueous phase to move back through the organic phase. In this work, we experimentally investigate the dynamics of periodic alteration of the pressure gradient across a bi-phasic slug, and characterize the resulting enhanced interfacial area on the bi-phasic mass transfer rate. We demonstrate the enhanced mass transfer rate of the oscillatory flow strategy compared to the continuous multi-phase approach using bi-phasic Pd catalyzed carbon-carbon and carbon-nitrogen cross coupling reactions. NSERC Postdoctoral Fellowship, Novartis Center for Continuous Manufacturing.

  8. Predictors of biphasic reactions in the emergency department for patients with anaphylaxis.

    PubMed

    Lee, Sangil; Bellolio, M Fernanda; Hess, Erik P; Campbell, Ronna L

    2014-01-01

    A biphasic reaction is the recurrence of anaphylaxis symptoms within 72 hours of the initial anaphylactic event, without re-exposure to the trigger. Biphasic reactions are uncommon and unpredictable, and risk factors for biphasic reactions are poorly understood. To identify predictors of biphasic anaphylactic reactions in patients with anaphylaxis in the emergency department (ED). Patients of all ages who presented to the ED and met diagnostic criteria for anaphylaxis from April 2008 to January 2013 at an academic medical center with 73,000 annual patient visits were consecutively included. We collected data on patient characteristics, suspected triggers, signs and symptoms, ED management, and disposition. Univariate analyses were performed to estimate the association between potential predictor variables and biphasic reactions. We report associations as odds ratios (OR) and corresponding 95% CIs. Among 541 patients with anaphylaxis, median age was 34.6 years (interquartile range, 18-52 years), and 320 (59%) were female patients. Twenty-one patients (4%) had biphasic reactions. Two pediatric patients, ages of 5 years old and 16 years old, developed a biphasic reaction. The median time between the resolution of initial symptoms and onset of the biphasic reaction was 7 hours (range, 1-72 hours). Biphasic reactions were associated with a history of prior anaphylaxis (OR 2.6 [95% CI, 1.1-6.4]; P = .029), unknown precipitant (OR 2.6 [95% CI, 1.1-6.2]; P = .03), symptoms of diarrhea (OR 4.5 [95% CI, 1.4-14.0]; P = .024), and wheezing (OR 2.6 [95% CI, 1.4-8.9]; P = .029). Patients with a history of prior anaphylaxis, an unknown precipitant, or who present with symptoms of diarrhea or wheezing may be at increased risk for a biphasic reaction. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. A novel clinical tool to classify facioscapulohumeral muscular dystrophy phenotypes.

    PubMed

    Ricci, Giulia; Ruggiero, Lucia; Vercelli, Liliana; Sera, Francesco; Nikolic, Ana; Govi, Monica; Mele, Fabiano; Daolio, Jessica; Angelini, Corrado; Antonini, Giovanni; Berardinelli, Angela; Bucci, Elisabetta; Cao, Michelangelo; D'Amico, Maria Chiara; D'Angelo, Grazia; Di Muzio, Antonio; Filosto, Massimiliano; Maggi, Lorenzo; Moggio, Maurizio; Mongini, Tiziana; Morandi, Lucia; Pegoraro, Elena; Rodolico, Carmelo; Santoro, Lucio; Siciliano, Gabriele; Tomelleri, Giuliano; Villa, Luisa; Tupler, Rossella

    2016-06-01

    Based on the 7-year experience of the Italian Clinical Network for FSHD, we revised the FSHD clinical form to describe, in a harmonized manner, the phenotypic spectrum observed in FSHD. The new Comprehensive Clinical Evaluation Form (CCEF) defines various clinical categories by the combination of different features. The inter-rater reproducibility of the CCEF was assessed between two examiners using kappa statistics by evaluating 56 subjects carrying the molecular marker used for FSHD diagnosis. The CCEF classifies: (1) subjects presenting facial and scapular girdle muscle weakness typical of FSHD (category A, subcategories A1-A3), (2) subjects with muscle weakness limited to scapular girdle or facial muscles (category B subcategories B1, B2), (3) asymptomatic/healthy subjects (category C, subcategories C1, C2), (4) subjects with myopathic phenotype presenting clinical features not consistent with FSHD canonical phenotype (D, subcategories D1, D2). The inter-rater reliability study showed an excellent concordance of the final four CCEF categories with a κ equal to 0.90; 95 % CI (0.71; 0.97). Absolute agreement was observed for categories C and D, an excellent agreement for categories A [κ = 0.88; 95 % CI (0.75; 1.00)], and a good agreement for categories B [κ = 0.79; 95 % CI (0.57; 1.00)]. The CCEF supports the harmonized phenotypic classification of patients and families. The categories outlined by the CCEF may assist diagnosis, genetic counseling and natural history studies. Furthermore, the CCEF categories could support selection of patients in randomized clinical trials. This precise categorization might also promote the search of genetic factor(s) contributing to the phenotypic spectrum of disease.

  10. Injectable biphasic calcium phosphate bioceramic: The HYDROS concept.

    PubMed

    Baroth, Serge; Bourges, Xavier; Goyenvalle, Eric; Aguado, Eric; Daculsi, Guy

    2009-01-01

    A new biphasic calcium phosphate ceramic material has been developed in our laboratory. It is composed of 60% of hydroxyapatite and 40% of beta-tricalcium phosphate, based on three granulometries (submicron, round microporous 80-200 mum and macro microporous 0.5-1 mm particles) and hydrated with water leading the formation of a putty filler for bone repair. Biocompatibility and osteogenicity were tested by filling femoral epiphyses critical size bone defect and lumbar muscles in rabbit. After 3, 6 and 12 weeks of implantation, explants were treated for histology. Results revealed the biocompatibility of the material and intensive resorption of the submicron particle fraction followed by important bone ingrowth whereas osteoconduction was provided by the larger particles.

  11. High-side Digitally Current Controlled Biphasic Bipolar Microstimulator

    PubMed Central

    Hanson, Timothy L.; Ómarsson, Björn; O'Doherty, Joseph E.; Peikon, Ian D.; Lebedev, Mikhail; Nicolelis, Miguel AL.

    2012-01-01

    Electrical stimulation of nervous tissue has been extensively used as both a tool in experimental neuroscience research and as a method for restoring of neural functions in patients suffering from sensory and motor disabilities. In the central nervous system, intracortical microstimulation (ICMS) has been shown to be an effective method for inducing or biasing perception, including visual and tactile sensation. ICMS also holds promise for enabling brain-machine-brain interfaces (BMBIs) by directly writing information into the brain. Here we detail the design of a high-side, digitally current-controlled biphasic, bipolar microstimulator, and describe the validation of the device in vivo. As many applications of this technique, including BMBIs, require recording as well as stimulation, we pay careful attention to isolation of the stimulus channels and parasitic current injection. With the realized device and standard recording hardware - without active artifact rejection - we are able to observe stimulus artifacts of less than 2 ms in duration. PMID:22328184

  12. Surface modification of biphasic calcium phosphate bioceramic powders

    NASA Astrophysics Data System (ADS)

    Yang, W. Z.; Zhou, D. L.; Yin, G. F.; Li, G. D.

    2008-11-01

    Biphasic calcium phosphate (BCP)/poly L-lactide (PLLA) biocomposite is proven to be a promising bone graft material or scaffold for bone tissue engineering. To improve the interfacial compatibility of BCP bioceramic with biopolymer-PLLA, BCP powders were surface-modified in different condition to graft polymer groups onto the surface of the BCP powders. L-lactide and L-lactic acid (LA) oligomer were used to modify the BCP surface with stannous octanoate (Sn(Oct) 2) and stannous chloride (SnCl 2) as catalyst, respectively. Results show that the surface modification effect is obvious and the amount of grafted organic group is above 6.5 wt.%. Sn(Oct) 2 and SnCl 2 are the optimal catalysts for the surface grafting reaction of L-lactide and L-LA oligomer, respectively. The surface grafting slightly increase the particle size of BCP powders and reduce the tendency for their agglomeration.

  13. High-side digitally current controlled biphasic bipolar microstimulator.

    PubMed

    Hanson, Timothy L; Ómarsson, Björn; O'Doherty, Joseph E; Peikon, Ian D; Lebedev, Mikhail A; Nicolelis, Miguel A L

    2012-05-01

    Electrical stimulation of nervous tissue has been extensively used as both a tool in experimental neuroscience research and as a method for restoring of neural functions in patients suffering from sensory and motor disabilities. In the central nervous system, intracortical microstimulation (ICMS) has been shown to be an effective method for inducing or biasing perception, including visual and tactile sensation. ICMS also holds promise for enabling brain-machine-brain interfaces (BMBIs) by directly writing information into the brain. Here we detail the design of a high-side, digitally current-controlled biphasic, bipolar microstimulator, and describe the validation of the device in vivo. As many applications of this technique, including BMBIs, require recording as well as stimulation, we pay careful attention to isolation of the stimulus channels and parasitic current injection. With the realized device and standard recording hardware-without active artifact rejection-we are able to observe stimulus artifacts of less than 2 ms in duration.

  14. AQUEOUS BIPHASE EXTRACTION FOR PROCESSING OF FINE COAL

    SciTech Connect

    K. Osseo-Asare; X. Zeng

    2001-06-30

    Ever-stringent environmental constraints dictate that future coal cleaning technologies be compatible with micron-size particles. This research program seeks to develop an advanced coal cleaning technology uniquely suited to micron-size particles, i.e., aqueous biphase extraction. The partitioning behaviors of hematite in the dextran (Dex)/Triton X-100 (TX100) and polyethylene glycol (PEG)/dextran systems were investigated and the effects of some ionic surfactants on solid partition were studied. In both biphase systems, the particles stayed in the bottom dextran-rich phase under all pH conditions. This behavior is attributable to the fact that the hydrophilic oxide particles prefer the more hydrophilic bottom phase. Also, the strong favorable interaction between dextran and ferric oxide facilitates the dispersion of the solids in the polysaccharide-rich phase. In the Dex/TX100 system, addition of sodium dodecylsulfate (SDS) or potassium oleate had no effect on the solid partition; on the other hand, addition of dodecyltrimethylammonium bromide (DTAB) transferred the particles to the top phase or interface at high pH values. In the PEG/Dex system, the preferred location of hematite remained the bottom phase in the presence of either SDS or DTAB. The effects of anionic surfactants on the partition behavior are attributable to the fact that they are not able to replace the strongly adsorbed polysaccharide layer on the ferric oxide surface. The results with the cationic surfactant are due to electrostatic interaction between the cationic surfactant and the charged surface of the solid particles. The difference in solids partitioning in the two systems is the result of the different distribution of DTAB in these systems. In the Dex/TX100 system, DTAB prefers the top surfactant-rich phase, while it concentrates in the bottom phase in the PEG/dextran system.

  15. Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways

    PubMed Central

    Alvau, Antonio; Escoffier, Jessica; Krapf, Dario; Sánchez-Cárdenas, Claudia; Salicioni, Ana M.; Darszon, Alberto; Visconti, Pablo E.

    2016-01-01

    Mammalian sperm acquire fertilizing ability in the female tract in a process known as capacitation. At the molecular level, capacitation is associated with up-regulation of a cAMP-dependent pathway, changes in intracellular pH, intracellular Ca2+ and an increase in tyrosine phosphorylation. How these signaling systems interact during capacitation is not well understood. Results presented in this study indicate that Ca2+ ions have a biphasic role in the regulation of cAMP-dependent signaling. Media without added Ca2+ salts (nominal zero Ca2+) still contain micromolar concentrations of this ion. Sperm incubated in this medium did not undergo PKA activation or the increase in tyrosine phosphorylation suggesting that these phosphorylation pathways require Ca2+. However, chelation of the extracellular Ca2+ traces by EGTA induced both cAMP-dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA effect in nominal zero Ca2+ media was mimicked by two calmodulin antagonists, W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These results suggest that Ca2+ ions regulate sperm cAMP and tyrosine phosphorylation pathways in a biphasic manner and that some of its effects are mediated by calmodulin. Interestingly, contrary to wild type mouse sperm, sperm from CatSper1 KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon incubation in nominal zero Ca2+ media. Therefore, sperm lacking Catsper Ca2+ channels behave as wild-type sperm incubated in the presence of EGTA. This latter result suggests that Catsper transports the Ca2+ involved in the regulation of cAMP-dependent and tyrosine phosphorylation pathways required for sperm capacitation. PMID:25597298

  16. Biphasic effects of losartan potassium on immobility in mice.

    PubMed

    Vijayapandi, Pandi; Nagappa, Anantha Naik

    2005-08-01

    The effects of losartan potassium, an angiotensin AT(1) receptor blocker on immobility in forced swim test have been studied. Effect of losartan potassium, nortriptyline HCl, fluoxetine HCl and reserpine per se and in combination on forced swimming-induced immobility in mice have also been studied. In mice, losartan potassium elicits biphasic responses i.e. positive responses at lower doses (0.1, 1.0 and 5 mg/kg, i.p.) in the forced swim test, a test of potential antidepressant activity and vice versa at higher dose (20 and 100 mg/kg, i.p.). In chronic studies, enhancement in immobility was observed for losartan potassium (3 and 30 mg/kg, p.o., 21 days). In acute combination studies, losartan potassium (1 and 5 mg/kg) significantly reversed the reserpine-induced immobility, but vice versa at 100 mg/kg. Losartan potassium (0.1 and 5 mg/kg) potentiate antidepressant activity of nortriptyline (30 mg/kg, i.p.) in mice, but vice versa at 100 mg/kg. Likewise, Losartan potassium (100 mg/kg), significantly reversed antidepressant activity of fluoxetine HCl, but at 0.1 and 5 mg/kg, failed to modify fluoxetine HCl induced immobility. The obtained biphasic effect of losartan potassium on immobility in mice might be due to inhibitory effect on AT(1) receptor at lower dose and pronounced effect on AT(2) receptor at higher dose (large concentrations of losartan potassium can displace Angiotensin II (Ang II) from its AT(1) receptor to AT(2) receptor.

  17. Copper: a biphasic regulator of caprine sperm forward progression.

    PubMed

    Roy, Debarun; Dey, Souvik; Majumder, Gopal Chandra; Bhattacharyya, Debdas

    2014-02-01

    Copper is essential for spermatogenesis and its presence has been demonstrated in male and female reproductive fluids in several mammalian species. However, little is known about the physiological significance of this trace element in the regulation of forward progression of mammalian sperm cells which is essential for sperm fertility potential in vivo. The purpose of this investigation was to determine the physiological role of the bivalent copper ion (Cu(2+)) on mammalian sperm forward motility using a chemically-defined medium and caprine cauda epididymal sperm model. Sperm forward motility was significantly enhanced by Cu(2+) in a dose-dependent manner; maximal activation (approx 20%) was noted at the 5 µM level of the metal. Above 10 µM Cu(2+) sperm motility decreased, showing that Cu(2+) exerts a biphasic regulation on sperm motility. These findings have been confirmed using a spectrophotometric motility assay, an objective method of motility analysis. At lower concentrations (up to 5 µM), copper enhanced sperm membrane lipid peroxidation as well as the level of intra-sperm cyclic adenosine mono phosphate (c-AMP), but at a higher level it caused marked inhibition of both of the biochemical parameters. The observed correlation of Cu(2+)-dependent biphasic modulation of sperm membrane lipid peroxidation and intrasperm c-AMP with sperm forward motility is consistent with the view that Cu(2+) regulation of sperm motility is mediated by membrane lipid peroxidation, which in turn modulates the level of intra-sperm c-AMP, a well-known activator of sperm motility.

  18. Mouse phenotyping.

    PubMed

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  19. External cardioversion of atrial fibrillation: comparison of biphasic vs monophasic waveform shocks.

    PubMed

    Ricard, P; Lévy, S; Boccara, G; Lakhal, E; Bardy, G

    2001-04-01

    It is well established in transthoracic ventricular defibrillation that biphasic truncated waveform shocks are associated with superior defibrillation efficacy when compared with damped sine wave monophasic waveform shocks. The aim of this study was to explore whether biphasic waveform shocks were superior to monophasic waveform shocks for external cardioversion of atrial fibrillation (AF). Fifty-seven patients in whom cardioversion of AF was indicated were randomized in this prospective study, to transthoracic cardioversion with either monophasic damped sine waveform shocks or biphasic impedance compensating waveform shocks. In the group randomized to monophasic waveform shocks (27 patients), a first shock of 150 J was delivered, followed (if necessary) by a 360 J shock. In the biphasic waveform group (30 patients), the first shock had an energy of 150 J and (if necessary) a second 150 J was delivered. All shocks were delivered in the anterolateral chest pad position. Sinus rhythm was restored in 16 patients (51%) with the first monophasic shock and in 27 patients (86%) with the first biphasic shock. The difference was statistically significant (P=0.02). After the second shock, sinus rhythm was obtained in a total of 24 patients (88%) with monophasic shocks and in 28 patients (93%) with biphasic shocks. No complication was observed in either group and cardiac enzymes (CK, CKmb, troponin I, myoglobin) did not show any significant changes. This study suggests that at the same energy level of 150 J, biphasic impedance compensating waveform shocks are superior to monophasic damped sine waveform shocks cardioversion of atrial fibrillation.

  20. Biphasic versus monophasic shock for external cardioversion of atrial flutter: a prospective, randomized trial.

    PubMed

    Mortensen, Kai; Risius, Tim; Schwemer, Tjark F; Aydin, Muhammet Ali; Köster, Ralf; Klemm, Hanno U; Lutomsky, Boris; Meinertz, Thomas; Ventura, Rodolfo; Willems, Stephan

    2008-01-01

    External cardioversion is effective to terminate persistent atrial flutter. Biphasic shocks have been shown to be superior to monophasic shocks for ventricular defibrillation and atrial fibrillation cardioversion. The purpose of this trial was to compare the efficacy of rectilinear biphasic versus standard damped sine wave monophasic shocks in symptomatic patients with typical atrial flutter. 135 consecutive patients were screened, 95 (70 males, mean age 62 +/- 13 years) were included. Patients were randomly assigned to a monophasic or biphasic cardioversion protocol. Forty-seven patients randomized to the monophasic protocol received sequential shocks of 100, 150, 200, 300 and 360 J. Forty-eight patients with the biphasic protocol received 50, 75, 100, 150 or 200 J. First-shock efficacy with 50-Joule, biphasic shocks (23/48 patients, 48%) was significantly greater than with the 100-Joule, monophasic waveform (13/47 patients, 28%, p = 0.04). The cumulative second-shock efficacy with the 50- and 75-Joule, biphasic waveform (39/48 patients, 81%) was significantly greater than with the 100- and 150-Joule, monophasic waveform (25/47 patients, 53%, p < 0.05). The cumulative efficacy for the higher energy levels showed naturally no significant difference between the two groups. The amount of the mean delivered energy was significantly lower in the biphasic group (76 +/- 39 J) compared to the monophasic one (177 +/- 78 J, p < 0.05). For transthoracic cardioversion of typical atrial flutter, biphasic shocks have greater efficacy and the mean delivered current is lower than for monophasic shocks. Therefore, biphasic cardioversion with lower starting energies should be recommended. (c) 2008 S. Karger AG, Basel.

  1. Electron transport in zinc-blende wurtzite biphasic gallium nitride nanowires and GaNFETs

    SciTech Connect

    Jacobs, Benjamin W.; Ayres, Virginia M.; Stallcup, Richard E.; Hartman, Alan; Tupta, Mary Ann; Baczewski, Andrew David; Crimp, Martin A.; Halpern, Joshua B.; He, Maoqi; Shaw, Harry C.

    2007-10-19

    Two-point and four-point probe electrical measurements of a biphasic gallium nitride nanowire and current–voltage characteristics of a gallium nitride nanowire based field effect transistor are reported. The biphasic gallium nitride nanowires have a crystalline homostructure consisting of wurtzite and zinc-blende phases that grow simultaneously in the longitudinal direction. There is a sharp transition of one to a few atomic layers between each phase. Here, all measurements showed high current densities. Evidence of single-phase current transport in the biphasic nanowire structure is discussed.

  2. Electron transport in zinc-blende wurtzite biphasic gallium nitride nanowires and GaNFETs

    DOE PAGES

    Jacobs, Benjamin W.; Ayres, Virginia M.; Stallcup, Richard E.; ...

    2007-10-19

    Two-point and four-point probe electrical measurements of a biphasic gallium nitride nanowire and current–voltage characteristics of a gallium nitride nanowire based field effect transistor are reported. The biphasic gallium nitride nanowires have a crystalline homostructure consisting of wurtzite and zinc-blende phases that grow simultaneously in the longitudinal direction. There is a sharp transition of one to a few atomic layers between each phase. Here, all measurements showed high current densities. Evidence of single-phase current transport in the biphasic nanowire structure is discussed.

  3. Evaluation of Magnetic Nanoparticle-Labeled Chondrocytes Cultivated on a Type II Collagen–Chitosan/Poly(Lactic-co-Glycolic) Acid Biphasic Scaffold

    PubMed Central

    Su, Juin-Yih; Chen, Shi-Hui; Chen, Yu-Pin; Chen, Wei-Chuan

    2017-01-01

    Chondral or osteochondral defects are still controversial problems in orthopedics. Here, chondrocytes labeled with magnetic nanoparticles were cultivated on a biphasic, type II collagen–chitosan/poly(lactic-co-glycolic acid) scaffold in an attempt to develop cultures with trackable cells exhibiting growth, differentiation, and regeneration. Rabbit chondrocytes were labeled with magnetic nanoparticles and characterized by scanning electron microscopy (SEM), transmission electron (TEM) microscopy, and gene and protein expression analyses. The experimental results showed that the magnetic nanoparticles did not affect the phenotype of chondrocytes after cell labeling, nor were protein and gene expression affected. The biphasic type II collagen–chitosan/poly(lactic-co-glycolic) acid scaffold was characterized by SEM, and labeled chondrocytes showed a homogeneous distribution throughout the scaffold after cultivation onto the polymer. Cellular phenotype remained unaltered but with increased gene expression of type II collagen and aggrecan, as indicated by cell staining, indicating chondrogenesis. Decreased SRY-related high mobility group-box gene (Sox-9) levels of cultured chondrocytes indicated that differentiation was associated with osteogenesis. These results are encouraging for the development of techniques for trackable cartilage regeneration and osteochondral defect repair which may be applied in vivo and, eventually, in clinical trials. PMID:28054960

  4. Evaluation of Magnetic Nanoparticle-Labeled Chondrocytes Cultivated on a Type II Collagen-Chitosan/Poly(Lactic-co-Glycolic) Acid Biphasic Scaffold.

    PubMed

    Su, Juin-Yih; Chen, Shi-Hui; Chen, Yu-Pin; Chen, Wei-Chuan

    2017-01-04

    Chondral or osteochondral defects are still controversial problems in orthopedics. Here, chondrocytes labeled with magnetic nanoparticles were cultivated on a biphasic, type II collagen-chitosan/poly(lactic-co-glycolic acid) scaffold in an attempt to develop cultures with trackable cells exhibiting growth, differentiation, and regeneration. Rabbit chondrocytes were labeled with magnetic nanoparticles and characterized by scanning electron microscopy (SEM), transmission electron (TEM) microscopy, and gene and protein expression analyses. The experimental results showed that the magnetic nanoparticles did not affect the phenotype of chondrocytes after cell labeling, nor were protein and gene expression affected. The biphasic type II collagen-chitosan/poly(lactic-co-glycolic) acid scaffold was characterized by SEM, and labeled chondrocytes showed a homogeneous distribution throughout the scaffold after cultivation onto the polymer. Cellular phenotype remained unaltered but with increased gene expression of type II collagen and aggrecan, as indicated by cell staining, indicating chondrogenesis. Decreased SRY-related high mobility group-box gene (Sox-9) levels of cultured chondrocytes indicated that differentiation was associated with osteogenesis. These results are encouraging for the development of techniques for trackable cartilage regeneration and osteochondral defect repair which may be applied in vivo and, eventually, in clinical trials.

  5. AQUEOUS BIPHASE EXTRACTION FOR PROCESSING OF FINE COAL

    SciTech Connect

    K. Osseo-Asare; X. Zeng

    2001-06-30

    Ever-stringent environmental constraints dictate that future coal cleaning technologies be compatible with micron-size particles. This research program seeks to develop an advanced coal cleaning technology uniquely suited to micron-size particles, i.e., aqueous biphase extraction. The partitioning behaviors of silica in the polyethylene glycol (PEG)/dextran (Dex) and dextran/Triton X-100 (TX100) systems have been investigated, and the effects of sodium dodecylsulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) on solid partition have been studied. In both biphase systems, silica particles stayed in the top PEG-rich phase at low pH. With increase in pH, the particles moved from the top phase to the interface, then to the bottom phase. At very high pH, the solids preferred the top phase again. These trends are attributable to variations in the polymer/solid and nonionic surfactant/solid interactions. Addition of ionic surfactants into these two systems introduces a weakly charged environment, since ionic surfactants concentrate into one phase, either the top phase or the bottom phase. Therefore, coulombic forces also play a key role in the partition of silica particles because electrostatic attractive or repulsive forces are produced between the solid surface and the ionic-surfactant-concentrated phase. For the PEG/dextran system in the presence of SDS, SiO{sub 2} preferred the bottom dextran-rich phase above its pH{sub PZC}. However, addition of DTAB moved the oxide particles from the top phase to the interface, and then to the bottom phase, with increase in pH. These different behaviors are attributable to the fact that SDS and DTAB concentrated into the opposite phase of the PEG/dextran system. On the other hand, in the dextran/Triton X-100 system, both ionic surfactants concentrated in the top surfactant-rich phase and formed mixed micelles with TX100. Therefore, addition of the anionic surfactant, SDS, moved the silica particles from top phase to the

  6. AQUEOUS BIPHASE EXTRACTION FOR PROCESSING OF FINE COAL

    SciTech Connect

    K. Osseo-Asare

    2000-06-02

    Ever-stringent environmental constraints dictate that future coal cleaning technologies be compatible with micron-size particles. This research program seeks to develop an advanced coal cleaning technology uniquely suited to micron-size particles, i.e., aqueous biphase extraction. The partitioning behavior of fly ash in the PEG-2000 Na{sub 2}SO{sub 4}/H{sub 2}O system was studied and the solid in each fraction was characterized by CHN analysis (carbon content), X-ray diffraction (XRD; crystal component), and inductively coupled plasma spectrophotometry (ICP; elemental composition in the ash). In the pH range from 2 to 5, the particles separated into two different layers, i.e., the polymer-rich (top) and salt-rich (bottom) layers. However, above pH 5, the particles in the polymer-rich phase split into two zones. The percent carbon content of the solids in the upper zone ({approximately}80 wt%) was higher than that in the parent sample (63.2 wt%), while the lower zone in the polymer-rich phase had the same percent ash content as the original sample. The particles in the salt-rich phase were mainly composed of ash (with < 4 wt% carbon content). However, when the solid concentration in the whole system increased from 1 wt% to 2 wt%, this 3-fraction phenomenon only occurred above pH 10. XRD results showed that the main crystal components in the ash included quartz, hematite, and mullite. The ICP results showed that Si, Al, and Fe were the major elements in the fly ash, with minor elements of Na, K, Ca, Mg, and Ba. The composition of the ash in the lower zone of the polymer-rich phase remained almost the same as that in the parent fly ash. The largest amount of product ({approximately}60% yield) with the highest carbon content ({approximately}80 wt% C) was obtained in the range pH 6-9. Based on the experimental results obtained, a flowsheet is proposed for the beneficiation of high-carbon fly ash with the aqueous biphase extraction process.

  7. Biphasic vasodilator action of troglitazone on the renal microcirculation.

    PubMed

    Arima, Shuji; Kohagura, Kentaro; Takeuchi, Kazuhisa; Taniyama, Yoshihiro; Sugawara, Akira; Ikeda, Yukio; Abe, Michiaki; Omata, Ken; Ito, Sadayoshi

    2002-02-01

    Recent studies have demonstrated that thiazolidinediones, novel antidiabetic compounds that improve the insulin sensitivity, lower BP and decrease urinary protein excretion. However, neither the target vasculature nor the underlying mechanism for their actions is well understood. In this study, the action of troglitazone (Tro), a thiazolidinedione compound, on the glomerular afferent (Af-Arts) and efferent (Ef-Arts) arterioles, crucial vascular segments to the control of glomerular hemodynamics, were directly examined. Rabbit Af-Arts or Ef-Arts were microdissected from the superficial cortex and perfused at constant pressure. Increasing doses of Tro (10(-8) to 10(-5) M) were added to both the bath and lumen of preconstricted arterioles. In Af-Arts, Tro caused dose-dependent and biphasic dilation. Tro at 10(-5) M increased the diameter by 28 +/- 6% (n = 8, P < 0.01) until 20 min, with the diameter remaining at this level for 60 min, and then Tro began to dilate Af-Arts again. At 120 min, Tro at 10(-5) M further increased the diameter by 23 +/- 4% (n = 6). Disrupting the endothelium had no effect on either dilation (n = 7 or n = 5). Pretreatment with SKF 96365 (50 microM), which inhibits both voltage- and receptor-operated calcium channels, abolished the early-phase dilation without affecting the late-phase dilation; 20 or 120 min after adding Tro at 10(-5) M, the diameter increased by 4 +/- 2% (n = 7) or 28 +/- 3% (n = 6), respectively. In contrast to Af-Arts, Tro caused monophasic dilation in Ef-Arts; Tro at 10(-5) M did not cause significant dilation until 80 min, and at 120 min the diameter increased by 37 +/- 4% (n = 5). These results suggest that in the Af-Art Tro has biphasic endothelium-independent vasodilator action, which is partly mediated by an inhibition of calcium influx. This vasodilator action may play a role in the BP-lowering effect of Tro. In addition, by dilating the postglomerular Ef-Art, Tro may decrease the glomerular capillary pressure and

  8. Progressive and biphasic cardiac responses during extreme mountain ultramarathon.

    PubMed

    Maufrais, Claire; Millet, Grégoire P; Schuster, Iris; Rupp, Thomas; Nottin, Stéphane

    2016-05-15

    Investigations on the cardiac function consequences of mountain ultramarathon (MUM) >100 h are lacking. The present study assessed the progressive cardiac responses during the world's most challenging MUM (Tor des Géants; Italy; 330 km; 24,000 m of cumulative elevation gain). Resting echocardiographic evaluation of morphology, function, and mechanics of left and right ventricle (LV and RV) including speckle tracking echocardiography was conducted in 15 male participants (46 ± 13 yr) before (pre), during (mid; 148 km), and after (post) the race. Runners completed the race in 126 ± 15 h. From pre to post, the increase in stroke volume (SV) (103 ± 19 vs. 110 ± 23 vs. 116 ± 21 ml; P < 0.001 at pre, mid, and post) was concomitant to the increase in LV early filling (peak E; 72.9 ± 15.7 vs. 74.6 ± 13.1 vs. 82.1 ± 11.5 cm/s; P < 0.05). Left and right atrial end-diastolic areas, RV end-diastolic area, and LV end-diastolic volume were 12-19% higher at post compared with pre (P < 0.05). Resting heart rate and LV systolic strain rates demonstrated a biphasic adaptation with an increase from pre to mid (55 ± 8 vs. 72 ± 11 beats/min, P < 0.001) and a return to baseline values from mid to post (59 ± 8 beats/min). Significant correlations were found between pre-to-post percent changes in peak E and LV end-diastolic volume (r = 0.63, P < 0.05) or RV (r = 0.82, P < 0.001) or atrial end-diastolic areas (r = 0.83, P < 0.001). An extreme MUM induced a biphasic pattern of heart rate in parallel with specific cardiac responses characterized by a progressive increase in diastolic filling, biventricular volumes, and SV. The underlying mechanisms and their clinical implications remain challenging for the future.

  9. Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

    SciTech Connect

    Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia; Chuai, Manli; Lee, Kenneth Ka Ho; Wan, Chao; Yang, Xuesong

    2014-11-15

    increased in mesenchymal cell mass treated by low concentration of Dex. Mmp-13 expression was obviously up-regulated by Dex in both mesenchymal cells and primary chondrocyte cultures. And Col10a1 expression was also increased by Dex exposure in chondrocyte. In summary, we have revealed that different concentrations of Dex exposure during early gestation could exert a biphasic effect on vertebrate skeletal development. - Highlights: • Chick embryos occurred shortening of the long bone following Dex exposure. • Dex suppressed chondrocytes proliferation and promoted apoptosis. • Dex exposure decreased ALP production and up-regulated Runx-2 and Mmp-13. • Dex exhibited biphasic effects on chondrogenic proliferation and nodule formation. • The hypertrophy and ossification were accelerated by Dex both in vivo and in vitro.

  10. Aqueous biphasic plutonium oxide extraction process with pH and particle control

    DOEpatents

    Chaiko, D.J.; Mensah-Biney, R.

    1997-04-29

    A method is described for simultaneously partitioning a metal oxide and silica from a material containing silica and the metal oxide, using a biphasic aqueous medium having immiscible salt and polymer phases. 2 figs.

  11. Biphasic metaplastic sarcomatoid carcinoma of the breast: report of a case.

    PubMed

    Haruki, Tomohiro; Maeta, Hiroyuki; Sawazumi, Yuko; Miyasaka, Shigeto; Morimoto, Keisuke; Ishikawa, Noriyoshi; Nakamoto, Shu; Taniguchi, Iwao

    2009-01-01

    A 69-year-old woman was admitted to our hospital with the complaint of a right breast mass. As a result of thorough examinations, she was diagnosed with breast cancer and underwent breast-conserving surgery. The pathological findings of the resected specimen showed that the tumor consisted of intermingled carcinomatous and sarcomatous components with a transition zone. On immunohistochemical study, the sarcomatous cells in this transition zone showed partial positive staining for CD10, the myoepithelial marker, suggesting that the myoepithelial cells had transformed into sarcoma, and then this biphasic tumor was formed. Finally, she was diagnosed with biphasic metaplastic sarcomatoid carcinoma of the breast. Biphasic metaplastic sarcomatoid carcinoma of the breast is a relatively rare but aggressive disease. The pathological diagnosis is often controversial, requiring detailed immunohistochemical analysis. We report our experience with a case of biphasic metaplastic sarcomatoid carcinoma of the breast.

  12. Small-sized granules of biphasic bone substitutes support fast implant bed vascularization

    PubMed Central

    Barbeck, M; Dard, M; Kokkinopoulou, M; Markl, J; Booms, P; Sader, RA; Kirkpatrick, CJ; Ghanaati, S

    2015-01-01

    The present study investigated the influence of granule size of 2 biphasic bone substitutes (BoneCeramic® 400–700 μm and 500–1000 μm) on the induction of multinucleated giant cells (MNGCs) and implant bed vascularization in a subcutaneous implantation model in rats. Furthermore, degradation mechanisms and particle phagocytosis of both materials were examined by transmission electron microscopy (TEM). Both granule types induced tissue reactions involving primarily mononuclear cells and only small numbers of MNGCs. Higher numbers of MNGCs were detected in the group with small granules starting on day 30, while higher vascularization was observed only at day 10 in this group. TEM analysis revealed that both mono- and multinucleated cells were involved in the phagocytosis of the materials. Additionally, the results allowed recognition of the MNGCs as the foreign body giant cell phenotype. Histomorphometrical analysis of the size of phagocytosed particles showed no differences between the 2 granule types. The results indicate that granule size seems to have impact on early implant bed vascularization and also on the induction of MNGCs in the late phase of the tissue reaction. Furthermore, the results revealed that a synthetic bone substitute material can induce tissue reactions similar to those of some xenogeneic materials, thus pointing to a need to elucidate their “ideal” physical characteristics. The results also show that granule size in the range studied did not alter phagocytosis by mononuclear cells. Finally, the investigation substantiates the differentiation of material-induced MNGCs, which are of the foreign body giant cell type. PMID:26083163

  13. High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

    PubMed

    Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

    2015-09-01

    Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

  14. Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks.

    PubMed

    Mittal, S; Ayati, S; Stein, K M; Schwartzman, D; Cavlovich, D; Tchou, P J; Markowitz, S M; Slotwiner, D J; Scheiner, M A; Lerman, B B

    2000-03-21

    Clinical studies have shown that biphasic shocks are more effective than monophasic shocks for ventricular defibrillation. The purpose of this study was to compare the efficacy of a rectilinear biphasic waveform with a standard damped sine wave monophasic waveform for the transthoracic cardioversion of atrial fibrillation. In this prospective, randomized, multicenter trial, patients undergoing transthoracic cardioversion of atrial fibrillation were randomized to receive either damped sine wave monophasic or rectilinear biphasic shocks. Patients randomized to the monophasic protocol (n=77) received sequential shocks of 100, 200, 300, and 360 J. Patients randomized to the biphasic protocol (n=88) received sequential shocks of 70, 120, 150, and 170 J. First-shock efficacy with the 70-J biphasic waveform (60 of 88 patients, 68%) was significantly greater than that with the 100-J monophasic waveform (16 of 77 patients, 21%, P<0.0001), and it was achieved with 50% less delivered current (11+/-1 versus 22+/-4 A, P<0.0001). Similarly, the cumulative efficacy with the biphasic waveform (83 of 88 patients, 94%) was significantly greater than that with the monophasic waveform (61 of 77 patients, 79%; P=0.005). The following 3 variables were independently associated with successful cardioversion: use of a biphasic waveform (relative risk, 4.2; 95% confidence intervals, 1.3 to 13.9; P=0.02), transthoracic impedance (relative risk, 0.64 per 10-Omega increase in impedance; 95% confidence intervals, 0.46 to 0.90; P=0.005), and duration of atrial fibrillation (relative risk, 0.97 per 30 days of atrial fibrillation; 95% confidence intervals, 0.96 to 0.99; P=0.02). For transthoracic cardioversion of atrial fibrillation, rectilinear biphasic shocks have greater efficacy (and require less energy) than damped sine wave monophasic shocks.

  15. Biphasic transthoracic defibrillation causes fewer ECG ST-segment changes after shock.

    PubMed

    Reddy, R K; Gleva, M J; Gliner, B E; Dolack, G L; Kudenchuk, P J; Poole, J E; Bardy, G H

    1997-08-01

    Electrocardiographic abnormalities are common after transthoracic defibrillation. ECG ST-segment changes are especially problematic after defibrillation and may indicate ischemic or shock-induced cardiac dysfunction after resuscitation. Biphasic defibrillation waveforms, compared with monophasic waveforms, diminish shock-induced cardiac dysfunction in laboratory preparations. This effect has not been validated in human subjects. We therefore evaluated in a prospective, blinded fashion the effect of biphasic and monophasic transthoracic defibrillation on the ECG ST segment in 30 consecutive patients during surgery for the implantation of a cardioverter-defibrillator. In each patient two low-energy truncated biphasic transthoracic defibrillation shocks (115 and 130 J) were compared with a standard clinical 200 J monophasic damped-sine wave shock. The biphasic shocks and the damped-sine wave shock have been demonstrated to have equal defibrillation efficacy of 97%. Fifteen-second ECG signals recorded across transthoracic defibrillation electrodes were digitized before ventricular fibrillation induction and immediately after each defibrillation attempt. The ST segments 80 msec after the J point were analyzed in a blinded fashion by two reviewers. The ST-segment deflection, QRS-interval duration, QT interval, and heart rate after each therapy were compared with baseline values. ECG ST-segment elevation was significantly greater with the 200-J damped-sine waveform than with either biphasic waveform. The ECG ST-segment levels were -.55 +/- .36 at baseline, -.76 +/- .36 mm after internal shock, -.02-.36 mm after 115-J biphasic shock, .21 +/- .38 mm after 130-J biphasic shock, and 2.09 +/- .37 mm after 200-J damped-sine wave shock (P<.0001). QRS-interval duration, QT interval, and heart rate did not change significantly with any waveform. Transthoracic defibrillation with biphasic waveforms results in less postshock ECG evidence of myocardial dysfunction (injury or ischemia

  16. Micrometer-scale mixing with Pickering emulsions: biphasic reactions without stirring.

    PubMed

    Zhang, Wenjuan; Fu, Luman; Yang, Hengquan

    2014-02-01

    A general strategy that avoids stirring for organic/aqueous reactions involving solid catalysts is reported. The strategy involves converting a conventional biphasic system into a Pickering emulsion phase with micrometer-scale droplets ensuring good mixing. In test reactions, nitrotoluene reduction and epoxidation of allylic alcohols, the reaction efficiency is comparable to conventional stirrer-driven biphasic catalysis reaction systems. Short diffusion distances, arising from the compartmentalization of densely packed droplets, play an important role in boosting the reaction efficiency.

  17. Oscillatory three-phase flow reactor for studies of bi-phasic catalytic reactions.

    PubMed

    Abolhasani, Milad; Bruno, Nicholas C; Jensen, Klavs F

    2015-05-28

    A multi-phase flow strategy, based on oscillatory motion of a bi-phasic slug within a fluorinated ethylene propylene (FEP) tubular reactor, under inert atmosphere, is designed and developed to address mixing and mass transfer limitations associated with continuous slug flow chemistry platforms for studies of bi-phasic catalytic reactions. The technique is exemplified with C-C and C-N Pd catalyzed coupling reactions.

  18. Biphasic modulation of cell growth by recombinant human galectin-1.

    PubMed

    Adams, L; Scott, G K; Weinberg, C S

    1996-06-13

    Human soluble galactose-binding lectin (galectin-1) has been expressed as an Escherichia coli fusion protein, following the amplification by polymerase chain reaction of cDNA prepared from a human osteosarcoma cell line. The fusion protein is a functional beta-galactoside-binding lectin, as is the recombinant galectin when purified from the cleaved fusion protein. The recombinant galectin has a biphasic effect on cell proliferation. Unlike the fusion protein, it functions as a human cell growth inhibitor, confirming earlier findings with natural human galectin-1, though it is less effective than the natural galectin. This reaction is not significantly inhibited by lactose, and is thus largely independent of the beta-galactoside-binding site. At lower concentrations, recombinant galectin-1 is mitogenic, this activity being susceptible to inhibition by lactose, and thus attributable to the beta-galactoside-binding ability of the protein. Some tumour cells are susceptible to the growth-inhibitory effect, and the galectin-1 gene is expressed in both normal and tumour cells.

  19. Neutron Polarization Analysis for Biphasic Solvent Extraction Systems

    DOE PAGES

    Motokawa, Ryuhei; Endo, Hitoshi; Nagao, Michihiro; ...

    2016-06-16

    Here we performed neutron polarization analysis (NPA) of extracted organic phases containing complexes, comprised of Zr(NO3)4 and tri-n-butyl phosphate, which enabled decomposition of the intensity distribution of small-angle neutron scattering (SANS) into the coherent and incoherent scattering components. The coherent scattering intensity, containing structural information, and the incoherent scattering compete over a wide range of magnitude of scattering vector, q, specifically when q is larger than q* ≈ 1/Rg, where Rg is the radius of gyration of scatterer. Therefore, it is important to determine the incoherent scattering intensity exactly to perform an accurate structural analysis from SANS data when Rgmore » is small, such as the aforementioned extracted coordination species. Although NPA is the best method for evaluating the incoherent scattering component for accurately determining the coherent scattering in SANS, this method is not used frequently in SANS data analysis because it is technically challenging. In this study, we successfully demonstrated that experimental determination of the incoherent scattering using NPA is suitable for sample systems containing a small scatterer with a weak coherent scattering intensity, such as extracted complexes in biphasic solvent extraction systems.« less

  20. Comparison between FEBio and Abaqus for biphasic contact problems

    PubMed Central

    Jin, Zhongmin; Fisher, John; Wilcox, Ruth

    2013-01-01

    Articular cartilage plays an important role in the function of diarthrodial joints. Computational methods have been used to study the biphasic mechanics of cartilage, and Abaqus has been one of the most widely used commercial software packages for this purpose. A newly developed open-source finite element solver, FEBio, has been developed specifically for biomechanical applications. The aim of this study was to undertake a direct comparison between FEBio and Abaqus for some practical contact problems involving cartilage. Three model types, representing a porous flat-ended indentation test, a spherical-ended indentation test, and a conceptual natural joint contact model, were compared. In addition, a parameter sensitivity study was also performed for the spherical-ended indentation test to investigate the effects of changes in the input material properties on the model outputs, using both FEBio and Abaqus. Excellent agreement was found between FEBio and Abaqus for all of the model types and across the range of material properties that were investigated. PMID:23804955

  1. Biphasic effect of linoleic acid on connexin 46 hemichannels

    PubMed Central

    Evangelista-Martínez, Flavio; León-Paravic, Carmen G.; Altenberg, Guillermo A.; Reuss, Luis

    2011-01-01

    Connexins form hemichannels at undocked plasma membranes and gap-junction channels (GJCs) at intercellular contacting zones. Under physiological conditions, hemichannels have low open probabilities, but their activation under pathological conditions, such as ischemia, induces and/or accelerates cell death. Connexin 46 (Cx46) is a major connexin of the lens, and mutations of this connexin induce cataracts. Here, we report the effects of linoleic acid (LA) on the electrical properties of Cx46 GJCs and hemichannels expressed in Xenopus laevis oocytes. LA has a biphasic effect, increasing hemichannel current at 0.1 μM and decreasing it at concentrations of 100 μM or higher. The effects of extracellular and microinjected LA conjugated to coenzyme A (LA-CoA) suggest that the current activation site is accessible from the intracellular but not extracellular compartment, whereas the current inhibitory site is either located in a region of the hemichannel pore inaccessible to intracellular LA-CoA, or requires crossing of LA through an organelle membrane. Experiments with other fatty acids demonstrated that the block of hemichannels depends on the presence of a hydrogenated double bond at position 9 and is directly proportional to the number of double bonds. Experiments in paired oocytes expressing Cx46 showed that LA does not affect GJCs. The block by unsaturated fatty acids reported here opens the possibility that increases in the concentration of these lipids in the lens induce cataract formation by blocking Cx46 hemichannels. PMID:21360038

  2. Evolution of the optimum bidirectional (+/- biphasic) wave for defibrillation.

    PubMed

    Geddes, L A; Havel, W

    2000-01-01

    Introduction of the asymmetric bidirectional (+/- biphasic) current waveform has made it possible to achieve ventricular defibrillation with less energy and current than are needed with a unidirectional (monophasic) waveform. The symmetrical bidirectional (sinusoidal) waveform was used for the first human-heart defibrillation. Subsequent studies employed the underdamped and overdamped sine waves, then the trapezoidal (monophasic) wave. Studies were then undertaken to investigate the benefit of adding a second identical and inverted wave; little success rewarded these efforts until it was discovered that the second inverted wave needed to be much less in amplitude to lower the threshold for defibrillation. However, there is no physiologic theory that explains the mechanism of action of the bidirectional wave, nor does any theory predict the optimum amplitude and time dimensions for the second inverted wave. The authors analyze the research that shows that the threshold defibrillation energy is lowest when the charge in the second, inverted phase is slightly more than a third of that in the first phase. An ion-flux, spatial-K+ summation hypothesis is presented that shows the effect on myocardial cells of adding the second inverted current pulse.

  3. Biphasic Oxidation of Oxy-Hemoglobin in Bloodstains

    PubMed Central

    Bremmer, Rolf H.; de Bruin, Daniel M.; de Joode, Maarten; Buma, Wybren Jan; van Leeuwen, Ton G.; Aalders, Maurice C. G.

    2011-01-01

    Background In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO2) to met-hemoglobin (met-Hb) and hemichrome (HC). The fractions of HbO2, met-Hb and HC in a bloodstain can be used for age determination of bloodstains. In this study, we further analyze the conversion of HbO2 to met-Hb and HC, and determine the effect of temperature and humidity on the conversion rates. Methodology The fractions of HbO2, met-Hb and HC in a bloodstain, as determined by quantitative analysis of optical reflectance spectra (450–800 nm), were measured as function of age, temperature and humidity. Additionally, Optical Coherence Tomography around 1300 nm was used to confirm quantitative spectral analysis approach. Conclusions The oxidation rate of HbO2 in bloodstains is biphasic. At first, the oxidation of HbO2 is rapid, but slows down after a few hours. These oxidation rates are strongly temperature dependent. However, the oxidation of HbO2 seems to be independent of humidity, whereas the transition of met-Hb into HC strongly depends on humidity. Knowledge of these decay rates is indispensable for translating laboratory results into forensic practice, and to enable bloodstain age determination on the crime scene. PMID:21789186

  4. Nucleic Acid Sample Preparation using Spontaneous Biphasic Plug Flow

    PubMed Central

    Thomas, Peter C.; Strotman, Lindsay N.; Theberge, Ashleigh B.; Berthier, Erwin; O’Connell, Rachel; Loeb, Jennifer M.; Berry, Scott M.; Beebe, David J.

    2013-01-01

    Nucleic acid (NA) extraction and purification has become a common technique in both research and clinical laboratories. Current methods require repetitive wash steps with a pipette that is laborious and time consuming making it inefficient for clinical settings. We present here a simple technique that relies on spontaneous biphasic plug flow inside a capillary to achieve sample preparation. By filling the sample with oil, aqueous contaminants were displaced from the captured NA without pipetting wash buffers or use of external force and equipment. mRNA from mammalian cell culture was purified and PCR amplification showed similar threshold cycle values as those obtained from a commercially available kit. HIV viral like particles were spiked into serum and a 5-fold increase in viral RNA extraction yield was achieved compared to the conventional wash method. In addition, viral RNA was successfully purified from human whole blood, and a limit of detection of approximately 14 copies of RNA extracted per sample. The results demonstrate the utility of the current technique for nucleic acid purification for clinical purposes, and the overall approach provides a potential method to implement nucleic acid testing in low resource settings. PMID:23941230

  5. Nucleic acid sample preparation using spontaneous biphasic plug flow.

    PubMed

    Thomas, Peter C; Strotman, Lindsay N; Theberge, Ashleigh B; Berthier, Erwin; O'Connell, Rachel; Loeb, Jennifer M; Berry, Scott M; Beebe, David J

    2013-09-17

    Nucleic acid (NA) extraction and purification has become a common technique in both research and clinical laboratories. Current methods require repetitive wash steps with a pipet that are laborious and time-consuming, making the procedure inefficient for clinical settings. We present here a simple technique that relies on spontaneous biphasic plug flow inside a capillary to achieve sample preparation. By filling the sample with oil, aqueous contaminants were displaced from the captured NA without pipetting wash buffers or use of external force and equipment. mRNA from mammalian cell culture was purified, and polymerase chain reaction (PCR) amplification showed similar threshold cycle values as those obtained from a commercially available kit. Human immunodeficiency virus (HIV) viral-like particles were spiked into serum and a 5-fold increase in viral RNA extraction yield was achieved compared to the conventional wash method. In addition, viral RNA was successfully purified from human whole blood, and a limit of detection of approximately 14 copies of RNA extracted per sample was determined. The results demonstrate the utility of the current technique for nucleic acid purification for clinical purposes, and the overall approach provides a potential method to implement nucleic acid testing in low-resource settings.

  6. Neutron Polarization Analysis for Biphasic Solvent Extraction Systems

    SciTech Connect

    Motokawa, Ryuhei; Endo, Hitoshi; Nagao, Michihiro; Heller, William T.

    2016-06-16

    Here we performed neutron polarization analysis (NPA) of extracted organic phases containing complexes, comprised of Zr(NO3)4 and tri-n-butyl phosphate, which enabled decomposition of the intensity distribution of small-angle neutron scattering (SANS) into the coherent and incoherent scattering components. The coherent scattering intensity, containing structural information, and the incoherent scattering compete over a wide range of magnitude of scattering vector, q, specifically when q is larger than q* ≈ 1/Rg, where Rg is the radius of gyration of scatterer. Therefore, it is important to determine the incoherent scattering intensity exactly to perform an accurate structural analysis from SANS data when Rg is small, such as the aforementioned extracted coordination species. Although NPA is the best method for evaluating the incoherent scattering component for accurately determining the coherent scattering in SANS, this method is not used frequently in SANS data analysis because it is technically challenging. In this study, we successfully demonstrated that experimental determination of the incoherent scattering using NPA is suitable for sample systems containing a small scatterer with a weak coherent scattering intensity, such as extracted complexes in biphasic solvent extraction systems.

  7. Osteochondral tissue engineering with biphasic scaffold: current strategies and techniques.

    PubMed

    Shimomura, Kazunori; Moriguchi, Yu; Murawski, Christopher D; Yoshikawa, Hideki; Nakamura, Norimasa

    2014-10-01

    The management of osteoarthritis (OA) remains challenging and controversial. Although several clinical options exist for the treatment of OA, regeneration of the damaged articular cartilage has proved difficult due to the limited healing capacity. With the advancements in tissue engineering and cell-based technologies over the past decade, new therapeutic options for patients with osteochondral lesions potentially exist. This review will focus on the feasibility of tissue-engineered biphasic scaffolds, which can mimic the native osteochondral complex, for osteochondral repair and highlight the recent development of these techniques toward tissue regeneration. Moreover, basic anatomy, strategy for osteochondral repair, the design and fabrication methods of scaffolds, as well as the choice of cells, growth factor, and materials will be discussed. Specifically, we focus on the latest preclinical animal studies using large animals and clinical trials with high clinical relevance. In turn, this will facilitate an understanding of the latest trends in osteochondral repair and contribute to the future application of such clinical therapies in patients with OA.

  8. Neutron Polarization Analysis for Biphasic Solvent Extraction Systems

    SciTech Connect

    Motokawa, Ryuhei; Endo, Hitoshi; Nagao, Michihiro; Heller, William T.

    2016-06-16

    Here we performed neutron polarization analysis (NPA) of extracted organic phases containing complexes, comprised of Zr(NO3)4 and tri-n-butyl phosphate, which enabled decomposition of the intensity distribution of small-angle neutron scattering (SANS) into the coherent and incoherent scattering components. The coherent scattering intensity, containing structural information, and the incoherent scattering compete over a wide range of magnitude of scattering vector, q, specifically when q is larger than q* ≈ 1/Rg, where Rg is the radius of gyration of scatterer. Therefore, it is important to determine the incoherent scattering intensity exactly to perform an accurate structural analysis from SANS data when Rg is small, such as the aforementioned extracted coordination species. Although NPA is the best method for evaluating the incoherent scattering component for accurately determining the coherent scattering in SANS, this method is not used frequently in SANS data analysis because it is technically challenging. In this study, we successfully demonstrated that experimental determination of the incoherent scattering using NPA is suitable for sample systems containing a small scatterer with a weak coherent scattering intensity, such as extracted complexes in biphasic solvent extraction systems.

  9. Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

    PubMed Central

    Fan, Fan; Ji, Chen; Wu, Yumei; Ferguson, Shawn M.; Tamarina, Natalia; Philipson, Louis H.; Lou, Xuelin

    2015-01-01

    Alterations in insulin granule exocytosis and endocytosis are paramount to pancreatic β cell dysfunction in diabetes mellitus. Here, using temporally controlled gene ablation specifically in β cells in mice, we identified an essential role of dynamin 2 GTPase in preserving normal biphasic insulin secretion and blood glucose homeostasis. Dynamin 2 deletion in β cells caused glucose intolerance and substantial reduction of the second phase of glucose-stimulated insulin secretion (GSIS); however, mutant β cells still maintained abundant insulin granules, with no signs of cell surface expansion. Compared with control β cells, real-time capacitance measurements demonstrated that exocytosis-endocytosis coupling was less efficient but not abolished; clathrin-mediated endocytosis (CME) was severely impaired at the step of membrane fission, which resulted in accumulation of clathrin-coated endocytic intermediates on the plasma membrane. Moreover, dynamin 2 ablation in β cells led to striking reorganization and enhancement of actin filaments, and insulin granule recruitment and mobilization were impaired at the later stage of GSIS. Together, our results demonstrate that dynamin 2 regulates insulin secretory capacity and dynamics in vivo through a mechanism depending on CME and F-actin remodeling. Moreover, this study indicates a potential pathophysiological link between endocytosis and diabetes mellitus. PMID:26413867

  10. Biphasic regulation of lysosomal exocytosis by oxidative stress.

    PubMed

    Ravi, Sreeram; Peña, Karina A; Chu, Charleen T; Kiselyov, Kirill

    2016-11-01

    Oxidative stress drives cell death in a number of diseases including ischemic stroke and neurodegenerative diseases. A better understanding of how cells recover from oxidative stress is likely to lead to better treatments for stroke and other diseases. The recent evidence obtained in several models ties the process of lysosomal exocytosis to the clearance of protein aggregates and toxic metals. The mechanisms that regulate lysosomal exocytosis, under normal or pathological conditions, are only beginning to emerge. Here we provide evidence for the biphasic effect of oxidative stress on lysosomal exocytosis. Lysosomal exocytosis was measured using the extracellular levels of the lysosomal enzyme beta-hexosaminidase (ß-hex). Low levels or oxidative stress stimulated lysosomal exocytosis, but inhibited it at high levels. Deletion of the lysosomal ion channel TRPML1 eliminated the stimulatory effect of low levels of oxidative stress. The inhibitory effects of oxidative stress appear to target the component of lysosomal exocytosis that is driven by extracellular Ca(2+). We propose that while moderate oxidative stress promotes cellular repair by stimulating lysosomal exocytosis, at high levels oxidative stress has a dual pathological effect: it directly causes cell damage and impairs damage repair by inhibiting lysosomal exocytosis. Harnessing these adaptive mechanisms may point to pharmacological interventions for diseases involving oxidative proteotoxicity or metal toxicity.

  11. Comparison between FEBio and Abaqus for biphasic contact problems.

    PubMed

    Meng, Qingen; Jin, Zhongmin; Fisher, John; Wilcox, Ruth

    2013-09-01

    Articular cartilage plays an important role in the function of diarthrodial joints. Computational methods have been used to study the biphasic mechanics of cartilage, and Abaqus has been one of the most widely used commercial software packages for this purpose. A newly developed open-source finite element solver, FEBio, has been developed specifically for biomechanical applications. The aim of this study was to undertake a direct comparison between FEBio and Abaqus for some practical contact problems involving cartilage. Three model types, representing a porous flat-ended indentation test, a spherical-ended indentation test, and a conceptual natural joint contact model, were compared. In addition, a parameter sensitivity study was also performed for the spherical-ended indentation test to investigate the effects of changes in the input material properties on the model outputs, using both FEBio and Abaqus. Excellent agreement was found between FEBio and Abaqus for all of the model types and across the range of material properties that were investigated.

  12. Biphasic Ngn3 expression in the developing pancreas

    PubMed Central

    Villasenor, Alethia; Chong, Diana C.; Cleaver, Ondine

    2008-01-01

    Ngn3 is a bHLH transcription factor critical for the specification of endocrine cells in the pancreatic Islets of Langerhans. Previous studies in mouse embryos have reported transient expression of Ngn3 in scattered cells within the developing pancreatic epithelium during midgestation (Schwitzgebel et al., 2000). Specifically, these Ngn3-expressing cells have been shown to be progenitor cells fated to give rise to islet endocrine cells (Gradwohl et al., 2000). Here, we characterize the expression of Ngn3 transcripts and protein throughout pancreatic development. Interestingly, we identify and define a dramatic and previously unnoticed gap in developmental Ngn3 expression. We show that both Ngn3 transcript and protein expression occur in two distinct temporal waves, the first occurring early from approximately E8.75 to E11.0, and the second initiating at approximately E12.0. Strikingly, this observed biphasic expression correlates with the ‘first’ and ‘second’ transitions, which encompass two distinct waves of embryonic endocrine differentiation. In addition, our studies demonstrate that Ngn3 transcripts are markedly more widespread in the pancreatic epithelium than NGN3 protein, indicating that post-transcriptional regulation is likely to play a critical role during endocrine differentiation. PMID:18924236

  13. Evaluation of a biphasic in vitro dissolution test for estimating the bioavailability of carbamazepine polymorphic forms.

    PubMed

    Deng, Jia; Staufenbiel, Sven; Bodmeier, Roland

    2017-07-15

    The purpose of this study was to discriminate three crystal forms of carbamazepine (a BCS II drug) by in vitro dissolution testing and to correlate in vitro data with published in vivo data. A biphasic dissolution system (phosphate buffer pH6.8 and octanol) was used to evaluate the dissolution of the three polymorphic forms and to compare it with conventional single phase dissolution tests performed under sink and non-sink conditions. Similar dissolution profiles of three polymorphic forms were observed in the conventional dissolution test under sink conditions. Although a difference in dissolution was seen in the single phase dissolution test under non-sink conditions as well as in the aqueous phase of the biphasic test, little relevance for in vivo data was observed. In contrast, the biphasic dissolution system could discriminate between the different polymorphic forms in the octanol phase with a ranking of form III>form I>dihydrate form. This was in agreement with the in vivo performance. The dissolved drug available for oral absorption, which was dominated by dissolution and solution-mediated phase transformation, could be reflected in the biphasic dissolution test. Moreover, a good correlation was established between in vitro dissolution in the octanol phase of the biphasic test and in vivo pharmacokinetic data (R(2)=0.99). The biphasic dissolution method is a valuable tool to discriminate between different crystal forms in the formulations of poorly soluble drugs. Copyright © 2017. Published by Elsevier B.V.

  14. Novel Measurements of Aerosol Particle Interfaces Using Biphasic Microfluidics

    NASA Astrophysics Data System (ADS)

    Metcalf, A. R.; Dutcher, C. S.

    2014-12-01

    Secondary organic aerosol (SOA) particles are nearly ubiquitous in the atmosphere and yet there remains large uncertainties in their formation processes and ambient properties. These particles are complex microenvironments, which can contain multiple interfaces due to internal aqueous-organic phase partitioning and to the external liquid-vapor surface. These aerosol interfaces can profoundly affect the fate of condensable organic compounds emitted into the atmosphere by altering the way in which organic vapors interact with the ambient aerosol. Aerosol interfaces affect particle internal structure, species uptake, equilibrium partitioning, activation to cloud condensation or ice nuclei, and optical properties. For example, organic thin films can shield the core of the aerosol from the ambient environment, which may disrupt equilibrium partitioning and mass transfer. To improve our ability to accurately predict the fate of SOA in the atmosphere, we must improve our knowledge of aerosol interfaces and their interactions with the ambient environment. Few technologies exist to accurately probe aerosol interfaces at atmospherically-relevant conditions. In this talk, a novel method using biphasic microscale flows will be introduced for generating, trapping, and perturbing complex interfaces at atmospherically relevant conditions. These microfluidic experiments utilize high-speed imaging to monitor interfacial phenomena at the microscale and are performed with phase contrast and fluorescence microscopy on a temperature-controlled inverted microscope stage. From these experiments, interfacial thermodynamic properties such as surface tension, rheological properties such as interfacial moduli, and kinetic properties such as mass transfer coefficients can be measured or inferred. Chemical compositions of the liquid phases studied here span a range of viscosities and include electrolyte and water soluble organic acid species often observed in the atmosphere, such as mixtures

  15. Core-shell nanoreactors for efficient aqueous biphasic catalysis.

    PubMed

    Zhang, Xuewei; Cardozo, Andrés F; Chen, Si; Zhang, Wenjing; Julcour, Carine; Lansalot, Muriel; Blanco, Jean-François; Gayet, Florence; Delmas, Henri; Charleux, Bernadette; Manoury, Eric; D'Agosto, Franck; Poli, Rinaldo

    2014-11-17

    Water-borne phosphine-functionalized core-cross-linked micelles (CCM) consisting of a hydrophobic core and a hydrophilic shell were obtained as stable latexes by reversible addition-fragmentation chain transfer (RAFT) in water in a one-pot, three-step process. Initial homogeneous aqueous-phase copolymerization of methacrylic acid (MAA) and poly(ethylene oxide) methyl ether methacrylate (PEOMA) is followed by copolymerization of styrene (S) and 4-diphenylphosphinostyrene (DPPS), yielding P(MAA-co-PEOMA)-b-P(S-co-DPPS) amphiphilic block copolymer micelles (M) by polymerization-induced self-assembly (PISA), and final micellar cross-linking with a mixture of S and diethylene glycol dimethacrylate. The CCM were characterized by dynamic light scattering and NMR spectroscopy to evaluate size, dispersity, stability, and the swelling ability of various organic substrates. Coordination of [Rh(acac)(CO)2 ] (acac=acetylacetonate) to the core-confined phosphine groups was rapid and quantitative. The CCM and M latexes were then used, in combination with [Rh(acac)(CO)2 ], to catalyze the aqueous biphasic hydroformylation of 1-octene, in which they showed high activity, recyclability, protection of the activated Rh center by the polymer scaffold, and low Rh leaching. The CCM latex gave slightly lower catalytic activity but significantly less Rh leaching than the M latex. A control experiment conducted in the presence of the sulfoxantphos ligand pointed to the action of the CCM as catalytic nanoreactors with substrate and product transport into and out of the polymer core, rather than as a surfactant in interfacial catalysis.

  16. Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles for stimulated osteoinductive response.

    PubMed

    Anderson, Joel M; Patterson, Jessica L; Vines, Jeremy B; Javed, Amjad; Gilbert, Shawn R; Jun, Ho-Wook

    2011-12-27

    Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. The structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanoparticles. Recreating this biphasic assembly, a bone ECM analogous scaffold comprising self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. PAs were endowed with biomolecular ligand signaling using a synthetically inscribed peptide sequence (i.e., RGDS) and integrated with HA nanoparticles to form a biphasic nanomatrix hydrogel. It was hypothesized the biphasic hydrogel would induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and improve bone healing as mediated by RGDS ligand signaling within PA nanofibers and embedded HA mineralization source. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation. After demonstrating initial viability, long-term cellularity and osteoinduction of encapsulated hMSCs in different PA hydrogels were studied in vitro. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. A preliminary animal study demonstrated bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration.

  17. Percutaneous biphasic electrical stimulation for treatment of obstructive sleep apnea syndrome.

    PubMed

    Hu, Lianggang; Xu, Xiaomei; Gong, Yongsheng; Fan, Xiaofang; Wang, Liangxing; Zhang, Jianhua; Zeng, Yanjun

    2008-01-01

    In this paper, we study the effect of stimulation of the genioglossus with percutaneous biphasic electrical pulses on patients with the obstructive sleep apnea syndrome (OSAS). The experiment was conducted in 22 patients clinically diagnosed with OSAS. The patients were monitored with polysomnography (PSG) in the trial. When the sleep apnea was detected, the genioglossus was stimulated with percutaneous biphasic electrical pulses that were automatically regulated by a microcontroller to achieve the optimal effect. The percutaneous biphasic electrical stimulation caused contraction of the genioglossus, forward movement of the tongue, and relieving of the glossopharyngeal airway obstruction. The SaO2, apnea time, hypoxemia time, and change of respiratory disturbance index (RDI) were compared in patients with treatment and without treatment. With percutaneous biphasic electrical stimulation of the genioglossus, the OSAS patients showed apnea time decreased (P < 0.01), RDI decreased (P < 0.01), and SaO2 increased (P < 0.01). No tissue injury or major discomfort was noticed during the trial. The stimulation of genioglossus with percutaneous biphasic electrical current pulse is an effective method for treating OSAS.

  18. Distribution of cortical granules and meiotic maturation of canine oocytes in bi-phasic systems.

    PubMed

    Apparicio, Maricy; Mostachio, Giuliano Q; Motheo, Tathiana F; Alves, Aracelle E; Padilha, Luciana; Pires-Butler, Eliandra A; Savi, Paula A P; Uscategui, Ricardo A R; Luvoni, Gaia C; Vicente, Wilter R R

    2015-09-01

    The aim of this study was to evaluate the influence of different bi-phasic systems with gonadotrophins and steroids on in vitro maturation rates of oocytes obtained from bitches at different reproductive stages (follicular, luteal, anoestrous). In System A (control) oocytes were matured for 72h in base medium (BM) with 10IUmL(-1) human chorionic gonadotrophin (hCG), 1μgmL(-1) progesterone (P4) and 1μgmL(-1) oestradiol (E2); in bi-phasic System B oocytes were matured for 48h in BM with hCG and for 24h in BM with P4; in bi-phasic System C oocytes were matured for 48h in BM with hCG, P4 and E2, and for 24h in BM with P4; in System D, oocytes were cultured in BM without hormonal supplementation. Data were analysed by ANOVA. There was a positive effect of the bi-phasic systems on germinal vesicle breakdown, metaphase I and metaphase II rates, irrespective of reproductive status (P<0.05). Bi-phasic systems were also beneficial for cortical granule distribution (an indication of cytoplasmic maturation) and its relationship to nuclear status: 74.5% of the oocytes cultured in System B and 85.4% of those cultured in System C presented both nuclear and cytoplasmic maturation (P<0.001). The stage of the oestrous cycle did not influence maturation rates.

  19. A biphasic scaffold based on silk and bioactive ceramic with stratified properties for osteochondral tissue regeneration.

    PubMed

    Li, Jiao Jiao; Kim, Kyungsook; Roohani-Esfahani, Seyed-Iman; Guo, Jin; Kaplan, David L; Zreiqat, Hala

    2015-07-14

    Significant clinical challenges encountered in the effective long-term treatment of osteochondral defects have inspired advancements in scaffold-based tissue engineering techniques to aid repair and regeneration. This study reports the development of a biphasic scaffold produced via a rational combination of silk fibroin and bioactive ceramic with stratified properties to satisfy the complex and diverse regenerative requirements of osteochondral tissue. Structural examination showed that the biphasic scaffold contained two phases with different pore morphologies to match the cartilage and bone segments of osteochondral tissue, which were joined at a continuous interface. Mechanical assessment showed that the two phases of the biphasic scaffold imitated the load-bearing behaviour of native osteochondral tissue and matched its compressive properties. In vitro testing showed that different compositions in the two phases of the biphasic scaffold could direct the preferential differentiation of human mesenchymal stem cells towards the chondrogenic or osteogenic lineage. By featuring simple and reproducible fabrication and a well-integrated interface, the biphasic scaffold strategy established in this study circumvented the common problems experienced with integrated scaffold designs and could provide an effective approach for the regeneration of osteochondral tissue.

  20. Small biphase wellhead plant for the Cerro Prieto Mexico geothermal field

    SciTech Connect

    Oropeza, A.; Hays, L.

    1996-12-31

    In a system of geothermal wells in a geothermal field, there are different production conditions of the flows, temperatures and pressures. At plants where the installed capacity requires the use of many wells, it is necessary to regulate the well`s pressure to ensure a stable condition for the turbines. Reducing the steam pressure on the wellhead is achieved by using an orifice plate (flash orifice). Use of an orifice plate results in a waste or loss of well pressure that could be utilized for production of electricity. The Cerro Prieto field, operated by the Comision Federal de Electricidad (CFE), has many wells operating at a very high pressure and producing a lot of water. Much of this pressure and water is not utilized in the production of electricity. With the purpose of taking advantage of this pressure CFE has evaluated a proposal by Biphase Energy Co. Biphase has designed and patented a turbine that works directly with the steam and water mixture coming from the wellhead, acting as a separator. Biphase has developed a model of its turbine and successfully operated it in Coso Hot Springs California. Knowing this CFE has signed an agreement with Biphase Energy Company to install and operate a biphasic turbine at the Cerro Prieto geothermal field located near Mexicali, Mexico.

  1. Evaluation of the finite element software ABAQUS for biomechanical modelling of biphasic tissues.

    PubMed

    Wu, J Z; Herzog, W; Epstein, M

    1998-02-01

    The biphasic cartilage model proposed by Mow et al. (1980) has proven successful to capture the essential mechanical features of articular cartilage. In order to analyse the joint contact mechanics in real, anatomical joints, the cartilage model needs to be implemented into a suitable finite element code to approximate the irregular surface geometries of such joints. However, systematic and extensive evaluation of the capacity of commercial software for modelling the contact mechanics with biphasic cartilage layers has not been made. This research was aimed at evaluating the commercial finite element software ABAQUS for analysing biphasic soft tissues. The solutions obtained using ABAQUS were compared with those obtained using other finite element models and analytical solutions for three numerical tests: an unconfined indentation test, a test with the contact of a spherical cartilage surface with a rigid plate, and an axi-symmetric joint contact test. It was concluded that the biphasic cartilage model can be implemented into the commercial finite element software ABAQUS to analyse practical joint contact problems with biphasic articular cartilage layers.

  2. X-linked MCT8 gene mutations: characterization of the pediatric neurologic phenotype.

    PubMed

    Holden, Kenton R; Zuñiga, Oscar F; May, Melanie M; Su, Humberto; Molinero, Marco R; Rogers, R Curtis; Schwartz, Charles E

    2005-10-01

    We report a family with X-linked mental retardation that has a novel mutation in the monocarboxylate transporter 8 (MCT8) gene associated with a characteristic neurodevelopmental phenotype with early childhood hypotonia that progresses to spasticity and global developmental delays. Affected patients experience moderate to severe psychomotor delays and congenital hypotonia, develop a myopathic facies, have diminished muscle bulk and generalized muscle weakness, develop progressive spasticity and movement disorders, and have limited speech but alert, affable personalities. Acquired microcephaly and abnormal myelination on brain magnetic resonance imaging can be present. Normal monocarboxylate transporter 8 gene functioning appears to be necessary for normal thyroid-associated metabolism in neurons. Abnormal thyroid function tests appear to be a consistent finding in the absence of typical signs of thyroid dysfunction. Although the phenotype appears to be consistent, and although the neurotoxic effects of abnormal central and peripheral neuromuscular system thyroid metabolism might be partly or wholly responsible for the neurologic phenotype reported, the exact mechanism remains unclear.

  3. A finite element implementation for biphasic contact of hydrated porous media under finite deformation and sliding

    PubMed Central

    Guo, Hongqiang; Shah, Mitul; Spilker, Robert L.

    2014-01-01

    The study of biphasic soft tissues contact is fundamental to understanding the biomechanical behavior of human diarthrodial joints. However, to date, few biphasic finite element contact analysis for 3D physiological geometries under finite deformation has been developed. The objective of this paper is to develop a hyperelastic biphasic contact implementation for finite deformation and sliding problem. An augmented Lagrangian method was used to enforce the continuity of contact traction and fluid pressure across the contact interface. The finite element implementation was based on a general purpose software, COMSOL Multiphysics. The accuracy of the implementation is verified using example problems, for which solutions are available by alternative analyses. The implementation was proven to be robust and able to handle finite deformation and sliding. PMID:24496915

  4. Pretreatment of Eucalyptus in biphasic system for furfural production and accelerated enzymatic hydrolysis.

    PubMed

    Zhang, Xiudong; Bai, Yuanyuan; Cao, Xuefei; Sun, Runcang

    2017-08-01

    Herein, an efficient biphasic pretreatment process was developed to improve the production of furfural (FF) and glucose from Eucalyptus. The influence of formic acid and NaCl on FF production from xylose in water and various biphasic systems was investigated. Results showed that the addition of formic acid and NaCl significantly promoted the FF yield, and the biphasic system of MIBK (methyl isobutyl ketone)/water exhibited the best performance for FF production. Then the Eucalyptus was pretreated in the MIBK/water system, and a maximum FF yield of 82.0% was achieved at 180°C for 60min. Surface of the pretreated Eucalyptus became relatively rough and loose, and its crystallinity index increased obviously due to the removal of hemicelluloses and lignin. The pretreated Eucalyptus samples showed much higher enzymatic hydrolysis rates (26.2-70.7%) than the raw Eucalyptus (14.5%). Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Shock-induced termination of reentrant cardiac arrhythmias: Comparing monophasic and biphasic shock protocols

    SciTech Connect

    Bragard, Jean Simic, Ana; Elorza, Jorge; Grigoriev, Roman O.; Fenton, Flavio H.; Cherry, Elizabeth M.; Gilmour, Robert F.; Otani, Niels F.

    2013-12-15

    In this article, we compare quantitatively the efficiency of three different protocols commonly used in commercial defibrillators. These are based on monophasic and both symmetric and asymmetric biphasic shocks. A numerical one–dimensional model of cardiac tissue using the bidomain formulation is used in order to test the different protocols. In particular, we performed a total of 4.8 × 10{sup 6} simulations by varying shock waveform, shock energy, initial conditions, and heterogeneity in internal electrical conductivity. Whenever the shock successfully removed the reentrant dynamics in the tissue, we classified the mechanism. The analysis of the numerical data shows that biphasic shocks are significantly more efficient (by about 25%) than the corresponding monophasic ones. We determine that the increase in efficiency of the biphasic shocks can be explained by the higher proportion of newly excited tissue through the mechanism of direct activation.

  6. Shock-induced termination of reentrant cardiac arrhythmias: Comparing monophasic and biphasic shock protocols

    NASA Astrophysics Data System (ADS)

    Bragard, Jean; Simic, Ana; Elorza, Jorge; Grigoriev, Roman O.; Cherry, Elizabeth M.; Gilmour, Robert F.; Otani, Niels F.; Fenton, Flavio H.

    2013-12-01

    In this article, we compare quantitatively the efficiency of three different protocols commonly used in commercial defibrillators. These are based on monophasic and both symmetric and asymmetric biphasic shocks. A numerical one-dimensional model of cardiac tissue using the bidomain formulation is used in order to test the different protocols. In particular, we performed a total of 4.8 × 106 simulations by varying shock waveform, shock energy, initial conditions, and heterogeneity in internal electrical conductivity. Whenever the shock successfully removed the reentrant dynamics in the tissue, we classified the mechanism. The analysis of the numerical data shows that biphasic shocks are significantly more efficient (by about 25%) than the corresponding monophasic ones. We determine that the increase in efficiency of the biphasic shocks can be explained by the higher proportion of newly excited tissue through the mechanism of direct activation.

  7. Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve.

    PubMed

    Celik, Ilhan; Sürücü, Oguzkan; Dietz, Carsten; Heymach, John V; Force, Jeremy; Höschele, Iris; Becker, Christian M; Folkman, Judah; Kisker, Oliver

    2005-12-01

    We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.

  8. Shock-induced termination of reentrant cardiac arrhythmias: Comparing monophasic and biphasic shock protocols

    PubMed Central

    Bragard, Jean; Simic, Ana; Elorza, Jorge; Grigoriev, Roman O.; Cherry, Elizabeth M.; Gilmour, Robert F.; Otani, Niels F.; Fenton, Flavio H.

    2013-01-01

    In this article, we compare quantitatively the efficiency of three different protocols commonly used in commercial defibrillators. These are based on monophasic and both symmetric and asymmetric biphasic shocks. A numerical one–dimensional model of cardiac tissue using the bidomain formulation is used in order to test the different protocols. In particular, we performed a total of 4.8 × 106 simulations by varying shock waveform, shock energy, initial conditions, and heterogeneity in internal electrical conductivity. Whenever the shock successfully removed the reentrant dynamics in the tissue, we classified the mechanism. The analysis of the numerical data shows that biphasic shocks are significantly more efficient (by about 25%) than the corresponding monophasic ones. We determine that the increase in efficiency of the biphasic shocks can be explained by the higher proportion of newly excited tissue through the mechanism of direct activation. PMID:24387558

  9. Photoinduced biphasic hydrogen evolution: decamethylosmocene as a light-driven electron donor.

    PubMed

    Ge, Peiyu; Olaya, Astrid J; Scanlon, Micheál D; Hatay Patir, Imren; Vrubel, Heron; Girault, Hubert H

    2013-07-22

    Excitation of the weak electron donor decamethylosmocene on illumination with white light produces an excited-state species capable of reducing organically solubilized protons under biphasic conditions. Insight into the mechanism and kinetics of light-driven biphasic hydrogen evolution are obtained by analysis with gas chromatography, cyclic voltammetry, and UV/Vis and (1)H NMR spectroscopy. Formation of decamethylosmocenium hydride, which occurs prior to hydrogen evolution, is a rapid step relative to hydrogen release and takes place independently of light activation. Remarkably, hydride formation occurs with greater efficiency (ca. 90% conversion) under biphasic conditions than when the reaction is carried out in an acidified single organic phase (ca. 20% conversion). Cyclic voltammetry studies reveal that decamethylosmocene has a higher proton affinity than either decamethylferrocene or osmocene.

  10. Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level.

    PubMed

    Klank, Rebecca L; Decker Grunke, Stacy A; Bangasser, Benjamin L; Forster, Colleen L; Price, Matthew A; Odde, Thomas J; SantaCruz, Karen S; Rosenfeld, Steven S; Canoll, Peter; Turley, Eva A; McCarthy, James B; Ohlfest, John R; Odde, David J

    2017-01-03

    While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.

  11. Investigation of the feasibility of a biphase turbine for industrial process energy recovery. Final report

    SciTech Connect

    Helgeson, N.

    1985-06-28

    Tests were conducted to assess the technical applicability of the Biphase turbine to two process streams. A Biphase impulse turbine was tested on a flashing Selexol stream used for removal of CO/sub 2/ from process gases. The experimental results showed that the two-phase nozzle performance of the flashing Selexol stream was substantially below equilibrium calculation predictions. Consequently, the turbine power generated by this expanding two-phase flow was below predicted values, and was approximately equivalent to the liquid hydraulic power available. Additional gas-liquid phase separation occurred on the rotor such that overall separation efficiency reached 98% of that which occurred in the long residence time settling tank (equilibrium). The Biphase reaction turbine was tested on a flashing natural gas/crude oil stream. Nozzle, rotary and overall turbine performance were in good agreement with pre-test predictions for power generation and efficiency of operation. 141 figs., 35 tabs.

  12. Dissolved nutrients and atrazine removal by column-scale monophasic and biphasic rain garden model systems.

    PubMed

    Yang, Hanbae; McCoy, Edward L; Grewal, Parwinder S; Dick, Warren A

    2010-08-01

    Rain gardens are bioretention systems that have the potential to reduce peak runoff flow and improve water quality in a natural and aesthetically pleasing manner. We compared hydraulic performance and removal efficiencies of nutrients and atrazine in a monophasic rain garden design versus a biphasic design at a column-scale using simulated runoff. The biphasic rain garden was designed to increase retention time and removal efficiency of runoff pollutants by creating a sequence of water saturated to unsaturated conditions. We also evaluated the effect of C substrate availability on pollutant removal efficiency in the biphasic rain garden. Five simulated runoff events with various concentrations of runoff pollutants (i.e. nitrate, phosphate, and atrazine) were applied to the monophasic and biphasic rain gardens once every 5d. Hydraulic performance was consistent over the five simulated runoff events. Peak flow was reduced by approximately 56% for the monophasic design and 80% for the biphasic design. Both rain garden systems showed excellent removal efficiency of phosphate (89-100%) and atrazine (84-100%). However, significantly (p<0.001) higher removal of nitrate was observed in the biphasic (42-63%) compared to the monophasic rain garden (29-39%). Addition of C substrate in the form of glucose increased removal efficiency of nitrate significantly (p<0.001), achieving up to 87% removal at a treatment C/N ratio of 2.0. This study demonstrates the importance of retention time, environmental conditions (i.e. saturated/unsaturated conditions), and availability of C substrate for bioremediation of pollutants, especially nitrates, in rain gardens. (c) 2010 Elsevier Ltd. All rights reserved.

  13. A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering

    PubMed Central

    Choy, Andrew Tsz Hang; Chan, Barbara Pui

    2015-01-01

    Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering. PMID:26115332

  14. Citrate-Based Biphasic Scaffolds for the Repair of Large Segmental Bone Defects

    PubMed Central

    Guo, Ying; Tran, Richard T.; Xie, Denghui; Nguyen, Dianna Y.; Gerhard, Ethan; Guo, Jinshan; Wang, Yuchen; Tang, Jiajun; Zhang, Zhongming; Bai, Xiaochun; Yang, Jian

    2014-01-01

    Attempts to replicate native tissue architecture have lead to the design of biomimetic scaffolds focused on improving functionality. In this study, biomimetic citrate-based poly (octanediol citrate) – click hydroxyapatite (POC-Click-HA) scaffolds were developed to simultaneously replicate the compositional and architectural properties of native bone tissue while providing immediate structural support for large segmental defects following implantation. Biphasic scaffolds were fabricated with 70% internal phase porosity and various external phase porosities (between 5–50%) to mimic the bimodal distribution of cancellous and cortical bone, respectively. Biphasic POC-Click-HA scaffolds displayed compressive strengths up to 37.45 ± 3.83 MPa, which could be controlled through the external phase porosity. The biphasic scaffolds were also evaluated in vivo for the repair of 10-mm long segmental radial defects in rabbits and compared to scaffolds of uniform porosity as well as autologous bone grafts after 5, 10, and 15 weeks of implantation. The results showed that all POC-Click-HA scaffolds exhibited good biocompatibility and extensive osteointegration with host bone tissue. Biphasic scaffolds significantly enhanced new bone formation with higher bone densities in the initial stages after implantation. Biomechanical and histomorphometric analysis supported a similar outcome with biphasic scaffolds providing increased compression strength, interfacial bone ingrowth, and periosteal remodeling in early time points, but were comparable to all experimental groups after 15 weeks. These results confirm the ability of biphasic scaffold architectures to restore bone tissue and physiological functions in the early stages of recovery, and the potential of citrate-based biomaterials in orthopedic applications. PMID:24829094

  15. Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

    PubMed Central

    Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

    2016-01-01

    Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the

  16. Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak.

    PubMed

    Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J; Eisner, David A; Venetucci, Luigi

    2016-02-01

    Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay. In the presence of β-adrenergic stimulation, RyR-mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase. Two forms of Ca leak have been studied, Ca-sensitising (induced by caffeine) and non-sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient. Only Ca-sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine. Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca-sensitising and non-sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca(2+)]i with fluo-3 in voltage-clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non-sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca(2+)]i , increased diastolic [Ca(2+)]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l(-1)) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow

  17. Dissection of the biphasic nature of hypoxia-induced motogenic action in bone marrow-derived human mesenchymal stem cells.

    PubMed

    Busletta, Chiara; Novo, Erica; Valfrè Di Bonzo, Lorenzo; Povero, Davide; Paternostro, Claudia; Ievolella, Monica; Mareschi, Katia; Ferrero, Ivana; Cannito, Stefania; Compagnone, Alessandra; Bandino, Andrea; Colombatto, Sebastiano; Fagioli, Franca; Parola, Maurizio

    2011-06-01

    Hypoxic conditions have been reported to facilitate preservation of undifferentiated mesenchymal stem cell (MSC) phenotype and positively affect their colony-forming potential, proliferation, and migration/mobilization. In this study, designed to dissect mechanisms underlying hypoxia-dependent migration of bone marrow-derived human MSC (hMSC), signal transduction, and molecular mechanisms were evaluated by integrating morphological, molecular, and cell biology techniques, including the wound healing assay (WHA) and modified Boyden's chamber assay (BCA) to monitor migration. Exposure of hMSCs to moderate hypoxia resulted in a significant increase of migration of hMSCs in both WHA (from 6 to 20 hours) and BCA (within 6 hours). Mechanistic experiments outlined the following sequence of hypoxia-dependent events: (a) very early (15 minutes) increased generation of intracellular reactive oxygen species (ROS), which (b) was sufficient to switch on activation of extracellular regulated kinase 1/2 and c-Jun N-terminal protein kinase 1/2, found to be relevant for the early phase of hMSC migration; (c) hypoxia inducible factor-1 (HIF-1)-dependent increased expression of vascular endothelial growth factor (VEGF) (facilitated by ROS) and its progressive release that was responsible for (d) a delayed and sustained migration of hMSCs. These results suggest that hypoxia-dependent migration relies on a previously unrecognized biphasic scenario involving an early phase, requiring generation of ROS, and a delayed phase sustained by HIF-1-dependent expression and release of VEGF.

  18. Aqueous biphasic extraction process with pH and particle control

    DOEpatents

    Chaiko, D.J.; Mensah-Biney, R.

    1995-05-02

    A process for aqueous biphasic extraction of metallic oxides and the like from substances containing silica. Control of media pH enables efficient and effective partition of mixture components. The inventive method may be employed to remove excess silica from kaolin clay. 2 figs.

  19. Aqueous biphasic extraction process with pH and particle control

    DOEpatents

    Chaiko, David J.; Mensah-Biney, R.

    1995-01-01

    A process for aqueous biphasic extraction of metallic oxides and the like from substances containing silica. Control of media pH enables efficient and effective partition of mixture components. The inventive method may be employed to remove excess silica from kaolin clay.

  20. Selection of Xenobiotic-Degrading Microorganisms in a Biphasic Aqueous-Organic System

    PubMed Central

    Ascon-Cabrera, Miguel; Lebeault, Jean-Michel

    1993-01-01

    Microbial selection on mixtures of chlorinated and nonchlorinated compounds that are poorly soluble in water and/or toxic to growing microbial cells was examined in both biphasic aqueous-organic and monophasic aqueous systems. A biphasic system in which silicone oil was used as the organic phase permitted the acceleration of acclimation, leading to rapid selection and to an increase in xenobiotic compound degradation. In contrast, acclimation, selection, and degradation were very slow in the monophasic aqueous system. The variation in microbial growth rate with the degree of dispersion (i.e., dispersion at different silicone oil concentrations and agitation rates), and cell adhesion to the silicone oil indicate that the performance of the biphasic aqueous-organic system is dependent on the interfacial area between the two phases and that microbial activity is important at this interface. Therefore, the biphasic water-silicone oil system could be used for microbial selection in the presence of xenobiotic compounds that are toxic and have low water solubility. PMID:16348949

  1. Recycling nanoparticle catalysts without separation based on a pickering emulsion/organic biphasic system.

    PubMed

    Liu, Huifang; Zhang, Zhiming; Yang, Hengquan; Cheng, Fangqin; Du, Zhiping

    2014-07-01

    A conceptually novel methodology is explored for in situ recycling of nanoparticle catalysts based on transforming a conventional organic/aqueous biphasic system into a Pickering emulsion/organic biphasic system (PEOBS). The suggested PEOBS exists as two phases, with the nanoparticle catalyst "anchored" in the Pickering emulsion phase, but is "continuous" between the organic phase and the continuous phase of the Pickering emulsion. Aqueous hydrogenations are used to evaluate the reaction performances of PEOBS, and the underlying principles of PEOBS are preliminarily elaborated. The unique properties of PEOBS lead to many intriguing findings, which are unlikely to be achieved in the reported biphasic systems. PEOBS exhibits more than a fourfold enhancement in catalysis efficiency in comparison with a conventional biphasic system. Impressively, PEOBS enables the organic product to be facilely isolated through simple decantation and the nanoparticle catalyst can be recycled in situ without the need for "separation". Its recycling effectiveness is justified by ten reaction cycles without significant catalyst loss. The simple protocol, in conjunction with the stability to simultaneously achieve high catalysis efficiency and excellent catalyst recyclability, makes PEOBS a promising methodology to develop more sustainable nanocatalysis.

  2. A pilot trial of square biphasic pulse deep brain stimulation for dystonia: The BIP dystonia study.

    PubMed

    Almeida, Leonardo; Martinez-Ramirez, Daniel; Ahmed, Bilal; Deeb, Wissam; Jesus, Sol De; Skinner, Jared; Terza, Matthew J; Akbar, Umer; Raike, Robert S; Hass, Chris J; Okun, Michael S

    2017-04-01

    Dystonia often has inconsistent benefits and requires more energy-demanding DBS settings. Studies suggest that squared biphasic pulses could provide significant clinical benefit; however, dystonia patients have not been explored. To assess safety and tolerability of square biphasic DBS in dystonia patients. This study included primary generalized or cervical dystonia patients with bilateral GPi DBS. Square biphasic pulses were implemented and patients were assessed at baseline, immediately postwashout, post-30-minute washout, 1 hour post- and 2 hours postinitiation of investigational settings. Ten participants completed the study. There were no patient-reported or clinician-observed side effects. There was improvement across time on the Toronto Western Spasmodic Torticollis Rating Scale (χ(2)  = 10.7; P = 0.031). Similar improvement was detected in objective gait measurements. Square biphasic stimulation appears safe and feasible in dystonia patients with GPi DBS. Further studies are needed to evaluate possible effectiveness particularly in cervical and gait features. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  3. Modeling Biphasic Environmental Decay of Pathogens and Implications for Risk Analysis.

    PubMed

    Brouwer, Andrew F; Eisenberg, Marisa C; Remais, Justin V; Collender, Philip A; Meza, Rafael; Eisenberg, Joseph N S

    2017-02-21

    As the appreciation for the importance of the environment in infectious disease transmission has grown, so too has interest in pathogen fate and transport. Fate has been traditionally described by simple exponential decay, but there is increasing recognition that some pathogens demonstrate a biphasic pattern of decay-fast followed by slow. While many have attributed this behavior to population heterogeneity, we demonstrate that biphasic dynamics can arise through a number of plausible mechanisms. We examine the identifiability of a general model encompassing three such mechanisms: population heterogeneity, hardening off, and the existence of viable-but-not-culturable states. Although the models are not fully identifiable from longitudinal sampling studies of pathogen concentrations, we use a differential algebra approach to determine identifiable parameter combinations. Through case studies using Cryptosporidium and Escherichia coli, we show that failure to consider biphasic pathogen dynamics can lead to substantial under- or overestimation of disease risks and pathogen concentrations, depending on the context. More reliable models for environmental hazards and human health risks are possible with an improved understanding of the conditions in which biphasic die-off is expected. Understanding the mechanisms of pathogen decay will ultimately enhance our control efforts to mitigate exposure to environmental contamination.

  4. An effective biphase system accelerates hesperidinase-catalyzed conversion of rutin to isoquercitrin

    PubMed Central

    Wang, Jun; Gong, An; Yang, Cai-Feng; Bao, Qi; Shi, Xin-Yi; Han, Bei-Bei; Wu, Xiang-Yang; Wu, Fu-An

    2015-01-01

    Isoquercitrin is a rare, natural ingredient with several biological activities that is a key precursor for the synthesis of enzymatically modified isoquercitrin (EMIQ). The enzymatic production of isoquercitrin from rutin catalyzed by hesperidinase is feasible; however, the bioprocess is hindered by low substrate concentration and a long reaction time. Thus, a novel biphase system consisting of [Bmim][BF4]:glycine-sodium hydroxide (pH 9) (10:90, v/v) and glyceryl triacetate (1:1, v/v) was initially established for isoquercitrin production. The biotransformation product was identified using liquid chromatography-mass spectrometry, and the bonding mechanism of the enzyme and substrate was inferred using circular dichroism spectra and kinetic parameters. The highest rutin conversion of 99.5% and isoquercitrin yield of 93.9% were obtained after 3 h. The reaction route is environmentally benign and mild, and the biphase system could be reused. The substrate concentration was increased 2.6-fold, the reaction time was reduced to three tenths the original time. The three-dimensional structure of hesperidinase was changed in the biphase system, which α-helix and random content were reduced and β-sheet content was increased. Thus, the developed biphase system can effectively strengthen the hesperidinase-catalyzed synthesis of isoquercitrin with high yield. PMID:25731802

  5. Cell surface energy, contact angles and phase partition. II. Bacterial cells in biphasic aqueous mixtures.

    PubMed

    Gerson, D F; Akit, J

    1980-11-04

    Partition coefficients in biphasic mixtures of poly(ethylene glycol) and Dextran are compared to cell surface energies obtained from contact angles of each liquid phase on cell layers. Linear relationships are observed between these two independent measurements for a variety of bacterial cells. The results demonstrate the importance of interfacial phenomena and contact angles in the phase-partition process.

  6. Engineering anisotropic biphasic Janus-type polymer nanofiber scaffold networks via centrifugal jet spinning.

    PubMed

    Khang, Alex; Ravishankar, Prashanth; Krishnaswamy, Aditya; Anderson, Patrick K; Cone, Stephanie G; Liu, Zizhao; Qian, Xianghong; Balachandran, Kartik

    2017-11-01

    Biphasic materials, comprised of an ordered arrangement of two different material phases within a material, have the potential for a wide variety of applications including filtration, protective clothing and tissue engineering. This study reports for the first time, a process for engineering biphasic Janus-type polymeric nanofiber (BJPNF) networks via the centrifugal jet spinning technique. BJPNF alignment and fiber diameter was dependent on fabrication rotational speed as well as solution composition. The biphasic character of these BJPNFs, which was controlled via the rotational speed of fabrication, was confirmed at the individual nanofiber scale using energy dispersive X-ray spectroscopy, and at the bulk, macro-scale using attenuated total reflectance-Fourier transform infrared spectroscopy. Biphasic character was also demonstrated at the functional level via differing affinities on either side of the BJPNF for cell attachment. Our work thus presents a method for fabricating BJPNF scaffold networks where there might be a need for different properties on either side of a material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2455-2464, 2017. © 2016 Wiley Periodicals, Inc.

  7. Biphasic Electrical Field Stimulation Aids in Tissue Engineering of Multicell-Type Cardiac Organoids

    PubMed Central

    Chiu, Loraine L.Y.; Iyer, Rohin K.; King, John-Paul

    2011-01-01

    The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence. PMID:18783322

  8. Biphasic electrical field stimulation aids in tissue engineering of multicell-type cardiac organoids.

    PubMed

    Chiu, Loraine L Y; Iyer, Rohin K; King, John-Paul; Radisic, Milica

    2011-06-01

    The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence.

  9. Strontium substituted calcium phosphate biphasic ceramics obtained by a powder precipitation method.

    PubMed

    Kim, Hae-Won; Koh, Young-Hag; Kong, Young-Min; Kang, Jun-Gu; Kim, Hyoun-Ee

    2004-10-01

    Strontium (Sr) substituted calcium phosphate ceramics were fabricated using a powder precipitation method. The Sr ions were added up to 8 mol % to replace the Ca ions during the powder preparation. Composition analysis showed that the added Sr was not fully incorporated within the as-precipitated apatite structure, presumably being washed out during the powder preparation. After calcination, the Sr containing powders were crystallized into apatite and tricalcium phosphate (TCP), that is, biphasic calcium phosphates were formed. The amount of TCP increased with increasing the Sr addition. The lattice parameters of the calcined powders increased gradually with Sr substitution in both the a- and c-axis. However, the obtained values deviated slightly from the calculated ones at higher Sr additions (>4%) due to the partial substitution of Sr ions. The microstructure of the sintered bodies changed with the Sr addition due to the formation of TCP. The Vickers hardness increased slightly from 5.2 to 5.5 MPa with increasing Sr addition, which was driven by the HA+TCP biphasic formation. The osteoblast-like cells cultured on the Sr-substituted biphasic sample spread and grew actively. The proliferation rate of the cells was higher in the samples containing more Sr. The alkaline phosphate activity of the cells was expressed to a higher degree with increasing Sr addition. These observations confirmed the enhanced cell viability and differentiation of the Sr-substituted biphasic calcium phosphate ceramics.

  10. Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration.

    PubMed

    Son, Jun-Sik; Kim, Su-Gwan; Oh, Ji-Su; Appleford, Mark; Oh, Sunho; Ong, Joo L; Lee, Kyu-Bok

    2011-12-15

    This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical-like shells were composed of porous hydroxyapatite (HA) with a hollow interior using a polymeric template-coating technique; the inner trabecular-like core consisted of porous poly(D,L-lactic acid) (PLA) that was loaded with dexamethasone (DEX) and was directly produced using a particle leaching/gas forming technique to create the inner diameter of the HA scaffold. It was observed that the HA and PLA parts of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore structures, and the boundary between both parts was tightly connected without any gaps. It was found that the structure of the combination scaffold was analogous to that of natural bone based on micro-computed tomography analysis. Additionally, the dense, uniform apatite layer was formed on the surface of the HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully released from the PLA of the biphasic scaffold over a 1-month period. This release caused human embryonic palatal mesenchyme cells to proliferate, differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded that this functionally graded scaffold is similar to natural bone and represents a potential bone-substitute material.

  11. Biphasic Dose Response in Low Level Light Therapy – An Update

    PubMed Central

    Huang, Ying-Ying; Sharma, Sulbha K; Carroll, James; Hamblin, Michael R

    2011-01-01

    Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments. PMID:22461763

  12. Developmental modularity and phenotypic novelty within a biphasic life cycle: morphogenesis of a cone snail venom gland.

    PubMed

    Page, Louise R

    2012-01-07

    The venom gland of predatory cone snails (Conus spp.), which secretes neurotoxic peptides that rapidly immobilize prey, is a proposed key innovation for facilitating the extraordinary feeding behaviour of these gastropod molluscs. Nevertheless, the unusual morphology of this gland has generated controversy about its evolutionary origin and possible homologues in other gastropods. I cultured feeding larvae of Conus lividus and cut serial histological sections through the developing foregut during larval and metamorphic stages to examine the development of the venom gland. Results support the hypothesis of homology between the venom gland and the mid-oesophageal gland of other gastropods. They also suggest that the mid-region of the gastropod foregut, like the anterior region, is divisible into dorsal and ventral developmental modules that have different morphological, functional and ontogenetic fates. In larvae of C. lividus, the ventral module of the middle foregut transformed into the anatomically novel venom gland of the post-metamorphic stage by rapidly pinching-off from the main dorsal channel of the mid-oesophagus, an epithelial remodelling process that may be similar to other cases where epithelial tubes and vesicles arise from a pre-existing epithelial sheet. The developmental remodelling mechanism could have facilitated an abrupt evolutionary transition to the derived morphology of this important gastropod feeding innovation.

  13. Developmental modularity and phenotypic novelty within a biphasic life cycle: morphogenesis of a cone snail venom gland

    PubMed Central

    Page, Louise R.

    2012-01-01

    The venom gland of predatory cone snails (Conus spp.), which secretes neurotoxic peptides that rapidly immobilize prey, is a proposed key innovation for facilitating the extraordinary feeding behaviour of these gastropod molluscs. Nevertheless, the unusual morphology of this gland has generated controversy about its evolutionary origin and possible homologues in other gastropods. I cultured feeding larvae of Conus lividus and cut serial histological sections through the developing foregut during larval and metamorphic stages to examine the development of the venom gland. Results support the hypothesis of homology between the venom gland and the mid-oesophageal gland of other gastropods. They also suggest that the mid-region of the gastropod foregut, like the anterior region, is divisible into dorsal and ventral developmental modules that have different morphological, functional and ontogenetic fates. In larvae of C. lividus, the ventral module of the middle foregut transformed into the anatomically novel venom gland of the post-metamorphic stage by rapidly pinching-off from the main dorsal channel of the mid-oesophagus, an epithelial remodelling process that may be similar to other cases where epithelial tubes and vesicles arise from a pre-existing epithelial sheet. The developmental remodelling mechanism could have facilitated an abrupt evolutionary transition to the derived morphology of this important gastropod feeding innovation. PMID:21593033

  14. A comparison between mechano-electrochemical and biphasic swelling theories for soft hydrated tissues.

    PubMed

    Wilson, W; van Donkelaar, C C; Huyghe, J M

    2005-02-01

    Biological tissues like intervertebral discs and articular cartilage primarily consist of interstitial fluid, collagen fibrils and negatively charged proteoglycans. Due to the fixed charges of the proteoglycans, the total ion concentration inside the tissue is higher than in the surrounding synovial fluid (cation concentration is higher and the anion concentration is lower). This excess of ion particles leads to an osmotic pressure difference, which causes swelling of the tissue. In the last decade several mechano-electrochemical models, which include this mechanism, have been developed. As these models are complex and computationally expensive, it is only possible to analyze geometrically relatively small problems. Furthermore, there is still no commercial finite element tool that includes such a mechano-electrochemical theory. Lanir (Biorheology, 24, pp. 173-187, 1987) hypothesized that electrolyte flux in articular cartilage can be neglected in mechanical studies. Lanir's hypothesis implies that the swelling behavior of cartilage is only determined by deformation of the solid and by fluid flow. Hence, the response could be described by adding a deformation-dependent pressure term to the standard biphasic equations. Based on this theory we developed a biphasic swelling model. The goal of the study was to test Lanir's hypothesis for a range of material properties. We compared the deformation behavior predicted by the biphasic swelling model and a full mechano-electrochemical model for confined compression and 1D swelling. It was shown that, depending on the material properties, the biphasic swelling model behaves largely the same as the mechano-electrochemical model, with regard to stresses and strains in the tissue following either mechanical or chemical perturbations. Hence, the biphasic swelling model could be an alternative for the more complex mechano-electrochemical model, in those cases where the ion flux itself is not the subject of the study. We propose

  15. Eosinophilia-myalgia syndrome: myopathic electrodiagnostic characteristics.

    PubMed

    Tanhehco, J L; Wiechers, D O; Golbus, J; Neely, S E

    1992-05-01

    Eosinophilia-myalgia syndrome (EMS) is a disorder characterized by generalized muscle pain and eosinophilia. The etiology of this syndrome appears to be related to the ingestion of L-tryptophan. Most studies to date describe an associated peripheral neuropathy or combined myopathy and peripheral neuropathy. This report presents 2 EMS patients with myopathy, confirmed by muscle biopsy in 1 case and electrophysiology in both cases. No clinical evidence of neuropathy was found. Both routine and single fiber electromyography failed to demonstrate abnormalities, suggesting neuropathy. Electrodiagnostic abnormalities paralleled the clinical course. After 10 months, both patients continued to have symptoms of muscle cramping and reduced endurance, with mild electromyographic abnormalities, perhaps reflecting changes in their motor unit.

  16. Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and pathological phenotype.

    PubMed

    Quinlivan, Ros; Mitsuahashi, Satomi; Sewry, Caroline; Cirak, Sebahattin; Aoyama, Chieko; Mooore, David; Abbs, Stephen; Robb, Stephanie; Newton, Tina; Moss, Celia; Birchall, Daniel; Sugimoto, Hiroyuki; Bushby, Kate; Guglieri, Michela; Muntoni, Francesco; Nishino, Ichizo; Straub, Volker

    2013-07-01

    Three patients with CHKB deficient muscular dystrophy are described which broadens the previously described phenotype. Blood smear in one patient showed Jordans anomaly (vacuolated leukocytes). Gastrointestinal features occurred in two patients and there appeared to be acute deterioration with infection/general anaesthesia. Brain imaging showed no structural changes but brain magnetic resonance proton spectroscopy (MRS) demonstrated significant reduction in choline:N-acetyl aspartate and choline:creatine ratios in keeping with a general decrease in the amount of choline and phosphocholine-based substrate. Muscle pathology showed either myopathic or dystrophic features, uneven oxidative enzyme staining, COX deficient fibres and peripherally located large mitochondria. CHKB activity was reduced in all three patients and complex 1 activity was significantly reduced in one patient.

  17. Efficacy of transthoracic cardioversion of atrial fibrillation using a biphasic, truncated exponential shock waveform at variable initial shock energies.

    PubMed

    Rashba, Eric J; Gold, Michael R; Crawford, Fred A; Leman, Robert B; Peters, Robert W; Shorofsky, Stephen R

    2004-12-15

    Biphasic shocks are more effective than damped sine wave monophasic shocks for transthoracic cardioversion (CV) of atrial fibrillation (AF), but the optimal protocol for CV with biphasic shocks has not been defined. We conducted a prospective, randomized study of 120 consecutive patients with persistent AF to delineate the dose-response curve for CV of AF with a biphasic truncated exponential shock waveform and to identify clinical predictors of shock efficacy. Our data suggest that the initial shock energy for CV with this waveform should be 200 J if the patient weighs <90 kg and 360 J if the patient weighs >/=90 kg.

  18. Bi-phasic growth of Listeria monocytogenes in chemically defined medium at low temperatures.

    PubMed

    Tyrovouzis, Nikolaos A; Angelidis, Apostolos S; Stoforos, Nikolaos G

    2014-09-01

    The present work reports a novel observation regarding the growth of L. monocytogenes in modified Welshimer's broth (MWB) at low temperatures. Specifically, the direct monitoring of the growth of L. monocytogenes Scott A using plate count data revealed that the pathogen displays a bi-phasic growth pattern in MWB at 7 °C. This bi-phasic growth pattern is masked (not observed) when optical density (OD) measurements are used to monitor growth due to the inability of OD readings to detect L. monocytogenes population density increases up to 10(7) CFU/mL. This bi-phasic growth phenomenon was further investigated as a function of growth temperature (4 °C, 7 °C, 10 °C, 14 °C and 18 °C), medium composition (by altering the MWB composition by ten-fold increases in different sets of medium constituents), inoculum level (10(2), 10(3), 10(4), 10(5), 10(6), and 10(7) CFU/mL) and L. monocytogenes strain (10 strains). The growth of L. monocytogenes Scott A in MWB at 7 °C, 10 °C and 14 °C was consistently bi-phasic and independent of growth rate; at 18 °C, growth was consistently mono-phasic (single-phase, typical sigmoid growth curves), whereas no growth was observed at 4 °C. The tested modifications in the composition of MWB did not influence the bi-phasic nature of L. monocytogenes Scott A growth at 7 °C, and, overall, we could not point out any strain-, or serotype-specific effects. On the other hand, the initial inoculum level appears to affect the form of the growth curve, as there was a shift towards mono-phasic growth in trials with increasing initial inocula. A mathematical model, based on a stepwise response and described through two sequential sigmoid curves, was used to describe bi-phasic growth and estimate the kinetic parameters of L. monocytogenes growth. An alternative hypothesis, based on the assumption of the existence of two subpopulations, possessing different growth kinetics, materialized under the stress imposed on L. monocytogenes cells due to the

  19. Efficacy and safety of biphasic insulin aspart and biphasic insulin lispro mix in patients with type 2 diabetes: A review of the literature

    PubMed Central

    Kumar, Ajay

    2016-01-01

    Type 2 diabetes (T2D) represents an escalating burden worldwide, particularly in China and India. Compared with Caucasians, Asian people with diabetes have lower body mass index, increased visceral adiposity, and postprandial glucose (PPG)/insulin resistance. Since postprandial hyperglycemia contributes significantly to total glycemic burden and is associated with heightened cardiovascular risk, targeting PPG early in T2D is paramount. Premixed insulin regimens are widely used in Asia due to their convenience and effectiveness. Data from randomized controlled trials and observational studies comparing efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) with biphasic insulin lispro mix (LM 25/50) and versus other insulin therapies or oral antidiabetic drugs (OADs) in T2D demonstrated that BIAsp 30 and LM 25/50 were associated with similar or greater improvements in glycemic control versus comparator regimens, such as basal–bolus insulin, in insulin-naÏve, and prior insulin users. Studies directly comparing BIAsp 30 and LM 25 provided conflicting glycemic control results. Safety data generally showed increased hypoglycemia and weight gain with premixed insulins versus basal–bolus insulin or OADs. However, large observational trials documented improvements in glycated hemoglobin, PPG, and hypoglycemia with BIAsp 30 in multi-ethnic patient populations. In summary, this literature review demonstrates that premixed insulin regimens are an appropriate and effective treatment choice in T2D. PMID:27186543

  20. Formation of a Fluorous/Organic Biphasic Supramolecular Octopus Assembly for Enhanced Porphyrin Phosphorescence in Air

    DOE PAGES

    Yang, Chi; Arvapally, Ravi K.; Tekarli, Sammer M.; ...

    2015-03-03

    The trinuclear triangle-shaped system [tris{3,5-bis(heptafluoropropyl)-1,2,4-triazolatosilver(I)}] (1) and the multi-armed square-shaped metalloporphyrin PtOEP or the free porphyrin base H2OEP serve as excellent octopus hosts (OEP=2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine). Coupling of the fluorous/organic molecular octopi 1 and H2OEP or PtOEP by strong quadrupole-quadrupole and metal- interactions affords the supramolecular assemblies [1PtOEP] or [1H(2)OEP] (2a), which feature nanoscopic cavities surrounding the upper triangular and lower square cores. The fluorous/organic biphasic configuration of [1PtOEP] leads to an increase in the phosphorescence of PtOEP under ambient conditions. Guest molecules can be included in the biphasic double-octopus assembly in three different site-selective modes.

  1. Origin and correction of magnetic field inhomogeneity at the interface in biphasic NMR samples.

    PubMed

    Martin, Bryan T; Chingas, G C; McDougal, Owen M

    2012-05-01

    The use of susceptibility matching to minimize spectral distortion of biphasic samples layered in a standard 5 mm NMR tube is described. The approach uses magic angle spinning (MAS) to first extract chemical shift differences by suppressing bulk magnetization. Then, using biphasic coaxial samples, magnetic susceptibilities are matched by titration with a paramagnetic salt. The matched phases are then layered in a standard NMR tube where they can be shimmed and examined. Linewidths of two distinct spectral lines, selected to characterize homogeneity in each phase, are simultaneously optimized. Two-dimensional distortion-free, slice-resolved spectra of an octanol/water system illustrate the method. These data are obtained using a 2D stepped-gradient pulse sequence devised for this application. Advantages of this sequence over slice-selective methods are that acquisition efficiency is increased and processing requires only conventional software.

  2. Biphasic catalysis using amphiphilic polyphenols-chelated noble metals as highly active and selective catalysts

    PubMed Central

    Mao, Hui; Yu, Hong; Chen, Jing; Liao, Xuepin

    2013-01-01

    In the field of catalysis, it is highly desired to develop novel catalysts that combine the advantages of both homogeneous and heterogeneous catalysts. Here we disclose that the use of plant pholyphenol as amphiphilic large molecule ligand/stabilizer allows for the preparation of noble metal complex and noble metal nanoparticle catalysts. These catalysts are found to be highly selective and active in aqueous-organic biphasic catalysis of cinnamaldehyde and quinoline, and can be reused at least 3 times without significant loss of activity. Moreover, the catalytic activity and reusability of the catalysts can be rationally controlled by simply adjusting the content of polyphenols in the catalysts. Our strategy may be extended to design a wide range of aqueous-organic biphasic catalysis system. PMID:23863916

  3. A biphasic hyperelastic model for the analysis of fluid and mass transport in brain tissue.

    PubMed

    García, José Jaime; Smith, Joshua H

    2009-02-01

    A biphasic hyperelastic finite element model is proposed for the description of the mechanical behavior of brain tissue. The model takes into account finite deformations through an Ogden-type hyperelastic compressible function and a hydraulic conductivity dependent on deformation. The biphasic equations, implemented here for spherical symmetry using an updated Lagrangian algorithm, yielded radial coordinates and fluid velocities that were used with the convective-diffusive equation in order to predict mass transport in the brain. Results of the model were equal to those of a closed-form solution under infinitesimal deformations, however, for a wide range of material parameters, the model predicted important increments in the infusion sphere, reductions of the fluid velocities, and changes in the species content distribution. In addition, high localized deformation and stresses were obtained at the infusion sphere. Differences with the infinitesimal solution may be mainly attributed to geometrical nonlinearities related to the increment of the infusion sphere and not to material nonlinearities.

  4. Biphasic Kinetic Behavior of Nitrate Reductase from Heterocystous, Nitrogen-Fixing Cyanobacteria 1

    PubMed Central

    Martin-Nieto, José; Flores, Enrique; Herrero, Antonia

    1992-01-01

    Nitrate reductase activity from filamentous, heterocyst-forming cyanobacteria showed a biphasic kinetic behavior with respect to nitrate as the variable substrate. Two kinetic components were detected, the first showing a higher affinity for nitrate (Km, 0.05-0.25 mm) and a lower catalytic activity and the second showing a lower affinity for nitrate (Km, 5-25 mm) and a higher (3- to 5-fold) catalytic activity. In contrast, among unicellular cyanobacteria, most representatives studied exhibited a monophasic, Michaelis-Menten kinetic pattern for nitrate reductase activity. Biphasic kinetics remained unchanged with the use of different assay conditions (i.e. cell disruption or permeabilization, two different electron donors) or throughout partial purification of the enzyme. PMID:16652939

  5. Microstructure Evolution of Biphasic TiNi1+ x Sn Thermoelectric Materials

    NASA Astrophysics Data System (ADS)

    Verma, Nisha; Douglas, Jason E.; Krämer, Stephan; Pollock, Tresa M.; Seshadri, Ram; Levi, Carlos G.

    2016-08-01

    The effects of thermal treatment on the microstructure of biphasic materials comprising half-Heusler (hH) and full-Heusler (fH) phases, as well as on their associated thermal conductivity, are discussed. The focus of this study was on a biphasic hH/fH alloy of nominal stoichiometry TiNi1.2Sn, synthesized by containerless (magnetic levitation) induction melting. The alloy samples were exposed to various heat treatments to generate microstructures containing second-phase precipitates ranging in size from ~10 nm to a few micrometers. The materials were characterized with regard to morphology, size, shape, and orientation relationship of the fH and hH phases, both of which were present as precipitates within larger regions of the counterpart phase. The solidification path of the alloy and its implications for the subsequent microstructure evolution during heat treatment were elucidated, and relationships with the ensuing thermal conductivity were characterized.

  6. Tracking performance of unbalanced QPSK demodulators. II - Biphase Costas loop with active arm filters

    NASA Technical Reports Server (NTRS)

    Simon, M. K.

    1978-01-01

    In a Costas loop study for biphase modulation conducted by Simon and Lindsey (1977), it was demonstrated that considerable improvement in tracking performance could be obtained by employing active arm filters of the integrate-and-dump type as opposed to passive arm filters. An investigation is conducted concerning the possibility to obtain a similar performance improvement for an unbalanced quadriphase-shift-keying (QPSK) modulation. It is found that the biphase Costas loop can be used as an efficient demodulator of QPSK in cases in which the ratio of data rates is of the same order of magnitude as the inverse of the power ratio. These cases involve approximately equal signal energies in the two channels.

  7. A biphasic mercury-ion sensor: exploiting microfluidics to make simple anilines competitive ligands.

    PubMed

    Petzoldt, Martin; Eschenbaum, Carsten; Schwaebel, S Thimon; Broedner, Kerstin; Lemmer, Uli; Hamburger, Manuel; Bunz, Uwe H F

    2015-10-05

    Combining the molecular wire effect with a biphasic sensing approach (analyte in water, sensor-dye in 2-methyltetrahydrofuran) and a microfluidic flow setup leads to the construction of a mercury-sensitive module. We so instantaneously detect Hg(2+) ions in water at a 500 μM concentration. The sensor, conjugated non-water soluble polymer 1 (XFPF), merely supports dibutylaniline substituents as binding units. Yet, selective and sensitive detection of Hg(2+) -ions is achieved in water. The enhancement in sensory response, when comparing the reference compound 2 to that of 1 in a biphasic system in a microfluidic chip is >10(3) . By manipulation of the structure of 1, further powerful sensor systems should be easily achieved.

  8. A biphasic parameter estimation method for quantitative analysis of dynamic renal scintigraphic data

    NASA Astrophysics Data System (ADS)

    Koh, T. S.; Zhang, Jeff L.; Ong, C. K.; Shuter, B.

    2006-06-01

    Dynamic renal scintigraphy is an established method in nuclear medicine, commonly used for the assessment of renal function. In this paper, a biphasic model fitting method is proposed for simultaneous estimation of both vascular and parenchymal parameters from renal scintigraphic data. These parameters include the renal plasma flow, vascular and parenchymal mean transit times, and the glomerular extraction rate. Monte Carlo simulation was used to evaluate the stability and confidence of the parameter estimates obtained by the proposed biphasic method, before applying the method on actual patient study cases to compare with the conventional fitting approach and other established renal indices. The various parameter estimates obtained using the proposed method were found to be consistent with the respective pathologies of the study cases. The renal plasma flow and extraction rate estimated by the proposed method were in good agreement with those previously obtained using dynamic computed tomography and magnetic resonance imaging.

  9. Biphasic and boundary lubrication mechanisms in artificial hydrogel cartilage: A review.

    PubMed

    Murakami, Teruo; Yarimitsu, Seido; Nakashima, Kazuhiro; Sakai, Nobuo; Yamaguchi, Tetsuo; Sawae, Yoshinori; Suzuki, Atsushi

    2015-12-01

    Various studies on the application of artificial hydrogel cartilage to cartilage substitutes and artificial joints have been conducted. It is expected in clinical application of artificial hydrogel cartilage that not only soft-elastohydrodynamic lubrication but biphasic, hydration, gel-film and boundary lubrication mechanisms will be effective to sustain extremely low friction and minimal wear in daily activities similar to healthy natural synovial joints with adaptive multimode lubrication. In this review article, the effectiveness of biphasic lubrication and boundary lubrication in hydrogels in thin film condition is focused in relation to the structures and properties of hydrogels. As examples, the tribological behaviors in three kinds of poly(vinyl alcohol) hydrogels with high water content are compared, and the importance of lubrication mechanism in biomimetic artificial hydrogel cartilage is discussed to extend the durability of cartilage substitute.

  10. A method for separating water soluble organics from a process stream by aqueous biphasic extraction

    SciTech Connect

    Chaiko, David J.; Mego, William A.

    1997-12-01

    The present invention relates to a method for separating water-miscible organic species from a process stream by aqueous biphasic extraction. In particular, the method includes extracting the organic species into a polymer-rich phase of an aqueous biphase system in which the process stream comprises the salt-rich phase, and, next, separating the polymer from the extracted organic species by contacting the loaded, polymer-rich phase with a water-immiscible organic phase. Alternatively, the polymer can be separated from the extracted organic species by raising the temperature of the loaded, polymer-rich phase above the cloud point, such that the polymer and the water-soluble organic species separate into two distinct aqueous phases. In either case, a substantially salt-free, concentrated aqueous solution containing the organic species is recovered.

  11. Mesenchymal stem cells combined with biphasic calcium phosphate ceramics promote bone regeneration.

    PubMed

    Livingston, T L; Gordon, S; Archambault, M; Kadiyala, S; McIntosh, K; Smith, A; Peter, S J

    2003-03-01

    The reconstruction and repair of large bone defects, resulting from trauma, cancer or metabolic disorders, is a major clinical challenge in orthopaedics. Clinically available biological and synthetic grafts have clear limitations that necessitate the development of new graft materials and/or strategies. Human mesenchymal stem cells (MSCs), obtained from the adult bone marrow, are multipotent cells capable of differentiating into various mesenchymal tissues. Of particular interest is the ability of these cells to differentiate into osteoblasts, or bone-forming cells. At Osiris, we have extensively characterized MSCs and have demonstrated MSCs can induce bone repair when implanted in vivo in combination with a biphasic calcium phosphate, specifically hydroxyapatite/tricalcium phosphate. This article reviews previous and current studies utilizing mesenchymal stem cells and biphasic calcium phosphates in bone repair.

  12. Lithium chloride has a biphasic effect on prostate cancer stem cells and a proportional effect on midkine levels

    PubMed Central

    Erguven, Mine; Oktem, Gulperi; Kara, Ali Nail; Bilir, Ayhan

    2016-01-01

    Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels of differentiation growth factor midkine (MK) are increased in PCa. Cancer and/or the treatment process itself may lead to psychiatric disorders. Lithium chloride (LiCl) has anti-manic properties and has been used in cancer therapy; however, it has a queried safety profile. In addition, cancer stem cells are responsible for the heterogeneous phenotype of tumor cells; they are involved in progression, metastasis, recurrence and therapy resistance in various cancer types. The aims of the present study were to investigate the effect of different concentrations of LiCl on PCa stem cells (whether a shift from tumorigenic to non-tumorigenic cells occurs) and to determine if these results can be explained through changes in MK levels. Monolayer and spheroid cultures of human prostate stem cells and non-stem cells were incubated with low (1, 10 µM) and high (100, 500 µM) concentrations of LiCl for 72 h. Cell proliferation, apoptotic indices, MK levels and ultrastructure were evaluated. Cells stimulated with low concentrations showed high proliferation, low apoptotic indices, high MK levels and more healthy ultrastructure. Opposite results were obtained at high concentrations. Furthermore, stem cells were more sensitive to stimulation and more resistant to inhibition than non-stem cells. LiCl exhibited concentration-dependent effects on stem cell and non-stem cell groups. MK levels were not involved in the biphasic effect of LiCl; however, they were proportionally affected. To the best of our knowledge, the present study was the first to show the effect of LiCl on PCa stem cells through MK. PMID:27703531

  13. Deriving sulfamethoxazole dissipation endpoints in pasture soils using first order and biphasic kinetic models.

    PubMed

    Srinivasan, Prakash; Sarmah, Ajit K; Rohan, Maheswaran

    2014-08-01

    Single first-order (SFO) kinetic model is often used to derive the dissipation endpoints of an organic chemical in soil. This model is used due to its simplicity and requirement by regulatory agencies. However, using the SFO model for all types of decay pattern could lead to under- or overestimation of dissipation endpoints when the deviation from first-order is significant. In this study the performance of three biphasic kinetic models - bi-exponential decay (BEXP), first-order double exponential decay (FODED), and first-order two-compartment (FOTC) models was evaluated using dissipation datasets of sulfamethoxazole (SMO) antibiotic in three different soils under varying concentration, depth, temperature, and sterile conditions. Corresponding 50% (DT50) and 90% (DT90) dissipation times for the antibiotics were numerically obtained and compared against those obtained using the SFO model. The fit of each model to the measured values was evaluated based on an array of statistical measures such as coefficient of determination (R(2)adj), root mean square error (RMSE), chi-square (χ(2)) test at 1% significance, Bayesian Information Criteria (BIC) and % model error. Box-whisker residual plots were also used to compare the performance of each model to the measured datasets. The antibiotic dissipation was successfully predicted by all four models. However, the nonlinear biphasic models improved the goodness-of-fit parameters for all datasets. Deviations from datasets were also often less evident with the biphasic models. The fits of FOTC and FODED models for SMO dissipation datasets were identical in most cases, and were found to be superior to the BEXP model. Among the biphasic models, the FOTC model was found to be the most suitable for obtaining the endpoints and could provide a mechanistic explanation for SMO dissipation in the soils.

  14. [The design of the external defibrillator using the truncated exponential biphasic waveform].

    PubMed

    Song, Er-mei; Wu, Xiao-mei; Yang, Cui-wei; Fang, Zu-xiang

    2006-01-01

    The external defibrillator is an emergency instrument used very widely in clinics. It plays an important role in rescuing ventricle fibrillation (VF) patients. We have designed an external defibrillator using the truncated exponential biphasic waveform. The system consists of three parts: the ECG collection module, the control module and the defibrillator module. They are introduced respectively, listing the main problems and the methods to solve them. Some experiments have been done and the corresponding results are given.

  15. Electronic and structural characteristics of zinc-blende wurtzite biphasic homostructure GaN nanowires

    DOE PAGES

    Jacobs, Benjamin W.; Ayres, Virginia M.; Petkov, Mihail P.; ...

    2007-04-07

    Here, we report a new biphasic crystalline wurtzite/zinc-blende homostructure in gallium nitride nanowires. Cathodoluminescence was used to quantitatively measure the wurtzite and zinc-blende band gaps. High-resolution transmission electron microscopy was used to identify distinct wurtzite and zinc-blende crystalline phases within single nanowires through the use of selected area electron diffraction, electron dispersive spectroscopy, electron energy loss spectroscopy, and fast Fourier transform techniques. A mechanism for growth is identified.

  16. Volume-controlled versus biphasic positive airway pressure ventilation in leukopenic patients with severe respiratory failure.

    PubMed

    Kiehl, M; Schiele, C; Stenzinger, W; Kienast, J

    1996-05-01

    To study comparatively the effects of volume-controlled vs. biphasic positive airway pressure mechanical ventilation on respiratory mechanics and oxygenation in leukopenic patients with severe respiratory failure. Prospective, comparative study. Medical intensive care unit of a university hospital. Leukopenic (<1000 leukocytes/microliter) patients (n=20) after cytoreductive chemotherapy requiring mechanical ventilation for severe respiratory failure (Murray score of > 2.5). Patients were assigned in a consecutive, alternating manner to receive either volume-controlled or biphasic positive airway pressure mechanical ventilation, starting within 12 to 24 hrs after endotracheal intubation. Tidal volume, inspiratory flow, peak inspiratory and positive end-expiratory pressures, FIO2, and arterial blood gas analyses were recorded hourly for a study period of 48 hrs. Biphasic positive airway pressure ventilation was associated with a significant reduction in peak inspiratory pressure (mean differences at 24, 36, and 48 hrs: 4.4, 3.4, and 4.2 cm H2O; p = .024, .019, and .013, respectively) and positive end-expiratory pressures (mean differences at 24, 36, and 48 hrs: 1.6, 1.4, and 1.5 cm H20; p = .023, .024, and .023, respectively) at significantly lower FIO2 (mean differences at 12, 24, 36, and 48 hrs; p = .007, .015, .016, and .011, respectively). PaO2/FIO2 ratios and CO2 removal were similar under ventilatory conditions. Biphasic positive airway pressure ventilation offers the advantage of significantly reduced peak inspiratory and positive end-expiratory pressures at a lower FIO2 and with at least similar oxygenation and CO2 removal as achieved by volume-controlled mechanical ventilation. Our results are in line with previous reports on nonleukopenic patients and suggest that the positive effects of pressure-limited mechanical ventilation are independent of circulating white blood cells. Further studies are mandatory to demonstrate clinical benefit in this critically

  17. A case of protracted hypotension as unique symptom of a biphasic anaphylaxis to amoxicillin.

    PubMed

    Zisa, G; Riccobono, F; Calamari, A M; D'Antonio, C D; Galimberti, M

    2009-04-01

    We are reporting a case of one patient who have experienced itching of palms and soles, thorax erythema, conjunctive injection immediately after oral administration of amoxicillin, and hypotension after 3 hours. In E.D. hypotension was monitored because he was a cardiopatic but it wasn't treated even if it was protracted. A positive result of immediate-reading intradermal test with amoxicillin at 2 mg/ml concentration was found confirming the diagnosis of allergic biphasic anaphylaxis to amoxicillin.

  18. A numerical method for biphasic curve fitting with a programmable calculator.

    PubMed

    Ristanović, D; Ristanović, D; Malesević, J; Milutinović, B

    1982-01-01

    Elimination kinetics of bromsulphalein (BSP) after a single injection into the circulation of rats were examined by means of a four-compartment model. BSP plasma concentrations were measured colorimetrically. A program written for the Texas Instruments TI-59 programmable calculator is presented, which will calculate the fractional blood clearance of BSP using an iteration procedure. A simple method of fitting biphasic decay curves to experimental data is also proposed.

  19. Nitric oxide interacts with salicylate to regulate biphasic ethylene production during the hypersensitive response.

    PubMed

    Mur, Luis A J; Laarhoven, Lucas J J; Harren, Frans J M; Hall, Michael A; Smith, Aileen R

    2008-11-01

    C(2)H(4) is associated with plant defense, but its role during the hypersensitive response (HR) remains largely uncharacterized. C(2)H(4) production in tobacco (Nicotiana tabacum) following inoculation with HR-eliciting Pseudomonas syringae pathovars measured by laser photoacoustic detection was biphasic. A first transient rise (C(2)H(4)-I) occurred 1 to 4 h following inoculation with HR-eliciting, disease-forming, and nonpathogenic strains and also with flagellin (flg22). A second (avirulence-dependent) rise, at approximately 6 h (C(2)H(4)-II), was only seen with HR-eliciting strains. Tobacco leaves treated with the C(2)H(4) biosynthesis inhibitor, aminoethoxyvinylglycine, suggested that C(2)H(4) influenced the kinetics of a HR. Challenging salicylate hydroxylase-expressing tobacco lines and tissues exhibiting systemic acquired resistance suggested that C(2)H(4) production was influenced by salicylic acid (SA). Disrupted expression of a C(2)H(4) biosynthesis gene in salicylate hydroxylase tobacco plants implicated transcriptional control as a mechanism through which SA regulates C(2)H(4) production. Treating leaves to increase oxidative stress or injecting with SA initiated monophasic C(2)H(4) generation, but the nitric oxide (NO) donor sodium nitroprusside initiated biphasic rises. To test whether NO influenced biphasic C(2)H(4) production during the HR, the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester was coinoculated with the avirulent strain of P. syringae pv phaseolicola into tobacco leaves. The first transient C(2)H(4) rise appeared to be unaffected by N(G)-nitro-L-arginine methyl ester, but the second rise was reduced. These data suggest that NO and SA are required to generate the biphasic pattern of C(2)H(4) production during the HR and may influence the kinetics of HR formation.

  20. A Phenomenological Model of the Electrically Stimulated Auditory Nerve Fiber: Temporal and Biphasic Response Properties

    PubMed Central

    Horne, Colin D. F.; Sumner, Christian J.; Seeber, Bernhard U.

    2016-01-01

    We present a phenomenological model of electrically stimulated auditory nerve fibers (ANFs). The model reproduces the probabilistic and temporal properties of the ANF response to both monophasic and biphasic stimuli, in isolation. The main contribution of the model lies in its ability to reproduce statistics of the ANF response (mean latency, jitter, and firing probability) under both monophasic and cathodic-anodic biphasic stimulation, without changing the model's parameters. The response statistics of the model depend on stimulus level and duration of the stimulating pulse, reproducing trends observed in the ANF. In the case of biphasic stimulation, the model reproduces the effects of pseudomonophasic pulse shapes and also the dependence on the interphase gap (IPG) of the stimulus pulse, an effect that is quantitatively reproduced. The model is fitted to ANF data using a procedure that uniquely determines each model parameter. It is thus possible to rapidly parameterize a large population of neurons to reproduce a given set of response statistic distributions. Our work extends the stochastic leaky integrate and fire (SLIF) neuron, a well-studied phenomenological model of the electrically stimulated neuron. We extend the SLIF neuron so as to produce a realistic latency distribution by delaying the moment of spiking. During this delay, spiking may be abolished by anodic current. By this means, the probability of the model neuron responding to a stimulus is reduced when a trailing phase of opposite polarity is introduced. By introducing a minimum wait period that must elapse before a spike may be emitted, the model is able to reproduce the differences in the threshold level observed in the ANF for monophasic and biphasic stimuli. Thus, the ANF response to a large variety of pulse shapes are reproduced correctly by this model. PMID:26903850

  1. A case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Hazama, Kyoko; Shiihara, Takashi; Tsukagoshi, Hiroyuki; Hasegawa, Shunji; Dowa, Yuri; Watanabe, Mio

    2017-10-01

    Mumps is a common childhood viral disease characterized by fever and swelling of the parotid gland. The prognosis is generally good, although some complications, such as encephalitis (0.1%), exist. Acute encephalopathy with biphasic seizures and late reduced diffusion is the most common type of acute encephalopathy. However, this type of encephalopathy has not been reported in association with mumps infection. A previously healthy 3-year-old Japanese boy had a brief convulsion after fever for 3days, and then had conscious disturbance and parotitis. After several days, he had a second brief convulsion and was admitted. Increased serum amylase levels and presence of anti-mumps immunoglobulin M antibody confirmed mumps parotitis. The patient had another brief seizure later the day of admission. He did not have status or cluster seizures, although the biphasic nature of his seizures, conscious disturbance between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic resonance images were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion. In Japan, the mumps vaccine is not administered as a part of routine immunizations. It thus has low coverage (30-40%), and as a result, mumps infections are still common. However, this is the first case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion. This case may be representative of only a minority of patients with mumps-associated central nervous system involvement. Nevertheless, this diagnostic possibility may be considered. In order to prevent mumps-related complications, routine mumps vaccination might be warranted. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. Aqueous Biphasic Systems Based on Salting-Out Polyethylene Glycol or Ionic Solutions: Strategies for Actinide or Fission Product Separations

    SciTech Connect

    Rogers, Robin D.; Gutowski, Keith E.; Griffin, Scott T.; Holbrey, John D.

    2004-03-29

    Aqueous biphasic systems can be formed by salting-out (with kosmotropic, waterstructuring salts) water soluble polymers (e.g., polyethylene glycol) or aqueous solutions of a wide range of hydrophilic ionic liquids based on imidazolium, pyridinium, phosphonium and ammonium cations. The use of these novel liquid/liquid biphases for separation of actinides or other fission products associated with nuclear wastes (e.g., pertechnetate salts) has been demonstrated and will be described in this presentation.

  3. Production of Furfural from Process-Relevant Biomass-Derived Pentoses in a Biphasic Reaction System

    DOE PAGES

    Mittal, Ashutosh; Black, Stuart K.; Vinzant, Todd B.; ...

    2017-05-16

    Furfural is an important fuel precursor which can be converted to hydrocarbon fuels and fuel intermediates. In this work, the production of furfural by dehydration of process-relevant pentose rich corn stover hydrolyzate using a biphasic batch reaction system has been investigated. Methyl isobutyl ketone (MIBK) and toluene have been used to extract furfural and enhance overall furfural yield by limiting its degradation to humins. The effects of reaction time, temperature, and acid concentration (H2SO4) on pentose conversion and furfural yield were investigated. For the dehydration of 8 wt % pentose-rich corn stover hydrolyzate under optimum reaction conditions, 0.05 M H2SO4,more » 170 degrees C for 20 min with MIBK as the solvent, complete conversion of xylose (98-100%) and a furfural yield of 80% were obtained. Under these same conditions, except with toluene as the solvent, the furfural yield was 77%. Additionally, dehydration of process-relevant pentose rich corn stover hydrolyzate using solid acid ion-exchange resins under optimum reaction conditions has shown that Purolite CT275 is as effective as H2SO4 for obtaining furfural yields approaching 80% using a biphasic batch reaction system. In conclusion, this work has demonstrated that a biphasic reaction system can be used to process biomass-derived pentose rich sugar hydrolyzates to furfural in yields approaching 80%.« less

  4. Clinical efficacy of a wearable defibrillator in acutely terminating episodes of ventricular fibrillation using biphasic shocks.

    PubMed

    Reek, Sven; Geller, J Christoph; Meltendorf, Ulf; Wollbrueck, Anke; Szymkiewicz, Steven J; Klein, Helmut U

    2003-10-01

    The Wearable Cardioverter Defibrillator (WCD) automatically detects and treats ventricular tachyarrhythmias without the need for assistance from a bystander, while at the same time allowing the patient to ambulate freely. It represents an alternative to emergency medical services for outpatient populations with a temporary risk of sudden cardiac death. While the original devices used a monophasic truncated exponential waveform for cardioversion/defibrillation shocks, a new, biphasic shock was developed for the next device generation. In 12 patients undergoing electrophysiological testing for ventricular tachyarrhythmias, termination of electrically induced ventricular fibrillation (VF) was attempted via the WCD. In 22 episodes, induced VF was promptly terminated by the first 70 J (n=12) or 100 J (n=10) biphasic shocks. Time between arrhythmia initiation and shock delivery was 22 +/- 6 seconds (70 J) and 21 +/- 6 seconds (100 J) (P=NS). The measured transthoracic impedance was 71 +/- 5 Ohms (64-79 Ohms) for the 70 J shock and 64 +/- 8 Ohms (47-72 Ohms) for the 100 J shock. The present study demonstrates that a single low energy biphasic shock delivered by the WCD, reliably terminates electrically induced VF (100% of episodes). The results of this study suggest that there is an acceptable safety margin to the maximum output of the device (150 J). Despite our promising data, we recommend that programming all shocks for maximum energy output should be done when using the WCD in ambulatory patients.

  5. Biphasic transient kinetics are a property of a single site in horse liver alcohol dehydrogenase.

    PubMed

    Anderson, D C; Dahlquist, F W

    1982-07-20

    The transient kinetics under single turnover conditions of the dimeric enzyme horse liver alcohol dehydrogenase (LADH) are often biphasic with nearly equal amplitudes in the fast and slow components of the reaction. These observations have been the basis for the suggestion that this enzyme displays half of the sites reactivity or kinetic site-site interactions in its catalytic cycle [Bernhard, S.A., Dunn, M.F., Luisi, P.L., & Shack, P. (1970) Biochemistry 9, 185]. Alternatively, the biphasic kinetics could be the result of a complex mechanistic path at a single site with no kinetic interactions between the active sites [Kvassman, J., & Pettersson, G. (1976) Eur. J. Biochem. 62, 279; Kvassman, J., & Pettersson, G. (1978) Eur. J. Biochem. 87, 417]. To resolve this question, we have prepared LADH in which one of the two active sites is occupied by the strongly bound, slowly exchanging ternary complex inhibitors NAD with trifluoroethanol or NAD with pyrazole. These half-inhibited dimers show essentially the same biphasic transient kinetics as the native enzyme. These results strongly support mechanisms in which the observed kinetics are a property of each independently functioning site of the dimer. The possibility of half of the sites reactivity or kinetic site-site interaction appears to be ruled out.

  6. Simulation by two calcium store models of myocardial dynamic properties: potentiation, staircase, and biphasic tension development.

    PubMed

    Wussling, M; Szymanski, G

    1986-04-01

    Most considerations and models concerning myocardial dynamic properties e.g. potentiation and staircase, are based upon the existence of storage structures in the heart muscle cell. The phenomenon of biphasic tension development (or two-component contraction) in heart muscle preparations of several mammalian species suggests that the sarcoplasmic reticulum is one, but by no means the major, source of activator calcium for the contractile system. The simulation of dynamic properties including biphasic tension development was performed in two steps by a simple "two-Ca store-model" and by an "expanded two-Ca store-model" with following results: Increasing potentiation indicated a decrease in the degree of coupling between the Ca stores. A shift of the interval strength curve to lower intervals as well as a decrease of the steady state contraction height implies a decrease of both, the coupling and the leakage time constant. There was no standard relation between staircase phenomena and structure parameters. Analog displays showed a late (or second) component at prolongated stimulation intervals, in the transient phase after a rest period, in the case of perfectly coupled or uncoupled stores, and at great time constant tau p (which characterizes the calcium pump activity). It is concluded that the late component of biphasic tension development is due to direct activation by the transsarcolemmal Ca flux of the myofilaments, whereas the early component is caused by the release of stored calcium. In the absence of an early component neither potentiation nor marked treppe may be expected.

  7. (*) Fabrication and Characterization of Biphasic Silk Fibroin Scaffolds for Tendon/Ligament-to-Bone Tissue Engineering.

    PubMed

    Font Tellado, Sònia; Bonani, Walter; Balmayor, Elizabeth R; Foehr, Peter; Motta, Antonella; Migliaresi, Claudio; van Griensven, Martijn

    2017-08-01

    Tissue engineering is an attractive strategy for tendon/ligament-to-bone interface repair. The structure and extracellular matrix composition of the interface are complex and allow for a gradual mechanical stress transfer between tendons/ligaments and bone. Thus, scaffolds mimicking the structural features of the native interface may be able to better support functional tissue regeneration. In this study, we fabricated biphasic silk fibroin scaffolds designed to mimic the gradient in collagen molecule alignment present at the interface. The scaffolds had two different pore alignments: anisotropic at the tendon/ligament side and isotropic at the bone side. Total porosity ranged from 50% to 80% and the majority of pores (80-90%) were <100-300 μm. Young's modulus varied from 689 to 1322 kPa depending on the type of construct. In addition, human adipose-derived mesenchymal stem cells were cultured on the scaffolds to evaluate the effect of pore morphology on cell proliferation and gene expression. Biphasic scaffolds supported cell attachment and influenced cytoskeleton organization depending on pore alignment. In addition, the gene expression of tendon/ligament, enthesis, and cartilage markers significantly changed depending on pore alignment in each region of the scaffolds. In conclusion, the biphasic scaffolds fabricated in this study show promising features for tendon/ligament-to-bone tissue engineering.

  8. A comparison of lipase-catalyzed ester hydrolysis in reverse micelles, organic solvents, and biphase systems

    SciTech Connect

    Yang, F.; Russell, A.J.

    1995-07-05

    The performance of lipases from Candida rugosa and wheat germ have been investigated in three reaction media using three acetate hydrolyses as model reactions (ethyl acetate, allyl acetate, and prenyl acetate). The effect of substrate properties and water content were studied for each system (organic solvent, biphasic system, and reverse micelles). Not unexpectedly, the effect of water content is distinct for each system, and the optimal water content for enzyme activity is not always the same as that for productivity. A theoretical model has been used to simulate and predict enzyme performance in reverse micelles, and a proposed partitioning model for biphasic systems agrees well with experimental results. While the highest activities observed were in the micellar system, productivity in microemulsions is limited by low enzyme concentrations. Biphasic systems, however, support relatively good activity and productivity. The addition of water to dry organic solvents, combined with the dispersion of lyophilized enzyme powders in the solvent, resulted in significant enzyme aggregation, which not surprisingly limits the applicability of the ``anhydrous`` enzyme suspension approach.

  9. Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds.

    PubMed

    Schek, Rachel M; Taboas, Juan M; Segvich, Sharon J; Hollister, Scott J; Krebsbach, Paul H

    2004-01-01

    Tissue engineering has provided an alternative to traditional strategies to repair cartilage damaged by injury or degenerative disease. A successful strategy to engineer osteochondral tissue will mimic the natural contour of the articulating surface, achieve native mechanical properties and functional load-bearing ability, and lead to integration with host cartilage and underlying subchondral bone. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match articular geometry. The objective of this study was to utilize materials and biological factors in an integrated approach to regenerate a multitissue interface. Biphasic composite scaffolds manufactured by IBD and SFF fabrication were used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-L-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein 7 (BMP-7) in the ceramic phase and fully differentiated chondrocytes in the polymeric phase. After subcutaneous implantation into mice, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects.

  10. Synthesis and characterization of magnesium substituted biphasic mixtures of controlled hydroxyapatite/{beta}-tricalcium phosphate ratios

    SciTech Connect

    Kannan, S.; Lemos, I.A.F.; Rocha, J.H.G.; Ferreira, J.M.F. . E-mail: jmf@cv.ua.pt

    2005-10-15

    The present paper investigates the preparation of magnesium (Mg) substituted biphasic mixtures of different hydroxyapatite (HAP)/{beta}-tricalcium phosphate ({beta}-TCP) ratios through aqueous precipitation method. The concentrations of added magnesium (Mg) were varied with the calcium in order to obtain constant (Ca+Mg)/P ratios of 1.67 ranging from 1.62+0.05, 1.58+0.09 and 1.54+0.13, respectively. The as prepared powders were calcined at different temperatures to study the phase behaviour and thermal stability. The powders were characterized by the following analytical techniques: TG-DTA, X-ray diffraction and FT-IR. The results have shown that substitution of Mg in the calcium-deficient apatites resulted in the formation of biphasic mixtures of different HAP/{beta}-TCP ratios after heating above 700 deg. C. The ratios of the formation of phase mixtures were dependent on the calcium deficiency in the apatites with the higher deficiency having the strongest impact on the increased formation of {beta}-TCP and the substituted Mg was found to stabilize the {beta}-TCP phase. - Graphical abstract: Role of Mg in the behaviour of calcium-deficient apatites during calcination to form biphasic mixtures.

  11. Synchronized oscillations of dimers in biphasic charged fd-virus suspensions

    NASA Astrophysics Data System (ADS)

    Kang, K.; Piao, S. H.; Choi, H. J.

    2016-08-01

    Micron-sized colloidal spheres that are dispersed in an isotropic-nematic biphasic host suspension of charged rods (fd-virus particles) are shown to spontaneously form dimers, which exhibit a synchronized oscillatory motion. Dimer formation is not observed in the monophase of isotropic and nematic suspensions. The synchronized oscillations of dimers are connected to the inhomogeneous state of the host suspension of charged rods (fd viruses) where nematic domains are in coexistence with isotropic regions. The synchronization of oscillations occurs in bulk states, in the absence of an external field. With a low field strength of an applied electric field, the synchronization is rather reduced, but it recovers again when the field is turned off. In this Rapid Communication, we report this observation as an example of the strange attractor, occurring in the mixture of PS (polystyrene) dimers in an isotropic-nematic coexistence biphasic fd-virus network. Furthermore, we highlight that the synchronization of PS-dimer oscillations is the result of a global bifurcation diagram, driven by a delicate balance between the short-attractive "twisted" interaction of PS dimers and long-ranged electrostatic repulsive interactions of charged fd rods. The interest is then in the local enhancement of "twist-nematic" elasticity in reorientation of the dimer oscillations. An analysis of image-time correlations is provided with the data movies and Fourier transforms of averaged orientations for the synchronized oscillations of dimers in the biphasic I -N coexistence concentration of charged fd-virus suspensions.

  12. Modeling non-isothermal heat inactivation of microorganisms having biphasic isothermal survival curves.

    PubMed

    Corradini, Maria G; Normand, Mark D; Peleg, Micha

    2007-05-30

    Biphasic isothermal inactivation constitutes a special case of non-linear mortality kinetics. It can be modeled with a primary model that contains an 'If' statement and three temperature dependent survival parameters: the first and second logarithmic inactivation rate constants and the time of the transition from one phase to the other. The temperature dependence of the two inactivation rates of Salmonella enteritidis and that of the transition time determined from published data could be described by empirical logistic terms. These were used to construct an inactivation rate equation for non-isothermal heating and cooling regimes. The resulting differential equation, despite having an 'If' statement in its formulation, could be easily solved numerically for simple as well elaborate temperature profiles. The solutions for a variety of realistic heat treatment histories indicated that when the heating or cooling rate is high enough, the biphasic character of the inactivation disappears. This is true regardless of whether the rate at the first phase is higher than at the second, the most common scenario, or vice versa. Theoretically, the same will happen with inactivation caused by a non thermal agent whose intensity increases or diminishes, in biphasic growth under rapidly varying conditions and in enzymatic activity or inactivation.

  13. The effect of collagen fibril orientation on the biphasic mechanics of articular cartilage.

    PubMed

    Meng, Qingen; An, Shuqiang; Damion, Robin A; Jin, Zhongmin; Wilcox, Ruth; Fisher, John; Jones, Alison

    2017-01-01

    The highly inhomogeneous distribution of collagen fibrils may have important effects on the biphasic mechanics of articular cartilage. However, the effect of the inhomogeneity of collagen fibrils has mainly been investigated using simplified three-layered models, which may have underestimated the effect of collagen fibrils by neglecting their realistic orientation. The aim of this study was to investigate the effect of the realistic orientation of collagen fibrils on the biphasic mechanics of articular cartilage. Five biphasic material models, each of which included a different level of complexity of fibril reinforcement, were solved using two different finite element software packages (Abaqus and FEBio). Model 1 considered the realistic orientation of fibrils, which was derived from diffusion tensor magnetic resonance images. The simplified three-layered orientation was used for Model 2. Models 3-5 were three control models. The realistic collagen orientations obtained in this study were consistent with the literature. Results from the two finite element implementations were in agreement for each of the conditions modelled. The comparison between the control models confirmed some functions of collagen fibrils. The comparison between Models 1 and 2 showed that the widely-used three-layered inhomogeneous model can produce similar fluid load support to the model including the realistic fibril orientation; however, an accurate prediction of the other mechanical parameters requires the inclusion of the realistic orientation of collagen fibrils.

  14. Activation of ganglion cells in wild-type and rd1 mouse retinas with monophasic and biphasic current pulses

    NASA Astrophysics Data System (ADS)

    Jensen, Ralph J.; Rizzo, Joseph F. III

    2009-06-01

    We and other research groups are designing an electronic retinal prosthesis to provide vision for patients who are blind due to photoreceptor degeneration. In this study, we examined the effect of stimulus waveform on the amount of current needed to activate retinal ganglion cells (RGCs) when the retinal neural network is stimulated. Isolated retinas of wild-type and rd1 mice were stimulated with cathodal and anodal monophasic current pulses of 1 ms duration and symmetric biphasic current pulses (1 ms per phase) delivered through an electrode that was located subretinally. For both wild-type and rd1 mouse retinas, cathodal current pulses were least effective in activating most RGCs. The median threshold current for a cathodal current pulse was 2.0-4.4 fold higher than the median threshold current for either an anodal or a biphasic current pulse. In wild-type mouse retinas, the median threshold current for activating RGCs with anodal current pulses was 23% lower than that with biphasic current pulses. In rd1 mouse retinas, the median threshold currents for anodal and biphasic current pulses were about the same. However, the variance in thresholds of rd1 RGCs for biphasic pulse stimulation was much smaller than for anodal pulse stimulation. Thus, a symmetric biphasic current pulse may be the best stimulus for activating the greatest number of RGCs in retinas devoid of photoreceptors.

  15. 16-Channel biphasic current-mode programmable charge balanced neural stimulation.

    PubMed

    Li, Xiaoran; Zhong, Shunan; Morizio, James

    2017-08-14

    Neural stimulation is an important method used to activate or inhibit action potentials of the neuronal anatomical targets found in the brain, central nerve and peripheral nerve. The neural stimulator system produces biphasic pulses that deliver balanced charge into tissue from single or multichannel electrodes. The timing and amplitude of these biphasic pulses are precisely controlled by the neural stimulator software or imbedded algorithms. Amplitude mismatch between the anodic current and cathodic current of the biphasic pulse will cause permanently damage for the neural tissues. The main goal of our circuit and layout design is to implement a 16-channel biphasic current mode programmable neural stimulator with calibration to minimize the current mismatch caused by inherent complementary metal oxide semiconductor (CMOS) manufacturing processes. This paper presents a 16-channel constant current mode neural stimulator chip. Each channel consists of a 7-bit controllable current DAC used as sink and source current driver. To reduce the LSB quantization error and the current mismatch, an automatic calibration circuit and flow diagram is presented in this paper. There are two modes of operation of the stimulator chip-namely, stimulation mode and calibration mode. The chip also includes a digital interface used to control the stimulator parameters and calibration levels specific for each individual channel. This stimulator Application Specific Integrated Circuit (ASIC) is designed and fabricated in a 0.18 μm High-Voltage CMOS technology that allows for ±20 V power supply. The full-scale stimulation current was designed to be at 1 mA per channel. The output current was shown to be constant throughout the timing cycles over a wide range of electrode load impedances. The calibration circuit was also designed to reduce the effect of CMOS process variation of the P-channel metal oxide semiconductor (PMOS) and N-channel metal oxide semiconductor (NMOS) devices that will

  16. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial

    PubMed Central

    Raina, D. B.; Gupta, A.; Petersen, M. M.; Hettwer, W.; McNally, M.; Tägil, M.; Zheng, M-H.; Kumar, A.

    2016-01-01

    Objectives We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1. PMID:27784668

  17. Operation and Performance of a Biphase Turbine Power Plant at the Cerro Prieto Geothermal Field (Final Report)

    SciTech Connect

    Hays, Lance G.

    2000-09-01

    A full scale, wellhead Biphase turbine was manufactured and installed with the balance of plant at Well 103 of the Cerro Prieto geothermal resource in Baja, California. The Biphase turbine was first synchronized with the electrical grid of Comision Federal de Electricidad on August 20, 1997. The Biphase power plant was operated from that time until May 23, 2000, a period of 2 years and 9 months. A total of 77,549 kWh were delivered to the grid. The power plant was subsequently placed in a standby condition pending replacement of the rotor with a newly designed, higher power rotor and replacement of the bearings and seals. The maximum measured power output of the Biphase turbine, 808 kWe at 640 psig wellhead pressure, agreed closely with the predicted output, 840 kWe. When combined with the backpressure steam turbine the total output power from that flow would be increased by 40% above the power derived only from the flow by the present flash steam plant. The design relations used to predict performance and design the turbine were verified by these tests. The performance and durability of the Biphase turbine support the conclusion of the Economics and Application Report previously published, (Appendix A). The newly designed rotor (the Dual Pressure Rotor) was analyzed for the above power condition. The Dual Pressure Rotor would increase the power output to 2064 kWe by incorporating two pressure letdown stages in the Biphase rotor, eliminating the requirement for a backpressure steam turbine. The power plant availability was low due to deposition of solids from the well on the Biphase rotor and balance of plant problems. A great deal of plant down time resulted from the requirement to develop methods to handle the solids and from testing the apparatus in the Biphase turbine. Finally an online, washing method using the high pressure two-phase flow was developed which completely eliminated the solids problem. The availability of the Biphase turbine itself was 100

  18. Enhancing productivity for cascade biotransformation of styrene to (S)-vicinal diol with biphasic system in hollow fiber membrane bioreactor.

    PubMed

    Gao, Pengfei; Wu, Shuke; Praveen, Prashant; Loh, Kai-Chee; Li, Zhi

    2017-03-01

    Biotransformation is a green and useful tool for sustainable and selective chemical synthesis. However, it often suffers from the toxicity and inhibition from organic substrates or products. Here, we established a hollow fiber membrane bioreactor (HFMB)-based aqueous/organic biphasic system, for the first time, to enhance the productivity of a cascade biotransformation with strong substrate toxicity and inhibition. The enantioselective trans-dihydroxylation of styrene to (S)-1-phenyl-1,2-ethanediol, catalyzed by Escherichia coli (SSP1) coexpressing styrene monooxygenase and an epoxide hydrolase, was performed in HFMB with organic solvent in the shell side and aqueous cell suspension in the lumen side. Various organic solvents were investigated, and n-hexadecane was found as the best for the HFMB-based biphasic system. Comparing to other reported biphasic systems assisted by HFMB, our system not only shield much of the substrate toxicity but also deflate the product recovery burden in downstream processing as the majority of styrene stayed in organic phase while the diol product mostly remained in the aqueous phase. The established HFMB-based biphasic system enhanced the production titer to 143 mM, being 16-fold higher than the aqueous system and 1.6-fold higher than the traditional dispersive partitioning biphase system. Furthermore, the combination of biphasic system with HFMB prevents the foaming and emulsification, thus reducing the burden in downstream purification. HFMB-based biphasic system could serve as a suitable platform for enhancing the productivity of single-step or cascade biotransformation with toxic substrates to produce useful and valuable chemicals.

  19. Topical Delivery of Interferon Alpha by Biphasic Vesicles: Evidence for a Novel Nanopathway across the Stratum Corneum

    SciTech Connect

    Foldvari, M.; Badea, B; Wettig, S; Baboolal, D; Kumar, P; Creagh, A; Haynes, C

    2010-01-01

    Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN {alpha}), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN {alpha} intercellularly, to a depth of 70 {micro}m, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN {alpha} by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN {alpha} below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN {alpha}. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.

  20. Biphasic shocks compared with monophasic damped sine wave shocks for direct ventricular defibrillation during open heart surgery.

    PubMed

    Schwarz, Birgit; Bowdle, T Andrew; Jett, G Kimble; Mair, Peter; Lindner, Karl H; Aldea, Gabriel S; Lazzara, Robert G; O'Grady, Sharon G; Schmitt, Paul W; Walker, Robert G; Chapman, Fred W; Tacker, Willis A

    2003-05-01

    Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves. Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used. Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated; P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J; P = 0.003), less cumulative energy (12.6 vs. 23.4 J; P = 0.002), and fewer shocks (2.5 vs. 3.5; P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested. Biphasic shocks are substantially more effective than monophasic shocks for direct defibrillation. The dose-response curve guides selection of first-shock energy for traditional step-up protocols. Starting at 5 J optimizes for lowest threshold and cumulative energy, whereas 10 or 20 J optimizes for more rapid defibrillation and fewer shocks.

  1. Trauma whole-body MDCT: an assessment of image quality in conventional dual-phase and modified biphasic injection.

    PubMed

    Hakim, Wasim; Kamanahalli, Raghavendra; Dick, Elizabeth; Bharwani, Nishat; Fetherston, Shirley; Kashef, Elika

    2016-07-01

    To compare the image quality of conventional arterial and portal venous (PV) phase multidetector CT (MDCT) with two biphasic injection protocols in polytrauma patients. 60 consecutive patients with polytrauma underwent body 256-slice MDCT with a conventional protocol or 1 of 2 single-pass biphasic protocols: Group A, arterial (30 s) and PV (60 s) phase acquisitions; Group B, "biphasic" contrast injection with a single acquisition at 60 s; and Group C, "modified biphasic" injection with a single acquisition at a 70-s delay. Images were analyzed for arterial, venous and parenchymal attenuation profiles with regions of interest in the major arteries, veins and solid abdominal organs. A 5-point scoring system was used to assess the image quality, with 5 representing excellent arterial, venous and parenchymal opacification and <3 representing non-diagnostic opacification. In addition, the effective dose (millisieverts) was compared between the groups. In 93% of patients, image quality was scored as good or excellent (≥4). All studies were of satisfactory diagnostic quality. Overall, venous and arterial attenuation profiles were comparable. Attenuation profiles in the solid abdominal viscera were significantly higher (p < 0.01) using both biphasic protocols than with arterial or PV phase of conventional protocols. Effective doses were higher in Group A. Comparable image quality can be achieved using a biphasic i.v. contrast injection protocol with single MDCT acquisition with less radiation and reduction in acquisition time. For these particular biphasic injection protocols, we have shown that image quality is comparable with a conventional protocol. This has been achieved by comparing enhanced densities of specific structures, as well as gestalt scoring by assessors, on a 256-slice MDCT.

  2. Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in spinal and bulbar muscular atrophy.

    PubMed

    Cortes, Constanza J; Ling, Shuo-Chien; Guo, Ling T; Hung, Gene; Tsunemi, Taiji; Ly, Linda; Tokunaga, Seiya; Lopez, Edith; Sopher, Bryce L; Bennett, C Frank; Shelton, G Diane; Cleveland, Don W; La Spada, Albert R

    2014-04-16

    X-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult-onset muscle weakness and lower motor neuron degeneration. SBMA is caused by CAG-polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) gene. Pathological findings include motor neuron loss, with polyQ-AR accumulation in intranuclear inclusions. SBMA patients exhibit myopathic features, suggesting a role for muscle in disease pathogenesis. To determine the contribution of muscle, we developed a BAC mouse model featuring a floxed first exon to permit cell-type-specific excision of human AR121Q. BAC fxAR121 mice develop systemic and neuromuscular phenotypes, including shortened survival. After validating termination of AR121 expression and full rescue with ubiquitous Cre, we crossed BAC fxAR121 mice with Human Skeletal Actin-Cre mice. Muscle-specific excision prevented weight loss, motor phenotypes, muscle pathology, and motor neuronopathy and dramatically extended survival. Our results reveal a crucial role for muscle expression of polyQ-AR in SBMA and suggest muscle-directed therapies as effective treatments.

  3. A Lagrange multiplier mixed finite element formulation for three-dimensional contact of biphasic tissues.

    PubMed

    Yang, Taiseung; Spilker, Robert L

    2007-06-01

    A three-dimensional (3D) contact finite element formulation has been developed for biological soft tissue-to-tissue contact analysis. The linear biphasic theory of Mow, Holmes, and Lai (1984, J. Biomech., 17(5), pp. 377-394) based on continuum mixture theory, is adopted to describe the hydrated soft tissue as a continuum of solid and fluid phases. Four contact continuity conditions derived for biphasic mixtures by Hou et al. (1989, ASME J. Biomech. Eng., 111(1), pp. 78-87) are introduced on the assumed contact surface, and a weighted residual method has been used to derive a mixed velocity-pressure finite element contact formulation. The Lagrange multiplier method is used to enforce two of the four contact continuity conditions, while the other two conditions are introduced directly into the weighted residual statement. Alternate formulations are possible, which differ in the choice of continuity conditions that are enforced with Lagrange multipliers. Primary attention is focused on a formulation that enforces the normal solid traction and relative fluid flow continuity conditions on the contact surface using Lagrange multipliers. An alternate approach, in which the multipliers enforce normal solid traction and pressure continuity conditions, is also discussed. The contact nonlinearity is treated with an iterative algorithm, where the assumed area is either extended or reduced based on the validity of the solution relative to contact conditions. The resulting first-order system of equations is solved in time using the generalized finite difference scheme. The formulation is validated by a series of increasingly complex canonical problems, including the confined and unconfined compression, the Hertz contact problem, and two biphasic indentation tests. As a clinical demonstration of the capability of the contact analysis, the gleno-humeral joint contact of human shoulders is analyzed using an idealized 3D geometry. In the joint, both glenoid and humeral head

  4. Biphasic fermentation is an efficient strategy for the overproduction of δ-endotoxin from Bacillus thuringiensis.

    PubMed

    Jisha, Veloorvalappil Narayanan; Smitha, Robinson Babysarojam; Priji, Prakasan; Sajith, Sreedharan; Benjamin, Sailas

    2015-02-01

    This study illustrates a biphasic solid-state fermentation (SSF) strategy for the overproduction of δ-endotoxin from Bacillus thuringiensis subsp. kurstaki (Btk) and also purification of δ-endotoxin from the solid-fermented medium. The fermentation strategy had two phases (biphasic); i.e., the first short phase was semisolid state (12 h), and the remaining long phase was strict SSF. To achieve the biphasic SSF, after 12 h (150 rpm, 37 °C) fermentation of the medium [Luria-Bertani (LB) supplemented with 30 % (w/v) raw soybean flour (phase I)], the supernatant in it was completely centrifuged out (1,000 × g, 10 min) aseptically for harvesting the extracellular enzymes as by-product. The resultant wet solid matter without free-flowing liquid but with embedded Btk was incubated 60 h more (phase II) for enhancing δ-endotoxin production at static condition (37 °C). Coupled with this, δ-endotoxin was purified by the modified phase separation method, and its purity was physically confirmed by both staining and microscopic techniques. The maximum δ-endotoxin yield from solid medium (48 h) was 15.8 mg/mL (recovery was 55-59 %) LB-equivalent, while that of LB control (recovery was 95 %) was only 0.43 mg/mL (72 h), i.e., thus, in comparison, 36.74-fold more yield in solid medium obtained by 24 h less gestation period. The purified crystal proteins showed apparent molecular weights (MWs) of 45, 35, and 6 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Briefly, this unique study physically demonstrates how Btk δ-endotoxin is purified (95-99 % purity) from solid-fermented matter for the first time, coupled with its overproduction at the expense of only 21.5 % higher production cost.

  5. Development of calcium phosphate/sulfate biphasic cement for vital pulp therapy.

    PubMed

    Chang, Kai-Chun; Chang, Chia-Chieh; Chen, Wei-Tang; Hsu, Chung-King; Lin, Feng-Huei; Lin, Chun-Pin

    2014-12-01

    Bioactive calcium phosphate cement (CPC) has been used widely to repair bone defects because of its excellent biocompatibility and bioactivity. However, the poor handling properties, low initial mechanical strength, and long setting time of CPC limit its application in vital pulp therapy (VPT). The aim of this study was to synthesize biphasic calcium phosphate/sulfate cements and evaluate the feasibility of applying these cements in VPT. The physical, chemical, and mechanical properties of CPC were improved by mixing the cement with various amounts of α-calcium sulfate hemihydrate (CSH). The hydration products and crystalline phases of the materials were characterized using scanning electron microscopy and X-ray diffraction analysis. In addition, the physical properties, such as the setting time, compressive strength, viscosity, and pH were determined. Water-soluble tetrazolium salt-1 and lactase dehydrogenase were used to evaluate cell viability and cytotoxicity. The developed CPC (CPC/CSH cement), which contains 50wt% CSH cement, exhibited no obvious temperature increase or pH change during setting when it was used as a paste. The initial setting time of the CPC/CSH biphasic cement was substantially shorter than that of CPC, and the initial mechanical strength was 23.7±5.6MPa. The CPC/CSH cement exhibited higher viscosity than CPC and, thus, featured acceptable handling properties. X-ray diffraction analysis revealed that the relative peak intensity for hydroxyapatite increased, and the intensity for calcium sulfate dehydrate decreased as the amount of CPC was increased. The cell viability and cytotoxicity test results indicated that the CPC/CSH cement did not harm dental pulp cells. The developed CPC/CSH biphasic cement exhibits substantial potential for application in VPT. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  6. Isoattenuating insulinomas at biphasic contrast-enhanced CT: frequency, clinicopathologic features and perfusion characteristics.

    PubMed

    Zhu, Liang; Xue, Hua-Dan; Sun, Hao; Wang, Xuan; He, Yong-Lan; Jin, Zheng-Yu; Zhao, Yu-Pei

    2016-10-01

    We aimed to determine the frequency of isoattenuating insulinomas, to investigate their clinicopathological features and to assess their regional pancreatic perfusion characteristics. Institutional review board approval was obtained, and patient informed consent was waived. From July 2010 to June 2014, 170 patients (66 male, 104 female) with endogenous hyperinsulinemic hypoglycemia underwent biphasic contrast-enhanced CT before surgery, and 129 of those patients also received preoperative whole-pancreas CT perfusion. A total of 181 tumours were proved histopathologically after surgery. Enhancement pattern and regional pancreatic perfusion characteristics were analyzed. Clinical features, tumour size and pathological grading were investigated. The frequency of isoattenuating tumours was 24.9 %. Tumour size and WHO grading was not significantly different between isoattenuating and hyperattenuating tumours. Tumour-free regions had identical blood flow (BF) regardless of their location (p = 0.35). Isoattenuating tumour-harbouring regions had lower BF compared with hyperattenuating tumour-harbouring regions; both showed higher BF compared with tumour-free neighbourhood regions (all p < 0.01). For patients with isoattenuating tumours, the overall hospital stay was longer (p < 0.01). A substantial subset of insulinomas were isoattenuating on biphasic CT. CT perfusion showed higher BF in tumour-harbouring regions compared to tumour-free regions, providing a clue for tumour regionalization. • About a quarter of all insulinomas were isoattenuating on biphasic contrast-enhanced CT. • CT perfusion finds tumour-harbouring regions have higher blood-flow compared to tumour-free regions. • CT perfusion provides important information for tumour regionalization, for isoattenuating tumours.

  7. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes.

    PubMed

    Holman, Rury R; Thorne, Kerensa I; Farmer, Andrew J; Davies, Melanie J; Keenan, Joanne F; Paul, Sanjoy; Levy, Jonathan C

    2007-10-25

    Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal, though evidence supporting specific insulin regimens is limited. In an open-label, controlled, multicenter trial, we randomly assigned 708 patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Outcome measures at 1 year were the mean glycated hemoglobin level, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. At 1 year, mean glycated hemoglobin levels were similar in the biphasic group (7.3%) and the prandial group (7.2%) (P=0.08) but higher in the basal group (7.6%, P<0.001 for both comparisons). The respective proportions of patients with a glycated hemoglobin level of 6.5% or less were 17.0%, 23.9%, and 8.1%; respective mean numbers of hypoglycemic events per patient per year were 5.7, 12.0, and 2.3; and respective mean weight gains were 4.7 kg, 5.7 kg, and 1.9 kg. Rates of adverse events were similar among the three groups. A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. The addition of biphasic or prandial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain. (Current Controlled Trials number, ISRCTN51125379 [controlled-trials.com].). Copyright 2007 Massachusetts Medical Society.

  8. Activated microglia in acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Fujita, Yuji; Takanashi, Jun-Ichi; Takei, Haruka; Ota, Setsuo; Fujii, Katsunori; Sakuma, Hiroshi; Hayashi, Masaharu

    2016-07-15

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. The exact pathogenesis of and the best therapeutic strategy for AESD are uncertain. We firstly performed a brain biopsy in a 2-year-old boy with AESD associated with RS viral infection, which revealed activated ameoboid microglia accumulation around degenerated neuron, and astrogliosis in the affected cortex. Glutamate released from activated microglia may play an important role in the pathogenesis of AESD, which is compatible with the previous report of magnetic resonance spectroscopy showing elevated glutamate. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Repair of porcine articular cartilage defect with a biphasic osteochondral composite.

    PubMed

    Jiang, Ching-Chuan; Chiang, Hongsen; Liao, Chun-Jen; Lin, Yu-Ju; Kuo, Tzong-Fu; Shieh, Chang-Shun; Huang, Yi-You; Tuan, Rocky S

    2007-10-01

    Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native

  10. Use of Biphasic Continuous Positive Airway Pressure in Premature Infant with Cleft Lip–Cleft Palate

    PubMed Central

    George, Lovya; Jain, Sunil K.

    2015-01-01

    Preterm infants (PIs) often require respiratory support due to surfactant deficiency. Early weaning from mechanical ventilation to noninvasive respiratory support decreases ventilation-associated irreversible lung damage. This wean is particularly challenging in PIs with cleft lip and cleft palate due to anatomical difficulties encountered in maintaining an adequate seal for positive pressure ventilation. PI with a cleft lip and palate often fail noninvasive respiratory support and require continued intubation and mechanical ventilation. We are presenting the first case report of a PI with cleft lip and palate who was managed by biphasic nasal continuous positive airway pressure. PMID:26495158

  11. Steroid biotransformations in biphasic systems with Yarrowia lipolytica expressing human liver cytochrome P450 genes

    PubMed Central

    2012-01-01

    Background Yarrowia lipolytica efficiently metabolizes and assimilates hydrophobic compounds such as n-alkanes and fatty acids. Efficient substrate uptake is enabled by naturally secreted emulsifiers and a modified cell surface hydrophobicity and protrusions formed by this yeast. We were examining the potential of recombinant Y. lipolytica as a biocatalyst for the oxidation of hardly soluble hydrophobic steroids. Furthermore, two-liquid biphasic culture systems were evaluated to increase substrate availability. While cells, together with water soluble nutrients, are maintained in the aqueous phase, substrates and most of the products are contained in a second water-immiscible organic solvent phase. Results For the first time we have co-expressed the human cytochromes P450 2D6 and 3A4 genes in Y. lipolytica together with human cytochrome P450 reductase (hCPR) or Y. lipolytica cytochrome P450 reductase (YlCPR). These whole-cell biocatalysts were used for the conversion of poorly soluble steroids in biphasic systems. Employing a biphasic system with the organic solvent and Y. lipolytica carbon source ethyl oleate for the whole-cell bioconversion of progesterone, the initial specific hydroxylation rate in a 1.5 L stirred tank bioreactor was further increased 2-fold. Furthermore, the product formation was significantly prolonged as compared to the aqueous system. Co-expression of the human CPR gene led to a 4-10-fold higher specific activity, compared to the co-overexpression of the native Y. lipolytica CPR gene. Multicopy transformants showed a 50-70-fold increase of activity as compared to single copy strains. Conclusions Alkane-assimilating yeast Y. lipolytica, coupled with the described expression strategies, demonstrated its high potential for biotransformations of hydrophobic substrates in two-liquid biphasic systems. Especially organic solvents which can be efficiently taken up and/or metabolized by the cell might enable more efficient bioconversion as compared

  12. Lipase in biphasic alginate beads as a biocatalyst for esterification of butyric acid and butanol in aqueous media.

    PubMed

    Ng, Choong Hey; Yang, Kun-Lin

    2016-01-01

    Esterification of organic acids and alcohols in aqueous media is very inefficient due to thermodynamic constraints. However, fermentation processes used to produce organic acids and alcohols are often conducted in aqueous media. To produce esters in aqueous media, biphasic alginate beads with immobilized lipase are developed for in situ esterification of butanol and butyric acid. The biphasic beads contain a solid matrix of calcium alginate and hexadecane together with 5 mg/mL of lipase as the biocatalyst. Hexadecane in the biphasic beads serves as an organic phase to facilitate the esterification reaction. Under optimized conditions, the beads are able to catalyze the production of 0.16 mmol of butyl butyrate from 0.5 mmol of butyric acid and 1.5 mmol of butanol. In contrast, when monophasic beads (without hexadecane) are used, only trace amount of butyl butyrate is produced. One main application of biphasic beads is in simultaneous fermentation and esterification (SFE) because the organic phase inside the beads is very stable and does not leach out into the culture medium. SFE is successfully conducted with an esterification yield of 6.32% using biphasic beads containing iso-octane even though the solvent is proven toxic to the butanol-producing Clostridium spp.

  13. Phenotype definition in epilepsy.

    PubMed

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  14. Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial.

    PubMed

    Page, Richard L; Kerber, Richard E; Russell, James K; Trouton, Tom; Waktare, Johan; Gallik, Donna; Olgin, Jeff E; Ricard, Philippe; Dalzell, Gavin W; Reddy, Ramakota; Lazzara, Ralph; Lee, Kerry; Carlson, Mark; Halperin, Blair; Bardy, Gust H

    2002-06-19

    This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation (AF). Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation, but data regarding biphasic shocks for conversion of AF are still emerging. In an international, multicenter, randomized, double-blind clinical trial, we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF. Patients received up to five shocks, as necessary for conversion: 100 J, 150 J, 200 J, a fourth shock at maximum output for the initial waveform (200 J biphasic, 360 J monophasic) and a final cross-over shock at maximum output of the alternate waveform. Analysis included 107 monophasic and 96 biphasic patients. The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels (100 J: 60% vs. 22%, p < 0.0001; 150 J: 77% vs. 44%, p < 0.0001; 200 J: 90% vs. 53%, p < 0.0001). Through four shocks, at a maximum of 200 J, biphasic performance was similar to monophasic performance at 360 J (91% vs. 85%, p = 0.29). Biphasic patients required fewer shocks (1.7 +/- 1.0 vs. 2.8 +/- 1.2, p < 0.0001) and lower total energy delivered (217 +/- 176 J vs. 548 +/- 331 J, p < 0.0001). The biphasic shock waveform was also associated with a lower frequency of dermal injury (17% vs. 41%, p < 0.0001). For the cardioversion of AF, a biphasic shock waveform has greater efficacy, requires fewer shocks and lower delivered energy, and results in less dermal injury than a monophasic shock waveform.

  15. Fluorocarbon compatibilized gold-silica nanocomposites for recyclable regioselective hydroamination of alkynes in a fluorous biphasic system

    NASA Astrophysics Data System (ADS)

    Merican, Zulkifli; Vu, Bao Khanh; Solovyeva, Vera A.; Rodionov, Valentin O.; Khe, Cheng Seong; Rajalingam, Sokkalingam; Vasant, Pandian

    2016-11-01

    The synthesis and characterization of the mesoporous silica-supported gold (Au@mSiO2) nanoparticles compatibilized with the outer shelled superhydrophobic fluorous (F) "tails" was described. The concept of fluorous biphasic separation was applied in the recycling of the synthesized fluorous material during hydroamination reactions of various alkynes. In the presence of perfluoromethylcyclohexane and heptane as a biphasic liquid system, the F-Au@mSiO2 was found to be a highly active catalyst for hydroamination of various alkynes with anilines, and a near quantitative yield for an imine product and produced a relatively minimal formation of a corresponding hydrolyzed ketone by-product. If perfluoromethylcyclohexane and heptane was used as a biphasic solvent, hydroamination at a lower reaction temperature can also be realized leading to an improved recyclability and conversion.

  16. Invariance of the magnetic behavior and AMI in ferromagnetic biphase films with distinct non-magnetic metallic spacers

    NASA Astrophysics Data System (ADS)

    Silva, E. F.; Gamino, M.; Andrade, A. M. H. de; Vázquez, M.; Correa, M. A.; Bohn, F.

    2017-02-01

    We investigate the quasi-static magnetic, magnetotransport, and dynamic magnetic properties in ferromagnetic biphase films with distinct non-magnetic metallic spacer layers. We observe that the nature of the non-magnetic metallic spacer material does not have significant influence on the overall biphase magnetic behavior, and, consequently, on the magnetotransport and dynamic magnetic responses. We focus on the magnetoimpedance effect and verify that the films present asymmetric magnetoimpedance effect. Moreover, we explore the possibility of tuning the linear region of the magnetoimpedance curves around zero magnetic field by varying the probe current frequency in order to achieve higher sensitivity values. The invariance of the magnetic behavior and the asymmetric magnetoimpedance effect in ferromagnetic biphase films with distinct non-magnetic metallic spacers place them as promising candidates for probe element and open possibilities to the development of lower-cost high sensitivity linear magnetic field sensor devices.

  17. Fabrication of Biphase BiVO4 Particles with Enhanced Photocatalytic Performance via a Surfactant-Free Hydrothermal Route

    NASA Astrophysics Data System (ADS)

    Qian, Hongzhi; Lai, Min; Huang, Xiaogu; Wang, Wei; Xu, Chaoqi; Yong, Haibo; Wen, Yan; Zhou, Yingjie

    2016-04-01

    Biphase bismuth vanadate (BiVO4) particles have been synthesized using a surfactant-free hydrothermal strategy. Biphase BiVO4 were formed at pH=3, 5 and 7 with a bandgap between 2.28eV and 2.86eV, which are those of monoclinic and tetragonal phases, respectively. Photocatalytic tests on the degradation of rhodamine B (RhB) under visible-light irradiation showed that biphase BiVO4 with both monoclinic and tetragonal structures synthesized at pH=3 achieved enhanced photocatalytic performance in comparison with pure monoclinic and tetragonal phases, which was attributed to the heterostructures leading to low recombination rate of electron-hole pairs.

  18. Phenotypic switching in bacteria

    NASA Astrophysics Data System (ADS)

    Merrin, Jack

    Living matter is a non-equilibrium system in which many components work in parallel to perpetuate themselves through a fluctuating environment. Physiological states or functionalities revealed by a particular environment are called phenotypes. Transitions between phenotypes may occur either spontaneously or via interaction with the environment. Even in the same environment, genetically identical bacteria can exhibit different phenotypes of a continuous or discrete nature. In this thesis, we pursued three lines of investigation into discrete phenotypic heterogeneity in bacterial populations: the quantitative characterization of the so-called bacterial persistence, a theoretical model of phenotypic switching based on those measurements, and the design of artificial genetic networks which implement this model. Persistence is the phenotype of a subpopulation of bacteria with a reduced sensitivity to antibiotics. We developed a microfluidic apparatus, which allowed us to monitor the growth rates of individual cells while applying repeated cycles of antibiotic treatments. We were able to identify distinct phenotypes (normal and persistent) and characterize the stochastic transitions between them. We also found that phenotypic heterogeneity was present prior to any environmental cue such as antibiotic exposure. Motivated by the experiments with persisters, we formulated a theoretical model describing the dynamic behavior of several discrete phenotypes in a periodically varying environment. This theoretical framework allowed us to quantitatively predict the fitness of dynamic populations and to compare survival strategies according to environmental time-symmetries. These calculations suggested that persistence is a strategy used by bacterial populations to adapt to fluctuating environments. Knowledge of the phenotypic transition rates for persistence may provide statistical information about the typical environments of bacteria. We also describe a design of artificial

  19. Switching from biphasic human insulin to biphasic insulin aspart 30 in type 2 diabetes: results from the ASEAN subgroup of the A₁chieve study.

    PubMed

    Hussein, Zanariah; Lim-Abrahan, Mary Anne; Jain, Anand B; Goh, Su Yen; Soewondo, Pradana

    2013-04-01

    To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in ASEAN type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) in the non-interventional 24-week A₁chieve study. Indonesian, Malaysian, Filipino and Singaporean patients switched from BHI to BIAsp 30 at their physicians' discretion were included. The incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia was the primary endpoint. Changes in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), lipids, body weight and systolic blood pressure were also evaluated. Quality of life (QoL) was measured using the EQ-5D questionnaire. For the 465 patients included (mean ± SD age: 56 ± 10.3 years, diabetes duration: 9.7 ± 7.1 years, baseline HbA1c: 9.4 ± 1.8%), the mean pre-study BHI dose was 0.62 ± 0.28 IU/kg and 63.4% were dosing BHI twice daily (bid). The mean baseline BIAsp 30 dose was 0.65 ± 0.27 U/kg, titrated up to 0.71 ± 0.28 U/kg over 24 weeks, and most patients continued bid dosing. No SADRs or major hypoglycaemic episodes were reported. The proportion of patients reporting overall hypoglycaemia decreased significantly from 10.8% at baseline to 3.4% at Week 24 (p < 0.0001). Significant improvements in glycaemic control were noted (HbA1c: -1.4 ± 1.7%, FPG: -56.7 ± 72.5 mg/dL, post-breakfast PPPG: -84.8 ± 82.8 mg/dL, p < 0.001). Mean QoL improved by +6.6 ± 14.6 points (p < 0.001). BIAsp 30 was well-tolerated and significantly increased glycaemic control in this ASEAN subgroup poorly controlled on BHI. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Method for separating water soluble organics from a process stream by aqueous biphasic extraction

    DOEpatents

    Chaiko, David J.; Mego, William A.

    1999-01-01

    A method for separating water-miscible organic species from a process stream by aqueous biphasic extraction is provided. An aqueous biphase system is generated by contacting a process stream comprised of water, salt, and organic species with an aqueous polymer solution. The organic species transfer from the salt-rich phase to the polymer-rich phase, and the phases are separated. Next, the polymer is recovered from the loaded polymer phase by selectively extracting the polymer into an organic phase at an elevated temperature, while the organic species remain in a substantially salt-free aqueous solution. Alternatively, the polymer is recovered from the loaded polymer by a temperature induced phase separation (cloud point extraction), whereby the polymer and the organic species separate into two distinct solutions. The method for separating water-miscible organic species is applicable to the treatment of industrial wastewater streams, including the extraction and recovery of complexed metal ions from salt solutions, organic contaminants from mineral processing streams, and colorants from spent dye baths.

  1. Accounting for phase drifts in SSVEP-based BCIs by means of biphasic stimulation.

    PubMed

    Wu, Hung-Yi; Lee, Po-Lei; Chang, Hsiang-Chih; Hsieh, Jen-Chuen

    2011-05-01

    This study proposes a novel biphasic stimulation technique to solve the issue of phase drifts in steady-state visual evoked potential (SSVEPs) in phase-tagged systems. Phase calibration was embedded in stimulus sequences using a biphasic flicker, which is driven by a sequence with alternating reference and phase-shift states. Nine subjects were recruited to participate in off-line and online tests. Signals were bandpass filtered and segmented by trigger signals into reference and phase-shift epochs. Frequency components of SSVEP in the reference and phase-shift epochs were extracted using the Fourier method with a 50% overlapped sliding window. The real and imaginary parts of the SSVEP frequency components were organized into complex vectors in each epoch. Hotelling's t-square test was used to determine the significances of nonzero mean vectors. The rejection of noisy data segments and the validation of gaze detections were made based on p values. The phase difference between the valid mean vectors of reference and phase-shift epochs was used to identify user's gazed targets in this system. Data showed an average information transfer rate of 44.55 and 38.21 bits/min in off-line and online tests, respectively.

  2. Removal of textile dyes from textile dye effluent using TBAB based aqueous biphasic systems.

    PubMed

    Dilip, Meghna; Venkateswaran, P; Palanivelu, K

    2005-07-01

    Aqueous biphasic systems (ABS) are useful for the extraction of dye molecules from aqueous solution. Thus, they can be used in textile dye bath effluent treatment. The partitioning behavior of two commercially used textile dyes-Cibacron Scarlet LS 2G and Astacryl Red 3B were investigated in a TBAB-salt aqueous biphasic systems. It was found that all three salts, namely sodium chloride, sodium sulphate and sodium carbonate, investigated caused partitioning of dye into the upper TBAB rich phase. The efficiency of separation increased in the order NaCl < Na2SO4 < Na2CO. It was found that the cationic dye partitioned better than the anionic dye in the system. A concentration of 5 g/l of dye was extracted into the upper layer. Alteration of solution pH did not cause any significant difference in distribution ratios. Studies were extended to actual dye bath effluent and small scale up studies carried out. Efficiencies of removal obtained in all cases were extremely good with maximum efficiencies above 98 %.

  3. Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle

    SciTech Connect

    Ikeda, Shin-ichi; Kizaki, Takako; Haga, Shukoh; Ohno, Hideki; Takemasa, Tohru

    2008-04-04

    Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1{alpha} and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found that the exercise induced a biphasic increase in the expression of respiratory enzymes mRNA. The second phase of the increase was accompanied by an increase in PGC-1{alpha} protein, but the other was not. Administration of SB203580 (SB), an inhibitor of p38 MAPK, suppressed the increase in PGC-1{alpha} expression and respiratory enzymes mRNA in both phases. These data suggest that p38 MAPK is associated with the exercise-induced expression of PGC-1{alpha} and biphasic increase in respiratory enzyme mRNAs in mouse skeletal muscle under physiological conditions.

  4. Bioabsorbable zinc ion induced biphasic cellular responses in vascular smooth muscle cells

    PubMed Central

    Ma, Jun; Zhao, Nan; Zhu, Donghui

    2016-01-01

    Bioabsorbable metal zinc (Zn) is a promising new generation of implantable scaffold for cardiovascular and orthopedic applications. In cardiovascular stent applications, zinc ion (Zn2+) will be gradually released into the surrounding vascular tissues from such Zn-containing scaffolds after implantation. However, the interactions between vascular cells and Zn2+ are still largely unknown. We explored the short-term effects of extracellular Zn2+ on human smooth muscle cells (SMCs) up to 24 h, and an interesting biphasic effect of Zn2+ was observed. Lower concentrations (<80 μM) of Zn2+ had no adverse effects on cell viability but promoted cell adhesion, cell spreading, cell proliferation, cell migration, and enhanced the expression of F-actin and vinculin. Cells treated with such lower concentrations of Zn2+ displayed an elongated shape compared to controls without any treatment. In contrast, cells treated with higher Zn2+ concentrations (80–120 μM) had opposite cellular responses and behaviors. Gene expression profiles revealed that the most affected functional genes were related to angiogenesis, inflammation, cell adhesion, vessel tone, and platelet aggregation. Results indicated that Zn has interesting concentration-dependent biphasic effects on SMCs with low concentrations being beneficial to cellular functions. PMID:27248371

  5. Prostaglandin E2 (PGE2) Exerts Biphasic Effects on Human Tendon Stem Cells

    PubMed Central

    Zhang, Jianying; Wang, James H-C.

    2014-01-01

    Prostaglandin E2 (PGE2) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE2 (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE2 markedly enhanced hTSC proliferation. The expression levels of stem cell marker genes, specifically SSEA-4 and Stro-1, were more extensive in hTSCs treated with low concentrations of PGE2 than in cells treated with high levels of PGE2. Moreover, high levels of PGE2 induced hTSCs to differentiate aberrantly into non-tenocytes, which was evident by the high levels of PPARγ, collagen type II, and osteocalcin expression in hTSCs treated with PGE2 at concentrations >1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo. PMID:24504456

  6. Cranial muscle development in frogs with different developmental modes: direct development versus biphasic development.

    PubMed

    Ziermann, Janine M; Diogo, Rui

    2014-04-01

    Normal development in anurans includes a free swimming larva that goes through metamorphosis to develop into the adult frog. We have investigated cranial muscle development and adult cranial muscle morphology in three different anuran species. Xenopus laevis is obligate aquatic throughout lifetime, Rana(Lithobates) pipiens has an aquatic larvae and a terrestrial adult form, and Eleutherodactylus coqui has direct developing juveniles that hatch from eggs deposited on leaves (terrestrial). The adult morphology shows hardly any differences between the investigated species. Cranial muscle development of E. coqui shows many similarities and only few differences to the development of Rana (Lithobates) and Xenopus. The differences are missing muscles of the branchial arches (which disappear during metamorphosis of biphasic anurans) and a few heterochronic changes. The development of the mandibular arch (adductor mandibulae) and hyoid arch (depressor mandibulae) muscles is similar to that observed in Xenopus and Rana (Lithobates), although the first appearance of these muscles displays a midmetamorphic pattern in E. coqui. We show that the mix of characters observed in E. coqui indicates that the larval stage is not completely lost even without a free swimming larval stage. Cryptic metamorphosis is the process in which morphological changes in the larva/embryo take place that are not as obvious as in normal metamorphosing anurans with a clear biphasic lifestyle. During cryptic metamorphosis, a normal adult frog develops, indicating that the majority of developmental mechanisms towards the functional adult cranial muscles are preserved.

  7. Primary Esophageal Extranasal NK/T Cell Lymphoma With Biphasic Morphology

    PubMed Central

    Ye, Zi-Yin; Cao, Qing-Hua; Liu, Fang; Lu, Xiao-Fang; Li, Shu-Rong; Li, Chang-Zhao; Chen, Shao-Hong

    2015-01-01

    Abstract We report a case of esophageal extranasal NK/T cell lymphoma with biphasic morphologic features revealed by a deep large piecemeal biopsy. A 40-year-old man present with pharyngalgia, dysphagia, recurrent fever, and 5-kg weight loss for 8 months. Endoscopy demonstrated progressing longitudinal ulcers and mucosal bridges along the esophagus. The first and second biopsies obtained superficial mucosa with scattered bland-looking small lymphocytes. A subsequent large piecemeal snare abscission for biopsy showed atypical lymphoid cells infiltrating into the deep lamina propria and muscularis mucosae, whereas the superficial lamina propria was highly edematous with scant small lymphocytes. Immunohistochemical studies confirmed that both underlying atypical cells and superficial small lymphocytes were neoplastic, sharing an identical immunophenotype: positive for CD2, CD3, CD43, CD8, CD56, TIA-1 and granzyme B. Epstein-Barr virus–encoded small RNAs were found in both cells. The histologic findings were diagnostic of primary esophageal extranasal NK/T cell lymphoma. However, the patient developed bone marrow depression during chemotherapy and died of massive cerebral hemorrhage after the first cycle of chemotherapy. Primary esophageal extranodal NK/T cell lymphoma nasal type is extremely rare. We show the biphasic morphology of this disease, which highlights the importance of deep biopsy for accurate diagnosis. PMID:26181557

  8. Method for separating water soluble organics from a process stream by aqueous biphasic extraction

    SciTech Connect

    Chaiko, D.J.; Mego, W.A.

    1999-09-07

    A method for separating water-miscible organic species from a process stream by aqueous biphasic extraction is provided. An aqueous biphase system is generated by contacting a process stream comprised of water, salt, and organic species with an aqueous polymer solution. The organic species transfer from the salt-rich phase to the polymer-rich phase, and the phases are separated. Next, the polymer is recovered from the loaded polymer phase by selectively extracting the polymer into an organic phase at an elevated temperature, while the organic species remain in a substantially salt-free aqueous solution. Alternatively, the polymer is recovered from the loaded polymer by a temperature induced phase separation (cloud point extraction), whereby the polymer and the organic species separate into two distinct solutions. The method for separating water-miscible organic species is applicable to the treatment of industrial wastewater streams, including the extraction and recovery of complexed metal ions from salt solutions, organic contaminants from mineral processing streams, and colorants from spent dye baths.

  9. Occurrence of amylose-lipid complexes in teff and maize starch biphasic pastes.

    PubMed

    Wokadala, Obiro Cuthbert; Ray, Suprakas Sinha; Emmambux, Mohammad Naushad

    2012-09-01

    The occurrence of amylose-lipid complexes was determined in maize and teff starch biphasic pastes i.e. peak viscosity pastes at short and prolonged pasting times. Maize and teff starches were pasted for 11.5 and 130 min with or without added stearic acid followed by thermo-stable alpha-amylase hydrolysis in a rapid visco-analyzer. X-ray diffraction analysis of pastes before and residues after hydrolysis showed crystalline V-amylose diffraction patterns for the starches pasted for a prolonged time with added stearic acid while less distinct V-amylose patterns with non-complexed stearic acid peaks were observed with a short pasting time. Differential scanning calorimetry of pastes before and residues after paste hydrolysis showed that Type I amylose-lipid complexes were formed after pasting for the short duration with added stearic acid, while Type II complexes are formed after pasting for the prolonged time. The present research provides evidence that amylose-lipid complexes play an important role in starch biphasic pasting.

  10. Biphasic mode of antibacterial action of aminoglycoside antibiotics-loaded elastic hydroxyapatite-glucan composite.

    PubMed

    Belcarz, Anna; Zima, Aneta; Ginalska, Grażyna

    2013-09-15

    Following the quest for new composite materials for bone tissue engineering, a novel elastic hydroxyapatite-glucan composite loaded with two aminoglycoside antibiotics was prepared. The porosity of the composite and the drug release profiles in closed-loop and semi-open systems were tested. The antibacterial activity of the drug was estimated against two Gram-positive and two Gram-negative bacterial strains causing orthopedic infections. It was found that the loaded antibiotic acted in a biphasic mode. The majority of the drug was released within 48-119 h in a pore-dependent manner and inhibited the bacterial growth in the culture medium. However, a small residual amount of the drug was bound to the composite microstructure via ionic interactions and acted as a short-lived barrier against bacterial adhesion to the composite, although the surrounding medium was no longer protected against bacterial infection. Sub-inhibitory concentrations of the released drug were observed in the medium only during the last two days of the experiment (minimized risk of occurrence of drug-resistant strains). Thus the novel drug-loaded elastic hydroxyapatite-glucan composite, demonstrating a biphasic mode of antibacterial action, may be recommended for antibiotic prophylaxis in bone substitute implantation, with less emphasis on the treatment of bone infections.

  11. A biphasic approach for the study of lift generation in soft porous media

    NASA Astrophysics Data System (ADS)

    Wu, Qianhong; Santhanam, Sridhar; Nathan, Rungun; Wang, Qiuyun

    2017-04-01

    Lift generation in highly compressible porous media under rapid compression continues to be an important topic in porous media flow. Although significant progress has been made, how to model different lifting forces during the compression process remains unclear. This is mainly because the input parameters of the existing theoretical studies, including the Darcy permeability of the porous media and the viscous damping coefficient of its solid phase, were manually adjusted so as to match the experimental data. In the current paper, we report a biphasic approach to experimentally and theoretically treat this limitation. Synthetic fibrous porous materials, whose permeability were precisely measured, were subsequently exposed to sudden impacts using a porous-walled cylinder-piston apparatus. The obtained time-dependent compression of the porous media, along with the permeability data, was applied in two different theoretical models to predict the pore pressure generation, a plug flow model and a consolidation model [Q. Wu et al., J. Fluid Mech. 542, 281 (2005a)]. Comparison between the theory and the experiments on the pore pressure distribution proved the validity of the consolidation model. Furthermore, a viscoelastic model, containing a nonlinear spring in conjunction with a linear viscoelastic generalized Maxwell mechanical module, was developed to characterize the solid phase lifting force. The model matched the experimental data very well. The paper presented herein, as one of the series studies on this topic, provides an important biphasic approach to characterize different forces that contribute to the lift generation in a soft porous medium under rapid compression.

  12. Aqueous biphasic extraction of uranium and thorium from contaminated soils. Final report

    SciTech Connect

    Chaiko, D.J.; Gartelmann, J.; Henriksen, J.L.; Krause, T.R.; Deepak; Vojta, Y.; Thuillet, E.; Mertz, C.J.

    1995-07-01

    The aqueous biphasic extraction (ABE) process for soil decontamination involves the selective partitioning of solutes and fine particulates between two immiscible aqueous phases. The biphase system is generated by the appropriate combination of a water-soluble polymer (e.g., polyethlene glycol) with an inorganic salt (e.g., sodium carbonate). Selective partitioning results in 99 to 99.5% of the soil being recovered in the cleaned-soil fraction, while only 0.5 to 1% is recovered in the contaminant concentrate. The ABE process is best suited to the recovery of ultrafine, refractory material from the silt and clay fractions of soils. During continuous countercurrent extraction tests with soil samples from the Fernald Environmental Management Project site (Fernald, OH), particulate thorium was extracted and concentrated between 6- and 16-fold, while the uranium concentration was reduced from about 500 mg/kg to about 77 mg/kg. Carbonate leaching alone was able to reduce the uranium concentration only to 146 mg/kg. Preliminary estimates for treatment costs are approximately $160 per ton of dry soil. A detailed flowsheet of the ABE process is provided.

  13. Superabsorbent biphasic system based on poly(lactic acid) and poly(acrylic acid)

    NASA Astrophysics Data System (ADS)

    Sartore, Luciana; Pandini, Stefano; Baldi, Francesco; Bignotti, Fabio

    2016-05-01

    In this research work, biocomposites based on crosslinked particles of poly(acrylic acid), commonly used as superabsorbent polymer (SAP), and poly-L-lactic acid (PLLA) were developed to elucidate the role of the filler (i.e., polymeric crosslinked particles) on the overall physico-mechanical behavior and to obtain superabsorbent thermoplastic products. Samples prepared by melt-blending of components in different ratios showed a biphasic system with a regular distribution of particles, with diameter ranging from 5 to 10 μm, within the PLLA polymeric matrix. The polymeric biphasic system, coded PLASA i.e. superabsorbent poly(lactic acid), showed excellent swelling properties, demonstrating that cross-linked particles retain their superabsorbent ability, as in their free counterparts, even if distributed in a thermoplastic polymeric matrix. The thermal characteristics of the biocomposites evidence enhanced thermal stability in comparison with neat PLLA and also mechanical properties are markedly modified by addition of crosslinked particles which induce regular stiffening effect. Furthermore, in aqueous environments the particles swell and are leached from PLLA matrix generating very high porosity. These new open-pore PLLA foams, produced in absence of organic solvents and chemical foaming agents, with good physico-mechanical properties appear very promising for several applications, for instance in tissue engineering for scaffold production.

  14. Biopolymer-stabilized Pt nanoparticles colloid: a highly active and recyclable catalyst for biphasic catalysis

    NASA Astrophysics Data System (ADS)

    Wang, Yujia; Shen, Yueyue; Qiu, Yunfei; Zhang, Ting; Liao, Yang; Zhao, Shilin; Ma, Jun; Mao, Hui

    2016-10-01

    Noble metal nanoparticles are promising candidates to replace conventional bulk counterparts owing to their high activity and selectivity. To enable catalyst recovery, noble metal nanoparticles are often supported onto solid matrices to prepare heterogeneous catalyst. Although recycle of noble metal nanoparticles is realized by heterogenization, a loss of activity is usually encountered. In the present investigation, Pt nanoparticles with tunable particle size (1.85-2.80 nm) were facilely prepared by using polyphenols as amphiphilic stabilizers. The as-prepared Pt nanoparticles colloid solution could be used as highly active catalyst in aqueous-organic biphasic catalysis. The phenolic hydroxyls of polyphenols could constrain Pt nanoparticles in aqueous phase, and simultaneously, the aromatic scaffold of polyphenols ensured effective interactions between substrates and Pt nanoparticles. As a consequence, the obtained polyphenols-stabilized Pt nanoparticles exhibited high activity and cycling stability in biphasic hydrogenation of a series of unsaturated compounds. Compared with conventional heterogeneous Pt-C and Pt-Al2O3 catalysts, polyphenols-stabilized Pt nanoparticles showed obvious advantage both in activity and cycling stability.

  15. New resource for the computation of cartilage biphasic material properties with the interpolant response surface method

    PubMed Central

    Keenan, Kathryn E.; Kourtis, Lampros C.; Besier, Thor F.; Lindsey, Derek P.; Gold, Garry E.; Delp, Scott L.; Beaupre, Gary S.

    2009-01-01

    Cartilage material properties are important for understanding joint function and diseases, but can be challenging to obtain. Three biphasic material properties (aggregate modulus, Poisson's ratio and permeability) can be determined using an analytical or finite element model combined with optimisation to find the material properties values that best reproduce an experimental creep curve. The purpose of this study was to develop an easy-to-use resource to determine biphasic cartilage material properties. A Cartilage Interpolant Response Surface was generated from interpolation of finite element simulations of creep indentation tests. Creep indentation tests were performed on five sites across a tibial plateau. A least-squares residual search of the Cartilage Interpolant Response Surface resulted in a best-fit curve for each experimental condition with corresponding material properties. These sites provided a representative range of aggregate moduli (0.48–1.58 MPa), Poisson's ratio (0.00–0.05) and permeability (1.7 × 10−15−5.4 × 10−15 m4/N s) values found in human cartilage. PMID:19675978

  16. A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair.

    PubMed

    Ryan, Alan J; Lackington, William A; Hibbitts, Alan J; Matheson, Austyn; Alekseeva, Tijna; Stejskalova, Anna; Roche, Phoebe; O'Brien, Fergal J

    2017-10-04

    Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze-drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Fabrication of nano structural biphasic materials from phosphogypsum waste and their in vitro applications

    SciTech Connect

    Mohamed, Khaled R.; Mousa, Sahar M.; El Bassyouni, Gehan T.

    2014-02-01

    Graphical abstract: (a) Schema of the process, (b) TEM of nano particles of biphasic materials and (c) SEM of post-immersion. - Highlights: • Ratio of HA and β-TCP phases were controlled by thermal treatment. • HA partially decomposed into β-TCP with other bioactive phases. • Calcined HA at 900 °C is the best for the bioactivity behavior. - Abstract: In this study, a novel process of preparing biphasic calcium phosphate (BCP) is proposed. Also its bioactivity for the utilization of the prepared BCP as a biomaterial is studied. A mixture of calcium hydroxyapatite (HAP) and tricalcium phosphate (β-TCP) could be obtained by thermal treatment of HAP which was previously prepared from phosphogypsum (PG) waste. The chemical and phase composition, morphology and particle size of prepared samples was characterized by X-ray diffraction (XRD), Infrared spectroscopy (IR), Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). The bioactivity was investigated by soaking of the calcined samples in simulated body fluid (SBF). Results confirmed that the calcination temperatures played an important role in the formation of calcium phosphate (CP) materials. XRD results indicated that HAP was partially decomposed into β-TCP. The in vitro data confirmed that the calcined HAP forming BCP besides other phases such as pyrophosphate and silica are bioactive materials. Therefore, BCP will be used as good biomaterials for medical applications.

  18. Investigation of biphasic tumor oxygen dynamics induced by hyperoxic gas intervention: the dynamic phantom approach

    NASA Astrophysics Data System (ADS)

    Kim, Jae G.; Liu, Hanli

    2008-01-01

    We have developed dynamic tumor vascular phantoms and utilized them to investigate the biphasic behavior of increases in light absorption, which is directly associated with oxygenated hemoglobin concentration that was observed in vivo from rat breast tumor experiments during carbogen/oxygen inhalation. The experimental setup for the phantom study included a continuous-wave, multichannel, near-infrared spectroscopy (NIRS) system and syringe pumps to drive the simulated blood through the dynamic vascular phantoms. The results from such phantom experiments clearly show that the two time constants observed in tumor oxygenation dynamics in vivo can result from two different perfusion rates or two different blood flow velocities. We provide experimental support for our previous hypothesis: the biphasic tumor hemodynamic feature stems from a well-perfused and poorly perfused region that could be detected with the two time constants of the NIRS signals. With a multichannel approach, noninvasive NIRS measurements may have useful and prognostic values to quantify the therapeutic effects of cancer treatments.

  19. Non-conventional solvents in liquid phase microextraction and aqueous biphasic systems.

    PubMed

    An, Jiwoo; Trujillo-Rodríguez, María J; Pino, Verónica; Anderson, Jared L

    2017-06-02

    The development of rapid, convenient, and high throughput sample preparation approaches such as liquid phase microextraction techniques have been continuously developed over the last decade. More recently, significant attention has been given to the replacement of conventional organic solvents used in liquid phase microextraction techniques in order to reduce toxic waste and to improve selectivity and/or extraction efficiency. With these objectives, non-conventional solvents have been explored in liquid phase microextraction and aqueous biphasic systems. The utilized non-conventional solvents include ionic liquids, magnetic ionic liquids, and deep eutectic solvents. They have been widely used as extraction solvents or additives in various liquid phase microextraction modes including dispersive liquid-liquid microextraction, single-drop microextraction, hollow fiber-liquid phase microextraction, as well as in aqueous biphasic systems. This review provides an overview into the use of non-conventional solvents in these microextraction techniques in the past 5 years (2012-2016). Analytical applications of the techniques are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma.

    PubMed

    Troxell, Megan L; Higgins, John P

    2016-11-01

    Kidney transplant recipients are at increased risk for malignancy, with about 5% incidence of cancer in native end-stage kidneys. Carcinoma in the renal allograft is far less common. Prior studies have demonstrated a propensity for renal cell carcinomas (RCCs) of papillary subtypes in end-stage kidneys, and perhaps in allograft kidneys, but most allograft studies lack detailed pathologic review and predate the current classification system. We reviewed our experience with renal carcinoma in kidney allografts at 2 academic centers applying the International Society of Urological Pathology classification, informed by immunohistochemistry. The incidence of renal allograft carcinoma was about 0.26% in our population. Of 12 allograft carcinomas, 6 were papillary (50%), 4 were clear cell (33%), 1 was clear cell (tubulo)papillary, and 1 chromophobe. Two of the papillary carcinomas had distinctive biphasic glomeruloid architecture matching the newly named "biphasic squamoid alveolar" pattern and were difficult to classify on core biopsies. The 2 cell types had different immunophenotypes in our hands (eosinophilic cells: RCC-/CK34betaE12+ weight keratin +/cyclin D1+; clear cells: RCC+/cytokeratin high molecular weight negative to weak/cyclin D1-). None of the patients experienced cancer recurrences or metastasis. Our study confirms the predilection for papillary RCCs in kidney allografts and highlights the occurrence of rare morphologic variants. Larger studies are needed with careful pathologic review, which has been lacking in the literature.

  1. Biphasic investigation of contact mechanics in natural human hips during activities.

    PubMed

    Li, Junyan; Hua, Xijin; Jin, Zhongmin; Fisher, John; Wilcox, Ruth K

    2014-06-01

    The aim of this study was to determine the cartilage contact mechanics and the associated fluid pressurisation of the hip joint under eight daily activities, using a three-dimensional finite element hip model with biphasic cartilage layers and generic geometries. Loads with spatial and temporal variations were applied over time and the time-dependent performance of the hip cartilage during walking was also evaluated. It was found that the fluid support ratio was over 90% during the majority of the cycles for all the eight activities. A reduced fluid support ratio was observed for the time at which the contact region slid towards the interior edge of the acetabular cartilage, but these occurred when the absolute level of the peak contact stress was minimal. Over 10 cycles of gait, the peak contact stress and peak fluid pressure remained constant, but a faster process of fluid exudation was observed for the interior edge region of the acetabular cartilage. The results demonstrate the excellent function of the hip cartilage within which the solid matrix is prevented from high levels of stress during activities owing to the load shared by fluid pressurisation. The findings are important in gaining a better understanding of the hip function during daily activities, as well as the pathology of hip degeneration and potential for future interventions. They provide a basis for future subject-specific biphasic investigations of hip performance during activities.

  2. Regulation of the demographic structure in isomorphic biphasic life cycles at the spatial fine scale.

    PubMed

    Vieira, Vasco Manuel Nobre de Carvalho da Silva; Mateus, Marcos Duarte

    2014-01-01

    Isomorphic biphasic algal life cycles often occur in the environment at ploidy abundance ratios (Haploid:Diploid) different from 1. Its spatial variability occurs within populations related to intertidal height and hydrodynamic stress, possibly reflecting the niche partitioning driven by their diverging adaptation to the environment argued necessary for their prevalence (evolutionary stability). Demographic models based in matrix algebra were developed to investigate which vital rates may efficiently generate an H:D variability at a fine spatial resolution. It was also taken into account time variation and type of life strategy. Ploidy dissimilarities in fecundity rates set an H:D spatial structure miss-fitting the ploidy fitness ratio. The same happened with ploidy dissimilarities in ramet growth whenever reproductive output dominated the population demography. Only through ploidy dissimilarities in looping rates (stasis, breakage and clonal growth) did the life cycle respond to a spatially heterogeneous environment efficiently creating a niche partition. Marginal locations were more sensitive than central locations. Related results have been obtained experimentally and numerically for widely different life cycles from the plant and animal kingdoms. Spore dispersal smoothed the effects of ploidy dissimilarities in fertility and enhanced the effects of ploidy dissimilarities looping rates. Ploidy dissimilarities in spore dispersal could also create the necessary niche partition, both over the space and time dimensions, even in spatial homogeneous environments and without the need for conditional differentiation of the ramets. Fine scale spatial variability may be the key for the prevalence of isomorphic biphasic life cycles, which has been neglected so far.

  3. Influence of Biphasic Stimulation on Olfactory Ensheathing Cells for Neuroprosthetic Devices

    PubMed Central

    Hassarati, Rachelle T.; Foster, L. John R.; Green, Rylie A.

    2016-01-01

    The recent success of olfactory ensheathing cell (OEC) assisted regeneration of injured spinal cord has seen a rising interest in the use of these cells in tissue-engineered systems. Previously shown to support neural cell growth through glial scar tissue, OECs have the potential to assist neural network formation in living electrode systems to produce superior neuroprosthetic electrode surfaces. The following study sought to understand the influence of biphasic electrical stimulation (ES), inherent to bionic devices, on cell survival and function, with respect to conventional metallic and developmental conductive hydrogel (CH) coated electrodes. The CH utilized in this study was a biosynthetic hydrogel consisting of methacrylated poly(vinyl-alcohol) (PVA), heparin and gelatin through which poly(3,4-ethylenedioxythiophene) (PEDOT) was electropolymerised. OECs cultured on Pt and CH surfaces were subjected to biphasic ES. Image-based cytometry yielded little significant difference between the viability and cell cycle of OECs cultured on the stimulated and passive samples. The significantly lower voltages measured across the CH electrodes (147 ± 3 mV) compared to the Pt (317 ± 5 mV), had shown to influence a higher percentage of viable cells on CH (91–93%) compared to Pt (78–81%). To determine the functionality of these cells following electrical stimulation, OECs co-cultured with PC12 cells were found to support neural cell differentiation (an indirect measure of neurotrophic factor production) following ES. PMID:27757072

  4. Formation of a fluorous/organic biphasic supramolecular octopus assembly for enhanced porphyrin phosphorescence in air.

    PubMed

    Yang, Chi; Arvapally, Ravi K; Tekarli, Sammer M; Salazar, Gustavo A; Elbjeirami, Oussama; Wang, Xiaoping; Omary, Mohammad A

    2015-04-13

    The trinuclear triangle-shaped system [tris{3,5-bis(heptafluoropropyl)-1,2,4-triazolatosilver(I)}] (1) and the multi-armed square-shaped metalloporphyrin PtOEP or the free porphyrin base H2OEP serve as excellent octopus hosts (OEP=2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine). Coupling of the fluorous/organic molecular octopi 1 and H2OEP or PtOEP by strong quadrupole-quadrupole and metal-π interactions affords the supramolecular assemblies [1⋅PtOEP] or [1⋅H2OEP] (2 a), which feature nanoscopic cavities surrounding the upper triangular and lower square cores. The fluorous/organic biphasic configuration of [1⋅PtOEP] leads to an increase in the phosphorescence of PtOEP under ambient conditions. Guest molecules can be included in the biphasic double-octopus assembly in three different site-selective modes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. New resource for the computation of cartilage biphasic material properties with the interpolant response surface method.

    PubMed

    Keenan, Kathryn E; Kourtis, Lampros C; Besier, Thor F; Lindsey, Derek P; Gold, Garry E; Delp, Scott L; Beaupre, Gary S

    2009-08-01

    Cartilage material properties are important for understanding joint function and diseases, but can be challenging to obtain. Three biphasic material properties (aggregate modulus, Poisson's ratio and permeability) can be determined using an analytical or finite element model combined with optimisation to find the material properties values that best reproduce an experimental creep curve. The purpose of this study was to develop an easy-to-use resource to determine biphasic cartilage material properties. A Cartilage Interpolant Response Surface was generated from interpolation of finite element simulations of creep indentation tests. Creep indentation tests were performed on five sites across a tibial plateau. A least-squares residual search of the Cartilage Interpolant Response Surface resulted in a best-fit curve for each experimental condition with corresponding material properties. These sites provided a representative range of aggregate moduli (0.48-1.58 MPa), Poisson's ratio (0.00-0.05) and permeability (1.7 x 10(- 15)-5.4 x 10(- 15) m(4)/N s) values found in human cartilage. The resource is freely available from https://simtk.org/home/va-squish.

  6. A new rhenanite (beta-NaCaPO(4)) and hydroxyapatite biphasic biomaterial for skeletal repair.

    PubMed

    Jalota, Sahil; Bhaduri, Sarit B; Tas, A Cuneyt

    2007-02-01

    Biphasic beta-rhenanite (beta-NaCaPO(4))-hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2)) biomaterials were prepared by using a one-pot, solution-based synthesis procedure at the physiological pH of 7.4, followed by low-temperature (300-600 degrees C) calcination in air for 6 h. Calcination was for the sole purpose of crystallization. An aqueous solution of Ca(NO(3))(2). 4H(2)O was rapidly added to a solution of Na(2)HPO(4) and NaHCO(3), followed by immediate removal of gel-like, poorly-crystallized precursor precipitates from the mother liquors of pH 7.4. Freeze-dried precursors were found to be nanosize with an average particle size of 45 nm and a surface area of 128 m(2)/g. Upon calcination in air, precursor powders crystallized into biphasic (60% HA-40% rhenanite) biomaterials, while retaining their submicron particle sizes and high surface areas. beta-rhenanite is a high solubility sodium calcium phosphate phase. Samples were characterized by XRD, FTIR, SEM, TEM, ICP-AES, TG, DTA, DSC, and surface area measurements.

  7. Sterility testing of a total nutrient admixture with a biphasic blood-culture system.

    PubMed

    Murray, P R; Sandrock, M J

    1991-11-01

    The ability of a biphasic blood-culture system to detect microbial contamination of a total nutrient admixture (TNA) was studied. A TNA consisting of amino acids, dextrose, lipid emulsion, electrolytes, and trace elements was prepared under aseptic conditions. Septi-Chek blood-culture bottles were then injected with a TNA sample and with one of various dilutions of five bacterial or fungal suspensions, and an agar slide unit was attached to each bottle. One bottle was injected only with a TNA sample. The bottles were incubated and examined once daily. Each bottle was inverted immediately after inoculation and at each observation time to allow the broth to wash over the agar slide unit. Because the lipid contained in the TNA caused the broth in all bottles to become turbid, it was impossible to determine whether microbial growth was present in the broth. Microbial growth, however, became evident in 24-72 hours on all slide units except the one attached to the bottle that had been injected only with TNA. The Septi-Chek biphasic blood-culture system appears to be useful in evaluating the sterility of TNAs.

  8. Differential Biphasic Transcriptional Host Response Associated with Coevolution of Hemagglutinin Quasispecies of Influenza A Virus

    PubMed Central

    Manchanda, Himanshu; Seidel, Nora; Blaess, Markus F.; Claus, Ralf A.; Linde, Joerg; Slevogt, Hortense; Sauerbrei, Andreas; Guthke, Reinhard; Schmidtke, Michaela

    2016-01-01

    Severe influenza associated with strong symptoms and lung inflammation can be caused by intra-host evolution of quasispecies with aspartic acid or glycine in hemagglutinin position 222 (HA-222D/G; H1 numbering). To gain insights into the dynamics of host response to this coevolution and to identify key mechanisms contributing to copathogenesis, the lung transcriptional response of BALB/c mice infected with an A(H1N1)pdm09 isolate consisting HA-222D/G quasispecies was analyzed from days 1 to 12 post infection (p.i). At day 2 p.i. 968 differentially expressed genes (DEGs) were detected. The DEG number declined to 359 at day 4 and reached 1001 at day 7 p.i. prior to recovery. Interestingly, a biphasic expression profile was shown for the majority of these genes. Cytokine assays confirmed these results on protein level exemplarily for two key inflammatory cytokines, interferon gamma and interleukin 6. Using a reverse engineering strategy, a regulatory network was inferred to hypothetically explain the biphasic pattern for selected DEGs. Known regulatory interactions were extracted by Pathway Studio 9.0 and integrated during network inference. The hypothetic gene regulatory network revealed a positive feedback loop of Ifng, Stat1, and Tlr3 gene signaling that was triggered by the HA-G222 variant and correlated with a clinical symptom score indicating disease severity. PMID:27536272

  9. Elimination of the biphasic pharmacodynamics of 15d-PGJ2 by controlling its release from a nanoemulsion

    PubMed Central

    Abbasi, Saed; Kajimoto, Kazuaki; Harashima, Hideyoshi

    2016-01-01

    15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has a dual action of stimulating anti-inflammation and anti-proliferation when exogenously administered at high doses. However, at lower doses, it can be toxic inducing opposite actions, ie, stimulation of both inflammation and cell proliferation. This biphasic phenomenon of 15d-PGJ2 is believed to be due to its multitarget behavior. In this study, we provide a strategy for controlling such biphasic pharmacodynamics by separating its dual actions while retaining the beneficial one by using a nanoemulsion (NE). The 15d-PGJ2 was encapsulated in the NE composed of triolein/distearoyl phosphatidylcholine/Tween 80 at a high encapsulation ratio (>83%). Furthermore, NE enhanced drug retention by slowing down its release rate, which was, unconventionally, inversely dependent on the total surface area of the NE system. Next, focusing on the biphasic effect on cell proliferation, we found that the 15d-PGJ2-loaded slow-release NE showed only a dose-dependent inhibition of the viability of a mouse macrophage cell line, RAW264.7, although a fast-release NE as well as free 15d-PGJ2 exerted a biphasic effect. The observed slow-release kinetics are believed to be responsible for elimination of the biphasic pharmacodynamics of 15d-PGJ2 mainly for two reasons: 1) a high proportion of 15d-PGJ2 that is retained in the NE was delivered to the cytosol, where proapoptotic targets are located and 2) 15d-PGJ2 was able to bypass cell membrane-associated targets that lead to the induction of cellular proliferation. Collectively, our strategy of eliminating the 15d-PGJ2-induced biphasic pharmacodynamics was based on the delivery of 15d-PGJ2 to its desired site of action, excluding undesired sites, on a subcellular level. PMID:27354798

  10. Two novel MYH7 proline substitutions cause Laing Distal Myopathy-like phenotypes with variable expressivity and neck extensor contracture.

    PubMed

    Feinstein-Linial, Miora; Buvoli, Massimo; Buvoli, Ada; Sadeh, Menachem; Dabby, Ron; Straussberg, Rachel; Shelef, Ilan; Dayan, Daniel; Leinwand, Leslie Anne; Birk, Ohad S

    2016-08-12

    Human skeletal muscles express three major myosin heavy chain (MyHC) isoforms: MyHCIIx (MYH1) in fast type 2B muscle fibers, MyHCIIa (MYH2) in fast type 2A fibers and MyHCI/β-cardiac MyHC (MYH7) in slow type I skeletal fibers and cardiac ventricles. In line with its expression pattern, MYH7 mutations have been reported in association with hypertrophic or dilated cardiomyopathy, skeletal myopathies or a combination of both. We analyzed the clinical and molecular phenotype of two unrelated families of Jewish Moroccan ancestry that presented with apparently autosomal dominant inheritance of progressive Laing-like distal myopathy with non-specific myopathic changes, but uncommon marked contractures and wasting of the neck extensors. Clinical phenotyping, whole exome sequencing and restriction analysis, generation of mutants followed by cell culture transfection and imaging. Using whole exome sequencing we identified in both families two novel heterozygous proline substitutions located in exon 31 of MYH7 within its rod domain: c.4309G>C (p.Ala1437Pro) and c.4301G>C (p.Arg1434Pro). Here we show that the phenotype caused by these mutations includes marked cervical muscle contracture, and report that the severity of the phenotype varies significantly, to the extent of non-penetrance in one of the families. Finally, we provide evidence that both proline substitutions impair myosin self-assembly in non-muscle cells transfected with β-myosin constructs carrying the mutations, but do not prevent incorporation of the mutant molecules into the sarcomere. This study expands our clinical and molecular knowledge of MYH7 rod mutations causing skeletal myopathies, and underscores the importance of discussing disease penetrance during genetic counseling.

  11. Optical resolution of racemic 2-hydroxy octanoic acid by lipase-catalyzed hydrolysis in a biphasic membrane reactor.

    PubMed

    Sakaki, Keiji; Itoh, Naotsugu

    2003-10-01

    Racemic 2-hydroxy octanoic acid methyl ester was optically resolved by lipase-catalyzed hydrolysis in a biphasic membrane reactor using hydrophilic/hydrophobic capillary membranes. In a buffer/hexane biphasic membrane reactor using hydrophilic ultrafiltration membranes, (S)-2-hydroxy octanoic acid was recovered from the aqueous phase at 59-67% yield and 0.9-0.92 enantiomeric excess (ee), and the ester of (R)-isomer was recovered from the organic phase at 73-75% yield and 0.92-0.99 ee.

  12. A penetration-based finite element method for hyperelastic 3D biphasic tissues in contact: Part 1--Derivation of contact boundary conditions.

    PubMed

    Un, Kerem; Spilker, Robert L

    2006-02-01

    In this study, we extend the penetration method, previously introduced to simulate contact of linear hydrated tissues in an efficient manner with the finite element method, to problems of nonlinear biphasic tissues in contact. This paper presents the derivation of contact boundary conditions for a biphasic tissue with hyperelastic solid phase using experimental kinematics data. Validation of the method for calculating these boundary conditions is demonstrated using a canonical biphasic contact problem. The method is then demonstrated on a shoulder joint model with contacting humerus and glenoid tissues. In both the canonical and shoulder examples, the resulting boundary conditions are found to satisfy the kinetic continuity requirements of biphasic contact. These boundary conditions represent input to a three-dimensional nonlinear biphasic finite element analysis; details of that finite element analysis will be presented in a manuscript to follow.

  13. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype.

  14. Ru-Catalyzed Estragole Isomerization under Homogeneous and Ionic Liquid Biphasic Conditions

    PubMed Central

    2017-01-01

    The isomerization of estragole to trans-anethole is an important reaction and is industrially performed using an excess of NaOH or KOH in ethanol at high temperatures with very low selectivity. Simple Ru-based transition-metal complexes, under homogeneous, ionic liquid (IL)-supported (biphasic) and “solventless” conditions, can be used for this reaction. The selectivity of this reaction is more sensitive to the solvent/support used than the ligands associated with the metal catalyst. Thus, under the optimized reaction conditions, 100% conversion can be achieved in the estragole isomerization, using as little as 4 × 10–3 mol % (40 ppm) of [RuHCl(CO)(PPh3)3] in toluene, reflecting a total turnover number (TON) of 25 000 and turnover frequencies (TOFs) of up to 500 min–1 at 80 °C. Using a dimeric Ru precursor, [RuCl(μ-Cl)(η3:η3-C10H16)]2, in ethanol associated with P(OEt)3, a TON of 10 000 and a TOF of 125 min–1 are obtained with 100% conversion and 99% selectivity. These two Ru catalytic systems can be transposed to biphasic IL systems by using ionic-tagged P-ligands such as 1-(3-(diphenylphosphanyl)propyl)-2,3-dimethylimidazolium bis(trifluoromethanesulfonyl)imide immobilized in 1-(3-hydroxypropyl)-2,3-dimethylimidazolium bis(trifluoromethanesulfonyl) imide with up to 99% selectivity and almost complete estragole conversion. However, the reaction is much slower than that performed under solventless or homogeneous conditions. The use of ionic-tagged ligands significantly reduces the Ru leaching to the organic phase, compared to that in reactions performed under homogeneous conditions, where the catalytic system loses catalytic performance after the second recycling. Detailed kinetic investigations of the reaction catalyzed by [RuHCl(CO)(PPh3)3] indicate that a simplified kinetic model (a monomolecular reversible first-order reaction) is adequate for fitting the homogeneous reaction at 80 °C and under biphasic conditions. However, the kinetics of

  15. Bi-phasic titanium dioxide nanoparticles doped with nitrogen and neodymium for enhanced photocatalysis

    NASA Astrophysics Data System (ADS)

    Gomez, Virginia; Bear, Joseph C.; McNaughter, Paul D.; McGettrick, James D.; Watson, Trystan; Charbonneau, Cecile; O'Brien, Paul; Barron, Andrew R.; Dunnill, Charles W.

    2015-10-01

    Bi-phasic or multi-phasic composite nanoparticles for use in photocatalysis have been produced by a new synthetic approach. Sol-gel methods are used to deposit multiple layers of active material onto soluble substrates. In this work, a layer of rutile (TiO2) was deposited onto sodium chloride pellets followed by an annealing step and a layer of anatase. After dissolving the substrate, bi-phasic nanoparticles containing half anatase and half rutile TiO2; with ``Janus-like'' characteristics are obtained. Nitrogen and neodymium doping of the materials were observed to enhance the photocatalytic properties both under UV and white light irradiation. The unique advantage of this synthetic method is the ability to systematically dope separate sides of the nanoparticles. Nitrogen doping was found to be most effective on the anatase side of the nanoparticle while neodymium was found to be most effective on the rutile side. Rhodamine B dye was effectively photodegraded by co-doped particles under white light.Bi-phasic or multi-phasic composite nanoparticles for use in photocatalysis have been produced by a new synthetic approach. Sol-gel methods are used to deposit multiple layers of active material onto soluble substrates. In this work, a layer of rutile (TiO2) was deposited onto sodium chloride pellets followed by an annealing step and a layer of anatase. After dissolving the substrate, bi-phasic nanoparticles containing half anatase and half rutile TiO2; with ``Janus-like'' characteristics are obtained. Nitrogen and neodymium doping of the materials were observed to enhance the photocatalytic properties both under UV and white light irradiation. The unique advantage of this synthetic method is the ability to systematically dope separate sides of the nanoparticles. Nitrogen doping was found to be most effective on the anatase side of the nanoparticle while neodymium was found to be most effective on the rutile side. Rhodamine B dye was effectively photodegraded by co

  16. Pathophysiology of protein aggregation and extended phenotyping in filaminopathy

    PubMed Central

    Serdaroglu-Oflazer, Piraye; Leber, Yvonne; Odgerel, Zagaa; van der Ven, Peter F. M.; Olivé, Montse; Ferrer, Isidro; Onipe, Adekunle; Mihaylov, Mariya; Bilbao, Juan M.; Lee, Hee S.; Höhfeld, Jörg; Djinović-Carugo, Kristina; Kong, Kester; Tegenthoff, Martin; Peters, Sören A.; Stenzel, Werner; Vorgerd, Matthias; Goldfarb, Lev G.; Fürst, Dieter O.

    2012-01-01

    Mutations in FLNC cause two distinct types of myopathy. Disease associated with mutations in filamin C rod domain leading to expression of a toxic protein presents with progressive proximal muscle weakness and shows focal destructive lesions of polymorphous aggregates containing desmin, myotilin and other proteins in the affected myofibres; these features correspond to the profile of myofibrillar myopathy. The second variant associated with mutations in the actin-binding domain of filamin C is characterized by weakness of distal muscles and morphologically by non-specific myopathic features. A frameshift mutation in the filamin C rod domain causing haploinsufficiency was also found responsible for distal myopathy with some myofibrillar changes but no protein aggregation typical of myofibrillar myopathies. Controversial data accumulating in the literature require re-evaluation and comparative analysis of phenotypes associated with the position of the FLNC mutation and investigation of the underlying disease mechanisms. This is relevant and necessary for the refinement of diagnostic criteria and developing therapeutic approaches. We identified a p.W2710X mutation in families originating from ethnically diverse populations and re-evaluated a family with a p.V930_T933del mutation. Analysis of the expanded database allows us to refine clinical and myopathological characteristics of myofibrillar myopathy caused by mutations in the rod domain of filamin C. Biophysical and biochemical studies indicate that certain pathogenic mutations in FLNC cause protein misfolding, which triggers aggregation of the mutant filamin C protein and subsequently involves several other proteins. Immunofluorescence analyses using markers for the ubiquitin–proteasome system and autophagy reveal that the affected muscle fibres react to protein aggregate formation with a highly increased expression of chaperones and proteins involved in proteasomal protein degradation and autophagy. However

  17. (R)-PAC biosynthesis in [BMIM][PF₆]/aqueous biphasic system using Saccharomyces cerevisiae BY4741 cells.

    PubMed

    Kandar, Smita; Suresh, A K; Noronha, Santosh B

    2015-02-01

    (R)-phenylacetylcarbinol or (R)-PAC is a pharmaceutical precursor of (1R, 2S) ephedrine and (1S, 2S) pseudoephedrine. Biotransformation of benzaldehyde and glucose by pyruvate decarboxylase produces (R)-PAC. This biotransformation suffers from toxicity of the substrate, product [(R)-PAC] and by-product (benzyl alcohol). In the present study, ionic liquid/aqueous biphasic system was employed to enhance (R)-PAC production. Fermented broth was the reaction medium in which Saccharomyces cerevisiae BY4741 was the source of pyruvate decarboxylase. Hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) was the non-aqueous phase in which toxic compounds reside. Biocompatibility of [BMIM][PF6] and adequate distribution coefficients of benzaldehyde, (R)-PAC and benzyl alcohol were determined. A Box-Behnken design and response surface methodology were used for the optimization of biotransformation variables in order to maximize (R)-PAC yield and productivity. The results showed higher (R)-PAC yield and productivity of ∼1.5-fold each in the biphasic biotransformation of phase volume ratio 0.05 as compared to the monophasic (conventional) biotransformation. Moreover, the level of major by-product benzyl alcohol was also 3.5-fold lower in biphasic biotransformation. [BMIM][PF6]/aqueous biphasic system is a new approach which could intensify the (R)-PAC production.

  18. INVESTIGATION OF AQUEOUS BIPHASIC SYSTEMS FOR THE SEPARATIONS OF LIGNINS FROM CELLULOSE IN THE PAPER PULPING PROCESS. (R826732)

    EPA Science Inventory

    In efforts to apply a polymer-based aqueous biphasic system (ABS) extraction to the paper pulping process, the study of the distribution of various lignin and cellulosic fractions in ABS and the effects of temperature on system composition and solute partitioning have been inv...

  19. Multifunctional catalysts based on carbon nanotubes and titanate nanotubes for oxidation of organic compounds in biphasic systems.

    PubMed

    Santos, S R A; Jardim, I S; Bicalho, H A; Binatti, I; Sousa, E M B; Peres, A M; Resende, R R; Lorençon, E

    2016-12-01

    Amphiphilic catalysts composed of carbon nanotubes (CNTs) and titanate nanotubes (TiNTs) have been successfully synthesized by refluxing anatase TiO2 and functionalised CNTs in concentrated NaOH solution. The prepared materials were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis (TGA), and N2 physisorption isotherms. The catalytic activity of the synthesized composites was first evaluated in the oxidation of methyl yellow (MY) using H2O2 as oxidant in a single liquid phase system and in a biphasic water/oil mixture. The results of these experiments indicated that the catalytic activities of nanocomposites were very similar in the single liquid-phase oxidation. However, the modification of TiNTs with CNTs led to a substantially enhanced MY oxidation in the biphasic system. The nanocomposites show excellent interaction with both hydrophilic and hydrophobic compounds and thus stabilise emulsions. Under biphasic conditions, the catalysts can be easily separated and recycled, retaining catalytic activity even after eight runs. Additionally, the hybrid materials show superior catalytic activity and selectivity in the biphasic oxidation of benzyl alcohol with H2O2, as compared to pure TiNTs.

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

    PubMed

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

    2016-05-18

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 ± 2.1 mm(3)) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.

  1. INVESTIGATION OF AQUEOUS BIPHASIC SYSTEMS FOR THE SEPARATIONS OF LIGNINS FROM CELLULOSE IN THE PAPER PULPING PROCESS. (R826732)

    EPA Science Inventory

    In efforts to apply a polymer-based aqueous biphasic system (ABS) extraction to the paper pulping process, the study of the distribution of various lignin and cellulosic fractions in ABS and the effects of temperature on system composition and solute partitioning have been inv...

  2. Biphasic gene expression changes elicited by Phakopsora pachyrhizi in soybean correlates with fungal penetration and haustoria formation

    USDA-ARS?s Scientific Manuscript database

    Inoculation of soybean plants with Phakopsora pachyrhizi, the causal organism of Asian soybean rust, elicits a biphasic response characterized by a burst of differential gene expression in the first 12 h. A quiescent period occurs from 24 to 48 h after inoculation in which P. pachyrhizi continues t...

  3. Comparison of three novel biphasic scaffolds for one-stage treatment of osteochondral defects in a sheep model.

    PubMed

    Gervaso, F; Mangiavini, L; Di Giancamillo, A; Boschetti, F; Izzo, D; Zani, D D; Di Giancamillo, M; Tessaro, I; Domenicucci, M; Scalera, F; Domeneghini, C; Crovace, A M; Sannino, A; Peretti, G M

    2016-01-01

    In the last years, several tissue engineering techniques have been applied to develop different kinds of osteochondral substitutes to overcome the scarce reparative properties of this tissue. The aim of this study was to generate and compare three biphasic scaffolds in an osteochondral lesion in a large-animal model. A critical osteochondral defect was generated in the medial femoral condyle of 18 skeletally mature sheep. Three defects were left untreated, the remaining lesions were divided into three groups: 5 lesions were treated with a biphasic scaffold made of collagen type I and small cylinders of Magnesium Hydroxyapatite; 5 lesions were treated with a biphasic substituted formed by collagen type I and Wollastonite, 5 lesions were treated with a scaffold made of collagen type I and small cylinders of Wollastonite/Hydroxyapatite. Animals were sacrificed after 3 months and samples were analyzed by CT and MRI, macroscopic evaluation and histology. Our study demonstrated that one of these novel biphasic scaffolds possesses the potential for being applied for one-stage procedures for osteochondral defects.

  4. Facile synthesis and photocatalytic activity of bi-phase dispersible Cu-ZnO hybrid nanoparticles.

    PubMed

    Liu, Xiao; Liu, HongLing; Zhang, WenXing; Li, XueMei; Fang, Ning; Wang, XianHong; Wu, JunHua

    2015-01-01

    Bi-phase dispersible Cu-ZnO hybrid nanoparticles were synthesized by one-pot non-aqueous nanoemulsion with the use of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-PPO-PEO) as the surfactant. The transmission electron microscopy (TEM) and X-ray diffraction (XRD) show high crystallinity of the Cu-ZnO hybrid nanoparticles and an average particle size of ~19.4 nm. The ultraviolet-visible light absorbance spectrometry (UV-vis) and photoluminescence spectrophotometry (PL) demonstrate well dispersibility and excellent optical performance of Cu-ZnO hybrid nanoparticles both in organic and aqueous solvent. The X-ray photoelectron spectroscopy (XPS) confirms Cu(1+) and Cu(2+) in ZnO. The observation using Sudan red (III) as probe molecule reveals that the Cu-ZnO hybrid nanoparticles possess enhanced photocatalytic activity and stability which are promising for potential applications in photocatalysis.

  5. Aqueous biphasic systems for metal separations : a microcalorimetric analysis of polymer/salt interactions.

    SciTech Connect

    Chaiko, D. J.; Hatton, T. A.; Zaslavsky, B.

    1999-05-03

    Certain radionuclide ions (e.g., TcO{sub 4}{sup 16}) exhibit unusually strong Affinities toward the polymer-rich phase in aqueous biphase systems generated by combinations of salt solutions with polymers such as poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG). Thus, aqueous polymer phases could potentially be used to selectively extract these ions during pretreatment of radioactive tank wastes at Hanford. To help develop a fundamental understanding of the interactions between various ions and polymers in aqueous solution, interaction enthalpies between sodium perrhenate and a random copolymer of PEG and PPG (UCON-50) were measured by microcalorimetric titration. An entropy compensation effect was observed in this system in which changes in enthalpic interactions were balanced by entropy changes such that the interaction free energy remained constant and approximately equal to zero.

  6. Research on the Influence of Technological Forging Parameters on the Quality of Biphasic Titanium Alloys

    NASA Astrophysics Data System (ADS)

    Mashekov, S. A.; Smaylova, N. T.; Alshynova, A. M.; Mashekova, A. S.

    2015-12-01

    The deflected mode (DM) during the preparation of the broach in the flat and combined baizes and also on radial forging machine (RFM) was investigated for creating the rational technology of a broach and determining the optimum size of the angles of rotation and single squeeze reduction. The quantitative data was obtained by the method of final elements and the MSC.Super Forge program; the main consistent patterns of stress-strain state (SSS) distribution and temperature while modeling forging in flat and combined baizes, also on RFM with various angles of rotation and sizes of squeeze reduction were determined. The rational trial technology of forging of biphasic titanium alloys was developed and tested.

  7. Effect of nanostructure on osteoinduction of porous biphasic calcium phosphate ceramics.

    PubMed

    Li, Bo; Liao, Xiaoling; Zheng, Li; Zhu, Xiangdong; Wang, Zhe; Fan, Hongsong; Zhang, Xingdong

    2012-10-01

    In order to evaluate the effect of the nanostructure of calcium phosphate ceramics on osteoinductive potential, porous biphasic calcium phosphate (BCP) ceramics with a nano- or submicron structure were prepared via microwave sintering and compared to conventional BCP ceramics. The selective protein adsorption of bovine serum albumin and lysozyme (LSZ) and the osteogenic differentiation of human mesenchymal stem cells in vitro was investigated. Porous BCP nanoceramics showed higher ability to adsorb proteins, especially low molecular weight protein of LSZ, than conventional BCP ceramics, and the BCP nanoceramics promoted bone sialoprotein expression more than conventional BCP did. Further in vivo study to investigate ectopic bone formation and bone repair efficiency proved the highly osteoinductive potential of nanostructured BCP ceramics. The results suggest that nanostructured BCP ceramics have the potential to become a new generation of bioceramics for bone tissue engineering grafts. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Interaction between hydroxypropyl methylcellulose and biphasic calcium phosphate after steam sterilisation: capillary gas chromatography studies

    PubMed Central

    Bourges, Xavier; Schmitt, Michel; Amouriq, Yves; Daculsi, Guy; Legeay, Gilbert; Weiss, Pierre

    2001-01-01

    The purpose of this study was to check the chemical stability of an injectable bone substitute (IBS) composed of a 50/50 w/w mixture of a 2.92% hydroxypropyl methylcellulose (HPMC) solution in deionised water containing biphasic calcium phosphate (BCP) granules (60% hydroxyapatite/40% β-tricalcium phosphate w/w). After separation of the organic and mineral phases, capillary gas chromatography (GC) was used to study the possible modification of HPMC due to the contact with BCP granules following steam sterilisation and 32 days of storage at room temperature. HPMC was extracted from IBS in aqueous medium, and a dialytic method was then use to extract calcium phosphate salts from HPMC. The percentage of HPMC extracted from BCP was 98.5% ± 0.5% as measured by a UV method. GC showed no chemical modifications after steam sterilisation and storage. PMID:11556737

  9. Biphasic Superoxide Generation in Potato Tubers. A Self-Amplifying Response to Stress1

    PubMed Central

    Johnson, S.M.; Doherty, S.J.; Croy, R.R.D.

    2003-01-01

    Potato (Solanum tuberosum) cultivars differ quantitatively in their responses to mechanical stress including the ability to synthesize melanin pigments in tuber tissues. Investigations into the cellular events induced by mechanical stress on tuber tissues have shown that an early cellular response is a significant and rapid synthesis of superoxide radicals. This burst of radical production distinctively displays a reproducible biphasic pattern over time with peaks of generation at 2 and 5 h. A concomitant consequence of the generation of these free radicals is elevated levels of oxidatively modified tuber proteins. Both radical generation and protein modification vary between cultivars but both are directly proportional to the amount of melanin pigments produced. Cell-free extracts of mechanically stressed tissues, pectic fragments, and scission products generated from cell walls are able to induce superoxide generation in non-stressed tissues, indicating the participation of a biologically active factor that induces a further a phase of radical synthesis. PMID:12644693

  10. Association, partition, and surface activity in biphasic systems displaying relaxation oscillations.

    PubMed

    Pradines, Vincent; Tadmouri, Rawad; Lavabre, Dominique; Micheau, Jean-Claude; Pimienta, Véronique

    2007-11-06

    Several biphasic systems giving rise to periodical Marangoni instability have been analyzed from the point of view of the physicochemical properties of the involved compounds. In each case, the compound at the origin of the oscillatory behavior has been identified: the reactant cetyltrimethylammonium bromide (CTAB) for the CTAB/picric acid (PH) system and the product of reaction dodecyl sulfate tetraalkylammonium (TAADS) for the sodium dodecyl sulfate/tetraalkylammonium bromide (SDS/TAAB) system. The properties of the latter system have been varied progressively by increasing the chain length of the tetraalkylammonium ion. Oscillations were observed whichever the direction of transfer (from water to dichloromethane and from dichloromethane to water). The comparison of the dynamic interfacial tension, recorded during transfer, to equilibrium measurements shows that the instability is favored when partition is highly in favor of the organic phase. The main criteria for the appearance of the instability are a high surface activity and a low interfacial adsorption.

  11. Light controlled reversible inversion of nanophosphor-stabilized Pickering emulsions for biphasic enantioselective biocatalysis.

    PubMed

    Chen, Zhaowei; Zhou, Li; Bing, Wei; Zhang, Zhijun; Li, Zhenhua; Ren, Jinsong; Qu, Xiaogang

    2014-05-21

    In this work, by utilizing photochromic spiropyrans conjugated upconversion nanophosphors, we have successfully prepared NIR/visible light tuned interfacially active nanoparticles for the formulation of Pickering emulsions with reversible inversion properties. By loading a model enantioselective biocatalytic active bacteria Alcaligenes faecalis ATCC 8750 in the aqueous phase, we demonstrated for the first time that the multifunctional Pickering emulsion not only highly enhanced its catalytic performance but also relieved the substrate inhibition effect. In addition, product recovery, and biocatalysts and colloid emulsifiers recycling could be easily realized based on the inversion ability of the Pickering emulsion. Most importantly, the utilization of NIR/visible light to perform the reversible inversion without any chemical auxiliaries or temperature variation showed little damage toward the biocatalysts, which was highlighted by the high catalytic efficiency and high enantioselectivity even after 10 cycles. The NIR/visible light controlled Pickering emulsion showed promising potential as a powerful technique for biocatalysis in biphasic systems.

  12. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process

    NASA Astrophysics Data System (ADS)

    Li, Chen; Wang, Zhuan-Hua; Yu, Deng-Guang; Williams, Gareth R.

    2014-05-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned.

  13. Injectable Hydrogel Composite Based Gelatin-PEG and Biphasic Calcium Phosphate Nanoparticles for Bone Regeneration

    NASA Astrophysics Data System (ADS)

    Van, Thuy Duong; Tran, Ngoc Quyen; Nguyen, Dai Hai; Nguyen, Cuu Khoa; Tran, Dai Lam; Nguyen, Phuong Thi

    2016-05-01

    Gelatin hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility. In this study, we introduce poly-ethylene glycol (PEG)—grafted gelatin containing tyramine moieties which have been utilized for in situ enzyme-mediated hydrogel preparation. The hydrogel can be used to load nanoparticles of biphasic calcium phosphate, a mixture of hydroxyapatite and β-tricalcium phosphate, and forming injectable bio-composites. Proton nuclear magnetic resonance (1H NMR) spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the gelatin. The hydrogel composite was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with bio-mineralization on the hydrogel composite surfaces was well-observed after 2 weeks soaking in simulated body fluid solution. The obtained results indicated that the hydrogel composite could be a potential injectable material for bone regeneration.

  14. Biphasic Palladium-Catalyzed Hydroesterification in a Polyol Phase: Selective Synthesis of Derived Monoesters.

    PubMed

    Pruvost, Romain; Boulanger, Jérôme; Léger, Bastien; Ponchel, Anne; Monflier, Eric; Ibert, Mathias; Mortreux, André; Sauthier, Mathieu

    2015-06-22

    The palladium-catalyzed hydroesterification reaction was performed with polyols and olefins in a liquid/liquid biphasic system composed of unreacted polyol on the one hand and apolar reaction products/organic solvents on the other hand. The palladium-based catalyst was immobilized in the polyol phase thanks to the use of cationic triarylphosphines possessing pendent protonated amino groups in the acidic reaction medium or to the sulfonated phosphine TPPTS (trisodium triphenylphosphine-3,3',3''-trisulfonate). Owing to the insolubility of the products in the catalytic phase, this approach allowed the synthesis of monoesters of polyols with high selectivities as well as the easy separation of the catalyst through simple decantation.

  15. Facile synthesis and photocatalytic activity of bi-phase dispersible Cu-ZnO hybrid nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Xiao; Liu, HongLing; Zhang, WenXing; Li, XueMei; Fang, Ning; Wang, XianHong; Wu, JunHua

    2015-04-01

    Bi-phase dispersible Cu-ZnO hybrid nanoparticles were synthesized by one-pot non-aqueous nanoemulsion with the use of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-PPO-PEO) as the surfactant. The transmission electron microscopy (TEM) and X-ray diffraction (XRD) show high crystallinity of the Cu-ZnO hybrid nanoparticles and an average particle size of ~19.4 nm. The ultraviolet-visible light absorbance spectrometry (UV-vis) and photoluminescence spectrophotometry (PL) demonstrate well dispersibility and excellent optical performance of Cu-ZnO hybrid nanoparticles both in organic and aqueous solvent. The X-ray photoelectron spectroscopy (XPS) confirms Cu1+ and Cu2+ in ZnO. The observation using Sudan red (III) as probe molecule reveals that the Cu-ZnO hybrid nanoparticles possess enhanced photocatalytic activity and stability which are promising for potential applications in photocatalysis.

  16. Two distinct enzymes contribute to biphasic S6 phosphorylation in serum-stimulated chicken embryo fibroblasts.

    PubMed Central

    Sweet, L J; Alcorta, D A; Erikson, R L

    1990-01-01

    Serum stimulation of quiescent chicken embryo fibroblasts resulted in a time-dependent, biphasic activation of S6 kinase activity. Chromatographic fractionation of serum-stimulated cell lysates resolved two distinct S6 kinase activities. Anti-Xenopus S6 kinase II antiserum immunoprecipitated a 90,000-Mr S6 kinase but did not cross-react with a smaller, 65,000-Mr S6 kinase. Phosphopeptide analysis confirmed that the 90,000- and 65,000-Mr proteins were structurally unrelated and established that the 65,000-Mr protein isolated by the current protocol was the same serum-stimulated chicken embryo fibroblast S6 kinase as that previously characterized (J. Blenis, C. J. Kuo, and R. L. Erikson, J. Biol. Chem. 262:14373-14376, 1987). These results demonstrate the contribution of two distinct S6 kinases to total serum-stimulated ribosomal protein S6 phosphorylation. Images PMID:2342462

  17. [Biphasic response of the human nervous system to geomagnetic storms studied by EEG].

    PubMed

    Belov, D P; Getmanenko, O V; Kiselev, B V

    2001-03-01

    In two subjects: a male phlegmatic, 56, and a female melancholic, 22, the EEG was recorded at resting. The EEG patterns were juxtaposed with the geomagnetic activity index Ar and the solar activity index SF, as well as between themselves. The results revealed qualitatively similar biphasic responses: a generalised diminishing of the EEG spatial synchronisation and, on the next day, a generalised augmentation of the phenomenon, as compared with a prolonged quiet period. A general unspecific stress response is supposed to underlie the aforementioned dynamics, whereas a reduced cortical tone during a magnetic storm and an enhanced one after its cessation correspond to the two phases observed. Specifics of responses in both subjects corresponded to their individual profiles of interhemisphere asymmetry.

  18. Perfluorinated quaternary ammonium salts of polyoxometalate anions: Fluorous biphasic oxidation catalysis with and without fluorous solvents

    SciTech Connect

    Maayan, Galia; Fish, Richard H.; Neumann, Ronny

    2003-05-28

    Perfluorinated quaternary ammonium cations, [CF{sub 3}(CF{sub 2}){sub 7}(CH{sub 2}){sub 3}]{sub 3}CH{sub 3}N{sup +} (RFN{sup +}), were synthesized and used as counter cations for the [WZnM{sub 2}(H{sub 2}O){sub 2}(ZnW{sub 9}O{sub 34}){sub 2}]{sup 12-} (M = Mn(II), Zn(II)), polyoxometalate. The (RFN{sup +}){sub 12}[WZnM{sub 2}(H{sub 2}O){sub 2}(ZnW9O{sub 34}){sub 2}] compounds were fluorous biphasic catalysts for alcohol and alkenol oxidation, and alkene epoxidation with aqueous hydrogen peroxide. Reaction protocols with or without a fluorous solvent were tested. The catalytic activity and selectivity was affected both by the hydrophobicity of the solvent and the substrate.

  19. Characterization of a biphasic neoplasm in a Madagascar tree boa (Sanzinia madagascariensis).

    PubMed

    Bera, M M; Veeramachaneni, D N R; Pandher, K

    2008-03-01

    We describe a disseminated biphasic neoplasm in a young Madagascar tree boa utilizing transmission electron and light microscopy. Discrete neoplastic cells identified within pulmonary capillaries and hepatic sinusoids represented the leukemic phase. Spindloid cells represented the sarcomatous phase, which comprised hepatic and fat body nodules. A zone of transition of the neoplastic cells, from discrete to spindloid, was noted along the periphery of the hepatic and fat body nodules. Ultrastructural examination elucidated similar nuclear features in the discrete and spindloid neoplastic cells and revealed collagen fibers within the spindloid neoplastic cells. These ultrastructural findings indicate that the discrete and spindloid cells represent a single neoplastic process with a subpopulation of cells exhibiting mesenchymal differentiation.

  20. Experimental study on bi-phase flow Air-Oil in Water Emulsion

    NASA Astrophysics Data System (ADS)

    Arnone, Davide; Poesio, Pietro

    2015-11-01

    Bi-phase slug flow oil-in-water emulsion [5%-20%] and air through a horizontal pipe (inner diameter 22mm) is experimentally studied. A test with water and air has been performed as comparison. First we create and analyze the flow pattern map to identify slug flow liquid and air inlet conditions. Flow maps are similar for all the used liquid. A video analysis procedure using an high speed camera has been created to obtain all the characteristics of unit slugs: slug velocity, slug length, bubble velocity, bubbles length and slug frequency. We compare translational velocity and frequency with models finding a good agreement. We calculate the pdfs of the lengths to find the correlations between mean values and STD on different air and liquid superficial velocities. We also perform pressure measurements along the pipe. We conclude that the percentage of oil-in- water has no influence on results in terms of velocity, lengths, frequency and pressure drop.

  1. Microwave assisted synthesis & properties of nano HA-TCP biphasic calcium phosphate

    NASA Astrophysics Data System (ADS)

    Ghomash Pasand, E.; Nemati, A.; Solati-Hashjin, M.; Arzani, K.; Farzadi, A.

    2012-05-01

    Biphasic calcium phosphate (BCP) nanopowders were synthesized by using microwave and non-microwave irradiation assisted processes. The synthesized powders were pressed under a pressure of 90 MPa, and then were sintered at 1000-1200°C for 1 h. The mechanical properties of the samples were investigated. The formed phases and microstructures were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results showed that the synthesis time was shorter, along with a more homogeneous microstructure, when the microwave irradiation assisted method was applied. The compression strength and the Young's modulus of the samples synthesized with microwave irradiation were about 60 MPa and 3 GPa, but those of the samples synthesized without microwave irradiation were about 30 MPa and 2 GPa, respectively. XRD patterns of the microwave irradiation assisted and non-microwave irradiation assisted nanopowders showed the coexistence of hydroxyapatite (HA) and tricalcium phosphate (TCP) phases in the system.

  2. Selection of xenobiotic-degrading microorganisms in a biphasic aqueous-organic system

    SciTech Connect

    Ascon-Cabrera, M.; Lebeault, J.M. )

    1993-06-01

    The selection of microorganisms able to grow on xenobiotic compounds is the first problem to solve in the biodegradation process. While many genera of microorganisms which use xenobiotic compounds as growth substrates have been isolated, attempts to isolate strains in the presence of a specific xenobiotic are no always sucessful. This paper describes the performance of a biphasic water-silicone oil system for selection of microorganisms in the presence of two industrial mixtures: (1) 1,2-dichlorobenzene and 1,2,3- and 1,2,4-trichlorobenzenes and (2) ethyl butyrate, 2-ethylbutyraldehyde, butyraldehyde, ethyl acetate, and ethanol. Factors responsible for improvement of xenobiotic compound degradation in this system and possible applications in biodegradation processes are discussed. 33 refs., 6 figs., 3 tabs.

  3. Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II

    PubMed Central

    Fang, Xiaodong; Luo, Jianying; Nishihama, Ryuichi; Wloka, Carsten; Dravis, Christopher; Travaglia, Mirko; Iwase, Masayuki; Vallen, Elizabeth A.

    2010-01-01

    Cytokinesis in animal and fungal cells utilizes a contractile actomyosin ring (AMR). However, how myosin II is targeted to the division site and promotes AMR assembly, and how the AMR coordinates with membrane trafficking during cytokinesis, remains poorly understood. Here we show that Myo1 is a two-headed myosin II in Saccharomyces cerevisiae, and that Myo1 localizes to the division site via two distinct targeting signals in its tail that act sequentially during the cell cycle. Before cytokinesis, Myo1 localization depends on the septin-binding protein Bni5. During cytokinesis, Myo1 localization depends on the IQGAP Iqg1. We also show that the Myo1 tail is sufficient for promoting the assembly of a “headless” AMR, which guides membrane deposition and extracellular matrix remodeling at the division site. Our study establishes a biphasic targeting mechanism for myosin II and highlights an underappreciated role of the AMR in cytokinesis beyond force generation. PMID:21173112

  4. A new biphasic osteoinductive calcium composite material with a negative Zeta potential for bone augmentation

    PubMed Central

    Smeets, Ralf; Kolk, Andreas; Gerressen, Marcus; Driemel, Oliver; Maciejewski, Oliver; Hermanns-Sachweh, Benita; Riediger, Dieter; Stein, Jamal M

    2009-01-01

    The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants. PMID:19523239

  5. Pickering interfacial catalysis for biphasic systems: from emulsion design to green reactions.

    PubMed

    Pera-Titus, Marc; Leclercq, Loïc; Clacens, Jean-Marc; De Campo, Floryan; Nardello-Rataj, Véronique

    2015-02-09

    Pickering emulsions are surfactant-free dispersions of two immiscible fluids that are kinetically stabilized by colloidal particles. For ecological reasons, these systems have undergone a resurgence of interest to mitigate the use of synthetic surfactants and solvents. Moreover, the use of colloidal particles as stabilizers provides emulsions with original properties compared to surfactant-stabilized emulsions, microemulsions, and micellar systems. Despite these specific advantages, the application of Pickering emulsions to catalysis has been rarely explored. This Minireview describes very recent examples of hybrid and composite amphiphilic materials for the design of interfacial catalysts in Pickering emulsions with special emphasis on their assets and challenges for industrially relevant biphasic reactions in fine chemistry, biofuel upgrading, and depollution.

  6. Biomechanical behaviour of a jawbone loaded with a prosthetic system supported by monophasic and biphasic implants

    PubMed Central

    INCHINGOLO, F.; PARACCHINI, L.; DE ANGELIS, F.; CIELO, A.; OREFICI, A.; SPITALERI, D.; SANTACROCE, L.; GHENO, E.; PALERMO, A.

    2016-01-01

    SUMMARY Modern implantology is based on the use of endosseous dental implants and on the study of osseointegration processes. The loss of marginal bone around a dental implant can be caused by many factors; the proper distribution of the masticatory loads is important and is closely dependent on the quality and quantity of bone tissue surrounding the implant. In fact, bone has the ability to adapt its microstructure, through processes of resorption and neoformation of new bone matrix, as a result of the mechanical stimuli that are generated during the chewing cycles. The purpose of this article is to redefine in a modern key and in light of current industrial and engineering technology, clinical and biomechanical concepts that characterize the monophasic implants, in order to assess proper use by evaluating the biomechanical differences with the biphasic implants. PMID:28280534

  7. Tunable biphasic drug release from ethyl cellulose nanofibers fabricated using a modified coaxial electrospinning process

    PubMed Central

    2014-01-01

    This manuscript reports a new type of drug-loaded core-shell nanofibers that provide tunable biphasic release of quercetin. The nanofibers were fabricated using a modified coaxial electrospinning process, in which a polyvinyl chloride (PVC)-coated concentric spinneret was employed. Poly (vinyl pyrrolidone) (PVP) and ethyl cellulose (EC) were used as the polymer matrices to form the shell and core parts of the nanofibers, respectively. Scanning and transmission electron microscopy demonstrated that the nanofibers had linear morphologies and core-shell structures. The quercetin was found to be present in the nanofibers in the amorphous physical status, on the basis of X-ray diffraction results. In vitro release profiles showed that the PVP shell very rapidly freed its drug cargo into the solution, while the EC core provided the succedent sustained release. Variation of the drug loading permitted the release profiles to be tuned. PMID:24940180

  8. A biphasic process of resistance among suspects: The mobilization and decline of self-regulatory resources.

    PubMed

    Madon, Stephanie; Guyll, Max; Yang, Yueran; Smalarz, Laura; Marschall, Justin; Lannin, Daniel G

    2017-04-01

    We conducted two experiments to test whether police interrogation elicits a biphasic process of resistance from suspects. According to this process, the initial threat of police interrogation mobilizes suspects to resist interrogative influence in a manner akin to a fight or flight response, but suspects' protracted self-regulation of their behavior during subsequent questioning increases their susceptibility to interrogative influence in the long-run. In Experiment 1 (N = 316), participants who were threatened by an accusation of misconduct exhibited responses indicative of mobilization and more strongly resisted social pressure to acquiesce to suggestive questioning than did participants who were not accused. In Experiment 2 (N = 160), self-regulatory decline that was induced during questioning about misconduct undermined participants' ability to resist suggestive questioning. These findings support a theoretical account of the dynamic and temporal nature of suspects' responses to police interrogation over the course of questioning. (PsycINFO Database Record

  9. Biphasic responses of the honeybee heart to nanomolar concentrations of amitraz.

    PubMed

    Papaefthimiou, Chrisovalantis; Papachristoforou, Alexandros; Theophilidis, George

    2013-09-01

    Amitraz is a pesticide targeting the octopaminergic receptors. In a previous study, octopamine, a biogenic amine, was found to induce a biphasic effect on the honeybee heart, inhibition at low concentrations and excitation at high concentrations. Furthermore, the honeybee heart was found to be far more sensitive to octopamine compared to other insect hearts. The objective of the present study was to investigate the effects of amitraz on the electrical and mechanical properties of the honeybee heart ex vivo and on the heart rate in vivo. In ex vivo conditions, amitraz at 10(-12) M caused a significant inhibition in the mechanical (p<0.05, n=4) and electrical properties (p<0.05, n=4). Higher concentrations such as 10(-9) and 10(-6) M induced a biphasic effect, with total inhibition for 7.86±1.26 min (n=7), followed by strong excitation of spontaneously-generated contractions (n=7). The initial elimination of heart activity was caused by strong hyperpolarization, while the subsequent excitation was caused by a depolarization in the membrane potential of pacemaker cells at 10(-9) M (n=8). In the in vivo experiments, abdominal injection or oral application of 0.20 ng of amitraz per bee induced a persistent increase of 134.28±4.07% (p<0.05, n=4) in the frequency of the cardiac action potentials. The above responses clearly show that the heart of the honeybee is extremely vulnerable to amitraz, which is nevertheless still used inside beehives, ostensibly to "protect" the honeybees against their main parasite, Varroa destructor. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Assessing composition and structure of soft biphasic media from Kelvin–Voigt fractional derivative model parameters

    NASA Astrophysics Data System (ADS)

    Zhang, Hongmei; Wang, Yue; Fatemi, Mostafa; Insana, Michael F.

    2017-03-01

    Kelvin–Voigt fractional derivative (KVFD) model parameters have been used to describe viscoelastic properties of soft tissues. However, translating model parameters into a concise set of intrinsic mechanical properties related to tissue composition and structure remains challenging. This paper begins by exploring these relationships using a biphasic emulsion materials with known composition. Mechanical properties are measured by analyzing data from two indentation techniques—ramp-stress relaxation and load-unload hysteresis tests. Material composition is predictably correlated with viscoelastic model parameters. Model parameters estimated from the tests reveal that elastic modulus E 0 closely approximates the shear modulus for pure gelatin. Fractional-order parameter α and time constant τ vary monotonically with the volume fraction of the material’s fluid component. α characterizes medium fluidity and the rate of energy dissipation, and τ is a viscous time constant. Numerical simulations suggest that the viscous coefficient η is proportional to the energy lost during quasi-static force-displacement cycles, E A . The slope of E A versus η is determined by α and the applied indentation ramp time T r. Experimental measurements from phantom and ex vivo liver data show close agreement with theoretical predictions of the η -{{E}A} relation. The relative error is less than 20% for emulsions 22% for liver. We find that KVFD model parameters form a concise features space for biphasic medium characterization that described time-varying mechanical properties. The experimental work was carried out at the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Methodological development, including numerical simulation and all data analysis, were carried out at the school of Life Science and Technology, Xi’an JiaoTong University, 710049, China.

  11. New technetium-99m generator technologies utilizing polyethylene glycol-based aqueous biphasic systems

    SciTech Connect

    Rogers, R.D.; Bond, A.H.; Zhang, Jianhua; Horwitz, P.

    1995-12-31

    Two new schemes for TcO{sub 4}{sup {minus}}/MoO{sub 4}{sup 2{minus}} separations from OH{sup {minus}} and MoO{sub 4}{sup 2{minus}} media using polyethylene glycol (PEG)-based aqueous biphasic systems (ABS) have been developed. The two most important salt solutions in current {sup 99m}Tc-generator technologies, OH{sup {minus}} and MoO{sub 4}{sup 2{minus}}, also salt out PEG to form ABS. In liquid/liquid PEG- ABS, pertechnetate can be separated from molybdate with separation factors as high as 10,000. Stripping is accomplished by reduction of the TcO{sub 4}{sup {minus}} and back extraction into a salt solution. the strip solution can be the salt of an imaging agent (e.g., Na{sub 4}HEDPA) and thus may, under the appropriate conditions, be injected directly into the human body. {sup 99m}TcO{sub 4}{sup {minus}} can also be concentrated from a dilute load solution of {sup 99}MoO{sub 4}{sup 2{minus}} in NaOH using an aqueous biphasic extraction chromatographic technique (ABEC). A rinse with K{sub 2}CO{sub 3} assures that all {sup 99}MoO{sub 4}{sup 2{minus}} is removed from the column and this is confirmed by a rapid drop in {sup 99}Mo activity by the fourth free column volume (fcv) of rinse. The {sup 99m}TcO{sub 4}{sup {minus}} is then eluted with water. This chromatographic separation affords 94% of the {sup 99m}TcO{sub 4}{sup {minus}} activity in 5 fcv, with the y spectrum showing less than 2 {times} 10{sup {minus}4} of the original {sup 99}Mo activity.

  12. A biphasic model for micro-indentation of a hydrogel-based contact lens.

    PubMed

    Chen, Xiaoming; Dunn, Alison C; Sawyer, W Gregory; Sarntinoranont, Malisa

    2007-04-01

    The stiffness and hydraulic permeability of soft contact lenses may influence its clinical performance, e.g., on-eye movement, fitting, and wettability, and may be related to the occurrence of complications; e.g., lesions. It is therefore important to determine these properties in the design of comfortable contact lenses. Micro-indentation provides a nondestructive means of measuring mechanical properties of soft, hydrated contact lenses. However, certain geometrical and material considerations must be taken into account when analyzing output force-displacement (F-D) data. Rather than solely having a solid response, mechanical behavior of hydrogel contact lenses can be described as the coupled interaction between fluid transport through pores and solid matrix deformation. In addition, indentation of thin membranes ( approximately 100 microm) requires special consideration of boundary conditions at lens surfaces and at the indenter contact region. In this study, a biphasic finite element model was developed to simulate the micro-indentation of a hydrogel contact lens. The model accounts for a curved, thin hydrogel membrane supported on an impermeable mold. A time-varying boundary condition was implemented to model the contact interface between the impermeable spherical indenter and the lens. Parametric studies varying the indentation velocities and hydraulic permeability show F-D curves have a sensitive region outside of which the force response reaches asymptotic limits governed by either the solid matrix (slow indentation velocity, large permeability) or the fluid transport (high indentation velocity, low permeability). Using these results, biphasic properties (Young's modulus and hydraulic permeability) were estimated by fitting model results to F-D curves obtained at multiple indentation velocities (1.2 and 20 microm/s). Fitting to micro-indentation tests of Etafilcon A resulted in an estimated permeability range of 1.0 x 10(-15) to 5.0 x 10(-15) m(4)N s and

  13. Biphasic cultivation strategy to avoid Epo-Fc aggregation and optimize protein expression.

    PubMed

    Kaisermayer, Christian; Reinhart, David; Gili, Andreas; Chang, Martina; Aberg, Per-Mikael; Castan, Andreas; Kunert, Renate

    2016-06-10

    In biphasic cultivations, the culture conditions are initially kept at an optimum for rapid cell growth and biomass accumulation. In the second phase, the culture is shifted to conditions ensuring maximum specific protein production and the protein quality required. The influence of specific culture parameters is cell line dependent and their impact on product quality needs to be investigated. In this study, a biphasic cultivation strategy for a Chinese hamster ovary (CHO) cell line expressing an erythropoietin fusion protein (Epo-Fc) was developed. Cultures were run in batch mode and after an initial growth phase, cultivation temperature and pH were shifted. Applying a DoE (Design of Experiments) approach, a fractional factorial design was used to systematically evaluate the influence of cultivation temperature and pH as well as their synergistic effect on cell growth as well as on recombinant protein production and aggregation. All three responses were influenced by the cultivation temperature. Additionally, an interaction between pH and temperature was found to be related to protein aggregation. Compared with the initial standard conditions of 37°C and pH 7.05, a parameter shift to low temperature and acidic pH resulted in a decrease in the aggregate fraction from 75% to less than 1%. Furthermore, the synergistic effect of temperature and pH substantially lowered the cell-specific rates of glucose and glutamine consumption as well as lactate and ammonium production. The optimized culture conditions also led to an increase of the cell-specific rates of recombinant Epo-Fc production, thus resulting in a more economic bioprocess.

  14. [Biphasic ceramic wedge and plate fixation with locked adjustable screws for open wedge tibial osteotomy].

    PubMed

    Lavallé, F; Pascal-Mousselard, H; Rouvillain, J L; Ribeyre, D; Delattre, O; Catonné, Y

    2004-10-01

    The aim of this radiological study was to evaluate the use of a biphasic ceramic wedge combined with plate fixation with locked adjustable screws for open wedge tibial osteotomy. Twenty-six consecutive patients (27 knees) underwent surgery between December 1999 and March 2002 to establish a normal lower-limb axis. The series included 6 women and 20 men, mean age 50 years (16 right knees and 11 left knees). Partial weight-bearing with crutches was allowed on day 1. A standard radiological assessment was performed on day 1, 90, and 360 (plain AP and lateral stance films of the knee). A pangonogram was performed before surgery and at day 360. Presence of a lateral metaphyseal space, development of peripheral cortical bridges, and osteointegration of the bone substitute-bone interface were evaluated used to assess bone healing. The medial tibial angle between the line tangent to the tibial plateau and the anatomic axis of the tibia (beta) was evaluated to assess preservation of postoperative correction. The HKA angle was determined. Three patients were lost to follow-up and 23 patients (24 knees) were retained for analysis. At last follow-up, presence of peripheral cortical bridges and complete filling of the lateral metaphyseal space demonstrated bone healing in all patients. Good quality osteointegration was achieved since 21 knees did not present an interface between the bone substitute and native bone (homogeneous transition zone). The beta angle was unchanged for 23 knees. A normal axis was observed in patients (16 knees) postoperatively. Use of a biphasic ceramic wedge in combination with plate fixation with locked adjustable screws is a reliable option for open wedge tibial osteotomy. The bone substitute fills the gap well. Tolerance and integration are optimal. Bone healing is achieved. Plate fixation with protected weight bearing appears to be a solid assembly, maintaining these corrections.

  15. Frequent biphasic cellular responses of permanent fish cell cultures to deoxynivalenol (DON)

    SciTech Connect

    Pietsch, Constanze; Bucheli, Thomas D.; Wettstein, Felix E.; Burkhardt-Holm, Patricia

    2011-10-01

    Contamination of animal feed with mycotoxins is a major problem for fish feed mainly due to usage of contaminated ingredients for production and inappropriate storage of feed. The use of cereals for fish food production further increases the risk of a potential contamination. Potential contaminants include the mycotoxin deoxynivalenol (DON) which is synthesized by globally distributed fungi of the genus Fusarium. The toxicity of DON is well recognized in mammals. In this study, we confirm cytotoxic effects of DON in established permanent fish cell lines. We demonstrate that DON is capable of influencing the metabolic activity and cell viability in fish cells as determined by different assays to indicate possible cellular targets of this toxin. Evaluation of cell viability by measurement of membrane integrity, mitochondrial activity and lysosomal function after 24 h of exposure of fish cell lines to DON at a concentration range of 0-3000 ng ml{sup -1} shows a biphasic effect on cells although differences in sensitivity occur. The cell lines derived from rainbow trout are particularly sensitive to DON. The focus of this study lies, furthermore, on the effects of DON at different concentrations on production of reactive oxygen species (ROS) in the different fish cell lines. The results show that DON mainly reduces ROS production in all cell lines that were used. Thus, our comparative investigations reveal that the fish cell lines show distinct species-related endpoint sensitivities that also depend on the type of tissue from which the cells were derived and the severity of exposure. - Highlights: > DON uptake by cells is not extensive. > All fish cell lines are sensitive to DON. > DON is most cytotoxic to rainbow trout cells. > Biphasic cellular responses were frequently observed. > Our results are similar to studies on mammalian cell lines.

  16. In situ synthesis of magnesium-substituted biphasic calcium phosphate and in vitro biodegradation

    SciTech Connect

    Kim, Tae-Wan; Lee, Hyeong-Shin; Kim, Dong-Hyun; Jin, Hyeong-Ho; Hwang, Kyu-Hong; Lee, Jong Kook; Park, Hong-Chae; Yoon, Seog-Young

    2012-09-15

    Highlights: ► Mg–BCP were successfully prepared through in situ aqueous co-precipitation method. ► The amount of β-TCP phase was changed with the magnesium substitution level. ► The substitution of magnesium led to a decrease in the unit cell volume. ► Mg–BCP could be able to develop a new apatite phase on the surface faster than BCP. -- Abstract: In situ preparation of magnesium (Mg) substituted biphasic calcium phosphate (BCP) of hydroxyapatite (HAp)/β-tricalcium phosphate (β-TCP) were carried out through aqueous co-precipitation method. The concentrations of added magnesium were varied with the calcium in order to obtain constant (Ca + Mg)/P ratios of 1.602. X-ray diffraction (XRD) and Fourier transformed infrared (FTIR) spectroscopy were used to characterize the structure of synthesized magnesium substituted BCP powders. The results have shown that substitution of magnesium in the calcium deficient apatites revealed the formation of biphasic mixtures of different HAp/β-TCP ratios after heating at 1000 °C. The ratios of the formation of phase mixtures were dependent on the content of magnesium. After immersing in Hanks’ balanced salt solution (HBSS) for 1 week, 1 wt% magnesium substituted BCP powders were degraded and precipitation started to be formed with small granules consisting of number of flake-like crystal onto the surface of synthesized powders. On the other hand, in the case of pure BCP powders, the formation of new precipitates was detected after immersion in HBSS for 2 weeks. On the basis of these results, magnesium substituted BCP could be able to develop a new apatite phase on the surface in contact with physiological fluids faster than BCP does. In addition, the retention time to produce the new apatite phase in implantation operation for the BCP powder could be controlled by the amount of magnesium substitution.

  17. Kinetics of Horseradish Peroxidase-Catalyzed Nitration of Phenol in a Biphasic System.

    PubMed

    Kong, Mingming; Zhang, Yang; Li, Qida; Dong, Runan; Gao, Haijun

    2017-02-28

    The use of peroxidase in the nitration of phenols is gaining interest as compared with traditional chemical reactions. We investigated the kinetic characteristics of phenol nitration catalyzed by horseradish peroxidase (HRP) in an aqueous-organic biphasic system using n-butanol as the organic solvent and NO2(-) and H2O2 as substrates. The reaction rate was mainly controlled by the reaction kinetics in the aqueous phase when appropriate agitation was used to enhance mass transfer in the biphasic system. The initial velocity of the reaction increased with increasing HRP concentration. Additionally, an increase in the substrate concentrations of phenol (0-2 mM in organic phase) or H2O2 (0-0.1 mM in aqueous phase) enhanced the nitration efficiency catalyzed by HRP. In contrast, high concentrations of organic solvent decreased the kinetic parameter Vmax/Km. No inhibition of enzyme activity was observed when the concentrations of phenol and H2O2 were at or below 10 mM and 0.1 mM, respectively. On the basis of the peroxidase catalytic mechanism, a double-substrate ping-pong kinetic model was established. The kinetic parameters were Km(H2O2)= 1.09 mM, Km(PhOH) = 9.45 mM, and Vmax = 0.196 mM/min. The proposed model was well fit to the data obtained from additional independent experiments under the suggested optimal synthesis conditions. The kinetic model developed in this paper lays a foundation for further comprehensive study of enzymatic nitration kinetics.

  18. Temperature dependence of microwave absorption phenomena in single and biphase soft magnetic microwires

    NASA Astrophysics Data System (ADS)

    El Kammouni, Rhimou; Vázquez, Manuel; Lezama, Luis; Kurlyandskaya, Galina; Kraus, Ludek

    2014-11-01

    The microwave absorption phenomena of single and biphase magnetic microwires with soft magnetic behavior have been investigated as a function of DC applied magnetic field using two alternative techniques: (i) absorption measurements in the temperature range of 4-300 K using a spectrometer operating at X-band frequency, at 9.5 GHz, and (ii) room-temperature, RT, ferromagnetic resonance measurements in a network analyzer in the frequency range up to 20 GHz. Complementary low-frequency magnetic characterization was performed in a Vibrating Sample Magnetometer. Studies have been performed for 8 μm diameter small-magnetostriction amorphous CoFeSiB single-phase microwire, coated by micrometric Pyrex layer, and after electroplating an external shell, 2 μm or 4 μm thick, of FeNi alloys. For single phase CoFeSiB microwire, a single absorption is observed, whose DC field dependence of resonance frequency at RT fits to a Kittel-law behavior for in-plane magnetized thin film. The temperature dependence behavior shows a monotonic increase in the resonance field, Hr, with temperature. A parallel reduction of the circular anisotropy field, HK, is deduced from the temperature dependence of hysteresis loops. For biphase, CoFeSiB/FeNi, microwires, the absorption phenomena at RT also follow the Kittel condition. The observed opposite evolution with temperature of resonance field, Hr, in 2 and 4 μm thick FeNi samples is interpreted considering the opposite sign of magnetostriction of the respective FeNi layers. The stress-induced magnetic anisotropy field, HK, in the FeNi shell is deduced to change sign at around 130 K.

  19. Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells

    SciTech Connect

    Asp, Vendela; Ulleras, Erik; Lindstroem, Veronica; Bergstroem, Ulrika; Oskarsson, Agneta; Brandt, Ingvar

    2010-02-01

    The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO{sub 2}-DDE) has been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) treatment. ACC is a rare malignant disorder with poor prognosis, and the current pharmacological therapy o,p'-DDD (mitotane) has limited efficacy and causes severe adverse effects. 3-MeSO{sub 2}-DDE is bioactivated by cytochrome P450 (CYP) 11B1 in mice and causes formation of irreversibly bound protein adducts, reduced glucocorticoid secretion, and cell death in the adrenal cortex of several animal species. The present study was carried out to assess similarities and differences between mice and humans concerning the adrenocorticolytic effects of 3-MeSO{sub 2}-DDE. The results support previous indications that humans are sensitive to the adrenocorticolytic actions of 3-MeSO{sub 2}-DDE by demonstrating protein adduct formation and cytotoxicity in the human adrenocortical cell line H295R. However, neither the irreversible binding nor the cytotoxicity of 3-MeSO{sub 2}-DDE in H295R cells was inhibited by the CYP11B1 inhibitor etomidate. We also report biphasic responses to 3-MeSO{sub 2}-DDE in cortisol and aldosterone secretion as well as in mRNA levels of the steroidogenic genes StAR, CYP11B1 and CYP11B2. Hormone levels and mRNA levels were increased at lower concentrations of 3-MeSO{sub 2}-DDE, while higher concentrations decreased hormone levels. These biphasic responses were not observed with o,p'-DDD or with the precursor DDT metabolite p,p'-DDE. Based on these results, 3-MeSO{sub 2}-DDE remains a viable lead compound for drug design, although the adrenocorticolytic effects of 3-MeSO{sub 2}-DDE in human cells seem more complex than in murine cells.

  20. Regulation of the Demographic Structure in Isomorphic Biphasic Life Cycles at the Spatial Fine Scale

    PubMed Central

    Vieira, Vasco Manuel Nobre de Carvalho da Silva; Mateus, Marcos Duarte

    2014-01-01

    Isomorphic biphasic algal life cycles often occur in the environment at ploidy abundance ratios (Haploid:Diploid) different from 1. Its spatial variability occurs within populations related to intertidal height and hydrodynamic stress, possibly reflecting the niche partitioning driven by their diverging adaptation to the environment argued necessary for their prevalence (evolutionary stability). Demographic models based in matrix algebra were developed to investigate which vital rates may efficiently generate an H:D variability at a fine spatial resolution. It was also taken into account time variation and type of life strategy. Ploidy dissimilarities in fecundity rates set an H:D spatial structure miss-fitting the ploidy fitness ratio. The same happened with ploidy dissimilarities in ramet growth whenever reproductive output dominated the population demography. Only through ploidy dissimilarities in looping rates (stasis, breakage and clonal growth) did the life cycle respond to a spatially heterogeneous environment efficiently creating a niche partition. Marginal locations were more sensitive than central locations. Related results have been obtained experimentally and numerically for widely different life cycles from the plant and animal kingdoms. Spore dispersal smoothed the effects of ploidy dissimilarities in fertility and enhanced the effects of ploidy dissimilarities looping rates. Ploidy dissimilarities in spore dispersal could also create the necessary niche partition, both over the space and time dimensions, even in spatial homogeneous environments and without the need for conditional differentiation of the ramets. Fine scale spatial variability may be the key for the prevalence of isomorphic biphasic life cycles, which has been neglected so far. PMID:24658603

  1. Unique biphasic band shape of the visible circular dichroism of bacteriorhodopsin in purple membrane

    PubMed Central

    Cassim, Joseph Y.

    1992-01-01

    Over a decade and a half ago, when the first visible membrane suspension circular dichroic (CD) spectrum of the purple membrane (PM) was presented, two mechanisms were proposed to account for the observed biphasic shaped CD band: (a) excitonic interactions among the retinals of the sole protein bacteriorhodopsin (bR) in the crystalline structure of the PM, and (b) combination of CD bands with opposite rotational strengths due to a retinal-apoprotein heterogeneity of the bR molecules or due to two possible close-lying long-wavelength transitions of the retinal of the bR with opposite rotational strengths. Since that time, an impressive body of experimental and theoretical evidence has been accumulated, mostly consistent with an exciton model but many at serious odds with any heterogeneity or multiple transition model. Recently, a number of articles have appeared reporting analyses of new experimental observations which are proposed to cast serious doubts on the viability of the exciton model, and therefore, may revive the heterogeneity or multiple transition model as an explanation for the unique shape of the CD band of the PM. The intent of this article is to demonstrate that if all observations found in literature baring on this question are considered in toto and in a consistent manner, they can be interpreted without exception by excitons, and furthermore, that there is no plausible evidence available to warrant the revival of the heterogeneity or multiple transition model as an explanation for the unique shape of the biphasic CD band of the PM. PMID:19431860

  2. Survival Kinetics of Starving Bacteria Is Biphasic and Density-Dependent

    PubMed Central

    Phaiboun, Andy; Zhang, Yiming; Park, Boryung; Kim, Minsu

    2015-01-01

    In the lifecycle of microorganisms, prolonged starvation is prevalent and sustaining life during starvation periods is a vital task. In the literature, it is commonly assumed that survival kinetics of starving microbes follows exponential decay. This assumption, however, has not been rigorously tested. Currently, it is not clear under what circumstances this assumption is true. Also, it is not known when such survival kinetics deviates from exponential decay and if it deviates, what underlying mechanisms for the deviation are. Here, to address these issues, we quantitatively characterized dynamics of survival and death of starving E. coli cells. The results show that the assumption – starving cells die exponentially – is true only at high cell density. At low density, starving cells persevere for extended periods of time, before dying rapidly exponentially. Detailed analyses show intriguing quantitative characteristics of the density-dependent and biphasic survival kinetics, including that the period of the perseverance is inversely proportional to cell density. These characteristics further lead us to identification of key underlying processes relevant for the perseverance of starving cells. Then, using mathematical modeling, we show how these processes contribute to the density-dependent and biphasic survival kinetics observed. Importantly, our model reveals a thrifty strategy employed by bacteria, by which upon sensing impending depletion of a substrate, the limiting substrate is conserved and utilized later during starvation to delay cell death. These findings advance quantitative understanding of survival of microbes in oligotrophic environments and facilitate quantitative analysis and prediction of microbial dynamics in nature. Furthermore, they prompt revision of previous models used to analyze and predict population dynamics of microbes. PMID:25838110

  3. Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

    2015-08-01

    The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

  4. Novel biphasic separations utilising highly selective molecularly imprinted polymers as biorecognition solvent extraction agents.

    PubMed

    Castell, Oliver K; Allender, Christopher J; Barrow, David A

    2006-10-15

    Molecularly imprinted polymers (MIPs) represent a class of artificial receptors that promise an environmentally robust alternative to naturally occurring biorecognition elements of biosensing devices and systems. However, in general, the performance of conventional MIPs in aqueous environments is poor. In the study reported here, this limitation has been addressed by the novel application of MIPs as a solvent extraction solid phase in a biphasic solvent system. This paper describes a previously unreported use of MIPs as solvent extraction reagents, their successful application to aqueous sample media and the opportunities for utilisation of this unique system in novel biosensing and separation procedures. This study demonstrates the development of a novel biphasic solvent system utilising MIP in the extracting phase to enhance both efficiency and selectivity of a simple two phase liquid extraction. Monodisperse propranolol imprinted polymer microspheres [p(divinylbenzene-co-methacrylic acid)] were prepared by precipitation polymerisation. Initially, the affinity of the polymers for (R,S)-propranolol was assessed by established techniques whereby the MIP demonstrated greater affinity for the template than did the non-imprinted control polymer (NIP). Importantly, MIP performance was also assessed using the novel dual solvent system. The depletion of (R,S)-propranolol from the aqueous phase into the polymer containing organic phase was determined. When compared to control extractions containing no polymer the presence of MIP in the extracting solvent phase resulted in an increased extraction of (R,S)-propranolol from the aqueous phase. Importantly, this extraction was significantly greater in the presence of MIP when compared to NIP. This unique principle generates opportunities for MIP based extractions and chemical enrichments in industrial applications, offering commercial, ecological and practical advantages to traditional solvent extraction techniques. The

  5. Use of microindentation to characterize the mechanical properties of articular cartilage: comparison of biphasic material properties across length scales.

    PubMed

    Miller, G J; Morgan, E F

    2010-08-01

    Small scale mechanical testing techniques offer new possibilities for defining changes in mechanical properties that accompany the morphological, histological, and biochemical abnormalities of osteoarthritis (OA). The goal of this study was to investigate the use of microindentation in characterizing the biphasic material properties of articular cartilage. Direct comparisons of the biphasic properties (E, k and nu) determined using microindentation were made to those determined on the same specimens using standard macroscale testing techniques. Deep-zone bovine articular cartilage specimens (n=10) were tested in macroscale confined and unconfined compression. For microindentation testing, the biphasic properties were determined by conducting finite element simulations of the microindentation experiments for different combinations of values of biphasic properties and identifying the combination yielding the best match to each microindentation curve. Paired t-tests were performed to compare each of E, k and nu between the macro- and microscale. The microscale values for E, k and nu were 0.74 (0.53, 0.95)MPa, 0.66 (0.022, 0.110)x10(-16)m(4)/Ns, and 0.16 (0.08, 0.24), respectively. A significant difference between the macro- and microscale measurements was observed for k (P<0.0001), but not for E or nu (P=0.88, 0.16). The agreement in Young's modulus and Poisson's ratio between the results of the microindentation and macroscale tests supports the use of microindentation for characterization of some of the biphasic material properties of articular cartilage. The observed differences in permeability between macro- and microscales are consistent with evidence in the literature of a length-scale dependence to this property. Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Biolog phenotype microarrays.

    PubMed

    Shea, April; Wolcott, Mark; Daefler, Simon; Rozak, David A

    2012-01-01

    Phenotype microarrays nicely complement traditional genomic, transcriptomic, and proteomic analysis by offering opportunities for researchers to ground microbial systems analysis and modeling in a broad yet quantitative assessment of the organism's physiological response to different metabolites and environments. Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally defined nutrients to measure the impact of hundreds of carbon, nitrogen, phosphorous, and sulfur sources on redox reactions that result from compound-induced effects on the electron transport chain. Over the years, we have used Biolog's reproducible and highly sensitive assays to distinguish closely related bacterial isolates, to understand their metabolic differences, and to model their metabolic behavior using flux balance analysis. This chapter describes Biolog phenotype microarray system components, reagents, and methods, particularly as they apply to bacterial identification, characterization, and metabolic analysis.

  7. A Complex Phenotype of Peripheral Neuropathy, Myopathy, Hoarseness and Hearing Loss is Linked to an Autosomal Dominant Mutation in MYH14

    PubMed Central

    Choi, Byung-Ok; Kang, Sung Hee; Hyun, Young Se; Kanwal, Sumaria; Park, Sun Wha; Koo, Heasoo; Kim, Sang-Beom; Choi, Young-Chul; Yoo, Jeong Hyun; Kim, Jong-Won; Park, Kee Duk; Choi, Kyoung-Gyu; Kim, Song Ja; Züchner, Stephan; Chung, Ki Wha

    2011-01-01

    Both peripheral neuropathy and distal myopathy are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. A complex phenotype of peripheral neuropathy, myopathy, hoarseness and hearing loss was diagnosed in a large autosomal dominant Korean family. A high density SNP-based linkage study mapped the underlying gene to a region on chromosome 19q13.3. The maximum multipoint LOD score was 3.794. Sequencing of 34 positional candidate genes in the segregating haplotype revealed a novel c.2822G>T (p.Arg941Leu) mutation in the gene MYH14, which encodes the nonmuscle myosin heavy chain 14. Clinically we observed a sequential pattern of the onset of muscle weakness starting from the anterior to the posterior leg muscle compartments followed by involvement of intrinsic hand and proximal muscles. The hearing loss and hoarseness followed the onset of distal muscle weakness. Histopathologic and electrodiagnostic studies revealed both chronic neuropathic and myopathic features in the affected patients. While mutations in MYH14 have been shown to cause nonsyndromic autosomal dominant hearing loss (DFNA4), the peripheral neuropathy, myopathy, and hoarseness have not been associated with MYH14. Therefore, we suggest that the identified mutation in MYH14 significantly expands the phenotypic spectrum of this gene. PMID:21480433

  8. Comb polymer architecture and particle size effects on the behavior of biphasic nanoparticle inks for direct-write assembly

    NASA Astrophysics Data System (ADS)

    Yoshikawa, Jun

    Biphasic nanoparticle mixtures composed of attractive and repulsive colloidal species enable the direct-write assembly of 3D structures with much finer features than those produced by pure colloidal gels. These mixtures rely on the use of comb polymer dispersants to render one particle population stable, while the other population is attractive. In this thesis, we systematically investigate the effects of comb polymer architecture and particle size ratio on the behavior of biphasic nanoparticle inks with the overarching aim of further advancing the direct-write assembly of 3D colloidal structures. We first investigated the effects of both pure polyelectrolytes, poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA), and comb polymer dispersants composed of a PMAA backbone with methoxy-poly(ethylene oxide) (mPEO) teeth of varying molecular weights on the stability of barium titanate (BaTiO 3) suspensions. While each dispersant imparts stability to BaTiO 3 nanoparticles at low ionic strength (< 0.01 M), only the PMAA-mPEO comb polymer with the longest teeth (MWteeth = 2000) provides stability at higher ionic strengths over a broad range of particle sizes and counterion valencies. These results provide guidelines for tailoring the molecular architecture and functionality of comb polymer dispersants for optimal stabilization of the repulsive particle population within the biphasic inks. Next, particle size effects on the rheological properties of biphasic nanoparticle suspensions are studied. Shear elastic modulus, shear yield stress, and compressive yield stress are measured for mixtures of varying total volume fraction, attractive-to-repulsive volume fraction, and particle size ratio between attractive and repulsive species. Our observations indicate that the repulsive particles hinder the formation of the attractive gel network. The time required for shear elastic modulus to approach a steady-state value increases with the fraction of repulsive species

  9. Down Syndrome: Cognitive Phenotype

    ERIC Educational Resources Information Center

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  10. Down Syndrome: Cognitive Phenotype

    ERIC Educational Resources Information Center

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  11. Cell-Envelope Remodeling as a Determinant of Phenotypic Antibacterial Tolerance in Mycobacterium tuberculosis

    PubMed Central

    2016-01-01

    The mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. We investigate whether changes in NaCl concentration toward physiologically higher values affect antibacterial efficacy against Mycobacterium tuberculosis (Mtb), the causal agent of human tuberculosis. Indeed, multiclass phenotypic antibacterial tolerance is observed during Mtb growth in physiologic saline. This includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several aminoglycosides, and quinolones. By employing organism-wide metabolomic and lipidomic approaches combined with phenotypic tests, we identified a time-dependent biphasic adaptive response after exposure of Mtb to physiological levels of NaCl. A first rapid, extensive, and reversible phase was associated with changes in core and amino acid metabolism. In a second phase, Mtb responded with a substantial remodelling of plasma membrane and outer lipid membrane composition. We demonstrate that phenotypic tolerance at physiological concentrations of NaCl is the result of changes in plasma and outer membrane lipid remodeling and not changes in core metabolism. Altogether, these results indicate that physiologic saline-induced antibacterial tolerance is kinetically coupled to cell envelope changes and demonstrate that metabolic changes and growth arrest are not the cause of phenotypic tolerance observed in Mtb exposed to physiologic concentrations of NaCl. Importantly, this work uncovers a role for bacterial cell envelope remodeling in antibacterial tolerance, alongside well-documented allterations in respiration, metabolism, and growth rate. PMID:27231718

  12. Sinus Floor Augmentation Comparing an In Situ Hardening Biphasic Calcium Phosphate (Hydroxyapatite/β-Tricalcium Phosphate) Bone Graft Substitute with a Particulate Biphasic Calcium Phosphate (Hydroxyapatite/β-Tricalcium Phosphate) Bone Graft Substitute: An Experimental Study in Sheep.

    PubMed

    Wildburger, Angelika; Bubalo, Vladimir; Magyar, Marton; Nagursky, Heiner; Jakse, Norbert; Schmelzeisen, Rainer; Sauerbier, Sebastian

    2017-07-01

    The aim of the present split-mouth study in sheep was to assess the influence of in situ hardening properties of a biphasic calcium phosphate (BCP) bone graft substitute (BGS) (ratio hydroxyapatite/β-tricalcium phosphate = 60/40) compared with a particulate BGS with the same biphasic core-granule composition without in situ hardening properties on sinus floor augmentation. Therefore, bilateral sinus floor augmentation was performed in eight sheep. Poly(lactide-co-glycolide) (PLGA)-coated, in situ hardening biphasic BGS (PLGA-NMP [N-Methyl-2-pyrrolidone]-BCP) was placed at the test site, and a particulate biphasic BGS without PLGA coating (BCP) was used for the contralateral site as a control. Animals were sacrificed after 21 weeks. Sinus augmentation sites were analyzed histologically. The volume was analyzed by computed tomography. Histomorphometric parameters were assessed for the 12 and 21 weeks' time points. Slopes of new bone formation over time were compared with a linear growth regression model. Bone formation after 12 and 21 weeks of healing was 8.94% (±3.74) and 19.82% (±6.29) for PLGA-NMP-BCP and 7.00% (±2.58) and 14.38% (±4.51) for BCP, respectively. The bone growth rate for PLGA-NMP-BCP was higher than the growth rate for BCP (probability 97.5%). The total fraction of calcified hard tissue (% bone fraction + % biomaterial) was around 46% for both tested biomaterials, 21 weeks after sinus floor augmentation. The in situ hardening BGS (PLGA-NMP-BCP) performed better than the particulate material (BCP) in terms of bone formation rate. The in situ hardening properties of the PLGA-NMP-BCP material mediated by the PLGA coating and NMP solution as plasticizer had no negative influence on the bone formation.

  13. Biphasic effect of bimoclomol on calcium handling in mammalian ventricular myocardium

    PubMed Central

    Nánási, Péter P; Sárközi, Sándor; Szigeti, Gyula; Jóna, István; Szegedi, Csaba; Szabó, Ágnes; Bányász, Tamás; Magyar, János; Szigligeti, Péter; Körtvély, Ágnes; Csernoch, László; Kovács, László; Jednákovits, Andrea

    2000-01-01

    Concentration-dependent effects of bimoclomol, the novel heat shock protein coinducer, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea-pig hearts loaded with the fluorescent calcium indicator dye Fura-2. Bimoclomol had a biphasic effect on contractility: both peak left ventricular pressure and the rate of force development significantly increased at a concentration of 10 nM or higher. The maximal effect was observed between 0.1 and 1 μM, and the positive inotropic action disappeared by further increasing the concentration of bimoclomol. The drug increased systolic calcium concentration with a similar concentration-dependence. In contrast, diastolic calcium concentration increased monotonically in the presence of bimoclomol. Thus low concentrations of the drug (10–100 nM) increased, whereas high concentrations (10 μM) decreased the amplitude of intracellular calcium transients.Effects of bimoclomol on action potential configuration was studied in isolated canine ventricular myocytes. Action potential duration was increased at low (10 nM), unaffected at intermediate (0.1–1 μM) and decreased at high (10–100 μM) concentrations of the drug.In single canine sarcoplasmic calcium release channels (ryanodine receptor), incorporated into artificial lipid bilayer, bimoclomol significantly increased the open probability of the channel in the concentration range of 1–10 μM. The increased open probability was associated with increased mean open time. The effect of bimoclomol was again biphasic: the open probability decreased below the control level in the presence of 1 mM bimoclomol.Bimoclomol (10 μM–1 mM) had no significant effect on the rate of calcium uptake into sarcoplasmic reticulum vesicles of the dog, indicating that in vivo calcium reuptake might not substantially be affected by the drug.In conclusion, the positive inotropic action of bimoclomol is likely due to the activation of the

  14. Biphasic action of iodine in excess at different doses on ovary in adult rats.

    PubMed

    Mahapatra, Dakshayani; Chandra, Amar K

    2017-01-01

    Iodine consumption in excess of its recommended levels over a prolonged period of time is well known to cause thyroid disorders. The thyroid hormones on the other hand are responsible in maintenance of the physiology of the reproductive system. Excess iodine intake affects male reproductive physiology. However, the effects of excess iodine on the ovarian structure and function is yet to be established. The present study has thus been undertaken to investigate the effect of excess iodine on the ovarian physiology. Excess iodine was administered through oral gavage in the form of potassium iodide (KI) for duration of 60days, at two different doses. The doses used were 100 EI, i.e., 100 times more than the recommended level but tolerable to the thyroid gland and 500 EI, i.e., 500 times more than the recommended level that altered thyroid physiology. The animals were divided into three groups, one control group, and the other two receiving two separate doses (100 EI and 500 EI) of excess KI. Estrous cyclical changes, ovarian morphological changes, ovarian iodine accumulation and ovarian steroidogenic enzyme activities were analysed. The thyroid functional status was studied from the serum thyroid hormones levels. The overall results revealed a biphasic action of excess iodine that depends on its dose. At 100 EI, excess iodine did not alter thyroid physiology but lead to the development of a hypoestrogenic state. There was an increased accumulation of iodine in the ovary with decreased activity of ovarian steroidogenic enzymes and lowered serum estradiol levels. However, at 500 EI, excess iodine developed a hyperthyroid condition, which further leads to a hyperestrogenic state. There was an increased activity of serum steroidogenic enzymes as well as elevated serum estradiol levels. Fertility index was zero in both the 100 EI and 500 EI treated groups of experimental animals. Thus excess iodine (100 EI) ingestion within tolerable range though maintained a euthyroid

  15. Phenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark

    PubMed Central

    Werlauff, Ulla; Duno, Morten; Vissing, John

    2017-01-01

    Objective: Congenital myopathy as a nosologic entity has long been recognized, but knowledge of overall and subtype prevalence and phenotype-genotype relationship is scarce, especially in the adult population. Methods: A national cohort of 107 patients ≥5 years diagnosed with congenital myopathy were prospectively assessed clinically, histologically, and genetically. Results: Twenty-five patients were excluded because of atypical features or alternative etiologies. The remaining 82 were on average 28 years old. Histologic examination revealed 14 (17%) with core disease, 15 (18%) centronuclear myopathy, 12 (15%) nemaline rods, 27 (33%) congenital fiber-type disproportion or type I predominance, and 14 (17%) nonspecific myopathic changes. Genetic etiology was identified in 46 patients (56.1%); 22.0% were heterozygous or compound heterozygous for mutations in RYR1, 7.3% had DNM2 mutations, and 7.3% NEB mutations. Less than 5% had mutations in ACTA1, TPM2/3, MTM1, TTN, SEPN1, or SC4NA. A genetic cause was established in 83% with specific histology (cores/rods/centronuclear myopathy) vs 29% with unspecific histology. The detailed clinical examination found gene-dependent discrepancies in the pattern of muscle affection and walking ability. Although walking ability was delayed in patients with ACTA1, TPM2/3, and RYR1 mutations, it was within normal limits in patients with NEB and DNM2 mutations. Conclusions: We found that overall, genetic and histologic prevalence of congenital myopathy in Denmark differs from previous retrospective reports. Less RYR1 and more DNM2 and NEB mutations and less core histology were present in our cohort. These differences may be explained by our prospective design, the older cohort of patients, and by differences in genetic background. PMID:28357410

  16. Use of the electrically driven emulsion-phase contactor for a biphasic liquid-liquid enzyme system

    SciTech Connect

    Scott, T.C.; Cosgrove, J.M.; DePaoli, D.W.

    1995-12-31

    An alternative approach to the operation of bioprocessing systems within non-aqueous environments would require the development of reaction systems that would provide effective interfacial contact between the biocatalyst, contained within an aqueous phase, and the organic phase containing the substrate. A biphasic liquid-liquid (BLL) reactor that provides for intimate liquid-liquid contact would be the most probable approach for this application. For the BLL reactions considered in this work, the overall effectiveness of the system will depend on both compatibility of the biocatalyst with the chemical species present and intrinsic reaction and interfacial transport phenomena typically involved with liquid-liquid operations. The focus of this article is to investigate the removal and oxidation of p-cresol dissolved in toluene by aqueous-phase horseradish peroxidase. Contacting of the liquid-liquid biphasic enzyme system is carried out in an advanced solvent extraction contacting device, the electrically driven emulsion-phase contactor (EPC).

  17. Biphasic Liquid Crystal and the Simultaneous Measurement of Isotropic and Anisotropic Parameters by Spatially Resolved NMR Spectroscopy.

    PubMed

    Reller, Malin; Wesp, Svenja; Koos, Martin R M; Reggelin, Michael; Luy, Burkhard

    2017-06-23

    Residual dipolar couplings and other anisotropic NMR parameters are powerful tools for molecular structure elucidation when conventional techniques do not suffice. With current liquid crystalline preparations it is necessary to prepare two samples to extract isotropic and anisotropic data from spectra and to derive the residual dipolar couplings. Here, we present the preparation, measurement, and interpretation of a novel biphasic liquid crystalline phase where a single sample can be used to generate both isotropic and anisotropic data. First, we introduce the synthesis of the chiral polymer leading to the biphasic liquid crystal. Second, we present two approaches to measure spatially selective CLIP-HSQC spectra. From these spectra, we extracted the couplings, performed an assignment of diastereotopic protons, and achieved the enantiomeric discrimination of isopinocampheol as a well-studied test molecule. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Catalytic conversion of corncob and corncob pretreatment hydrolysate to furfural in a biphasic system with addition of sodium chloride.

    PubMed

    Qing, Qing; Guo, Qi; Zhou, Linlin; Wan, Yilun; Xu, Youqing; Ji, Huilong; Gao, Xiaohang; Zhang, Yue

    2017-02-01

    Catalytic conversion of corncob pretreatment hydrolysate and raw corncob into furfural in a modified biphasic system by SO4(2-)/SnO2(-) MMT solid catalyst has been developed. The influence of the organic solvent type, organic to water phase ratio, sodium chloride concentration, reaction temperature and time on the furfural production were comparatively evaluated. The results showed that furfural yields of 81.7% and 66.1% were achieved at 190°C for 15mins and 190°C for 20mins, respectively, for corncob pretreatment hydrolysate and raw corncob by this solid catalyst. The solid catalyst used in this study exhibited good stability and high efficiency applied in the modified biphasic system in addition to excellent recyclability. The proposed catalytic system displayed high performance for catalytic conversion of lignocellulosic biomass into important platform chemicals and has great potential in industrial application.

  19. Phosphorus-doped TiO2 catalysts with stable anatase-brookite biphase structure: synthesis and photocatalytic performance.

    PubMed

    Feng, Huajun; Zhang, Min-Hong; Yu, Liya E

    2013-07-01

    Phosphorus-doped (P-doped) TiO2 catalysts with a stable anatase-brookite biphase structure were successfully synthesized by integrating ultrasonication with phosphorus doping and Pluronic P123 surfactant. The synthesized catalysts were characterized using X-ray diffraction, transmission electron microscopy, nitrogen adsorption-desorption, Fourier transform infrared, and UV-visible diffuse reflectance spectra. Ultrasonication facilitates the appearance of brookite phase. Phosphorus doping was demonstrated an effective strategy to stabilize the anatase-brookite biphase structure and inhibits undesirable grain growth. Triblock copolymer Pluronic P123 used in the reaction facilitates the formation of catalyst particles with mesoporous structure and large surface area and prevents particles from agglomeration. The low band-gap of brookite phase enables the synthesized P-doped TiO2 catalysts outperform commercial P25 TiO2 and N-doped TiO2 in the degradation of methylene blue under both solar light and visible light irradiation.

  20. Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus.

    PubMed

    Yamaguchi, Hiroshi; Tanaka, Tsukasa; Maruyama, Azusa; Nagase, Hiroaki

    2016-01-01

    Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy). Septic encephalopathy (SE) is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE) could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure.

  1. Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus

    PubMed Central

    Tanaka, Tsukasa; Maruyama, Azusa; Nagase, Hiroaki

    2016-01-01

    Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy). Septic encephalopathy (SE) is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE) could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure. PMID:27051542

  2. Mechanism of conduction block in amphibian myelinated axon induced by biphasic electrical current at ultra-high frequency.

    PubMed

    Tai, Changfeng; Guo, Dong; Wang, Jicheng; Roppolo, James R; de Groat, William C

    2011-11-01

    The mechanism of axonal conduction block induced by ultra-high frequency (≥ 20 kHz) biphasic electrical current was investigated using a lumped circuit model of the amphibian myelinated axon based on Frankenhaeuser-Huxley (FH) equations. The ultra-high frequency stimulation produces constant activation of both sodium and potassium channels at the axonal node under the block electrode causing the axonal conduction block. This blocking mechanism is different from the mechanism when the stimulation frequency is between 4 kHz and 10 kHz, where only the potassium channel is constantly activated. The minimal stimulation intensity required to induce a conduction block increases as the stimulation frequency increases. The results from this simulation study are useful to guide future animal experiments to reveal the different mechanisms underlying nerve conduction block induced by high-frequency biphasic electrical current.

  3. Optimization and phenotype allocation.

    PubMed

    Jost, Jürgen; Wang, Ying

    2014-01-01

    We study the phenotype allocation problem for the stochastic evolution of a multitype population in a random environment. Our underlying model is a multitype Galton–Watson branching process in a random environment. In the multitype branching model, different types denote different phenotypes of offspring, and offspring distributions denote the allocation strategies. Two possible optimization targets are considered: the long-term growth rate of the population conditioned on nonextinction, and the extinction probability of the lineage. In a simple and biologically motivated case, we derive an explicit formula for the long-term growth rate using the random Perron–Frobenius theorem, and we give an approximation to the extinction probability by a method similar to that developed by Wilkinson. Then we obtain the optimal strategies that maximize the long-term growth rate or minimize the approximate extinction probability, respectively, in a numerical example. It turns out that different optimality criteria can lead to different strategies.

  4. Dose-dependent biphasic leptin-induced proliferation is caused by non-specific IL-6/NF-κB pathway activation in human myometrial cells

    PubMed Central

    Barrichon, Marina; Hadi, Tarik; Wendremaire, Maeva; Ptasinski, Clémentine; Seigneuric, Renaud; Marcion, Guillaume; Delignette, Marc; Marchet, Jacques; Dumas, Monique; Sagot, Paul; Bardou, Marc; Garrido, Carmen; Lirussi, Frédéric

    2015-01-01

    Background and Purpose Leptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour (PTL), as it is able to prevent in vitro uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence. Experimental Approach We stimulated human primary myometrial smooth muscle cells with leptin in the presence or absence of receptor antagonists or signalling pathway inhibitors. Key Results Leptin induced myometrial cell proliferation in a biphasic manner. At 6.25 ng·mL−1, leptin-induced proliferation was mediated by the leptin receptor and required the early activation of ERK1/2. At a concentration above 25 ng·mL−1, leptin induced direct non-specific stimulation of the IL-6 receptor, leading to NF-κB activation, and exerted anti-proliferative effects. However, at 50 ng·mL−1, leptin re-induces proliferation via IL-6 receptor stimulation that requires STAT3 and delayed ERK1/2 activation. Conclusions and Implications These data bring new insights into leptin signalling-induced myometrial proliferation and its interrelationship with the IL-6/IL-6 receptor axis. In the light of our previous work, the present study emphasizes the potential value of leptin in the pharmacological management of PTL and it also strengthens the hypothesis that leptin might be a contributory factor in the parturition-related disorders observed in obese women. PMID:25653112

  5. Evaluation of a Unique Defibrillation Unit with Dual-Vector Biphasic Waveform Capabilities: Towards a Miniaturized Defibrillator.

    PubMed

    Okamura, Hideo; Desimone, Christopher V; Killu, Ammar M; Gilles, Emily J; Tri, Jason; Asirvatham, Roshini; Ladewig, Dejae J; Suddendorf, Scott H; Powers, Joanne M; Wood-Wentz, Christina M; Gray, Peter D; Raymond, Douglas M; Savage, Shelley J; Savage, Walter T; Bruce, Charles J; Asirvatham, Samuel J; Friedman, Paul A

    2017-02-01

    Automated external defibrillators can provide life-saving therapies to treat ventricular fibrillation. We developed a prototype unit that can deliver a unique shock waveform produced by four independent capacitors that is delivered through two shock vectors, with the rationale of providing more robust shock pathways during emergent defibrillation. We describe the initial testing and feasibility of this unique defibrillation unit, features of which may enable downsizing of current defibrillator devices. We tested our defibrillation unit in four large animal models (two canine and two swine) under general anesthesia. Experimental defibrillation thresholds (DFT) were obtained by delivery of a unique waveform shock pulse via a dual-vector pathway with four defibrillation pads (placed across the chest). DFTs were measured and compared with those of a commercially available biphasic defibrillator (Zoll M series, Zoll Medical, Chelmsford, MA, USA) tested in two different vectors. Shocks were delivered after 10 seconds of stable ventricular fibrillation and the output characteristics and shock outcome recorded. Each defibrillation series used a step-down to failure protocol to define the defibrillation threshold. A total of 96 shocks were delivered during ventricular fibrillation in four large animals. In comparison to the Zoll M series, which delivered a single-vector, biphasic shock, the energy required for successful defibrillation using the unique dual-vector biphasic waveform did not differ significantly (P = 0.65). Our early findings support the feasibility of a unique external defibrillation unit using a dual-vector biphasic waveform approach. This warrants further study to leverage this unique concept and work toward a miniaturized, portable shock delivery system. © 2016 Wiley Periodicals, Inc.

  6. Biventricular takotsubo cardiomyopathy in an elderly woman with uncontrolled type 2 diabetes: the biphasic echocardiographic and clinical pattern.

    PubMed

    Kochanowski, Janusz; Piatkowski, Radoslaw; Budnik, Monika; Jasik, Mariusz; Roik, Marek; Opolski, Grzegorz

    2016-12-01

    We describe a case of an elderly woman who was diagnosed with a biventricular takotsubo cardiomyopathy (TTC) with combination of emotional stress and poorly controlled type 2 diabetes. We observed significant correlation between biphasic improvement of right (after 4 days) and left ventricle function (after 4 weeks) with normalization glycemic status. To our knowledge, this is the first reported case in the literature of biventricular TTC with such metabolic disturbances.

  7. Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design.

    PubMed

    Cui, Haitao; Zhu, Wei; Nowicki, Margaret; Zhou, Xuan; Khademhosseini, Ali; Zhang, Lijie Grace

    2016-09-01

    A biphasic artificial vascularized bone construct with regional bioactive factors is presented using dual 3D bioprinting platform technique, thereby forming a large functional bone grafts with organized vascular networks. Biocompatible mussel-inspired chemistry and "thiol-ene" click reaction are used to regionally immobilize bioactive factors during construct fabrication for modulating or improving cellular events. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Synergistic biosynthesis of biphasic ethylene and reactive oxygen species in response to hemibiotrophic Phytophthora parasitica in tobacco plants.

    PubMed

    Wi, Soo Jin; Ji, Na Ri; Park, Ky Young

    2012-05-01

    We observed the biphasic production of ethylene and reactive oxygen species (ROS) in susceptible tobacco (Nicotiana tabacum 'Wisconsin 38') plants after shoot inoculation with Phytophthora parasitica var nicotianae. The initial transient increase in ROS and ethylene at 1 and 3 h (phase I), respectively, was followed by a second massive increase at 48 and 72 h (phase II), respectively, after pathogen inoculation. This biphasic pattern of ROS production significantly differed from the hypersensitive response exhibited by cryptogein-treated wild-type tobacco plants. The biphasic increase in ROS production was mediated by both NADPH oxidase isoforms, respiratory burst oxidase homolog (Rboh) D and RbohF. Conversely, different 1-aminocyclopropane-1-carboxylic acid synthase members were involved in specific phases of ethylene production: NtACS4 in the first phase and NtACS1 in the second phase. Biphasic production of ROS was inhibited in transgenic antisense plant lines expressing 1-aminocyclopropane-1-carboxylic acid synthase/oxidase or ethylene-insensitive3 as well as in transgenic plants impaired in ROS production. All tested transgenic plants were more tolerant against P. parasitica var nicotianae infection as determined based on trypan blue staining and pathogen proliferation. Further, silencing of NtACS4 blocked the second massive increase in ROS production as well as pathogen progression. Pathogen tolerance was due to the inhibition of ROS and ethylene production, which further resulted in lower activation of ROS-detoxifying enzymes. Accordingly, the synergistic inhibition of the second phase of ROS and ethylene production had protective effects against pathogen-induced cell damage. We conclude that the levels of ethylene and ROS correlate with compatible P. parasitica proliferation in susceptible plants.

  9. Biphasic-to-monophasic successive Co-assembly approach to yolk-shell structured mesoporous organosilica nanoparticles.

    PubMed

    Dang, Meng; Teng, Zhaogang; Su, Xiaodan; Tao, Jun; Hao, Qing; Ma, Xiaobo; Zhang, Yunlei; Li, Yanjiao; Tian, Ying; Zhang, Junjie; Lu, Guangming; Wang, Lianhui

    2017-12-01

    In this work, we report a facile biphasic-to-monophasic successive co-assembly approach to synthesize yolk-shell structured mesoporous organosilica nanoparticles (MONs). The yolk-shell structured MONs possess ethane-bridged frameworks, high surface area (1023m(2)g(-1)), radially oriented mesochannels (3.8nm), large pore volume (0.99cm(3)g(-1)), and tunable diameter (147-324nm) and shell thickness (23-53nm). The biphasic-to-monophasic successive co-assembly method is intrinsically simple and requires neither sacrificial templates nor multistep coating processes. The key of the method is that the interiors of the mesostructured organosilica nanospheres grown in the biphasic system have a lower condensation degree and Si-C-C-Si species content than the outer shells formed in the monophasic system. Thus, the interior layer is attracted by OH(-1) anions and dissolved in the monophasic system, forming the yolk-shell structures. In vitro cytotoxicity and haemolysis assays demonstrate that the ethane-bridged yolk-shell MONs possess excellent biocompatibility. Furthermore, the chemotherapy drug doxorubicin (DOX) is loaded into the yolk-shell MONs to kill drug-resistant MCF-7/ADR human breast cancer cells. Compared with free DOX and DOX-loaded typical MONs, the DOX-loaded yolk-shell MONs have higher chemotherapeutic efficacy against MCF-7/ADR cells, suggesting the great potential of yolk-shell MONs synthesized via the biphasic-to-monophasic successive co-assembly approach in the biomedical field. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  11. Design of Surface-Active Artificial Enzyme Particles to Stabilize Pickering Emulsions for High-Performance Biphasic Biocatalysis.

    PubMed

    Chen, Zhaowei; Zhao, Chuanqi; Ju, Enguo; Ji, Haiwei; Ren, Jinsong; Binks, Bernard P; Qu, Xiaogang

    2016-02-24

    Surface-active artificial enzymes (SAEs) are designed and constructed by a general and novel strategy. These SAEs can simultaneously stabilize Pickering emulsions and catalyze biphasic biotransformation with superior enzymatic stability and good re-usability; for example, for the interfacial conversion of hydrophobic p-nitrophenyl butyrate into yellow water-soluble p-nitrophenolate catalyzed by esterase-mimic SAE. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Single cell dynamic phenotyping

    PubMed Central

    Patsch, Katherin; Chiu, Chi-Li; Engeln, Mark; Agus, David B.; Mallick, Parag; Mumenthaler, Shannon M.; Ruderman, Daniel

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype tracking, and data filtering to remove erroneous cell tracks using the novel Tracking Aberration Measure (TrAM). Our workflow is broadly applicable across imaging platforms and analysis software. By applying this workflow to cancer cell assays, we reduced aberrant cell track prevalence from 17% to 2%. The cost of this improvement was removing 15% of the well-tracked cells. This enabled detection of significant motility differences between cell lines. Similarly, we avoided detecting a false change in translocation kinetics by eliminating the true cause: varied proportions of unresponsive cells. Finally, by systematically seeking heterogeneous behaviors, we detected subpopulations that otherwise could have been missed, including early apoptotic events and pre-mitotic cells. We provide optimized protocols for specific applications and step-by-step guidelines for adapting them to a variety of biological systems. PMID:27708391

  13. Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma.

    PubMed

    Wu, Di; Hiroshima, Kenzo; Yusa, Toshikazu; Ozaki, Daisuke; Koh, Eitetsu; Sekine, Yasuo; Matsumoto, Shinji; Nabeshima, Kazuki; Sato, Ayuko; Tsujimura, Tohru; Yamakawa, Hisami; Tada, Yuji; Shimada, Hideaki; Tagawa, Masatoshi

    2017-02-01

    Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.

  14. Cytocompatibility evaluation of microwave sintered biphasic calcium phosphate scaffolds synthesized using pH control.

    PubMed

    Wagner, Darcy E; Jones, Andrew D; Zhou, Huan; Bhaduri, Sarit B

    2013-04-01

    Compounds belonging to the calcium phosphate (CaP) system are known to be major constituents of bone and are bioactive to different extents in vitro and in vivo. Their chemical similarity makes them prime candidates for implants and bone tissue engineering scaffolds. CaP nanoparticles of amorphous hydroxyapatite (aHA) and dicalcium phosphate dihydrate (DCPD) were synthesized using chemical precipitation. Uniaxially pressed aHA and DCPD powders were subjected to microwave radiation to promote solid state phase transformations resulting in crystalline hydroxyapatite (HA), tricalcium phosphate (TCP) and biphasic compositions: HA/TCP and TCP/calcium pyrophosphate (CPP) and their subsequent densification. Phase composition of microwave sintered compacts was confirmed via X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Solution pH during crystal growth was found to have a profound effect on particle morphology and post-sintered phases, despite constant sintering temperature. Cytocompatibility assessment using 7F2 cells, corresponding to adult mouse osteoblasts, on microwave and conventional, furnace sintered samples demonstrated that manufacturing method does not impact cellular viability after 24 h or proliferation over 7 days. New CaP deposition and extracellular matrix components were observed in vitro via scanning electron microscopy (SEM). Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis.

    PubMed

    Huang, Yan-Feng; Zhu, Da-Jian; Chen, Xiao-Wu; Ouyang, Man-Zhao; Zhang, Wei-Jie

    2015-01-01

    The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles. MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a). ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels.

  16. Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis

    PubMed Central

    Huang, Yan-Feng; Zhu, Da-Jian; Chen, Xiao-Wu; Ouyang, Man-Zhao; Zhang, Wei-Jie

    2015-01-01

    Objectives. The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles. Methods. MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Results. Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a). Conclusions. ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels. PMID:26788499

  17. Rat lungs show a biphasic formation of new alveoli during postnatal development.

    PubMed

    Tschanz, Stefan A; Salm, Lilian A; Roth-Kleiner, Matthias; Barré, Sebastien F; Burri, Peter H; Schittny, Johannes C

    2014-07-01

    Roughly 90% of the gas-exchange surface is formed by alveolarization of the lungs. To the best of our knowledge, the formation of new alveoli has been followed in rats only by means of morphological description or interpretation of semiquantitative data until now. Therefore, we estimated the number of alveoli in rat lungs between postnatal days 4 and 60 by unambiguously counting the alveolar openings. We observed a bulk formation of new alveoli between days 4 and 21 (17.4 times increase from 0.8 to 14.3 millions) and a second phase of continued alveolarization between days 21 and 60 (1.3 times increase to 19.3 million). The (number weighted) mean volume of the alveoli decreases during the phase of bulk alveolarization from ∼593,000 μm(3) at day 4 to ∼141,000 μm(3) at day 21, but increases again to ∼298,000 μm(3) at day 60. We conclude that the "bulk alveolarization" correlates with the mechanism of classical alveolarization (alveolarization before the microvascular maturation is completed) and that the "continued alveolarization" follows three proposed mechanisms of late alveolarization (alveolarization after microvascular maturation). The biphasic pattern is more evident for the increase in alveolar number than for the formation of new alveolar septa (estimated as the length of the free septal edge). Furthermore, a striking negative correlation between the estimated alveolar size and published data on retention of nanoparticles was detected.

  18. Striatal dopamine release and biphasic pattern of locomotor and motor activity under gas narcosis.

    PubMed

    Balon, Norbert; Risso, Jean-Jacques; Blanc, François; Rostain, Jean-Claude; Weiss, Michel

    2003-05-02

    Inert gas narcosis is a neurological syndrome appearing when humans or animals are exposed to hyperbaric inert gases (nitrogen, argon) composed by motor and cognitive impairments. Inert gas narcosis induces a decrease of the dopamine release at the striatum level, structure involved in the regulation of the extrapyramidal motricity. We have investigated, in freely moving rats exposed to different narcotic conditions, the relationship between the locomotor and motor activity and the striatal dopamine release, using respectively a computerized device that enables a quantitative analysis of this behavioural disturbance and voltammetry. The use of 3 MPa of nitrogen, 2 MPa of argon and 0.1 MPa of nitrous oxide, revealed after a transient phase of hyperactivity, a lower level of the locomotor and motor activity, in relation with the decrease of the striatal dopamine release. It is concluded that the striatal dopamine decrease could be related to the decrease of the locomotor and motor hyperactivity, but that other(s) neurotransmitter(s) could be primarily involved in the behavioural motor disturbances induced by narcotics. This biphasic effect could be of major importance for future pharmacological investigations, and motor categorization, on the basic mechanisms of inert gas at pressure.

  19. Remifentanil administration reveals biphasic phMRI temporal responses in rat consistent with dynamic receptor regulation

    PubMed Central

    Liu, Christina H.; Greve, Doug N.; Dai, Guangping; Marota, John J.A.; Mandeville, Joseph B.

    2007-01-01

    Many pharmacological stimuli influence multiple neurotransmitter systems in the brain, and the dynamics of the functional brain response can vary regionally. In this study, the temporal response of cerebral blood volume (CBV) was employed to spatially segment cerebral effects due to infusion of a potent mu-opioid receptor agonist. Repeated intravenous injection of 10 ug/kg remifentanil in rats caused reproducible regional positive, negative, and biphasic changes in CBV. Three temporal processes were identified in the cerebral response and analyzed within the framework of the general linear model. Firstly, a slow component identified CBV changes that were almost exclusively negative, and the spatial distribution was similar to the inhibition produced by morphine (200 ug/kg). The largest CBV reductions occurred in caudate, accumbens, ventral hippocampus, cingulate, and piriform cortex. Secondly, a more rapid temporal component corresponded primarily with a regional distribution of positive changes in CBV consistent with GABAergic inhibition of hippocampal interneurons and associated projections. Thirdly, a response with the dynamics of mean arterial blood pressure correlated positively with CBV changes in hypothalamus, consistent with a central mechanism for control of blood pressure. We propose that the dominant source of the temporal variance in signal is dynamic modulation of drug targets by receptor endocytosis, an established effect in vitro. These results suggest that the temporal response of fMRI signal reflects underlying neurobiological processes, so that temporal decomposition strategies may aid interpretation of pharmacological mechanisms by identifying interconnected regions or those associated with common neural targets and processes. PMID:17169578

  20. Antibacterial activity evaluation of bioactive glass and biphasic calcium phosphate nanopowders mixtures

    NASA Astrophysics Data System (ADS)

    Nazemi, Zahra; Mehdikhani-Nahrkhalaji, Mehdi; Haghbin-Nazarpak, Masoumeh; Staji, Hamid; Kalani, Mohammad Mehdi

    2016-12-01

    The aim of this work was to evaluate the antibacterial activity of bioactive glass (BG) and biphasic calcium phosphate (BCP) nanopowders mixtures for the first time. 37S BG and BCP (50% HA-50% β-TCP) nanopowders were prepared via sol-gel technique. Characterization techniques such as X-ray diffraction, scanning electron microscopy, transition electron microscopy, and X-ray fluorescent. The antibacterial activity was studied using Escherichia coli and Salmonella typhi as gram-negative, and Staphylococcus aureus as gram-positive bacteria. The antibacterial effect of BG, BCP nanopowders, and their mixtures was evaluated at different concentrations. The 37S BG nanopowders showed minimum bactericidal concentration at 25 mg/ml. At broth concentrations below 300 mg/ml, BCP showed no antibacterial activity. BCP and BG nanopowders mixture (M2) with 60/40 ratio of BCP/BG showed noticeable antibacterial effect. It was concluded that BCP and 37S BG nanopowders mixture could be used as a good candidate for dental and orthopedic applications.

  1. Study on biphasic material model and mechanical analysis of knee joint cartilage

    NASA Astrophysics Data System (ADS)

    Nakatani, A.; Sakashita, A.

    2008-02-01

    A material model of articular cartilage is formulated, and fundamental problems are analyzed. The soft tissue is assumed to comprise two phases: solid and fluid. The biphasic theory proposed by Spilker and Suh (1990) to deal with such materials is reviewed, and some new additional analyses are carried out on the basis of this theory. Assuming the elasticity for the solid phase and introducing the pressure, which is defined by the product of the volume change and penalty coefficient, it is shown that the viscoelastic property of the soft tissue can be reproduced. A preferable solution is obtained for the solid phase by using the reduction integral, even if a high-order interpolation function is used. However, the high-order element cannot satisfactorily capture the velocity distribution of fluids. The pressure distribution is studied by assuming the change in the surface characteristics of the cartilage tissue with the progress of osteoarthritis. The pressure is strongly related to the lubrication conditions, i.e., perfect lubrication, perfect adhesion, and partial adhesion.

  2. Biological and abiotic dechlorination of highly chlorinated dioxins in biphasic microcosms

    SciTech Connect

    Barkovskii, A.; Adriaens, P.

    1995-12-31

    A novel experimental approach to help increase the rates and extent of reductive dechlorination of polychlorinated dibenzo-p-dioxins (PCDD) is presented. Biphasic microcosms emulsions containing eluted microorganisms derived from historically contaminated Passaic River (New Jersey) sediments, and 4% (v/v) of decane, were spiked with mg/L of octaCDD. The microcosms were amended separately with three polyphenolic compounds--catechol, resorcinol, and 3,4-dihydroxybenzoate--to help improve electron transfer during reductive dechlorination. Abiotic controls containing phenolic compounds only, and pasteurized cells were monitored along with the active microcosms. Lesser-chlorinated congeners were observed in all treatments, including killed cells, indicating the potential not only for biological and abiotic, but also biogenic dechlorination mechanisms. After 3 months of incubation, tetraCDD isomers were produced in biological incubations only, and up to 30% of the spiked octaCDD was removed. Polyphenolic compounds first appear to transiently complex with the dioxins prior to further dechlorination, and did not increase the dechlorination rates over unamended cells. Whereas the 2,3,7,8-/1,4,6,9-substitution ratio of heptachlorinated congeners increased in all treatments, 2,3,7,8-substituted hexaCDDs congeners were identified mainly in active cell incubations. Further isomer-specific analysis may thus enable distinction between abiotic and biotic dechlorination processes in anaerobic sediments.

  3. Biphasic modulation of fatty acid synthase by hydrogen peroxide in Saccharomyces cerevisiae.

    PubMed

    Matias, Ana C; Marinho, H Susana; Cyrne, Luísa; Herrero, Enrique; Antunes, Fernando

    2011-11-01

    Taking into account published contradictory results concerning the regulation of fatty acid synthase (Fas) by H(2)O(2), we carried out a systematic study where two methods of H(2)O(2) delivery (steady-state and bolus addition) and the effect of a wide range of H(2)O(2) concentrations were investigated. A decrease in Fas activity was observed for cells exposed to 100 and 150μM H(2)O(2) in a steady-state, while a bolus addition of the same H(2)O(2) concentrations did not alter Fas activity. Similar results were observed for the mRNA levels of FAS1, the gene that encodes Fas subunit β. However, the exposure to a steady-state 50μM H(2)O(2) dose lead to an increase in FAS1 mRNA levels, showing a biphasic modulation of Fas by H(2)O(2). The results obtained emphasize that cellular effects of H(2)O(2) can vary over a narrow range of concentrations. Therefore, a tight control of H(2)O(2) exposure, which can be achieved by exposing H(2)O(2) in a steady-state, is important for cellular studies of H(2)O(2)-dependent redox regulation.

  4. Effect of biphasic calcium phosphate scaffold porosities on odontogenic differentiation of human dental pulp cells.

    PubMed

    AbdulQader, Sarah T; Rahman, Ismail A; Thirumulu, Kannan P; Ismail, Hanafi; Mahmood, Zuliani

    2016-04-01

    Calcium phosphates (CaP) of different porosities have been widely and successfully used as scaffolds with osteoblast cells for bone tissue regeneration. However, the effects of scaffold porosities on cell viability and differentiation of human dental pulp cells for dentin tissue regeneration are not well known. In this study, biphasic calcium phosphate (BCP) scaffolds of 20/80 hydroxyapatite to beta tricalcium phosphate ratio with a mean pore size of 300 μm were prepared into BCP1, BCP2, BCP3, and BCP4 of 25%, 50%, 65%, and 75% of total porosities, respectively. The extracts of these scaffolds were assessed with regard to cell viability, proliferation, and differentiation of human dental pulp cells. The high alkalinity, and more calcium and phosphate ions release that were exhibited by BCP3 and BCP4 decreased the viability and proliferation of human dental pulp cells as compared to BCP1 and BCP2. BCP2 significantly increased both cell viability and cell proliferation. However, the cells cultured with BCP3 extract revealed high alkaline phosphatase (ALP) activity and high expression of odontoblast related genes, collagen type I alpha 1, dentin matrix protein-1, and dentin sialophosphoprotein as compared to that cultured with BCP1, BCP2, and BCP4 extracts. The results highlight the effect of different scaffold porosities on the cell microenvironment and demonstrate that BCP3 scaffold of 65% porosity can support human dental pulp cells differentiation for dentin tissue regeneration. © The Author(s) 2016.

  5. Predictive score for early diagnosis of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD).

    PubMed

    Tada, Hiroko; Takanashi, Jun-ichi; Okuno, Hideo; Kubota, Masaya; Yamagata, Takanori; Kawano, Gou; Shiihara, Takashi; Hamano, Shin-ichiro; Hirose, Shinichi; Hayashi, Takuya; Osaka, Hitoshi; Mizuguchi, Masashi

    2015-11-15

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) at onset manifests an early seizure (ES) usually lasting more than 30 min. Following ES, some patients exhibit almost clear consciousness with no neurological symptoms, and no MRI abnormality for a few days, which may lead to an initial misdiagnosis of prolonged febrile seizures (PFS). To allow an early diagnosis of AESD, we retrospectively analyzed clinical manifestations, laboratory data, and radiologic and EEG findings in patients with AESD (n=62) having ES of over 30 min, and ones with PFS (n=54), using logistic regression analyses. Multivariate logistic regression analysis revealed that an age below 1.5 years and a Glasgow Coma Scale score of 14 or less than 14 (Japan Coma Scale score of 1 or higher) were high risk factors of developing AESD. We proposed an AESD prediction score system consisting of consciousness level, age, duration of convulsions, enforcement of mechanical intubation, and aspartate aminotransferase, blood glucose and creatinine levels (full score: 9), the mean scores in AESD and PFS being 5.9 and 1.8, which were significantly different (p<0.001). We herein propose a scoring system for differentiating patients with AESD and PFS around the time of ES (score of 4 or more than 4 suggesting AESD), which may contribute to early therapeutic intervention and an improved neurologic outcome.

  6. Biphasic responses of human vascular smooth muscle cells to magnesium ion

    PubMed Central

    Ma, Jun; Zhao, Nan; Zhu, Donghui

    2016-01-01

    Magnesium-based alloys are promising in biodegradable cardiovascular stent applications. The degradation products of magnesium stents may have significant impacts on the surrounding vascular cells. However, knowledge on the interactions between magnesium ion and vascular cells at the molecular and cellular levels is still largely missing. Vascular smooth muscle cell (SMC) plays an important role in the pathogenesis of restenosis and wound healing after stent implantation. This study evaluated the short-term effects of extracellular magnesium ion (Mg2+) on the cellular behaviors of SMCs. Cellular responses to Mg2+ were biphasic and in a concentration-dependent manner. Low concentrations (10 mM) of Mg2+ increased cell viability, cell proliferation rate, cell adhesion, cell spreading, cell migration rate, and actin expression. In contrast, higher concentrations (40–60 mM) of Mg2+ had deleterious effects on cells. Gene expression analysis revealed that Mg2+ altered the expressions of genes mostly related to cell adhesion, cell injury, angiogenesis, inflammation, coagulation, and cell growth. Finding from this study provides some valuable information on SMC responses toward magnesium ions at the cellular and molecular levels, and guidance for future controlled release of magnesium from the stent material. PMID:26402437

  7. Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors

    PubMed Central

    Vedvyas, Yogindra; Shevlin, Enda; Zaman, Marjan; Min, Irene M.; Park, Spencer; Park, Susan; Kwon, Keon-Woo; Smith, Turner; Luo, Yonghua; Kim, Dohyun; Kim, Young; Law, Benedict; Ting, Richard; Jin, Moonsoo M.

    2016-01-01

    Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood analyses to discern T cell activity. While useful, these data are 1-dimensional and lack spatiotemporal information related to treatment efficacy or toxicity. We utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), and PET, to quantitatively and longitudinally visualize whole-body T cell distribution and antitumor dynamics using a clinically approved radiotracer. Initial evaluations determined that SSTR2-expressing T cells were detectable at low densities with high sensitivity and specificity. SSTR2-based PET was applied to ACT of chimeric antigen receptor (CAR) T cells targeting intercellular adhesion molecule-1, which is overexpressed in anaplastic thyroid tumors. Timely CAR T cell infusions resulted in survival of tumor-bearing mice, while later infusions led to uniform death. Real-time PET imaging revealed biphasic T cell expansion and contraction at tumor sites among survivors, with peak tumor burden preceding peak T cell burden by several days. In contrast, nonsurvivors displayed unrelenting increases in tumor and T cell burden, indicating that tumor growth was outpacing T cell killing. Thus, longitudinal PET imaging of SSTR2-positive ACT dynamics enables prognostic, spatiotemporal monitoring with unprecedented clarity and detail to facilitate comprehensive therapy evaluation with potential for clinical translation. PMID:27882353

  8. Bone in-growth induced by biphasic calcium phosphate ceramic in femoral defect of dogs.

    PubMed

    Manjubala, I; Sastry, T P; Kumar, R V Suresh

    2005-04-01

    Biphasic calcium phosphate (BCP) ceramics consisting of hydroxyapatite (HA) and tricalcium phosphate (TCP) has been used as a bone graft material during the last decade. In this paper, we report the bone in-growth induced by BCP ceramic in the experimentally created circular defects in the femur of dogs. This BCP ceramic consists of 55% hydroxyapatite (HA) and 45% b-tricalcium phosphate (TCP) prepared in situ by the microwave method. The defects were created as 4-mm holes on the lateral aspect of the femur of dogs and the holes were packed with the implant material. The defective sites were radiographed at a period of 4, 8, and 12 weeks postoperatively. The radiographical results showed that the process of ossification started after 4 weeks and the defect was completely filled with new woven bone after 12 weeks. Histological examination of the tissue showed the formation of osteoblast inducing the osteogenesis in the defect. The collageneous fibrous matrix and the complete Haversian system were observed after 12 weeks. The blood serum was collected postoperatively and biochemical assays for alkaline phosphatase activity were carried out. The measurement of alkaline phosphatase activity levels also correlated with the formation of osteoblast-like cells. This microwave-prepared BCP ceramic has proved to be a good biocompatible implant as well as osteoconductive and osteoinductive materials to fill bone defects.

  9. Quantifying Cartilage Contact Modulus, Tension Modulus, and Permeability With Hertzian Biphasic Creep.

    PubMed

    Moore, A C; DeLucca, J F; Elliott, D M; Burris, D L

    2016-10-01

    This paper describes a new method, based on a recent analytical model (Hertzian biphasic theory (HBT)), to simultaneously quantify cartilage contact modulus, tension modulus, and permeability. Standard Hertzian creep measurements were performed on 13 osteochondral samples from three mature bovine stifles. Each creep dataset was fit for material properties using HBT. A subset of the dataset (N = 4) was also fit using Oyen's method and FEBio, an open-source finite element package designed for soft tissue mechanics. The HBT method demonstrated statistically significant sensitivity to differences between cartilage from the tibial plateau and cartilage from the femoral condyle. Based on the four samples used for comparison, no statistically significant differences were detected between properties from the HBT and FEBio methods. While the finite element method is considered the gold standard for analyzing this type of contact, the expertise and time required to setup and solve can be prohibitive, especially for large datasets. The HBT method agreed quantitatively with FEBio but also offers ease of use by nonexperts, rapid solutions, and exceptional fit quality (R(2 )= 0.999 ± 0.001, N = 13).

  10. Interfacial Tensions of Aged Organic Aerosol Particle Mimics Using a Biphasic Microfluidic Platform.

    PubMed

    Metcalf, Andrew R; Boyer, Hallie C; Dutcher, Cari S

    2016-02-02

    Secondary organic aerosol (SOA) particles are a major component of atmospheric particulate matter, yet their formation processes and ambient properties are not well understood. These complex particles often contain multiple interfaces due to internal aqueous- and organic-phase partitioning. Aerosol interfaces can profoundly affect the fate of condensable organic compounds emitted into the atmosphere by altering the way in which ambient organic vapors interact with suspended particles. To accurately predict the evolution of SOA in the atmosphere, we must improve our understanding of aerosol interfaces. In this work, biphasic microscale flows are used to measure interfacial tension of reacting methylglyoxal, formaldehyde, and ammonium sulfate aqueous mixtures with a surrounding oil phase. Our experiments show a suppression of interfacial tension as a function of organic content that remains constant with reaction time for methylglyoxal-ammonium sulfate systems. We also reveal an unexpected time dependence of interfacial tension over a period of 48 h for ternary solutions of both methylglyoxal and formaldehyde in aqueous ammonium sulfate, indicating a more complicated behavior of surface activity where there is competition among dissolved organics. From these interfacial tension measurements, the morphology of aged atmospheric aerosols with internal liquid-liquid phase separation is inferred.

  11. [Biphasic effect of angiotensin II on conditioned reflectory reaction patterns in albino rats].

    PubMed

    Hecht, K; Hecht, T; Poppei, M; Treptow, K; Choinowski, S; Nitschkoff, S

    1975-01-01

    40 male albino rats were used to investigate the influence of one single i. v. dose of 10 ng/kg Angiotensin II upon established and stabilized conditional-reflectory response pattern (two-dimensional conditional-reflectory decision process and periodicities of conditional-reflectory processes). At normotonous blood-pressure values, Angiotensin II exerted a biphasic action on the conditional-reflectory response pattern. In the first phase of action (up to 30 min after injection) there prevailed centralnervous inhibition processes, while the second phase of action (30-70 min after injection) was marked by a general centralnervous excitation, which is reflected by extremely short times of response, and a pronounced sensitivity to optic, acoustic and tactile stimuli. The decision capacity of the animals was considerably reduced in both phases. The periodicities of conditional-reflectory processes (duration of periods in the minute range) are strongly disturbed in the first phase of action, and tend to normal in the second phase. Furthermore, Angiotensin II was found to have a selective, hierarchically ordered influence with regard to the duration and intensity of action. Thus, the information processing activity of the CNS underwent most pronounced changes. The centralnervous regulatory functions were less affected; the blood pressure regulation showed little and transient influence by Angiotensin II. In the discussion, the neurotropic and algogenic action of Angiotensin II, and the relation of the octapeptide effect with pathogenetic mechanisms of experimental neurotically induced hypertonia are dealt with.

  12. Good's buffers as novel phase-forming components of ionic-liquid-based aqueous biphasic systems.

    PubMed

    Luís, Andreia; Dinis, Teresa B V; Passos, Helena; Taha, Mohamed; Freire, Mara G

    2015-09-15

    Aiming at the development of self-buffering and benign extraction/separation processes, this work reports a novel class of aqueous biphasic systems (ABS) composed of ionic liquids (ILs) and organic biological buffers (Good's buffers, GBs). A large array of ILs and GBs was investigated, revealing than only the more hydrophobic and fluorinated ILs are able to form ABS. For these systems, the phase diagrams, tie-lines, tie-line lengths, and critical points were determined at 25 °C. The ABS were then evaluated as alternative liquid-liquid extraction strategies for two amino acids (L-phenylalanine and L-tryptophan). The single-step extraction efficiencies for the GB-rich phase range between 22.4 and 100.0 % (complete extraction). Contrarily to the most conventional IL-salt ABS, in most of the systems investigated, the amino acids preferentially migrate for the most biocompatible and hydrophilic GB-rich phase. Remarkably, in two of the studied ABS, L-phenylalanine completely partitions to the GB-rich phase while L-tryptophan shows a preferential affinity for the opposite phase. These results show that the extraction efficiencies of similar amino acids can be tailored by the design of the chemical structures of the phase-forming components, creating thus new possibilities for the use of IL-based ABS in biotechnological separations.

  13. Kinetic modelling and microbial community assessment of anaerobic biphasic fixed film bioreactor treating distillery spent wash.

    PubMed

    Acharya, Bhavik K; Pathak, Hilor; Mohana, Sarayu; Shouche, Yogesh; Singh, Vasdev; Madamwar, Datta

    2011-08-01

    Anaerobic digestion, microbial community structure and kinetics were studied in a biphasic continuously fed, upflow anaerobic fixed film reactor treating high strength distillery wastewater. Treatment efficiency of the bioreactor was investigated at different hydraulic retention times (HRT) and organic loading rates (OLR 5-20 kg COD m⁻³ d⁻¹). Applying the modified Stover-Kincannon model to the reactor, the maximum removal rate constant (U(max)) and saturation value constant (K(B)) were found to be 2 kg m⁻³ d⁻¹ and 1.69 kg m⁻³ d⁻¹ respectively. Bacterial community structures of acidogenic and methanogenic reactors were assessed using culture-independent analyses. Sequencing of 16S rRNA genes exhibited a total of 123 distinct operational taxonomic units (OTUs) comprising 49 from acidogenic reactor and 74 (28 of eubacteria and 46 of archaea) from methanogenic reactor. The findings reveal the role of Lactobacillus sp. (Firmicutes) as dominant acid producing organisms in acidogenic reactor and Methanoculleus sp. (Euryarchaeotes) as foremost methanogens in methanogenic reactor.

  14. Forging And Milling Contribution On Residual Stresses For A Textured Biphasic Titanium Alloy

    SciTech Connect

    Deleuze, C.; Fabre, A.; Barrallier, L.; Molinas, O.

    2011-01-17

    Ti-10V-2Fe-3Al is a biphasic titanium alloy ({alpha}+{beta}) used in aeronautical applications for its mechanical properties, such as its yield strength of 1200 MPa and it weighs 40% less than steel. This alloy is particularly useful for vital parts with complex geometry, because of its high forging capability. In order to predict the capability for fatigue lifetime, the designers need to know the residual stresses. X-Ray diffraction is the main experimental technique used to determine residual stresses on the surface. In this case, stress levels are primarily influenced by the complex forging and milling process. On this alloy in particular, it may be difficult to characterize stress due to modification of the microstructure close to the surface. Results obtained by x-ray analysis depend on the correct definition of the shape of the diffraction peaks. The more precisely defined the position of the peak, the more accurately the stresses are evaluated. This paper presents a method to detect if residual stresses can be characterized by x-ray diffraction. The characterization of hardness seems to be a relevant technique to quickly analyze the capability of x-ray diffraction to determine residual stresses.

  15. Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration.

    PubMed

    Matsuoka, Hiroshi; Obama, Hiroya; Kelly, Meghan L; Matsui, Toshimitsu; Nakamoto, Masaru

    2005-08-12

    EphB6 is a unique member in the Eph family of receptor tyrosine kinases in that its kinase domain contains several alterations in conserved amino acids and is catalytically inactive. Although EphB6 is expressed both in a variety of embryonic and adult tissues, biological functions of this receptor are largely unknown. In the present study, we examined the function of EphB6 in cell adhesion and migration. We demonstrated that EphB6 exerted biphasic effects in response to different concentrations of the ephrin-B2 ligand; EphB6 promoted cell adhesion and migration when stimulated with low concentrations of ephrin-B2, whereas it induced repulsion and inhibited migration upon stimulation with high concentrations of ephrin-B2. A truncated EphB6 receptor lacking the cytoplasmic domain showed monophasic-positive effects on cell adhesion and migration, indicating that the cytoplasmic domain is essential for the negative effects. EphB6 is constitutively associated with the Src family kinase Fyn. High concentrations of ephrin-B2 induced tyrosine phosphorylation of EphB6 through an Src family kinase activity. These results indicate that EphB6 can both positively and negatively regulate cell adhesion and migration, and suggest that tyrosine phosphorylation of the receptor by an Src family kinase acts as the molecular switch for the functional transition.

  16. Substitution of osteoporotic alveolar bone by biphasic calcium phosphate/poly-DL-lactide-co-glycolide biomaterials.

    PubMed

    Ajduković, Zorica; Zorica, Ajduković; Ignjatović, Nenad; Nenad, Ignjatović; Petrović, Dragan; Dragan, Petrović; Uskoković, Dragan; Dragan, Uskoković

    2007-01-01

    Lost bone tissue due to osteoporosis makes dentistry very difficult. The aim of thisstudy is to reconstruct the bone tissue with composite biomaterials and to estimate the optical density and alveolar ridge height of the mandible. Research is conducted on 30 postmenopausal women aged from 46 to 62 years, with diagnosed osteoporosis and defects in alveolar bones caused by extraction of paradontopathic teeth, enucleation of cysts and periapical changes, extraction of impacted teeth,or by trauma.Biphasic calcium phosphate/poly-DL-lactide-co-glycolide (BCP/PLGA) composite is implanted into the defects of alveolar bones. Six weeks after implantation of BCP/PLGA, the alveolar bone density in the region of premolars on the experimental side of the jaw is found to be lower than that on the untreated, control, side of the jaw. On thecontrary, 24 weeks after implantation, it is significantly higher compared with the density of the control side. A significant increase in optical density of alveolar bones in the region of premolars on the experimental side compared with the control one is noticed. These results indicate a high level of osteoregeneration and osteoblast activity. Synthetic BCP/PLGA composite belongs to the group of biomaterials, which facilitate formation of new bones and rehabilitation of alveolar bones weakened by osteoporosis. Because of its osteoconductive characteristics, BCP/PLGA composite is supposed to be the material of choice for replacement of bone tissue in the future.

  17. Biphasic effects of acetylstrophanthidin on automaticity in guinea pig ventricular muscle.

    PubMed

    Karagueuzian, H S; Katzung, B G

    1982-04-23

    The effects of acetylstrophanthidin (AS) on depolarization-induced automaticity and contractility of guinea pig papillary muscle were studied in a single sucrose gap chamber with microelectrode and current-clamp techniques. The concentration used, 1.4-1.8 microM, never induced automaticity in preparations at their normal resting potential. Twenty min after superfusion with AS, action potential duration (APD) was prolonged and the force of contraction increased. These were associated with an increase in slope of phase 4 depolarization and an increase in the membrane resistance (Rm) of muscles depolarized with small constant current pulses. With longer (50-80 min) periods of AS superfusion, APD became shorter, Rm decreased to less than predrug values, and in depolarized preparations, the slope of phase 4 decreased. Contractility remained unchanged throughout this second phase. All of these effects were fully reversible upon 60 min of superfusion with AS-free Tyrode solution. We suggest that the biphasic effects of AS on the automaticity of depolarized ventricular muscle cells are caused by an initial decrease followed by a later increase in transmembrane potassium conductance.

  18. Changes in biphasic electrode impedance with protein adsorption and cell growth

    PubMed Central

    Newbold, Carrie; Richardson, Rachael; Millard, Rodney; Huang, Christie; Milojevic, Dusan; Shepherd, Robert; Cowan, Robert

    2012-01-01

    This study was undertaken to assess the contribution of protein adsorption and cell growth to increases in electrode impedance that occur immediately following implantation of cochlear implant electrodes and other neural stimulation devices. An in vitro model of the electrode-tissue interface was used. Radiolabelled albumin in phosphate buffered saline was added to planar gold electrodes and electrode impedance measured using a charge-balanced biphasic current pulse. The polarisation impedance component increased with protein adsorption, while no change to access resistance was observed. The maximum level of protein adsorbed was measured at 0.5 μg/cm2, indicating a tightly packed monolayer of albumin molecules on the gold electrode and resin substrate. Three cell types were grown over the electrodes, macrophage cell line J774, dissociated fibroblasts and epithelial cell line MDCK, all of which created a significant increase in electrode impedance. As cell cover over electrodes increased, there was a corresponding increase in the initial rise in voltage, suggesting cell cover mainly contributes to the access resistance of the electrodes. Only a small increase in the polarisation component of impedance was seen with cell cover. PMID:20841637

  19. Biphasic changes in body temperature produced by intracerebroventricular injections of histamine in the cat.

    PubMed

    Clark, W G; Cumby, H R

    1976-09-01

    1. Intracerebroventricular administration of histamine to cats caused hypothermia followed by a rise in body temperature. 2-Methylhistamine caused a similar biphasic response, while 3-methylhistamine had no effect on body temperature and 4-methylhistamine produced a delayed hyperthermia. Some tolerance to the hypothermic activity developed when a series of closely spaced injections of histamine was given. 2. Doses of histamine and 2-methylhistamine which altered body temperature when given centrally were ineffective when infused or injected I.V. 3. Pyrilamine, an H1-receptor antagonist, prevented the hypothermic response to histamine. 4. Hypothermic responses to histamine at an environmental temperature of 22 degrees C were comparable to responses in a cold room at 4 degrees C in both resting animals and animals acting to depress a lever to escape an external heat load. A change in error signal from the thermostat could account for these results. However, lesser degrees of hypothermia developed when histamine was given to animals in a hot environment. In some, but not all animals, this smaller response could be attributed to inadequate heat loss in spite of maximal activation of heat-loss mechanisms. 5. The hyperthermic response to histamine was antagonized by central, but not peripheral, injection of metiamide, an H2-receptor antagonist. 6. The results indicate that histamine and related agents can act centrally to cause both hypothermia, mediated by H1-receptors, and hyperthermia, mediated by H2-receptors.

  20. Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system.

    PubMed

    Chiavegatto, S; Nasello, A G; Bernardi, M M

    1998-01-01

    The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H3-antagonist thioperamide and was also induced by the H3-agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activity. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H1-receptor activation. The participation of H2-receptors requires further investigation.

  1. Estimation of the biphasic property in a female's menstrual cycle from cutaneous temperature measured during sleep.

    PubMed

    Chen, Wenxi; Kitazawa, Masumi; Togawa, Tatsuo

    2009-09-01

    This paper proposes a method to estimate a woman's menstrual cycle based on the hidden Markov model (HMM). A tiny device was developed that attaches around the abdominal region to measure cutaneous temperature at 10-min intervals during sleep. The measured temperature data were encoded as a two-dimensional image (QR code, i.e., quick response code) and displayed in the LCD window of the device. A mobile phone captured the QR code image, decoded the information and transmitted the data to a database server. The collected data were analyzed by three steps to estimate the biphasic temperature property in a menstrual cycle. The key step was an HMM-based step between preprocessing and postprocessing. A discrete Markov model, with two hidden phases, was assumed to represent higher- and lower-temperature phases during a menstrual cycle. The proposed method was verified by the data collected from 30 female participants, aged from 14 to 46, over six consecutive months. By comparing the estimated results with individual records from the participants, 71.6% of 190 menstrual cycles were correctly estimated. The sensitivity and positive predictability were 91.8 and 96.6%, respectively. This objective evaluation provides a promising approach for managing premenstrual syndrome and birth control.

  2. Biphasic calcium phosphates: influence of three synthesis parameters on the HA/beta-TCP ratio.

    PubMed

    Bouler, J M; LeGeros, R Z; Daculsi, G

    2000-09-15

    Hydroxyapatite (HA) contents measurements were conducted on eight biphasic calcium phosphate (BCP) samples obtained by sintering calcium-deficient apatite formed previously by hydrolyzing a dicalcium phosphate dihydrate (DCPD) powder. We evaluated the influences and interactions of three synthesis factors: alkalinity, process duration, and concentration of the water suspension in DCPD. Those parameters were varied simultaneously between two limit levels. Experiments used a factorial design method (FDM) allowing optimization of the number of samples as well as statistical analysis of results. FDM showed that HA content, in a defined experimental area, can be described by a first-order polynomial equation in which the initial alcalinity and the DCPD/water ratio are the major influences. Experiment prove that pH measured at the end of the hydrolysis was predictive of the HA content in the final BCP. This study leads up to an isoresponse line diagram which will allow the synthesis of some BCP with fitted HA/beta-tricalcium phosphate ratios.

  3. Extraction of Biomolecules Using Phosphonium-Based Ionic Liquids + K3PO4 Aqueous Biphasic Systems

    PubMed Central

    Louros, Cláudia L. S.; Cláudio, Ana Filipa M.; Neves, Catarina M. S. S.; Freire, Mara G.; Marrucho, Isabel M.; Pauly, Jérôme; Coutinho, João A. P.

    2010-01-01

    Aqueous biphasic systems (ABS) provide an alternative and efficient approach for the extraction, recovery and purification of biomolecules through their partitioning between two liquid aqueous phases. In this work, the ability of hydrophilic phosphonium-based ionic liquids (ILs) to form ABS with aqueous K3PO4 solutions was evaluated for the first time. Ternary phase diagrams, and respective tie-lines and tie-lines length, formed by distinct phosphonium-based ILs, water, and K3PO4 at 298 K, were measured and are reported. The studied phosphonium-based ILs have shown to be more effective in promoting ABS compared to the imidazolium-based counterparts with similar anions. Moreover, the extractive capability of such systems was assessed for distinct biomolecules (including amino acids, food colourants and alkaloids). Densities and viscosities of both aqueous phases, at the mass fraction compositions used for the biomolecules extraction, were also determined. The evaluated IL-based ABS have been shown to be prospective extraction media, particularly for hydrophobic biomolecules, with several advantages over conventional polymer-inorganic salt ABS. PMID:20480041

  4. Biphasic and Stage-Associated Expression of CPEB4 in Hepatocellular Carcinoma

    PubMed Central

    Lee, Ming-Che; Chang, Ying-Chen; Hwang, Pei-Ing; Huang, Yi-Shuian; Cheng, Ching-Feng

    2016-01-01

    Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a sequence-specific RNA-binding protein and translational regulator, with expression associated with tumor progression. Nevertheless, CPEB4 seems to play paradoxical roles in cancers–an oncogenic promoter in pancreatic ductal adenocarcinoma (PDA) and glioblastomas but a tumor suppressor in hepatocellular carcinoma (HCC). To assess whether CPEB4-regulated carcinogenesis is tissue-specific, we reevaluated the role of CPEB4 in HCC. Although proliferation of hepatocytes appeared normal in CPEB4-knockout (KO) mice after partial hepatectomy, knockdown (KD) of CPEB4 in HepG2 liver cancer cells promoted colony formation in vitro. Moreover, the growth of CPEB4-KD cells was accelerated in an in vivo xenograft mouse model. In tumorous and adjacent non-tumorous paired liver specimens from 49 HCC patients, the protein level of CPEB4 was significantly upregulated in early-stage HCC but decreased toward late-stage HCC. This finding agrees with changes in CPEB4 mRNA level from analysis of two sets of HCC microarray data from the Gene Expression Omnibus (GEO) database. Taken together, downregulation of CPEB4 likely occurs at the late cancer stage to facilitate HCC progression. Biphasic alteration of CPEB4 expression during HCC progression suggests its complicated role in tumorigenesis. PMID:27158894

  5. A biphasic viscohyperelastic fibril-reinforced model for articular cartilage: formulation and comparison with experimental data.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2007-01-01

    Experiments in articular cartilage have shown highly nonlinear stress-strain curves under finite deformations, nonlinear tension-compression response as well as intrinsic viscous effects of the proteoglycan matrix and the collagen fibers. A biphasic viscohyperelastic fibril-reinforced model is proposed here, which is able to describe the intrinsic viscoelasticity of the fibrillar and nonfibrillar components of the solid phase, the nonlinear tension-compression response and the nonlinear stress-strain curves under tension and compression. A viscohyperelastic constitutive equation was used for the matrix and the fibers encompassing, respectively, a hyperelastic function used previously for the matrix and a hyperelastic law used before to represent biological connective tissues. This model, implemented in an updated Lagrangian finite element code, displayed good ability to follow experimental stress-strain equilibrium curves under tension and compression for human humeral cartilage. In addition, curve fitting of experimental reaction force and lateral displacement unconfined compression curves showed that the inclusion of viscous effects in the matrix allows the description of experimental data with material properties for the fibers consistent with experimental tensile tests, suggesting that intrinsic viscous effects in the matrix of articular cartilage plays an important role in the mechanical response of the tissue.

  6. Primary pulmonary biphasic synovial sarcoma: a case report and literature review.

    PubMed

    Alcaraz-García, Pedro; Díaz-Palacios, Salvador; Castillo-Canto, Carlos; Gatica-Pérez, Amancio; Sánchez-González, Jesús Armando

    2012-01-01

    Primary synovial sarcomas of the lung are extremely rare, constituting 0.1% to 0.5% of lung cancers. The first case was reported by Gaertner in 1996. We present the case of a 15-year-old female who presented with cough, white-colored secretions, right-sided chest pain and progressive dyspnea. Physical examination revealed increased exertion during breathing with no cyanosis. The presence of right scapular pulmonary condensation syndrome was observed. Chest x-ray demonstrated homogeneous opacity occupying the lower two thirds of the right hemithorax. Posterolateral thoracotomy with right lower and medium lobectomy was performed. Because there was evidence of upper lobe tumor, it was decided to carry out a right pneumonectomy. Histopathological diagnosis was biphasic synovial sarcoma. The presentation of pulmonary synovial sarcoma generally shows a peripheral location with a nonencapsulated and well-circumscribed tumor. Size ranges from 0.6 to 17 cm (mean: 5 cm). Histology is often characterized by a monophasic pattern. Diagnosis is difficult except for a uniform spindle cell pattern. Most synovial sarcomas show immunoreactivity for cytokeratin and/or epithelial membrane antigen. Cytogenetic characteristic of synovial sarcoma are t(X; 18)(p11, q11). Patient prognosis for pulmonary synovial sarcoma is poor with an overall 5-year survival rate of 50%.

  7. Biphasic responses of human vascular smooth muscle cells to magnesium ion.

    PubMed

    Ma, Jun; Zhao, Nan; Zhu, Donghui

    2016-02-01

    Magnesium-based alloys are promising in biodegradable cardiovascular stent applications. The degradation products of magnesium stents may have significant impacts on the surrounding vascular cells. However, knowledge on the interactions between magnesium ion and vascular cells at the molecular and cellular levels is still largely missing. Vascular smooth muscle cell (SMC) plays an important role in the pathogenesis of restenosis and wound healing after stent implantation. This study evaluated the short-term effects of extracellular magnesium ion (Mg(2+)) on the cellular behaviors of SMCs. Cellular responses to Mg(2+) were biphasic and in a concentration-dependent manner. Low concentrations (10 mM) of Mg(2+) increased cell viability, cell proliferation rate, cell adhesion, cell spreading, cell migration rate, and actin expression. In contrast, higher concentrations (40-60 mM) of Mg(2+) had deleterious effects on cells. Gene expression analysis revealed that Mg(2+) altered the expressions of genes mostly related to cell adhesion, cell injury, angiogenesis, inflammation, coagulation, and cell growth. Finding from this study provides some valuable information on SMC responses toward magnesium ions at the cellular and molecular levels, and guidance for future controlled release of magnesium from the stent material. © 2015 Wiley Periodicals, Inc.

  8. Aerosol Particle Interfacial Thermodynamics and Phase Partitioning Measurements Using Biphasic Microfluidics

    NASA Astrophysics Data System (ADS)

    Dutcher, Cari; Metcalf, Andrew

    2015-03-01

    Secondary organic aerosol particles are nearly ubiquitous in the atmosphere and yet there remain large uncertainties in their formation processes and ambient properties. These particles are complex microenvironments, which can contain multiple interfaces due to internal aqueous-organic phase partitioning and to the external liquid-vapor surface. Interfacial properties affect the ambient aerosol morphology, or internal structure of the particle, which in turn can affect the way a particle interacts with an environment of condensable clusters and organic vapors. To improve our ability to accurately predict ambient aerosol morphology, we must improve our knowledge of aerosol interfaces and their interactions with the ambient environment. Unfortunately, many techniques employed to measure interfacial properties do so in bulk solutions or in the presence of a ternary (e.g. solid) phase. In this talk, a novel method using biphasic microscale flows will be introduced for generating, trapping, and perturbing complex interfaces at atmospherically relevant conditions. These microfluidic experiments utilize high-speed imaging to monitor interfacial phenomena at the microscale and are performed with phase contrast and fluorescence microscopy on a temperature-controlled inverted microscope stage. From these experiments, interfacial thermodynamic properties such as surface or interfacial tension, rheological properties such as interfacial moduli, and kinetic properties such as mass transfer coefficients can be measured or inferred.

  9. Automated biphasic morphological assessment of hepatitis B-related liver fibrosis using second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Wang, Tong-Hong; Chen, Tse-Ching; Teng, Xiao; Liang, Kung-Hao; Yeh, Chau-Ting

    2015-08-01

    Liver fibrosis assessment by biopsy and conventional staining scores is based on histopathological criteria. Variations in sample preparation and the use of semi-quantitative histopathological methods commonly result in discrepancies between medical centers. Thus, minor changes in liver fibrosis might be overlooked in multi-center clinical trials, leading to statistically non-significant data. Here, we developed a computer-assisted, fully automated, staining-free method for hepatitis B-related liver fibrosis assessment. In total, 175 liver biopsies were divided into training (n = 105) and verification (n = 70) cohorts. Collagen was observed using second harmonic generation (SHG) microscopy without prior staining, and hepatocyte morphology was recorded using two-photon excitation fluorescence (TPEF) microscopy. The training cohort was utilized to establish a quantification algorithm. Eleven of 19 computer-recognizable SHG/TPEF microscopic morphological features were significantly correlated with the ISHAK fibrosis stages (P < 0.001). A biphasic scoring method was applied, combining support vector machine and multivariate generalized linear models to assess the early and late stages of fibrosis, respectively, based on these parameters. The verification cohort was used to verify the scoring method, and the area under the receiver operating characteristic curve was >0.82 for liver cirrhosis detection. Since no subjective gradings are needed, interobserver discrepancies could be avoided using this fully automated method.

  10. Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes

    PubMed Central

    Kobayashi, Hiroshi; Chang, Song Ho; Mori, Daisuke; Itoh, Shozo; Hirata, Makoto; Hosaka, Yoko; Taniguchi, Yuki; Okada, Keita; Mori, Yoshifumi; Yano, Fumiko; Chung, Ung-il; Akiyama, Haruhiko; Kawaguchi, Hiroshi; Tanaka, Sakae; Saito, Taku

    2016-01-01

    In vitro studies have shown that Rela/p65, a key subunit mediating NF-κB signalling, is involved in chondrogenic differentiation, cell survival and catabolic enzyme production. Here, we analyse in vivo functions of Rela in embryonic limbs and adult articular cartilage, and find that Rela protects chondrocytes from apoptosis through induction of anti-apoptotic genes including Pik3r1. During skeletal development, homozygous knockout of Rela leads to impaired growth through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela does not alter growth. In articular cartilage, homozygous knockout of Rela at 7 weeks leads to marked acceleration of osteoarthritis through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela results in suppression of osteoarthritis development through inhibition of catabolic gene expression. Haploinsufficiency or a low dose of an IKK inhibitor suppresses catabolic gene expression, but does not alter anti-apoptotic gene expression. The biphasic regulation of chondrocytes by Rela contributes to understanding the pathophysiology of osteoarthritis. PMID:27830706

  11. A formal model of asynchronous communication and its use in mechanically verifying a biphase mark protocol

    NASA Technical Reports Server (NTRS)

    Moore, J. Strother

    1992-01-01

    In this paper we present a formal model of asynchronous communication as a function in the Boyer-Moore logic. The function transforms the signal stream generated by one processor into the signal stream consumed by an independently clocked processor. This transformation 'blurs' edges and 'dilates' time due to differences in the phases and rates of the two clocks and the communications delay. The model can be used quantitatively to derive concrete performance bounds on asynchronous communications at ISO protocol level 1 (physical level). We develop part of the reusable formal theory that permits the convenient application of the model. We use the theory to show that a biphase mark protocol can be used to send messages of arbitrary length between two asynchronous processors. We study two versions of the protocol, a conventional one which uses cells of size 32 cycles and an unconventional one which uses cells of size 18. We conjecture that the protocol can be proved to work under our model for smaller cell sizes and more divergent clock rates but the proofs would be harder.

  12. Micropore-induced Capillarity Enhances Bone Distribution in vivo in Biphasic Calcium Phosphate Scaffolds

    PubMed Central

    Rustom, Laurence E.; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W.; Lu, Yan; Markel, Mark D.; Picart, Catherine; Wagoner Johnson, Amy J.

    2016-01-01

    The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF¯, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF¯ of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. PMID:27544807

  13. Work Stress and Alcohol Use: Developing and Testing a Biphasic Self-Medication Model.

    PubMed

    Frone, Michael R

    2016-01-01

    This study developed and tested a moderated-mediation model of work stress and alcohol use, based on the biphasic (stimulant and sedative) effects of alcohol and the self-medication and stress-vulnerability models of alcohol use. The model proposes that exposure to work stressors can increase both negative affect and work fatigue, and that these two sources of strain can subsequently motivate the use of alcohol. However, the relations of negative affect and work fatigue to alcohol use are conditional on the joint moderating effects of alcohol outcome expectancies and gender. Data were collected from a national probability sample of 2,808 U.S. workers. Supporting the model, the results indicated that work stressor exposure was conditionally related via negative affect to heavy alcohol use among both men and women holding strong tension reduction alcohol expectancies and to after work alcohol use among men holding strong tension reduction alcohol expectancies. Also, work stressor exposure was conditionally related via work fatigue to both heavy alcohol use and workday alcohol use among men holding strong fatigue reduction alcohol expectancies. The results have application in the identification of individuals at higher risk of problematic alcohol use and are relevant to workplace safety and to the design of appropriate interventions.

  14. Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process.

    PubMed

    Yang, Liu; He, Jianfeng; Shen, Yi; Li, Xiaowei; Sun, Jielin; Czajkowsky, Daniel M; Shao, Zhifeng

    2016-08-16

    Our quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition.

  15. High-solids biphasic CO2-H2O pretreatment of lignocellulosic biomass.

    PubMed

    Luterbacher, Jeremy S; Tester, Jefferson W; Walker, Larry P

    2010-10-15

    A high pressure (200 bar) CO(2)-H(2)O process was developed for pretreating lignocellulosic biomass at high-solid contents, while minimizing chemical inputs. Hardwood was pretreated at 20 and 40 (wt.%) solids. Switchgrass, corn stover, big bluestem, and mixed perennial grasses (a co-culture of big bluestem and switchgrass) were pretreated at 40 (wt.%) solids. Operating temperatures ranged from 150 to 250 degrees C, and residence times from 20 s to 60 min. At these conditions a biphasic mixture of an H(2)O-rich liquid (hydrothermal) phase and a CO(2)-rich supercritical phase coexist. Following pretreatment, samples were then enzymatically hydrolyzed. Total yields, defined as the fraction of the theoretical maximum, were determined for glucose, hemicellulose sugars, and two degradation products: furfural and 5-hydroxymethylfurfural. Response surfaces of yield as a function of temperature and residence time were compared for different moisture contents and biomass species. Pretreatment at 170 degrees C for 60 min gave glucose yields of 77%, 73%, and 68% for 20 and 40 (wt.%) solids mixed hardwood and mixed perennial grasses, respectively. Pretreatment at 160 degrees C for 60 min gave glucan to glucose yields of 81% for switchgrass and 85% for corn stover.

  16. Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process

    PubMed Central

    Yang, Liu; He, Jianfeng; Shen, Yi; Li, Xiaowei; Sun, Jielin; Czajkowsky, Daniel M.; Shao, Zhifeng

    2016-01-01

    Our quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition. PMID:27527905

  17. Extraction of biomolecules using phosphonium-based ionic liquids + K(3)PO(4) aqueous biphasic systems.

    PubMed

    Louros, Cláudia L S; Cláudio, Ana Filipa M; Neves, Catarina M S S; Freire, Mara G; Marrucho, Isabel M; Pauly, Jérôme; Coutinho, João A P

    2010-04-15

    Aqueous biphasic systems (ABS) provide an alternative and efficient approach for the extraction, recovery and purification of biomolecules through their partitioning between two liquid aqueous phases. In this work, the ability of hydrophilic phosphonium-based ionic liquids (ILs) to form ABS with aqueous K(3)PO(4) solutions was evaluated for the first time. Ternary phase diagrams, and respective tie-lines and tie-lines length, formed by distinct phosphonium-based ILs, water, and K(3)PO(4) at 298 K, were measured and are reported. The studied phosphonium-based ILs have shown to be more effective in promoting ABS compared to the imidazolium-based counterparts with similar anions. Moreover, the extractive capability of such systems was assessed for distinct biomolecules (including amino acids, food colourants and alkaloids). Densities and viscosities of both aqueous phases, at the mass fraction compositions used for the biomolecules extraction, were also determined. The evaluated IL-based ABS have been shown to be prospective extraction media, particularly for hydrophobic biomolecules, with several advantages over conventional polymer-inorganic salt ABS.

  18. Improved extraction of fluoroquinolones with recyclable ionic-liquid-based aqueous biphasic systems.

    PubMed

    Almeida, Hugo F D; Freire, Mara G; Marrucho, Isabel M

    2016-05-07

    In the past few years, the improvement of advanced analytical tools allowed to confirm the presence of trace amounts of metabolized and unchanged active pharmaceutical ingredients (APIs) in wastewater treatment plants (WWTPs) as well as in freshwater surfaces. It is known that the continuous contact with APIs, even at very low concentrations (ng L(-1)-μg L(-1)), leads to serious human health problems. In this context, this work shows the feasibility of using ionic-liquid-based aqueous biphasic systems (IL-based ABS) in the extraction of quinolones present in aqueous media. In particular, ABS composed of imidazolium- and phosphonium-based ILs and aluminium-based salts (already used in water treatment plants) were evaluated in one-step extractions of six fluoroquinolones (FQs), namely ciprofloxacin, enrofloxacin, moxifloxacin, norfloxacin, ofloxacin and sarafloxacin, and extraction efficiencies up to 98% were obtained. Despite the large interest devoted to IL-based ABS as extractive systems of outstanding performance, their recyclability/reusability has seldomly been studied. An efficient extraction/cleaning process of the IL-rich phase is here proposed by FQs induced precipitation. The recycling of the IL and its further reuse without losses in the ABS extractive performance for FQs were established, as confirmed by the four consecutive removal/extraction cycles evaluated. This novel recycling strategy supports IL-based ABS as sustainable and cost-efficient extraction platforms.

  19. Water-dispersible TiO2 nanoparticles via a biphasic solvothermal reaction method.

    PubMed

    Mohan, Rajneesh; Drbohlavova, Jana; Hubalek, Jaromir

    2013-12-01

    A biphasic solvothermal reaction method has been used for the synthesis of TiO2 nanoparticles (NPs). In this method, hydrolysis and nucleation occur at the interface of organic phase (titanium (IV) n-propoxide and stearic acid dissolved in toluene) and water phase (tert-butylamine dissolved in water) resulting in the nucleation of the stearic acid-capped TiO2 NPs. These NPs are hydrophilic due to hydrophobic stearic acid ligands and could be dispersed in toluene, but not in water. These stearic acid-capped TiO2 NPs were surface-modified with 2,3-dimercaptosuccinic acid (DMSA) in order to make them water soluble. The resultant TiO2 NPs were easily redispersed in water without any noticeable aggregation. The Rietveld profile fitting of X-ray diffraction (XRD) pattern of the TiO2 NPs revealed highly crystalline anatase structure. The average crystallite size of TiO2 NPs was calculated to be 6.89 nm, which agrees with TEM results. These results have important implications for the use of TiO2 in biomedical, environmental, and industrial applications.

  20. Remedy for fictive negative pressures in biphasic finite element models of the intervertebral disc during unloading.

    PubMed

    Schmidt, Hendrik; Galbusera, Fabio; Wilke, Hans-Joachim; Shirazi-Adl, Aboulfazl

    2011-03-01

    Previous biphasic finite element studies investigated the temporal response of a spinal segment under rather simplified loading conditions with no attention to unloading and recovery phases. Employment of existing constitutive relations in porous media yields rather large suction-type pore pressures in the disc as the load suddenly disappears. Such negative pressures are absent in vivo and are hence fictive. The aim of this study was to search for remedies to avoid the computation of negative pressures upon unloading. Partial saturation for the disc or a rest load (RL) higher than 400 N totally eliminated the negative pressures. Decreasing the voids ratio (VR) also led to a reduced negative pressure. When defining a partial saturated disc or using a lower VR in combination with a boundary pressure of 0.25 MPa and a RL of 350 N, no negative pressure was calculated. It appears that the constraint of full saturation and a high mobile fluid fraction of the disc tissues along with inadequate tissue properties are the likely causes of negative pressures during unloading.

  1. Biphasic Fluence-Response Curves for Phytochrome-Mediated Kalanchoë Seed Germination 1

    PubMed Central

    Rethy, Roger; Dedonder, Andrée; De Petter, Edwin; Van Wiemeersch, Luc; Fredericq, Henri; De Greef, Jan; Steyaert, Herman; Stevens, Hilde

    1987-01-01

    The fluence-response curves for the effect of two red pulses separated by 24 hours on the germination of Kalanchoe blossfeldiana Poelln. cv Vesuv seeds, incubated on gibberellic acid (GA3) are biphasic for suboptimal concentrations. The response in the low fluence range corresponds with a classical red/far-red reversible phytochrome mediated reaction. GA3 induces an additional response in the very low fluence range, which is also phytochrome mediated. The sensitivity to phytochrome-far-red absorbing form (Pfr), however, is increased about 20,000-fold, so that even far-red fluences become saturating. Both in the very low and low fluence response range, the maximal responses induced by saturating fluences are modulated by the GA3 concentration. GA3 having no direct influence on the phytochrome phototransformations, alters the Pfr requirement and determines the responding seed population fraction in the very low and low fluence range. The effet of GA3 appears to be on the transduction chain of the phytochrome signal. PMID:16665187

  2. A biphasic memory curve in the chambered nautilus, Nautilus pompilius L. (Cephalopoda: Nautiloidea).

    PubMed

    Crook, Robyn; Basil, Jennifer

    2008-06-01

    Cephalopods are an exceptional taxon for examining the competing influences of ecology and evolutionary history on brain and behaviour. Coleoid cephalopods (octopuses, cuttlefishes and squids) have evolved specialised brains containing dedicated learning and memory centres, and rely on plastic behaviours to hunt prey effectively and communicate intricate visual displays. Their closest living relative, the primitive nautilus, is the sole remnant of an ancient lineage that has persisted since the Cambrian. Nautilus brains are the simplest among the extant cephalopods, and the absence of dedicated learning and memory regions may represent an ancestral condition. It is assumed that the absence of these regions should limit memory storage and recall in nautilus, but this assumption has never been tested. Here we describe the first evidence of learning and memory in chambered nautilus (Nautilus pompilius). Using a Pavlovian conditioning paradigm, we demonstrate that chambered nautilus exhibits temporally separated short- and long-term memory stores, producing a characteristic biphasic memory curve similar to that of cuttlefishes. Short-term memory persisted for less than 1 h post-training, whereas long-term memory was expressed between 6 and 24 h after training. Despite lacking the dedicated neural regions that support learning and memory in all other extant cephalopods, nautilus expressed a similar memory profile to coleoids. Thus the absence of these regions in the nautilus brain does not appear to limit memory expression, as hypothesised. Our results provide valuable insights into the evolution of neural structures supporting memory.

  3. Biphasic synovial sarcoma in a 19-year-old pregnant woman: a case report.

    PubMed

    Adameşteanu, Mădălina Olivia; Scurtu, Răzvan; Lascăr, Ioan; Vâlcu, Marek; Popescu, Şerban Arghir; Sebe, Ioana Teona

    2015-01-01

    Synovial sarcoma is a rare malignant tumor of mesenchymal multipotent cells. We hereby present a case of synovial sarcoma of the upper left thigh. A 19-year-old patient was referred to our clinic by another hospital in Bucharest, Romania, for a soft tissue mass in the left upper thigh. Local examination of the left thigh revealed a 15÷13 cm, ovoid, painful upon touch, soft tissue mass occupying the proximal-medial aspect of the thigh. Bilateral inguinal nodes' enlargement was noticed. Upon suspecting regional node involvement, the surgical team decided to perform left limb amputation due to tumor size and the proximity to major arterial and nervous trunks as well as the femoral shaft, making curative surgery and 'free of disease' resection margins improbable. The patient refused the operation. The surgical team (plastic surgeon, orthopedic surgeon) decided to attempt limb-sparing surgery. After tumor resection, free-of-disease surgical margins were achieved. The pathological examination as well as the immunohistochemistry (IHC) diagnosed a large biphasic synovial sarcoma warranting oncologic treatment. The association between tumor growth and pregnancy poses important therapeutic problems, such as the use of preoperative chemotherapy, potential pregnancy termination, limb amputation versus limb salvage intervention and types of protocols of chemotherapy or radiotherapy indicated.

  4. In vitro Biphasic Effect of Honey Bee Venom on Basophils from Screened Healthy Blood Donors

    PubMed Central

    Zanoni, Giovanna; Ortolani, Riccardo; Vella, Antonio

    2011-01-01

    Apis mellifera L. bee venom is the most studied hymenoptera allergen, but many aspects of its action on human basophils remain unclear. Allergologists seek evidence of the effectiveness of bee venom immunotherapy as this approach is the chosen treatment for systemic allergic reactions. The effect of bee venom on human basophils in vitro has not been studied in detail for many reasons, including the paucity of basophils in peripheral blood, inter-individual basophil response variability, and the reliability and predictability of basophil activation tests. We conducted a brief preliminary survey of the effect of Apis bee venom on healthy asymptomatic (non-allergic) subjects. A dose of an aqueous commercial extract of Apis bee venom as high as 10 µg/mL activated resting basophils (CD63=+80-90%, CD203c=+30%), while it inhibited the expression of CD63 (-50%) following basophil stimulation by the soluble agonists formyl-Met-Leu-Phe or anti-IgE. The activation of resting basophils appeared to be dose-related. Only when basophils were activated with an IgE-mediated agonist, did bee venom extract exhibit a possible priming mechanism at the lowest doses used only via CD63, while it was ineffective via CD203c. Autocrine interleukin-3 may play a role in the observed biphasic behavior. PMID:21217927

  5. Effect of particle size on osteoinductive potential of microstructured biphasic calcium phosphate ceramic.

    PubMed

    Wang, Liao; Barbieri, Davide; Zhou, Hongyu; de Bruijn, Joost D; Bao, Chongyun; Yuan, Huipin

    2015-06-01

    Material factors such as chemistry, surface microstructure and geometry have shown their influence on osteoinduction of calcium phosphate ceramics. Hereby we report that osteoinduction of a micro-structured biphasic calcium phosphate ceramic (BCP) has a relation with the particle sizes. BCP particles with the size of 212-300 µm, 106-212 µm, 45-106 µm, and smaller than 45 µm were prepared and implanted in paraspinal muscle of dogs for 12 weeks. Histological evaluation of the explants showed abundant bone in all samples with particle size of 212-300 µm, 106-212 µm, and 45-106 µm, while no bone was seen in any sample having particle size smaller than 45 µm. Bone was formed as early as 3 weeks after implantation in implants having BCP particles bigger than 45 µm and the volume of the formed bone was similar among the implants with particles larger than 45 µm after 12 weeks implantation. The results herein show that a size limitation of microstructured calcium phosphate ceramic particles for osteoinduction. It is most likely that the particle size affect inductive bone formation via macroporous structures for body fluid infiltration, cell/tissue ingrowth and angiogenesis. © 2014 Wiley Periodicals, Inc.

  6. Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling.

    PubMed

    Smith, Geoffrey A; Uchida, Kenji; Weiss, Arthur; Taunton, Jack

    2016-05-01

    To drive lymphocyte proliferation and differentiation, common γ-chain (γc) cytokine receptors require hours to days of sustained stimulation. JAK1 and JAK3 kinases are found together in all γc-receptor complexes, but how their respective catalytic activities contribute to signaling over time is not known. Here we dissect the temporal requirements for JAK3 kinase activity with a selective covalent inhibitor (JAK3i). By monitoring phosphorylation of the transcription factor STAT5 over 20 h in CD4(+) T cells stimulated with interleukin 2 (IL-2), we document a second wave of signaling that is much more sensitive to JAK3i than the first wave. Selective inhibition of this second wave is sufficient to block cyclin expression and entry to S phase. An inhibitor-resistant JAK3 mutant (C905S) rescued all effects of JAK3i in isolated T cells and in mice. Our chemical genetic toolkit elucidates a biphasic requirement for JAK3 kinase activity in IL-2-driven T cell proliferation and will find broad utility in studies of γc-receptor signaling.

  7. Preparation, characterization and in vitro dissolution behavior of porous biphasic α/β-tricalcium phosphate bioceramics.

    PubMed

    Xie, Lu; Yu, Haiyang; Deng, Yi; Yang, Weizhong; Liao, Li; Long, Qin

    2016-02-01

    The ideal bone tissue engineering scaffolds are long-cherished with the properties of interconnected macroporous structures, adjustable degradation and excellent biocompatibility. Here, a series of porous α/β-tricalcium phosphate (α/β-TCP) biphasic bioceramics with different phase ratios of α-TCP and β-TCP were successfully synthesized by heating an amorphous calcium phosphate precursor. The chemical and morphological characterization showed that α- and β-TCP phases co-existed in the α/β-TCP bioceramics and they had interconnected pore structures with size between 200 and 500μm. The in vitro dissolution behavior and bioactivity of the dual α/β-TCP were also probed in static and dynamic SBF for the first time. The results revealed that α/β-TCP scaffolds had good in vitro bioactivity, as the formation of bone-like apatite layers was induced on the scaffolds after mineralization in SBF. Moreover, dissolution rate of α/β-TCP bioceramics in dynamic environment was higher than that under static condition. Compared with monophasic TCP ceramics, these porous α/β-TCP bioceramics displayed a tailored dissolution rate proportionate to the TCP content (α and β) in the materials. Further, the degradation profile of porous α/β-TCP was well-described by Avrami equation. The porous dual α/β-TCP bioceramics with controllable degradation behavior hold great potential to be applied in bone tissue engineering as bone substitutes.

  8. Clinical review: Biphasic positive airway pressure and airway pressure release ventilation

    PubMed Central

    Putensen, Christian; Wrigge, Hermann

    2004-01-01

    This review focuses on mechanical ventilation strategies that allow unsupported spontaneous breathing activity in any phase of the ventilatory cycle. By allowing patients with the acute respiratory distress syndrome to breathe spontaneously, one can expect improvements in gas exchange and systemic blood flow, based on findings from both experimental and clinical trials. In addition, by increasing end-expiratory lung volume, as occurs when using biphasic positive airway pressure or airway pressure release ventilation, recruitment of collapsed or consolidated lung is likely to occur, especially in juxtadiaphragmatic lung legions. Traditional approaches to mechanical ventilatory support of patients with acute respiratory distress syndrome require adaptation of the patient to the mechanical ventilator using heavy sedation and even muscle relaxation. Recent investigations have questioned the utility of sedation, muscle paralysis and mechanical control of ventilation. Furthermore, evidence exists that lowering sedation levels will decrease the duration of mechanical ventilatory support, length of stay in the intensive care unit, and overall costs of hospitalization. Based on currently available data, we suggest considering the use of techniques of mechanical ventilatory support that maintain, rather than suppress, spontaneous ventilatory effort, especially in patients with severe pulmonary dysfunction. PMID:15566621

  9. Enhanced tunability afforded by aqueous biphasic systems formed by fluorinated ionic liquids and carbohydrates.

    PubMed

    Ferreira, Ana M; Esteves, Pedro D O; Boal-Palheiros, Isabel; Pereiro, Ana B; Rebelo, Luís Paulo N; Freire, Mara G

    2016-02-21

    This work unveils the formation of novel aqueous biphasic systems (ABS) formed by perfluoroalkylsulfonate-based ionic liquids (ILs) and a large number of carbohydrates (monosaccharides, disaccharides and polyols) aiming at establishing more benign alternatives to the salts commonly used. The respective ternary phase diagrams were determined at 298 K. The aptitude of the carbohydrates to induce phase separation closely follows their hydration capability, while the length of the IL cation/anion fluorinated chain also plays a crucial role. Finally, these systems were investigated as liquid-liquid extraction strategies for four food dyes. Single-step extraction efficiencies for the carbohydrate-rich phase up to 94% were obtained. Remarkably and contrarily to the most investigated IL-salt ABS, most dyes preferentially migrate for the most hydrophilic and biocompatible carbohydrate-rich phase - an outstanding advantage when envisaging the products recovery and further use. On the other hand, more hydrophobic dyes preferentially partition to the IL-rich phase, disclosing therefore these novel systems as highly amenable to be tuned by the proper choice of the phase-forming components.

  10. Enhanced tunability afforded by aqueous biphasic systems formed by fluorinated ionic liquids and carbohydrates†

    PubMed Central

    Boal-Palheiros, Isabel; Pereiro, Ana B.; Rebelo, Luís Paulo N.; Freire, Mara G.

    2016-01-01

    This work unveils the formation of novel aqueous biphasic systems (ABS) formed by perfluoroalkylsulfonate-based ionic liquids (ILs) and a large number of carbohydrates (monosaccharides, disaccharides and polyols) aiming at establishing more benign alternatives to the salts commonly used. The respective ternary phase diagrams were determined at 298 K. The aptitude of the carbohydrates to induce phase separation closely follows their hydration capability, while the length of the IL cation/anion fluorinated chain also plays a crucial role. Finally, these systems were investigated as liquid–liquid extraction strategies for four food dyes. Single-step extraction efficiencies for the carbohydrate-rich phase up to 94% were obtained. Remarkably and contrarily to the most investigated IL-salt ABS, most dyes preferentially migrate for the most hydrophilic and biocompatible carbohydrate-rich phase – an outstanding advantage when envisaging the products recovery and further use. On the other hand, more hydrophobic dyes preferentially partition to the IL-rich phase, disclosing therefore these novel systems as highly amenable to be tuned by the proper choice of the phase-forming components. PMID:27667966

  11. Biphasic products of dicalcium phosphate-rich cement with injectability and nondispersibility.

    PubMed

    Ko, Chia-Ling; Chen, Jian-Chih; Hung, Chun-Cheng; Wang, Jen-Chyan; Tien, Yin-Chun; Chen, Wen-Cheng

    2014-06-01

    In this study, a calcium phosphate cement was developed using tetracalcium phosphate and surface-modified dicalcium phosphate anhydrous (DCPA). This developed injectable bone graft substitute can be molded to the shape of the bone cavity and set in situ through the piping system that has an adequate mechanical strength, non-dispersibility, and biocompatibility. The materials were based on the modified DCPA compositions of calcium phosphate cement (CPC), where the phase ratio of the surface-modified DCPA is higher than that of the conventional CPC for forming dicalcium phosphate (DCP)-rich cement. The composition and morphology of several calcium phosphate cement specimens during setting were analyzed via X-ray diffractometry and transmission electron microscopy coupled with an energy dispersive spectroscopy system. The compressive strength of DCP-rich CPCs was greater than 30MPa after 24h of immersion in vitro. The reaction of the CPCs produced steady final biphasic products of DCPs with apatite. The composites of calcium phosphate cements derived from tetracalcium phosphate mixed with surface-modified DCPA exhibited excellent mechanical properties, injectability, and interlocking forces between particles, and they also featured nondispersive behavior when immersed in a physiological solution.

  12. Water-dispersible TiO2 nanoparticles via a biphasic solvothermal reaction method

    PubMed Central

    2013-01-01

    A biphasic solvothermal reaction method has been used for the synthesis of TiO2 nanoparticles (NPs). In this method, hydrolysis and nucleation occur at the interface of organic phase (titanium (IV) n-propoxide and stearic acid dissolved in toluene) and water phase (tert-butylamine dissolved in water) resulting in the nucleation of the stearic acid-capped TiO2 NPs. These NPs are hydrophilic due to hydrophobic stearic acid ligands and could be dispersed in toluene, but not in water. These stearic acid-capped TiO2 NPs were surface-modified with 2,3-dimercaptosuccinic acid (DMSA) in order to make them water soluble. The resultant TiO2 NPs were easily redispersed in water without any noticeable aggregation. The Rietveld profile fitting of X-ray diffraction (XRD) pattern of the TiO2 NPs revealed highly crystalline anatase structure. The average crystallite size of TiO2 NPs was calculated to be 6.89 nm, which agrees with TEM results. These results have important implications for the use of TiO2 in biomedical, environmental, and industrial applications. PMID:24289214

  13. Biphasic changes in the level and composition of Dunaliella salina plasma membrane diacylglycerols following hypoosmotic shock

    SciTech Connect

    Ha, Kwonsoo; Thompson, G.A. )

    1992-01-21

    Hypoosmotic shock has been shown to trigger an immediate and selective increase of plasma membrane diacylglycerols (DAG) in the green alga Dunaliella salina, coinciding with an approximately equivalent loss of phosphatidylinositol 4,5-bisphosphate from this membrane. Following a slight decline in amount, DAG levels of the plasma membrane resumed their rise by 2 min after the shock and by 40 min had achieved a maximum concentration equivalent to 230% of DAG levels in unstressed cells. This second, more sustained increase of plasma membrane DAG was matched by a DAG increase in the microsome-enriched cytoplasmic membrane fraction, commencing at 2 min and peaking at 140% of control values. The changing pattern of DAG molecular species produced in the plasma membrane during the early phases of hypoosmotic stress was compatible with their derivation from phospholipase C hydrolysis of inositol phospholipids and phophatidylcholine. From 8 min following hypoosmotic shock, as relatively larger scale DAG accumulations developed in the cytoplasmic membranes, the molecular species composition changed to reflect a marked increase in de novo synthesis of sn-1-oleoyl, sn-2-palmitoylglycerol, and dioleoylglycerol. The radioisotope labeling data with Na{sub 2} {sup 14}CO{sub 3} confirmed that the biphasic formation of DAG triggered by hypoosmotic shock culminates in a large-scale de novo synthesis of DAG. This is the first clear evidence for de novo synthesis as a source of DAG following PIP{sub 2}-mediated signaling.

  14. A flow reactor setup for photochemistry of biphasic gas/liquid reactions.

    PubMed

    Schachtner, Josef; Bayer, Patrick; Jacobi von Wangelin, Axel

    2016-01-01

    A home-built microreactor system for light-mediated biphasic gas/liquid reactions was assembled from simple commercial components. This paper describes in full detail the nature and function of the required building elements, the assembly of parts, and the tuning and interdependencies of the most important reactor and reaction parameters. Unlike many commercial thin-film and microchannel reactors, the described set-up operates residence times of up to 30 min which cover the typical rates of many organic reactions. The tubular microreactor was successfully applied to the photooxygenation of hydrocarbons (Schenck ene reaction). Major emphasis was laid on the realization of a constant and highly reproducible gas/liquid slug flow and the effective illumination by an appropriate light source. The optimized set of conditions enabled the shortening of reaction times by more than 99% with equal chemoselectivities. The modular home-made flow reactor can serve as a prototype model for the continuous operation of various other reactions at light/liquid/gas interfaces in student, research, and industrial laboratories.

  15. Biphasic effect of L-5-HTP in the Vogel conflict model.

    PubMed

    Hjorth, S; Söderpalm, B; Engel, J A

    1987-01-01

    The effect of L-5-HTP (25 400 mg/kg IP) following inhibition of the peripheral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg IP) was investigated in a test modified from Vogel's drinking conflict model. At 50 mg/kg an anti-conflict action was detected, while higher doses (100-400 mg/kg) decreased punished responding. A lower dose (25 mg/kg) had no effect. Non-specific effects--such as alterations in muscle tone, in motivation to drink or in the sensitivity to electrical shock--could not explain the anxiolytic- and anxiogenic-like actions of 50 and 100 mg/kg, respectively. The bi-phasic effect of L-5-HTP is discussed in terms of different subpopulations of central serotoninergic receptors, possibly exerting opposing influences on conflict responding. The study emphasises the importance of 5-HT mechanisms in anxiety, and the possibility of finding novel anxiolytics among drugs selectively affecting central 5-HT neurotransmission.

  16. A 24 Vpp compliant biphasic stimulator for inductively powered animal behavior studies.

    PubMed

    Nag, Sudip; Sharma, Dinesh; Thakor, Nitish V

    2013-01-01

    Stimulation of biological neurons using electrical charges has gained popularity in neuro-engineering studies. Wireless power delivery to electrical stimulators is an essential requirement for long term and maintenance-free implantable applications. Voltage compliance is often a limiting factor in these systems. We present an inductively powered biphasic stimulator that is capable of exhibiting 24 Vpp load voltage compliance, while harvesting up to 13 V. The stimulator can deliver currents ranging from 10 µA to 6 mA. The inductive energy harvesting system operates at a low carrier frequency of 134.2 KHz for enhanced depth of penetration in biological medium. The near-field harvester works reliably for up to 50 mm inter-antenna distance. Noise performance and charge balancing accuracy have also been improved due to the absence of a boost switching circuit and floating current source based architecture. In-vivo motor and visual cortex stimulations have been performed using epi-dural screw electrodes on an awake behaving and anesthetized Wister rat.

  17. Formation of Biphasic Hydroxylapatite-Beta Magnesium Tricalcium Phosphate in Heat Treated Salmonid Vertebrae.

    PubMed

    Butler, Don H; Shahack-Gross, Ruth

    2017-06-15

    Ichthyoarchaeological evidence is uncommon at ancient hunter-gatherer sites from various regions and timeframes. This research contributes to the development of microarchaeological techniques useful for identifying fishing economies in situations where classifiable bones are unavailable. Specifically, traces of heat altered bone mineral in domestic hearths are expected to provide markers for discarded fish remains. We used a series of laboratory incineration experiments to characterize the mineralogy of burned salmonid vertebrae. Fourier transform infrared spectroscopy and x-ray diffraction distinguished the formation of beta magnesium tricalcium phosphate (βMgTCP) at temperatures as low as 600 °C. Bones from a sample of game mammals and birds did not form this phase at temperatures below 1,000 °C. We propose that this neoformed mineral can serve as a proxy for hunter-gatherer salmonid fishing when typical ichthyoarchaeological evidence is absent. Using Fourier transform infrared spectroscopy, it will be possible to rapidly and inexpensively determine the presence of βMgTCP in fragmentary burned bone remains associated with combustion features. The occurrence of βMgTCP in archaeological hearth features will offer a new means of further evaluating the temporal, geographic, and cultural scope of salmonid harvesting. We also acknowledge the value of biphasic hydroxylapatite-βMgTCP recovered from Atlantic salmon vertebrae as a bioceramic.

  18. Water-dispersible TiO2 nanoparticles via a biphasic solvothermal reaction method

    NASA Astrophysics Data System (ADS)

    Mohan, Rajneesh; Drbohlavova, Jana; Hubalek, Jaromir

    2013-12-01

    A biphasic solvothermal reaction method has been used for the synthesis of TiO2 nanoparticles (NPs). In this method, hydrolysis and nucleation occur at the interface of organic phase (titanium (IV) n-propoxide and stearic acid dissolved in toluene) and water phase ( tert-butylamine dissolved in water) resulting in the nucleation of the stearic acid-capped TiO2 NPs. These NPs are hydrophilic due to hydrophobic stearic acid ligands and could be dispersed in toluene, but not in water. These stearic acid-capped TiO2 NPs were surface-modified with 2,3-dimercaptosuccinic acid (DMSA) in order to make them water soluble. The resultant TiO2 NPs were easily redispersed in water without any noticeable aggregation. The Rietveld profile fitting of X-ray diffraction (XRD) pattern of the TiO2 NPs revealed highly crystalline anatase structure. The average crystallite size of TiO2 NPs was calculated to be 6.89 nm, which agrees with TEM results. These results have important implications for the use of TiO2 in biomedical, environmental, and industrial applications.

  19. Biphasic effect of Syzygium aromaticum flower bud on reproductive physiology of male mice.

    PubMed

    Mishra, R K; Singh, S K

    2016-11-01

    The flower buds of Syzygium aromaticum (clove) have been used for the treatment of male sexual disorders in indigenous medicines of Indian subcontinent. Therefore to evaluate the efficacy of Syzygium aromaticum on the male reproductive health, chronic oral exposure of aqueous extract of flower buds of Syzygium in three doses (15 mg, 30 mg and 60 mg kg(-1) BW) were studied for a single spermatogenic cycle (35 days) in Parkes (P) strain mice. Lower dose (15 mg) of Syzygium aromaticum flower buds increased serum testosterone level and testicular hydroxysteroid dehydrogenase (HSD) activities and improved sperm motility, sperm morphology, secretory activity of epididymis and seminal vesicle, and number of litters per female. On the other hand, higher doses (30 and 60 mg) of the treatment adversely affected above parameters. Further, higher doses of the extract also had adverse effects on daily sperm production, 1C cell population and on histology of testis. In conclusion, Syzygium aromaticum flower buds extract exhibits biphasic effect on reproductive physiology of male mice. Lower dose of Syzygium aromaticum flower bud extract is androgenic in nature and may have a viable future as an indigenous sexual rejuvenator, while higher doses adversely affected functional physiology of reproductive organs. © 2016 Blackwell Verlag GmbH.

  20. Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

    PubMed

    Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

    2015-06-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

  1. First calorimetric determination of heat of extraction of 248Cm in a bi-phasic system

    SciTech Connect

    Leigh R. Martin; Peter R. Zalupski

    2011-06-01

    This report presents a summary of the work performed to meet FCR&D level 2 milestone M21SW050201, 'Complete the first calorimetric determination of heat of extraction of 248Cm in a bi-phasic system'. This work was carried out under the auspices of the Thermodynamics and Kinetics FCR&D work package. To complement previous work undertaken under this work package we have extended out heat of extraction studies by di-2-ethyl-hexyl-phosphoric acid to curium. This report also details the heat of extraction of samarium in the same system. This work was performed to not only test the methodology but also to check for consistency with the heats of extraction obtained with those in the prior literature. The heat of extraction for samarium that was obtained in this study was -9.6 kJ mol-1, which is in reasonable agreement with the previously obtained value of -10.9 kJ mol-1. The curium heat of extraction was performed under two sets of conditions and the obtained heats of extraction were in reasonable agreement with each other at -16.0 {+-} 1.1 and -16.8 {+-} 1.5 kJ mol-1.

  2. Biphasic effect of falcarinol on caco-2 cell proliferation, DNA damage, and apoptosis.

    PubMed

    Young, Jette F; Duthie, Susan J; Milne, Lesley; Christensen, Lars P; Duthie, Garry G; Bestwick, Charles S

    2007-02-07

    The polyacetylene falcarinol, isolated from carrots, has been shown to be protective against chemically induced colon cancer development in rats, but the mechanisms are not fully understood. In this study CaCo-2 cells were exposed to falcarinol (0.5-100 microM) and the effects on proliferation, DNA damage, and apoptosis investigated. Low-dose falcarinol exposure (0.5-10 microM) decreased expression of the apoptosis indicator caspase-3 concomitantly with decreased basal DNA strand breakage. Cell proliferation was increased (1-10 microM), whereas cellular attachment was unaffected by <10 microM falcarinol. At concentrations above 20 microM falcarinol, proliferation of CaCo-2 cells decreased and the number of cells expressing active caspase-3 increased simultaneously with increased cell detachment. Furthermore, DNA single-strand breakage was significantly increased at concentrations above 10 microM falcarinol. Thus, the effects of falcarinol on CaCo-2 cells appear to be biphasic, inducing pro-proliferative and apoptotic characteristics at low and high concentrations of falcarinol, respectively.

  3. The polyacetylenes falcarinol and falcarindiol affect stress responses in myotube cultures in a biphasic manner.

    PubMed

    Young, Jette F; Christensen, Lars P; Theil, Peter K; Oksbjerg, Niels

    2008-01-01

    The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, celery, celeriac and other umbelliferous vegetables, on the stress responses in primary myotube cultures, were studied. Biphasic responses on cellular stress responses in myotube cultures were investigated by exposing them to various concentrations of falcarinol and falcarindiol for 24 h before testing effects of 100 microM H(2)O(2) on the intracellular formation of reactive oxygen species (ROS), transcription of the antioxidative enzyme cytosolic glutathione peroxidase (cGPx), and the heat shock proteins (HSP) HSP70 and HO1. At low concentrations (1.6 to 25 microM) polyacetylenes caused a slightly accelerated intra-cellular ROS formation, increased cGPx transcription and decreased HSP70 and HO1 transcription. The increased cGPx transcription may be interpreted as an adaptive response to the increased ROS formation and may have caused a reduced demand for the protective functions of the HSPs. ROS formation, however, was substantially decreased after pre-incubation with both polyacetylenes at 50 and 100 microM, the cGPx transcription was reduced and the HSP70 and HO1 transcription increased, indicating a need for the protective and repairing functions of the HSPs. In conclusion, pre-incubation with low concentrations of both polyacetylenes prior to H(2)O(2) exposure induced a cytoprotective effect whereas higher concentrations had adverse effects.

  4. The Polyacetylenes Falcarinol and Falcarindiol Affect Stress Responses in Myotube Cultures in a Biphasic Manner

    PubMed Central

    Young, Jette F.; Christensen, Lars P.; Theil, Peter K.; Oksbjerg, Niels

    2008-01-01

    The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, celery, celeriac and other umbelliferous vegetables, on the stress responses in primary myotube cultures, were studied. Biphasic responses on cellular stress responses in myotube cultures were investigated by exposing them to various concentrations of falcarinol and falcarindiol for 24 h before testing effects of 100 μM H2O2 on the intracellular formation of reactive oxygen species (ROS), transcription of the antioxidative enzyme cytosolic glutathione peroxidase (cGPx), and the heat shock proteins (HSP) HSP70 and HO1. At low concentrations (1.6 to 25 μM) polyacetylenes caused a slightly accelerated intra-cellular ROS formation, increased cGPx transcription and decreased HSP70 and HO1 transcription. The increased cGPx transcription may be interpreted as an adaptive response to the increased ROS formation and may have caused a reduced demand for the protective functions of the HSPs. ROS formation, however, was substantially decreased after pre-incubation with both polyacetylenes at 50 and 100 μM, the cGPx transcription was reduced and the HSP70 and HO1 transcription increased, indicating a need for the protective and repairing functions of the HSPs. In conclusion, pre-incubation with low concentrations of both polyacetylenes prior to H2O2 exposure induced a cytoprotective effect whereas higher concentrations had adverse effects. PMID:18846258

  5. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss.

    PubMed

    Clugston, Robin D; Huang, Li-Shin; Blaner, William S

    2015-09-01

    The alcohol-induced depletion of hepatic retinoid stores correlates with the progression of liver injury; however, the mechanisms underlying alcohol's effects have not been fully elucidated. Our goal was to gain a mechanistic understanding of alcohol-induced hepatic retinoid depletion. Wild-type and mutant mice were continuously fed alcohol through Lieber-DeCarli liquid diets, with matched control animals pair fed an isocaloric alcohol-free diet to ensure equal nutrient and calorie intake between groups. A systematic analysis of tissue retinol and retinyl ester levels was performed with HPLC, complemented by gene and protein expression analyses. Our results delineated 2 phases of alcohol-induced depletion of hepatic retinoid. Initially, ∼15% of hepatic retinoid content was mobilized from the liver, causing extrahepatic tissue retinoid levels to increase. Subsequently, there was a precipitous drop in hepatic retinoid content (>60%), without further retinoid accumulation in the periphery. Follow-up studies in mutant mice revealed roles for RBP, CRBP1, and CD36 in retinoid mobilization and extrahepatic retinoid uptake, as well as a role for CYP2E1 in the catabolism of hepatic retinoid. In summary, alcohol has a biphasic effect on hepatic retinoid stores, characterized by an initial phase of rapid mobilization to extrahepatic tissues followed by extensive catabolism within the liver. © FASEB.

  6. Complex biphase nature of the superconducting dome of the FeSe phase diagram

    NASA Astrophysics Data System (ADS)

    Svitlyk, V.; Raba, M.; Dmitriev, V.; Rodière, P.; Toulemonde, P.; Chernyshov, D.; Mezouar, M.

    2017-07-01

    Single crystal synchrotron x-ray diffraction as a function of temperature and pressure has revealed a complex biphase mixture in superconducting FeSe. Based on our experimental results, we construct a phase diagram where structural behavior and superconducting properties of FeSe are found to be correlated. We show that below 6 GPa, where pressure promotes the superconducting critical temperature, the FeSe structure is composed of two-dimensional layers of edge-shared FeS e4 tetrahedra, while above 6 GPa, the superconductivity is strongly suppressed on formation of a new orthorhombic polymorph characterized by a three-dimensional network of face sharing FeS e6 octahedra. Therefore, changes in topology and connectivity of the FeSe structure are found to be detrimental to superconductivity. The previously controversial crystal structure of the high-pressure polymorph of FeSe was unambiguously determined in the present paper. High-pressure FeSe adopts an orthorhombic MnP-type structure (Pnma) which corresponds to a slightly distorted hexagonal NiAs-type arrangement (P 63/m m c ). The structural transformation from the low- to high-pressure FeSe polymorph is first order in nature and is manifested as antiparallel displacements within the Fe and Se sublattices.

  7. A flow reactor setup for photochemistry of biphasic gas/liquid reactions

    PubMed Central

    Schachtner, Josef; Bayer, Patrick

    2016-01-01

    Summary A home-built microreactor system for light-mediated biphasic gas/liquid reactions was assembled from simple commercial components. This paper describes in full detail the nature and function of the required building elements, the assembly of parts, and the tuning and interdependencies of the most important reactor and reaction parameters. Unlike many commercial thin-film and microchannel reactors, the described set-up operates residence times of up to 30 min which cover the typical rates of many organic reactions. The tubular microreactor was successfully applied to the photooxygenation of hydrocarbons (Schenck ene reaction). Major emphasis was laid on the realization of a constant and highly reproducible gas/liquid slug flow and the effective illumination by an appropriate light source. The optimized set of conditions enabled the shortening of reaction times by more than 99% with equal chemoselectivities. The modular home-made flow reactor can serve as a prototype model for the continuous operation of various other reactions at light/liquid/gas interfaces in student, research, and industrial laboratories. PMID:27829887

  8. A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

    PubMed Central

    2016-01-01

    Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs) which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22)(p13;q12) translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22)(p13;q12) translocation disclosed loss of the EWSR1 gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH) confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of the EWSR1 and WT1 gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs. PMID:27403364

  9. Post-stimulation block of frog sciatic nerve by high-frequency (kHz) biphasic stimulation.

    PubMed

    Yang, Guangning; Xiao, Zhiying; Wang, Jicheng; Shen, Bing; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2017-04-01

    This study determined if high-frequency biphasic stimulation can induce nerve conduction block that persists after the stimulation is terminated, i.e., post-stimulation block. The frog sciatic nerve-muscle preparation was used in the study. Muscle contraction force induced by low-frequency (0.5 Hz) nerve stimulation was recorded to indicate the occurrence and recovery of nerve block induced by the high-frequency (5 or 10 kHz) biphasic stimulation. Nerve block was observed during high-frequency stimulation and after termination of the stimulation. The recovery from post-stimulation block occurred in two distinct phases. During the first phase, the complete block induced during high-frequency stimulation was maintained. The average maximal duration for the first phase was 107 ± 50 s. During the second phase, the block gradually or abruptly reversed. The duration of both first and second phases was dependent on stimulation intensity and duration but not frequency. Stimulation of higher intensity (1.4-2 times block threshold) and longer duration (5 min) produced the longest period (249 ± 58 s) for a complete recovery. Post-stimulation block can be induced by high-frequency biphasic stimulation, which is important for future investigations of the blocking mechanisms and for optimizing the stimulation parameters or protocols in clinical applications.

  10. Design and application of a biphasic system that enhances productivity of Daucus carota-catalyzed asymmetric reduction.

    PubMed

    Xiong, Weisi; Wang, Xiaobing; Kong, Lingyi

    2015-08-01

    To develop a biphasic system for use in plant tissue-mediated biotransformations to overcome the low water solubilities of substrates and inhibitory effects of products. Commonly-used organic solvents and ionic liquid were assayed using the biphasic system to reduce water-insoluble benzoyl cyanide by Daucus carota (wild carrot) tissue. Dibutyl phthalate was the most suitable solvent. The optimal moisture content of dibutyl phthalate, the ratio of biomass to substrate, and the concentration of benzoyl cyanide were 50 % (v/v), 100 g mM(-1), and 12 mM l(-1), respectively. Under these conditions, 91 % of molar conversion and 99 % ee of the optical purity of the product were obtained; a high (R)-cyanohydrin concentration of 1.36 g l(-1) was achieved. The proposed biphasic system can be used in industrial applications, particularly in the biotransformation of water-insoluble compounds. This method can also be used to prepare a wide range of value-added products by synthetically manipulating the final chiral (R)-mandelic acid and its derivatives.

  11. Biphasic toxicodynamic features of some antimicrobial agents on microbial growth: a dynamic mathematical model and its implications on hormesis

    PubMed Central

    2010-01-01

    Background In the present work, we describe a group of anomalous dose-response (DR) profiles and develop a dynamic model that is able to explain them. Responses were obtained from conventional assays of three antimicrobial agents (nisin, pediocin and phenol) against two microorganisms (Carnobacterium piscicola and Leuconostoc mesenteroides). Results Some of these anomalous profiles show biphasic trends which are usually attributed to hormetic responses. But they can also be explained as the result of the time-course of the response from a microbial population with a bimodal distribution of sensitivity to an effector, and there is evidence suggesting this last origin. In light of interest in the hormetic phenomenology and the possibility of confusing it with other phenomena, especially in the bioassay of complex materials we try to define some criteria which allow us to distinguish between sensu stricto hormesis and biphasic responses due to other causes. Finally, we discuss some problems concerning the metric of the dose in connection with the exposure time, and we make a cautionary suggestion about the use of bacteriocins as antimicrobial agents. Conclusions The mathematical model proposed, which combines the basis of DR theory with microbial growth kinetics, can generate and explain all types of anomalous experimental profiles. These profiles could also be described in a simpler way by means of bisigmoidal equations. Such equations could be successfully used in a microbiology and toxicology context to discriminate between hormesis and other biphasic phenomena. PMID:20723220

  12. Biphasic regulation of the transcription factor ABORTED MICROSPORES (AMS) is essential for tapetum and pollen development in Arabidopsis.

    PubMed

    Ferguson, Alison C; Pearce, Simon; Band, Leah R; Yang, Caiyun; Ferjentsikova, Ivana; King, John; Yuan, Zheng; Zhang, Dabing; Wilson, Zoe A

    2017-01-01

    Viable pollen is essential for plant reproduction and crop yield. Its production requires coordinated expression at specific stages during anther development, involving early meiosis-associated events and late pollen wall formation. The ABORTED MICROSPORES (AMS) transcription factor is a master regulator of sporopollenin biosynthesis, secretion and pollen wall formation in Arabidopsis. Here we show that it has complex regulation and additional essential roles earlier in pollen formation. An inducible-AMS reporter was created for functional rescue, protein expression pattern analysis, and to distinguish between direct and indirect targets. Mathematical modelling was used to create regulatory networks based on wild-type RNA and protein expression. Dual activity of AMS was defined by biphasic protein expression in anther tapetal cells, with an initial peak around pollen meiosis and then later during pollen wall development. Direct AMS-regulated targets exhibit temporal regulation, indicating that additional factors are associated with their regulation. We demonstrate that AMS biphasic expression is essential for pollen development, and defines distinct functional activities during early and late pollen development. Mathematical modelling suggests that AMS may competitively form a protein complex with other tapetum-expressed transcription factors, and that biphasic regulation is due to repression of upstream regulators and promotion of AMS protein degradation.

  13. Biphasic toxicodynamic features of some antimicrobial agents on microbial growth: a dynamic mathematical model and its implications on hormesis.

    PubMed

    Murado, Miguel A; Vázquez, José A

    2010-08-19

    In the present work, we describe a group of anomalous dose-response (DR) profiles and develop a dynamic model that is able to explain them. Responses were obtained from conventional assays of three antimicrobial agents (nisin, pediocin and phenol) against two microorganisms (Carnobacterium piscicola and Leuconostoc mesenteroides). Some of these anomalous profiles show biphasic trends which are usually attributed to hormetic responses. But they can also be explained as the result of the time-course of the response from a microbial population with a bimodal distribution of sensitivity to an effector, and there is evidence suggesting this last origin. In light of interest in the hormetic phenomenology and the possibility of confusing it with other phenomena, especially in the bioassay of complex materials we try to define some criteria which allow us to distinguish between sensu stricto hormesis and biphasic responses due to other causes. Finally, we discuss some problems concerning the metric of the dose in connection with the exposure time, and we make a cautionary suggestion about the use of bacteriocins as antimicrobial agents. The mathematical model proposed, which combines the basis of DR theory with microbial growth kinetics, can generate and explain all types of anomalous experimental profiles. These profiles could also be described in a simpler way by means of bisigmoidal equations. Such equations could be successfully used in a microbiology and toxicology context to discriminate between hormesis and other biphasic phenomena.

  14. Design and development of a low-cost biphasic charge-balanced functional electric stimulator and its clinical validation

    PubMed Central

    Shendkar, Chandrashekhar; Lenka, Prasanna K.; Biswas, Abhishek; Kumar, Ratnesh

    2015-01-01

    Functional electric stimulators that produce near-ideal, charge-balanced biphasic stimulation waveforms with interphase delay are considered safer and more efficacious than conventional stimulators. An indigenously designed, low-cost, portable FES device named InStim is developed. It features a charge-balanced biphasic single channel. The authors present the complete design, mathematical analysis of the circuit and the clinical evaluation of the device. The developed circuit was tested on stroke patients affected by foot drop problems. It was tested both under laboratory conditions and in clinical settings. The key building blocks of this circuit are low dropout regulators, a DC–DC voltage booster and a single high-power current source OP-Amp with current-limiting capabilities. This allows the device to deliver high-voltage, constant current, biphasic pulses without the use of a bulky step-up transformer. The advantages of the proposed design over the currently existing devices include improved safety features (zero DC current, current-limiting mechanism and safe pulses), waveform morphology that causes less muscle fatigue, cost-effectiveness and compact power-efficient circuit design with minimal components. The device is also capable of producing appropriate ankle dorsiflexion in patients having foot drop problems of various Medical Research Council scale grades. PMID:26609419

  15. Design and development of a low-cost biphasic charge-balanced functional electric stimulator and its clinical validation.

    PubMed

    Shendkar, Chandrashekhar; Lenka, Prasanna K; Biswas, Abhishek; Kumar, Ratnesh; Mahadevappa, Manjunatha

    2015-10-01

    Functional electric stimulators that produce near-ideal, charge-balanced biphasic stimulation waveforms with interphase delay are considered safer and more efficacious than conventional stimulators. An indigenously designed, low-cost, portable FES device named InStim is developed. It features a charge-balanced biphasic single channel. The authors present the complete design, mathematical analysis of the circuit and the clinical evaluation of the device. The developed circuit was tested on stroke patients affected by foot drop problems. It was tested both under laboratory conditions and in clinical settings. The key building blocks of this circuit are low dropout regulators, a DC-DC voltage booster and a single high-power current source OP-Amp with current-limiting capabilities. This allows the device to deliver high-voltage, constant current, biphasic pulses without the use of a bulky step-up transformer. The advantages of the proposed design over the currently existing devices include improved safety features (zero DC current, current-limiting mechanism and safe pulses), waveform morphology that causes less muscle fatigue, cost-effectiveness and compact power-efficient circuit design with minimal components. The device is also capable of producing appropriate ankle dorsiflexion in patients having foot drop problems of various Medical Research Council scale grades.

  16. [Phenotype specific therapy of COPD].

    PubMed

    Rothe, Thomas

    2014-12-10

    COPD is not a homogenous disease but consists of at least four different phenotypes: Emphysema, COPD with chronic bronchitis, asthma-COPD overlap syndrome (ACOS), and COPD with recurrent exacerbations. With differentiation, treatment can be designed phenotype-specific. Some modern drugs are not indicated in all phenotypes.

  17. `Weak A' phenotypes

    PubMed Central

    Cartron, J. P.; Gerbal, A.; Hughes-Jones, N. C.; Salmon, C.

    1974-01-01

    Thirty-five weak A samples including fourteen A3, eight Ax, seven Aend, three Am and three Ae1 were studied in order to determine their A antigen site density, using an IgG anti-A labelled with 125I. The values obtained ranged between 30,000 A antigen sites for A3 individuals, and 700 sites for the Ae1 red cells. The hierarchy of values observed made it possible to establish a quantitative relationship between the red cell agglutinability of these phenotypes measured under standard conditions, and their antigen site density. PMID:4435836

  18. The cellular microscopy phenotype ontology.

    PubMed

    Jupp, Simon; Malone, James; Burdett, Tony; Heriche, Jean-Karim; Williams, Eleanor; Ellenberg, Jan; Parkinson, Helen; Rustici, Gabriella

    2016-01-01

    Phenotypic data derived from high content screening is currently annotated using free-text, thus preventing the integration of independent datasets, including those generated in different biological domains, such as cell lines, mouse and human tissues. We present the Cellular Microscopy Phenotype Ontology (CMPO), a species neutral ontology for describing phenotypic observations relating to the whole cell, cellular components, cellular processes and cell populations. CMPO is compatible with related ontology efforts, allowing for future cross-species integration of phenotypic data. CMPO was developed following a curator-driven approach where phenotype data were annotated by expert biologists following the Entity-Quality (EQ) pattern. These EQs were subsequently transformed into new CMPO terms following an established post composition process. CMPO is currently being utilized to annotate phenotypes associated with high content screening datasets stored in several image repositories including the Image Data Repository (IDR), MitoSys project database and the Cellular Phenotype Database to facilitate data browsing and discoverability.

  19. Bioimaging for quantitative phenotype analysis.

    PubMed

    Chen, Weiyang; Xia, Xian; Huang, Yi; Chen, Xingwei; Han, Jing-Dong J

    2016-06-01

    With the development of bio-imaging techniques, an increasing number of studies apply these techniques to generate a myriad of image data. Its applications range from quantification of cellular, tissue, organismal and behavioral phenotypes of model organisms, to human facial phenotypes. The bio-imaging approaches to automatically detect, quantify, and profile phenotypic changes related to specific biological questions open new doors to studying phenotype-genotype associations and to precisely evaluating molecular changes associated with quantitative phenotypes. Here, we review major applications of bioimage-based quantitative phenotype analysis. Specifically, we describe the biological questions and experimental needs addressable by these analyses, computational techniques and tools that are available in these contexts, and the new perspectives on phenotype-genotype association uncovered by such analyses.

  20. Quantification of Microbial Phenotypes

    PubMed Central

    Martínez, Verónica S.; Krömer, Jens O.

    2016-01-01

    Metabolite profiling technologies have improved to generate close to quantitative metabolomics data, which can be employed to quantitatively describe the metabolic phenotype of an organism. Here, we review the current technologies available for quantitative metabolomics, present their advantages and drawbacks, and the current challenges to generate fully quantitative metabolomics data. Metabolomics data can be integrated into metabolic networks using thermodynamic principles to constrain the directionality of reactions. Here we explain how to estimate Gibbs energy under physiological conditions, including examples of the estimations, and the different methods for thermodynamics-based network analysis. The fundamentals of the methods and how to perform the analyses are described. Finally, an example applying quantitative metabolomics to a yeast model by 13C fluxomics and thermodynamics-based network analysis is presented. The example shows that (1) these two methods are complementary to each other; and (2) there is a need to take into account Gibbs energy errors. Better estimations of metabolic phenotypes will be obtained when further constraints are included in the analysis. PMID:27941694

  1. The biphasic nature of hypoxia-induced directional migration of activated human hepatic stellate cells.

    PubMed

    Novo, Erica; Povero, Davide; Busletta, Chiara; Paternostro, Claudia; di Bonzo, Lorenzo Valfrè; Cannito, Stefania; Compagnone, Alessandra; Bandino, Andrea; Marra, Fabio; Colombatto, Sebastiano; David, Ezio; Pinzani, Massimo; Parola, Maurizio

    2012-03-01

    Liver fibrogenesis is sustained by pro-fibrogenic myofibroblast-like cells (MFs), mainly originating from activated hepatic stellate cells (HSC/MFs) or portal (myo)fibroblasts, and is favoured by hypoxia-dependent angiogenesis. Human HSC/MFs were reported to express vascular-endothelial growth factor (VEGF) and VEGF-receptor type 2 and to migrate under hypoxic conditions. This study was designed to investigate early and delayed signalling mechanisms involved in hypoxia-induced migration of human HSC/MFs. Signal transduction pathways and intracellular generation of reactive oxygen species (ROS) were evaluated by integrating morphological, cell, and molecular biology techniques. Non-oriented and oriented migration were evaluated by using wound healing assay and the modified Boyden's chamber assay, respectively. The data indicate that hypoxia-induced migration of HSC/MFs is a biphasic process characterized by the following sequence of events: (a) an early (15 min) and mitochondria-related increased generation of intracellular ROS which (b) was sufficient to switch on activation of ERK1/2 and JNK1/2 that were responsible for the early phase of oriented migration; (c) a delayed and HIF-1α-dependent increase in VEGF expression (facilitated by ROS) and its progressive, time-dependent release in the extracellular medium that (d) was mainly responsible for sustained migration of HSC/MFs. Finally, immunohistochemistry performed on HCV-related fibrotic/cirrhotic livers revealed HIF-2α and haem-oxygenase-1 positivity in hepatocytes and α-SMA-positive MFs, indicating that MFs were likely to be exposed in vivo to both hypoxia and oxidative stress. In conclusion, hypoxia-induced migration of HSC/MFs involves an early, mitochondrial-dependent ROS-mediated activation of ERK and JNK, followed by a delayed- and HIF-1α-dependent up-regulation and release of VEGF.

  2. Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons.

    PubMed

    Sun, Yan-Gang; Pita-Almenar, Juan D; Wu, Chia-Shan; Renger, John J; Uebele, Victor N; Lu, Hui-Chen; Beierlein, Michael

    2013-01-30

    Cholinergic neurons in the basal forebrain and the brainstem form extensive projections to a number of thalamic nuclei. Activation of cholinergic afferents during distinct behavioral states can regulate neuronal firing, transmitter release at glutamatergic and GABAergic synapses, and synchrony in thalamic networks, thereby controlling the flow of sensory information. These effects are thought to be mediated by slow and persistent increases in extracellular ACh levels, resulting in the modulation of populations of thalamic neurons over large temporal and spatial scales. However, the synaptic mechanisms underlying cholinergic signaling in the thalamus are not well understood. Here, we demonstrate highly reliable cholinergic transmission in the mouse thalamic reticular nucleus (TRN), a brain structure essential for sensory processing, arousal, and attention. We find that ACh release evoked by low-frequency stimulation leads to biphasic excitatory-inhibitory (E-I) postsynaptic responses, mediated by the activation of postsynaptic α4β2 nicotinic ACh receptors (nAChRs) and M2 muscarinic ACh receptors (mAChRs), respectively. In addition, ACh can bind to mAChRs expressed near cholinergic release sites, resulting in autoinhibition of release. We show that the activation of postsynaptic nAChRs by transmitter release from only a small number of individual axons is sufficient to trigger action potentials in TRN neurons. Furthermore, short trains of cholinergic synaptic inputs can powerfully entrain ongoing TRN neuronal activity. Our study demonstrates fast and precise synaptic E-I signaling mediated by ACh, suggesting novel computational mechanisms for the cholinergic control of neuronal activity in thalamic circuits.

  3. Single-Step Purification of Ovalbumin from Egg White Using Aqueous Biphasic Systems

    PubMed Central

    Pereira, Matheus M.; Cruz, Rafaela A. P.; Almeida, Mafalda R.; Lima, Álvaro S.; Coutinho, João A. P.; Freire, Mara G.

    2016-01-01

    The ability of aqueous biphasic systems (ABS) composed of polyethylene glycols of different molecular weights (PEG 400, 600 and 1000) and buffered aqueous solutions of potassium citrate/citric acid (pH = 5.0 - 8.0) to selectively extract ovalbumin from egg white was here investigated. Phase diagrams, tie-lines and tie-line lengths were determined at 25ºC and the partitioning of ovalbumin in these systems was then evaluated. Aiming at optimizing the selective extraction of ovalbumin in the studied ABS, factors such as pH, PEG molecular weight and amount of the phase-forming components were initially investigated with pure commercial ovalbumin. In almost all ABS, it was observed a preferential partitioning of ovalbumin to the polymer-rich phase, with extraction efficiencies higher than 90%. The best ABS were then applied in the purification of ovalbumin from the real egg white matrix. In order to ascertain on the ovalbumin purity and yield, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion high performance liquid chromatography (SE-HPLC) analyses were conducted, confirming that the isolation/purification of ovalbumin from egg white was completely achieved in a single-step with a recovery yield of 65%. The results obtained show that polymer-salt-based ABS allow the selective extraction of ovalbumin from egg white with a simpler approach and better performance than previously reported. Finally, it is shown that ovalbumin can be completely recovered from the PEG-rich phase by an induced precipitation using an inexpensive and sustainable separation platform which can be easily applied on an industrial scale. PMID:27642253

  4. Microstructural control of modular peptide release from microporous biphasic calcium phosphate.

    PubMed

    Polak, Samantha J; Lee, Jae Sung; Murphy, William L; Tadier, Solène; Grémillard, Laurent; Lightcap, Ian V; Wagoner Johnson, Amy J

    2017-03-01

    Drug release from tissue scaffolds is commonly controlled by using coatings and carriers, as well as by varying the binding affinity of molecules being released. This paper considers modulating synthetic peptide incorporation and release through the use of interconnected microporosity in biphasic calcium phosphate (BCP) and identifies the microstructural characteristics important to the release using experiments and a model of relative diffusivity. First, the release of three modular peptides designed to include an osteocalcin-inspired binding sequence based on bone morphogenic protein-2 (BMP-2) was compared and one was selected for further study. Next, the incorporation and release of the peptide from four types of substrates were compared: non-microporous (NMP) substrates had no microporosity; microporous (MP) substrates were either 50% microporous with 5μm pores (50/5), 60% microporous with 5μm pores (60/5), or 50% microporous with 50μm pores (50/50). Results showed that MP substrates incorporated significantly more peptide than NMP ones, but that the three different microporous substrates all incorporated the same total amount of peptide. NMP had a markedly lower release rate compared to each of three of the MP samples, though the initial burst release was the highest. The initial release and the release rate for the 60/5 samples were different from the 50/50, though they were not statistically different from the 50/5. The model indicated that the pore interconnection to pore size ratio, affecting the constriction between pores, had the greatest influence on the calculated relative diffusivity. While the model was consistent with the trends observed experimentally, the quantitative experimental results suggested that to attain an appreciable difference in release characteristics, both pore size and pore fraction should be changed for this system. These results contribute to rational scaffold design by showing that microstructure, specifically microporosity

  5. Electrochemical assessment of water|ionic liquid biphasic systems towards cesium extraction from nuclear waste.

    PubMed

    Stockmann, T Jane; Zhang, Jing; Montgomery, Anne-Marie; Ding, Zhifeng

    2014-04-22

    A room temperature ionic liquid (IL) composed of a quaternary alkylphosphonium (trihexyltetradecylphosphonium, P66614(+)) and tetrakis(pentafluorophenyl)borate anion (TB(-)) was employed within a water|P66614TB (w|P66614TB or w|IL) biphasic system to evaluate cesium ion extraction in comparison to that with a traditional water|organic solvent (w|o) combination. (137)Cs is a major contributor to the radioactivity of spent nuclear fuel as it leaves the reactor, and its extraction efficiency is therefore of considerable importance. The extraction was facilitated by the ligand octyl(phenyl)-N,N'-diisobutylcarbamoylphosphine oxide (CMPO) used in TRans-Uranium EXtraction processes and investigated through well established liquid|liquid electrochemistry. This study gave access to the metal ion to ligand (1:n) stoichiometry and overall complexation constant, β, of the interfacial complexation reaction which were determined to be 1:3 and 1.6×10(11) at the w|P66614TB interface while the study at w|o elicited an n equal to 1 with β equal to 86.5. Through a straightforward relationship, these complexation constant values were converted to distribution coefficients, δ(α), with the ligand concentrations studied for comparison to other studies present in the literature; the w|o and w|IL systems gave δ(α) of 2 and 8.2×10(7), respectively, indicating a higher overall extraction efficiency for the latter. For the w|o system, the metal ion-ligand stoichiometries were confirmed through isotopic distribution analysis of mass spectra obtained by the direct injection of an emulsified water-organic solvent mixture into an electron spray ionization mass spectrometer.

  6. Clinical feasibility of a novel biphasic osteochondral composite for matrix-associated autologous chondrocyte implantation.

    PubMed

    Chiang, H; Liao, C-J; Hsieh, C-H; Shen, C-Y; Huang, Y-Y; Jiang, C-C

    2013-04-01

    Matrix-associated autologous chondrocyte implantation has been used to treat cartilage defects. We developed a biphasic cylindrical osteochondral composite construct for such use, and conducted this study to determine its feasibility for treating osteochondral lesions in human knees. Ten patients with symptomatic osteochondral lesions at femoral condyles were treated by replacing pathological tissue with the construct of dl-poly-lactide-co-glycolide, whose lower body was impregnated with β-tricalcium phosphate and served as osseous phase. The construct had a chamber to load double-minced autologous cartilage, serving as source of chondrocytes. Osteochondral lesion was drill-fashioned a pit of identical dimension as the construct. Chondrocyte-laden construct was press-fit to fill the pit. Postoperative outcome was evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS) scale up to 24 months. Magnetic resonance image was taken, and sample tissue was collected with second-look arthroscopic needle biopsy at 12 months. Outcome parameters were primarily safety of surgery, and secondarily postoperative change in KOOS and regeneration of hyaline cartilage and cancellous bone. No patient experienced serious adverse events. Postoperative mean KOOS in "symptoms" subscale had not changed significantly from pre-operation until 24 months; whereas those in the other four subscales were significantly higher than pre-operation at 12 and 24 months. Second-look arthroscopy showed completely filled grafted sites, with regenerate cartilaginous surfaces flushed with surrounding native joint surface. Microscopically, regenerated cartilage appeared hyaline. This novel construct for chondrocyte implantation is safe for surgical application in knee. It repairs osteochondral lesions of femoral condyles by successful regeneration of hyaline cartilage. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  7. FK506 induces biphasic Ca2+ release from microsomal vesicles of rat pancreatic acinar cells.

    PubMed

    Ozawa, Terutaka

    2006-07-01

    The effect of the immunosuppressant drug FK506 on microsomal Ca2+ release was investigated in rat pancreatic acinar cells. When FK506 (0.1-200 microM) was added to the microsomal vesicles at a steady state of ATP-dependent 45Ca2+ uptake, FK506 caused a dose-dependent and a biphasic release of 45Ca2+. Almost 10% of total 45Ca2+ uptake was released at FK506 concentrations up to 10 microM (Km=0.47 microM), and 60% of total 45Ca2+ uptake was released at FK506 concentrations over 10 microM (Km=55 microM). Preincubation of the vesicles with cyclic ADP-ribose (cADPR, 0.5 microM) increased the FK506 (< or =10 microM)-induced 45Ca2+ release (Ozawa T, Biochim Biophys Acta 1693: 159-166, 2004). Preincubation with heparin (200 microg/ml) resulted in significant inhibition of the FK506 (30 microM)-induced 45Ca2+ release. Subsequent addition of inositol 1,4,5-trisphosphate (IP3, 5 microM) after FK506 (100 microM)-induced 45Ca2+ release did not cause any release of 45Ca2+. These results indicate that two types of FK506-induced Ca2+ release mechanism operate in the endoplasmic reticulum of rat pancreatic acinar cells: a high-affinity mechanism of Ca2+ release, which involves activation of the ryanodine receptor, and a low-affinity mechanism of Ca2+ release, which involves activation of the IP3 receptor.

  8. Evaluation of a biphasic media assay for pyrazinamide drug susceptibility testing of Mycobacterium tuberculosis.

    PubMed

    Gonzalo, X; Drobniewski, F; Hoffner, S; Werngren, J

    2014-11-01

    Pyrazinamide is a key first-line tuberculosis drug. Reliable drug susceptibility testing (DST) data are of clinical importance, but in vitro testing is challenging since the activity of pyrazinamide is pH sensitive. The BACTEC MGIT 960 is considered the principal reference technique, but Wayne's test is an alternative, although it may be difficult to interpret. A further alternative is the use of a biphasic media assay (BMA). The objective of this work was to evaluate the BMA against the MGIT method and with screening of pncA gene mutations. Twenty strains were inoculated in tubes containing 2 mL of Löwenstein-Jensen (LJ) medium and 2 mL of semi-solid Kirchner medium with a critical concentration of 66 mg/L pyrazinamide at a pH of 5.2 or 5.5, incubated for 2 weeks and visually read. The results obtained were compared with MGIT 960 and DNA sequencing. Results were obtained in duplicate for 19 strains. One strain failed to grow on two occasions and only one result was available. Reproducibility was 95%. Eleven of the 19 strains were susceptible to pyrazinamide, whereas 7 were resistant. One strain was susceptible initially and pyrazinamide resistant on repeat testing. At pH 5.5, two strains reported as susceptible at pH 5.2 gave resistant results. The BMA might serve as a reliable low-cost DST alternative for pyrazinamide, particularly in laboratories using locally made solid media for DST. Its major drawback is the time to result. A reliable and affordable test method for the detection of pyrazinamide resistance is needed, especially in settings where multidrug-resistant tuberculosis is increasing. Proficiency testing should be routinely introduced wherever pyrazinamide DST is performed. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Nicotinic receptor-mediated biphasic effect on neuronal excitability in chick lateral spiriform neurons.

    PubMed

    Liu, Y-B; Guo, J-Z; Chiappinelli, V A

    2007-09-21

    Local neuronal circuits integrate synaptic information with different excitatory or inhibitory time windows. Here we report that activation of nicotinic acetylcholine receptors (nAChRs) leads to biphasic effects on excitability in chick lateral spiriform (SPL) neurons during whole cell recordings in brain slices. Carbachol (100 microM in the presence of 1 microM atropine) produced an initial short-term increase in the firing rates of SPL neurons (125+/-14% of control) that was mediated by postsynaptic nAChRs. However, after 3 min exposure to nicotinic agonists, the firing rate measured during an 800 ms depolarizing pulse declined to 19+/-7% (100 microM carbachol) or 26+/-8% (10 microM nicotine) of the control rate and remained decreased for 10-20 min after washout of the agonists. Similarly, after 60 s of electrically-stimulated release of endogenous acetylcholine (ACh) from cholinergic afferent fibers, there was a marked reduction (45+/-5% of control) in firing rates in SPL neurons. All of these effects were blocked by the nAChR antagonist dihydro-beta-erythroidine (30 microM). The inhibitory effect was not observed in Ca(2+)-free buffer. The nAChR-mediated inhibition depended on active G-proteins in SPL neurons and was prevented by the GABA(B) receptor antagonist phaclofen (200 microM), while the GABA(B) receptor agonist baclofen (10 microM) decreased firing rate in SPL neurons to 13+/-1% of control. The inhibitory response thus appears to be due to a nAChR-mediated enhancement of presynaptic GABA release, which then activates postsynaptic GABA(B) receptors. In conclusion, activation of nAChRs in the SPL initiates a limited time window for an excitatory period, after which a prolonged inhibitory effect turns off this window. The prolonged inhibitory effect may serve to protect SPL neurons from excessive excitation.

  10. Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response

    PubMed Central

    Gardiner, Sheila M; March, Julie E; Kemp, Philip A; Bennett, Terence

    2004-01-01

    A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg−1) in conscious, male, Sprague–Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0–5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30–120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred. Pretreatment with indomethacin or NG nitro-L-arginine methylester (L-NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and L-NAME together prevented all haemodynamic responses to hUII. Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol. In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation. Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs. One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid- or prostanoid- and NO-mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia). PMID:15339862

  11. Bio-Impedance Characterization Technique with Implantable Neural Stimulator Using Biphasic Current Stimulus

    PubMed Central

    Lo, Yi-Kai; Chang, Chih-Wei; Liu, Wentai

    2016-01-01

    Knowledge of the bio-impedance and its equivalent circuit model at the electrode-electrolyte/tissue interface is important in the application of functional electrical stimulation. Impedance can be used as a merit to evaluate the proximity between electrodes and targeted tissues. Understanding the equivalent circuit parameters of the electrode can further be leveraged to set a safe boundary for stimulus parameters in order not to exceed the water window of electrodes. In this paper, we present an impedance characterization technique and implement a proof-of-concept system using an implantable neural stimulator and an off-the-shelf microcontroller. The proposed technique yields the parameters of the equivalent circuit of an electrode through large signal analysis by injecting a single low-intensity biphasic current stimulus with deliberately inserted inter-pulse delay and by acquiring the transient electrode voltage at three well-specified timings. Using low-intensity stimulus allows the derivation of electrode double layer capacitance since capacitive charge-injection dominates when electrode overpotential is small. Insertion of the inter-pulse delay creates a controlled discharge time to estimate the Faradic resistance. The proposed method has been validated by measuring the impedance of a) an emulated Randles cells made of discrete circuit components and b) a custom-made platinum electrode array in-vitro, and comparing estimated parameters with the results derived from an impedance analyzer. The proposed technique can be integrated into implantable or commercial neural stimulator system at low extra power consumption, low extra-hardware cost, and light computation. PMID:25569999

  12. Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion.

    PubMed

    Peyton, Shelly R; Putnam, Andrew J

    2005-07-01

    Increasing evidence suggests that mechanical cues inherent to the extracellular matrix (ECM) may be equally as critical as its chemical identity in regulating cell behavior. We hypothesized that the mechanical properties of the ECM directly regulate the motility of vascular smooth muscle cells (SMCs) and tested this hypothesis using polyacrylamide substrates with tunable mechanical properties. Quantification of the migration speed on uniformly compliant hydrogels spanning a range of stiffnesses (Young's moduli values from 1.0 to 308 kPa for acrylamide/bisacrylamide ratios between 5/0.1% and 15/1.2%, respectively) revealed a biphasic dependence on substrate compliance, suggesting the existence of an optimal substrate stiffness capable of supporting maximal migration. The value of this optimal stiffness shifted depending on the concentration of ECM protein covalently attached to the substrate. Specifically, on substrates presenting a theoretical density of 0.8 microg/cm(2) fibronectin, the maximum speed of 0.74 +/- 0.09 microm/min was achieved on a 51.9 kPa gel; on substrates presenting a theoretical density of 8.0 microg/cm(2) fibronectin, the maximum speed of 0.72 +/- 0.06 microm/min occurred on a softer 21.6 kPa gel. Pre-treatment of cells with Y27632, an inhibitor of the Rho/Rho-kinase (ROCK) pathway, reduced these observed maxima to values comparable to those on non-optimal stiffnesses. In parallel, quantification of TritonX-insoluble vinculin via Western blotting, coupled with qualitative fluorescent microscopy, revealed that the formation of focal adhesions and actin stress fibers also depends on ECM stiffness. Combined, these data suggest that the mechanical properties of the underlying ECM regulate Rho-mediated contractility in SMCs by disrupting a presumptive cell-ECM force balance, which in turn regulates cytoskeletal assembly and ultimately, cell migration. (c) 2004 Wiley-Liss, Inc.

  13. Evaluation of a post-processing approach for multiscale analysis of biphasic mechanics of chondrocytes.

    PubMed

    Sibole, Scott C; Maas, Steve; Halloran, Jason P; Weiss, Jeffrey A; Erdemir, Ahmet

    2013-10-01

    Understanding the mechanical behaviour of chondrocytes as a result of cartilage tissue mechanics has significant implications for both evaluation of mechanobiological function and to elaborate on damage mechanisms. A common procedure for prediction of chondrocyte mechanics (and of cell mechanics in general) relies on a computational post-processing approach where tissue-level deformations drive cell-level models. Potential loss of information in this numerical coupling approach may cause erroneous cellular-scale results, particularly during multiphysics analysis of cartilage. The goal of this study was to evaluate the capacity of first- and second-order data passing to predict chondrocyte mechanics by analysing cartilage deformations obtained for varying complexity of loading scenarios. A tissue-scale model with a sub-region incorporating representation of chondron size and distribution served as control. The post-processing approach first required solution of a homogeneous tissue-level model, results of which were used to drive a separate cell-level model (same characteristics as the sub-region of control model). The first-order data passing appeared to be adequate for simplified loading of the cartilage and for a subset of cell deformation metrics, for example, change in aspect ratio. The second-order data passing scheme was more accurate, particularly when asymmetric permeability of the tissue boundaries was considered. Yet, the method exhibited limitations for predictions of instantaneous metrics related to the fluid phase, for example, mass exchange rate. Nonetheless, employing higher order data exchange schemes may be necessary to understand the biphasic mechanics of cells under lifelike tissue loading states for the whole time history of the simulation.

  14. Hyperpolarized gas diffusion MRI of biphasic lung inflation in short- and long-term emphysema models.

    PubMed

    Xin, Yi; Cereda, Maurizio; Kadlecek, Stephen; Emami, Kiarash; Hamedani, Hooman; Duncan, Ian; Rajaei, Jennia; Hughes, Liam; Meeder, Natalie; Naji, Joseph; Profka, Harrilla; Bolognese, Brian J; Foley, Joseph P; Podolin, Patricia L; Rizi, Rahim R

    2017-08-01

    During lung inflation, airspace dimensions are affected nonlinearly by both alveolar expansion and recruitment, potentially confounding the identification of emphysematous lung by hyperpolarized helium-3 diffusion magnetic resonance imaging (HP MRI). This study aimed to characterize lung inflation over a broad range of inflation volume and pressure values in two different models of emphysema, as well as in normal lungs. Elastase-treated rats (n = 7) and healthy controls (n = 7) were imaged with HP MRI. Gradual inflation was achieved by incremental changes to both inflation volume and airway pressure. The apparent diffusion coefficient (ADC) was measured at each level of inflation and fitted to the corresponding airway pressures as the second-order response equation, with minimizing residue (χ(2) < 0.001). A biphasic ADC response was detected, with an initial ADC increase followed by a decrease at airway pressures >18 cmH2O. Discrimination between treated and control rats was optimal when airway pressure was intermediate (between 10 and 11 cmH2O). Similar findings were confirmed in mice following long-term exposure to cigarette smoke, where optimal discrimination between treated and healthy mice occurred at a similar airway pressure as in the rats. We subsequently explored the evolution of ADC measured at the intermediate inflation level in mice after prolonged smoke exposure and found a significant increase (P < 0.01) in ADC over time. Our results demonstrate that measuring ADC at intermediate inflation enhances the distinction between healthy and diseased lungs, thereby establishing a model that may improve the diagnostic accuracy of future HP gas diffusion studies. Copyright © 2017 the American Physiological Society.

  15. Single-Step Purification of Ovalbumin from Egg White Using Aqueous Biphasic Systems.

    PubMed

    Pereira, Matheus M; Cruz, Rafaela A P; Almeida, Mafalda R; Lima, Álvaro S; Coutinho, João A P; Freire, Mara G

    2016-06-01

    The ability of aqueous biphasic systems (ABS) composed of polyethylene glycols of different molecular weights (PEG 400, 600 and 1000) and buffered aqueous solutions of potassium citrate/citric acid (pH = 5.0 - 8.0) to selectively extract ovalbumin from egg white was here investigated. Phase diagrams, tie-lines and tie-line lengths were determined at 25ºC and the partitioning of ovalbumin in these systems was then evaluated. Aiming at optimizing the selective extraction of ovalbumin in the studied ABS, factors such as pH, PEG molecular weight and amount of the phase-forming components were initially investigated with pure commercial ovalbumin. In almost all ABS, it was observed a preferential partitioning of ovalbumin to the polymer-rich phase, with extraction efficiencies higher than 90%. The best ABS were then applied in the purification of ovalbumin from the real egg white matrix. In order to ascertain on the ovalbumin purity and yield, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion high performance liquid chromatography (SE-HPLC) analyses were conducted, confirming that the isolation/purification of ovalbumin from egg white was completely achieved in a single-step with a recovery yield of 65%. The results obtained show that polymer-salt-based ABS allow the selective extraction of ovalbumin from egg white with a simpler approach and better performance than previously reported. Finally, it is shown that ovalbumin can be completely recovered from the PEG-rich phase by an induced precipitation using an inexpensive and sustainable separation platform which can be easily applied on an industrial scale.

  16. Direct 3D powder printing of biphasic calcium phosphate scaffolds for substitution of complex bone defects.

    PubMed

    Castilho, Miguel; Moseke, Claus; Ewald, Andrea; Gbureck, Uwe; Groll, Jürgen; Pires, Inês; Teßmar, Jörg; Vorndran, Elke

    2014-03-01

    The 3D printing technique based on cement powders is an excellent method for the fabrication of individual and complex bone substitutes even in the case of large defects. The outstanding bone remodeling capacity of biphasic calcium phosphates (BCPs) containing hydroxyapatite (HA) as well as tricalcium phosphate (TCP) in varying ratios makes the adaption of powder systems resulting in BCP materials to this fabrication technique a desirable aim. This study presents the synthesis and characterization of a novel powder system for the 3D printing process, intended for the production of complexly shaped BCP scaffolds by a hydraulic setting reaction of calcium carbonate and TCP with phosphoric acid. The HA/TCP ratio in the specimens could be tailored by the calcium/phosphate ratio of the starting powder. The scaffolds could be fabricated with a dimensional accuracy of >96.5% and a minimal macro pore size of 300 µm. Independent of the phase composition the printed specimens showed a microporosity of approximately 68%, while the compressive strength strongly depended on the chemical composition and increased with rising TCP content in the scaffolds to a maximum of 1.81 MPa. Post-treatment of the scaffolds with a polylactic-co-glycolic acid-solution enhanced the mechanical properties by a factor of 8. In vitro studies showed that all BCP scaffolds were cytocompatible and enhanced the cell viability as well as the cell proliferation, as compared with pure TCP. Cell proliferation is even better on BCP when compared to HA and cell viability is in a similar range on these materials.

  17. Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

    PubMed Central

    Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

    2011-01-01

    Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

  18. Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

    PubMed

    Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

    2017-05-17

    His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

  19. Response of stem cells from different origins to biphasic calcium phosphate bioceramics.

    PubMed

    Lobo, Sonja E; Glickman, Robert; da Silva, Wagner N; Arinzeh, Treena L; Kerkis, Irina

    2015-08-01

    Biphasic calcium phosphate (BCP) bioceramics have been successfully applied in a broad variety of presentation forms and with different ratios of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). BCPs have been loaded with stem cells from different origins for bone tissue engineering purposes, but evidence of stem cell behavior on different compositions (various HA/β-TCP ratios) and physical features of BCPs is limited. We compared the adhesion, proliferation, viability and osteogenic potential of human mesenchymal stem cells (MSCs) on granular BCPs with equal HA/β-TCP ratio of diverse particle sizes and on porous blocks which had different chemical compositions. In addition, the osteogenic differentiation of MSCs was compared to adipose-derived (ADSC) and dental pulp (DPSC) stem cells, as well as to pre-osteoblasts on a particulate BCP. MSCs growing on granular BCPs demonstrated increased number as compared to MSCs growing on blocks. Cells proliferated to a greater extent on small granular BCPs, while large granular BCPs and blocks promoted cell differentiation. Surprisingly, the expression of genes involved in osteogenesis was upregulated in MSCs on bioceramics in basal medium which indicates that BCPs may have osteoinductive potential. This was confirmed with the upregulation of osteochondrogenic markers, at different time points, when stem cells from various tissues were grown on the BCP. This study demonstrates that BCPs, depending on their physical features and chemical composition, modulate stem cell behavior, and that stem cells from different origins are inherently distinct in their gene expression profile and can be triggered toward osteochondrogenic fate by BCPs.

  20. Atomic scale modeling of iron-doped biphasic calcium phosphate bioceramics.

    PubMed

    Gomes, Sandrine; Kaur, Amandeep; Grenèche, Jean-Marc; Nedelec, Jean-Marie; Renaudin, Guillaume

    2017-03-01

    Biphasic calcium phosphates (BCPs) are bioceramics composed of hydroxyapatite (HAp, Ca10(PO4)6(OH)2) and beta-Tricalcium Phosphate (β-TCP, Ca3(PO4)2). Because their chemical and mineral composition closely resembles that of the mineral component of bone, they are potentially interesting candidates for bone repair surgery, and doping can advantageously be used to improve their biological behavior. However, it is important to describe the doping mechanism of BCP thoroughly in order to be able to master its synthesis and then to fully appraise the benefit of the doping process. In the present paper we describe the ferric doping mechanism: the crystallographic description of our samples, sintered at between 500°C and 1100°C, was provided by Rietveld analyses on X-ray powder diffraction, and the results were confirmed using X-ray absorption spectroscopy and (57)Fe Mössbauer spectrometry. The mechanism is temperature-dependent, like the previously reported zinc doping mechanism. Doping was performed on the HAp phase, at high temperature only, by an insertion mechanism. The Fe(3+) interstitial site is located in the HAp hexagonal channel, shifted from its centre to form a triangular three-fold coordination. At lower temperatures, the Fe(3+) are located at the centre of the channel, forming linear two-fold coordinated O-Fe-O entities. The knowledge of the doping mechanism is a prerequisite for a correct synthesis of the targeted bioceramic with the adapted (Ca+Fe)/P ratio, and so to be able to correctly predict its potential iron release or magnetic properties.

  1. Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion.

    PubMed

    Lee, Hsin-Ling; Chen, Chwen-Lih; Yeh, Steve T; Zweier, Jay L; Chen, Yeong-Renn

    2012-04-01

    Mitochondrial electron transport chain (ETC) is the major source of reactive oxygen species during myocardial ischemia-reperfusion (I/R) injury. Ischemic defect and reperfusion-induced injury to ETC are critical in the disease pathogenesis of postischemic heart. The properties of ETC were investigated in an isolated heart model of global I/R. Rat hearts were subjected to ischemia for 30 min followed by reperfusion for 1 h. Studies of mitochondrial function indicated a biphasic modulation of electron transfer activity (ETA) and ETC protein expression during I/R. Analysis of ETAs in the isolated mitochondria indicated that complexes I, II, III, and IV activities were diminished after 30 min of ischemia but increased upon restoration of flow. Immunoblotting analysis and ultrastructural analysis with transmission electron microscopy further revealed marked downregulation of ETC in the ischemic heart and then upregulation of ETC upon reperfusion. No significant difference in the mRNA expression level of ETC was detected between ischemic and postischemic hearts. However, reperfusion-induced ETC biosynthesis in myocardium can be inhibited by cycloheximide, indicating the involvement of translational control. Immunoblotting analysis of tissue homogenates revealed a similar profile in peroxisome proliferator-activated receptor-γ coactivator-1α expression, suggesting its essential role as an upstream regulator in controlling ETC biosynthesis during I/R. Significant impairment caused by ischemic and postischemic injury was observed in the complexes I- III. Analysis of NADH ferricyanide reductase activity indicated that injury of flavoprotein subcomplex accounts for 50% decline of intact complex I activity from ischemic heart. Taken together, our findings provide a new insight into the molecular mechanism of I/R-induced mitochondrial dysfunction.

  2. Biphasic role of dopamine on female sexual behaviour via D2 receptors in the mediobasal hypothalamus.

    PubMed

    Fabre-Nys, Claude; Chesneau, Didier; de la Riva, Carlos; Hinton, Michael R; Locatelli, Alain; Ohkura, Satoshi; Kendrick, Keith M

    2003-03-01

    Dopamine has been implicated in the control of sexual behaviour, but its role seems quite complex and controversial. The aim of the present experiments was to investigate the effects of dopamine (DA) acting on D2 receptors in the mediobasal hypothalamus (MBH) on sexual behaviour in female sheep. To achieve this, the D2 agonist, quinpirole, was administered bilaterally via microdialysis probes into the MBH of ovariectomized ewes either before or after oestradiol (E2) administration. Quinpirole (100 ng/ml) infused for 6 h just before E2 hastened the onset of oestrus behaviour and the luteinizing hormone surge, whereas the same treatment given 6-12 h or 18-21 h after E2 decreased the intensity of sexual receptivity without affecting LH or prolactin secretion. We then tested the hypothesis that E2 stimulates the onset of oestrus partly by decreasing DA activation of D2 receptors. In this case the D2 antagonists pimozide or spiperone (100 ng/ml) were infused into the MBH via microdialysis probes for 11 h in the absence of E2 administration. A significant number of ewes showed induction of receptivity with both antagonists, although its intensity was significantly lower than that induced by E2. These treatments generally did not significantly alter extracellular concentrations of monoamines or aminoacids although quinpirole modulated the ability of sexual interactions to increase noradrenaline release. These experiments show that DA acts via D2 receptors in the MBH to control female sexual behaviour in a biphasic manner: the onset of sexual motivation and receptivity requiring an initial increase in activation followed by a decrease. This dual action could explain some of the controversies concerning DA action on sexual behaviour.

  3. Evaluation of a Post-Processing Approach for Multiscale Analysis of Biphasic Mechanics of Chondrocytes

    PubMed Central

    Sibole, Scott C.; Maas, Steve; Halloran, Jason P.; Weiss, Jeffrey A.; Erdemir, Ahmet

    2014-01-01

    Understanding the mechanical behavior of chondrocytes as a result of cartilage tissue mechanics has significant implications for both evaluation of mechanobiological function and to elaborate on damage mechanisms. A common procedure for prediction of chondrocyte mechanics (and of cell mechanics in general) relies on a computational post-processing approach where tissue level deformations drive cell level models. Potential loss of information in this numerical coupling approach may cause erroneous cellular scale results, particularly during multiphysics analysis of cartilage. The goal of this study was to evaluate the capacity of 1st and 2nd order data passing to predict chondrocyte mechanics by analyzing cartilage deformations obtained for varying complexity of loading scenarios. A tissue scale model with a sub-region incorporating representation of chondron size and distribution served as control. The postprocessing approach first required solution of a homogeneous tissue level model, results of which were used to drive a separate cell level model (same characteristics as the subregion of control model). The 1st data passing appeared to be adequate for simplified loading of the cartilage and for a subset of cell deformation metrics, e.g., change in aspect ratio. The 2nd order data passing scheme was more accurate, particularly when asymmetric permeability of the tissue boundaries were considered. Yet, the method exhibited limitations for predictions of instantaneous metrics related to the fluid phase, e.g., mass exchange rate. Nonetheless, employing higher-order data exchange schemes may be necessary to understand the biphasic mechanics of cells under lifelike tissue loading states for the whole time history of the simulation. PMID:23809004

  4. Mechanisms of the biphasic effects of peroxides on the retinal vasculature of newborn and adult pigs.

    PubMed

    Abran, D; Hardy, P; Varma, D R; Chemtob, S

    1995-09-01

    We tested whether the ontogenic differences in the constrictor effects of peroxides on the retinal vasculature were modulated by dilator cyclo-oxygenase products. Retinal arteriole (100-200 microns) vasomotor response to H2O2, t-butyl hydroperoxide, and cumene hydroperoxide were studied in isolated eyecup preparations using video camera monitoring of vessel diameter. A time- and dose-dependent biphasic retinal vasomotor response to all peroxides was observed on tissues of newborn and adult pigs. A rapid vasoconstriction (first 2 min) was followed by a relaxation which was greater in the adult than in the newborn tissues. The constrictor as well as the dilator response to peroxides and the observed increase in prostanoids were blocked by the cyclo-oxygenase inhibitor indomethacin. The peroxide-induced relaxation was inhibited or markedly attenuated by the prostaglandin I2 synthase blockers, trans-2-phenyl cyclopropylamine and minoxidil on tissues of newborn and adult animals. These agents also prevented the increase of the prostaglandin I2 receptor-coupled second messenger, cyclic 3',5'-adenosine monophosphate. Our data indicate that prostaglandin I2 plays a major role in counteracting the initial constrictor effects of peroxides in the retinal vasculature, and that the reversal of this constriction is greater in the adult than the newborn. These findings suggest that reduced reversal of vasoconstriction by the dilator prostaglandin I2 during an oxidative stress in the newborn may facilitate vasoconstriction by the dilator prostaglandin I2 during an oxidative stress in the newborn may facilitate neovascularization in retinopathy of prematurity.

  5. Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats

    PubMed Central

    Zhou, Rong; Ding, Xiao-li; Liu, Liang-ming

    2014-01-01

    Aim: Ryanodine receptor 2 (RyR2) is a critical component of intracellular Ca2+ signaling in vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats. Methods: SD rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries (SMA) rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca2+ release in VSMCs was assessed using Fura-2/AM. Results: The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage (30 min), but decreased in the late stage (2 h) of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 min or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine (1 mmol/L) significantly increased Ca2+ release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA. Conclusion: RyR2-mediated Ca2+ release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia. PMID:25263335

  6. Porous hydroxyapatite and biphasic calcium phosphate ceramics promote ectopic osteoblast differentiation from mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Zhang, Lingli; Hanagata, Nobutaka; Maeda, Megumi; Minowa, Takashi; Ikoma, Toshiyuki; Fan, Hongsong; Zhang, Xingdong

    2009-04-01

    Because calcium phosphate (Ca-P) ceramics have been used as bone substitutes, it is necessary to investigate what effects the ceramics have on osteoblast maturation. We prepared three types of Ca-P ceramics with different Ca-P ratios, i.e. hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), and biphasic calcium phosphate (BCP) ceramics with dense-smooth and porous structures. Comprehensive gene expression microarray analysis of mouse osteoblast-like cells cultured on these ceramics revealed that porous Ca-P ceramics considerably affected the gene expression profiles, having a higher potential for osteoblast maturation. In the in vivo study that followed, porous Ca-P ceramics were implanted into rat skeletal muscle. Sixteen weeks after the implantation, more alkaline-phosphatase-positive cells were observed in the pores of hydroxyapatite and BCP, and the expression of the osteocalcin gene (an osteoblast-specific marker) in tissue grown in pores was also higher in hydroxyapatite and BCP than in β-TCP. In the pores of any Ca-P ceramics, 16 weeks after the implantation, we detected the expressions of marker genes of the early differentiation stage of chondrocytes and the complete differentiation stage of adipocytes, which originate from mesenchymal stem cells, as well as osteoblasts. These marker gene expressions were not observed in the muscle tissue surrounding the implanted Ca-P ceramics. These observations indicate that porous hydroxyapatite and BCP had a greater potential for promoting the differentiation of mesenchymal stem cells into osteoblasts than β-TCP.

  7. Tuning the Interfacial Activity of Mesoporous Silicas for Biphasic Interface Catalysis Reactions.

    PubMed

    Xue, Fen; Zhang, Yabin; Zhang, Fengwei; Ren, Xiaomin; Yang, Hengquan

    2017-03-08

    Interface-active particle materials that are able to assemble at the oil/water interface so as to stabilize droplets, are gaining unprecedented interest due to the intriguing applications in catalysis and materials synthesis, etc. In contrast to these potential applications, this kind of materials are still limited and cannot meet some particular demands of practical utilizations such as rationally designed interfacial activity and high stability against concentrated salts. In this contribution, interface-active mesoporous silica nanospheres (MSS@CxZy) are synthesized through simultaneous incorporation of extremely hydrophilic zwitterionic moiety and hydrophobic octyl moiety in the shell. The textural properties of these materials are characterized by transmission electron microscopy (TEM), powder X-ray diffraction (XRD), and nitrogen sorption. The successful decoration of these functionalities in the shell is confirmed by Fourier transform infrared spectra (FT-IR), (13)C nuclear cross-polar magnetic resonance ((13)C CP/MAS NMR), and (29)Si nuclear cross-polar magnetic resonance ((29)Si CP/MAS NMR). The prepared mesoporous silicas exhibit tunable interfacial activity, so that oil-in-water (O/W) and water-in-oil (W/O) Pickering emulsions can be easily obtained by varying the molar fraction of these two functionalities. The MSS@CxZy-stabilized Pickering emulsions exhibit high stability to coalescence even at 6.0 M NaCl and have relatively low surface coverage of droplets due to electrostatic repulsion, which is normally difficult to obtain for conventional particles. Interestingly, such interface-active mesoporous silicas can also carry polyoxometalate that is hosted in the nanopore to assemble at the oil/water interface and thus efficiently promotes biphasic epoxidation reactions without any external stirring, exemplifying an innovative application of theses developed mesoporous silicas.

  8. Bio-impedance characterization technique with implantable neural stimulator using biphasic current stimulus.

    PubMed

    Lo, Yi-Kai; Chang, Chih-Wei; Liu, Wentai

    2014-01-01

    Knowledge of the bio-impedance and its equivalent circuit model at the electrode-electrolyte/tissue interface is important in the application of functional electrical stimulation. Impedance can be used as a merit to evaluate the proximity between electrodes and targeted tissues. Understanding the equivalent circuit parameters of the electrode can further be leveraged to set a safe boundary for stimulus parameters in order not to exceed the water window of electrodes. In this paper, we present an impedance characterization technique and implement a proof-of-concept system using an implantable neural stimulator and an off-the-shelf microcontroller. The proposed technique yields the parameters of the equivalent circuit of an electrode through large signal analysis by injecting a single low-intensity biphasic current stimulus with deliberately inserted inter-pulse delay and by acquiring the transient electrode voltage at three well-specified timings. Using low-intensity stimulus allows the derivation of electrode double layer capacitance since capacitive charge-injection dominates when electrode overpotential is small. Insertion of the inter-pulse delay creates a controlled discharge time to estimate the Faradic resistance. The proposed method has been validated by measuring the impedance of a) an emulated Randles cells made of discrete circuit components and b) a custom-made platinum electrode array in-vitro, and comparing estimated parameters with the results derived from an impedance analyzer. The proposed technique can be integrated into implantable or commercial neural stimulator system at low extra power consumption, low extra-hardware cost, and light computation.

  9. HAp granules encapsulated oxidized alginate-gelatin-biphasic calcium phosphate hydrogel for bone regeneration.

    PubMed

    Sarker, Avik; Amirian, Jhaleh; Min, Young Ki; Lee, Byong Taek

    2015-11-01

    Bone repair in the critical size defect zone using 3D hydrogel scaffold is still a challenge in tissue engineering field. A novel type of hydrogel scaffold combining ceramic and polymer materials, therefore, was fabricated to meet this challenge. In this study, oxidized alginate-gelatin-biphasic calcium phosphate (OxAlg-Gel-BCP) and spherical hydroxyapatite (HAp) granules encapsulated OxAlg-Gel-BCP hydrogel complex were fabricated using freeze-drying method. Detailed morphological and material characterizations of OxAlg-Gel-BCP hydrogel (OGB00), 25wt% and 35wt% granules encapsulated hydrogel (OGB25 and OGB35) were carried out for micro-structure, porosity, chemical constituents, and compressive stress analysis. Cell viability, cell attachment, proliferation and differentiation behavior of rat bone marrow-derived stem cell (BMSC) on OGB00, OGB25 and OGB35 scaffolds were confirmed by MTT assay, Live-Dead assay, and confocal imaging in vitro experiments. Finally, OGB00 and OGB25 hydrogel scaffolds were implanted in the critical size defect of rabbit femoral chondyle for 4 and 8 weeks. The micro-CT analysis and histological studies conducted by H&E and Masson's trichrome demonstrated that a significantly higher (***p<0.001) and earlier bone formation happened in case of 25% HAp granules encapsulated OxAlg-Gel-BCP hydrogel than in OxAlg-Gel-BCP complex alone. All results taken together, HAp granules encapsulated OxAlg-Gel-BCP system can be a promising 3D hydrogel scaffold for the healing of a critical bone defect.

  10. Biphasic thermoelectric materials derived from the half-Heusler/full-Heusler system Ti-Ni-Sn

    NASA Astrophysics Data System (ADS)

    Douglas, Jason Everett

    Among the possible avenues for increasing the efficiency of global energy usage, thermoelectrics are an exciting, solid-state option. Thermoelectric materials, which convert an internal temperature gradient into a voltage and vice versa, have found applications in refrigeration as well as power generation from waste heat. TiNiSn, a semiconductor of the half-Heusler (hH) crystal structure, is of particular interest due to its very favorable electronic transport properties, conductivity (sigma) and Seebeck coefficient ( S), at relevant temperature regimes (between 600 K and 900 K). Unfortunately, its overall efficiency is hampered by a comparatively high thermal conductivity (kappa). In the design of thermoelectric materials, a number of approaches have been taken to increase the thermoelectric figure of merit, ZT = ( S2sigma/kappa)T, where T is temperature. In this work we examine how microstructure can be used to alter these thermoelectric propertiesin a biphasic Ti-Ni-Sn materials containing full-Heusler (fH) TiNi2Sn embedded within hH thermoelectric TiNiSn. We explored a wide range of Ni compositions in TiNi1+xSn--from stoichiometric TiNiSn to high Heusler volume fraction, TiNi1.25Sn--materials prepared by levitation induction melting followed by annealing. Phase distributions and microstructure were characterized using synchrotron x-ray diffraction and optical and electron microscopy. In a sample of the nominal composition TiNi1.15Sn, a significant decrease in thermal conductivity (about 30%) is observed for the biphasic material despite the metallic second-phase particles existing at the micrometer scale; a 50% increase in the electrical conductivity is also measured. These result in a maximum figure of merit, ZT, of 0.44 at 800 K, which is 25% greater than is observed for the x = 0 sample. Density functional theory calculations using hybrid functionals were performed to determine band alignments between the half- and full-Heusler compounds, as well as

  11. Verapamil exerts biphasic modulation on phenobarbital transport across the blood-brain barrier: evidence from an in vivo and in vitro study.

    PubMed

    Yao, Dan; Yang, Zhi-Hong; Liu, Li; Li, Jia; Yu, Yun-Li; Zhang, Lu-Lu; Pan, Xian; Liu, Xiao-Dong; Xie, Lin; Wang, Guang-Ji

    2011-04-01

    The aim of the study was to report a concentration-dependently biphasic effect of verapamil (VER) on the transport of phenobarbital (PB) across the blood-brain barrier (BBB) in vitro and in vivo. The uptake of PB by rat brain microvessel endothelial cells (rBMECs) and transport of PB across the rBMEC monolayer from apical to basolateral and basolateral to apical were evaluated in the presence of VER. The effect of VER on PB pharmacological activity on the central nervous system (CNS) and brain distribution of PB in mice were further investigated. The results showed that VER regulated the uptake of PB by rBMECs in a concentration-dependently biphasic manner. The uptake of PB by rBMECs was decreased by low concentrations of VER (1-25 μΜ), but increased by high concentrations of VER (50-300 μM). The biphasic regulation was also observed in transport experiment. In vivo studies showed that VER altered the pharmacological effect of PB on CNS and brain concentration of PB in a biphasic manner. In contrast to low doses of VER (0.125-0.5 mg/kg) that shortened the duration time of PB-induced loss of the righting reflex, high doses of VER (2-4 mg/kg) prolonged the duration time. Further study demonstrated that brain concentration of PB was decreased by 0.125 mg/kg VER, but increased by 2 mg/kg VER. The concentration-dependently biphasic regulation was also confirmed in the uptake of rhodamine 123 by rBMECs. Our results suggested that VER may regulate the transport of PB across BBB in a concentration-dependently biphasic manner and the biphasic regulation may be involved in P-gp function.

  12. An ontology for microbial phenotypes.

    PubMed

    Chibucos, Marcus C; Zweifel, Adrienne E; Herrera, Jonathan C; Meza, William; Eslamfam, Shabnam; Uetz, Peter; Siegele, Deborah A; Hu, James C; Giglio, Michelle G

    2014-11-30

    Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria. The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds. We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.

  13. A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex.

    PubMed

    Vaquette, Cédryck; Fan, Wei; Xiao, Yin; Hamlet, Stephen; Hutmacher, Dietmar W; Ivanovski, Saso

    2012-08-01

    This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum.

  14. Probing the limit of magnesium uptake by β-tricalcium phosphate in biphasic mixtures formed from calcium deficient apatites

    SciTech Connect

    Kumar, P. Nandha; Mishra, Sandeep K.; Kannan, S.

    2015-11-15

    A series of magnesium doped non-stoichiometric calcium deficient apatites were synthesized through an aqueous precipitation route. The resultant structural changes during heat treatment were investigated by X-ray diffraction, Raman and FT-IR spectroscopy and Rietveld refinement. The results confirmed the formation of biphasic mixtures comprising Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2} and β-Ca{sub 3}(PO{sub 4}){sub 2} after heat treatment at 1000 °C with the preferential occupancy of Mg{sup 2+} at the crystal lattice of β-Ca{sub 3}(PO{sub 4}){sub 2}. The concentration of Mg{sup 2+} uptake in β-Ca{sub 3}(PO{sub 4}){sub 2} is limited till reaching the stoichiometric ratio of (Ca+Mg)/P=1.67 and beyond this stoichiometric value [(Ca+Mg)/P>1.67], Mg{sup 2+} precipitates as Mg(OH){sub 2} and thereafter gets converted to MgO during heat treatment. Any kind of Mg{sup 2+} uptake in the crystal lattice of Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2} is discarded from the investigation. - Highlights: • Aqueous co-precipitation of calcium deficient apatites with excess magnesium (Mg{sup 2+}) additions. • Heat treatments beyond 800 °C results in the formation of biphasic apatite mixtures. • Mg{sup 2+} gets accommodated at the β-Ca{sub 3}(PO{sub 4}){sub 2} lattice of biphasic mixtures. • Mg{sup 2+} additions exceeding stoichiometric value (Ca/P>1.67) results in its formation as MgO. • Mg{sup 2+} occupancy at β-Ca{sub 3}(PO{sub 4}){sub 2} lattice delays its allotropic conversion α-Ca{sub 3}(PO{sub 4}){sub 2} till 1350 °C.

  15. Regeneration of a goat femoral head using a tissue-specific, biphasic scaffold fabricated with CAD/CAM technology.

    PubMed

    Ding, Chunming; Qiao, Zhiguang; Jiang, Wenbo; Li, Haowei; Wei, Jianhe; Zhou, Guangdong; Dai, Kerong

    2013-09-01

    Tissue engineering is considered as a promising approach for the regeneration of biological joint theoretically and thus provides a potential treatment option for advanced osteoarthritis. However, no significant progresses so far have been made in regenerating biological joint. In this study, a biphasic scaffold, which was consisted of polylactic acid-coated polyglycolic acid (PGA/PLA) scaffold and poly-ε-caprolactone/hydroxyapatite (PCL/HA) scaffold, was designed and used for regeneration of goat femoral head. The content of PLA and HA was optimized to a proper ratio, thus the scaffolds could achieve appropriate stiffness which was more conducive to articular cartilage and bone regeneration respectively. Furthermore, computer-aided design and manufacturing (CAD/CAM) technology was employed to fabricate the biphasic scaffolds into the desired shape and structure. The biphasic scaffolds with fine cell biocompatibility matched perfectly. Chondrocytes and bone marrow stromal cells (BMSCs) were seeded into the scaffolds for cartilage and bone regeneration respectively. After 10 weeks of implantation in nude mice subcutaneously, the cell-scaffold constructs successfully regenerated goat femoral heads. The regenerated femoral heads presented a precise appearance in shape and size similar to that of native goat femoral heads with a smooth, continuous, avascular, and homogeneous cartilage layer on the surface and stiff bone-like tissue in the microchannels of PCL/HA scaffold. Additionally, histological examination of the regenerated cartilage and bone showed typical histological structures and biophysical properties similar to that of native ones with specific matrix deposition and a well-integrated osteochondral interface. The strategy established in the study provides a promising approach for regenerating a biological joint which could be used to reconstruct the impaired joint.

  16. High-throughput mouse phenotyping.

    PubMed

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being gene