Using an innovative combination of quality-by-design and green analytical chemistry approaches for the development of a stability indicating UHPLC method in pharmaceutical products.

PubMed

Boussès, Christine; Ferey, Ludivine; Vedrines, Elodie; Gaudin, Karen

2015-11-10

An innovative combination of green chemistry and quality by design (QbD) approach is presented through the development of an UHPLC method for the analysis of the main degradation products of dextromethorphan hydrobromide. QbD strategy was integrated to the field of green analytical chemistry to improve method understanding while assuring quality and minimizing environmental impacts, and analyst exposure. This analytical method was thoroughly evaluated by applying risk assessment and multivariate analysis tools. After a scouting phase aimed at selecting a suitable stationary phase and an organic solvent in accordance with green chemistry principles, quality risk assessment tools were applied to determine the critical process parameters (CPPs). The effects of the CPPs on critical quality attributes (CQAs), i.e., resolutions, efficiencies, and solvent consumption were further evaluated by means of a screening design. A response surface methodology was then carried out to model CQAs as function of the selected CPPs and the optimal separation conditions were determined through a desirability analysis. Resulting contour plots enabled to establish the design space (DS) (method operable design region) where all CQAs fulfilled the requirements. An experimental validation of the DS proved that quality within the DS was guaranteed; therefore no more robustness study was required before the validation. Finally, this UHPLC method was validated using the concept of total error and was used to analyze a pharmaceutical drug product. Copyright © 2015 Elsevier B.V. All rights reserved.

[Chronic Pelvic Pain Syndrome and Personality--Association of Somatic Symptoms and Psychic Structure].

PubMed

Albrecht, Rebecca; Löwe, Bernd; A Brünahl, Christian; Riegel, Björn

2015-11-01

Despite its high prevalence, little is known about the aetiology and maintenance of Chronic Pelvic Pain Syndrome (CPPS). CPPS is is considered to be a multi-causal syndrome with discomfort and pain in the pelvis. Recent literature suggests that psychosocial factors are important for understanding CPPS. For example, CPPS has been associated with deficits in mentalization and bonding experiences. Our study aims to characterize features of personality disorders according to DSM-IV and psychic structure according to OPD-2 in CPPS patients. Furthermore, we examine the association of personality aspects with urological symptoms (NIH Questionnaire) and pain perception (MPQ Questionnaire). Personality aspects were assessed in a total of 109 patients from our CPPS outpatient clinic using standardized questionnaires. To characterize CPPS patients, we compared the sample's scores with reference groups, mostly the general population. In addition, the associations between personality aspects and both the urologic symptoms and pain perception were assessed using correlations. Missing data were replaced using multiple imputation methods. Compared to reference values, we found 'experiencing emotions' and 'creating relationships' as specific deficits in CPPS patients. Furthermore, patients' self-image (more dominant, higher depressive mood) differs from the general population. A higher pain perception was correlated with deficits in most personality aspects we measured. However, this was not the case for the severity of urological symptoms. Compared to the reference values, only a few personality aspects differed in CPPS patients but there was a correlational association between different personality traits and pain perception. Despite the extend of symptoms, pain perception is associated with difficulty (emotional ability) in dealing with emotions, self-management and relationships. These personality aspects should be taken into account when planning therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Coffee polyphenols extracted from green coffee beans improve skin properties and microcirculatory function.

PubMed

Fukagawa, Satoko; Haramizu, Satoshi; Sasaoka, Shun; Yasuda, Yuka; Tsujimura, Hisashi; Murase, Takatoshi

2017-09-01

Coffee polyphenols (CPPs), including chlorogenic acid, exert various physiological activities. The purpose of this study was to investigate the effects of CPPs on skin properties and microcirculatory function in humans. In this double-blind, placebo-controlled study, 49 female subjects with mildly xerotic skin received either a test beverage containing CPPs (270 mg/100 mL/day) or a placebo beverage for 8 weeks. The ingestion of CPPs significantly lowered the clinical scores for skin dryness, decreased transepidermal water loss, skin surface pH, and increased stratum corneum hydration and the responsiveness of skin blood flow during local warming. Moreover, the amounts of free fatty acids and lactic acid in the stratum corneum significantly increased after the ingestion of CPPs. These results suggest that an 8-week intake of CPPs improve skin permeability barrier function and hydration, with a concomitant improvement in microcirculatory function, leading to efficacy in the alleviation of mildly xerotic skin.

Chronic pelvic pain syndrome and semen quality of Korean men in their fourth decade.

PubMed

Byun, Jae Sang; Yoon, Tae Ki; Rhee, Hong Woo; Kim, Jin Hong; Shin, Jun Shik; Kim, Hong Seok; Bak, Chong Won

2012-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that adversely affects men across a wide range of ages. A number of pharmacologic and nonpharmacologic therapies for CP/CPPS have been investigated. Our study aimed to evaluate the prevalence of CPPS in Korean men in their thirties and to investigate the effect of CPPS and medical treatment on semen quality. Of 314 men with prostatitis, 74 patients with CPPS class IIIA (23.6%) were eligible for the study; these patients underwent combined α-blocker and cyclo-oxygenase 2 inhibitor therapy. These 74 men were prospectively studied at a medical center in Seoul, Korea. A number of parameters, including ejaculations per month, semen variables, and the levels of hormones (such as follicle-stimulating hormone, estradiol [E(2)], luteinizing hormone [LH], testosterone, and prolactin) were evaluated. The mean number of ejaculations per month, the mean number of daily hours spent sitting at work, smoking, body mass index, LH and E(2) levels, and semen parameters all showed significant differences (P < .0001) between the study patients and the controls. The combined regimen was effective in improving all aspects of semen quality except morphology (P < .05). CPPS class IIIA, which is notably prevalent among Korean men in the fourth decade of life, affects semen quality and poses a challenge to fertility. Proper treatment of CPPS class IIIA results in improved semen quality. Men with CPPS therefore require proper evaluation and treatment by andrologists/urologists before planning a natural conception.

Implementation of Cyber-Physical Production Systems for Quality Prediction and Operation Control in Metal Casting.

PubMed

Lee, JuneHyuck; Noh, Sang Do; Kim, Hyun-Jung; Kang, Yong-Shin

2018-05-04

The prediction of internal defects of metal casting immediately after the casting process saves unnecessary time and money by reducing the amount of inputs into the next stage, such as the machining process, and enables flexible scheduling. Cyber-physical production systems (CPPS) perfectly fulfill the aforementioned requirements. This study deals with the implementation of CPPS in a real factory to predict the quality of metal casting and operation control. First, a CPPS architecture framework for quality prediction and operation control in metal-casting production was designed. The framework describes collaboration among internet of things (IoT), artificial intelligence, simulations, manufacturing execution systems, and advanced planning and scheduling systems. Subsequently, the implementation of the CPPS in actual plants is described. Temperature is a major factor that affects casting quality, and thus, temperature sensors and IoT communication devices were attached to casting machines. The well-known NoSQL database, HBase and the high-speed processing/analysis tool, Spark, are used for IoT repository and data pre-processing, respectively. Many machine learning algorithms such as decision tree, random forest, artificial neural network, and support vector machine were used for quality prediction and compared with R software. Finally, the operation of the entire system is demonstrated through a CPPS dashboard. In an era in which most CPPS-related studies are conducted on high-level abstract models, this study describes more specific architectural frameworks, use cases, usable software, and analytical methodologies. In addition, this study verifies the usefulness of CPPS by estimating quantitative effects. This is expected to contribute to the proliferation of CPPS in the industry.

Reinventing Cell Penetrating Peptides Using Glycosylated Methionine Sulfonium Ion Sequences.

PubMed

Kramer, Jessica R; Schmidt, Nathan W; Mayle, Kristine M; Kamei, Daniel T; Wong, Gerard C L; Deming, Timothy J

2015-05-27

Cell penetrating peptides (CPPs) are intriguing molecules that have received much attention, both in terms of mechanistic analysis and as transporters for intracellular therapeutic delivery. Most CPPs contain an abundance of cationic charged residues, typically arginine, where the amino acid compositions, rather than specific sequences, tend to determine their ability to enter cells. Hydrophobic residues are often added to cationic sequences to create efficient CPPs, but typically at the penalty of increased cytotoxicity. Here, we examined polypeptides containing glycosylated, cationic derivatives of methionine, where we found these hydrophilic polypeptides to be surprisingly effective as CPPs and to also possess low cytotoxicity. X-ray analysis of how these new polypeptides interact with lipid membranes revealed that the incorporation of sterically demanding hydrophilic cationic groups in polypeptides is an unprecedented new concept for design of potent CPPs.

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome

PubMed Central

Lin, Guiting; Reed-Maldonado, Amanda B.; Lin, Maofan; Xin, Zhongcheng; Lue, Tom F.

2016-01-01

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS. PMID:27376284

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

PubMed

Lin, Guiting; Reed-Maldonado, Amanda B; Lin, Maofan; Xin, Zhongcheng; Lue, Tom F

2016-07-01

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.

Reinventing cell penetrating peptides using glycosylated methionine sulfonium ion sequences

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

Kramer, Jessica R.; Schmidt, Nathan W.; Mayle, Kristine M.

2015-04-15

Cell penetrating peptides (CPPs) are intriguing molecules that have received much attention, both in terms of mechanistic analysis and as transporters for intracellular therapeutic delivery. Most CPPs contain an abundance of cationic charged residues, typically arginine, where the amino acid compositions, rather than specific sequences, tend to determine their ability to enter cells. Hydrophobic residues are often added to cationic sequences to create efficient CPPs, but typically at the penalty of increased cytotoxicity. Here, we examined polypeptides containing glycosylated, cationic derivatives of methionine, where we found these hydrophilic polypeptides to be surprisingly effective as CPPs and to also possess lowmore » cytotoxicity. X-ray analysis of how these new polypeptides interact with lipid membranes revealed that the incorporation of sterically demanding hydrophilic cationic groups in polypeptides is an unprecedented new concept for design of potent CPPs.« less

Adrenocortical Hormone Abnormalities in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Dimitrakov, Jordan; Joffe, Hylton V.; Soldin, Steven J.; Bolus, Roger; Buffington, C.A. Tony; Nickel, J Curtis

2007-01-01

Objectives To identify adrenocortical hormone abnormalities as indicators of endocrine dysfunction in CP/CPPS. Methods We simultaneously measured the serum concentrations of 12 steroids in CP/CPPS and control patients, using isotope dilution liquid chromatography followed by atmospheric pressure photospray ionization and tandem mass spectrometry. Results Twenty-seven CP/CPPS patients and 29 age-matched asymptomatic healthy controls were evaluated. In the mineralocorticoid pathway, progesterone was significantly higher, whereas corticosterone and aldosterone concentrations were significantly lower, in CP/CPPS than in controls. In the glucocorticoid pathway, 11-deoxycortisol was significantly lower, and cortisol concentrations were not different between patients and controls. In the sex steroid pathway, androstenedione and testosterone concentrations were significantly higher in CP/CPPS than in controls. Estradiol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations were not different between patients and controls. NIH-CPSI total and pain domain scores correlated positively with 17-hydroxyprogesterone and aldosterone (P<0.001) and negatively with cortisol concentrations (P<0.001). Conclusions Results suggest reduced activity of CYP21A2 (P450c21), the enzyme that converts progesterone to corticosterone, and 17-hydroxyprogesterone to 11-deoxycortisol. Furthermore, these results provide insights into the biological basis of CP/CPPS. Follow-up studies should explore the possibility that CP/CPPS patients meet the diagnostic criteria for nonclassical CAH and if hormonal findings improve or worsen in parallel with symptom severity. PMID:18308097

Trace Detection of Metalloporphyrin-Based Coordination Polymer Particles via Modified Surface-Enhanced Raman Scattering Assisted by Surface Metallization.

PubMed

Sun, Yu; Caravella, Alessio

2016-01-01

This study proposed a facile method to detect metalloporphyrin-based coordination polymer particles (Z-CPPs) in aqueous solution by modified surface-enhanced Raman scattering (SERS). The SERS-active particles are photodeposited on the surface of Z-CPPs, offering an enhanced Raman signal for the trace detection of Z-CPPs.

Implementation of Cyber-Physical Production Systems for Quality Prediction and Operation Control in Metal Casting

PubMed Central

Lee, JuneHyuck; Noh, Sang Do; Kim, Hyun-Jung; Kang, Yong-Shin

2018-01-01

The prediction of internal defects of metal casting immediately after the casting process saves unnecessary time and money by reducing the amount of inputs into the next stage, such as the machining process, and enables flexible scheduling. Cyber-physical production systems (CPPS) perfectly fulfill the aforementioned requirements. This study deals with the implementation of CPPS in a real factory to predict the quality of metal casting and operation control. First, a CPPS architecture framework for quality prediction and operation control in metal-casting production was designed. The framework describes collaboration among internet of things (IoT), artificial intelligence, simulations, manufacturing execution systems, and advanced planning and scheduling systems. Subsequently, the implementation of the CPPS in actual plants is described. Temperature is a major factor that affects casting quality, and thus, temperature sensors and IoT communication devices were attached to casting machines. The well-known NoSQL database, HBase and the high-speed processing/analysis tool, Spark, are used for IoT repository and data pre-processing, respectively. Many machine learning algorithms such as decision tree, random forest, artificial neural network, and support vector machine were used for quality prediction and compared with R software. Finally, the operation of the entire system is demonstrated through a CPPS dashboard. In an era in which most CPPS-related studies are conducted on high-level abstract models, this study describes more specific architectural frameworks, use cases, usable software, and analytical methodologies. In addition, this study verifies the usefulness of CPPS by estimating quantitative effects. This is expected to contribute to the proliferation of CPPS in the industry. PMID:29734699

Prediction of cell penetrating peptides by support vector machines.

PubMed

Sanders, William S; Johnston, C Ian; Bridges, Susan M; Burgess, Shane C; Willeford, Kenneth O

2011-07-01

Cell penetrating peptides (CPPs) are those peptides that can transverse cell membranes to enter cells. Once inside the cell, different CPPs can localize to different cellular components and perform different roles. Some generate pore-forming complexes resulting in the destruction of cells while others localize to various organelles. Use of machine learning methods to predict potential new CPPs will enable more rapid screening for applications such as drug delivery. We have investigated the influence of the composition of training datasets on the ability to classify peptides as cell penetrating using support vector machines (SVMs). We identified 111 known CPPs and 34 known non-penetrating peptides from the literature and commercial vendors and used several approaches to build training data sets for the classifiers. Features were calculated from the datasets using a set of basic biochemical properties combined with features from the literature determined to be relevant in the prediction of CPPs. Our results using different training datasets confirm the importance of a balanced training set with approximately equal number of positive and negative examples. The SVM based classifiers have greater classification accuracy than previously reported methods for the prediction of CPPs, and because they use primary biochemical properties of the peptides as features, these classifiers provide insight into the properties needed for cell-penetration. To confirm our SVM classifications, a subset of peptides classified as either penetrating or non-penetrating was selected for synthesis and experimental validation. Of the synthesized peptides predicted to be CPPs, 100% of these peptides were shown to be penetrating.

Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

PubMed

Magistro, Giuseppe; Wagenlehner, Florian M E; Grabe, Magnus; Weidner, Wolfgang; Stief, Christian G; Nickel, J Curtis

2016-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that causes severe symptoms, bother, and quality-of-life impact in the 8.2% of men who are believed to be affected. Research suggests a complex pathophysiology underlying this syndrome that is mirrored by its heterogeneous clinical presentation. Management of patients diagnosed with CP/CPPS has always been a formidable task in clinical practice. Due to its enigmatic etiology, a plethora of clinical trials failed to identify an efficient monotherapy. A comprehensive review of published randomized controlled trials (RCTs) on the treatment of CP/CPPS and practical best evidence recommendations for management. Medline and the Cochrane database were screened for RCTs on the treatment of CP/CPPS from 1998 to December 2014, using the National Institutes of Health Chronic Prostatitis Symptom Index as an objective outcome measure. Published data in concert with expert opinion were used to formulate a practical best evidence statement for the management of CP/CPPS. Twenty-eight RCTs identified were eligible for this review and presented. Trials evaluating antibiotics, α-blockers, anti-inflammatory and immune-modulating substances, hormonal agents, phytotherapeutics, neuromodulatory drugs, agents that modify bladder function, and physical treatment options failed to reveal a clear therapeutic benefit. With its multifactorial pathophysiology and its various clinical presentations, the management of CP/CPPS demands a phenotypic-directed approach addressing the individual clinical profile of each patient. Different categorization algorithms have been proposed. First studies applying the UPOINTs classification system provided promising results. Introducing three index patients with CP/CPPS, we present practical best evidence recommendations for management. Our current understanding of the pathophysiology underlying CP/CPPS resulting in this highly variable syndrome does not speak in favor of a monotherapy for management. No efficient monotherapeutic option is available. The best evidence-based management of CP/CPPS strongly suggests a multimodal therapeutic approach addressing the individual clinical phenotypic profile. Chronic prostatitis/chronic pelvic pain syndrome presents a variable syndrome. Successful management of this condition is challenging. It appears that a tailored treatment strategy addressing individual patient characteristics is more effective than one single therapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Complementary and Alternative Medicine for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

2005-01-01

To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross-searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPPS. Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder. PMID:16322807

Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides.

PubMed

Dissanayake, Shama; Denny, William A; Gamage, Swarna; Sarojini, Vijayalekshmi

2017-03-28

Efficient intracellular trafficking and targeted delivery to the site of action are essential to overcome the current drawbacks of cancer therapeutics. Cell Penetrating Peptides (CPPs) offer the possibility of efficient intracellular trafficking, and, therefore the development of drug delivery systems using CPPs as cargo carriers is an attractive strategy to address the current drawbacks of cancer therapeutics. Additionally, the possibility of incorporating Tumor Targeting Peptides (TTPs) into the delivery system provides the necessary drug targeting effect. Therefore the conjugation of CPPs and/or TTPs with therapeutics provides a potentially efficient method of improving intracellular drug delivery mechanisms. Peptides used as cargo carriers in DDS have been shown to enhance the cellular uptake of drugs and thereby provide an efficient therapeutic benefit over the drug on its own. After providing a brief overview of various drug targeting approaches, this review focusses on peptides as carriers and targeting moieties in drug-peptide covalent conjugates and summarizes the most recent literature examples where CPPs on their own or CPPs together with TTPs have been conjugated to anticancer drugs such as Doxorubicin, Methotrexate, Paclitaxel, Chlorambucil etc. A short section on CPPs used in multicomponent drug delivery systems is also included. Copyright © 2017 Elsevier B.V. All rights reserved.

Negative Illness Perceptions are Associated with a Pro-nociceptive Modulation Profile and Augmented Pelvic Pain.

PubMed

Grinberg, Keren; Granot, Michal; Lowenstein, Lior; Abramov, Liora; Weissman-Fogel, Irit

2018-05-25

A patient's personal interpretations of a health threat or "illness perceptions" (IPs) are associated with their clinical outcomes. This study explored whether IPs are associated with pain severity and ability to modulate pain in women with chronic pelvic pain syndrome (CPPS), as well as the predictive value of IPs on Myofascial Physical Therapy (MPT) success. Illness Perceptions Questionnaire - Revised (IPQ-R), mechanical and heat pain thresholds, mechanical temporal summation (mTS), and conditioned pain modulation (CPM) were evaluated in CPPS patients (n=39) before, and 3 months after MPT. CPPS severity was obtained by the Brief Pain Inventory (BPI). Stronger perceptions of illness chronicity were correlated with less efficient CPM (r=0.488, P=0.002) and increased mechanical pain intensity (r=0.405, P=0.02). Lower perceptions of control over illness were associated with enhanced mTS (r=0.399, P=0.01). Higher BPI scores were correlated with emotional representations ("negative emotional representations") and severe consequences due to CPPS. Regression analyses revealed that negative IPs predict less efficient MPT. Cognitive representations play a unique role in CPPS expression and MPT outcomes. The interplay between negative IPs and a pro-nociceptive modulation profile, mediated by enhanced facilitatory and reduced inhibitory processes, may be involved in the manifestation of CPPS.

[International focuses in the studies of chronic pelvic pain syndrome: A social network analysis].

PubMed

Wen, Li-Jie; Pan, Xian-Wei; Yang, Bo

2016-10-01

To analyze the internationally published literature relevant to chronic pelvic pain syndrome (CPPS) using bibliometrics and social network analysis, and investigate the current status and focuses of CPPS studies. We identified 692 publications on CPPS by searching PubMed up to December 2015, extracted their subject headings, calculated the frequencies of the headings, and constructed a co-occurrence network of the high-frequency (≥10) subject headings. Then we studied the features and structure of the co-occurrence network by analyzing its attributes and topological structure. The density of the constructed co-occurrence network was 0.111, with an average distance of 2.886 and a clustering coefficient of 0.685. Its low density, long average distance and high clustering coefficient indicated that it was a sparse network, with a slow speed of information spreading among nodes but a strong potential coherence, which suggested that the current topics in the study of CPPS were scattered and weakly correlated, with a high possibility of being integrated. Based on the topological structure of the co-occurrence network, the topics in the study of CPPS were divided into six aspects: diagnosis and classification, drug therapy, treatment, etiology, microbiology, psychology, and epidemiology, the more important of which were diagnosis and classification, drug therapy, treatment and etiology. A system has been formed in the studies of CPPS, focusing on the diagnosis, drug therapy, and etiology of the disease. However, the research topics are relatively scattered and frequently repeated. Therefore, more attention should be paid to the macrocosmic guidance and rational coordination of the researches on CPPS.

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS

PubMed Central

Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang

2018-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n = 50; median age 39.8, range 23–65) and age-matched controls (n = 61; median age 36.8, range 20–69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 –treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 –treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy. PMID:29731970

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.

PubMed

Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang; Wagenlehner, Florian; Schagdarsurengin, Undraga

2018-04-13

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( n = 50; median age 39.8, range 23-65) and age-matched controls ( n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes ( ESR1 and ESR2 ) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E 2 ) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E 2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E 2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E 2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E 2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.

A gene delivery system for insect cells mediated by arginine-rich cell-penetrating peptides.

PubMed

Chen, Yung-Jen; Liu, Betty Revon; Dai, Yun-Hao; Lee, Cheng-Yi; Chan, Ming-Huan; Chen, Hwei-Hsien; Chiang, Huey-Jenn; Lee, Han-Jung

2012-02-10

Most bioactive macromolecules, such as protein, DNA and RNA, basically cannot permeate into cells freely from outside the plasma membrane. Cell-penetrating peptides (CPPs) are a group of short peptides that possess the ability to traverse the cell membrane and have been considered as candidates for mediating gene and drug delivery into living cells. In this study, we demonstrate that three arginine-rich CPPs (SR9, HR9 and PR9) are able to form stable complexes with plasmid DNA and deliver DNA into insect Sf9 cells in a noncovalent manner. The transferred plasmid DNA containing enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) coding regions could be expressed in cells functionally assayed at both the protein and RNA levels. Furthermore, treatment of cells with CPPs and CPP/DNA complexes resulted in a viability of 84-93% indicating these CPPs are not cytotoxic. These results suggest that arginine-rich CPPs appear to be a promising tool for insect transgenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

PubMed

Morgia, Giuseppe; Russo, Giorgio Ivan; Urzì, Daniele; Privitera, Salvatore; Castelli, Tommaso; Favilla, Vincenzo; Cimino, Sebastiano

2017-06-30

The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies with greater sample size.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

A survey of cannabis (marijuana) use and self-reported benefit in men with chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Tripp, Dean A; Nickel, J Curtis; Katz, Laura; Krsmanovic, Adrijana; Ware, Mark A; Santor, Darcy

2014-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a chronic pelvic pain condition largely refractory to treatment. Cannabis (marijuana) use has been reported for a wide variety of chronic pain conditions, but no study has examined prevalence of cannabis use, symptom benefit or side effects, or frequency in CP/CPPS. Participants were recruited from an outpatient CP/CPPS urology clinic (n = 98) and online through the Prostatitis Foundation website (n = 244). Participants completed questionnaires (demographics, CP/CPPS, depression, cannabis). The clinic sample included Canadian patients and the online sample included primarily American patients. Due to differences, groups were examined separately. Almost 50% of respondents reported using cannabis (clinic n = 49; online n = 89). Of the cannabis users, 36.8% of clinic and 75% of online respondents reported that it improved their symptoms. Most of the respondents (from the clinic and online groups) reported that cannabis improved their mood, pain, muscle spasms, and sleep. However, they did not note any improvements for weakness, fatigue, numbness, ambulation, and urination. Overall, the effectiveness of cannabis for CP/CPPS was "somewhat/very effective" (57% clinic; 63% online). There were no differences between side effects or choice of consumption and most reported using cannabis rarely. These are the first estimates in men suffering from CP/CPPS and suggest that while cannabis use is prevalent, its medical use and benefit are unknown. This is an understudied area and the benefit or hazard for cannabis use awaits further study.

[Prostatic inflammation-induced chronic pelvic pain: Roles of substance P and c-fos in the spinal cord].

PubMed

Liu, Ying-jia; Song, Guo-hong; Zhang, Chen

2015-08-01

To explore the possible pain mechanism of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The models of CP/CPPS were established in male Wistar rats by the autoimmune method. The paw withdrawal threshold (PWT) was detected using Von Frey filament. The expressions of the substance P and c-fos in the prostate and spinal L5-S2 segments were determined by immunohistochemistry followed by analysis of their correlation with CP/CPPS. Compared with the control rats, the CP/CPPS models showed significantly decreased PWT (P < 0.05), remarkable prostatic inflammation, enlarged scope of lesions, and obvious interstitial lymphocytic infiltration (P < 0.05). Both the expressions of substance P and c-fos were markedly elevated in the prostate and spinal dorsal horn (L5-S2) of the rat models (P < 0.05), but the expression of substance P in the prostate exhibited no correlation with that in the spinal cord (r = 0.099, P = 0.338), nor did that of c-fos (r = 0.027, P = 0.454). The upregulated expressions of substance P and c-fos in the spinal cord L5-S2 sections may be associated with the pain mechanism of CP/CPPS.

Cell Penetrating Peptides in the Delivery of Biopharmaceuticals

PubMed Central

Munyendo, Were LL; Lv, Huixia; Benza-Ingoula, Habiba; Baraza, Lilechi D.; Zhou, Jianping

2012-01-01

The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development. PMID:24970133

Molecular cloning and analysis of the ergopeptine assembly system in the ergot fungus Claviceps purpurea.

PubMed

Correia, Telmo; Grammel, Nicolas; Ortel, Ingo; Keller, Ullrich; Tudzynski, Paul

2003-12-01

Claviceps purpurea produces the pharmacological important ergopeptines, a class of cyclol-structured alkaloid peptides containing D-lysergic acid. These compounds are assembled from D-lysergic acid and three different amino acids by the nonribosomal peptide synthetase enzymes LPS1 and LPS2. Cloning of alkaloid biosynthesis genes from C. purpurea has revealed a gene cluster including two NRPS genes, cpps 1 and cpps 2. Protein sequence data had assigned earlier cpps1 to encode the trimodular LPS1 assembling the tripeptide portion of ergopeptines. Here, we show by transcriptional analysis, targeted inactivation, analysis of disruption mutants, and heterologous expression that cpps 2 encodes the monomodular LPS2 responsible for D-lysergic acid activation and incorporation into the ergopeptine backbone. The presence of two distinct NRPS subunits catalyzing formation of ergot peptides is the first example of a fungal NRPS system consisting of different NRPS subunits.

[Application of quality by design in granulation process for Ginkgo leaf tablet (Ⅲ)： process control strategy based on design space].

PubMed

Cui, Xiang-Long; Xu, Bing; Sun, Fei; Dai, Sheng-Yun; Shi, Xin-Yuan; Qiao, Yan-Jiang

2017-03-01

In this paper, under the guidance of quality by design (QbD) concept, the control strategy of the high shear wet granulation process of the ginkgo leaf tablet based on the design space was established to improve the process controllability and product quality consistency. The median granule size (D50) and bulk density (Da) of granules were identified as critical quality attributes (CQAs) and potential critical process parameters (pCPPs) were determined by the failure modes and effect analysis (FMEA). The Plackeet-Burmann experimental design was used to screen pCPPs and the results demonstrated that the binder amount, the wet massing time and the wet mixing impeller speed were critical process parameters (CPPs). The design space of the high shear wet granulation process was developed within pCPPs range based on the Box-Behnken design and quadratic polynomial regression models. ANOVA analysis showed that the P-values of model were less than 0.05 and the values of lack of fit test were more than 0.1, indicating that the relationship between CQAs and CPPs could be well described by the mathematical models. D₅₀ could be controlled within 170 to 500 μm, and the bulk density could be controlled within 0.30 to 0.44 g•cm⁻³ by using any CPPs combination within the scope of design space. Besides, granules produced by process parameters within the design space region could also meet the requirement of tensile strength of the ginkgo leaf tablet.. Copyright© by the Chinese Pharmaceutical Association.

Quality by Design in the development of hydrophilic interaction liquid chromatography method with gradient elution for the analysis of olanzapine.

PubMed

Tumpa, Anja; Stajić, Ana; Jančić-Stojanović, Biljana; Medenica, Mirjana

2017-02-05

This paper deals with the development of hydrophilic interaction liquid chromatography (HILIC) method with gradient elution, in accordance with Analytical Quality by Design (AQbD) methodology, for the first time. The method is developed for olanzapine and its seven related substances. Following step by step AQbD methodology, firstly as critical process parameters (CPPs) temperature, starting content of aqueous phase and duration of linear gradient are recognized, and as critical quality attributes (CQAs) separation criterion S of critical pairs of substances are investigated. Rechtschaffen design is used for the creation of models that describe the dependence between CPPs and CQAs. The design space that is obtained at the end is used for choosing the optimal conditions (set point). The method is fully validated at the end to verify the adequacy of the chosen optimal conditions and applied to real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Category III Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Insights from The National Institutes of Health Chronic Prostatitis Collaborative Research Network Studies

PubMed Central

Nickel, J. Curtis; Alexander, Richard B.; Anderson, Rodney; Berger, Richard; Comiter, Craig V.; Datta, Nand S.; Fowler, Jackson E.; Krieger, John N.; Landis, J. Richard; Litwin, Mark S.; McNaughton-Collins, Mary; O'Leary, Michael P.; Pontari, Michel A.; Schaeffer, Anthony J.; Shoskes, Daniel A.; White, Paige; Kusek, John; Nyberg, Leroy

2010-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains an enigmatic medical condition. Creation of the (NIH) Chronic Prostatitis Collaborative Research Network (CPCRN) funded by the National Institutes of Health has stimulated a renewed interest in the research and clinical aspects of CP/CPPS. Landmark publications of the NIH-CPCRN over the last 10 years document a decade of progress. Insights from these CPCRN studies have improved our management of patients diagnosed with CP/CPPS and offer hope for continued progress. PMID:18765132

[Physiotherapeutic assessment of chronic pelvic pain syndrome : Development of a standardized physiotherapeutic assessment instrument for interprofessional cooperation in patients with chronic pelvic pain syndrome].

PubMed

Klotz, S G R; Ketels, G; Richardsen, B; Löwe, B; Brünahl, C A

2018-04-24

The chronic pelvic pain syndrome (CPPS) can be associated with physiotherapeutic findings. An interprofessional approach is recommended for patients with CPPS; however, no standardized physiotherapeutic assessment and documentation instrument for specific physiotherapeutic assessments exist, which is not only the foundation for physiotherapy but also for interprofessional communication. The aim was the development of a physiotherapeutic assessment instrument for patients with CPPS and therefore, to create a tool for clinical use, research and interprofessional communication. Based on an explorative literature search and an expert consensus, the first version of the instrument was developed as part of a specialized outpatient clinic. This version was applied clinically for 13 months, edited and finalized after another expert consensus. The developed instrument Physical Therapy Assessment for Chronic Pelvic Pain Syndrome (PTA-CPPS) lists external and internal groups of muscles for a systematic assessment of myofascial findings. Functional capacity, breathing movements as well as scars and regions of pain are recorded. A manual for the assessment protocol was developed as accompanying material. The developed instrument provides for the first time a physiotherapeutic assessment tool for patients with CPPS for interprofessional clinical and scientific use.

Alterations in regional homogeneity of resting-state cerebral activity in patients with chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Lin, Yusong; Bai, Yan; Liu, Peng; Yang, Xuejuan; Qin, Wei; Gu, Jianqin; Ding, Degang; Tian, Jie; Wang, Meiyun

2017-01-01

The purpose of this study was to explore the neural mechanism in Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) using resting-state functional magnetic resonance imaging. The functional magnetic resonance imaging was performed on 31 male CP/CPPS-patients and 31 age and education matched male healthy controls on a 3-T magnetic resonance imaging unit. A two-sample t-test was adopted to reveal the regional homogeneity between the patients and healthy controls. The mean regional homogeneity values in the alerted brain regions of patients were correlated with the clinical measurements by using Pearson's correlation analyses. The CP/CPPS-patients had significantly decreased regional homogeneity in the bilateral anterior cingulate cortices, insular cortices and right medial prefrontal cortex, while significantly increased regional homogeneity in the brainstem and right thalamus compared with the healthy controls. In the CP/CPPS-patients, the mean regional homogeneity value in the left anterior cingulate cortex, bilateral insular cortices and brainstem were respectively correlated with the National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscale. These brain regions are important in the pain modulation process. Therefore, an impaired pain modulatory system, either by decreased descending pain inhibition or enhanced pain facilitation, may explain the pain symptoms in CP/CPPS.

Molecular imaging analysis of intestinal insulin absorption boosted by cell-penetrating peptides by using positron emission tomography.

PubMed

Kamei, Noriyasu; Morishita, Mariko; Kanayama, Yousuke; Hasegawa, Koki; Nishimura, Mie; Hayashinaka, Emi; Wada, Yasuhiro; Watanabe, Yasuyoshi; Takayama, Kozo

2010-08-17

Molecular imaging technique by use of positron emission tomography (PET) is a noninvasive tool that allows one to quantitatively analyze the function of endogenous molecules and the pharmacokinetics of therapeutic agents in vivo. This technique is expected to be useful for evaluating the effectiveness of diverse drug delivery systems. We demonstrated previously that intestinal insulin absorption is increased significantly by coadministration of cell-penetrating peptides (CPPs), which are taken up effectively by several cells. However, the distribution behavior of insulin whose absorption is increased by CPPs is not clear. We used PET imaging and quantitatively analyzed the intestinal absorption and subsequent distribution of insulin and the effect of CPPs on its absorption and distribution. An unlabeled insulin solution containing tracer insulin, (68)Ga-DOTA-insulin, was administered with or without CPPs into a rat ileal closed loop. PET imaging showed that the CPPs, particularly D-R8 and L-penetratin, significantly increased the (68)Ga-DOTA-insulin level in the liver, kidney, and circulation. After absorption from the intestine, the (68)Ga-DOTA-insulin passed rapidly through the liver and accumulated in the kidney. The increase in the hepatic and renal distribution of (68)Ga-DOTA-insulin by each CPP coadministration was similar manner as that in intestinal absorption, suggesting that the increased accumulation of insulin in the liver and kidney induced by coadministration of CPPs was associated with the increased intestinal absorption of insulin. This is the first study to show that PET imaging enables one to quantitatively analyze the distribution behavior of intestinally absorbed insulin in several organs. This imaging methodology is likely to be useful for developing effective drug delivery systems targeted to specific organs. Copyright 2010 Elsevier B.V. All rights reserved.

The association of personality trait on treatment outcomes in patients with chronic prostatitis/chronic pelvic pain syndrome: an exploratory study.

PubMed

Koh, Jun Sung; Ko, Hyo Jung; Wang, Sheng-Min; Cho, Kang Joon; Kim, Joon Chul; Lee, Soo-Jung; Pae, Chi-Un; Serretti, Alessandro

2014-02-01

This study investigated the association of personality traits with the baseline clinical characteristics and treatment outcomes of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Subjects were evaluated at baseline and at week 12 following routine treatment for CP/CPPS using the Korean version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS; the Korean version of the Patient Health Questionnaire-9 (PHQ-9) to assess depression; the Korean version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatization; and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D), specifically the EQ-5D utility index and the EQ-5D visual analog scale (EQ-5D VAS), to assess quality of life (QoL). Personality traits including extraversion, agreeableness, conscientiousness, neuroticism, and openness were determined at baseline using the 44-item Big Five Inventory (BFI). The influence of personality traits on the clinical characteristics and treatment outcomes of patients with CP/CPPS was assessed using relevant statistical analyses. Neuroticism was associated with a significantly poorer treatment response and higher levels of depression and somatization. Extraversion, agreeableness, and conscientiousness had some influence on clinical characteristics but openness did not affect overall symptoms or the treatment response in patients with CP/CPPS. We found that neuroticism may be the most important personality trait associated with treatment response and the severity of depression and somatization in patients with CP/CPPS. However, our exploratory findings should be confirmed by additional studies with adequate power and improved designs. Copyright © 2013 Elsevier Inc. All rights reserved.

Direct effects of casein phosphopeptides on growth and differentiation of in vitro cultured osteoblastic cells (MC3T3-E1).

PubMed

Tulipano, Giovanni; Bulgari, Omar; Chessa, Stefania; Nardone, Alessandro; Cocchi, Daniela; Caroli, Anna

2010-02-25

Casein phosphopeptides (CPPs) obtained by enzymatic hydrolysis in vitro of caseins, have been shown to enhance calcium solubility and to increase the calcification of embryonic rat bones in their diaphyseal area. Little is known about the direct effects of CPPs on cultured osteoblastic cells. Calcium in the microenvironment surrounding bone cells is not only important for the mineralization of the extracellular matrix, but it is believed to provide preosteblasts with a signal that modulates their proliferation and differentiation. The aim of the present study was to investigate the direct effects of four selected casein phosphopeptides on osteoblastic cell (MC3T3-E1 cells) viability and differentiation. The selected peptides have been obtained by chemical synthesis and differed in the number of phosphorylated sites and in the amino acid spacing out two phosphorylated sites, in order to further characterize the relationship between structure and function. The results obtained in this work demonstrated that CPPs may directly affect osteoblast-like cell growth, calcium uptake and ultimately calcium deposition in the extracellular matrix. The effects exerted by distinct CPPs on osteogenesis in vitro can be either stimulatory or inhibitory. Differential short amino acid sequences in their molecules, like the -SpEE- and the -SpTSpEE-motifs, are likely the molecular determinants for their biological activities on osteoblastic cells. Moreover, two genetic variants of CPPs showing one amino acid change in their sequence may profoundly differ in their biological activities. Finally, our data may also suggest important clues about the role of intrinsic phosphorylated peptides derived from endogenous phosphorylated proteins in bone metabolism, apart from extrinsic CPPs. Copyright 2009 Elsevier B.V. All rights reserved.

Synthesis of CuO by Cu-CPPs with the determination of Cu(II) coordination modes from a novel complex of [Cu(terpyOH){sub 2}]·(HBTC)·2H{sub 2}O

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

Wang, Yu, E-mail: wangyu1012@hit.edu.cn; Chen, Gang, E-mail: gchen@hit.edu.cn; Han, Li

2013-10-15

In this study, we investigated the synthesis of CuO microrods by simple calcination of copper-based coordination polymer particles (Cu-CPPs) at high temperature in air. The photocatalytic activity of the CuO microrods was tested by the decomposition of aqueous solution of RhB, which was completely decomposed by irradiation with light. To analyze the relationship of metal ions and ligands in the Cu-CPPs, the single crystal of [Cu(terpyOH){sub 2}]∙(HBTC)∙2H{sub 2}O (1) (terpyOH=4′-hydroxy-2,2′:6′,2″-terpyridine, BTC=1,3,5-benzene tricarboxylate) was first prepared and characterized by X-ray single crystal structural analysis. A variety of hydrogen bonds constructing the 3D complex structure in [Cu(terpyOH){sub 2}]∙(HBTC)∙2H{sub 2}O (1) were observed.more » - Graphical abstract: Demonstrating a general method to synthesize CuO microrods via simple calcination of Cu-CPPs and Cu(II) coordination modes from a novel complex of [Cu(terpyOH){sub 2}]∙(HBTC)·2H{sub 2}O constructed by hydrogen bonding. Display Omitted - Highlights: • The formation of microrods CuO from thermal treatment of Cu-CPPs through an “escape-by-crafty-scheme” strategy has been studied. • Determination of Cu(II) coordination modes in Cu-CPPs from a novel complex of [Cu(terpyOH){sub 2}]∙(HBTC) 2H{sub 2}O. • Invested the behave of hydrogen bonding to construct the 3D complex structure. • Commendable photodegradation performance was observed.« less

The evolving clinical picture of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): A look at 1310 patients over 16 years.

PubMed

Doiron, R Christopher; Tripp, Dean A; Tolls, Victoria; Nickel, J Curtis

2018-06-01

Two decades of increasing understanding of etiopathogenesis and clinical phenotyping produces an impression the clinical face of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is changing. We sought to retrospectively analyze trends in CP/CPPS patients presenting to our clinic for evaluation over a 16-year period. Patients with CP/CPPS presenting to a tertiary clinic were evaluated prospectively from 1998-2014 with Chronic Prostatitis Symptom Index (CPSI) and UPOINT (urinary, psychosocial, organ-specific, infection, neurogenic, and tenderness) categorization. Patients were stratified in four cohorts, based on year of presentation, and we retrospectively analyzed variations in symptom scores and patterns, UPOINT categorization, and treatment modalities amongst cohorts. Mean age of the 1310 CP/CPPS patients was 44.7 years, while mean CPSI pain, urination, and total scores were 10.6, 4.8, and 23.3, respectively. The most prevalent UPOINT domain, urinary (U) (71.8%) was associated with a higher CPSI urination score (6.3), more frequent penile tip pain (37%), dysuria (48%), and more treatment with alpha-blockers (70%). Increase in UPOINT domains was associated with higher CPSI pain, quality of life (QoL), and total scores. Trends over time included increased prevalence of psychosocial (P), organ (O), and tenderness (T) domains, as well as increased use of alpha-blockers, neuromodulation, and phytotherapy as treatment modalities. There was little variation in age, CPSI scores, and pain locations over time. The changing clinical face of CP/CPPS reflects the increased recognition of psychosocial (P domain) and pelvic floor pain (T domain), along with the concomitant use of associated therapies. There was little variation of pain/urinary symptom patterns and QoL.

CiPerGenesis, A Mutagenesis Approach that Produces Small Libraries of Circularly Permuted Proteins Randomly Opened at a Focused Region: Testing on the Green Fluorescent Protein.

PubMed

Gaytán, Paul; Roldán-Salgado, Abigail; Yáñez, Jorge A; Morales-Arrieta, Sandra; Juárez-González, Víctor R

2018-06-12

Circularly permuted proteins (cpPs) represent a novel type of mutant proteins with original termini that are covalently linked through a peptide connector and opened at any other place of the polypeptide backbone to create new ends. cpPs are finding wide applications in biotechnology because their properties may be quite different from those of the parental protein. However, the actual challenge for the creation of successful cpPs is to identify those peptide bonds that can be broken to create new termini and ensure functional and well-folded cpPs. Herein, we describe CiPerGenesis, a combinatorial mutagenesis approach that uses two oligonucleotide libraries to amplify a circularized gene by PCR, starting and ending from a focused target region. This approach creates small libraries of circularly permuted genes that are easily cloned in the correct direction and frame using two different restriction sites encoded in the oligonucleotides. Once expressed, the protein libraries exhibit a unique sequence diversity, comprising cpPs that exhibit ordinary breakpoints between adjacent amino acids localized at the target region as well as cpPs with new termini containing user-defined truncations and repeats of some amino acids. CiPerGenesis was tested at the lid region G134-H148 of green fluorescent protein (GFP), revealing that the most fluorescent variants were those starting at Leu141 and ending at amino acids Tyr145, Tyr143, Glu142, Leu141, Lys140, and H139. Purification and biochemical characterization of some variants suggested a differential expression, solubility and maturation extent of the mutant proteins as the likely cause for the variability in fluorescence intensity observed in colonies.

Cell-penetrating peptides and antimicrobial peptides: how different are they?

PubMed Central

Henriques, Sónia Troeira; Melo, Manuel Nuno; Castanho, Miguel A. R. B.

2006-01-01

Some cationic peptides, referred to as CPPs (cell-penetrating peptides), have the ability to translocate across biological membranes in a non-disruptive way and to overcome the impermeable nature of the cell membrane. They have been successfully used for drug delivery into mammalian cells; however, there is no consensus about the mechanism of cellular uptake. Both endocytic and non-endocytic pathways are supported by experimental evidence. The observation that some AMPs (antimicrobial peptides) can enter host cells without damaging their cytoplasmic membrane, as well as kill pathogenic agents, has also attracted attention. The capacity to translocate across the cell membrane has been reported for some of these AMPs. Like CPPs, AMPs are short and cationic sequences with a high affinity for membranes. Similarities between CPPs and AMPs prompted us to question if these two classes of peptides really belong to unrelated families. In this Review, a critical comparison of the mechanisms that underlie cellular uptake is undertaken. A reflection and a new perspective about CPPs and AMPs are presented. PMID:16956326

Therapeutic effects of Qian-Yu decoction and its three extracts on carrageenan-induced chronic prostatitis/chronic pelvic pain syndrome in rats.

PubMed

Zhang, Keda; Zeng, Xiaobin; Chen, Yonggang; Zhao, Rong; Wang, Hui; Wu, Jinhu

2017-01-25

Qian-Yu decoction (QYD) is a traditional Chinese medicinal recipe composed of Radix astragali (Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao, Fabaceae ), Herba epimedii (Epimedium brevicornum Maxim., Berberidaceae), Herba leonuri (Leonurus japonicus Houtt., Lamiaceae), Cortex phellodendri (Phellodendron chinense Schneid., Rutaceae) and Radix achyranthis bidentatae (Achyranthes bidentata Bl., Amaranthaceae). This study aimed to evaluate the therapeutic activity of QYD against carrageenan-induced chronic prostatic/chronic pelvic pain syndrome (CP/CPPS) in rats and further elucidate its effective components. Three types of components, total polysaccharides, total flavonoids and total saponins were separately extracted from QYD. Carrageenan-induced CP/CPPS rats were intragastrically administered with lyophilized product of QYD, individual extracts and all the combined forms of extracts for three weeks. Prostatic index (PI) was determined and histopathological analysis was performed. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PEG2) in rat prostate tissues were measured using ELISA. The production of inducible nitric oxide synthase (iNOS) was evaluated by an enzymatic activity assay, and the release of nitric oxide (NO) was determined by a nitrate/nitrite assay. Treatment with QYD significantly ameliorated the histological changes of CP/CPPS rats and reduced the PI by 44.3%, with a marked downregulation of TNF-α (42.8% reduction), IL-1β (45.3%), COX-2 (36.6%), PGE2 (44.2%), iNOS (54.1%) and NO (46.0%). Each of three extracts attenuated the symptom of CP/CPPS, but much more weakly than QYD. The combined administration of three extracts showed efficacy comparable to that of QYD while better than that of any combination of two extracts. A principal component analysis of the six inflammatory mediators as variables indicated that the effects of TS on CP/CPPS were rather different from those of TF and TP, which were similar. QYD can be beneficial in prevention and treatment of CP/CPPS. Polysaccharides, flavonoids and saponins, as the major effective components of QYD, exert a cooperative effect on CP/CPPS.

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

PubMed

Hu, Y; Niu, X; Wang, G; Huang, J; Liu, M; Peng, B

2016-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function. © 2016 American Society of Andrology and European Academy of Andrology.

(R-X-R)4 -Motif Peptides Containing Conformationally Constrained Cyclohexane-Derived Spacers: Effect on Cellular Uptake.

PubMed

Bhosle, Govind S; Fernandes, Moneesha

2017-11-08

Arginine-rich peptides having the (R-X-R) n motif are among the most effective cell-penetrating peptides (CPPs). Herein we report a several-fold increase in the efficacy of such CPPs if the linear flexible spacer (-X-) in the (R-X-R) motif is replaced by constrained cyclic 1,4-substituted-cyclohexane-derived spacers. Internalization of these oligomers in mammalian cell lines was found to be an energy-dependent process. Incorporation of these constrained, non-proteinogenic amino acid spacers in the CPPs is shown to enhance their proteolytic stability. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

2016-04-01

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats. © 2015 Blackwell Verlag GmbH.

Chronic prostatitis/chronic pelvic pain syndrome: a review of evaluation and therapy.

PubMed

Polackwich, A S; Shoskes, D A

2016-06-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as NIH Category III Prostatitis is a highly prevalent syndrome with significant impact on quality of life. As a heterogeneous syndrome, there exists no 'one size fits all' therapy with level 1 evidence to guide therapy. This often leads to a nihilistic approach to patients and clinical outcomes are poor. In this review, we examine the evidence for CP/CPPS therapies and discuss our technique of clinical phenotyping combined with multimodal therapy. Review of Medline articles with terms 'non-bacterial prostatitis', 'abacterial prostatitis' and 'chronic pelvic pain syndrome'. Many individual therapies have been evaluated in the treatment of CP/CPPS; antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha blockers, pelvic floor physical therapy and cognitive behavior therapy. Each of these has been found to have varying success in alleviating symptoms. UPOINT is a system of clinical phenotyping for CP/CPPS patients that has 6 defined domains, which guide multimodal therapy. It has been validated to correlate with symptom burden and therapy guided by UPOINT leads to significant symptom improvement in 75-84% of patients based on three independent studies. CP/CPPS is a heterogeneous condition and, much like with prostate cancer, optimal therapy can only be achieved by classifying patients into clinically meaningful phenotypic groups (much like TNM) and letting the phenotype drive therapy.

A Portfolio for Optimal Collaboration of Human and Cyber Physical Production Systems in Problem-Solving

ERIC Educational Resources Information Center

Ansari, Fazel; Seidenberg, Ulrich

2016-01-01

This paper discusses the complementarity of human and cyber physical production systems (CPPS). The discourse of complementarity is elaborated by defining five criteria for comparing the characteristics of human and CPPS. Finally, a management portfolio matrix is proposed for examining the feasibility of optimal collaboration between them. The…

New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Pontari, Michel; Giusto, Laura

2013-11-01

To describe new developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome (CPPS). Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease, and a group with more systemic symptoms. Several other chronic pain conditions can be associated with chronic prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Markers of neurologic inflammation and autoimmune disease parallel changes in symptoms after treatment. Treatment options include new alpha-blockers, psychological intervention, and prostate-directed therapy. The areas of acupuncture and pelvic floor physical therapy/myofascial release have received increased recent attention and appear to be good options in these patients. Future therapy may include antibodies to mediators of neurogenic inflammation and even treatment of bacteria in the bowel. The diagnosis of chronic prostatitis/CPPS must include conditions traditionally outside the scope of urologic practice but important for the care of men with chronic pelvic pain. The treatment is best done using multiple simultaneous therapies aimed at the different aspects of the condition.

Characterisation of the bacterial community in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome and infertile men: a preliminary investigation

PubMed Central

Hou, Dong-Sheng; Long, Wen-Min; Shen, Jian; Zhao, Li-Ping; Pang, Xiao-Yan; Xu, Chen

2012-01-01

The expressed prostatic secretions (EPSs) of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), infertile men and normal men were subjected to microbiological study. EPSs were collected from the subjects, which included 26 normal men, 11 infertile patients and 51 CP/CPPS patients. DNA was extracted from each specimen, and the V3 regions of the 16S rRNA genes were amplified using universal bacterial primers. The results showed that the EPS 16S rRNA gene-positive rate in the CP/CPPS and infertile patients was much higher than in the normal men, but without any difference among the three patient groups. The denaturing gradient gel electrophoresis (DGGE) method was used to characterize the EPS bacterial community structure of the prostate fluid from patients with CP/CPPS or infertility issues. Principal component analysis (PCA) and partial least squares (PLS) analyses of PCR-DGGE profiles revealed that the EPS bacterial community structure differed among the three groups. Three bands were identified as the key factors responsible for the discrepancy between CP/CPPS patients and infertile patients (P<0.05). Two bands were identified as priority factors in the discrepancy of category IIIA and category IIIB prostatitis patients (P<0.05). According to this research, the ecological balance of the prostate and low urethra tract, when considered as a microenvironment, might play an important role in the maintenance of a healthy male reproductive tract. PMID:22635162

Comparison of National Institutes of Health-Chronic Prostatitis Symptom Index with International Index of Erectile Function 5 in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Large Cross-Sectional Study in China.

PubMed

Gao, Jingjing; Gao, Pan; Hao, Zongyao; Zhou, Zengrong; Liu, Jihong; Li, Hongjun; Xing, Junping; Zhou, Zhansong; Deng, Chunhua; Deng, Liwen; Wei, Qiang; Zhang, Xiansheng; Zhou, Jun; Fan, Song; Tai, Sheng; Yang, Chen; Shi, Kai; Huang, Yuanyuan; Ye, Zhangqun; Liang, Chaozhao

2015-01-01

The purpose of the study is to evaluate the relationship between NIH-CPSI and IIEF-5 in Chinese men with CP/CPPS. A large cross-sectional and multicenter survey was conducted from July 2012 to January 2014. Men were recruited from urology clinics which were located at the five cities in China. All men participated in the survey by completing a verbal questionnaire (consisted of sociodemographics, past medical history, sexual history, and self-estimated scales). The results showed that 1,280 men completed the survey. Based on the CP/CPPS definition, a total of 801 men were diagnosed as having CP/CPPS. Men with CP/CPPS reported higher scores of NIH-CPSI and lower scores of IIEF-5 than men without CP/CPPS. NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. The total scores of NIH-CPSI were significantly more strongly correlated with question 5 than other questions of IIEF-5. The total scores of IIEF-5 were significantly more strongly correlated with pain symptoms scores of NIH-CPSI. Strongest correlation was found between QoL impact and question 5 of IIEF-5. The findings suggested that NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. Strongest correlation was found between QoL impact and question 5 of IIEF-5.

Test Review: Children's Psychological Processing Scale (CPPS)

ERIC Educational Resources Information Center

McGill, Ryan J.

2013-01-01

The Children's Psychological Processing Scale (CPPS), authored by Milton J. Dehn and published by Schoolhouse Educational Services in 2012, is a third-party rating scale that can be administered to teachers who are familiar with children ages 5 to 12. The measure is designed to identify psychological processing deficits in children who are…

Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation

PubMed Central

Pota, Vincenzo; Sansone, Pasquale; Aurilio, Caterina; Pace, Maria Caterina

2017-01-01

Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation. PMID:29359045

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS Nano GO Consortium

PubMed Central

Xia, Tian; Hamilton, Raymond F.; Bonner, James C.; Crandall, Edward D.; Elder, Alison; Fazlollahi, Farnoosh; Girtsman, Teri A.; Kim, Kwang; Mitra, Somenath; Ntim, Susana A.; Orr, Galya; Tagmount, Mani; Taylor, Alexia J.; Telesca, Donatello; Tolic, Ana; Vulpe, Christopher D.; Walker, Andrea J.; Wang, Xiang; Witzmann, Frank A.; Wu, Nianqiang; Xie, Yumei; Zink, Jeffery I.; Nel, Andre

2013-01-01

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells. Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μg/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β. Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity. PMID:23649538

The heparin-binding domain of HB-EGF as an efficient cell-penetrating peptide for drug delivery.

PubMed

Luo, Zhao; Cao, Xue-Wei; Li, Chen; Wu, Miao-Dan; Yang, Xu-Zhong; Zhao, Jian; Wang, Fu-Jun

2016-11-01

Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30-HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C-terminus of MAP30 promoted the cellular uptake of recombinant MAP30-HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30-induced apoptosis through the activation of the mitochondrial- and death receptor-mediated signaling pathways. In addition, the MAP30-HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30-HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB-EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Quality by design in the chiral separation strategy for the determination of enantiomeric impurities: development of a capillary electrophoresis method based on dual cyclodextrin systems for the analysis of levosulpiride.

PubMed

Orlandini, S; Pasquini, B; Del Bubba, M; Pinzauti, S; Furlanetto, S

2015-02-06

Quality by design (QbD) concepts, in accordance with International Conference on Harmonisation Pharmaceutical Development guideline Q8(R2), represent an innovative strategy for the development of analytical methods. In this paper QbD principles have been comprehensively applied in the set-up of a capillary electrophoresis method aimed to quantify enantiomeric impurities. The test compound was the chiral drug substance levosulpiride (S-SUL) and the developed method was intended to be used for routine analysis of the pharmaceutical product. The target of analytical QbD approach is to establish a design space (DS) of critical process parameters (CPPs) where the critical quality attributes (CQAs) of the method have been assured to fulfil the desired requirements with a selected probability. QbD can improve the understanding of the enantioseparation process, including both the electrophoretic behavior of enantiomers and their separation, therefore enabling its control. The CQAs were represented by enantioresolution and analysis time. The scouting phase made it possible to select a separation system made by sulfated-β-cyclodextrin and a neutral cyclodextrin, operating in reverse polarity mode. The type of neutral cyclodextrin was included among other CPPs, both instrumental and related to background electrolyte composition, which were evaluated in a screening phase by an asymmetric screening matrix. Response surface methodology was carried out by a Doehlert design and allowed the contour plots to be drawn, highlighting significant interactions between some of the CPPs. DS was defined by applying Monte-Carlo simulations, and corresponded to the following intervals: sulfated-β-cyclodextrin concentration, 9-12 mM; methyl-β-cyclodextrin concentration, 29-38 mM; Britton-Robinson buffer pH, 3.24-3.50; voltage, 12-14 kV. Robustness of the method was examined by a Plackett-Burman matrix and the obtained results, together with system repeatability data, led to define a method control strategy. The method was validated and was finally applied to determine the enantiomeric purity of S-SUL in pharmaceutical dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate Bayesian approach.

PubMed

Fu, Zhibiao; Baker, Daniel; Cheng, Aili; Leighton, Julie; Appelbaum, Edward; Aon, Juan

2016-05-01

The principle of quality by design (QbD) has been widely applied to biopharmaceutical manufacturing processes. Process characterization is an essential step to implement the QbD concept to establish the design space and to define the proven acceptable ranges (PAR) for critical process parameters (CPPs). In this study, we present characterization of a Saccharomyces cerevisiae fermentation process using risk assessment analysis, statistical design of experiments (DoE), and the multivariate Bayesian predictive approach. The critical quality attributes (CQAs) and CPPs were identified with a risk assessment. The statistical model for each attribute was established using the results from the DoE study with consideration given to interactions between CPPs. Both the conventional overlapping contour plot and the multivariate Bayesian predictive approaches were used to establish the region of process operating conditions where all attributes met their specifications simultaneously. The quantitative Bayesian predictive approach was chosen to define the PARs for the CPPs, which apply to the manufacturing control strategy. Experience from the 10,000 L manufacturing scale process validation, including 64 continued process verification batches, indicates that the CPPs remain under a state of control and within the established PARs. The end product quality attributes were within their drug substance specifications. The probability generated with the Bayesian approach was also used as a tool to assess CPP deviations. This approach can be extended to develop other production process characterization and quantify a reliable operating region. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:799-812, 2016. © 2016 American Institute of Chemical Engineers.

In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides.

PubMed

Bolhassani, Azam; Jafarzade, Behnaz Sadat; Mardani, Golnaz

2017-01-01

The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full-length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose-dependent approach. A major disadvantage of PTD-fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non-covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP-based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

PubMed

Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

2017-12-01

This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

A Peptide-based Vector for Efficient Gene Transfer In Vitro and In Vivo

PubMed Central

Lehto, Taavi; Simonson, Oscar E; Mäger, Imre; Ezzat, Kariem; Sork, Helena; Copolovici, Dana-Maria; Viola, Joana R; Zaghloul, Eman M; Lundin, Per; Moreno, Pedro MD; Mäe, Maarja; Oskolkov, Nikita; Suhorutšenko, Julia; Smith, CI Edvard; Andaloussi, Samir EL

2011-01-01

Finding suitable nonviral delivery vehicles for nucleic acid–based therapeutics is a landmark goal in gene therapy. Cell-penetrating peptides (CPPs) are one class of delivery vectors that has been exploited for this purpose. However, since CPPs use endocytosis to enter cells, a large fraction of peptides remain trapped in endosomes. We have previously reported that stearylation of amphipathic CPPs, such as transportan 10 (TP10), dramatically increases transfection of oligonucleotides in vitro partially by promoting endosomal escape. Therefore, we aimed to evaluate whether stearyl-TP10 could be used for the delivery of plasmids as well. Our results demonstrate that stearyl-TP10 forms stable nanoparticles with plasmids that efficiently enter different cell-types in a ubiquitous manner, including primary cells, resulting in significantly higher gene expression levels than when using stearyl-Arg9 or unmodified CPPs. In fact, the transfection efficacy of stearyl-TP10 almost reached the levels of Lipofectamine 2000 (LF2000), however, without any of the observed lipofection-associated toxicities. Most importantly, stearyl-TP10/plasmid nanoparticles are nonimmunogenic, mediate efficient gene delivery in vivo, when administrated intramuscularly (i.m.) or intradermally (i.d.) without any associated toxicity in mice. PMID:21343913

Cell penetration: scope and limitations by the application of cell-penetrating peptides.

PubMed

Reissmann, Siegmund

2014-10-01

The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell-penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored in in vivo studies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging. This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood-brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline.

PubMed

Rees, Jon; Abrahams, Mark; Doble, Andrew; Cooper, Alison

2015-10-01

To improve awareness and recognition of chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among non-specialists and patients. To provide guidance to healthcare professionals treating patients with CBP and CP/CPPS, in both non-specialist and specialist settings. To promote efficient referral of care between non-specialists and specialists and the involvement of the multidisciplinary team (MDT). The guideline population were men with CBP or CP/CPPS (persistent or recurrent symptoms and no other urogenital pathology for ≥3 of the previous 6 months). Consensus recommendations for the guidelines were based on a search to identify literature on the diagnosis and management of CBP and CP/CPPS (published between 1999 and February 2014). A Delphi panel process was used where high-quality, published evidence was lacking. CBP and CP/CPPS can present with a wide range of clinical manifestations. The four main symptom domains are urogenital pain, lower urinary tract symptoms (LUTS - voiding or storage symptoms), psychological issues and sexual dysfunction. Patients should be managed according to their individual symptom pattern. Options for first-line treatment include antibiotics, α-adrenergic antagonists (if voiding LUTS are present) and simple analgesics. Repeated use of antibiotics, such as quinolones, should be avoided if there is no obvious symptomatic benefit from infection control or cultures do not support an infectious cause. Early use of treatments targeting neuropathic pain and/or referral to specialist services should be considered for patients who do not respond to initial measures. An MDT approach (urologists, pain specialists, nurse specialists, specialist physiotherapists, general practitioners, cognitive behavioural therapists/psychologists, and sexual health specialists) is recommended. Patients should be fully informed about the possible underlying causes and treatment options, including an explanation of the chronic pain cycle. Chronic prostatitis can present with a wide variety of signs and symptoms. Identification of individual symptom patterns and a symptom-based treatment approach are recommended. Further research is required to evaluate management options for CBP and CP/CPPS. © 2015 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Chronic prostatitis/chronic pelvic pain syndrome in adolescents compared with that in young adults.

PubMed

Lee, Keon-Cheol; Cho, In-Rae

2017-07-01

Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) has been studied mainly in adults; reports in adolescents are rare. We compared the clinical characteristics of adolescent CP/CPPS patients with those of young adults. We retrospectively analyzed 20 adolescents with CP/CPPS aged <20 years who visited our outpatient department from August 2005 to April 2012. The control group comprised 120 young adult CP/CPPS patients. A complete medical history, physical examination, the national institute of health-chronic prostatitis symptoms index (NIH-CPSI) questionnaire, urinalysis, expressed prostatic secretion (EPS) or semen analysis, transrectal prostate ultrasonography, and prostate-specific antigen (PSA) were performed. Based on the EPS or semen analysis, patients were divided into category III-A or III-B. The mean age was 16.5±2.0 and 32.8±5.0 years in the adolescent and control groups, respectively. A sexual activity history was seen in 2 patients; 9 and 11 patients were in category III-A and III-B, respectively. The PSA was 0.65±0.39 and 1.22±0.48 ng/mL in the adolescent and control groups, respectively. The prostate size was 12.4±4.4 and 21.0±4.9 g in the adolescent and control groups, respectively. The NIH-CPSI scores in the adolescent group were 9.2±5.2, 5.5±3.5, 7.5±3.2, and 22.2±8.1 for pain, voiding, quality of life (QoL) domains, and total scores, respectively. The adolescent group showed a tendency to exhibit high voiding symptom scores. CPPS has an equally severe impact on QoL in adults and adolescents. Apart from high voiding symptom scores in adolescents, no difference was found in terms of urologic clinical parameters.

The role of flower pollen extract in managing patients affected by chronic prostatitis/chronic pelvic pain syndrome: a comprehensive analysis of all published clinical trials.

PubMed

Cai, Tommaso; Verze, Paolo; La Rocca, Roberto; Anceschi, Umberto; De Nunzio, Cosimo; Mirone, Vincenzo

2017-04-21

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still a challenge to manage for all physicians. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of flower pollen extract would be helpful for physicians who are considering a phytotherapeutic approach to treating patients with CP/CPPS. A comprehensive search of the PubMed and Embase databases up to June 2016 was performed. This comprehensive analysis included both pre-clinical and clinical trials on the role of flower pollen extract in CP/CPPS patients. Moreover, a meta-analysis of available randomized controlled trials (RCTs) was performed. The NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and Quality of Life related questionnaires (QoL) were the most commonly used tools to evaluate the therapeutic efficacy of pollen extract. Pre-clinical studies demonstrated the anti-inflammatory and anti-proliferative role of pollen extract. 6 clinical, non-controlled studies including 206 patients, and 4 RCTs including 384 patients were conducted. The mean response rate in non-controlled studies was 83.6% (62.2%-96.0%). The meta-analysis revealed that flower pollen extract could significantly improve patients' quality of life [OR 0.52 (0.34-.0.81); p = 0.02]. No significant adverse events were reported. Most of these studies presented encouraging results in terms of variations in NIH-CPSI and QoL scores. These studies suggest that the use of flower pollen extract for the management of CP/CPPS patients is beneficial. Future publications of robust evidence from additional RCTs and longer-term follow-up would provide more support encouraging the use of flower pollen extracts for CP/CPPS patients.

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

PubMed

Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP

PubMed Central

Kutch, Jason J.; Yani, Moheb S.; Asavasopon, Skulpan; Kirages, Daniel J.; Rana, Manku; Cosand, Louise; Labus, Jennifer S.; Kilpatrick, Lisa A.; Ashe-McNalley, Cody; Farmer, Melissa A.; Johnson, Kevin A.; Ness, Timothy J.; Deutsch, Georg; Harris, Richard E.; Apkarian, A. Vania; Clauw, Daniel J.; Mackey, Sean C.; Mullins, Chris; Mayer, Emeran A.

2015-01-01

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing. PMID:26106574

Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

PubMed

Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

2018-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

PubMed Central

Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

2018-01-01

Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents. PMID:29563797

Chronic pelvic pain syndrome: role of a thorough clinical assessment.

PubMed

Quaghebeur, Jörgen; Wyndaele, Jean-Jacques

2015-04-01

Chronic pelvic pain syndrome (CPPS) presents with a variety of symptoms affecting multiple systems. There is no universal treatment that can be given to all patients with CPPS. The results of treatment depend greatly on an accurate diagnosis. A thorough clinical assessment, including a "four-step plan", should include paying special attention to the musculoskeletal system. This assessment is not difficult to perform and provides valuable information on possible muscular problems and neuropathy.

New paradigms in understanding chronic pelvic pain syndrome.

PubMed

Konkle, Katy S; Clemens, J Quentin

2011-08-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male pain condition that is associated with significant discomfort and disability. Despite significant efforts, there remains no definitive etiology or treatment of the spectrum of pelvic symptoms reported by these patients. The purpose of this review is to summarize important clinical and scientific findings related to CP/CPPS from the previous 2 years, and to evaluate their impact on our understanding of, and approach to, the disease.

Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

PubMed

Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

2017-01-01

We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

PubMed Central

Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

2014-01-01

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

Positioning, telling, and performing a male illness: Chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wood, Nicholas; Qureshi, Annum; Mughal, Fahim

2017-11-01

There is a paucity of illness accounts of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), despite a significant level of prevalence and burden of disease. This qualitative study thus elicited twelve accounts from men suffering with CP/CPPS. Narrative analysis was employed, focusing primarily on narrative content. Three major narrative themes were identified: (1) Medical stories: Blame and shame; (2) The Erratic nature of CP/CPPS; and (3) Ongoing struggles for coping and cures and the Search for meaning. Recommendations were made for health care providers and increasing the internal agency, support and activism of men with this debilitating condition. Statement of contribution What is already known on this subject? One qualitative account of this male illness (CP/CPPS) exists: an IPA study. Five cross-sectional themes: (1) Need for repeated confirmation - disease not life-threatening nor leading inexorably towards cancer; (2) Disturbed sleep and fatigue; (3) Concealing pain and problems - 'normalizing'; (4) Enduring pain by performing activities; and (5) Abrupt mood swings and limited sociality. What does this study add? Narrative analysis adds information as to how this illness is managed and survived over time. It challenges the findings (above) by providing an insider perspective. Novel narrative themes include meaning-making amongst others. Masculine performance and experiences are also crucial to this stigmatized illness. © 2017 The British Psychological Society.

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS Nano GO Consortium

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

Xia, Tian; Hamilton, Raymond F.; Bonner, James C.

2013-06-01

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different speciesmore » (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells. Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μ g/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β. Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity.« less

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP)

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90–95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17’s role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS. PMID:25933188

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines.

PubMed

Wierzbicki, Piotr M; Kogut-Wierzbicka, Marzena; Ruczynski, Jaroslaw; Siedlecka-Kroplewska, Kamila; Kaszubowska, Lucyna; Rybarczyk, Agnieszka; Alenowicz, Magdalena; Rekowski, Piotr; Kmiec, Zbigniew

2014-01-01

Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5-5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

Calcium-containing phosphopeptides pave the secretory pathway for efficient protein traffic and secretion in fungi.

PubMed

Martín, Juan F

2014-09-10

Casein phosphopeptides (CPPs) containing chelated calcium drastically increase the secretion of extracellular homologous and heterologous proteins in filamentous fungi. Casein phosphopeptides released by digestion of alpha - and beta-casein are rich in phosphoserine residues (SerP). They stimulate enzyme secretion in the gastrointestinal tract and enhance the immune response in mammals, and are used as food supplements. It is well known that casein phosphopeptides transport Ca2+ across the membranes and play an important role in Ca2+ homeostasis in the cells. Addition of CPPs drastically increases the production of heterologous proteins in Aspergillus as host for industrial enzyme production. Recent proteomics studies showed that CPPs alter drastically the vesicle-mediated secretory pathway in filamentous fungi, apparently because they change the calcium concentration in organelles that act as calcium reservoirs. In the organelles calcium homeostasis a major role is played by the pmr1 gene, that encodes a Ca2+/Mn2+ transport ATPase, localized in the Golgi complex; this transporter controls the balance between intra-Golgi and cytoplasmic Ca2+ concentrations. A Golgi-located casein kinase (CkiA) governs the ER to Golgi directionality of the movement of secretory proteins by interacting with the COPII coat of secretory vesicles when they reach the Golgi. Mutants defective in the casein-2 kinase CkiA show abnormal targeting of some secretory proteins, including cytoplasmic membrane amino acid transporters that in ckiA mutants are miss-targeted to vacuolar membranes. Interestingly, addition of CPPs increases a glyceraldehyde-3-phpshate dehydrogenase protein that is known to associate with microtubules and act as a vesicle/membrane fusogenic agent. In summary, CPPs alter the protein secretory pathway in fungi adapting it to a deregulated protein traffic through the organelles and vesicles what results in a drastic increase in secretion of heterologous and also of some homologous proteins.

Single-crystal phosphors for high-brightness white LEDs/LDs

NASA Astrophysics Data System (ADS)

Víllora, Encarnación G.; Arjoca, Stelian; Inomata, Daisuke; Shimamura, Kiyoshi

2016-03-01

White light-emitting diodes (wLEDs) are the new environmental friendly sources for general lighting purposes. For applications requiring a high-brightness, current wLEDs present overheating problems, which drastically decrease their emission efficiency, color quality and lifetime. This work gives an overview of the recent investigations on single-crystal phosphors (SCPs), which are proposed as novel alternative to conventional ceramic powder phosphors (CPPs). This totally new approach takes advantage of the superior properties of single-crystals in comparison with ceramic materials. SCPs exhibit an outstanding conversion efficiency and thermal stability up to 300°C. Furthermore, compared with encapsulated CPPs, SCPs possess a superior thermal conductivity, so that generated heat can be released efficiently. The conjunction of all these characteristics results in a low temperature rise of SCPs even under high blue irradiances, where conventional CPPs are overheated or even burned. Therefore, SCPs represent the ideal, long-demanded all-inorganic phosphors for high-brightness white light sources, especially those involving the use of high-density laser-diode beams.

Role of the visual experience-dependent nascent proteome in neuronal plasticity

PubMed Central

Liu, Han-Hsuan; McClatchy, Daniel B; Schiapparelli, Lucio; Shen, Wanhua; Yates, John R

2018-01-01

Experience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experience-dependent plasticity, we conducted a quantitative proteomic screen of the nascent proteome in response to visual experience in Xenopus optic tectum using bio-orthogonal metabolic labeling (BONCAT). We identified 83 differentially synthesized candidate plasticity proteins (CPPs). The CPPs form strongly interconnected networks and are annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs revealed the requirement for eukaryotic initiation factor three subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity in tectal neurons and behavioral plasticity in tadpoles. These results demonstrate that the nascent proteome is dynamic in response to visual experience and that de novo synthesis of machinery that regulates RNA splicing and protein translation is required for experience-dependent plasticity. PMID:29412139

Chinese urologists' practice patterns of diagnosing and treating chronic pelvic pain syndrome: a questionnaire survey.

PubMed

Zhang, Kai; Xu, Ben; Xiao, Yun-xiang; Shang, Xue-jun; Bai, Wen-jun; Wang, Xiao-feng; Liu, Ji-hong; Deng, Chun-hua

2014-08-18

To investigate the application of the Chinese Urological Association (CUA) guidelines on prostatitis and the effects on the clinical practice patterns of diagnosing and treating chronic pelvic pain syndrome (CPPS) among Chinese urologists. We conducted a questionnaire investigation of the CUA guidelines on prostatitis among the urologists from 399 hospitals in 63 cities of China, and performed statistical analyses on all the eligible questionnaires collected. Of the 2 251 questionnaires distributed, 2 046 (90.9%) were eligible, of which 92.5% were from the urologists in tertiary or secondary hospitals, of whom 72.3% had senior or intermediate professional titles, and 90.2% had studied the CUA guidelines. Most respondents agreed that Type III prostatitis was a clinical syndrome, of which the diagnosis should be made after other conditions with similar symptoms had been ruled out and the aim was to relieve pain, alleviate urination symptoms and improve quality of life. Those who had and those who had not studied the CUA guidelines differed in their viewpoints on CPPS as illustrated in the guidelines. In clinical practice, the most common treatment options for CPPS were pharmaceutical therapy (95.0%), life style adjustment (88.9%), and psychotherapy (79.9%), and the most frequently prescribed drugs were phytotherapy (84.5%), α-blockers (79.0%) and antibiotics (64.0%). CUA guidelines on prostatitis has gained a nationwide application and promoted the standardization of the management of CPPS in China.

Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats.

PubMed

Liu, Y-J; Song, G-H; Liu, G T

2016-08-01

According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect. © 2016 Blackwell Verlag GmbH.

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

PubMed Central

Breser, María L.; Salazar, Florencia C.; Rivero, Viginia E.; Motrich, Rubén D.

2017-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain. PMID:28824626

Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway.

PubMed

Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Flórez, Martha G; Jami, Mohammad S; Paniagua, Miguel A; Martín, Juan F

2012-01-10

The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins.

A prospective study on association of prostatic calcifications with sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

PubMed

Zhao, Zhigang; Xuan, Xujun; Zhang, Jingwei; He, Jun; Zeng, Guohua

2014-10-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common debilitating condition of unclear etiology. Sexual dysfunction is an important component of the clinical phenotype of CP/CPPS. Patients often have prostatic calcifications, but a link to sexual dysfunction is unknown. The aim of this study was to evaluate the association of prostatic calcifications with sexual dysfunction in this condition. A total of 358 males with CP/CPPS were consecutively enrolled, and a prospectively maintained database of these patients was analyzed. Calcifications were diagnosed using ultrasound imaging of the prostate. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Sexual dysfunction was evaluated using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire and 5-item Premature Ejaculation Diagnostic Tool scales. The variables were compared between patients with prostatic calcifications and those without using the Student's t-test, Wilcoxon unpaired test, or chi-square test. Logistic regression models were developed to explore a possible association between prostatic calcifications and sexual dysfunction. Measurable calcifications in the prostate were found in 175 (48.9%) of the 358 patients. Patients with calcifications were more likely to have higher white blood cell counts or positive bacteria cultures in their prostatic fluid, longer symptoms duration, and lower scores for the total IIEF-15, IIEF-erectile function, and IIEF-intercourse satisfaction domains (P < 0.001 for each). However, the scores for CPSI, premature ejaculation, and IIEF-orgasmic function, IIEF-sexual desire, and IIEF-overall satisfaction domains were identical between men with and without calcifications (P > 0.05 for each). Furthermore, logistic regression analyses revealed that intraprostatic calcification is significantly associated with self-assessed erectile dysfunction (ED) (odds ratio:3.632, 95% confidence interval: 2.405-5.822, P < 0.001). Our results showed that prostatic calcifications are significantly associated with the presence of ED in CP/CPPS males. © 2014 International Society for Sexual Medicine.

Long-term effect of extracorporeal shock wave therapy on the treatment of chronic pelvic pain syndrome due to non bacterial prostatitis.

PubMed

Moayednia, Amir; Haghdani, Saeid; Khosrawi, Saeid; Yousefi, Elham; Vahdatpour, Babak

2014-04-01

There is limited evidence about the chronic pelvic pain syndrome (CPPS) treatment by shockwave therapy, and the aim of this study was to evaluate the effect of extracorporeal shockwave therapy on CPPS due to non bacterial prostatitis in a long-term period. In a follow-up survey, 40 patients with CPPS (that were randomly distributed into the treatment or sham groups were evaluated at 16, 20, and 24 weeks. In the treatment group, patients were treated by extracorporeal shock wave therapy (ESWT) once a week for 4 weeks by a protocol of 3000 impulses, 0.25 mJ/m(2) and 3 Hz of frequency. 0.05 mJ/m(2) were added in each week. In the sham group, the same protocol was applied, but with the probe being turned off. The follow-up assessments were done by visual analog scale for pain and National Institutes of Health-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Data were compared using independent t-test or analysis of variences. Three patients did not complete the study protocol, 37 patients were evlauated (19 patients in treatment and 18 patients in the sham group). At week 24, the mean of pain score, urinary score, quality-of-life and NIH-CPSI score between two groups were not statistically different. Although, ESWT therapy as a safe and effective therapy in CPPS in short-term follow-up has been established, its long-term efficacy was not supported by this study.

Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway

PubMed Central

2012-01-01

Background The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Results Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. Conclusions In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins. PMID:22234238

Acupuncture versus Sham Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain

PubMed Central

Lee, Shaun Wen Huey; Liong, Men Long; Yuen, Kah Hay; Leong, Wing Seng; Chee, Christopher; Cheah, Phaik Yeong; Choong, Weng Pho; Wu, Yue; Khan, Nurzalina; Choong, Wooi Long; Yap, Hin Wai; Krieger, John N.

2015-01-01

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) afflicts 2–10% of adult men. Available therapies offer little or no proven benefit. Because acupuncture represents an attractive “natural” therapy, we compared the efficacy of acupuncture to sham acupuncture for CP/CPPS Methods Participants met US National Institutes of Health (NIH) consensus criteria for CP/CPPS, aged ≥ 20 years old, with total score ≥ 15 on the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) and symptoms for at least 3 of the preceding 6 months were randomized 1:1 to acupuncture or sham acupuncture. Treatment consisted of twice weekly 30-minute sessions for 10 weeks (20 sessions total), without needle stimulation, herbs or adjuvants. The primary response criterion was a six-point decrease from baseline to week 10 in NIH-CPSI total score (range 0–43). Results Thirty-two (73%) of 44 participants responded in the acupuncture group compared to 21 (47%) of 45 sham group participants (relative risk [RR] 1.81, 95% confidence interval [CI], 1.3–3.1, p=0.02,). Long-term responses 24 weeks after completing therapy without additional treatment occurred in 14 (32%) of 44 acupuncture group participants and in 6 (13%) of 45 sham group participants (RR 2.39, 95% CI, 1.0–5.6, p=0.04). Conclusion After 10 weeks of treatment, acupuncture proved almost twice as likely as sham to improve CP/CPPS symptoms. Participants receiving acupuncture were 2.4 fold more likely to experience long-term benefit than participants receiving sham acupuncture. PMID:18187077

Therapy-related longitudinal brain perfusion changes in patients with chronic pelvic pain syndrome.

PubMed

Weisstanner, Christian; Mordasini, Livio; Thalmann, George N; Verma, Rajeev K; Rummel, Christian; Federspiel, Andrea; Kessler, Thomas M; Wiest, Roland

2017-08-03

The imaging method most frequently employed to identify brain areas involved in neuronal processing of nociception and brain pain perception is blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Arterial spin labelling (ASL), in contrast, offers advantages when slow varying changes in brain function are investigated. Chronic pelvic pain syndrome (CPPS) is a disorder of, mostly, young males that leads to altered pain perceptions in structures related to the pelvis. We aimed to investigate the potential of ASL to monitor longitudinal cranial blood flow (CBF) changes in patients with CPPS. In a randomised, placebo-controlled, double-blind single centre trial, we investigated treatment effects in CPPS after 12 weeks in patients that underwent sono-electro-magnetic therapy vs placebo. We investigated changes of CBF related to treatment outcome using pseudo-continuous arterial spin labelling (pCASL)-MRI. We observed CBF downregulation in the prefrontal cortex and anterior cingulate cortex and upregulation in the dorsolateral prefrontal cortex in responders. Nonresponders presented with CBF upregulation in the hippocampus. In patients with a history of CPPS of less than 12 months, there were significant correlations between longitudinal CBF changes and the Chronic Prostatitis Symptom Index pain subscore within the joint clusters anterior cingulate cortex and left anterior prefrontal cortex in responders, and the right hippocampus in nonresponders. We demonstrated therapy-related and stimulus-free longitudinal CBF changes in core areas of the pain matrix using ASL. ASL may act as a complementary noninvasive method to functional MRI and single-photon emission computed tomography / positron emission tomography, especially in the longitudinal assessment of pain response in clinical trials.

Anti-nanobacterial therapy for men with chronic prostatitis/chronic pelvic pain syndrome and prostatic stones: preliminary experience.

PubMed

Shoskes, Daniel A; Thomas, Kim D; Gomez, Eyda

2005-02-01

Category III chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a common debilitating condition of unclear etiology. Patients often have prostatic calcifications but a link to symptoms is controversial. Nanobacteria are implicated in stone formation in the urinary tract and, therefore, therapy to eliminate nanobacteria and the stones that they produce might have an impact on CPPS symptoms. A total of 16 men with recalcitrant CPPS refractory to multiple prior therapies were treated with comET (Nanobac Life Sciences, Tampa, Florida), which consists of 500 mg tetracycline, a proprietary nutraceutical and an ethylenediaminetetraacetic acid suppository daily. The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), transrectal ultrasound, and blood and urine tests for nanobacterial antigen were performed at the start and conclusion of 3 months of therapy. One patient was lost to followup. Mean NIH-CPSI total score +/- SD decreased from 25.7 +/- 1.6 to 13.7 +/- 2.0 (p <0.0001). Significant improvement was seen in each subscore domain. A total of 12 patients (80%) had at least 25% improvement on NIH-CPSI and 8 (53%) had at least 50% improvement. Nanobacterial antigen or antibody was found in 60% of serum and 40% of urine samples. In 10 patients who underwent transrectal ultrasound after therapy prostatic stones were decreased in size or resolved in 50%. Therapy designed to eliminate nanobacteria resulted in significant improvement in the symptoms of recalcitrant CPPS in the majority of men, whether due to the treatment of stone producing nanobacteria or through some other mechanism. Prospective placebo controlled trials are warranted.

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

PubMed

de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

2017-05-01

To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

A common pronociceptive pain modulation profile typifying subgroups of chronic pelvic pain syndromes is interrelated with enhanced clinical pain.

PubMed

Grinberg, Keren; Granot, Michal; Lowenstein, Lior; Abramov, Liora; Weissman-Fogel, Irit

2017-06-01

Provoked vestibulodynia (PVD) and painful bladder syndrome (PBS), subgroups of chronic pelvic pain syndromes (CPPS), are considered to share common biophysiological peripheral mechanisms. In addition, indications of a pronociceptive pain profile coexisting with psychological vulnerability suggest common dysfunctional pain processing and pain modulation in these 2 subgroups of CPPS. We therefore aimed at comparing the pain profile and psychological traits of patients with PVD and PBS to see whether the pain profile contributes to intersubject variability of clinical pain symptoms. Patients with PVD (n = 18) and PBS (n = 21) were compared with healthy controls (n = 20) in their responses to (1) pain psychophysical tests applied to both referred (suprapubis) and remote (hand) body areas and (2) pain-related psychological factors (pain catastrophizing, depression, anxiety, and somatization). We found a similar pronociceptive pain profile in the 2 subgroups of CPPS-enhanced facilitation (ie, hyperalgesia in the referred body area [P < 0.001]) and inefficient inhibition (ie, reduced conditioned pain modulation [P < 0.001] that were associated with both enhanced pain ratings evoked during trigger point examination [P < 0.037]) and higher Brief Pain Inventory ratings (P = 0.002). The latter was also correlated with pain catastrophizing (r = 0.504, P = 0.001) and depression symptoms (r = 0.361, P = 0.024). The findings suggest common mechanisms underlying a dysfunctional nociceptive system in both PVD and PBS. The intersubject variability in the level of dysfunction and its association with disease severity recommends a personalized pain treatment that may alleviate daily pain and dysfunction in patients with CPPS.

Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

PubMed

Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

2017-10-01

The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

Methods for testing Zernike phase plates and a report on silicon-based phase plates with reduced charging and improved ageing characteristics

PubMed Central

Marko, Michael; Meng, Xing; Hsieh, Chyongere; Roussie, James; Striemer, Christopher

2013-01-01

Imaging with Zernike phase plates is increasingly being used in cryo-TEM tomography and cryo-EM single-particle applications. However, rapid ageing of the phase plates, together with the cost and effort in producing them, present serious obstacles to widespread adoption. We are experimenting with phase plates based on silicon chips that have thin windows; such phase plates could be mass-produced and made available at moderate cost. The windows are coated with conductive layers to reduce charging, and this considerably extends the useful life of the phase plates compared to traditional pure-carbon phase plates. However, a compromise must be reached between robustness and transmission through the phase-plate film. Details are given on testing phase-plate performance by means of imaging an amorphous thin film and evaluating the power spectra of the images. PMID:23994351

Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy on Men With Chronic Pelvic Pain Syndrome Refractory to 3-As Therapy.

PubMed

Guu, Shiao-Jin; Geng, Jiun-Hung; Chao, I-Ting; Lin, Hui-Tzu; Lee, Yung-Chin; Juan, Yung-Shun; Liu, Chia-Chu; Wang, Chii-Jye; Tsai, Chia-Chun

2018-03-01

Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm prospective study. Patients with CPPS without more than a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH-CPSI, visual analog scale (VAS) score, International Prostate Symptom Score (IPSS), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT. Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist circumference was the only significant predictor of a successful response to LI-ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to traditional 3-As therapy. Further studies are needed to determine an adequate therapeutic protocol and important predictors in patients with different CPPS etiologies.

Constant proportion harvest policies: dynamic implications in the Pacific halibut and Atlantic cod fisheries.

PubMed

Yakubu, Abdul-Aziz; Li, Nianpeng; Conrad, Jon M; Zeeman, Mary-Lou

2011-07-01

Overfishing, pollution and other environmental factors have greatly reduced commercially valuable stocks of fish. In a 2006 Science article, a group of ecologists and economists warned that the world may run out of seafood from natural stocks if overfishing continues at current rates. In this paper, we explore the interaction between a constant proportion harvest policy and recruitment dynamics. We examine the discrete-time constant proportion harvest policy discussed in Ang et al. (2009) and then expand the framework to include stock-recruitment functions that are compensatory and overcompensatory, both with and without the Allee effect. We focus on constant proportion policies (CPPs). CPPs have the potential to stabilize complex overcompensatory stock dynamics, with or without the Allee effect, provided the rates of harvest stay below a threshold. If that threshold is exceeded, CPPs are known to result in the sudden collapse of a fish stock when stock recruitment exhibits the Allee effect. In case studies, we analyze CPPs as they might be applied to Gulf of Alaska Pacific halibut fishery and the Georges Bank Atlantic cod fishery based on harvest rates from 1975 to 2007. The best fit models suggest that, under high fishing mortalities, the halibut fishery is vulnerable to sudden population collapse while the cod fishery is vulnerable to steady decline to zero. The models also suggest that CPP with mean harvesting levels from the last 30 years can be effective at preventing collapse in the halibut fishery, but these same policies would lead to steady decline to zero in the Atlantic cod fishery. We observe that the likelihood of collapse in both fisheries increases with increased stochasticity (for example, weather variability) as predicted by models of global climate change. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of acupuncture on clinical symptoms and laboratory indicators for chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis.

PubMed

Liu, Bu-Ping; Wang, Yun-Ting; Chen, Si-da

2016-12-01

To systematically review the efficacy and safety of acupuncture for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PubMed, Cochrane library Central, Web of Science, Wang-fang Database, and CNKI were searched from their inception to June 30, 2016. Data of acupuncture for CP/CPPS following randomized controlled trials (RCTs) was included. The data were analyzed using the Cochrane Collaboration Review Manager. The primary data were the National Institute of Health-Chronic Prostatitis Index (NIH-CPSI) score at the end of follow-up. Ten RCTs were enrolled. Acupuncture was superior to the control in NIH-CPSI (MD -3.98, [95 % CI -5.78 to -2.19]; P < 0.0001) and response rate (RR 4.12, [95 % CI 1.67-10.18]; P = 0.002). Acupuncture was superior to sham acupuncture on NIH-CPSI, response rate, pain, urinary, and quality of life (QOL). Standard medication was inferior to acupuncture in terms of NIH-CPSI (MD -3.08, [95 % CI -5.57 to -0.60]; P = 0.02) and response rate (RR 2.03, [95 % CI 1.04-3.97]; P = 0.04), but standard medication was superior to acupuncture on improving urinary symptoms. There was no significant difference in the adverse events. Acupuncture/acupuncture plus standard medication significantly down-regulated IL-1β compared with standard medication in prostatic fluid. Acupuncture treating CP/CPPS is effective and safe. The effects of acupuncture on NIH-CPSI, response rate, pain symptoms, and QOF were superior to the control, but standard medication significantly improved urinary symptoms compared with acupuncture. Acupuncture can decrease the IL-1β in prostatic fluid for CP/CPPS.

Evaluation of cell-penetrating peptides (CPPs) as vehicles for intracellular delivery of antisense peptide nucleic acid (PNA).

PubMed

Bendifallah, Nadia; Rasmussen, Frank Winther; Zachar, Vladimir; Ebbesen, Peter; Nielsen, Peter E; Koppelhus, Uffe

2006-01-01

Cell-penetrating peptides (CPPs) are characterized by their ability to be internalized in mammalian cells. To investigate the relative potency of CPPs as carriers of medicinally relevant cargo, a positive read-out assay based on the ability of a peptide nucleic acid (PNA) oligomer to promote correct expression of a recombinant luciferase gene was employed. Seven different CPPs were included in the study: Transportan, oligo-arginine (R7-9), pTat, Penetratin, KFF, SynB3, and NLS. The CPP-PNA conjugates were synthesized by different conjugation chemistries: continuous synthesis, maleimide coupling, and ester or disulfide linkage. Under serum-free conditions PNA-SS-Transportan-amide (ortho)-PNA was found to be the most potent conjugate, resulting in maximum luciferase signal at a concentration of 1-2 microM. (D-Arg)9-PNA showed optimal efficacy at 5 microM but gave rise to only one-third of the luciferase signal obtained with the Transportan conjugate. The pTat- and KFF-PNA conjugates showed significantly lower efficacy. The penetratin-, SynB3-. and NLS-PNA conjugates showed only minimal or no activity. Serum was found to have a drastic negative impact on CPP-driven cellular uptake. PNA-SS-Transportan-acid (ortho) and (D-Arg)9-PNA were least sensitive to the presence of serum. Both the chemical nature and, in the case of Transportan, the position of the peptide PNA coupling were found to have a major impact on the transport capacity of the peptides. However, no simple relationship between linker type and antisense activity of the conjugates could be deduced from the data.

Cepstral analysis of normal and pathological voice in Spanish adults. Smoothed cepstral peak prominence in sustained vowels versus connected speech.

PubMed

Delgado-Hernández, Jonathan; León-Gómez, Nieves M; Izquierdo-Arteaga, Laura M; Llanos-Fumero, Yanira

In recent years, the use of cepstral measures for acoustic evaluation of voice has increased. One of the most investigated parameters is smoothed cepstral peak prominence (CPPs). The objectives of this paper are to establish the usefulness of this acoustic measure in the objective evaluation of alterations of the voice in Spanish and to determine what type of voice sample (sustained vowels or connected speech) is the most sensitive in evaluating the severity of dysphonia. Forty subjects participated in this study 40, 20 controls and 20 with dysphonia. Two voice samples were recorded for each subject (one sustained vowel/a/and four phonetically balanced sentences) and the CPPs was calculated using the Praat programme. Three raters perceptually evaluated the voice sample with the Grade parameter of GRABS scale. Significantly lower values were found in the dysphonic voices, both for/a/(t [38] = 4.85, P<.000) and for phrases (t [38] = 5,75, P<.000). In relation to the type of voice sample most suitable for evaluating the severity of voice alterations, a strong correlation was found with the acoustic-perceptual scale of CPPs calculated from connected speech (r s = -0.73) and moderate correlation with that calculated from the sustained vowel (r s = -0,56). The results of this preliminary study suggest that CPPs is a good measure to detect dysphonia and to objectively assess the severity of alterations in the voice. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Electronic transport properties in [n]cycloparaphenylenes molecular devices

NASA Astrophysics Data System (ADS)

Hu, Lizhi; Guo, Yandong; Yan, Xiaohong; Zeng, Hongli; Zhou, Jie

2017-07-01

The electronic transport of [n]cycloparaphenylenes ([n]CPPs) is investigated based on nonequilibrium Green's function formalism in combination with the density-functional theory. Negative differential resistance (NDR) phenomenon is observed. Further analysis shows that the reduction of the transmission peak induced by the bias changing near Fermi energy results in the NDR effect. Replacing the electrode (from carbon chain to Au electrode), doping with N atom and changing the size of the nanohoop (n = 5, 6, 8, 10) have also been studied and the NDR still exists, suggesting the NDR behavior is the intrinsic feature of such [n]CPPs systems, which would be quite useful in future nanoelectronic devices.

Singlet and triplet excitons and charge polarons in cycloparaphenylenes. A density functional theory study

DOE PAGES

Liu, Jin; Adamska, Lyudmyla; Doorn, Stephen K.; ...

2015-05-14

Conformational structure and the electronic properties of various electronic excitations in cycloparaphenylenes (CPPs) are calculated using hybrid Density Functional Theory (DFT). The results demonstrate that wavefunctions of singlet and triplet excitons as well as the positive and negative polarons remain fully delocalized in CPPs. In contrast, these excitations in larger CPP molecules become localized on several phenyl rings, which are locally planarized, while the undeformed ground state geometry is preserved on the rest of the hoop. As evidenced by the measurements of bond-length alternation and dihedral angles, localized regions show stronger hybridization between neighboring bonds and thus enhanced electronic communication.more » This effect is even more significant in the smaller hoops, where phenyl rings have strong quinoid character in the ground state. Thus, upon excitation, electron–phonon coupling leads to the self-trapping of the electronic wavefunction and release of energy from fractions of an eV up to two eVs, depending on the type of excitation and the size of the hoop. The impact of such localization on electronic and optical properties of CPPs is systematically investigated and compared with the available experimental measurements.« less

Bioactive Peptides Isolated from Casein Phosphopeptides Enhance Calcium and Magnesium Uptake in Caco-2 Cell Monolayers.

PubMed

Cao, Yong; Miao, Jianyin; Liu, Guo; Luo, Zhen; Xia, Zumeng; Liu, Fei; Yao, Mingfei; Cao, Xiaoqiong; Sun, Shengwei; Lin, Yanyin; Lan, Yaqi; Xiao, Hang

2017-03-22

The ability of casein phosphopeptides (CPPs) to bind and transport minerals has been previously studied. However, the single bioactive peptides responsible for the effects of CPPs have not been identified. This study was to purify calcium-binding peptides from CPPs and to determine their effects on calcium and magnesium uptake by Caco-2 cell monolayers. Five monomer peptides designated P1 to P5 were isolated and the amino acid sequences were determined using LC-MS/MS. Compared with the CPP-free control, all five monomeric peptides exhibited significant enhancing effects on the uptake of calcium and magnesium (P < 0.05). Interestingly, when calcium and magnesium were presented simultaneously with P5, magnesium was taken up with priority over calcium in the Caco-2 cell monolayers. For example, at 180 min, the amount of transferred magnesium and calcium was 78.4 ± 0.95 μg/well and 2.56 ± 0.64 μg/well, respectively, showing a more than 30-fold difference in the amount of transport caused by P5. These results provide novel insight into the mineral transport activity of phosphopeptides obtained from casein.

Social Determinants of Chronic Prostatitis/Chronic Pelvic Pain Syndrome Related Lifestyle and Behaviors among Urban Men in China: A Case-Control Study

PubMed Central

Chen, Chen; Chen, Liang; Han, Qingrong; Ye, Huarong

2016-01-01

Purpose. In order to find key risk factors of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among urban men in China, an age-matched case-control study was performed from September 2012 to May 2013 in Yichang, Hubei Province, China. Methodology. A total of 279 patients and 558 controls were recruited in this study. Data were collected by a self-administered questionnaire, including demographics, diet and lifestyle, psychological status, and a physical exam. Conditional logistic regression model was used to analyze collected data. Results. Chemical factors exposure, night shift, severity of mood, and poor self-health cognition were entered into the regression model, and result displayed that these four factors had odds ratios of 1.929 (95% CI, 1.321–2.819), 1.456 (95% CI, 1.087–1.949), 1.619 (95% CI, 1.280–2.046), and 1.304 (95% CI, 1.094–1.555), respectively, which suggested that these four factors could significantly affect CP/CPPS. Conclusion. These results suggest that many factors affect CP/CPPS, including biological, social, and psychological factors. PMID:27579305

Purification, Characterization, and Antioxidant Activity of Polysaccharides Isolated from Cortex Periplocae.

PubMed

Wang, Xiaoli; Zhang, Yifei; Liu, Zhikai; Zhao, Mingqin; Liu, Pengfei

2017-10-31

In this study, crude Cortex Periplocae polysaccharides (CCPPs) were extracted with water. CCPPs were decolored with AB-8 resin and deproteinated using papain-Sevage methods. Then, they were further purified and separated through DEAE-52 anion exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Three main fractions-CPP1, CPP2, and CPP3, (CPPs)-were obtained. The average molecular weights, monosaccharide analysis, surface morphology, and chemical compositions of the CPPs were investigated by high-performance gel permeation chromatography (HPGPC), gas chromatography-mass spectrometry (GC/MS), UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectrum, and nuclear magnetic resonance (NMR). In addition, the antioxidant activities of these three polysaccharides were investigated. The results indicated that all of the CPPs were composed of rhamnose, arabinose, mannose, glucose, and galactose. These three polysaccharides exhibited antioxidant activities in four assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical, reducing power, and total antioxidant activity in vitro. The data indicated that these three polysaccharides could be utilized as potential natural sources of alternative additives in the functional food, cosmetics, and pharmaceutical industries.

The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

PubMed

Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

2014-03-01

Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to deliver neuroprotective drugs to the CNS following injury and/or potential neuroprotectants in their own right.

Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach.

PubMed

Rose, Fabrice; Wern, Jeanette Erbo; Ingvarsson, Pall Thor; van de Weert, Marco; Andersen, Peter; Follmann, Frank; Foged, Camilla

2015-07-28

The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the PLGA hybrid matrix. This study demonstrates the complexity of formulation design for the engineering of a hybrid lipid-polymer nanoparticle adjuvant. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy of Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome: A Randomized, Controlled Trial

PubMed Central

Vahdatpour, Babak; Moayednia, Amir; Emadi, Masoud; Khorami, Mohammad Hatef; Haghdani, Saeid

2013-01-01

Objectives. To investigate the effectiveness of extracorporeal shock wave therapy (ESWT) for symptoms alleviation in chronic pelvic pain syndrome (CPPS). Materials and Methods. 40 patients with CPPS were randomly allocated into either the treatment or sham group. In the first group, patients were treated by ESWT once a week for 4 weeks by a defined protocol. In the sham group, the same protocol was applied but with the probe being turned off. The follow-up assessments were done at 1, 2, 3, and 12 weeks by Visual Analogue Scale (VAS) for pain and NIH-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Results. Pain domain scores at follow-up points in both treatment and sham groups were reduced, more so in the treatment group, which were significant at weeks 2, 3, and 12. Urinary scores became significantly different at weeks 3 and 12. Also, quality of life (QOL) and total NIH-CPSI scores at all four follow-up time points reduced more significantly in the treatment group as compared to the sham group. Noticeably, at week 12 a slight deterioration in all variables was observed compared to the first 3 weeks of the treatment period. Conclusions. our findings confirmed ESWT therapy as a safe and effective method in CPPS in short term. PMID:24000311

Efficacy of extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome: a randomized, controlled trial.

PubMed

Vahdatpour, Babak; Alizadeh, Farshid; Moayednia, Amir; Emadi, Masoud; Khorami, Mohammad Hatef; Haghdani, Saeid

2013-01-01

Objectives. To investigate the effectiveness of extracorporeal shock wave therapy (ESWT) for symptoms alleviation in chronic pelvic pain syndrome (CPPS). Materials and Methods. 40 patients with CPPS were randomly allocated into either the treatment or sham group. In the first group, patients were treated by ESWT once a week for 4 weeks by a defined protocol. In the sham group, the same protocol was applied but with the probe being turned off. The follow-up assessments were done at 1, 2, 3, and 12 weeks by Visual Analogue Scale (VAS) for pain and NIH-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Results. Pain domain scores at follow-up points in both treatment and sham groups were reduced, more so in the treatment group, which were significant at weeks 2, 3, and 12. Urinary scores became significantly different at weeks 3 and 12. Also, quality of life (QOL) and total NIH-CPSI scores at all four follow-up time points reduced more significantly in the treatment group as compared to the sham group. Noticeably, at week 12 a slight deterioration in all variables was observed compared to the first 3 weeks of the treatment period. Conclusions. our findings confirmed ESWT therapy as a safe and effective method in CPPS in short term.

A quality by design study applied to an industrial pharmaceutical fluid bed granulation.

PubMed

Lourenço, Vera; Lochmann, Dirk; Reich, Gabriele; Menezes, José C; Herdling, Thorsten; Schewitz, Jens

2012-06-01

The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale. The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described. Copyright © 2012 Elsevier B.V. All rights reserved.

Immune mediators of chronic pelvic pain syndrome

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Thumbikat, Praveen

2016-01-01

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease. PMID:24686526

Contemporary treatment options for chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Ismail, M; Mackenzie, K; Hashim, H

2013-07-01

The prostate gland, about the size a walnut, forms part of the male reproductive system and sits directly underneath the bladder surrounding the urethra. It is a fibromuscular exocrine gland that secretes a complex proteolytic fluid which constitutes one-third of the volume of the seminal fluid. Prostatitis refers to a group of disorders that affect the prostate and cause genitourinary pain, dysuria, urinary frequency and sexual dysfunction. The prevalence of prostatitis in the United States has been estimated to be around 9%, while the worldwide prevalence ranges from 2 to 10%, and 15% of men experience prostatitis-like symptoms at some point in their lives. There are a number of treatments which have been used for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), with only a small amount of high-level evidence. The current recommended treatment for CP/CPPS is predominantly a multimodal approach using a combination of antibiotics, α-blockers, antimuscarinic and anti-inflammatory drugs. The response to treatment and improvement in symptoms is very variable; therefore, as the evidence evolves, it is likely that treatment will become symptom specific rather than a generic, 'one strategy fits all' treatment for CP/CPPS. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides.

PubMed

Liu, Betty R; Winiarz, Jeffrey G; Moon, Jong-Sik; Lo, Shih-Yen; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2013-11-01

Semiconductor nanoparticles, also known as quantum dots (QDs), are widely used in biomedical imaging studies and pharmaceutical research. Cell-penetrating peptides (CPPs) are a group of small peptides that are able to traverse cell membrane and deliver a variety of cargoes into living cells. CPPs deliver QDs into cells with minimal nonspecific absorption and toxic effect. In this study, water-soluble, monodisperse, carboxyl-functionalized indium phosphide (InP)/zinc sulfide (ZnS) QDs coated with polyethylene glycol lipids (designated QInP) were synthesized for the first time. The physicochemical properties (optical absorption, fluorescence and charging state) and cellular internalization of QInP and CPP/QInP complexes were characterized. CPPs noncovalently interact with QInP in vitro to form stable CPP/QInP complexes, which can then efficiently deliver QInP into human A549 cells. The introduction of 500nM of CPP/QInP complexes and QInP at concentrations of less than 1μM did not reduce cell viability. These results indicate that carboxylated and polyethylene-glycolylated (PEGylated) bifunctionalized QInP are biocompatible nanoparticles with potential for use in biomedical imaging studies and drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Traps of carnivorous pitcher plants as a habitat: composition of the fluid, biodiversity and mutualistic activities

PubMed Central

Adlassnig, Wolfram; Peroutka, Marianne; Lendl, Thomas

2011-01-01

Background Carnivorous pitcher plants (CPPs) use cone-shaped leaves to trap animals for nutrient supply but are not able to kill all intruders of their traps. Numerous species, ranging from bacteria to vertrebrates, survive and propagate in the otherwise deadly traps. This paper reviews the literature on phytotelmata of CPPs. Pitcher Fluid as a Habitat The volumes of pitchers range from 0·2 mL to 1·5 L. In Nepenthes and Cephalotus, the fluid is secreted by the trap; the other genera collect rain water. The fluid is usually acidic, rich in O2 and contains digestive enzymes. In some taxa, toxins or detergents are found, or the fluid is extremely viscous. In Heliamphora or Sarracenia, the fluid differs little from pure water. Inquiline Diversity Pitcher inquilines comprise bacteria, protozoa, algae, fungi, rotifers, crustaceans, arachnids, insects and amphibia. The dominant groups are protists and Dipteran larvae. The various species of CPPs host different sets of inquilines. Sarracenia purpurea hosts up to 165 species of inquilines, followed by Nepenthes ampullaria with 59 species, compared with only three species from Brocchinia reducta. Reasons for these differences include size, the life span of the pitcher as well as its fluid. Mutualistic Activities Inquilines closely interact with their host. Some live as parasites, but the vast majority are mutualists. Beneficial activities include secretion of enzymes, feeding on the plant's prey and successive excretion of inorganic nutrients, mechanical break up of the prey, removal of excessive prey and assimilation of atmospheric N2. Conclusions There is strong evidence that CPPs influence their phytotelm. Two strategies can be distinguished: (1) Nepenthes and Cephalotus produce acidic, toxic or digestive fluids and host a limited diversity of inquilines. (2) Genera without efficient enzymes such as Sarracenia or Heliamphora host diverse organisms and depend to a large extent on their symbionts for prey utilization. PMID:21159782

Traps of carnivorous pitcher plants as a habitat: composition of the fluid, biodiversity and mutualistic activities.

PubMed

Adlassnig, Wolfram; Peroutka, Marianne; Lendl, Thomas

2011-02-01

Carnivorous pitcher plants (CPPs) use cone-shaped leaves to trap animals for nutrient supply but are not able to kill all intruders of their traps. Numerous species, ranging from bacteria to vertrebrates, survive and propagate in the otherwise deadly traps. This paper reviews the literature on phytotelmata of CPPs. Fluid as a Habitat The volumes of pitchers range from 0·2 mL to 1·5 L. In Nepenthes and Cephalotus, the fluid is secreted by the trap; the other genera collect rain water. The fluid is usually acidic, rich in O(2) and contains digestive enzymes. In some taxa, toxins or detergents are found, or the fluid is extremely viscous. In Heliamphora or Sarracenia, the fluid differs little from pure water. Diversity Pitcher inquilines comprise bacteria, protozoa, algae, fungi, rotifers, crustaceans, arachnids, insects and amphibia. The dominant groups are protists and Dipteran larvae. The various species of CPPs host different sets of inquilines. Sarracenia purpurea hosts up to 165 species of inquilines, followed by Nepenthes ampullaria with 59 species, compared with only three species from Brocchinia reducta. Reasons for these differences include size, the life span of the pitcher as well as its fluid. MUTUALISTIC: Activities Inquilines closely interact with their host. Some live as parasites, but the vast majority are mutualists. Beneficial activities include secretion of enzymes, feeding on the plant's prey and successive excretion of inorganic nutrients, mechanical break up of the prey, removal of excessive prey and assimilation of atmospheric N(2). There is strong evidence that CPPs influence their phytotelm. Two strategies can be distinguished: (1) Nepenthes and Cephalotus produce acidic, toxic or digestive fluids and host a limited diversity of inquilines. (2) Genera without efficient enzymes such as Sarracenia or Heliamphora host diverse organisms and depend to a large extent on their symbionts for prey utilization.

Common Questions About Chronic Prostatitis.

PubMed

Holt, James D; Garrett, W Allan; McCurry, Tyler K; Teichman, Joel M H

2016-02-15

Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic floor physical therapy, phytotherapy, and pain management techniques. The UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, tenderness) approach summarizes the various factors that may contribute to presentation and can guide treatment.

Systematic Review of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Zhou, Jing; Liu, Zhishun

2016-01-01

Abstract Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects >15% of adult men worldwide. The aim of the study was to assess the effects and safety of the use of acupuncture for CP/CPPS. MEDLINE, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wang-Fang Database, JCRM, and CiNii were searched from their inception through 30 November 2015. Grey literature databases and websites were also searched. No language limits were applied. Only randomized controlled trials (RCTs) with CP/CPPS treated by acupuncture were included. Two reviewers extracted data and assessed the risk of bias of RCTs using the Cochrane Risk of Bias Tools, respectively. Seven trials were included, involving 471 participants. The result of meta-analysis indicated that compared with sham acupuncture (MD: −6.09 [95%CI: −8.12 to −5.68]) and medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) (MD: −4.57 [95%CI: −7.58 to −1.56]), acupuncture was more effective at decreasing the total NIH-CPSI score. Real acupuncture was superior to sham acupuncture in improving symptoms (pain, voiding) and quality of life (Qof) domain subscores. Compared to sham acupuncture and medicine, acupuncture appears to be more effective at improving the global assessment. Two trials found that there is no significant difference between acupuncture and sham acupuncture in decreasing the IPSS score. Acupuncture failed to show more favorable effects in improving both symptoms and the Qof domain compared with medicine. Overall, current evidence supports acupuncture as an effective treatment for CP/CPPS-induced symptoms, particularly in relieving pain. Based on the meta-analysis, acupuncture is superior to sham acupuncture in improving symptoms and Qof. Acupuncture might be similar to medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) in its long-term effects, but evidence was limited due to high ROB among included trials as well as potential heterogeneity. Acupuncture is associated with rare and slightly adverse events. Protocol registration PROSPERO CRD42015027522. PMID:26986148

Q-marker based strategy for CMC research of Chinese medicine: A case study of Panax Notoginseng saponins.

PubMed

Zhong, Yi; Zhu, Jieqiang; Yang, Zhenzhong; Shao, Qing; Fan, Xiaohui; Cheng, Yiyu

2018-01-31

To ensure pharmaceutical quality, chemistry, manufacturing and control (CMC) research is essential. However, due to the inherent complexity of Chinese medicine (CM), CMC study of CM remains a great challenge for academia, industry, and regulatory agencies. Recently, quality-marker (Q-marker) was proposed to establish quality standards or quality analysis approaches of Chinese medicine, which sheds a light on Chinese medicine's CMC study. Here manufacture processes of Panax Notoginseng Saponins (PNS) is taken as a case study and the present work is to establish a Q-marker based research strategy for CMC of Chinese medicine. The Q-markers of Panax Notoginseng Saponins (PNS) is selected and established by integrating chemical profile with pharmacological activities. Then, the key processes of PNS manufacturing are identified by material flow analysis. Furthermore, modeling algorithms are employed to explore the relationship between Q-markers and critical process parameters (CPPs) of the key processes. At last, CPPs of the key processes are optimized in order to improving the process efficiency. Among the 97 identified compounds, Notoginsenoside R 1 , ginsenoside Rg 1 , Re, Rb 1 and Rd are selected as the Q-markers of PNS. Our analysis on PNS manufacturing show the extraction process and column chromatography process are the key processes. With the CPPs of each process as the inputs and Q-markers' contents as the outputs, two process prediction models are built separately for the extraction process and column chromatography process of Panax notoginseng, which both possess good prediction ability. Based on the efficiency models of extraction process and column chromatography process we constructed, the optimal CPPs of both processes are calculated. Our results show that the Q-markers derived from CMC research strategy can be applied to analyze the manufacturing processes of Chinese medicine to assure product's quality and promote key processes' efficiency simultaneously. Copyright © 2018 Elsevier GmbH. All rights reserved.

Impregnation quality of shredded semipreg after compression moulding

NASA Astrophysics Data System (ADS)

Vincent, G.; Balakrishnan, V.; de Bruijn, T. A.; Wijskamp, S.; Abdul Rasheed, M. I.

2017-10-01

Manufacturing of thermoplastic composites (TPC) inherently generates scrap, mainly in the form of offcuts or rejected parts. The growth of TPC over recent decades has now reached a point where developing specific recycling solutions for TPC waste has become crucial. While looking at the various steps during which scrap is produced, the nesting of semipreg or prepreg appears to be critical. This work aims to develop a route for recycling semipreg offcuts, comprising shredding and compression moulding. This article focuses on an experimental study of the compression moulding step of carbon fibres reinforced PPS (C/PPS) to investigate the uniformity and impregnation quality of plates. These plates were realised in a picture frame while varying both the fibre volume content between 30% and 50% and the processing parameters. Visual inspection and cross-sectional microscopy were performed to assess the quality of each plate. As a first step, the influence of the type of added matrix (film, powder, pellets) and the type of pre-impregnation (film, powder) was studied. Stacking of polymer powder with shredded powder-coated semipreg gave the best impregnation quality. It was also shown that longer dwell time at melt leads to better consolidation quality. However, the difficulty in obtaining good impregnation comes from the disentangled shredded material, which is composed of three forms: semipreg flakes, dry bundles and pieces of matrix. When dry bundles reach the mould surfaces during the filling of the mould or when they are packed together, the consolidation cycle hardly impregnates them and they remain dry afterwards. Furthermore, large local variations of fibre fraction were noticed, resulting from a random mould filling. Therefore, the recycling solution for shredded semipreg is feasible when the fibre fraction is reduced but improvements on the part variability still have to be made.

Retrofit implementation of Zernike phase plate imaging for cryo-TEM

PubMed Central

Marko, Michael; Leith, ArDean; Hsieh, Chyongere; Danev, Radostin

2011-01-01

In-focus phase-plate imaging is particularly beneficial for cryo-TEM because it offers a substantial overall increase in image contrast, without an electron dose penalty, and it simplifies image interpretation. We show how phase-plate cryo-TEM can be implemented with an appropriate existing TEM, and provide a basic practical introduction to use of thin-film (carbon) phase plates. We point out potential pitfalls of phase-plate operation, and discuss solutions. We provide information on evaluating a particular TEM for its suitability. PMID:21272647

Application of quality by design concept to develop a dual gradient elution stability-indicating method for cloxacillin forced degradation studies using combined mixture-process variable models.

PubMed

Zhang, Xia; Hu, Changqin

2017-09-08

Penicillins are typical of complex ionic samples which likely contain large number of degradation-related impurities (DRIs) with different polarities and charge properties. It is often a challenge to develop selective and robust high performance liquid chromatography (HPLC) methods for the efficient separation of all DRIs. In this study, an analytical quality by design (AQbD) approach was proposed for stability-indicating method development of cloxacillin. The structures, retention and UV characteristics rules of penicillins and their impurities were summarized and served as useful prior knowledge. Through quality risk assessment and screen design, 3 critical process parameters (CPPs) were defined, including 2 mixture variables (MVs) and 1 process variable (PV). A combined mixture-process variable (MPV) design was conducted to evaluate the 3 CPPs simultaneously and a response surface methodology (RSM) was used to achieve the optimal experiment parameters. A dual gradient elution was performed to change buffer pH, mobile-phase type and strength simultaneously. The design spaces (DSs) was evaluated using Monte Carlo simulation to give their possibility of meeting the specifications of CQAs. A Plackett-Burman design was performed to test the robustness around the working points and to decide the normal operating ranges (NORs). Finally, validation was performed following International Conference on Harmonisation (ICH) guidelines. To our knowledge, this is the first study of using MPV design and dual gradient elution to develop HPLC methods and improve separations for complex ionic samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Retrofit implementation of Zernike phase plate imaging for cryo-TEM.

PubMed

Marko, Michael; Leith, Ardean; Hsieh, Chyongere; Danev, Radostin

2011-05-01

In-focus phase-plate imaging is particularly beneficial for cryo-TEM because it offers a substantial overall increase in image contrast, without an electron dose penalty, and it simplifies image interpretation. We show how phase-plate cryo-TEM can be implemented with an appropriate existing TEM, and provide a basic practical introduction to use of thin-film (carbon) phase plates. We point out potential pitfalls of phase-plate operation, and discuss solutions. We provide information on evaluating a particular TEM for its suitability. Copyright © 2011 Elsevier Inc. All rights reserved.

Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

PubMed

Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

2016-01-01

Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

Application of ICH Q9 Quality Risk Management Tools for Advanced Development of Hot Melt Coated Multiparticulate Systems.

PubMed

Stocker, Elena; Becker, Karin; Hate, Siddhi; Hohl, Roland; Schiemenz, Wolfgang; Sacher, Stephan; Zimmer, Andreas; Salar-Behzadi, Sharareh

2017-01-01

This study aimed to apply quality risk management based on the The International Conference on Harmonisation guideline Q9 for the early development stage of hot melt coated multiparticulate systems for oral administration. N-acetylcysteine crystals were coated with a formulation composing tripalmitin and polysorbate 65. The critical quality attributes (CQAs) were initially prioritized using failure mode and effects analysis. The CQAs of the coated material were defined as particle size, taste-masking efficiency, and immediate release profile. The hot melt coated process was characterized via a flowchart, based on the identified potential critical process parameters (CPPs) and their impact on the CQAs. These CPPs were prioritized using a process failure mode, effects, and criticality analysis and their critical impact on the CQAs was experimentally confirmed using a statistical design of experiments. Spray rate, atomization air pressure, and air flow rate were identified as CPPs. Coating amount and content of polysorbate 65 in the coating formulation were identified as critical material attributes. A hazard and critical control points analysis was applied to define control strategies at the critical process points. A fault tree analysis evaluated causes for potential process failures. We successfully demonstrated that a standardized quality risk management approach optimizes the product development sustainability and supports the regulatory aspects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, Xianjin; Zhong, Shan; Xu, Tianyuan; Xia, Leilei; Zhang, Xiaohua; Zhu, Zhaowei; Zhang, Minguang; Shen, Zhoujun

2015-02-01

A variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models. We firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis-diphtheria-tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology. Histologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin. The histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.

η6-Cycloparaphenylene transition metal complexes: synthesis, structure, photophysical properties, and application to the selective monofunctionalization of cycloparaphenylenes.

PubMed

Kubota, Natsumi; Segawa, Yasutomo; Itami, Kenichiro

2015-01-28

The synthesis, structure, photophysical properties, and reactivity of cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are described. The η(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo, W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W). In the (1)H NMR spectra of these complexes, characteristic upfield-shifted singlet signals corresponding to the four hydrogen atoms attached to the coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the solid state and in solution. TD-DFT calculations suggested that the emerging high-wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP-Cr(CO)3, a rapid and highly monoselective CPP functionalization has been achieved. The established one-pot method, consisting of complexation, deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl-, boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to reacted starting material.

Chromatic characterization of ion-exchanged glass binary phase plates for mode-division multiplexing.

PubMed

Prieto-Blanco, Xesús; Montero-Orille, Carlos; Moreno, Vicente; Mateo, Eduardo F; Liñares, Jesús

2015-04-10

Mode-division multiplexing (MDM) in few-mode fibers is regarded as a promising candidate to increase optical network capacity. A fundamental element for MDM is a modal transformer to LP modes which can be implemented in a free-space basis by using multiregion phase plates, that is, LP plates. Likewise, several wavelengths have to be used due to wavelength multiplexing purposes, optical amplification tasks, and so on. In this work we show that efficient monolithic binary phase plates for different wavelengths can be fabricated by ion-exchange in glass and used for MDM tasks. We introduce an optical characterization method of the chromatic properties of such phase plates which combines the inverse Wentzel-Kramers-Brillouin (IWKB) together with Mach-Zehnder and Michelson-based interferometric techniques. The interferometric method provides a measurement of the phase step for several wavelengths, which characterizes the chromatic properties of the phase plate. Consequently, it is shown that the IWKB method allows us to design and characterize the phase plates in an easy and fast way.

Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes

NASA Astrophysics Data System (ADS)

Weinberger, Andreas; Walter, Vivien; MacEwan, Sarah R.; Schmatko, Tatiana; Muller, Pierre; Schroder, André P.; Chilkoti, Ashutosh; Marques, Carlos M.

2017-03-01

Although cationic cell-penetrating peptides (CPPs) are able to bind to cell membranes, thus promoting cell internalization by active pathways, attachment of cargo molecules to CPPs invariably reduces their cellular uptake. We show here that CPP binding to lipid bilayers, a simple model of the cell membrane, can be recovered by designing cargo molecules that self-assemble into spherical micelles and increase the local interfacial density of CPP on the surface of the cargo. Experiments performed on model giant unilamellar vesicles under a confocal laser scanning microscope show that a family of thermally responsive elastin-like polypeptides that exhibit temperature-triggered micellization can promote temperature triggered attachment of the micelles to membranes, thus rescuing by self-assembly the cargo-induced loss of the CPP affinity to bio-membranes.

Studies of proteoglycan involvement in CPP-mediated delivery.

PubMed

Wittrup, Anders; Zhang, Si-He; Belting, Mattias

2011-01-01

Cell-penetrating peptides (CPPs) are widely used to deliver macromolecular cargoes to intracellular sites of action. Many CPPs have been demonstrated to rely on cell surface heparan sulfate proteoglycans (HSPGs) for efficient cellular entry and delivery. In this chapter, we describe methods for the study of PG involvement in CPP uptake. We provide descriptions of how to determine whether uptake of a CPP of interest is dependent on PGs. We also provide detailed protocols for the purification of PGs by anion-exchange chromatography as well as the characterization of the HSPG core protein composition of a cell line of interest. Finally, we present methods for modulating the expression level of specific HSPG core proteins as a means to determine the core protein specificity in the uptake of a particular CPP.

Relationship between premature ejaculation and chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Lee, Jun Ho; Lee, Sung Won

2015-03-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common etiology of premature ejaculation (PE). However, the current data are insufficient to explain this relationship and to support routine screening of men with PE. This study aims to evaluate the relationship between PE and CP/CPPS. A cross-sectional study was conducted that included 8,261 men who had participated in a health examination. The Premature Ejaculation Diagnostic Tool (PEDT), the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and the International Index of Erectile Function-5 (IIEF) were used for assessment of symptoms. A full metabolic work-up and serum testosterone level checks were also performed. We then investigated the relationship using the Spearman correlation test, multiple linear regression, and logistic regression analyses. Associations of PEDT with NIH-CPSI. The mean age was 50.4 ± 5.5 years. In total, 2,205 (24.9%) men had prostatitis-like symptoms (NIH-CPSI pain score of ≥4 and perineal or ejaculatory pain), and 618 (7.0%) men had moderate to severe symptoms (NIH-CPSI pain score of ≥8). Additionally, 2,144 men (24.2%) were classified as demonstrating PE (PEDT > 10). The PEDT score was found to have a significant positive correlation with the NIH-CPSI pain domain score (correlation coefficient = 0.206; P < 0.001). After adjusting for age, metabolic syndrome status, testosterone level, and IIEF score, there was no change in the positive correlation between the NIH-CPSI pain domain score and PEDT score (Beta = 0.175; P < 0.001). After adjusting for age, testosterone level, metabolic syndrome, and IIEF score, the odds ratio (OR) for PE significantly increased with the severity of pelvic pain (mild prostatitis-like symptoms, OR for PE: 1.269, 95% confidence interval: 1.113-1.447; moderate to severe symptoms, OR for PE: 2.134: 95% confidence interval: 1.782-2.557). Our data showed a significant correlation between the PEDT score and the NIH-CPSI score. We suggest routine screening for CP/CPPS in men with PE and PE in men with CP/CPPS. © 2014 International Society for Sexual Medicine.

A prospective, 1-year trial using saw palmetto versus finasteride in the treatment of category III prostatitis/chronic pelvic pain syndrome.

PubMed

Kaplan, Steven A; Volpe, Michael A; Te, Alexis E

2004-01-01

This study was designed to assess the safety and efficacy of saw palmetto or finasteride in men with category III prostatitis/chronic pelvic pain syndrome (CP/CPPS). A prospective, randomized, open label, 1-year study was designed to assess the safety and efficacy of saw palmetto and finasteride in the treatment of men diagnosed with CP/CPPS. Patients were randomized to finasteride (5 mg once daily) or saw palmetto (325 mg daily) for 1 year. Patients were evaluated using the National Institutes of Health Chronic Prostatitis Symptom Index, individual domains (pain, urinary symptoms, quality of life and mean pain score) and the American Urological Association Symptom Score at baseline, 3, 6 and 12 months. A total of 64 consecutive men 24 to 58 years old (mean age 43.2) with a diagnosis of CP/CPPS were equally randomized to the 2 treatment arms. All 64 men had previously received antibiotics (duration of 3 to 93 weeks), 52 (82%) had been on alpha-blockade. There were 61, 57 and 56 patients evaluable at 3, 6 and 12 months, respectively. At 1 year mean total National Institutes of Health Chronic Prostatitis Symptom Index score decreased from 23.9 to 18.1 in the finasteride group (p <0.003), and from 24.7 to 24.6 in the saw palmetto arm (p = 0.41). In the finasteride arm the quality of life and pain domains were significantly improved at 1 year; however, urination was not. Adverse events included headache (3 cases) in the saw palmetto group and decreased libido (2 cases) in the finasteride group. At the end of the trial 13 of 32 (41%) and 21 of 32 (66%) opted to continue saw palmetto and finasteride, respectively. CP/CPPS treated with saw palmetto had no appreciable long-term improvement. In contrast, patients treated with finasteride had significant and durable improvement in all various parameters except voiding. Further studies are warranted to ascertain the mechanism and reproducibility of these effects in a placebo controlled trial.

Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease.

PubMed

Dinca, Ana; Chien, Wei-Ming; Chin, Michael T

2016-02-22

Protein therapy exhibits several advantages over small molecule drugs and is increasingly being developed for the treatment of disorders ranging from single enzyme deficiencies to cancer. Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa). Recombinant proteins that include a CPP tag to promote intracellular delivery show promise as therapeutic agents with encouraging success rates in both animal and human trials. This review highlights recent advances in protein-CPP therapy and discusses optimization strategies and potential detrimental effects.

Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells.

PubMed

Kaitsuka, Taku; Tomizawa, Kazuhito

2015-11-06

Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists.

PubMed

Grabus, Sheri D; Martin, Billy R; Brown, Sharon E; Damaj, M Imad

2006-03-01

Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.

Development of a design space and predictive statistical model for capsule filling of low-fill-weight inhalation products.

PubMed

Faulhammer, E; Llusa, M; Wahl, P R; Paudel, A; Lawrence, S; Biserni, S; Calzolari, V; Khinast, J G

2016-01-01

The objectives of this study were to develop a predictive statistical model for low-fill-weight capsule filling of inhalation products with dosator nozzles via the quality by design (QbD) approach and based on that to create refined models that include quadratic terms for significant parameters. Various controllable process parameters and uncontrolled material attributes of 12 powders were initially screened using a linear model with partial least square (PLS) regression to determine their effect on the critical quality attributes (CQA; fill weight and weight variability). After identifying critical material attributes (CMAs) and critical process parameters (CPPs) that influenced the CQA, model refinement was performed to study if interactions or quadratic terms influence the model. Based on the assessment of the effects of the CPPs and CMAs on fill weight and weight variability for low-fill-weight inhalation products, we developed an excellent linear predictive model for fill weight (R(2 )= 0.96, Q(2 )= 0.96 for powders with good flow properties and R(2 )= 0.94, Q(2 )= 0.93 for cohesive powders) and a model that provides a good approximation of the fill weight variability for each powder group. We validated the model, established a design space for the performance of different types of inhalation grade lactose on low-fill weight capsule filling and successfully used the CMAs and CPPs to predict fill weight of powders that were not included in the development set.

Metabolic engineering of the Stevia rebaudiana ent-kaurene biosynthetic pathway in recombinant Escherichia coli.

PubMed

Kong, Min Kyung; Kang, Hyun-Jun; Kim, Jin Ho; Oh, Soon Hwan; Lee, Pyung Cheon

2015-11-20

The ent-kaurene is a dedicated precursor pool and is responsible for synthesizing natural sweeteners such as steviol glycosides. In this study, to produce ent-kaurene in Escherichia coli, we modularly constructed and expressed two ent-kaurene genes encoding ent-copalyl diphosphate synthase (CPPS) and ent-kaurene synthase (KS) from Stevia rebaudiana known as a typical plant producing steviol glycoside. The CPPS and KS from S. rebaudiana were functionally expressed in a heterologous host E. coli. Furthermore, in order to enhance ent-kaurene production in E. coli, six geranylgeranyl diphosphate synthases (GGPPS) from various microorganisms and eight strains of E. coli as host were compared by measuring ent-kaurene production. The highest ent-kaurene production of approximately 41.1mg/L was demonstrated in E. coli strain MG1655 co-expressing synthetic CPPS-KS module and GGPPS from Rhodobacter sphaeroides. The ent-kaurene production was further increased up to 179.6 mg/L by overexpression of the three key enzymes for isoprenoid precursor, 1-deoxyxylulose-5-phosphate synthase (DXS), farnesyl diphosphate synthase (IspA) and isopentenyl diphosphate isomerase (IDI) from E. coli. Finally, the highest titer of ent-kaurene (578 mg/L) with a specific yield of ent-kaurene of 143.5mg/g dry cell weight was obtained by culturing E. coli strain MG1655 co-expressing the ent-kaurene module, DXS, IDI and IspA in 1L bioreactor containing 20 g/L glycerol. Copyright © 2015 Elsevier B.V. All rights reserved.

Translocation of cell-penetrating peptides into Candida fungal pathogens.

PubMed

Gong, Zifan; Karlsson, Amy J

2017-09-01

Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

Predictors of symptom severity in patients with chronic prostatitis and interstitial cystitis.

PubMed

Clemens, J Quentin; Brown, Sheila O; Kozloff, Lara; Calhoun, Elizabeth A

2006-03-01

Numerous studies have been performed to identify potential risk factors for CP/CPPS and IC. However, few studies have been done to identify predictors of disease severity. A total of 174 men with CP/CPPS and 111 women with IC completed questionnaires to quantify symptom severity and identify demographic, medical and psychosocial characteristics. Symptom severity was assessed with the National Institutes of Health CPSI in men, and the O'Leary-Sant ICSI and problem index in women. Univariate and multivariate analyses were performed to identify characteristics predictive of worse symptoms. The mean National Institutes of Health CPSI score in men was 15.32, and the mean O'Leary-Sant ICSI and problem index in women was 19.17. The most commonly reported comorbidities were allergies, sinusitis, erectile dysfunction and irritable bowel syndrome in men, and allergies, urinary incontinence, sinusitis and irritable bowel syndrome in women. In the 2 sexes self-reported urinary frequency and urgency, worse depression scores and lower education level were independent predictors of worse symptom severity. In men additional independent predictors were self-reported pelvic pain, fibromyalgia and previous heart attack, and in women an additional independent predictor was postmenopausal status. There are several common medical conditions associated with urological pelvic pain syndromes in men and women. Few of them were predictive of symptoms severity in this analysis. Self-reported pelvic pain symptoms, education and depression severity were the factors most strongly predictive of symptom severity in patients with CP/CPPS and IC.

Investigation on filter method for smoothing spiral phase plate

NASA Astrophysics Data System (ADS)

Zhang, Yuanhang; Wen, Shenglin; Luo, Zijian; Tang, Caixue; Yan, Hao; Yang, Chunlin; Liu, Mincai; Zhang, Qinghua; Wang, Jian

2018-03-01

Spiral phase plate (SPP) for generating vortex hollow beams has high efficiency in various applications. However, it is difficult to obtain an ideal spiral phase plate because of its continuous-varying helical phase and discontinued phase step. This paper describes the demonstration of continuous spiral phase plate using filter methods. The numerical simulations indicate that different filter method including spatial domain filter, frequency domain filter has unique impact on surface topography of SPP and optical vortex characteristics. The experimental results reveal that the spatial Gaussian filter method for smoothing SPP is suitable for Computer Controlled Optical Surfacing (CCOS) technique and obtains good optical properties.

Generalized viscothermoelasticity theory of dual-phase-lagging model for damping analysis in circular micro-plate resonators

NASA Astrophysics Data System (ADS)

Grover, D.; Seth, R. K.

2018-05-01

Analysis and numerical results are presented for the thermoelastic dissipation of a homogeneous isotropic, thermally conducting, Kelvin-Voigt type circular micro-plate based on Kirchhoff's Love plate theory utilizing generalized viscothermoelasticity theory of dual-phase-lagging model. The analytical expressions for thermoelastic damping of vibration and frequency shift are obtained for generalized dual-phase-lagging model and coupled viscothermoelastic plates. The scaled thermoelastic damping has been illustrated in case of circular plate and axisymmetric circular plate for fixed aspect ratio for clamped and simply supported boundary conditions. It is observed that the damping of vibrations significantly depend on time delay and mechanical relaxation times in addition to thermo-mechanical coupling in circular plate under resonance conditions and plate dimensions.

Linear optical pulse compression based on temporal zone plates.

PubMed

Li, Bo; Li, Ming; Lou, Shuqin; Azaña, José

2013-07-15

We propose and demonstrate time-domain equivalents of spatial zone plates, namely temporal zone plates, as alternatives to conventional time lenses. Both temporal intensity zone plates, based on intensity-only temporal modulation, and temporal phase zone plates, based on phase-only temporal modulation, are introduced and studied. Temporal zone plates do not exhibit the limiting tradeoff between temporal aperture and frequency bandwidth (temporal resolution) of conventional linear time lenses. As a result, these zone plates can be ideally designed to offer a time-bandwidth product (TBP) as large as desired, practically limited by the achievable temporal modulation bandwidth (limiting the temporal resolution) and the amount of dispersion needed in the target processing systems (limiting the temporal aperture). We numerically and experimentally demonstrate linear optical pulse compression by using temporal zone plates based on linear electro-optic temporal modulation followed by fiber-optics dispersion. In the pulse-compression experiment based on temporal phase zone plates, we achieve a resolution of ~25.5 ps over a temporal aperture of ~5.77 ns, representing an experimental TBP larger than 226 using a phase-modulation amplitude of only ~0.8π rad. We also numerically study the potential of these devices to achieve temporal imaging of optical waveforms and present a comparative analysis on the performance of different temporal intensity and phase zone plates.

Ponderomotive phase plate for transmission electron microscopes

DOEpatents

Reed, Bryan W [Livermore, CA

2012-07-10

A ponderomotive phase plate system and method for controllably producing highly tunable phase contrast transfer functions in a transmission electron microscope (TEM) for high resolution and biological phase contrast imaging. The system and method includes a laser source and a beam transport system to produce a focused laser crossover as a phase plate, so that a ponderomotive potential of the focused laser crossover produces a scattering-angle-dependent phase shift in the electrons of the post-sample electron beam corresponding to a desired phase contrast transfer function.

Progressive phase trends in plates with embedded acoustic black holes.

PubMed

Conlon, Stephen C; Feurtado, Philip A

2018-02-01

Acoustic black holes (ABHs) have been explored and demonstrated to be effective passive treatments for broadband noise and vibration control. Performance metrics for assessing damping concepts are often focused on maximizing structural damping loss factors. Optimally performing damping treatments can reduce the resonant response of a driven system well below the direct field response. This results in a finite structure whose vibration input-output response follows that of an infinite structure. The vibration mobility transfer functions between locations on a structure can be used to assess the structure's vibration response phase, and compare its phase response characteristics to those of idealized systems. This work experimentally explores the phase accumulation in finite plates, with and without embedded grids of ABHs. The measured results are compared and contrasted with theoretical results for finite and infinite uniform plates. Accumulated phase characteristics, their spatial dependence and limits, are examined for the plates and compared to theoretical estimates. The phase accumulation results show that the embedded acoustic black hole treatments can significantly enhance the damping of the plates to the point that their phase accumulation follows that of an infinite plate.

Range-expanding pests and pathogens in a warming world.

PubMed

Bebber, Daniel Patrick

2015-01-01

Crop pests and pathogens (CPPs) present a growing threat to food security and ecosystem management. The interactions between plants and their natural enemies are influenced by environmental conditions and thus global warming and climate change could affect CPP ranges and impact. Observations of changing CPP distributions over the twentieth century suggest that growing agricultural production and trade have been most important in disseminating CPPs, but there is some evidence for a latitudinal bias in range shifts that indicates a global warming signal. Species distribution models using climatic variables as drivers suggest that ranges will shift latitudinally in the future. The rapid spread of the Colorado potato beetle across Eurasia illustrates the importance of evolutionary adaptation, host distribution, and migration patterns in affecting the predictions of climate-based species distribution models. Understanding species range shifts in the framework of ecological niche theory may help to direct future research needs.

Synthesis of cell-penetrating peptides and their application in neurobiology.

PubMed

Dietz, Gunnar P H; Bähr, Mathias

2007-01-01

Short basic amino acid sequences, often called cell-penetrating peptides (CPPs), allow the delivery of proteins and other molecules into cells and across the blood-brain barrier (BBB). Although the ability of basic proteins to facilitate such trafficking is known for a long time, only the application of genetic methods and overexpression of fusion proteins in Escherichia coli has lead to a wide application of CPP in many research areas, including signal transduction, cancer, angiogenesis, apoptosis, bone development, cardioprotection, cell cycle, neurobiology, and many others. For the neuroscientist, CPPs are particularly attractive, as a number of articles in the last 5 years have reported their use for neuronal rescue in a number of models for neurodegenerative diseases in vitro and in vivo in rats, mice, or gerbils. Here, we give a detailed description of the protein purification methodology and applications in neuroscience.

Wide spectral range multiple orders and half-wave achromatic phase retarders fabricated from two lithium tantalite single crystal plates

NASA Astrophysics Data System (ADS)

Emam-Ismail, M.

2015-11-01

In a broad spectral range (300-2500 nm), we report the use of channeled spectra formed from the interference of polarized white light to extract the dispersion of the phase birefringence Δnp(λ) of the x- and y-cuts of lithium tantalite (LiTaO3:LT) plates. A new method named as wavenumber difference method is used to extract the spectral behavior of the phase birefringence of the x- and y- cuts of LT plates. The correctness of the obtained birefringence data is confirmed by using Jones vector method through recalculating the plates thicknesses. The spectral variation of the phase birefringence Δnp(λ) of the x- and y-cuts of LT plates is fitted to Cauchy dispersion function with relative error for both x- and y-cuts of order 2.4×10-4. The group birefringence dispersion Δng (λ) of the x- and y-cuts of LT plates is also calculated and fitted to Ghosh dispersion function with relative error for both x- and y-cuts of order 2.83×10-4. Furthermore, the phase retardation introduced by the x- and y-cuts of LT plates is also calculated. It is found that the amount of phase retardation confirms that the x- and y-cuts of LT plates can act as a multiple order half- and quarter-wave plates working at many different wavelengths through the spectral range 300-2500 nm. For the x- and y-cuts of LT plates, a large difference between group and phase birefringence is observed at a short wavelength (λ=300 nm); while such difference progressively diminished at longer wavelength (λ=2000 nm). In the near infrared region (NIR) region (700-2500 nm), a broad spectral full width at half maximum (FWHM) is observed for either x- or y-cut of LT plate which can act as if it is working as a zero order wave plate. Finally, an achromatic half-wave plate working at 598 nm and covering a wide spectral range (300-900 nm) is demonstrated experimentally by combining both x- and y-cuts of LT plates.

Long-life 3-axis satellite attitude sensing, phase 1

NASA Technical Reports Server (NTRS)

Arild, Tor

1987-01-01

The purpose was to investigate the feasibility of new, moderate-cost, high reliability navigation sensors for high-altitude satellites, using stellar sources to obviate the use of gyroscopic devices. The primary investigation focused on the need for developing a star tracker model to replace an old star tracker which is still needed for current probe and satellite programs. One innovative element of the proposed star tracker was the design, development, and testing of technology components related to a phase scrambler plate. The purpose of the phase scrambler plate is to convert the impulse response of the optical system from a point image to a uniformly bright, square, angularly large, in-focus image of the star source. A collimated star source was built and tested. A breadboard star tracker with an 8 x 8 degree field of view was designed and built. It was tested in normal quad-cell mode (without the phase scrambler plate) and with the phase scrambler plate. Although the phase scrambler plate was crudely made, the performance of the star tracker breadboard was greatly improved using the phase scrambler plate, instead of system defocus. If further developed, the phase scrambler plate may be added as a low-cost retroconversion to any objective lens to greatly improve quad-cell or CCD array tracking; applications include star trackers, laser metrology, laser machining optics, and surveying instrumentation.

Testing and Calibration of Phase Plates for JWST Optical Simulator

NASA Technical Reports Server (NTRS)

Gong, Qian; Chu, Jenny; Tournois, Severine; Eichhorn, William; Kubalak, David

2011-01-01

Three phase plates were designed to simulate the JWST segmented primary mirror wavefront at three on-orbit alignment stages: coarse phasing, intermediate phasing, and fine phasing. The purpose is to verify JWST's on-orbit wavefront sensing capability. Amongst the three stages, coarse alignment is defined to have piston error between adjacent segments being 30 m to 300 m, intermediate being 0.4 m to 10 m, and fine is below 0.4 m. The phase plates were made of fused silica, and were assembled in JWST Optical Simulator (OSIM). The piston difference was realized by the thickness difference of two adjacent segments. The two important parameters to phase plates are piston and wavefront errors. Dispersed Fringe Sensor (DFS) method was used for initial coarse piston evaluation, which is the emphasis of this paper. Point Diffraction Interferometer (PDI) is used for fine piston and wavefront error. In order to remove piston's 2 pi uncertainty with PDI, three laser wavelengths, 640nm, 660nm, and 780nm, are used for the measurement. The DHS test setup, analysis algorithm and results are presented. The phase plate design concept and its application (i.e. verifying the JWST on-orbit alignment algorithm) are described. The layout of JWST OSIM and the function of phase plates in OSIM are also addressed briefly.

Optimization of a Coupling Process for Insulin Degludec According to a Quality by Design (QbD) Paradigm.

PubMed

Nie, Lei; Hu, Mingming; Yan, Xu; Guo, Tingting; Wang, Haibin; Zhang, Sheng; Qu, Haibin

2018-05-03

This case study described a successful application of the quality by design (QbD) principles to a coupling process development of insulin degludec. Failure mode effects analysis (FMEA) risk analysis was first used to recognize critical process parameters (CPPs). Five CPPs, including coupling temperature (Temp), pH of desB30 solution (pH), reaction time (Time), desB30 concentration (Conc), and molar equivalent of ester per mole of desB30 insulin (MolE), were then investigated using a fractional factorial design. The curvature effect was found significant, indicating the requirement of second-order models. Afterwards, a central composite design was built with an augmented star and center points study. Regression models were developed for the CPPs to predict the purity and yield of predegludec using above experimental data. The R 2 and adjusted R 2 were higher than 96 and 93% for the two models respectively. The Q 2 values were more than 80% indicating a good predictive ability of models. MolE was found to be the most significant factor affecting both yield and purity of predegludec. Temp, pH, and Conc were also significant for predegludec purity, while Time appeared to remarkably influence the yield model. The multi-dimensional design space and normal operating region (NOR) with a robust setpoint were determined using a probability-based Monte-Carlo simulation method. The verified experimental results showed that the design space was reliable and effective. This study enriches the understanding of acetylation process and is instructional to other complicated operations in biopharmaceutical engineering.

Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice

PubMed Central

Khan, Yasmin; Pandy, Vijayapandi

2016-01-01

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence. PMID:27729866

Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice.

PubMed

Khan, Yasmin; Pandy, Vijayapandi

2016-01-01

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

COMPARISON OF BASELINE UROLOGIC SYMPTOMS IN MEN AND WOMEN IN THE MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN (MAPP) RESEARCH COHORT

PubMed Central

Clemens, J. Quentin; Clauw, Daniel J.; Kreder, Karl; Krieger, John N.; Kusek, John W.; Lai, H. Henry; Rodriguez, Larissa; Williams, David A.; Hou, Xiaoling; Stephens, Alisa; Landis, J Richard

2015-01-01

INTRODUCTION The clinical features of interstitial cystitis/ bladder pain syndrome (IC/BPS) are similar to those of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have directly compared the characteristics of these syndromes in men and women. METHODS The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network recruited 191 men and 233 women with IC/BPS or CP/CPPS. Baseline data included demographics, the Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), the Genitourinary Pain Index (GUPI), the American Urological Association Symptom Index (AUASI), Likert scales to assess urinary urgency, frequency, pain and overall symptom severity, and a single question about the most bothersome pelvic symptom. RESULTS After adjustment for age, income and symptom duration, measures of pain severity were similar across genders. Mean scores for the ICSI, ICPI and AUASI were significantly higher in women than men, reflecting more bladder-focused symptoms in women. The most bothersome single symptom in both men and women was pain in the pubic/bladder area (34% of men, 58% of women). The characteristics of the men and women in the MAPP cohort were similar to those reported in other research cohorts of IC/BPS and CP/CPPS. CONCLUSIONS Our findings indicate that pain severity is similar in both sexes, and that bladder-focused symptoms (urgency, suprapubic pain, frequency) are more common in women. However, a substantial proportion of men also report these types of bladder symptoms. PMID:25463989

Chronic prostatitis and comorbid non-urological overlapping pain conditions: A co-twin control study.

PubMed

Gasperi, Marianna; Krieger, John N; Forsberg, Christopher; Goldberg, Jack; Buchwald, Dedra; Afari, Niloofar

2017-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs. Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations. There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome. CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities. Published by Elsevier Inc.

Unit operation optimization for the manufacturing of botanical injections using a design space approach: a case study of water precipitation.

PubMed

Gong, Xingchu; Chen, Huali; Chen, Teng; Qu, Haibin

2014-01-01

Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

Calcium absorption is not increased by caseinophosphopeptides.

PubMed

Teucher, Birgit; Majsak-Newman, Gosia; Dainty, Jack R; McDonagh, David; FitzGerald, Richard J; Fairweather-Tait, Susan J

2006-07-01

One of the suggested health benefits of caseinophosphopeptides (CPPs) is their ability to enhance calcium absorption. This possibility is based on the assumption that they resist proteolysis in the upper gastrointestinal tract and maintain calcium in a soluble form at alkaline pH in the distal ileum. The effects of CPP-enriched preparations (containing candidate functional food ingredients) on calcium absorption from a calcium lactate drink were tested. A randomized crossover trial was undertaken in 15 adults in whom we measured the absorption of calcium from a calcium lactate drink (drink A: 400 mg Ca as lactate) and 2 preparations enriched with forms of CPP (1.7 g each; drinks B and C). Both drinks B and C contained 400 mg Ca as calcium lactate plus approximately 100 mg CPP-derived calcium). Each volunteer received the 3 drinks in random order. Absorption was measured by the dual-label calcium stable-isotope technique. The quantity of calcium absorbed was significantly lower from drink A (103 mg) than from drink B (117 mg; P = 0.012) or drink C (121 mg; P = 0.002), which indicated a positive effect of the CPPs. However, because the CPP preparations contributed additional calcium besides that found in the calcium lactate (drink A), fractional absorption of calcium from drink B (23%) was slightly but significantly (P = 0.015) lower than that from drink A (26%). The differences in calcium absorption are unlikely to have any biological significance. CPPs are unsuitable as candidate ingredients for functional foods that are designed to deliver improved calcium nutrition.

Carbon contamination in scanning transmission electron microscopy and its impact on phase-plate applications.

PubMed

Hettler, Simon; Dries, Manuel; Hermann, Peter; Obermair, Martin; Gerthsen, Dagmar; Malac, Marek

2017-05-01

We analyze electron-beam induced carbon contamination in a transmission electron microscope. The study is performed on thin films potentially suitable as phase plates for phase-contrast transmission electron microscopy. Electron energy-loss spectroscopy and phase-plate imaging is utilized to analyze the contamination. The deposited contamination layer is identified as a graphitic carbon layer which is not prone to electrostatic charging whereas a non-conductive underlying substrate charges. Several methods that inhibit contamination are evaluated and the impact of carbon contamination on phase-plate imaging is discussed. The findings are in general interesting for scanning transmission electron microscopy applications. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Multiple orbital angular momentum generated by dielectric hybrid phase element

NASA Astrophysics Data System (ADS)

Wang, Xuewen; Kuchmizhak, Aleksandr; Hu, Dejiao; Li, Xiangping

2017-09-01

Vortex beam carrying multiple orbital angular momentum provides a new degree of freedom to manipulate light leading to the various exciting applications as trapping, quantum optics, information multiplexing, etc. Helical wavefront can be generated either via the geometric or the dynamic phase arising from a space-variant birefringence (q-plate) or from phase accumulation through propagation (spiral-phase-plate), respectively. Using fast direct laser writing technique we fabricate and characterize novel hybrid q-plate generating vortex beam simultaneously carrying two different high-order topological charges, which arise from the spin-orbital conversion and the azimuthal height variation of the recorded structures. We approve the versatile concept to generate multiple-OAM vortex beams combining the spin-orbital interaction and the phase accumulation in a single micro-scale device, a hybrid dielectric phase plate.

Membrane Crossing and Membranotropic Activity of Cell-Penetrating Peptides: Dangerous Liaisons?

PubMed

Walrant, Astrid; Cardon, Sébastien; Burlina, Fabienne; Sagan, Sandrine

2017-12-19

Living organisms have to maintain a stable balance in molecules and ions in the changing environment in which they are living, a process known as homeostasis. At the level of cells, the plasma membrane has a major role in homeostasis, since this hydrophobic film prevents passive diffusion of large and hydrophilic molecules between the extracellular and intracellular milieu. Living organisms have evolved with highly sophisticated transport systems to control exchanges across this barrier: import of nutrients and fuel essential for their survival; recognition of chemical or physical messengers allowing information interchanges with surrounding cells. Besides specialized proteins, endocytosis mechanisms at the level of the lipid bilayer can transport molecules from the outside across the cell membrane, in an energy-dependent manner. The cell membrane is highly heterogeneous in its molecular composition (tens of different lipids, proteins, polysaccharides, and combinations of these) and dynamic with bending, deformation, and elastic properties that depend on the local composition of membrane domains. Many viruses, microorganisms, and toxins exploit the plasma membrane to enter into cells. Chemists develop strategies to target the plasma membrane with molecules capable of circumventing this hydrophobic barrier, in particular to transport and deliver nonpermeable drugs in cells for biotechnological or pharmaceutical purposes. Drug delivery systems are numerous and include lipid-, sugar-, protein-, and peptide-based delivery systems, since these biomolecules generally have good biocompatibility, biodegradability, environmental sustainability, cost effectiveness, and availability. Among those, cell-penetrating peptides (CPPs), reported for the first time in the early 1990s, are attracting major interest not only as potential drug delivery systems but also at the level of fundamental research. It was indeed demonstrated very early that these peptides, which generally correspond to highly cationic sequences, can still cross the cell membrane at 4 °C, a temperature at which all active transport and endocytosis pathways are totally inhibited. Therefore, how these charged hydrophilic peptides cross the hydrophobic membrane barrier is of utmost interest as a pure basic and physicochemical question. In this Account, we focus on cationic cell-penetrating peptides (CPPs) and the way they cross cell membranes. We summarize the history of this field that emerged around 20 years ago. CPPs were indeed first identified as protein-transduction domains from the human immunodeficiency virus (HIV) TAT protein and the Antennapedia homeoprotein, a transcription factor from Drosophila. We highlight our contribution to the elucidation of CPP internalization pathways, in particular translocation, which implies perturbation and reorganization of the lipid bilayer, and endocytosis depending on sulfated glycosaminoglycans. We show a particular role of Trp (indole side chain) and Arg (guanidinium side chain), which are essential amino acids for CPP internalization. Interactions with the cell-surface are not only Coulombic; H-bonds and hydrophobic interactions contribute also significantly to CPP entry. The capacity of CPPs to cross cell membrane is not related to their strength of membrane binding. Finally, we present optimized methods based on mass spectrometry and fluorescence spectroscopy that allow unequivocal quantification of CPPs inside cells or bound to the outer leaflet of the membrane, and discuss some limitations of the technique of flow cytometry that we have recently highlighted.

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

Young, P.E.

We are compiling a list of anticipated target spot sizes that are specified by the NIF users groups. This data will be used to anticipate demands for phase plates. The spot size also has an impact on the laser operation. Presently the phase plates are designed to sit in the leo section of the FOA (before the conversion crystals). Intensity modulations produced by the phase plates are nonlinearly proportional to the laser spot size. For spot sizes above 3 mm diameter, the intensity modulations are large enough that the damage threshold for the remainder of the FOA is exceeded. Formore » experiments requiring spot diameters larger than 3 ram, it is suggested that the phase plates sit in the 3{omega} section of the FOA. For planning purposes, the cost of the 3{omega} phase plates is presently projected to be more than that of a le0 phase plate due to the use of inclusion-free fused silica as the substrate material, This report is a summary of a meeting that we had on February 16, 2000 in order to catalogue the possible range of requested NIF spot sizes. Copies of the viewgraphs which were presented are also included.« less

In-line phase shift tomosynthesis

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

Hammonds, Jeffrey C.; Price, Ronald R.; Pickens, David R.

2013-08-15

Purpose: The purpose of this work is to (1) demonstrate laboratory measurements of phase shift images derived from in-line phase-contrast radiographs using the attenuation-partition based algorithm (APBA) of Yan et al.[Opt. Express 18(15), 16074–16089 (2010)], (2) verify that the APBA reconstructed images obey the linearity principle, and (3) reconstruct tomosynthesis phase shift images from a collection of angularly sampled planar phase shift images.Methods: An unmodified, commercially available cabinet x-ray system (Faxitron LX-60) was used in this experiment. This system contains a tungsten anode x-ray tube with a nominal focal spot size of 10 μm. The digital detector uses CsI/CMOS withmore » a pixel size of 50 × 50 μm. The phantoms used consisted of one acrylic plate, two polystyrene plates, and a habanero pepper. Tomosynthesis images were reconstructed from 51 images acquired over a ±25° arc. All phase shift images were reconstructed using the APBA.Results: Image contrast derived from the planar phase shift image of an acrylic plate of uniform thickness exceeded the contrast of the traditional attenuation image by an approximate factor of two. Comparison of the planar phase shift images from a single, uniform thickness polystyrene plate with two polystyrene plates demonstrated an approximate linearity of the estimated phase shift with plate thickness (−1600 rad vs −2970 rad). Tomographic phase shift images of the habanero pepper exhibited acceptable spatial resolution and contrast comparable to the corresponding attenuation image.Conclusions: This work demonstrated the feasibility of laboratory-based phase shift tomosynthesis and suggests that phase shift imaging could potentially provide a new imaging biomarker. Further investigation will be needed to determine if phase shift contrast will be able to provide new tissue contrast information or improved clinical performance.« less

Sono-electro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial.

PubMed

Kessler, Thomas M; Mordasini, Livio; Weisstanner, Christian; Jüni, Peter; da Costa, Bruno R; Wiest, Roland; Thalmann, George N

2014-01-01

To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6) than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023). Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. ClinicalTrials.gov NCT00688506.

Pregabalin for the Treatment of Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Pontari, Michel A.; Krieger, John N.; Litwin, Mark S.; White, Paige C.; Anderson, Rodney U.; McNaughton-Collins, Mary; Nickel, J. Curtis; Shoskes, Daniel A.; Alexander, Richard B.; O'Leary, Michael; Zeitlin, Scott; Chuai, Shannon; Landis, J. Richard; Cen, Liyi; Propert, Kathleen J.; Kusek, John W.; Nyberg, Leroy M.; Schaeffer, Anthony J.

2013-01-01

Background Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic. Methods This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006–2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed. Results Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIHCPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and sub-scores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups. Conclusion Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS. Trial Registration clinicaltrials.gov Identifier: NCT00371033 PMID:20876412

Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.

PubMed

Wagenlehner, Florian M E; van Till, J W Olivier; Houbiers, Jos G A; Martina, Reynaldo V; Cerneus, Dirk P; Melis, Joost H J M; Majek, Antoni; Vjaters, Egils; Urban, Michael; Ramonas, Henrikas; Shoskes, Daniel A; Nickel, J Curtis

2017-05-01

To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors. In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions, and analysis of the efficacy variables. The study was stopped for futility at preplanned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25 mg group showed the largest reduction of the primary end point National Institutes of Health Chronic Prostatitis Symptom Index total score (7.0 points), but the placebo group showed a mean reduction of 7.3 points (difference: 0.3 [95% confidence interval: -1.9, 2.6]). Micturition outcomes improved compared with placebo in all ASP3652 groups; for example, in the 300 mg twice daily group, voiding frequency decreased by -1.10 (95% CI: -2.0, -0.2) voids/24 hours vs placebo. Safety outcomes were comparable across the treatment groups. ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, the results indicate that FAAH inhibition may attenuate lower urinary tract symptoms. Dedicated studies in patients with lower urinary tract dysfunction are needed to confirm this. Copyright © 2017 Elsevier Inc. All rights reserved.

Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Tian, Jinhui; Zhou, Jing; Liu, Yali; Liu, Zhishun

2016-01-01

Alpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96–6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27–7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07–2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57–3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95–4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08–4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07–2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS. PMID:27759111

The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats

PubMed Central

Wenzel, Jennifer M.; Su, Zu-In; Shelton, Kerisa; Dominguez, Hiram M.; von Furstenberg, Victoria A.; Ettenberg, Aaron

2013-01-01

Human cocaine users report that the initial “high” produced by cocaine administration is followed by an anxiogenic “crash”. Given that cocaine has such robust and opposing properties, it is likely that both the positive and negative effects of cocaine contribute to an individual’s motivation to administer the drug. Despite this likelihood, the neurobiology underlying cocaine’s dual processes remains unclear. While much literature supports a role for dopamine (DA) in cocaine reward, it is uncertain if DA also contributes to the drug’s negative effects. Our laboratory has extensively utilized a modified conditioned place test to explore cocaine’s opponent processes. In this paradigm rats develop conditioned place preferences (CPPs) for an environment paired with the immediate/positive effects of cocaine, and conditioned place aversions (CPAs) for an environment paired with the delayed/negative effects present 15-min after i.v. injection. In the current study rats were conditioned to associate an environment with either the immediate or delayed effects of i.v. cocaine (1 mg/kg/0.1 ml) three hours after i.p. pre-treatment with either the DA D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg/ml) or saline vehicle. As expected, vehicle-treated control animals developed the normal pattern of CPPs for cocaine’s immediate effects or CPAs for the delayed effects of cocaine. However, while DA receptor antagonism prevented the expression of cocaine CPPs it did not alter the expression of cocaine-induced CPAs. These data confirm a role for DA transmission in cocaine reward but suggest that different neural pathways mediate the drug’s negative/anxiogenic properties. PMID:24012795

A novel murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by immunization with a spermine binding protein (p25) peptide

PubMed Central

Altuntas, Cengiz Z.; Veizi, Elias; Izgi, Kenan; Bicer, Fuat; Ozer, Ahmet; Grimberg, Kerry O.; Bakhautdin, Bakytzhan; Sakalar, Cagri; Tasdemir, Cemal; Tuohy, Vincent K.

2013-01-01

The pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is poorly understood. Inflammatory and autoimmune mechanisms may play a role. We developed a murine model of experimental autoimmune prostatitis (EAP) that mimics the human phenotype of CP/CPPS. Eight-week-old mice were immunized subcutaneously with prostate-specific peptides in an emulsion of complete Freund's adjuvant. Mice were euthanized 10 days after immunization, and lymph node cells were isolated and assessed for recall proliferation to each peptide. P25 99–118 was the most immunogenic peptide. T-cell and B-cell immunity and serum levels of C-reactive protein and nitrate/nitrite levels were evaluated over a 9-wk period. Morphometric studies of prostate, 24-h micturition frequencies, and urine volume per void were evaluated. Tactile referred hyperalgesia was measured using von Frey filaments to the pelvic region. The unpaired Student's t-test was used to analyze differences between EAP and control groups. Prostates from p25 99–118-immunized mice demonstrated elevated gene expression levels of TNF-α, IL-17A, IFN-γ, and IL-1β, not observed in control mice. Compared with controls, p25 99–118-immunized mice had significantly higher micturition frequency and decreased urine output per void, and they demonstrated elevated pelvic pain response. p25 99–118 immunization of male SWXJ mice induced prostate-specific autoimmunity characterized by prostate-confined inflammation, increased micturition frequency, and pelvic pain. This autoimmune prostatitis model provides a useful tool for exploring the pathophysiology and new treatments. PMID:23344231

Two-phase gas-liquid flow characteristics inside a plate heat exchanger

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

Nilpueng, Kitti; Wongwises, Somchai

In the present study, the air-water two-phase flow characteristics including flow pattern and pressure drop inside a plate heat exchanger are experimentally investigated. A plate heat exchanger with single pass under the condition of counter flow is operated for the experiment. Three stainless steel commercial plates with a corrugated sinusoidal shape of unsymmetrical chevron angles of 55 and 10 are utilized for the pressure drop measurement. A transparent plate having the same configuration as the stainless steel plates is cast and used as a cover plate in order to observe the flow pattern inside the plate heat exchanger. The air-watermore » mixture flow which is used as a cold stream is tested in vertical downward and upward flow. The results from the present experiment show that the annular-liquid bridge flow pattern appeared in both upward and downward flows. However, the bubbly flow pattern and the slug flow pattern are only found in upward flow and downward flow, respectively. The variation of the water and air velocity has a significant effect on the two-phase pressure drop. Based on the present data, a two-phase multiplier correlation is proposed for practical application. (author)« less

High precision refractometry based on Fresnel diffraction from phase plates.

PubMed

Tavassoly, M Taghi; Naraghi, Roxana Rezvani; Nahal, Arashmid; Hassani, Khosrow

2012-05-01

When a transparent plane-parallel plate is illuminated at a boundary region by a monochromatic parallel beam of light, Fresnel diffraction occurs because of the abrupt change in phase imposed by the finite change in refractive index at the plate boundary. The visibility of the diffraction fringes varies periodically with changes in incident angle. The visibility period depends on the plate thickness and the refractive indices of the plate and the surrounding medium. Plotting the phase change versus incident angle or counting the visibility repetition in an incident-angle interval provides, for a given plate thickness, the refractive index of the plate very accurately. It is shown here that the refractive index of a plate can be determined without knowing the plate thickness. Therefore, the technique can be utilized for measuring plate thickness with high precision. In addition, by installing a plate with known refractive index in a rectangular cell filled with a liquid and following the described procedures, the refractive index of the liquid is obtained. The technique is applied to measure the refractive indices of a glass slide, distilled water, and ethanol. The potential and merits of the technique are also discussed.

Clinical pharmacology of antiepileptic drug use: "clinical pearls about the perils of patty".

PubMed

Schraeder, P L; Lathers, C M

1995-12-01

This Clinical Pharmacology Problem Solving (CPPS) Unit is for use with fourth- or fifth-year pharmacy students and third- or fourth-year medical students during conferences held when they are taking either a rotation in Neurology or Clinical Pharmacology. It may also be used for house staff teaching of residents in Neurology, Pediatrics, Internal Medicine, and Family Practice and fellows in Clinical Pharmacology. This material was prepared for a Teaching Clinic in Clinical Pharmacology taught by Claire M. Lathers, PhD, FCP, Hugh J. Burford, PhD, FCP, and Cedric M. Smith, MD, FCP, and sponsored by the American College of Clinical Pharmacology, September 19-20, 1992, Washington, DC. This workbook includes: (1) an introduction to the Clinical Pharmacology Problem Solving (CPPS) Unit; (2) the learning objectives of the clinical simulation; (3) a pretest; (4) four clinical episodes occurring over many years in the life of a patient; (5) answers to the pretest; (6) a posttest; (7) answers to the posttest.

Wavefront-guided correction of ocular aberrations: Are phase plate and refractive surgery solutions equal?

NASA Astrophysics Data System (ADS)

Marchese, Linda E.; Munger, Rejean; Priest, David

2005-08-01

Wavefront-guided laser eye surgery has been recently introduced and holds the promise of correcting not only defocus and astigmatism in patients but also higher-order aberrations. Research is just beginning on the implementation of wavefront-guided methods in optical solutions, such as phase-plate-based spectacles, as alternatives to surgery. We investigate the theoretical differences between the implementation of wavefront-guided surgical and phase plate corrections. The residual aberrations of 43 model eyes are calculated after simulated refractive surgery and also after a phase plate is placed in front of the untreated eye. In each case, the current wavefront-guided paradigm that applies a direct map of the ocular aberrations to the correction zone is used. The simulation results demonstrate that an ablation map that is a Zernike fit of a direct transform of the ocular wavefront phase error is not as efficient in correcting refractive errors of sphere, cylinder, spherical aberration, and coma as when the same Zernike coefficients are applied to a phase plate, with statistically significant improvements from 2% to 6%.

Binary phase plates cannot improve laser beam quality.

PubMed

Siegman, A E

1993-05-01

Binary phase plates are often suggested as a means for improving the far-field brightness of beams coming from antiphased laser arrays or waveguide lasers operating in higher-order modes. Somewhat surprisingly, however, binary phase plates actually cannot improve at all the second-moment-based beam quality factor M(2) as usually defined for such beams. Even from a power-in-the-bucket viewpoint, their usefulness is debatable.

Optical phase plates as a creative medium for special effects in images

NASA Astrophysics Data System (ADS)

Shaoulov, Vesselin I.; Meyer, Catherine; Argotti, Yann; Rolland, Jannick P.

2001-12-01

A new paradigm and methods for special effects in images were recently proposed by artist and movie producer Steven Hylen. Based on these methods, images resembling painting may be formed using optical phase plates. The role of the mathematical and optical properties of the phase plates is studied in the development of these new art forms. Results of custom software as well as ASAP simulations are presented.

Carbon fiber content measurement in composite

NASA Astrophysics Data System (ADS)

Wang, Qiushi

Carbon fiber reinforced polymers (CFRPs) have been widely used in various structural applications in industries such as aerospace and automotive because of their high specific stiffness and specific strength. Their mechanical properties are strongly influenced by the carbon fiber content in the composites. Measurement of the carbon fiber content in CFRPs is essential for product quality control and process optimization. In this work, a novel carbonization-in-nitrogen method (CIN) is developed to characterize the fiber content in carbon fiber reinforced thermoset and thermoplastic composites. In this method, a carbon fiber composite sample is carbonized in a nitrogen environment at elevated temperatures, alongside a neat resin sample. The carbon fibers are protected from oxidization while the resin (the neat resin and the resin matrix in the composite sample) is carbonized under the nitrogen environment. The residue of the carbonized neat resin sample is used to calibrate the resin carbonization rate and calculate the amount of the resin matrix in the composite sample. The new method has been validated on several thermoset and thermoplastic resin systems and found to yield an accurate measurement of fiber content in carbon fiber polymer composites. In order to further understand the thermal degradation behavior of the high temperature thermoplastic polymer during the carbonization process, the mechanism and the kinetic model of thermal degradation behavior of carbon fiber reinforced poly (phenylene sulfide) (CPPS) are studied using thermogravimetry analysis (TGA). The CPPS is subjected to TGA in an air and nitrogen atmosphere at heating rates from 5 to 40°C min--1. The TGA curves obtained in air are different from those in nitrogen. This demonstrates that weight loss occurs in a single stage in nitrogen but in two stages in air. To elucidate this difference, thermal decomposition kinetics is analyzed by applying the Kissinger, Flynn-Wall-Ozawa, Coat-Redfern and Malek methods. The activation energy (Ea) of the solid-state process is determined to be 202 kJ mol--1 in an oxidative atmosphere using Kissinger's method, which is 10-15 kJ mol--1 more than the results calculated in a nitrogen atmosphere. The value of the activation energy obtained using Ozawa-Flynn methods is in agreement with that using the Kissinger method. Different degradation mechanisms are used to compare with this value. Based on the analytical result, the actual thermal degradation mechanism of the CPPS is a Dn deceleration type. The carbonization temperature range of the CPPS is the same as pure PPS resin.

Aerodynamics of a translating comb-like plate inspired by a fairyfly wing

NASA Astrophysics Data System (ADS)

Lee, Seung Hun; Kim, Daegyoum

2017-08-01

Unlike the smooth wings of common insects or birds, micro-scale insects such as the fairyfly have a distinctive wing geometry, comprising a frame with several bristles. Motivated by this peculiar wing geometry, we experimentally investigated the flow structure of a translating comb-like wing for a wide range of gap size, angle of attack, and Reynolds number, Re = O(10) - O(103), and the correlation of these parameters with aerodynamic performance. The flow structures of a smooth plate without a gap and a comb-like plate are significantly different at high Reynolds number, while little difference was observed at the low Reynolds number of O(10). At low Reynolds number, shear layers that were generated at the edges of the tooth of the comb-like plate strongly diffuse and eventually block a gap. This gap blockage increases the effective surface area of the plate and alters the formation of leading-edge and trailing-edge vortices. As a result, the comb-like plate generates larger aerodynamic force per unit area than the smooth plate. In addition to a quasi-steady phase after the comb-like plate travels several chords, we also studied a starting phase of the shear layer development when the comb-like plate begins to translate from rest. While a plate with small gap size can generate aerodynamic force at the starting phase as effectively as at the quasi-steady phase, the aerodynamic force drops noticeably for a plate with a large gap because the diffusion of the developing shear layers is not enough to block the gap.

Improved specimen reconstruction by Hilbert phase contrast tomography.

PubMed

Barton, Bastian; Joos, Friederike; Schröder, Rasmus R

2008-11-01

The low signal-to-noise ratio (SNR) in images of unstained specimens recorded with conventional defocus phase contrast makes it difficult to interpret 3D volumes obtained by electron tomography (ET). The high defocus applied for conventional tilt series generates some phase contrast but leads to an incomplete transfer of object information. For tomography of biological weak-phase objects, optimal image contrast and subsequently an optimized SNR are essential for the reconstruction of details such as macromolecular assemblies at molecular resolution. The problem of low contrast can be partially solved by applying a Hilbert phase plate positioned in the back focal plane (BFP) of the objective lens while recording images in Gaussian focus. Images recorded with the Hilbert phase plate provide optimized positive phase contrast at low spatial frequencies, and the contrast transfer in principle extends to the information limit of the microscope. The antisymmetric Hilbert phase contrast (HPC) can be numerically converted into isotropic contrast, which is equivalent to the contrast obtained by a Zernike phase plate. Thus, in-focus HPC provides optimal structure factor information without limiting effects of the transfer function. In this article, we present the first electron tomograms of biological specimens reconstructed from Hilbert phase plate image series. We outline the technical implementation of the phase plate and demonstrate that the technique is routinely applicable for tomography. A comparison between conventional defocus tomograms and in-focus HPC volumes shows an enhanced SNR and an improved specimen visibility for in-focus Hilbert tomography.

Additive-free size-controlled synthesis of gold square nanoplates using photochemical reaction in dynamic phase-separating media.

PubMed

Kajimoto, Shinji; Shirasawa, Daisuke; Horimoto, Noriko Nishizawa; Fukumura, Hiroshi

2013-05-14

Ultrafast phase separation of water and 2-butoxyethanol mixture was induced by nanosecond IR laser pulse irradiation. After a certain delay time, a UV laser pulse was introduced to induce photoreduction of aurate ions, which led to the formation of gold nanoparticles in dynamic phase-separating media. The structure and size of the nanoparticles varied depending on the delay time between the IR and UV pulses. For a delay time of 5 and 6 μs, gold square plates having edge lengths of 150 and 100 nm were selectively obtained, respectively. With a delay time of 3 μs, on the other hand, the size of the square plates varied widely from 100 nm to a few micrometers. The size of the gold square plates was also varied by varying the total irradiation time of the IR and UV pulses. The size distribution of the square plates obtained under different conditions suggests that the growth process of the square plates was affected by the size of the nanophases during phase separation. Electron diffraction patterns of the synthesized square plates showed that the square plates were highly crystalline with a Au(100) surface. These results showed that the nanophases formed during laser-induced phase separation can provide detergent-free reaction fields for size-controlled nanomaterial synthesis.

Transcriptional Characterization of Salmonella TAl00 in Growth and Stationary Phase: Mutagenesis of MX in Both Types of Cells

EPA Science Inventory

The Salmonella (Ames) mutagenicity assay can be performed using cells that are in different growth phases. Thus, the plate-incorporation assay involves plating stationary-phase cells with the mutagen, after which the cells undergo a brief lag phase and, consequently, are exposed ...

Two-phase flow patterns in adiabatic and diabatic corrugated plate gaps

NASA Astrophysics Data System (ADS)

Polzin, A.-E.; Kabelac, S.; de Vries, B.

2016-09-01

Correlations for two-phase heat transfer and pressure drop can be improved considerably, when they are adapted to specific flow patterns. As plate heat exchangers find increasing application as evaporators and condensers, there is a need for flow pattern maps for corrugated plate gaps. This contribution presents experimental results on flow pattern investigations for such a plate heat exchanger background, using an adiabatic visualisation setup as well as a diabatic setup. Three characteristic flow patterns were observed in the considered range of two-phase flow: bubbly flow, film flow and slug flow. The occurrence of these flow patterns is a function of mass flux, void fraction, fluid properties and plate geometry. Two different plate geometries having a corrugation angle of 27° and 63°, respectively and two different fluids (water/air and R365mfc liquid/vapor) have been analysed. A flow pattern map using the momentum flux is presented.

Accurate modelling of single-particle cryo-EM images quantifies the benefits expected from using Zernike phase contrast

PubMed Central

Hall, R. J.; Nogales, E.; Glaeser, R. M.

2011-01-01

The use of a Zernike-type phase plate in biological cryo-electron microscopy allows the imaging, without using defocus, of what are predominantly phase objects. It is thought that such phase-plate implementations might result in higher quality images, free from the problems of CTF correction that occur when images must be recorded at extremely high values of defocus. In single-particle cryo-electron microscopy it is hoped that these improvements in image quality will facilitate work on structures that have proved difficult to study, either because of their relatively small size or because the structures are not completely homogeneous. There is still a need, however, to quantify how much improvement can be gained by using a phase plate for single-particle cryo-electron microscopy. We present a method for quantitatively modelling the images recorded with 200 keV electrons, for single particles embedded in vitreous ice. We then investigate what difference the use of a phase-plate device could have on the processing of single-particle data. We confirm that using a phase plate results in single-particle datasets in which smaller molecules can be detected, particles can be more accurately aligned and problems of heterogeneity can be more easily addressed. PMID:21463690

Multistable Phase-Retardation Plate Based on Gelator-Doped Liquid Crystals

NASA Astrophysics Data System (ADS)

Ying-Guey Fuh, Andy; Chiang, Jou-Ting; Chien, Yu-Shein; Chang, Chih-Juang; Lin, Hui-Chi

2012-07-01

This work demonstrates a multistable, large phase-retardation plate using gelator-doped liquid crystals (LCs). Multistability is achieved by forming a rubbery LC gel at room temperature. Experimentally, the phase retardation (PR) of an LC-gel film can be varied and fixed by the thermoreversible association and dissociation of the gelator molecules. The PR of the LC plate ranging from 0.3-3.7π can be electrically controllable within 10 V. Half-wave and quarter-wave LC plates were also produced at applied voltages of 3.5 and 6.3 V, respectively. Their properties were examined and found to be stable.

Multistable Phase-Retardation Plate Based on Gelator-Doped Liquid Crystals

NASA Astrophysics Data System (ADS)

Fuh, Andy Ying-Guey; Chiang, Jou-Ting; Chien, Yu-Shein; Chang, Chih-Juang; Lin, Hui-Chi

2012-07-01

This work demonstrates a multistable, large phase-retardation plate using gelator-doped liquid crystals (LCs). Multistability is achieved by forming a rubbery LC gel at room temperature. Experimentally, the phase retardation (PR) of an LC-gel film can be varied and fixed by the thermoreversible association and dissociation of the gelator molecules. The PR of the LC plate ranging from 0.3--3.7π can be electrically controllable within 10 V. Half-wave and quarter-wave LC plates were also produced at applied voltages of 3.5 and 6.3 V, respectively. Their properties were examined and found to be stable.

Design and fabrication of a freeform phase plate for high-order ocular aberration correction

NASA Astrophysics Data System (ADS)

Yi, Allen Y.; Raasch, Thomas W.

2005-11-01

In recent years it has become possible to measure and in some instances to correct the high-order aberrations of human eyes. We have investigated the correction of wavefront error of human eyes by using phase plates designed to compensate for that error. The wavefront aberrations of the four eyes of two subjects were experimentally determined, and compensating phase plates were machined with an ultraprecision diamond-turning machine equipped with four independent axes. A slow-tool servo freeform trajectory was developed for the machine tool path. The machined phase-correction plates were measured and compared with the original design values to validate the process. The position of the phase-plate relative to the pupil is discussed. The practical utility of this mode of aberration correction was investigated with visual acuity testing. The results are consistent with the potential benefit of aberration correction but also underscore the critical positioning requirements of this mode of aberration correction. This process is described in detail from optical measurements, through machining process design and development, to final results.

Test results of a pumped two-phase mounting plate with ammonia. [designed for spacecraft thermal control

NASA Technical Reports Server (NTRS)

Swanson, T. D.; Mccabe, M. E., Jr.; Grote, M. G.

1987-01-01

The design, fabrication, and testing of full-scale prototype units of a two-phase mounting plate (TPMP), which will be used in a two-phase ammonia-based thermal control system for a large spacecraft, are described. The mounting plate uses an evaporator design in which liquid is mechanically pumped through porous feed tubes within the plate. The prototype TPMPs were tested with ammonia at heat loads over 3000 W (3.2 W/sq cm) and local heat fluxes of up to 4 W/sq cm. Calculated total heat transfer coefficients from these tests were between 0.8 and 1.0 W/sq cm per C. This represents a better than twenty-fold improvement over comparable single-phase heat transfer coefficients. Design diagrams are included.

Kinematics of the New Zealand plate boundary: Relative motion by GPS across networks of 1000 km and 50 km spacing

NASA Technical Reports Server (NTRS)

Meertens, Charles M.; Rocken, Christian; Perin, Barbara; Walcott, Richard

1993-01-01

The NASA/DOSE 'Kinematics of the New Zealand Plate Boundary' experiment is a four-year cooperative Global Positioning System (GPS) experiment involving 6 universities and institutions in New Zealand and the United States. The investigation covers two scales, the first on the scale of plates (approximately 1000 km) and the second is on the scale of the plate boundary zone (approximately 50 km). In the first portion of the experiment, phase A, the objective is to make direct measurements of tectonic plate motion between the Australian and Pacific plates using GPS in order to determine the Euler vector of this plate pair. The phase A portion of this experiment was initiated in December 1992 with the first-epoch baseline measurements on the large scale network. The network will be resurveyed two years later to obtain velocities. The stations which were observed for phase A are shown and listed. Additional regional stations which will be used for this study are listed and are part of either CIGNET or other global tracking networks. The phase A portion of the experiment is primarily the responsibility of the UNAVCO investigators. Therefore, this report concentrates on phase A. The first year of NASA funding for phase A included only support for the field work. Processing and analysis will take place with the second year of funding. The second part of the experiemnt measured relative motion between the Australian and Pacific plates across the pate boundary zone between Hokitika and Christchurch on the South Island of New Zealand. The extent and rate of deformation will be determined by comparisons with historical, conventional surveys and by repeated GPS measurements to be made in two years. This activity was the emphasis of the LDGO portion of the study. An ancillary experiment, phase C, concentrated on plate boundary deformation in the vicinity of Wellington and was done as part of training during the early portion of the field campaign. Details of the objectives of the field investigations are given in the appendix. An overview of the 1992 GPS field program is also given in the appendix.

Observation of Phase Objects by Using an X-ray Microscope with a Foucault Knife-Edge

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

Watanabe, N.; Sasaya, T.; Imai, Y.

2011-09-09

An x-ray microscope with a zone plate was assembled at the synchrotron radiation source of BL3C, Photon Factory. A Foucault knife-edge was set at the back focal plate of the objective zone plate and phase retrieval was tested by scanning the knife-edge. A preliminary result shows that scanning the knife-edge during exposure was effective for phase retrieval. Phase-contrast tomography was investigated using differential projection images calculated from two Schlieren images with the oppositely oriented knife-edges. Fairly good reconstruction images of polystyrene beads and spores could be obtained.

Structured light generation by magnetic metamaterial half-wave plates at visible wavelength

NASA Astrophysics Data System (ADS)

Zeng, Jinwei; Luk, Ting S.; Gao, Jie; Yang, Xiaodong

2017-12-01

Metamaterial or metasurface unit cells functioning as half-wave plates play an essential role for realizing ideal Pancharatnam-Berry phase optical elements capable of tailoring light phase and polarization as desired. Complex light beam manipulation through these metamaterials or metasurfaces unveils new dimensions of light-matter interactions for many advances in diffraction engineering, beam shaping, structuring light, and holography. However, the realization of metamaterial or metasurface half-wave plates in visible spectrum range is still challenging mainly due to its specific requirements of strong phase anisotropy with amplitude isotropy in subwavelength scale. Here, we propose magnetic metamaterial structures which can simultaneously exploit the electric field and magnetic field of light for achieving the nanoscale half-wave plates at visible wavelength. We design and demonstrate the magnetic metamaterial half-wave plates in linear grating patterns with high polarization conversion purity in a deep subwavelength thickness. Then, we characterize the equivalent magnetic metamaterial half-wave plates in cylindrical coordinate as concentric-ring grating patterns, which act like an azimuthal half-wave plate and accordingly exhibit spatially inhomogeneous polarization and phase manipulations including spin-to-orbital angular momentum conversion and vector beam generation. Our results show potentials for realizing on-chip beam converters, compact holograms, and many other metamaterial devices for structured light beam generation, polarization control, and wavefront manipulation.

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

Meiser, Jerome; Urbassek, Herbert M., E-mail: urbassek@rhrk.uni-kl.de

Using classical molecular dynamics simulations and the Meyer-Entel interaction potential, we study the martensitic transformation pathway in a pure iron bi-crystal containing a symmetric tilt grain boundary. Upon cooling the system from the austenitic phase, the transformation starts with the nucleation of the martensitic phase near the grain boundary in a plate-like arrangement. The Kurdjumov-Sachs orientation relations are fulfilled at the plates. During further cooling, the plates expand and merge. In contrast to the orientation relation in the plate structure, the complete transformation proceeds via the Pitsch pathway.

Cell penetrating peptides: a comparative transport analysis for 474 sequence motifs.

PubMed

Ramaker, Katrin; Henkel, Maik; Krause, Thorsten; Röckendorf, Niels; Frey, Andreas

2018-11-01

Delivering reagents into cells is a key demand in molecular medicine. The vehicle of choice is often cell penetrating peptides (CPPs), which can ferry conjugated cargo across membranes. Although numerous peptides have been shown to promote such uptake events, there has been no comprehensive comparison of individual performance under standardized conditions. We have devised a method to rapidly analyze the ability of a multitude of CPP conjugates to carry a model cargo into HeLa cells. Sequence information for 474 CPPs was collected from literature sources, and the respective peptides were synthesized and modified with carboxyfluorescein (FAM) as model cargo. All candidates were evaluated in an identical uptake test, and transport was quantified using cellular fluorescence intensities. Substantial differences in the ability to carry the fluorophore into the cells were observed, with transport performance differing by a factor of 70 between the best CPP investigated and cargo alone. Strong correlations were observed between uptake efficiency and both sequence length and the presence of positive net charge. A compilation of the 20 top performers with regard to cargo delivery performance and cell compatibility is provided.

The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes.

PubMed

Shoskes, Daniel A; Altemus, Jessica; Polackwich, Alan S; Tucky, Barbara; Wang, Hannah; Eng, Charis

2016-06-01

To study the urinary microbiome of patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) compared with controls. We identified 25 patients with CP/CPPS and 25 men who were either asymptomatic or only had urinary symptoms. Midstream urine was collected. Symptom severity was measured with the National Institutes of Health Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the urine pellet and bacterial-specific 16Sr-DNA-capture identified by MiSeq sequencing. Taxonomic and functional bioinformatic analyses used principal coordinate analysis (PCoA)/MacQIIME, LEfSe, and PiCRUSt algorithms. Patients and controls were similar ages (52.3 vs 57.0 years, P = .27). For patients, median duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0, and mean UPOINT domains was 3.6. Weighted 3D UniFrac PCoA revealed tighter clustering of controls distinct from the wider clustering of cases (P = .001; α-diversity P = .005). Seventeen clades were overrepresented in patients, for example, Clostridia, and 5 were underrepresented, eg, Bacilli, resulting in predicted perturbations in functional pathways. PiCRUSt inferred differentially regulated pathways between cases and controls that may be of relevance including sporulation, chemotaxis, and pyruvate metabolism. PCoA-derived microbiomic differences were noted for neurologic/systemic domains (P = .06), whereas LEfSe identified differences associated with each of the 6 clinical features. Urinary microbiomes from patients with CP/CPPS have significantly higher alpha(phylogenetic) diversity which cluster differently from controls, and higher counts of Clostridia compared with controls, resulting in predicted perturbations of functional pathways which could suggest metabolite-specific targeted treatment. Several measures of severity and clinical phenotype have significant microbiome differences. Copyright © 2016 Elsevier Inc. All rights reserved.

Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) induced by immunization with a novel peptide T2.

PubMed

Ihsan, Awais Ullah; Khan, Farhan Ullah; Nawaz, Waqas; Khan, Muhammad Zahid; Yang, Mengqi; Zhou, Xiaohui

2017-07-01

The exact etiological mechanism of Chronic Prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be beneficial in elucidating mechanisms involved in the pathogenesis of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). 40 male Sprague-Dawley rats with an average weight of 180-220g were equally distributed into five groups. The normal control group was injected with normal saline (.9% NACL), the CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA. Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin staining and Immunohistochemistry were used to investigate inflammatory cell infiltration and IL-1β in the prostate tissue respectively. ELISA technique was used to measure the serum level of CRP and TNF-α. T-test was used to analyze the results. Maximum infiltration of inflammatory cells and the highest level of IL-1β in the prostate tissue was observed in T2+AL(OH)3+CFA group as revealed by histopathology and Immunohistochemistry, respectively. Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-α and CRP as determined by ELISA technique. Our results demonstrated that T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We believe that our present model will be highly beneficial for investigation of the pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

2016-03-01

Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

Quantitative phase retrieval with arbitrary pupil and illumination

DOE PAGES

Claus, Rene A.; Naulleau, Patrick P.; Neureuther, Andrew R.; ...

2015-10-02

We present a general algorithm for combining measurements taken under various illumination and imaging conditions to quantitatively extract the amplitude and phase of an object wave. The algorithm uses the weak object transfer function, which incorporates arbitrary pupil functions and partially coherent illumination. The approach is extended beyond the weak object regime using an iterative algorithm. Finally, we demonstrate the method on measurements of Extreme Ultraviolet Lithography (EUV) multilayer mask defects taken in an EUV zone plate microscope with both a standard zone plate lens and a zone plate implementing Zernike phase contrast.

End plate assembly having a two-phase fluid-filled bladder and method for compressing a fuel cell stack

DOEpatents

Carlstrom, Jr., Charles M.

2001-01-01

An end plate assembly is disclosed for use in a fuel cell assembly in which the end plate assembly includes a housing having a cavity, and a bladder receivable in the cavity and engageable with the fuel cell stack. The bladder includes a two-phase fluid having a liquid portion and a vapor portion. Desirably, the two-phase fluid has a vapor pressure between about 100 psi and about 600 psi at a temperature between about 70 degrees C. to about 110 degrees C.

Synthesis and evaluation of amphiphilic peptides as nanostructures and drug delivery tools

NASA Astrophysics Data System (ADS)

Sayeh, Naser Ali

Intracellular delivery of cell-impermeable compounds in a variety cells using delivery systems have been extensively studied in recent years. Obtaining desirable cellular uptake levels often requires the administration of high quantities of drugs to achieve the expected intracellular biological effect. Thus, improving the translocation process across the plasma membrane will significantly reduce the quantity of required administered drug and consequently minimize the side effects in most of the cases. Efficient delivery of these molecules to the cells and tissues is a difficult challenge. Compounds with low cellular permeability are commonly considered to be of limited therapeutic value. Over the past few decades, several biomedical carriers, such as polymers, nanospheres, nanocapsules, liposomes, micelles, peptides and dendrimers have been widely used to deliver therapeutic and diagnostic agents to the cells. Biomaterials generated from nano-scale compounds have shown some promising data for delivery of many compounds in a number of diseases, such as viral infections, cancer, and genetic disorders. Although much progress has been achieved in this field, many challenges still remain, such as toxicity and limited stability. Liposomes suffer from poor stability in the bloodstream and leakage during storage. They tend to aggregate and fuse with or leak entrapped drugs, especially highly hydrophilic small molecules. For solid lipid nanoparticles (SLNs), drug expulsion after polymorphic transition during storage, inadequate loading capacity, and relatively high water content of the dispersions have been observed. Poly(lactic-coglycolic acid (PLGA) degrades in the body producing its original monomers of lactic acid and glycolic acid, which are the by-products of various metabolic pathways. However, this acidic microenvironment that occurs during degradation could negatively affect the stability of the loaded compound. Dendrimers can carry drugs as complexes or as conjugates although one limitation lies in the effort of controlling the rate of drug release. The encapsulated or complexed drugs tend to be released rapidly (before reaching the target site) and in the dendrimer--drug conjugates, it is the chemical linkage that controls the drug release. Thus, future studies in this field are urgently required to create more efficient and stable biomaterials. Peptides are considered as efficient vectors for achieving optimal cellular uptake. The potential use of peptides as drug delivery vectors received much attention by the discovery of several cell-penetrating peptides (CPPs). The first CPPs discovered in 1988, that were sequences from HIV-1 encoded TAT protein, TAT (48--60), and penetrated very efficiently through cell membranes of cultured mammalian cells. CPPs are a class of diverse peptides, typically with 8--25 amino acids, and unlike most peptides, they can cross the cellular membrane with more efficiency. CPPs have also shown to undergo self-assembly and generate nanostructures. The generation of self-assembled peptides and nanostructures occur through various types of interactions between functional groups of amino acid residues, such as electrostatic, hydrophobic, and hydrogen bonding. Appropriate design and functionalization of peptides are critical for generating nanostructures. Chemically CPPs are classified into two major groups: linear and cyclic peptides. It has been previously reported that linear peptides containing hydrophilic and hydrophobic amino acids could act as membrane protein stabilizers. These compounds are short hydrophilic or amphiphilic peptides that have positively charged amino acids, such as arginine, lysine or histidine, which can interact with the negative charge phospholipids layer on the cell membrane and translocate the cargo into the cells. Conjugation to cationic linear CPPs, such as TAT, penetratin, or oligoarginine efficiently improves the cellular uptake of large hydrophilic molecules, but the cellular uptake is predominantly via an unproductive endosomal pathway. Therefore, the biological effect is very limited, as the compounds are trapped in these compartments and cannot reach their biological targets in the cytoplasm or the nucleus. Mechanisms that promote endosomal escape or avoid endosomal route are required for improving bioavailability. Highly cationic CPPs preferentially interact with particular cell types, have limited plasma half-life, show toxicity, do not cross multicellular barriers such as vasculature epithelia or the blood-brain barrier, and efficient cargo delivery requires 9-15 arginine residues. Highly cationic CPPs are, therefore not ideal small molecule drug delivery vehicles. Linear CPPs are susceptible to hydrolysis by endogenous peptidases. Conjugation to cationic CPPs, such as TAT, penetratin, or oligoarginine efficiently improves the cellular uptake of large hydrophilic molecules, but the cellular uptake occurs predominantly via an unproductive endosomal pathway. Therefore, the biological effect is very limited, as the compounds are trapped in these compartments and cannot reach their biological targets in the cytoplasm or the nucleus. Mechanisms that promote endosomal escape or avoid endosomal route are required for improving bioavailability. Highly cationic CPPs preferentially interact with particular cell types, have limited plasma half-life, show toxicity, do not cross multicellular barriers such as vasculature epithelia or the blood-brain barrier, and efficient cargo delivery requires 9-15 arginine residues. Highly cationic linear CPPs are, therefore, have not become optimized as small molecule drug delivery vehicles. On the other hand, cyclic peptides containing hydrophilic and hydrophobic amino acids have shown greater potential as drug delivery tools due to their enhanced chemical and enzymatic stability. Parang's laboratory has reported that Amphiphilic Cyclic Peptides (ACPs) containing positively charged arginine and hydrophobic tryptophan residues as potential candidates for drug delivery. Cyclic peptides have several benefits compared to linear peptides, such as rigidness of structure and stability against proteolytic enzymes. The rigidity of the structure can enhance the binding affinity of ligands toward receptors by reducing the freedom of possible structural conformations. Cyclic peptides are also present in nature and have been developed as therapeutics. Cyclosporine, gramicidin S, polymoxin B, and daptomycin are well-known examples of cyclic peptide drugs. Parang's laboratory designed amphiphilic cyclic CPPs containing alternative tryptophan and arginine residues as the positively charged and hydrophobic residues, respectively. The peptides were efficient in improving the cellular delivery of anticancer and antiviral drugs. The cellular uptake mechanism of CPPs into cells is still a matter of some debate. The cellular entry of CPP can be influenced by the type of CPP, the cell line, the nature of the cargo, and the conditions of incubation. As described above, linear CPPs pass through the plasma membrane mostly via an energy-independent or endocytosis pathway. Moreover, the cellular delivery of CPP-conjugated molecules also occurs through endosomal pathway and a strong enzymatic degradation and an inadequate cytoplasmic release of intact molecules from the conjugates are expected, thus leading to an inefficient transfer into the cytoplasm. The best strategy to overcome this issue is to designing CPP that by pass the endosomal uptake or by increasing the escape rate from the endosome to improve the intracellular delivery of CPP-attached molecules. Parang laboratory has reported the cellular uptake of a number of cyclic peptides independent of endocytotic pathway. The extraordinary ability of cyclic peptides containing tryptophan and arginine, [WR]4 and [WR] 5 to spontaneously translocate across bilayers independent of an energy source is distinctly different from the behavior of the well-known, highly cationic CPPs, such as TAT and Arg9, which do not translocate across phospholipid bilayers, and enter cells mostly by active endocytosis. Alternatively, researchers have found that an effective cellular delivery vector can be improved developed by conjugating a CPP with a fatty acid chain. Amphiphilic peptides have also become a subject of major interest as potent antibacterial agents. Antimicrobial peptides (AMPs) are produced naturally by bacteria and are considered as the first line of host defense protecting living organisms from microorganisms. Various types of AMPs has been discovered, such as defensins, cecropins, magainins and cathelicidins, with significant different structures and bioactivity profiles. The mechanism of actions for these peptides were reported as effectors and regulators of the innate immune system by increasing production and release of chemokine, and enhancing wound healing and angiogenesis. They were able to suppress biofilm formation and induce the dissolution of existing biofilms. Thus, design of new AMPs and more cost effective sequences with highly activity are urgently needed. Although a number of cyclic peptides were discovered and reported as efficient cellular delivery agents or antimicrobial agent, a more systematic investigation is required to identify design rules for optimal entrapment, drug loading, and stability. The balance of many small forces determines the overall morphology, size, and functionality of the structures. A deeper understanding of these factors is required for guiding future research, and for customizing cyclic peptides for drug loading and cellular delivery applications. Thus, additional amphiphilic cyclic and linear peptides were designed with variable electrostatic and hydrophobic residues to optimize drug encapsulation. The diversity in ring size, amino acid number, position and sequences, number of rings, net charge, and hydrophobicity of side chains in cyclic peptides will allow us to explore requirements for generating peptides with optimized drug encapsulation and to establish correlations between the structure of peptides with their drug entrapment properties. Thus, the general objective of this dissertation was to design and evaluate additional cyclic or amphiphilic peptides as nanostructures, compare their efficiency in delivery of small molecules with the previously reported cyclic peptides containing tryptophan and arginine residues. This dissertation consists of three chapters. Chapter 1. MANUSCRIPT (published in Current Organic Chemistry 2014). The objective of this work was to design amphiphilic linear and cyclic peptides containing hydrophobic tryptophan W residues that were linked through a triazole ring to positively charged arginine R and lysine (K) residues. The peptides were synthesized through click chemistry between hydrophobic peptides containing alkyne and positively charged peptides containing azide groups. Characterization of their structures like solubility, CD, TEM, cytotoxicity were investigated. The conjugates were showed minimal cytotoxicity at two cell lines. The secondary structures of both peptides were similar to a distorted α-helix as shown by CD spectroscopy. TEM imaging also showed that linear-linear (WG(triazole-KR-NH2))3 and cyclic-linear [WG(triazole-KR-NH2)]3 peptides formed nano-sized structures. Chapter 2. MANUSCRIPT I (Submitted to Journal of Molecular Modeling). In this work, we investigated the structural and dynamical aspects of cyclic-linear peptide ([WG(triazole-KR-NH2)] 3 and linear-linear peptide (WG(triazole-KR-NH2))3) formed nanostructures compared to a drug delivery system with [WR]4. While [WR]4 was found to be an efficient molecular transporter for small molecule drugs, such as lamivudine and dasatinib, cyclic-linear peptide ([WG(triazole-KR-NH2)]3 was inefficient. Molecular modeling was used to explain the differential behavior of these peptides. We showed how the morphology of these systems can affect the drug delivery efficiency. The result of this work provided insights about optimizing the amphiphilic cyclic-linear trizaolyl peptides can be used to design compounds with more efficient drug delivery capabilities. Chapter 3. MANUSCRIPT II. The objective of this Chapter was to synthesize a different series of amphiphilic peptides for different objectives. First, the amphiphilic trizaolyl peptides in Chapter I were systematically modified by increasing the number of arginine and tryptophan sequence in cyclic and linear peptides. The rationale for the modification was to enhance the possibility of interaction with the cell membrane and therefore improving the cellular uptake process. Moreover, a new class of amphiphilic peptides consist of tryptophan and glutamic acid were conjugated with a peptide containing arginine and lysine residues using Fmoc chemistry. These peptides have an amide bond that generates more flexibility compared to a triazole ring. The chemical and biological properties will be evaluated in future and compared with amphiphilic triazolyl peptides. Finally, additional fatty acids with different length chains were conjugated with positively charged peptides to be evaluated as antibacterial agents. Stearic acid (C16) and myristic acid (C14) were conjugated with a peptides consisting of arginine azide and lysine amino acids to enhance the antibacterial activity. In summary, the work in this dissertation provided insights about the synthesis and characterization of a new class of amphiphilic triazolyl peptides as drug delivery carriers and amphiphilic peptides as antibacterial agents. Molecular modeling was used to explain why triazolyl peptides were unable to enhance the delivery of small molecule drugs compared to the previously synthesized cyclic peptides [WR]4 (Chapter 2) Modification of synthesized peptides in Chapter 1, by addition of more positively charged amino acids or reducing the rigidity by incorporating amide bonds instead of triazoly groups can be used to improve the cell penetrating properties. Finally, we conjugated amphiphilic peptides with different fatty acids (Chapter 3) to investigate their application as antibacterial agents.

Omnidirectional antenna having constant phase

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

Sena, Matthew

Various technologies presented herein relate to constructing and/or operating an antenna having an omnidirectional electrical field of constant phase. The antenna comprises an upper plate made up of multiple conductive rings, a lower ground-plane plate, a plurality of grounding posts, a conical feed, and a radio frequency (RF) feed connector. The upper plate has a multi-ring configuration comprising a large outer ring and several smaller rings of equal size located within the outer ring. The large outer ring and the four smaller rings have the same cross-section. The grounding posts ground the upper plate to the lower plate while maintainingmore » a required spacing/parallelism therebetween.« less

Mantle convection with plates and mobile, faulted plate margins.

PubMed

Zhong, S; Gurnis, M

1995-02-10

A finite-element formulation of faults has been incorporated into time-dependent models of mantle convection with realistic rheology, continents, and phase changes. Realistic tectonic plates naturally form with self-consistent coupling between plate and mantle dynamics. After the initiation of subduction, trenches rapidly roll back with subducted slabs temporarily laid out along the base of the transition zone. After the slabs have penetrated into the lower mantle, the velocity of trench migration decreases markedly. The inhibition of slab penetration into the lower mantle by the 670-kilometer phase change is greatly reduced in these models as compared to models without tectonic plates.

Efficient fabrication method of nano-grating for 3D holographic display with full parallax views.

PubMed

Wan, Wenqiang; Qiao, Wen; Huang, Wenbin; Zhu, Ming; Fang, Zongbao; Pu, Donglin; Ye, Yan; Liu, Yanhua; Chen, Linsen

2016-03-21

Without any special glasses, multiview 3D displays based on the diffractive optics can present high resolution, full-parallax 3D images in an ultra-wide viewing angle. The enabling optical component, namely the phase plate, can produce arbitrarily distributed view zones by carefully designing the orientation and the period of each nano-grating pixel. However, such 3D display screen is restricted to a limited size due to the time-consuming fabricating process of nano-gratings on the phase plate. In this paper, we proposed and developed a lithography system that can fabricate the phase plate efficiently. Here we made two phase plates with full nano-grating pixel coverage at a speed of 20 mm²/mins, a 500 fold increment in the efficiency when compared to the method of E-beam lithography. One 2.5-inch phase plate generated 9-view 3D images with horizontal-parallax, while the other 6-inch phase plate produced 64-view 3D images with full-parallax. The angular divergence in horizontal axis and vertical axis was 1.5 degrees, and 1.25 degrees, respectively, slightly larger than the simulated value of 1.2 degrees by Finite Difference Time Domain (FDTD). The intensity variation was less than 10% for each viewpoint, in consistency with the simulation results. On top of each phase plate, a high-resolution binary masking pattern containing amplitude information of all viewing zone was well aligned. We achieved a resolution of 400 pixels/inch and a viewing angle of 40 degrees for 9-view 3D images with horizontal parallax. In another prototype, the resolution of each view was 160 pixels/inch and the view angle was 50 degrees for 64-view 3D images with full parallax. As demonstrated in the experiments, the homemade lithography system provided the key fabricating technology for multiview 3D holographic display.

AUTOMATIC COUNTER

DOEpatents

Robinson, H.P.

1960-06-01

An automatic counter of alpha particle tracks recorded by a sensitive emulsion of a photographic plate is described. The counter includes a source of mcdulated dark-field illumination for developing light flashes from the recorded particle tracks as the photographic plate is automatically scanned in narrow strips. Photoelectric means convert the light flashes to proportional current pulses for application to an electronic counting circuit. Photoelectric means are further provided for developing a phase reference signal from the photographic plate in such a manner that signals arising from particle tracks not parallel to the edge of the plate are out of phase with the reference signal. The counting circuit includes provision for rejecting the out-of-phase signals resulting from unoriented tracks as well as signals resulting from spurious marks on the plate such as scratches, dust or grain clumpings, etc. The output of the circuit is hence indicative only of the tracks that would be counted by a human operator.

A succinct method to generate multi-type HCV beams with a spatial spiral varying retardation-plate

NASA Astrophysics Data System (ADS)

Qi, Junli; Zhang, Hui; Pan, Baoguo; Deng, Haifei; Yang, Jinhong; Shi, Bo; Wang, Hui; Du, Ang; Wang, Weihua; Li, Xiujian

2018-03-01

A simple novel and practical scheme is presented to generate high-power cylindrical vector (HCV) beams with a 36-segment spiral varying retardation-plate sandwiched between two quarter-wave plates (QWPs). Four kinds of HCV beams, such as radially polarized beam and azimuthally polarized beam, are formed by simply rotating two QWPs. A segmented spiral varying phase-plate with isotropy is used to modulate spatial phase distribution to generate in-phase HCV beams. The intensity distributions and polarizing properties of HCV beams are investigated and analyzed in detail. It is demonstrated experimentally that the system can effectively generate multi-type HCV beams with high purity up to 99%, and it can be manufactured as cylindrical vector beam converter commercially.

Joint research effort on vibrations of twisted plates, phase 1: Final results

NASA Technical Reports Server (NTRS)

Kielb, R. E.; Leissa, A. W.; Macbain, J. C.; Carney, K. S.

1985-01-01

The complete theoretical and experimental results of the first phase of a joint government/industry/university research study on the vibration characteristics of twisted cantilever plates are given. The study is conducted to generate an experimental data base and to compare many different theoretical methods with each other and with the experimental results. Plates with aspect ratios, thickness ratios, and twist angles representative of current gas turbine engine blading are investigated. The theoretical results are generated by numerous finite element, shell, and beam analysis methods. The experimental results are obtained by precision matching a set of twisted plates and testing them at two laboratories. The second and final phase of the study will concern the effects of rotation.

Evaluation of the Granada agar plate for detection of vaginal and rectal group B streptococci in pregnant women.

PubMed

Gil, E G; Rodríguez, M C; Bartolomé, R; Berjano, B; Cabero, L; Andreu, A

1999-08-01

Granada medium was evaluated for the detection of group B streptococci (GBS) in vaginal and rectal swabs compared with selective Columbia blood agar and selective Lim broth. From May 1996 to March 1998, 702 pregnant women (35 to 37 weeks of gestation) participated in this three-phase study; 103 (14.7%) of these women carried GBS. In the first phase of the experiment (n = 273 women), vaginorectal specimens were collected on the same swab; the sensitivities of Granada tube, selective Columbia blood agar, and Lim broth were 31.4, 94.3, and 74.3%, respectively. In the second and third phases (n = 429 women), vaginal and rectal specimens were collected separately; the sensitivities of Granada plate, selective Columbia blood agar, and Lim broth (subcultured at 4 h on selective Columbia agar in the second phase and at 18 to 24 h in Granada plate in the third phase) were 91.1, 83.9, and 75%, respectively, in the second phase and 88.5, 90.4, and 63.5%, respectively, in the third phase. There were no statistically significant differences in GBS recovery between the Granada agar plate and selective Columbia blood agar, but the Granada plate provided a clear advantage; the characteristic red-orange colonies produced overnight by GBS can be identified by the naked eye and is so specific that further identification is unnecessary. The use of the Granada tube and Lim broth did not result in increased isolation of GBS. In conclusion, the Granada agar plate is highly sensitive for detecting GBS in vaginal and rectal swabs from pregnant women and can provide results in 18 to 24 h.

Passive control of coherent structures in a modified backwards-facing step flow

NASA Astrophysics Data System (ADS)

Ormonde, Pedro C.; Cavalieri, André V. G.; Silva, Roberto G. A. da; Avelar, Ana C.

2018-05-01

We study a modified backwards-facing step flow, with the addition of two different plates; one is a baseline, impermeable plate and the second a perforated one. An experimental investigation is carried out for a turbulent reattaching shear layer downstream of the two plates. The proposed setup is a model configuration to study how the plate characteristics affect the separated shear layer and how turbulent kinetic energies and large-scale coherent structures are modified. Measurements show that the perforated plate changes the mean flow field, mostly by reducing the intensity of reverse flow close to the bottom wall. Disturbance amplitudes are significantly reduced up to five step heights downstream of the trailing edge of the plate, more specifically in the recirculation region. A loudspeaker is then used to introduce phase-locked, low-amplitude perturbations upstream of the plates, and phase-averaged measurements allow a quantitative study of large-scale structures in the shear-layer. The evolution of such coherent structures is evaluated in light of linear stability theory, comparing the eigenfunction of the Kelvin-Helmholtz mode to the experimental results. We observe a close match of linear-stability eigenfunctions with phase-averaged amplitudes for the two tested Strouhal numbers. The perforated plate is found to reduce the amplitude of the Kelvin-Helmholtz coherent structures in comparison to the baseline, impermeable plate, a behavior consistent with the predicted amplification trends from linear stability.

The Cell Cycle: An Activity Using Paper Plates to Represent Time Spent in Phases of the Cell Cycle

ERIC Educational Resources Information Center

Scherer, Yvette D.

2014-01-01

In this activity, students are given the opportunity to combine skills in math and geometry for a biology lesson in the cell cycle. Students utilize the data they collect and analyze from an online onion-root-tip activity to create a paper-plate time clock representing a 24-hour cell cycle. By dividing the paper plate into appropriate phases of…

The physics of transverse mode instability-induced nonlinear phase distortions in large area optical fiber amplifiers and their mitigation with applications in scaling of pulsed and continuous wave high-energy lasers

DTIC Science & Technology

2016-12-13

plate and novel all-fiber fused coupler. Such work has laid the platform to demonstrate the mitigation of thermal mode instability through vortex beam...at IIT Madras to experimentally validate the above results as well as to explore the generation of vortex modes through a spiral phase plate and...modes through spiral phase plates and novel all-fiber fused couplers. We have demonstrated the excitation of a vortex mode with charge 1 through a

An imaging method of wavefront coding system based on phase plate rotation

NASA Astrophysics Data System (ADS)

Yi, Rigui; Chen, Xi; Dong, Liquan; Liu, Ming; Zhao, Yuejin; Liu, Xiaohua

2018-01-01

Wave-front coding has a great prospect in extending the depth of the optical imaging system and reducing optical aberrations, but the image quality and noise performance are inevitably reduced. According to the theoretical analysis of the wave-front coding system and the phase function expression of the cubic phase plate, this paper analyzed and utilized the feature that the phase function expression would be invariant in the new coordinate system when the phase plate rotates at different angles around the z-axis, and we proposed a method based on the rotation of the phase plate and image fusion. First, let the phase plate rotated at a certain angle around the z-axis, the shape and distribution of the PSF obtained on the image surface remain unchanged, the rotation angle and direction are consistent with the rotation angle of the phase plate. Then, the middle blurred image is filtered by the point spread function of the rotation adjustment. Finally, the reconstruction images were fused by the method of the Laplacian pyramid image fusion and the Fourier transform spectrum fusion method, and the results were evaluated subjectively and objectively. In this paper, we used Matlab to simulate the images. By using the Laplacian pyramid image fusion method, the signal-to-noise ratio of the image is increased by 19% 27%, the clarity is increased by 11% 15% , and the average gradient is increased by 4% 9% . By using the Fourier transform spectrum fusion method, the signal-to-noise ratio of the image is increased by 14% 23%, the clarity is increased by 6% 11% , and the average gradient is improved by 2% 6%. The experimental results show that the image processing by the above method can improve the quality of the restored image, improving the image clarity, and can effectively preserve the image information.

Research and Development Program to Develop a Nondestructive Evaluation Instrument (X-Ray Diffraction) for Measuring Residual Stresses in a Wide Range of Naval Aviation Material. Phase 2

DTIC Science & Technology

1987-04-03

Using Cr KO Radiation 3-20 Smaary of Residual Stress for Navy Pensacola Nickel-Plated 3-64 Camshaft 75 £51 3-21 Surface Residual Stresses in Nickel-Plated...NAN - Pensacola. The data obtained from the H-3 camshafts produced perplexing results due to sLn 2 * splitting and non-linear d-spacing versus sin2...com- pressive stress values on one of the nickel-plated camshafts . An additional objective of the Phase II nickel-plating study was to under- stand the

Phase formation kinetics, hardness and magnetocaloric effect of sub-rapidly solidified LaFe11.6Si1.4 plates during isothermal annealing

NASA Astrophysics Data System (ADS)

Dai, Yuting; Xu, Zhishuai; Luo, Zhiping; Han, Ke; Zhai, Qijie; Zheng, Hongxing

2018-05-01

High-temperature phase transition behavior and intrinsic brittleness of NaZn13-type τ1 phase in La-Fe-Si magnetocaloric materials are two key problems from the viewpoint of materials production and practical applications. In the present work, the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation was introduced to quantitatively characterize the formation kinetics of τ1 phase in sub-rapidly solidified LaFe11.6Si1.4 plates during the isothermal annealing process. Avrami index was estimated to be 0.43 (∼0.5), which suggests that the formation of τ1 phase is in a diffusion-controlled one-dimensional growth mode. Meanwhile, it is found that the Vickers hardness as a function of annealing time for sub-rapidly solidified plates also agrees well with the JMAK equation. The Vickers hardness of τ1 phase was estimated to be about 754. Under a magnetic field change of 30 kOe, the maximum magnetic entropy change was about 22.31 J/(kg·K) for plates annealed at 1323 K for 48 h, and the effective magnetic refrigeration capacity reached 191 J/kg.

Transportan 10 improves the anticancer activity of cisplatin.

PubMed

Izabela, Rusiecka; Jarosław, Ruczyński; Magdalena, Alenowicz; Piotr, Rekowski; Ivan, Kocić

2016-05-01

The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non-cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a complex. Additionally, the complex was relatively safe for non-cancer cells. What is more, TP10 also produced an anticancer effect on HeLa and OS143B cell lines.

Broadband one-dimensional photonic crystal wave plate containing single-negative materials.

PubMed

Chen, Yihang

2010-09-13

The properties of the phase shift of wave reflected from one-dimensional photonic crystals consisting of periodic layers of single-negative (permittivity- or permeability-negative) materials are demonstrated. As the incident angle increases, the reflection phase shift of TE wave decreases, while that of TM wave increases. The phase shifts of both polarized waves vary smoothly as the frequency changes across the photonic crystal stop band. Consequently, the difference between the phase shift of TE and that of TM wave could remain constant in a rather wide frequency range inside the stop band. These properties are useful to design wave plate or retarder which can be used in wide spectral band. In addition, a broadband photonic crystal quarter-wave plate is proposed.

Amplitude and Wavelength Measurement of Sound Waves in Free Space using a Sound Wave Phase Meter

NASA Astrophysics Data System (ADS)

Ham, Sounggil; Lee, Kiwon

2018-05-01

We developed a sound wave phase meter (SWPM) and measured the amplitude and wavelength of sound waves in free space. The SWPM consists of two parallel metal plates, where the front plate was operated as a diaphragm. An aluminum perforated plate was additionally installed in front of the diaphragm, and the same signal as that applied to the sound source was applied to the perforated plate. The SWPM measures both the sound wave signal due to the diaphragm vibration and the induction signal due to the electric field of the aluminum perforated plate. Therefore, the two measurement signals interfere with each other due to the phase difference according to the distance between the sound source and the SWPM, and the amplitude of the composite signal that is output as a result is periodically changed. We obtained the wavelength of the sound wave from this periodic amplitude change measured in the free space and compared it with the theoretically calculated values.

Study of axial mixing, holdup and slip velocity of dispersed phase in a pulsed sieve plate extraction column using radiotracer technique.

PubMed

Ghiyas Ud Din; Imran Rafiq Chughtai; Hameed Inayat, Mansoor; Hussain Khan, Iqbal

2009-01-01

Axial mixing, holdup and slip velocity of dispersed phase which are parameters of fundamental importance in the design and operation of liquid-liquid extraction pulsed sieve plate columns have been investigated. Experiments for residence time distribution (RTD) analysis have been carried out for a range of pulsation frequency and amplitude in a liquid-liquid extraction pulsed sieve plate column with water as dispersed and kerosene as continuous phase using radiotracer technique. The column was operated in emulsion region and (99m)Tc in the form of sodium pertechnetate eluted from a (99)Mo/(99m)Tc generator was used to trace the dispersed phase. Axial dispersed plug flow model with open-open boundary condition and two points measurement method was used to simulate the hydrodynamics of dispersed phase. It has been observed that the axial mixing and holdup of dispersed phase increases with increase in pulsation frequency and amplitude until a maximum value is achieved while slip velocity decreases with increase in pulsation frequency and amplitude until it approaches a minimum value. Short lived and low energy radiotracer (99m)Tc in the form of sodium pertechnetate was found to be a good water tracer to study the hydrodynamics of a liquid-liquid extraction pulsed sieve plate column operating with two immiscible liquids, water and kerosene. Axial dispersed plug flow model with open-open boundary condition was found to be a suitable model to describe the hydrodynamics of dispersed phase in the pulsed sieve plate extraction column.

Phase-Scrambler Plate Spreads Point Image

NASA Technical Reports Server (NTRS)

Edwards, Oliver J.; Arild, Tor

1992-01-01

Array of small prisms retrofit to imaging lens. Phase-scrambler plate essentially planar array of small prisms partitioning aperture of lens into many subapertures, and prism at each subaperture designed to divert relatively large diffraction spot formed by that subaperture to different, specific point on focal plane.

Growth of second stage mineral in Lytechinus variegatus.

PubMed

Stock, S R; Seto, Jong; Deymier, A C; Rack, A; Veis, A

2017-10-30

Purpose and Aims: Sea urchin teeth consist of calcite and form in two stages with different magnesium contents. The first stage structures of independently formed plates and needle-prisms define the shape of the tooth, and the columns of the second stage mineral cements the first stage structures together and control the fracture behavior of the mature tooth. This study investigates the nucleation and growth of the second stage mineral. Scanning electron microscopy (SEM) and synchrotron microComputed Tomography characterized the structures of the second phase material found in developing of Lytechinus variegatus teeth. Although the column development is a continuous process, defining four phases of column formation captures the changes that occur in teeth of L. variegatus. The earliest phase consists of small 1-2 µm diameter hemispheres, and the second of 5-10 µm diameter, mound-like structures with a nodular surface, develops from the hemispheres. The mounds eventually bridge the syncytium between adjacent plates and form hyperboloid structures (phase three) that appear like mesas when plates separate during the fracture. The mesa diameter increases with time until the column diameter is significantly larger than its height, defining the fourth phase of column development. Energy dispersive x-ray spectroscopy confirms that the columns contain more magnesium than the underlying plates; the ratios of magnesium to calcium are consistent with compositions derived from x-ray diffraction. Columns grow from both bounding plates. The presence of first phase columns interspersed among third stage mesas indicates very localized control of mineralization.

Damage localization in aluminum plate with compact rectangular phased piezoelectric transducer array

NASA Astrophysics Data System (ADS)

Liu, Zenghua; Sun, Kunming; Song, Guorong; He, Cunfu; Wu, Bin

2016-03-01

In this work, a detection method for the damage in plate-like structure with a compact rectangular phased piezoelectric transducer array of 16 piezoelectric elements was presented. This compact array can not only detect and locate a single defect (through hole) in plate, but also identify multi-defects (through holes and surface defect simulated by an iron pillar glued to the plate). The experiments proved that the compact rectangular phased transducer array could detect the full range of plate structures and implement multiple-defect detection simultaneously. The processing algorithm proposed in this paper contains two parts: signal filtering and damage imaging. The former part was used to remove noise from signals. Continuous wavelet transform was applicable to signal filtering. Continuous wavelet transform can provide a plot of wavelet coefficients and the signal with narrow frequency band can be easily extracted from the plot. The latter part of processing algorithm was to implement damage detection and localization. In order to accurately locate defects and improve the imaging quality, two images were obtained from amplitude and phase information. One image was obtained with the Total Focusing Method (TFM) and another phase image was obtained with the Sign Coherence Factor (SCF). Furthermore, an image compounding technique for compact rectangular phased piezoelectric transducer array was proposed in this paper. With the proposed technique, the compounded image can be obtained by combining TFM image with SCF image, thus greatly improving the resolution and contrast of image.

Force-motion phase relations and aerodynamic performance of a plunging plate

NASA Astrophysics Data System (ADS)

Son, Onur; Cetiner, Oksan

2018-02-01

Due to the unsteady motion of a plunging plate, forces acting on the body experience a phase difference with respect to the motion. These phase relations are investigated experimentally for a harmonically plunging plate within an amplitude range of 0.05≤ {a/c}≤ 0.6, reduced frequency range of 0.78<{k}<7.06, and at a constant Reynolds number of 10,000. Both streamwise and cross-stream force components are found to have a phase lag following the motion; however, their variations are different. The phase lag of the force on the cross-stream direction increases as the amplitude increases. Drag-thrust transition has an influence on the streamwise force phase lags, which starts to increase when the thrust starts to be produced. Particle image velocimetry measurements are also performed to reveal the relations between vortex structures and force measurements. Leading edge vortex shedding characteristics are observed to be changing from drag occurring cases to thrust producing cases in parallel with the increment in phase lags.

Biomechanical analysis using FEA and experiments of a standard plate method versus three cable methods for fixing acetabular fractures with simultaneous THA.

PubMed

Aziz, Mina S R; Dessouki, Omar; Samiezadeh, Saeid; Bougherara, Habiba; Schemitsch, Emil H; Zdero, Radovan

2017-08-01

Acetabular fractures potentially account for up to half of all pelvic fractures, while pelvic fractures potentially account for over one-tenth of all human bone fractures. This is the first biomechanical study to assess acetabular fracture fixation using plates versus cables in the presence of a total hip arthroplasty, as done for the elderly. In Phase 1, finite element (FE) models compared a standard plate method versus 3 cable methods for repairing an acetabular fracture (type: anterior column plus posterior hemi-transverse) subjected to a physiological-type compressive load of 2207N representing 3 x body weight for a 75kg person during walking. FE stress maps were compared to choose the most mechanically stable cable method, i.e. lowest peak bone stress. In Phase 2, mechanical tests were then done in artificial hemipelvises to compare the standard plate method versus the optimal cable method selected from Phase 1. FE analysis results showed peak bone stresses of 255MPa (Plate method), 205MPa (Mears cable method), 250MPa (Kang cable method), and 181MPa (Mouhsine cable method). Mechanical tests then showed that the Plate method versus the Mouhsine cable method selected from Phase 1 had higher stiffness (662versus 385N/mm, p=0.001), strength (3210versus 2060N, p=0.009), and failure energy (8.8versus 6.2J, p=0.002), whilst they were statistically equivalent for interfragmentary sliding (p≥0.179) and interfragmentary gapping (p≥0.08). The Plate method had superior mechanical properties, but the Mouhsine cable method may be a reasonable alternative if osteoporosis prevents good screw thread interdigitation during plating. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

[Optimization of lime milk precipitation process of Lonicera Japonica aqueous extract based on quality by design concept].

PubMed

Shen, Jin-Jing; Gong, Xing-Chu; Pan, Jian-Yang; Qu, Hai-Bin

2017-03-01

Design space approach was applied in this study to optimize the lime milk precipitation process of Lonicera Japonica (Jinyinhua) aqueous extract. The evaluation indices for this process were total organic acid purity and amounts of 6 organic acids obtained from per unit mass of medicinal materials. Four critical process parameters (CPPs) including drop speed of lime milk, pH value after adding lime milk, settling time and settling temperature were identified by using the weighted standardized partial regression coefficient method. Quantitative models between process evaluation indices and CPPs were established by a stepwise regression analysis. A design space was calculated by a Monte-Carlo simulation method, and then verified. The verification test results showed that the operation within the design space can guarantee the stability of the lime milk precipitation process. The recommended normal operation space is as follows： drop speed of lime milk of 1.00-1.25 mL•min⁻¹, pH value of 11.5-11.7, settling time of 1.0-1.2 h, and settling temperature of 10-20 ℃.. Copyright© by the Chinese Pharmaceutical Association.

Process signatures in glatiramer acetate synthesis: structural and functional relationships.

PubMed

Campos-García, Víctor R; Herrera-Fernández, Daniel; Espinosa-de la Garza, Carlos E; González, German; Vallejo-Castillo, Luis; Avila, Sandra; Muñoz-García, Leslie; Medina-Rivero, Emilio; Pérez, Néstor O; Gracia-Mora, Isabel; Pérez-Tapia, Sonia Mayra; Salazar-Ceballos, Rodolfo; Pavón, Lenin; Flores-Ortiz, Luis F

2017-09-21

Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

Evaluating the process parameters of the dry coating process using a 2(5-1) factorial design.

PubMed

Kablitz, Caroline Désirée; Urbanetz, Nora Anne

2013-02-01

A recent development of coating technology is dry coating, where polymer powder and liquid plasticizer are layered on the cores without using organic solvents or water. Several studies evaluating the process were introduced in literature, however, little information about the critical process parameters (CPPs) is given. Aim of the study was the investigation and optimization of CPPs with respect to one of the critical quality attributes (CQAs), the coating efficiency of the dry coating process in a rotary fluid bed. Theophylline pellets were coated with hydroxypropyl methylcellulose acetate succinate as enteric film former and triethyl citrate and acetylated monoglyceride as plasticizer. A 2(5-1) design of experiments (DOEs) was created investigating five independent process parameters namely coating temperature, curing temperature, feeding/spraying rate, air flow and rotor speed. The results were evaluated by multilinear regression using the software Modde(®) 7. It is shown, that generally, low feeding/spraying rates and low rotor speeds increase coating efficiency. High coating temperatures enhance coating efficiency, whereas medium curing temperatures have been found to be optimum in terms of coating efficiency. This study provides a scientific base for the design of efficient dry coating processes with respect to coating efficiency.

Two-phase pressure drop reduction BWR assembly design

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

Dix, G.E.; Crowther, R.L.; Colby, M.J.

1991-05-21

This patent describes an improved fuel assembly for a boiling water reactor. It comprises: a fuel channel; a lower tie plate; an upper tie plate; the lower tie plate and the upper tie plate defining a two-dimensional matrix; at least one water rod the fuel rods being partial length rods.

Diffractive Alvarez lens

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

Barton, Ian M.; Dixit, Sham N.; Summers, Leslie J.

2000-01-01

A diffractive Alvarez lens is demonstrated that consists of two separate phase plates, each having complementary 16-level surface-relief profiles that contain cubic phase delays. Translation of these two components in the plane of the phase plates is shown to produce a variable astigmatic focus. Both spherical and cylindrical phase profiles are demonstrated with good accuracy, and the discrete surface-relief features are shown to cause less than {lambda}/10 wave-front aberration in the transmitted wave front over a 40 mmx80 mm region. (c) 2000 Optical Society of America.

Analysis of the aerodynamic interaction between two plunging plates in tandem at low Reynolds number for maximum propulsive efficiency

NASA Astrophysics Data System (ADS)

Ortega-Casanova, Joaquin; Fernandez-Feria, Ramon

2015-11-01

The thrust generated by two heaving plates in tandem is analysed for two particular sets of configurations of interest in forward flight: a plunging leading plate with the trailing plate at rest, and the two plates heaving with the same frequency and amplitude, but varying the phase difference. The thrust efficiency of the leading plate is augmented in relation to a single plate heaving with the same frequency and amplitude in most cases. In the first configuration, we characterize the range of nondimensional heaving frequencies and amplitudes of the leading plate for which the stationary trailing plate contributes positively to the global thrust. The maximum global thrust efficiency, reached for an advance ratio slightly less than unity and a reduced frequency close to 5, is about the same as the maximum efficiency for an isolated plate. But for low frequencies the tandem configuration with the trailing plate at rest is more thrust efficient than the isolated plate. In the second configuration, we find that the maximum thrust efficiency is reached for a phase lag of 180o (counterstroking), particularly for an advance ratio unity and a reduced frequency 4.4, and it is practically the same as in the other configuration and that for a single plate. Supported by the Ministerio de Economía y Competitividad of Spain Grant no. DPI2013-40479-P.

Focused terahertz waves generated by a phase velocity gradient in a parallel-plate waveguide.

PubMed

McKinney, Robert W; Monnai, Yasuaki; Mendis, Rajind; Mittleman, Daniel

2015-10-19

We demonstrate the focusing of a free-space THz beam emerging from a leaky parallel-plate waveguide (PPWG). Focusing is accomplished by grading the launch angle of the leaky wave using a PPWG with gradient plate separation. Inside the PPWG, the phase velocity of the guided TE1 mode exceeds the vacuum light speed, allowing the wave to leak into free space from a slit cut along the top plate. Since the leaky wave angle changes as the plate separation decreases, the beam divergence can be controlled by grading the plate separation along the propagation axis. We experimentally demonstrate focusing of the leaky wave at a selected location at frequencies of 100 GHz and 170 GHz, and compare our measurements with numerical simulations. The proposed concept can be valuable for implementing a flat and wide-aperture beam-former for THz communications systems.

Effect of nanostructure on rapid boiling of water on a hot copper plate: a molecular dynamics study

NASA Astrophysics Data System (ADS)

Fu, Ting; Mao, Yijin; Tang, Yong; Zhang, Yuwen; Yuan, Wei

2016-08-01

Molecular dynamic simulations are performed to study the effects of nanostructure on rapid boiling of water that is suddenly heated by a hot copper plate. The results show that the nanostructure has significant effects on energy transfer from solid copper plate to liquid water and phase change process from liquid water to vapor. The liquid water on the solid surface rapidly boil after contacting with an extremely hot copper plate and consequently a cluster of liquid water moves upward during phase change. The temperature of the water film when it separates from solid surface and its final temperature when the system is at equilibrium strongly depend on the size of the nanostructure. These temperatures increase with increasing size of nanostructure. Furthermore, a non-vaporized molecular layer is formed on the surface of the copper plate even continuous heat flux is passing into water domain through the plate.

High efficiency x-ray nanofocusing by the blazed stacking of binary zone plates

NASA Astrophysics Data System (ADS)

Mohacsi, I.; Karvinen, P.; Vartiainen, I.; Diaz, A.; Somogyi, A.; Kewish, C. M.; Mercere, P.; David, C.

2013-09-01

The focusing efficiency of binary Fresnel zone plate lenses is fundamentally limited and higher efficiency requires a multi step lens profile. To overcome the manufacturing problems of high resolution and high efficiency multistep zone plates, we investigate the concept of stacking two different binary zone plates in each other's optical near-field. We use a coarse zone plate with π phase shift and a double density fine zone plate with π/2 phase shift to produce an effective 4- step profile. Using a compact experimental setup with piezo actuators for alignment, we demonstrated 47.1% focusing efficiency at 6.5 keV using a pair of 500 μm diameter and 200 nm smallest zone width. Furthermore, we present a spatially resolved characterization method using multiple diffraction orders to identify manufacturing errors, alignment errors and pattern distortions and their effect on diffraction efficiency.

System for phase-contrast x-ray radiography using X pinch radiation and a method thereof

DOEpatents

Chandler, Katherine; Chelkovenko, Tatiana; Hammer, David; Pikuz, Sergei; Sinars, Daniel; Song, Byungmoo

2007-11-06

A radiograph system with an anode plate, a cathode plate, and a power source coupled to said anode plate and the cathode plate. At least two wires coupled between the anode plate and the cathode plate provide a configuration to form an X-pinch having a photon source size of less than five microns at energies above 2.5 keV. Material at the configuration forming the X-pinch vaporizes upon application of a suitable current to the wires forming a dense hot plasma and emitting a single x-ray pulse with sufficient photons having energies in the range of from about 2.5 keV to about 20 keV to provide a phase contrast image of an object in the path of the photons. Multiple simultaneous images may be formed of a plurality of objects. Suitable filters and x-ray detectors are provided.

Heat Pipe with Axial Wick

NASA Technical Reports Server (NTRS)

Ambrose, Jay H. (Inventor); Holmes, Rolland (Inventor)

2016-01-01

A heat pipe has an evaporator portion, a condenser portion, and at least one flexible portion that is sealingly coupled between the evaporator portion and the condenser portion. The flexible portion has a flexible tube and a flexible separator plate held in place within the flexible tube so as to divide the flexible tube into a gas-phase passage and a liquid-phase artery. The separator plate and flexible tube are configured such that the flexible portion is flexible in a plane that is perpendicular to the separator plate.

How Membrane-Active Peptides Get into Lipid Membranes.

PubMed

Sani, Marc-Antoine; Separovic, Frances

2016-06-21

The structure-function relationship for a family of antimicrobial peptides (AMPs) from the skin of Australian tree frogs is discussed and compared with that of peptide toxins from bee and Australian scorpion venoms. Although these membrane-active peptides induce a similar cellular fate by disrupting the lipid bilayer integrity, their lytic activity is achieved via different modes of action, which are investigated in relation to amino acid sequence, secondary structure, and membrane lipid composition. In order to better understand what structural features govern the interaction between peptides and lipid membranes, cell-penetrating peptides (CPPs), which translocate through the membrane without compromising its integrity, are also discussed. AMPs possess membrane lytic activities that are naturally designed to target the cellular membrane of pathogens or competitors. They are extremely diverse in amino acid composition and often show specificity against a particular strain of microbe. Since our antibiotic arsenal is declining precariously in the face of the rise in multiantibiotic resistance, AMPs increasingly are seen as a promising alternative. In an effort to understand their molecular mechanism, biophysical studies of a myriad of AMPs have been reported, yet no unifying mechanism has emerged, rendering difficult the rational design of drug leads. Similarly, a wide variety of cytotoxic peptides are found in venoms, the best known being melittin, yet again, predicting their activity based on a particular amino acid composition or secondary structure remains elusive. A common feature of these membrane-active peptides is their preference for the lipid environment. Indeed, they are mainly unstructured in solution and, in the presence of lipid membranes, quickly adsorb onto the surface, change their secondary structure, eventually insert into the hydrophobic core of the membrane bilayer, and finally disrupt the bilayer integrity. These steps define the molecular mechanism by which these membrane-active peptides lyse membranes. The last class of membrane-active peptides discussed are the CPPs, which translocate across the lipid bilayer without inducing severe disruption and have potential as drug vehicles. CPPs are typically highly charged and can show antimicrobial activity by targeting an intracellular target rather than via a direct membrane lytic mechanism. A critical aspect in the structure-function relationship of membrane-active peptides is their specific activity relative to the lipid membrane composition of the cell target. Cell membranes have a wide diversity of lipids, and those of eukaryotic and prokaryotic species differ greatly in composition and structure. The activity of AMPs from Australian tree frogs, toxins, and CPPs has been investigated within various lipid systems to assess whether a relationship between peptide and membrane composition could be identified. NMR spectroscopy techniques are being used to gain atomistic details of how these membrane-active peptides interact with model membranes and cells, and in particular, competitive assays demonstrate the difference between affinity and activity for a specific lipid environment. Overall, the interactions between these relatively small sized peptides and various lipid bilayers give insight into how these peptides function at the membrane interface.

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

2012-10-01

Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P < 0.001), -9.7 (95% CI -14.2 to -5.3; P < 0.001) and -1.7 (95% CI -3.2 to -0.2; P= 0.032) respectively, while α-blockers plus antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P < 0.001). • With respect to responder analysis compared with placebo, anti-inflammatories showed the greatest response rates (risk ratio 1.7, 95% CI 1.4-2.1; P < 0.001) followed by α-blockers (risk ratio 1.4, 95% CI 1.1-1.8; P= 0.013) and antibiotics (risk ratio 1.2, 95% CI 0.7-1.9; P= 0.527). α-blockers, antibiotics and/or anti-inflammatory/immune modulation therapy appear to be beneficial for some patients with CP/CPPS. • The magnitude of effect and the disconnect between mean CPSI decrease and response rates compared with placebo suggest that directed multimodal therapy, rather than mono-therapy, with these agents should be considered for optimal management of CP/CPPS. © 2012 BJU INTERNATIONAL.

78 FR 75371 - Diffusion-Annealed, Nickel-Plated Flat-Rolled Steel Products From Japan; Scheduling of the Final...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

...-Plated Flat-Rolled Steel Products From Japan; Scheduling of the Final Phase of an Antidumping... imports from Japan of diffusion-annealed, nickel- plated flat-rolled steel products, provided for... diffusion-annealed, nickel- plated flat-rolled steel products from Japan are being sold in the United States...

Design and test of a pumped two-phase mounting plate. [for spacecraft thermal control systems

NASA Technical Reports Server (NTRS)

Grote, M. G.; Swanson, T. D.

1985-01-01

The design, fabrication, and testing of the full-scale development unit of a pumped two-phase mounting plate (TPMP) used in advanced two-phase spacecraft thermal control systems are described. The mounting plate is tested with R-11 in the evaporator mode for total heat loads of over 3000 watts and local heat fluxes over 4 W/sq cm, and in the condenser mode with condenser loads from 60 to 400 watts and inlet qualities from 8 to 94 percent. The calculated heat-transfer coefficients are between 0.66 and 1.0 W/sq cm/C and are nearly independent of the flow rate and heat load except at very low heat loads. It is shown that the TPMP can be run with inlet conditions down to 22 C subcooling without any significant gradients in the plate and that it performs well with nonuniform heat fluxes.

Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice

NASA Astrophysics Data System (ADS)

Masocha, Willias; Kombian, Samuel B.; Edafiogho, Ivan O.

2016-02-01

Recently, we found that methyl 4-(4‧-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), an anticonvulsant enaminone, has antinociceptive activity in the hot plate test. In this study we evaluated the antinociceptive activity of five anilino enaminones E139, ethyl 4-(4‧-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E121), ethyl 4-(4‧-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E122), methyl 4-(4‧-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E138) and ethyl 4-(4‧-fluorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (BRG 19) using the formalin and hot plate tests. E139 has been reported to exert its effects via enhancement of extracellular GABA levels, thus tiagabine, a GABA transporter inhibitor, was evaluated as a control together with indomethacin. Tiagabine had antinociceptive activity in both phase 1 (neurogenic pain) and phase 2 (inflammatory pain) of the formalin test, whereas indomethacin had activity only in phase 2. E139 and E138 had antinociceptive activity in both phases of the formalin test, whereas E121 had activity only in phase 1 and BRG 19 had activity only in phase 2. E122 had no significant activity in either phase. In the hot plate test only E139 had antinociceptive activity. Administration of either bicuculline, a GABAA receptor antagonist, or CGP 35348, a GABAB receptor antagonist, blocked the antinociceptive activity of E139. In conclusion our results indicate that E139 has antinociceptive activity in the formalin and hot plate tests that are dependent on GABA receptors.

Surface thermodynamic analysis of fluid confined in a cone and comparison with the sphere-plate and plate-plate geometries.

PubMed

Zargarzadeh, Leila; Elliott, Janet A W

2013-10-22

The behavior of pure fluid confined in a cone is investigated using thermodynamic stability analysis. Four situations are explained on the basis of the initial confined phase (liquid/vapor) and its pressure (above/below the saturation pressure). Thermodynamic stability analysis (a plot of the free energy of the system versus the size of the new potential phase) reveals whether the phase transition is possible and, if so, the number and type (unstable/metastable/stable) of equilibrium states in each of these situations. Moreover we investigated the effect of the equilibrium contact angle and the cone angle (equivalent to the confinement's surface separation distance) on the free energy (potential equilibrium states). The results are then compared to our previous study of pure fluid confined in the gap between a sphere and a flat plate and the gap between two flat plates.1 Confined fluid behavior of the four possible situations (for these three geometries) can be explained in a unified framework under two categories based on only the meniscus shape (concave/convex). For systems with bulk-phase pressure imposed by a reservoir, the stable coexistence of pure liquid and vapor is possible only when the meniscus is concave.

JPRS Report, Environmental Issues

DTIC Science & Technology

1991-06-26

been coordinated by the National Environ- mental Policy Commission [Comision Nacional de Politica Ambiental ]. The first step was the creation of a...May 91 [Text] Santiago, 30 May (EFE)—The Permanent South Pacific Commission (CPPS), which comprises Colombia, Chile, Ecuador , and Peru, has lodged a...decisions. We are adopting measures that will create the State Secretariat for the Environment [Secretaria de Estado del Medio Ambiente ], which will be

Two-phase pressure drop reduction BWR assembly design

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

Dix, G.E.; Crowther, R.L.; Colby, M.J.

1992-05-12

This patent describes a boiling water reactor having discrete bundles of fuel rods confined within channel enclosed fuel assemblies, an improvement to a fuel bundle assembly for placement in the reactor. It comprises a fuel channel having vertically extending walls forming a continuous channel around a fuel assembly volume, the channel being open at the bottom end for engagement to a lower tie plate and open at the upper end for engagement to an upper tie plate; rods for placement within the chamber, each the rod containing fissile material for producing nuclear reaction when in the presence of sufficient moderatedmore » neutron flux; a lower tie plate for supporting the bundle of rods within the channel, the lower tie plate for supporting the bundle of rods within the channel, the lower tie plate joining the bottom of the channel to close the bottom end of the channel, the lower tie plate providing defined apertures for the inflow of water in the channel between the rods for the generating of steam during the nuclear reaction; the plurality of fuel rods extending from the lower tie plate wherein a single phase region of the water in the bundle is defined to an upward portion of the bundle wherein a two phase region of the water and steam in the bundle is defined during nuclear steam generating reaction in the fuel bundle.« less

Surface acoustic wave (SAW) vibration sensors.

PubMed

Filipiak, Jerzy; Solarz, Lech; Steczko, Grzegorz

2011-01-01

In the paper a feasibility study on the use of surface acoustic wave (SAW) vibration sensors for electronic warning systems is presented. The system is assembled from concatenated SAW vibration sensors based on a SAW delay line manufactured on a surface of a piezoelectric plate. Vibrations of the plate are transformed into electric signals that allow identification of the sensor and localization of a threat. The theoretical study of sensor vibrations leads us to the simple isotropic model with one degree of freedom. This model allowed an explicit description of the sensor plate movement and identification of the vibrating sensor. Analysis of frequency response of the ST-cut quartz sensor plate and a damping speed of its impulse response has been conducted. The analysis above was the basis to determine the ranges of parameters for vibrating plates to be useful in electronic warning systems. Generally, operation of electronic warning systems with SAW vibration sensors is based on the analysis of signal phase changes at the working frequency of delay line after being transmitted via two circuits of concatenated four-terminal networks. Frequencies of phase changes are equal to resonance frequencies of vibrating plates of sensors. The amplitude of these phase changes is proportional to the amplitude of vibrations of a sensor plate. Both pieces of information may be sent and recorded jointly by a simple electrical unit.

Coordinate measuring machine test standard apparatus and method

DOEpatents

Bieg, L.F.

1994-08-30

A coordinate measuring machine test standard apparatus and method are disclosed which includes a rotary spindle having an upper phase plate and an axis of rotation, a kinematic ball mount attached to the phase plate concentric with the axis of rotation of the phase plate, a groove mounted at the circumference of the phase plate, and an arm assembly which rests in the groove. The arm assembly has a small sphere at one end and a large sphere at the other end. The small sphere may be a coordinate measuring machine probe tip and may have variable diameters. The large sphere is secured in the kinematic ball mount and the arm is held in the groove. The kinematic ball mount includes at least three mounting spheres and the groove is an angular locating groove including at least two locking spheres. The arm may have a hollow inner core and an outer layer. The rotary spindle may be a ratio reducer. The device is used to evaluate the measuring performance of a coordinate measuring machine for periodic recertification, including 2 and 3 dimensional accuracy, squareness, straightness, and angular accuracy. 5 figs.

Coordinate measuring machine test standard apparatus and method

DOEpatents

Bieg, Lothar F.

1994-08-30

A coordinate measuring machine test standard apparatus and method which iudes a rotary spindle having an upper phase plate and an axis of rotation, a kinematic ball mount attached to the phase plate concentric with the axis of rotation of the phase plate, a groove mounted at the circumference of the phase plate, and an arm assembly which rests in the groove. The arm assembly has a small sphere at one end and a large sphere at the other end. The small sphere may be a coordinate measuring machine probe tip and may have variable diameters. The large sphere is secured in the kinematic ball mount and the arm is held in the groove. The kinematic ball mount includes at least three mounting spheres and the groove is an angular locating groove including at least two locking spheres. The arm may have a hollow inner core and an outer layer. The rotary spindle may be a ratio reducer. The device is used to evaluate the measuring performance of a coordinate measuring machine for periodic recertification, including 2 and 3 dimensional accuracy, squareness, straightness, and angular accuracy.

Pressurized planar electrochromatography, high-performance thin-layer chromatography and high-performance liquid chromatography--comparison of performance.

PubMed

Płocharz, Paweł; Klimek-Turek, Anna; Dzido, Tadeusz H

2010-07-16

Kinetic performance, measured by plate height, of High-Performance Thin-Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Pressurized Planar Electrochromatography (PPEC) was compared for the systems with adsorbent of the HPTLC RP18W plate from Merck as the stationary phase and the mobile phase composed of acetonitrile and buffer solution. The HPLC column was packed with the adsorbent, which was scrapped from the chromatographic plate mentioned. An additional HPLC column was also packed with adsorbent of 5 microm particle diameter, C18 type silica based (LiChrosorb RP-18 from Merck). The dependence of plate height of both HPLC and PPEC separating systems on flow velocity of the mobile phase and on migration distance of the mobile phase in TLC system was presented applying test solute (prednisolone succinate). The highest performance, amongst systems investigated, was obtained for the PPEC system. The separation efficiency of the systems investigated in the paper was additionally confirmed by the separation of test component mixture composed of six hormones. 2010 Elsevier B.V. All rights reserved.

Immobilization and functional reconstitution of antibody Fab fragment by solid-phase refolding.

PubMed

Kumada, Yoichi; Hamasaki, Kyoto; Nakagawa, Aya; Sasaki, Eiju; Shirai, Tatsunori; Okumura, Masahiro; Inoue, Manami; Kishimoto, Michimasa

2013-12-31

In this study, we demonstrated the successful preparation of a Fab antibody-immobilized hydrophilic polystyrene (phi-PS) plate via one- and two-step solid-phase refolding methods. Both polystyrene-binding peptide (PS-tag)-fused Fd fragment of heavy chain (Fab H-PS) and full-length of light-chain (Fab L-PS) were individually produced in insoluble fractions of Escherichia coli cells, and they were highly purified in the presence of 8M of urea. Antigen-binding activities of Fab antibody immobilized were correctly recovered by the one-step solid-phase refolding method that a mixture of Fab H-PS and Fab L-PS was immobilized in the presence of 0.5-2M urea, followed by surface washing of the phi-PS plate with PBST. These results indicate that by genetic fusion of a PS-tag, a complex between Fab H and Fab L was efficiently immobilized on the surface of a phi-PS plate even in the presence of a low concentration of urea, and was then correctly refolded to retain its high antigen-binding activity via removal of the urea. A two-step solid-phase refolding method whereby Fab H-PS and Fab L-PS were successively refolded on the surface of a phi-PS plate also resulted in Fab antibody formation on the plate. Furthermore, both the binding affinity and the specificity of the Fab antibody produced by the two-step method were highly maintained, according to the results of sandwich ELISA and competitive ELISA using Fab antibody-immobilized plate via two-step solid-phase refolding. Thus, the solid-phase refolding method demonstrated in this study should be quite useful for the preparation of a Fab antibody-immobilized PS surface with high efficiency from individually produced Fab H-PS and Fab L-PS. This method will be applicable to the preparation of a large Fab antibody library on the surface of a PS plate for use in antibody screening. © 2013. Published by Elsevier B.V. All rights reserved.

Effect of benzalkonium chloride on viability and energy metabolism in exponential- and stationary-growth-phase cells of Listeria monocytogenes.

PubMed

Luppens, S B; Abee, T; Oosterom, J

2001-04-01

The difference in killing exponential- and stationary-phase cells of Listeria monocytogenes by benzalkonium chloride (BAC) was investigated by plate counting and linked to relevant bioenergetic parameters. At a low concentration of BAC (8 mg liter(-1)), a similar reduction in viable cell numbers was observed for stationary-phase cells and exponential-phase cells (an approximately 0.22-log unit reduction), although their membrane potential and pH gradient were dissipated. However, at higher concentrations of BAC, exponential-phase cells were more susceptible than stationary-phase cells. At 25 mg liter(-1), the difference in survival on plates was more than 3 log units. For both types of cells, killing, i.e., more than 1-log unit reduction in survival on plates, coincided with complete inhibition of acidification and respiration and total depletion of ATP pools. Killing efficiency was not influenced by the presence of glucose, brain heart infusion medium, or oxygen. Our results suggest that growth phase is one of the major factors that determine the susceptibility of L. monocytogenes to BAC.

Design, fabrication, testing and delivery of a solar collector

NASA Technical Reports Server (NTRS)

Sims, W. H.; Ballheim, R. W.; Bartley, S. M.; Smith, G. W.

1976-01-01

A two phase program encompassing the redesign and fabrication of a solar collector which is low in cost and aesthetically appealing is described. Phase one work reviewed the current collector design and developed a low-cost design based on specific design/performance/cost requirements. Throughout this phase selected collector component materials were evaluated by testing and by considering cost, installation, maintainability and durability. The resultant collector design was composed of an absorber plate, insulation, frame, cover, desiccant and sealant. In Phase two, three collector prototypes were fabricated and evaluated for both nonthermal and thermal characteristics. Tests included static load tests of covers, burst pressure tests of absorber plates, and tests for optical characteristics of selective absorber plate coatings. The three prototype collectors were shipped to Marshall Space Flight Center for use in their solar heating and cooling test facility.

Microstructural analysis of as-processed U-10 wt.%Mo monolithic fuel plate in AA6061 matrix with Zr diffusion barrier

NASA Astrophysics Data System (ADS)

Perez, E.; Yao, B.; Keiser, D. D., Jr.; Sohn, Y. H.

2010-07-01

For higher U-loading in low-enriched U-10 wt.%Mo fuels, monolithic fuel plate clad in AA6061 is being developed as a part of Reduced Enrichment for Research and Test Reactor (RERTR) program. This paper reports the first characterization results from a monolithic U-10 wt.%Mo fuel plate with a Zr diffusion barrier that was fabricated as part of a plate fabrication campaign for irradiation testing in the Advanced Test Reactor (ATR). Both scanning and transmission electron microscopy (SEM and TEM) were employed for analysis. At the interface between the Zr barrier and U-10 wt.%Mo, going from Zr to U(Mo), UZr 2, γ-UZr, Zr solid-solution and Mo 2Zr phases were observed. The interface between AA6061 cladding and Zr barrier plate consisted of four layers, going from Al to Zr, (Al, Si) 2Zr, (Al, Si)Zr 3 (Al, Si) 3Zr, and AlSi 4Zr 5. Irradiation behavior of these intermetallic phases is discussed based on their constituents. Characterization of as-fabricated phase constituents and microstructure would help understand the irradiation behavior of these fuel plates, interpret post-irradiation examination, and optimize the processing parameters of monolithic fuel system.

Relative Motion of the Nazca (farallon) and South American Plates Since Late Cretaceous Time

NASA Astrophysics Data System (ADS)

Pardo-Casas, Federico; Molnar, Peter

1987-06-01

By combining reconstructions of the South American and African plates, the African and Antarctic plates, the Antarctic and Pacific plates, and the Pacific and Nazca plates, we calculated the relative positions and history of convergence of the Nazca and South American plates. Despite variations in convergence rates along the Andes, periods of rapid convergence (averaging more than 100 mm/a) between the times of anomalies 21 (49.5 Ma) and 18 (42 Ma) and since anomaly 7 (26 Ma) coincide with two phases of relatively intense tectonic activity in the Peruvian Andes, known as the late Eocene Incaic and Mio-Pliocene Quechua phases. The periods of relatively slow convergence (50 to 55 ± 30 mm/a at the latitude of Peru and less farther south) between the times of anomalies 30-31 (68.5 Ma) and 21 and between those of anomalies 13 (36 Ma) and 7 correlate with periods during which tectonic activity was relatively quiescent. Thus these reconstructions provide quantitative evidence for a correlation of the intensity of tectonic activity in the overriding plate at subduction zones with variations in the convergence rate.

Preparation and application of reversed phase chromatorotor for the isolation of natural products by centrifugal preparative chromatography

USDA-ARS?s Scientific Manuscript database

A method of preparation of Chromatorotor or plates with a reversed phase (RP) solid silica gel sorbent layer has been developed for preparative centrifugal chromatography. The RP-rotor plates consist of binder free RP solid SiO2 sorbent layers of different thicknesses paked between two supported cir...

Two-phase opening of Andaman Sea: a new seismotectonic insight

NASA Astrophysics Data System (ADS)

Khan, P. K.; Chakraborty, Partha Pratim

2005-01-01

High-resolution reconstruction of Benioff zone depth-dip angle trajectory for Burma-Java subduction margin between 2° and 17°N Lat. reveals two major episodes of plate geometry change expressed as abrupt deviation in subduction angle. Estimation of effective rate of subduction in different time slices (and then length of subducted slab) allowed drawing of isochrones in Ma interval through these trajectories for the time period 5-12 Ma. With these isochrones, the deformation events on the subducting Indian plate are constrained in time as of 4-5 and 11 Ma old. This well-constrained time connotation offered scope for the correlation of slab deformation events with the well-established two-phase opening history of the Andaman Sea. While the 11 Ma event recorded from southern part of the study area is correlated with early stretching and rifting phase, the 4-5 Ma event is interpreted as major forcing behind the spreading phase of the Andaman Sea. Systematic spatio-temporal evaluation of Indian plate obliquity on the Andaman Sea evolution shows its definite control on the early rifting phase, initiated towards south near northwest Sumatra. The much young spreading phase recorded towards north of 7° Lat. is possibly the result of late Miocene-Pliocene trench retreat and follow-up transcurrent movement (along Sagaing and Sumatran fault system) with NW-SE pull-apart extension. Nonconformity between plate shape and subduction margin geometry is interpreted as the causative force behind Mid-Miocene intraplate extension and tearing. Enhanced stretching in the overriding plate consequently caused active forearc subsidence, recorded all along this plate margin. Initial phase of the Andaman Sea opening presumably remains concealed in this early-middle Miocene forearc subsidence history. The late Miocene-Pliocene pull-apart opening and spreading was possibly initiated near the western part of the Mergui-Sumatra region and propagated northward in subsequent period. A temporary halt in rifting at this pull-apart stage and northeastward veering of the Andaman Sea Ridge (ASR) are related with uplifting of oceanic crust in post-middle Miocene time in form of Alcock and Sewell seamounts, lying symmetrically north and south of this spreading ridge.

Modeling of laser welding of steel and titanium plates with a composite insert

NASA Astrophysics Data System (ADS)

Isaev, V. I.; Cherepanov, A. N.; Shapeev, V. P.

2017-10-01

A 3D model of laser welding proposed before by the authors was extended to the case of welding of metallic plates made of dissimilar materials with a composite multilayer intermediate insert. The model simulates heat transfer in the welded plates and takes into account phase transitions. It was proposed to select the composition of several metals and dimensions of the insert to avoid the formation of brittle intermetallic phases in the weld joint negatively affecting its strength properties. The model accounts for key physical phenomena occurring during the complex process of laser welding. It is capable to calculate temperature regimes at each point of the plates. The model can be used to select the welding parameters reducing the risk of formation of intermetallic plates. It can forecast the dimensions and crystalline structure of the solidified melt. Based on the proposed model a numerical algorithm was constructed. Simulations were carried out for the welding of titanium and steel plates with a composite insert comprising four different metals: copper and niobium (intermediate plates) with steel and titanium (outer plates). The insert is produced by explosion welding. Temperature fields and the processes of melting, evaporation, and solidification were studied.

Interferometric space-mode multiplexing based on binary phase plates and refractive phase shifters.

PubMed

Liñares, Jesús; Prieto-Blanco, Xesús; Moreno, Vicente; Montero-Orille, Carlos; Mouriz, Dolores; Nistal, María C; Barral, David

2017-05-15

A Mach-Zehnder interferometer (MZI) that includes in an arm either a reflective image inverter or a Gouy phase shifter (RGPS) can (de)multiplex many types of modes of a few mode fiber without fundamental loss. The use of RGPSs in combination with binary phase plates for multiplexing purposes is studied for the first time, showing that the particular RGPS that shifts π the odd modes only multiplexes accurately low order modes. To overcome such a restriction, we present a new exact refractive image inverter, more compact and flexible than its reflective counterpart. Moreover, we show that these interferometers remove or reduce the crosstalk that the binary phase plates could introduce between the multiplexed modes. Finally, an experimental analysis of a MZI with both an approximated and an exact refractive image inverter is presented for the case of a bimodal multiplexing. Likewise, it is proven experimentally that a RGPS that shifts π/2 demultiplexes two odd modes which can not be achieved by any image inverter.

Using a visual plate waste study to monitor menu performance.

PubMed

Connors, Priscilla L; Rozell, Sarah B

2004-01-01

Two visual plate waste studies were conducted in 1-week phases over a 1-year period in an acute care hospital. A total of 383 trays were evaluated in the first phase and 467 in the second. Food items were ranked for consumption from a low (1) to high (6) score, with a score of 4.0 set as the benchmark denoting a minimum level of acceptable consumption. In the first phase two entrees, four starches, all of the vegetables, sliced white bread, and skim milk scored below the benchmark. As a result six menu items were replaced and one was modified. In the second phase all entrees scored at or above 4.0, as did seven vegetables, and a dinner roll that replaced sliced white bread. Skim milk continued to score below the benchmark. A visual plate waste study assists in benchmarking performance, planning menu changes, and assessing effectiveness.

Quantitative fluorescence spectroscopy and flow cytometry analyses of cell-penetrating peptides internalization pathways: optimization, pitfalls, comparison with mass spectrometry quantification

NASA Astrophysics Data System (ADS)

Illien, Françoise; Rodriguez, Nicolas; Amoura, Mehdi; Joliot, Alain; Pallerla, Manjula; Cribier, Sophie; Burlina, Fabienne; Sagan, Sandrine

2016-11-01

The mechanism of cell-penetrating peptides entry into cells is unclear, preventing the development of more efficient vectors for biotechnological or therapeutic purposes. Here, we developed a protocol relying on fluorometry to distinguish endocytosis from direct membrane translocation, using Penetratin, TAT and R9. The quantities of internalized CPPs measured by fluorometry in cell lysates converge with those obtained by our previously reported mass spectrometry quantification method. By contrast, flow cytometry quantification faces several limitations due to fluorescence quenching processes that depend on the cell line and occur at peptide/cell ratio >6.108 for CF-Penetratin. The analysis of cellular internalization of a doubly labeled fluorescent and biotinylated Penetratin analogue by the two independent techniques, fluorometry and mass spectrometry, gave consistent results at the quantitative and qualitative levels. Both techniques revealed the use of two alternative translocation and endocytosis pathways, whose relative efficacy depends on cell-surface sugars and peptide concentration. We confirmed that Penetratin translocates at low concentration and uses endocytosis at high μM concentrations. We further demonstrate that the hydrophobic/hydrophilic nature of the N-terminal extremity impacts on the internalization efficiency of CPPs. We expect these results and the associated protocols to help unraveling the translocation pathway to the cytosol of cells.

Nanoparticle transport across in vitro olfactory cell monolayers.

PubMed

Gartziandia, Oihane; Egusquiaguirre, Susana Patricia; Bianco, John; Pedraz, José Luis; Igartua, Manoli; Hernandez, Rosa Maria; Préat, Véronique; Beloqui, Ana

2016-02-29

Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

PubMed

Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

2015-01-01

Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells

PubMed Central

Liu, Betty R.; Huang, Yue-Wern; Aronstam, Robert S.; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy. PMID:26942714

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

PubMed

Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

Phase plate technology for laser marking of magnetic discs

DOEpatents

Neuman, Bill; Honig, John; Hackel, Lloyd; Dane, C. Brent; Dixit, Shamasundar

1998-01-01

An advanced design for a phase plate enables the distribution of spots in arbitrarily shaped patterns with very high uniformity and with a continuously or near-continuously varying phase pattern. A continuous phase pattern eliminates large phase jumps typically expected in a grating that provides arbitrary shapes. Large phase jumps increase scattered light outside of the desired pattern, reduce efficiency and can make the grating difficult to manufacture. When manufacturing capabilities preclude producing a fully continuous grating, the present design can be easily adapted to minimize manufacturing errors and maintain high efficiencies. This continuous grating is significantly more efficient than previously described Dammann gratings, offers much more flexibility in generating spot patterns and is easier to manufacture and replicate than a multi-level phase grating.

Hybrid carbon nanoparticles modified core-shell silica: a high efficiency carbon-based phase for hydrophilic interaction liquid chromatography.

PubMed

Ibrahim, Mohammed E A; Wahab, M Farooq; Lucy, Charles A

2014-04-11

Hydrophilic interaction liquid chromatography (HILIC) is a fast growing separation technique for hydrophilic and polar analytes. In this work, we combine the unique selectivity of carbon surfaces with the high efficiency of core-shell silica. First, 5 μm core-shell silica is electrostatically coated with 105 nm cationic latex bearing quaternary ammonium groups. Then 50 nm anionic carbon nanoparticles are anchored onto the surface of the latex coated core-shell silica particles to produce a hybrid carbon-silica phase. The hybrid phase shows different selectivity than ten previously classified HILIC column chemistries and 36 stationary phases. The hybrid HILIC phase has shape selectivity for positional isomeric pairs (phthalic/isophthalic and 1-naphthoic/2-naphthoic acids). Fast and high efficiency HILIC separations of biologically important carboxylates, phenols and pharmaceuticals are reported with efficiencies up to 85,000 plates m(-1). Reduced plate height of 1.9 (95,000 plates m(-1)) can be achieved. The hybrid phase is stable for at least 3 months of usage and storage under typical HILIC eluents. Copyright © 2014 Elsevier B.V. All rights reserved.

Droplet Impact Onto A Flat Plate: Inclined Verses Moving Surfaces

NASA Astrophysics Data System (ADS)

Tsai, Scott; Bird, James C.; Stone, Howard A.

2008-11-01

Much research has been conducted on the impact of droplets normal to flat surfaces. However, very little research has been carried out on oblique impacts, even though they occur frequently in nature and industry. We experiment with the effects of tangential and normal impact velocities on the behavior of a droplet as it impacts a flat plate. The plate is inclined in the first case, and in the second case the plate is rotated via an electric motor. The asymmetric nature of the impact causes asymmetric splashing, such that under certain conditions only part of the rim splashes. Using a high-speed camera, we demonstrate that the splash threshold of inclined and moving surfaces are quantitatively similar, with only small differences. We also develop a phase diagram of splashing showing which phase occurs given a tangential and normal impact velocity. Such a phase diagram is useful for both engineering design and for the evaluation of splash-prediction models.

Induction of a global stress response during the first step of Escherichia coli plate growth.

PubMed

Cuny, Caroline; Lesbats, Maïalène; Dukan, Sam

2007-02-01

We have investigated the first events that occur when exponentially grown cells are transferred from a liquid medium (Luria-Bertani [LB]) to a solid medium (LB agar [LBA]). We observed an initial lag phase of 180 min for the wild type MG1655 without any apparent growth. This lack of growth was independent of the bacterial physiological state (either the stationary or the exponential phase), the solid medium composition, or the number of cells on the plate, but it was dependent on the bacterial genotype. Using lacZ-reporter fusions and two-dimensional electrophoresis analysis, we observed that when cells from exponential-phase cultures were plated on LBA, several global regulons, like heat shock regulons (RpoH, RpoE, CpxAR) and oxidative-stress regulons (SoxRS, OxyR, Fur), were immediately induced. Our results indicate that in order to grow on plates, bacteria must not only adapt to new conditions but also perceive a real stress.

Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development.

PubMed

Iliou, Katerina; Malenović, Anđelija; Loukas, Yannis L; Dotsikas, Yannis

2018-02-05

A novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (QbD) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted. The selected critical quality attributes (CQAs) were the separation criterion s between the critical peak pair and the capacity factor k of the last eluted compound. The effect of the following critical process parameters (CPPs) on the CQAs was studied: %ACN content, the pH and the concentration of the buffer salt in the mobile phase, as well as the stationary phase of the analytical column. D-Optimal design was implemented to set the plan of experiments with UV detector. In order to define the design space, Monte Carlo simulations with 5000 iterations were performed. Acceptance criteria were met for C 8 column (50×4mm, 5μm) , and the region having probability π≥95% to achieve satisfactory values of all defined CQAs was computed. The working point was selected with the mobile phase consisting ‎of ACN, ammonium formate 11mM at a ratio 31/69v/v with pH=6,8 for the water phase. The LC protocol was transferred to LC-MS/MS and validated according to ICH guidelines. Copyright © 2017 Elsevier B.V. All rights reserved.

Anticipated improvement in laser beam uniformity using distributed phase plates with quasirandom patterns

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

Epstein, R.; Skupsky, S.

1990-08-01

The uniformity of focused laser beams, that has been modified with randomly phased distributed phase plates (C. B. Burckhardt, Appl. Opt. {bold 9}, 695 (1970); Kato and Mima, Appl. Phys. B {bold 29}, 186 (1982); Kato {ital et} {ital al}., Phys. Rev. Lett. {bold 53}, 1057 (1984); LLE Rev. {bold 33}, 1 (1987)), can be improved further by constructing patterns of phase elements which minimize phase correlations over small separations. Long-wavelength nonuniformities in the intensity distribution, which are relatively difficult to overcome in the target by thermal smoothing and in the laser by, e.g., spectral dispersion (Skupsky {ital et} {italmore » al}., J. Appl. Phys. {bold 66}, 3456 (1989); LLE Rev. {bold 36}, 158 (1989); {bold 37}, 29 (1989); {bold 37}, 40 (1989)), result largely from short-range phase correlations between phase plate elements. To reduce the long-wavelength structure, we have constructed phase patterns with smaller short-range correlations than would occur randomly. Calculations show that long-wavelength nonuniformities in single-beam intensity patterns can be reduced with these masks when the intrinsic phase error of the beam falls below certain limits. We show the effect of this improvement on uniformity for spherical irradiation by a multibeam system.« less

Nondestructive Determination of Moisture Content in Dry Fruits by Impedance and Phase angle measurements

USDA-ARS?s Scientific Manuscript database

Impedance (Z), and phase angle (') of a cylindrical parallel-plate capacitor with dry fruits between the plates was measured using a CI meter (Chari’s Impedance meter), at 1 and 9 MHz . Capacitance, C was derived from Z and ', and using the C, ', and Z values of a set of cherries whose moisture con...

Screening the ToxCast Phase II library for acute neurotoxicity using cortical neurons grown on multi-well microelectrode array (mwMEA) plates

EPA Science Inventory

We have used primary cortical neurons grown in multi-well microelectrode array (mwMEA) plates to screen the ToxCast Phase II library of 1055 unique compounds for the ability to cause acute neurotoxicity. Each compound was screened at a single high concentration of 40 µM...

Effect of fringe-artifact correction on sub-tomogram averaging from Zernike phase-plate cryo-TEM

PubMed Central

Kishchenko, Gregory P.; Danev, Radostin; Fisher, Rebecca; He, Jie; Hsieh, Chyongere; Marko, Michael; Sui, Haixin

2015-01-01

Zernike phase-plate (ZPP) imaging greatly increases contrast in cryo-electron microscopy, however fringe artifacts appear in the images. A computational de-fringing method has been proposed, but it has not been widely employed, perhaps because the importance of de-fringing has not been clearly demonstrated. For testing purposes, we employed Zernike phase-plate imaging in a cryo-electron tomographic study of radial-spoke complexes attached to microtubule doublets. We found that the contrast enhancement by ZPP imaging made nonlinear denoising insensitive to the filtering parameters, such that simple low-frequency band-pass filtering made the same improvement in map quality. We employed sub-tomogram averaging, which compensates for the effect of the “missing wedge” and considerably improves map quality. We found that fringes (caused by the abrupt cut-on of the central hole in the phase plate) can lead to incorrect representation of a structure that is well-known from the literature. The expected structure was restored by amplitude scaling, as proposed in the literature. Our results show that de-fringing is an important part of image-processing for cryo-electron tomography of macromolecular complexes with ZPP imaging. PMID:26210582

Silver plating ensures reliable diffusion bonding of dissimilar metals

NASA Technical Reports Server (NTRS)

1967-01-01

Dissimilar metals are reliably joined by diffusion bonding when the surfaces are electroplated with silver. The process involves cleaning and etching, anodization, silver striking, and silver plating with a conventional plating bath. It minimizes the formation of detrimental intermetallic phases and provides greater tolerance of processing parameters.

Controls on rheology of peridotite at a palaeosubduction interface: a transect across the base of the Oman-UAE ophiolite

NASA Astrophysics Data System (ADS)

Ambrose, T. K.; Wallis, D.; Hansen, L. N.; Waters, D. J.; Searle, M. P.

2017-12-01

Studies of experimentally deformed rocks and small-scale natural shear zones have demonstrated that volumetrically minor phases can control strain localisation by limiting grain growth and promoting grain-size sensitive deformation mechanisms. Such studies are often used to infer a critical role for minor phases in the development of plate boundaries. However, the role of of minor phases in strain localisation at plate boundaries remains to be tested by direct observation. To test the hypothesis that minor phases control strain localisation at plate boundaries, we conducted microstructural analyses of peridotite samples collected across the base of the Oman-UAE ophiolite. The base of the ophiolite is marked by the Semail thrust, which represents the now exhumed contact between subducted oceanic crust and the overlying mantle wedge. As such, the base of the ophiolite provides the opportunity to directly examine a former plate boundary. Our results demonstrate that the mean olivine grain size is inversely proportional to the abundance of minor phases (primarily pyroxene), consistent with suppression of grain growth by grain-boundary pinning. Our results also reveal that mean olivine grain size is proportional to CPO strength, suggesting that the fraction of strain accommodated by different deformation mechanisms varied spatially. Experimentally-derived flow laws indicate that under the inferred deformation conditions the viscosity of olivine was grain-size sensitive. As such, grain size, and thereby the abundance of minor phases, influenced viscosity during subduction-related deformation along the base of the mantle wedge. We calculate that viscosity and strain rate respectively decrease and increase by approximately an order of magnitude towards the base of the ophiolite. Our data indicate that this rheological weakening was primarily the result of more abundant secondary phases near the base of the ophiolite. Our interpretations are consistent with those of previous studies on experimentally deformed rocks and smaller-scale natural shear zones that indicate minor phases can strongly influence strain localisation. However, our study demonstrates for the first time that minor phases can control strain localisation at the scale of a major plate boundary.

Intelligent "Peptide-Gathering Mechanical Arm" Tames Wild "Trojan-Horse" Peptides for the Controlled Delivery of Cancer Nanotherapeutics.

PubMed

Shi, Nian-Qiu; Li, Yan; Zhang, Yong; Shen, Nan; Qi, Ling; Wang, Shu-Ran; Qi, Xian-Rong

2017-12-06

Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R 9 -liposome-based cargo delivery for tumor targeting. The peptide NGR, serving as a cell-targeting peptide for anchoring, and peptide PLGLAG, serving as a substrate peptide for deanchoring, were embedded in the Int PMA motif. The Int PMA construct was designed to be sensitive to tumor microenvironmental stimuli, including aminopeptidase N (CD13) and matrix metalloproteinases (MMP-2/9). Moreover, Int PMA could be specifically recognized by tumor tissues via CD13-mediated anchoring and released for cell entry by MMP-2/9-mediated deanchoring. To test the Int PMA design, a series of experiments were conducted in vitro and in vivo. Functional conjugates Int PMA-R 9 -poly(ethylene glycol) (PEG) 2000 -distearoylphosphatidyl-ethanolamine (DSPE) and R 9 -PEG 2000 -DSPE were synthesized by Michael addition reaction and were characterized by thin-layer chromatography and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The Int PMA-R 9 -modified doxorubicin-loaded liposomes (Int PMA-R 9 -Lip-DOX) exhibited a proper particle diameter (approximately 155 nm) with in vitro sustained release characteristics. Cleavage assay showed that Int PMA-R 9 peptide molecules could be cleaved by MMP-2/9 for completion of deanchoring. Flow cytometry and confocal microscopy studies indicated that Int PMA-R 9 -Lip-DOX can respond to both endogenous and exogenous stimuli in the presence/absence of excess MMP-2/9 and MMP-2/9 inhibitor (GM6001) and effectively function under competitive receptor-binding conditions. Moreover, Int PMA-R 9 -Lip-DOX generated more significant subcellular dispersions that were especially evident within endoplasmic reticulum (ER) and Golgi apparatus. Notably, Int PMA-R 9 -Lip-DOX could induce enhanced apoptosis, during which caspase 3/7 might be activated. In addition, Int PMA-R 9 -Lip-DOX displayed enhanced in vitro and in vivo antitumor efficacy versus "wild" R 9 -Lip-DOX. On the basis of investigations at the molecular level, cellular level, and animals' level, the control of Int PMA was effective and promoted selective delivery of R 9 -liposome cargo to the target site and reduced nonspecific uptake. This Int PMA-controlled strategy based on aminopeptidase-guided anchoring and protease-triggered deanchoring effectively curbed the wildness of CPPs and bolstered their effectiveness for in vivo delivery of nanotherapeutics. The specific nanocarrier delivery system used here could be adapted using a variety of intelligent designs based on combinations of multifunctional peptides that would specifically and preferentially bind to tumors versus nontumor tissues for tumor-localized accumulation in vivo. Thus, CPPs have a strong advantage for the development of intelligent nanomedicines for targeted tumor therapy.

Effect of LPSO and SFs on microstructure evolution and mechanical properties of Mg-Gd-Y-Zn-Zr alloy

NASA Astrophysics Data System (ADS)

Xu, Chao; Nakata, Taiki; Qiao, Xiaoguang; Zheng, Mingyi; Wu, Kun; Kamado, Shigeharu

2017-01-01

High performance Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr alloy with high strength and excellent ductility has been successfully developed by hot extrusion. The effect of plate-shaped long period stacking ordered (LPSO) phases and solute-segregated stacking faults (SFs) on the dynamically recrystallization (DRX) behavior was analyzed. The plate-shaped LPSO phases stimulate the DRX by particle stimulated nucleation mechanism, leading to higher DRX ratio and weaker basal texture. While for the alloy with dense fine SFs inside the original grains, discontinuous DRX initially occurs at the original grain boundaries, and the DRX is obviously restricted. Consequently, alloy containing dense SFs exhibits higher strength but lower ductility compared with alloy with plated-shaped LPSO phases.

Effect of LPSO and SFs on microstructure evolution and mechanical properties of Mg-Gd-Y-Zn-Zr alloy

PubMed Central

Xu, Chao; Nakata, Taiki; Qiao, Xiaoguang; Zheng, Mingyi; Wu, Kun; Kamado, Shigeharu

2017-01-01

High performance Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr alloy with high strength and excellent ductility has been successfully developed by hot extrusion. The effect of plate-shaped long period stacking ordered (LPSO) phases and solute-segregated stacking faults (SFs) on the dynamically recrystallization (DRX) behavior was analyzed. The plate-shaped LPSO phases stimulate the DRX by particle stimulated nucleation mechanism, leading to higher DRX ratio and weaker basal texture. While for the alloy with dense fine SFs inside the original grains, discontinuous DRX initially occurs at the original grain boundaries, and the DRX is obviously restricted. Consequently, alloy containing dense SFs exhibits higher strength but lower ductility compared with alloy with plated-shaped LPSO phases. PMID:28134297

Plate Speed-up and Deceleration during Continental Rifting: Insights from Global 2D Mantle Convection Models.

NASA Astrophysics Data System (ADS)

Brune, S.; Ulvrova, M.; Williams, S.

2017-12-01

The surface of the Earth is divided into a jigsaw of tectonic plates, some carrrying continents that disperse and aggregate through time, forming transient supercontinents like Pangea and Rodinia. Here, we study continental rifting using large-scale numerical simulations with self-consistent evolution of plate boundaries, where continental break-up emerges spontaneously due to slab pull, basal drag and trench suction forces.We use the StagYY convection code employing a visco-plastic rheology in a spherical annulus geometry. We consider an incompressible mantle under the Boussinesq approximation that is basally and internally heated.We show that continental separation follows a characteristic evolution with three distinctive phases: (1) A pre-rift phase that typically lasts for several hundreds of millions of years with tectonic quiescence in the suture and extensional stresses that are slowly building up. (2) A rift phase that further divides into a slow rift period of several tens of millions of years where stresses continuously increase followed by a rift acceleration period featuring an abrupt stress drop within several millions of years. The speed-up takes place before lithospheric break-up and therefore affects the structural architecture of the rifted margins. (3) The drifting phase with initially high divergence rates persists over tens of millions of years until the system adjust to new conditions and the spreading typically slows down.By illustrating the geodynamic connection between subduction dynamics and rift evolution, our results allow new interpretations of plate tectonic reconstructions. Rift acceleration within the second phase of rifting is compensated by enhanced convergence rates at subduction zones. This model outcome predicts enhanced subduction velocities, e.g. between North America and the Farallon plate during Central Atlantic rifting 200 My ago, or closure of potential back-arc basins such as in the proto-Andean ranges of South America during South Atlantic opening. Post-rift deceleration occurs when the global plate system re-equilibrates after continental rupture. This phenomenon of a plate slow-down after mechanical rupture is recorded by observations from rifted margins between Australia-Antarctica and Greenland-Eurasia.

Observation of FeGe skyrmions by electron phase microscopy with hole-free phase plate

NASA Astrophysics Data System (ADS)

Kotani, Atsuhiro; Harada, Ken; Malac, Marek; Salomons, Mark; Hayashida, Misa; Mori, Shigeo

2018-05-01

We report application of hole-free phase plate (HFPP) to imaging of magnetic skyrmion lattices. Using HFPP imaging, we observed skyrmions in FeGe, and succeeded in obtaining phase contrast images that reflect the sample magnetization distribution. According to the Aharonov-Bohm effect, the electron phase is shifted by the magnetic flux due to sample magnetization. The differential processing of the intensity in a HFPP image allows us to successfully reconstruct the magnetization map of the skyrmion lattice. Furthermore, the calculated phase shift due to the magnetization of the thin film was consistent with that measured by electron holography experiment, which demonstrates that HFPP imaging can be utilized for analysis of magnetic fields and electrostatic potential distribution at the nanoscale.

Phase plate technology for laser marking of magnetic discs

DOEpatents

Neuman, B.; Honig, J.; Hackel, L.; Dane, C.B.; Dixit, S.

1998-10-27

An advanced design for a phase plate enables the distribution of spots in arbitrarily shaped patterns with very high uniformity and with a continuously or near-continuously varying phase pattern. A continuous phase pattern eliminates large phase jumps typically expected in a grating that provides arbitrary shapes. Large phase jumps increase scattered light outside of the desired pattern, reduce efficiency and can make the grating difficult to manufacture. When manufacturing capabilities preclude producing a fully continuous grating, the present design can be easily adapted to minimize manufacturing errors and maintain high efficiencies. This continuous grating is significantly more efficient than previously described Dammann gratings, offers much more flexibility in generating spot patterns and is easier to manufacture and replicate than a multi-level phase grating. 3 figs.

Optical Near-Field Plates

DTIC Science & Technology

2015-04-08

AFRL-OSR-VA-TR-2015-0085 OPTICAL NEAR-FILED PLATES Roberto Merlin UNIVERSITY OF MICHIGAN Final Report 04/08/2015 DISTRIBUTION A: Distribution...03-2015 Final 09/01/2009-12/31/2014 Optical Near-Field Plates FA9550-09-1-0636 erlin, Roberto, D. The University of Michigan Ann Arbor, MI 48109...distribution unlimited Optical near-field plates were designed using antisymmetric plasmon modes to generate abrupt phase changes within a fraction of a

Buckling behavior of long symmetrically laminated plates subjected to combined loadings

NASA Technical Reports Server (NTRS)

Nemeth, Michael P.

1992-01-01

A parametric study is presented of the buckling behavior of infinitely long, symmetrically laminated anisotropic plates subjected to combined loadings. The loading conditions considered are axial tension and compression transverse tension and compression, and shear. Results obtained using a special-purpose analysis, well-suited for parametric studies, are presented for clamped and simply supported plates. Moreover, results are presented for some common laminate constructions, and generic buckling design charts are presented for a wide range of parameters. The generic design charts are presented in terms of useful nondimensional parameters, and the dependence of the nondimensional parameters on laminate fiber orientation, stacking sequence, and material properties is discussed. An important finding of the study is that the effects of anisotropy are much more pronounced in shear-loaded plates than in compression-loaded plates. In addition, the effects of anisotropy on plates subjected to combined loadings are generally manifested as a phase shift of self-similar buckling interaction curves. A practical application of this phase shift is that the buckling resistance of long plates can be improved by applying a shear loading with a specific orientation. In all cases considered in the study, the buckling coefficients of infinitely long plates are found to be independent of the bending stiffness ratio (D sub 11/D sub 22)(1/4).

Buckling behavior of long symmetrically laminated plates subjected to combined loads

NASA Technical Reports Server (NTRS)

Nemeth, Michael P.

1992-01-01

A parametric study of the buckling behavior of infinitely long symmetrically laminated anisotropic plates subjected to combined loadings is presented. The loading conditions considered are axial tension and compression, transverse tension and compression, and shear. Results obtained using a special purpose analysis, well suited for parametric studies are presented for clamped and simply supported plates. Moreover, results are presented for some common laminate constructions, and generic buckling design charts are presented for a wide range of parameters. The generic design charts are presented in terms of useful nondimensional parameters, and dependence of the nondimensional parameters on laminate fiber orientation, stacking sequence, and material properties is discussed. An important finding of the study is that the effects of anisotropy are much more pronounced in shear-loaded plates than in compression loaded plates. In addition, the effects of anisotropy on plates subjected to combined loadings are generally manifested as a phase shift of self-similar buckling interaction curves. A practical application of this phase shift is the buckling resistance of long plates can be improved by applying a shear loading with a specific orientation. In all cases considered, it is found that the buckling coefficients of infinitely long plates are independent of the bending stiffness ratio (D sub 11/D sub 22) sup 1/4.

Phase III Advanced Anodes and Cathodes Utilized in Energy Efficient Aluminum Production Cells

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

R.A. Christini; R.K. Dawless; S.P. Ray

2001-11-05

During Phase I of the present program, Alcoa developed a commercial cell concept that has been estimated to save 30% of the energy required for aluminum smelting. Phase ii involved the construction of a pilot facility and operation of two pilots. Phase iii of the Advanced Anodes and Cathodes Program was aimed at bench experiments to permit the resolution of certain questions to be followed by three pilot cells. All of the milestones related to materials, in particular metal purity, were attained with distinct improvements over work in previous phases of the program. NiO additions to the ceramic phase andmore » Ag additions to the Cu metal phase of the cermet improved corrosion resistance sufficiently that the bench scale pencil anodes met the purity milestones. Some excellent metal purity results have been obtained with anodes of the following composition: Further improvements in anode material composition appear to be dependent on a better understanding of oxide solubilities in molten cryolite. For that reason, work was commissioned with an outside consultant to model the MeO - cryolite systems. That work has led to a better understanding of which oxides can be used to substitute into the NiO-Fe2O3 ceramic phase to stabilize the ferrites and reduce their solubility in molten cryolite. An extensive number of vertical plate bench electrolysis cells were run to try to find conditions where high current efficiencies could be attained. TiB2-G plates were very inconsistent and led to poor wetting and drainage. Pure TiB2 did produce good current efficiencies at small overlaps (shadowing) between the anodes and cathodes. This bench work with vertical plate anodes and cathodes reinforced the importance of good cathode wetting to attain high current efficiencies. Because of those conclusions, new wetting work was commissioned and became a major component of the research during the third year of Phase III. While significant progress was made in several areas, much work needs to be done. The anode composition needs further improvements to attain commercial purity targets. At the present corrosion rate, the vertical plate anodes will wear too rapidly leading to a rapidly increasing anode-cathode gap and thermal instabilities in the cell. Cathode wetting as a function of both cathode plate composition and bath composition needs to be better understood to ensure that complete drainage of the molten aluminum off the plates occurs. Metal buildup appears to lead to back reaction and low current efficiencies.« less

Dynamic High-Pressure Behavior of Hierarchical Heterogeneous Geological Materials

DTIC Science & Technology

2016-04-01

sandwiched between two 25µm FEP copolymer layers attached to the copper driver plate . The total package thickness with thin-film epoxy on all bonding...public release. 3 OUTLINE Page # ABSTRACT 2 1. BACKGROUND 4 2. CHARACTERISTICS OF SAND INVESTIGATED 8 3. PLATE ...constituents, phases, inter-phase boundaries ; distributions in shock states; as well as the structural evolutions which can result in strain

Novel Structured Metal Bipolar Plates for Low Cost Manufacturing

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

Wang, Conghua

2013-08-15

Bipolar plates are an important component in fuel cell stacks and accounts for more than 75% of stack weight and volume, and 20% of the stack cost. The technology development of metal bipolar plates can effectively reduce the fuel cells stack weight and volume over 50%. The challenge is to protect metal plate from corrosion at low cost for the broad commercial applications. While most of today’s PEM fuel cell metallic bipolar plate technologies use some precious metal, the focus of this SBIR project is to develop a low cost, novel nano-structured metal bipolar plate technology without using any preciousmore » metal. The technology will meet the performance and cost requirements for automobile applications. Through the Phase I project, TreadStone has identified the corrosion resistant and electrically conductive titanium oxide for the metal bipolar plate surface protection for automotive PEM fuel cell applications. TreadStone has overcome the manufacturing issues to apply the coating on metal substrate surface, and has demonstrated the feasibility of the coated stainless steel plates by ex-situ evaluation tests and the in-situ fuel cell long term durability test. The test results show the feasibility of the proposed nano-structured coating as the low cost metal bipolar plates of PEM fuel cells. The plan for further technology optimization is also outlined for the Phase II project.« less

DETERMINING MOTOR INERTIA OF A STRESS-CONTROLLED RHEOMETER.

PubMed

Klemuk, Sarah A; Titze, Ingo R

2009-01-01

Viscoelastic measurements made with a stress-controlled rheometer are affected by system inertia. Of all contributors to system inertia, motor inertia is the largest. Its value is usually determined empirically and precision is rarely if ever specified. Inertia uncertainty has negligible effects on rheologic measurements below the coupled motor/plate/sample resonant frequency. But above the resonant frequency, G' values of soft viscoelastic materials such as dispersions, gels, biomaterials, and non-Newtonian polymers, err quadratically due to inertia uncertainty. In the present investigation, valid rheologic measurements were achieved near and above the coupled resonant frequency for a non-Newtonian reference material. At these elevated frequencies, accuracy in motor inertia is critical. Here we compare two methods for determining motor-inertia accurately. For the first (commercially-used) phase method, frequency responses of standard fluids were measured. Phase between G' and G" was analyzed at 5-70 Hz for motor inertia values of 50-150% of the manufacturer's nominal value. For a newly-devised two-plate method (10 mm and 60 mm parallel plates), dynamic measurements of a non-Newtonian standard were collected. Using a linear equation of motion with inertia, viscosity, and elasticity coefficients, G' expressions for both plates were equated and motor inertia was determined to be accurate (by comparison to the phase method) with a precision of ± 3%. The newly developed two-plate method had advantages of expressly eliminating dependence on gap, was explicitly derived from basic principles, quantified the error, and required fewer experiments than the commercially used phase method.

Generation of plate tectonics with two-phase grain-damage and pinning: Source-sink model and toroidal flow

NASA Astrophysics Data System (ADS)

Bercovici, David; Ricard, Yanick

2013-03-01

The grain-damage and pinning mechanism of Bercovici and Ricard (2012) for lithospheric shear-localization is employed in two-dimensional flow calculations to test its ability to generate toroidal (strike-slip) motion and influence plate evolution. This mechanism posits that damage to the interface between phases in a polycrystalline material like peridotite (composed primarily of olivine and pyroxene) increases the number of small Zener pinning surfaces, which then constrain mineral grains to ever smaller sizes, regardless of creep mechanism. This effect allows a self-softening feedback in which damage and grain-reduction can co-exist with a grain-size dependent diffusion creep rheology; moreover, grain growth and weak-zone healing are greatly impeded by Zener pinning thereby leading to long-lived relic weak zones. The fluid dynamical calculations employ source-sink driven flow as a proxy for convective poloidal flow (upwelling/downwelling and divergent/convergent motion), and the coupling of this flow with non-linear rheological mechanisms excites toroidal or strike-slip motion. The numerical experiments show that pure dislocation-creep rheology, and grain-damage without Zener pinning (as occurs in a single-phase assemblages) permit only weak localization and toroidal flow; however, the full grain-damage with pinning readily allows focussed localization and intense, plate-like toroidal motion and strike-slip deformation. Rapid plate motion changes are also tested with abrupt rotations of the source-sink field after a plate-like configuration is developed; the post-rotation flow and material property fields retain memory of the original configuration for extensive periods, leading to suboptimally aligned plate boundaries (e.g., strike-slip margins non-parallel to plate motion), oblique subduction, and highly localized, weak and long lived acute plate-boundary junctions such as at what is observed at the Aleutian-Kurile intersection. The grain-damage and pinning theory therefore readily satisfies key plate-tectonic metrics of localized toroidal motion and plate-boundary inheritance, and thus provides a predictive theory for the generation of plate tectonics on Earth and other planets.

Generation of plate tectonics via grain-damage and pinning

NASA Astrophysics Data System (ADS)

Bercovici, D.; Ricard, Y. R.

2012-12-01

Weakening and shear localization in the lithosphere are essential ingredients for understanding how and whether plate tectonics is generated from mantle convection on terrestrial planets. The grain-damage and pinning mechanism of Bercovici & Ricard (2012) for lithospheric shear--localization proposes that damage to the interface between phases in a polycrystalline material like peridotite (composed primarily of olivine and pyroxene) increases the number of small Zener pinning surfaces that constrain mineral grains to ever smaller sizes regardless of creep mechanism. This effect allows a self-softening feedback in which damage and grain-reduction can co-exist with a grain-size dependent diffusion creep rheology; moreoever, grain growth and weak-zone healing are greatly impeded by Zener pinning thereby leading to long-lived relic weak zones. This mechanism is employed in two-dimensional flow calculations to test its ability to generate toroidal (strike-slip) motion from convective type flow and to influence plate evolution. The fluid dynamical calculations employ source-sink driven flow as a proxy for convective poloidal flow (upwelling/downwelling and divergent/convergent motion), and the coupling of this flow with non-linear rheological mechanisms excites toroidal or strike-slip motion. The numerical experiments show that pure dislocation-creep rheology, and grain-damage without Zener pinning (as occurs in a single-phase assemblages) permit only weak localization and toroidal flow; however, the full grain-damage with pinning readily allows focussed localization and intense, plate-like toroidal motion and strike-slip deformation. Rapid plate motion changes are also tested with abrupt rotations of the source-sink field after a plate-like configuration is developed; the post-rotation flow and material property fields are found to never recover or lose memory of the original configuration, leading to suboptimally aligned plate boundaries (e.g., strike-slip margins non-parallel to plate motion), oblique subduction and highly localized, weak and long lived acute plate-boundary junctions such as at the Aleution-Kurile intersection. The grain-damage and pinning theory therefore readily satisfies key plate-tectonic metrics of localized toroidal motion and plate-boundary inheritance, and thus provides a predictive theory for the generation of plate tectonics on Earth and other planets. References: Bercovici, D., Ricard, Y., 2012. Mechanisms for the generation of plate tectonics by two-phase grain-damage and pinning. Phys. Earth Planet. Int. 202-203, 27--55.

Plate Kinematic model of the NW Indian Ocean and derived regional stress history of the East African Margin

NASA Astrophysics Data System (ADS)

Tuck-Martin, Amy; Adam, Jürgen; Eagles, Graeme

2015-04-01

Starting with the break up of Gondwana, the northwest Indian Ocean and its continental margins in Madagascar, East Africa and western India formed by divergence of the African and Indian plates and were shaped by a complicated sequence of plate boundary relocations, ridge propagation events, and the independent movement of the Seychelles microplate. As a result, attempts to reconcile the different plate-tectonic components and processes into a coherent kinematic model have so far been unsatisfactory. A new high-resolution plate kinematic model has been produced in an attempt to solve these problems, using seafloor spreading data and rotation parameters generated by a mixture of visual fitting of magnetic isochron data and iterative joint inversion of magnetic isochron and fracture zone data. Using plate motion vectors and plate boundary geometries derived from this model, the first-order regional stress pattern was modelled for distinct phases of margin formation. The stress pattern is correlated with the tectono-stratigraphic history of related sedimentary basins. The plate kinematic model identifies three phases of spreading, from the Jurassic to the Paleogene, which resulted in the formation of three main oceanic basins. Prior to these phases, intracontinental 'Karoo' rifting episodes in the late Carboniferous to late Triassic had failed to break up Gondwana, but initiated the formation of sedimentary basins along the East African and West Madagascan margins. At the start of the first phase of spreading (183 to 133 Ma) predominantly NW - SE extension caused continental rifting that separated Madagascar/India/Antarctica from Africa. Maximum horizontal stresses trended perpendicular to the local plate-kinematic vector, and parallel to the rift axes. During and after continental break-up and subsequent spreading, the regional stress regime changed drastically. The extensional stress regime became restricted to the active spreading ridges that in turn adopted trends normal to the plate divergence vector. Away from the active ridges, compressional horizontal stresses caused by ridge-push forces were transmitted through the subsiding oceanic lithosphere, with an SH max orientation parallel to plate divergence vectors. These changes are documented by the lower Bajocian continental breakup unconformity, which can be traced throughout East African basins. At 133 Ma, the plate boundary moved from north to south of Madagascar, incorporating it into the African plate and initiating its separation from Antarctica. The orientation of the plate divergence vector however did not change markedly. The second phase (89 - 61 Ma) led to the separation of India from Madagascar, initiating a new and dramatic change in stress orientation from N-S to ENE-WSW. This led to renewed tectonic activity in the sedimentary basins of western Madagascar. In the third phase (61 Ma to present) asymmetric spreading of the Carlsberg Ridge separated India from the Seychelles and the Mascarene Plateau via the southward propagation of the Carlsberg Ridge to form the Central Indian Ridge. The anti-clockwise rotation of the independent Seychelles microplate between chrons 28n (64.13 Ma) and 26n (58.38 Ma) and the opening of the short-lived Laxmi Basin (67 Ma to abandonment within chron 28n (64.13 - 63.10 Ma)) have been further constrained by the new plate kinematic model. Along the East African margin, SH max remained in a NE - SW orientation and the sedimentary basins experienced continued thick, deep water sediment deposition. Contemporaneously, in the sedimentary basins along East African passive margin, ridge-push related maximum horizontal stresses became progressively outweighed by local gravity-driven NE-SW maximum horizontal stresses trending parallel to the margin. These stress regimes are caused by sediment loading and extensional collapse of thick sediment wedges, predominantly controlled by margin geometry. Our study successfully integrates an interpretation of paleo-stress regimes constrained by the new high resolution plate kinematic and basin history to produce a margin scale tectono-stratigraphic framework that highlights the important interplay of plate boundary forces and basin formation events along the East African margin.

Controls on the T Phase Energy Fluxes Recorded on Juan Fernandez Island by Continental Seismic Wave Paths and Nazca Bathymetry

NASA Astrophysics Data System (ADS)

Sáez, Miguel; Ruiz, Sergio

2018-03-01

T phases from 54 South American earthquakes with Mw > 5.2 are observed at a broadband station on Juan Fernandez Island. We computed the T phase energy flux (TPEF) values of the seismograms. The TPEF values show a large dispersion that can be explained by considering the tectonic characteristics of the South American plate and the Nazca plate bathymetry. The TPEFs generated by the 2015 Illapel and 2017 Valparaíso seismic sequences were controlled by the positions of the interface events along the dip. The central and downdip interplate earthquakes were more efficient in the generation of T phases than the near-trench interplate earthquakes (depths of <15 km). The variations in the generation efficiency with depth are explained by the continental raypaths of the body waves and the incidence angles of waves entering the sound fixing and ranging channel. Additionally, we observed differences in the TPEFs from both earthquake sequences that were controlled by seamounts atop the Nazca plate along the T phase paths.

Heat Pipe Planets

NASA Astrophysics Data System (ADS)

Moore, W. B.; Simon, J. I.

2018-05-01

We propose that cooling via volcanic heat pipes may provide a universal model of the way terrestrial bodies transition from a magma-ocean state into subsequent single-plate, stagnant-lid convection or plate tectonic phases.

Shed vortex structure and phase-averaged velocity statistics in symmetric/asymmetric turbulent flat plate wakes

NASA Astrophysics Data System (ADS)

Rai, Man Mohan

2018-05-01

The near wake of a flat plate is investigated via direct numerical simulations. Many earlier experimental investigations have used thin plates with sharp trailing edges and turbulent boundary layers to create the wake. This results in large θ/DTE values (θ is the boundary layer momentum thickness toward the end of the plate and DTE is the trailing edge thickness). In the present study, the emphasis is on relatively thick plates with circular trailing edges (CTEs) resulting in θ/D values less than one (D is the plate thickness and the diameter of the CTE) and vigorous vortex shedding. The Reynolds numbers based on the plate length and D are 1.255 × 106 and 10 000, respectively. Two cases are computed: one with turbulent boundary layers on both the upper and lower surfaces of the plate (statistically the same, symmetric wake, Case TT) and the other with turbulent and laminar boundary layers on the upper and lower surfaces, respectively (asymmetric case, Case TL). The data and understanding obtained are of considerable engineering interest, particularly in turbomachinery where the pressure side of an airfoil can remain laminar or transitional because of a favorable pressure gradient and the suction side is turbulent. Shed-vortex structure and phase-averaged velocity statistics obtained in the two cases are compared here. The upper negative shed vortices in Case TL (turbulent separating boundary layer) are weaker than the lower positive ones (laminar separating boundary layer) at inception (a factor of 1.27 weaker in terms of peak phase-averaged spanwise vorticity at the first appearance of a peak). The upper vortices weaken rapidly as they travel downstream. A second feature of interest in Case TL is a considerable increase in the peak phase-averaged, streamwise normal intensity (random component) with increasing streamwise distance (x/D) that occurs near the positive vortex cores. This behavior is observed for a few diameters in the near wake. This is counter to Case TT where the peak value essentially decreases with increasing x/D. Both these effects are examined in detail, and the important contributors are identified.

Large-field high-contrast hard x-ray Zernike phase-contrast nano-imaging beamline at Pohang Light Source.

PubMed

Lim, Jun; Park, So Yeong; Huang, Jung Yun; Han, Sung Mi; Kim, Hong-Tae

2013-01-01

We developed an off-axis-illuminated zone-plate-based hard x-ray Zernike phase-contrast microscope beamline at Pohang Light Source. Owing to condenser optics-free and off-axis illumination, a large field of view was achieved. The pinhole-type Zernike phase plate affords high-contrast images of a cell with minimal artifacts such as the shade-off and halo effects. The setup, including the optics and the alignment, is simple and easy, and allows faster and easier imaging of large bio-samples.

Plate-tectonic boundary formation by grain-damage and pinning

NASA Astrophysics Data System (ADS)

Bercovici, David

2015-04-01

Shear weakening in the lithosphere is an essential ingredient for understanding how and why plate tectonics is generated from mantle convection on terrestrial planets. I present continued work on a theoretical model for lithospheric shear-localization and plate generation through damage, grain evolution and Zener pinning in two-phase (polycrystalline) lithospheric rocks. Grain size evolves through the competition between coarsening, which drives grain-growth, with damage, which drives grain reduction. The interface between phases controls Zener pinning, which impedes grain growth. Damage to the interface enhances the Zener pinning effect, which then reduces grain-size, forcing the rheology into the grain-size-dependent diffusion creep regime. This process thus allows damage and rheological weakening to co-exist, providing a necessary shear-localizing feedback. Moreover, because pinning inhibits grain-growth it promotes shear-zone longevity and plate-boundary inheritance. This theory has been applied recently to the emergence of plate tectonics in the Archean by transient subduction and accumulation of plate boundaries over 1Gyr, as well as to rapid slab detachment and abrupt tectonic changes. New work explores the saturation of interface damage at low interface curvature (e.g., because it is associated with larger grains that take up more of the damage, and/or because interface area is reduced). This effect allows three possible equilibrium grain-sizes for a given stress; a small-grain-size high-shear state in diffusion creep, a large grain-size low shear state in dislocation creep, and an intermediate state (often near the deformation map phase-boundary). The low and high grain-size states are stable, while the intermediate one is unstable. This implies that a material deformed at a given stress can acquire two stable deformation regimes, a low- and high- shear state; these are indicative of plate-like flows, i.e, the coexistence of both slowly deforming plates and rapidly deforming plate boundaries.

Morphology and structure of borides in as-cast titanium and gamma-titanium aluminide-based alloys

NASA Astrophysics Data System (ADS)

Kitkamthorn, Usanee

In this study, the morphology and structure of the borides in boron-modified Ti- and gamma-TiAl-based alloys have been investigated using SEM, TEM, and HRTEM. A variety of different boride morphologies was observed including plates, needles, and ribbons. For the plate and needle borides, the major boride phase is B27 TiB. The needle borides have their major axis parallel to [010], and are bounded by (100) and {101} type-facets. The plate borides develop the same types of facets as the needles and have habit planes parallel to the (100). There are high densities of intrinsic stacking faults on (100) in these borides and these correspond to thin embedded layers of the Bf structure. The plate borides do not exhibit well-defined ORs with respect to the surrounding phases, suggesting that they develop in the liquid melt and were then trapped by the growing solid. Needle borides are observed mostly at boundaries between lamellar colonies: these needles tend to occur in groups lying nearly parallel to one another and, in some cases, to adopt well-defined ORs with respect to the surrounding phases. Cored borides with metallic phases such as beta, alpha, o and alpha 2+gamma in the center are frequently observed, especially in the Ti-based alloy. These core phases usually adopt well-defined ORs with respect to the surrounding boride which enable low-energy coherent interfaces to form between the phases. The ribbon borides are comprised of thin boride flakes interspersed with thin metallic layers. The major boride phase in these flakes is Bf TiB. The habit plane of the flakes is (010) and there are high densities of faults on this plane corresponding to intergrowths of the Ti3B 4 and TiB2 phases, together with thin layers or occluded pockets of metallic B2 phase. Occasional faults are observed on {110} corresponding to embedded slabs of B27 TiB. There is a well-defined OR between the boride flakes and the B2 phase within the ribbons, but not with the surrounding matrix. The characteristics of these various borides are consistent with them forming as eutectic reaction products, with the exception of the finest needles and plates observed in Ti-based alloy.

Note: Measurement of synchrotron radiation phase-space beam properties to verify astigmatism compensation in Fresnel zone plate focusing optics

NASA Astrophysics Data System (ADS)

Kagoshima, Yasushi; Miyagawa, Takamasa; Kagawa, Saki; Takeda, Shingo; Takano, Hidekazu

2017-08-01

The intensity distribution in phase space of an X-ray synchrotron radiation beamline was measured using a pinhole camera method, in order to verify astigmatism compensation by a Fresnel zone plate focusing optical system. The beamline is equipped with a silicon double crystal monochromator. The beam size and divergence at an arbitrary distance were estimated. It was found that the virtual source point was largely different between the vertical and horizontal directions, which is probably caused by thermal distortion of the monochromator crystal. The result is consistent with our astigmatism compensation by inclining a Fresnel zone plate.

Chemically and compositionally modified solid solution disordered multiphase nickel hydroxide positive electrode for alkaline rechargeable electrochemical cells

DOEpatents

Ovshinsky, Stanford R.; Corrigan, Dennis; Venkatesan, Srini; Young, Rosa; Fierro, Christian; Fetcenko, Michael A.

1994-01-01

A high capacity, long cycle life positive electrode for use in an alkaline rechargeable electrochemical cell comprising: a solid solution nickel hydroxide material having a multiphase structure that comprises at least one polycrystalline .gamma.-phase including a polycrystalline .gamma.-phase unit cell comprising spacedly disposed plates with at least one chemical modifier incorporated around the plates, the plates having a range of stable intersheet distances corresponding to a 2.sup.+ oxidation state and a 3.5.sup.+, or greater, oxidation state; and at least one compositional modifier incorporated into the solid solution nickel hydroxide material to promote the multiphase structure.

Formation of III–V ternary solid solutions on GaAs and GaSb plates via solid-phase substitution reactions

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

Vasil’ev, V. I.; Gagis, G. S., E-mail: galina.gagis@gmail.com; Kuchinskii, V. I.

2015-07-15

Processes are considered in which ultrathin layers of III–V ternary solid solutions are formed via the delivery of Group-V element vapors to GaAs and GaSb semiconductor plates, with solid-phase substitution reactions occurring in the surface layers of these plates. This method can form defect-free GaAs{sup 1–x}P{sup x}, GaAs{sup x}Sb{sup 1–x}, and GaP{sup x}Sb{sup 1–x} layers with thicknesses of 10–20 nm and a content x of the embedded components of up to 0.04.

Numerical and experimental simulation of linear shear piezoelectric phased arrays for structural health monitoring

NASA Astrophysics Data System (ADS)

Wang, Wentao; Zhang, Hui; Lynch, Jerome P.; Cesnik, Carlos E. S.; Li, Hui

2017-04-01

A novel d36-type piezoelectric wafer fabricated from lead magnesium niobate-lead titanate (PMN-PT) is explored for the generation of in-plane horizontal shear waves in plate structures. The study focuses on the development of a linear phased array (PA) of PMN-PT wafers to improve the damage detection capabilities of a structural health monitoring (SHM) system. An attractive property of in-plane horizontal shear waves is that they are nondispersive yet sensitive to damage. This study characterizes the directionality of body waves (Lamb and horizontal shear) created by a single PMN-PT wafer bonded to the surface of a metallic plate structure. Second, a linear PA is designed from PMN-PT wafers to steer and focus Lamb and horizontal shear waves in a plate structure. Numerical studies are conducted to explore the capabilities of a PMN-PT-based PA to detect damage in aluminum plates. Numerical simulations are conducted using the Local Interaction Simulation Approach (LISA) implemented on a parallelized graphical processing unit (GPU) for high-speed execution. Numerical studies are further validated using experimental tests conducted with a linear PA. The study confirms the ability of an PMN-PT phased array to accurately detect and localize damage in aluminum plates.

Development of zinc-plated regenerator material

NASA Astrophysics Data System (ADS)

Y Xu, M.; Morie, T.; Tsuchiya, A.

2017-12-01

An effective way to improve the efficiency of a cryocooler is to improve the efficiency of the regenerator. In general, the heat capacity of materials decreases as temperature decreases. Thus, when temperature is below 40 K, lead or bismuth spheres are often used as regenerator materials. However, the pressure drop in a sphere regenerator is much larger than that in a screen regenerator. To overcome this dilemma, Xu et al. reported that cooling performance at the temperature of less than 40 K was improved when using tin-plated screens at the cold end of the regenerator. However, the reliability of tin at low temperatures is still not verified fully because of its phase transition from a normal β phase to an abnormal α phase, which may result in a significant reduction of the mechanical strength. In this paper, a zinc-plated screen is proposed as another potential alternative. A comparison test was performed with a two-stage GM cryocooler by replacing part of the first stage regenerator material, phosphorus bronze screens, with zinc-plated screens. Compared to a regenerator filled with bronze screens, the cooling capacity of the first stage increased by about 11% at 40 K and 60% at 30 K with these zinc-plated screens. The detailed experimental results are reported in this paper.

Carrier-envelope phase control by a composite plate.

PubMed

Ell, Richard; Birge, Jonathan R; Araghchini, Mohammad; Kärtner, Franz X

2006-06-12

We demonstrate a new concept to vary the carrier-envelope phase of a mode-locked laser by a composite plate while keeping all other pulse parameters practically unaltered. The effect is verified externally in an interferometric autocorrelator, as well as inside the cavity of an octave-spanning femtosecond oscillator. The carrier-envelope frequency can be shifted by half the repetition rate with negligible impact on pulse spectrum and energy.

Biological applications of phase-contrast electron microscopy.

PubMed

Nagayama, Kuniaki

2014-01-01

Here, I review the principles and applications of phase-contrast electron microscopy using phase plates. First, I develop the principle of phase contrast based on a minimal model of microscopy, introducing a double Fourier-transform process to mathematically formulate the image formation. Next, I explain four phase-contrast (PC) schemes, defocus PC, Zernike PC, Hilbert differential contrast, and schlieren optics, as image-filtering processes in the context of the minimal model, with particular emphases on the Zernike PC and corresponding Zernike phase plates. Finally, I review applications of Zernike PC cryo-electron microscopy to biological systems such as protein molecules, virus particles, and cells, including single-particle analysis to delineate three-dimensional (3D) structures of protein and virus particles and cryo-electron tomography to reconstruct 3D images of complex protein systems and cells.

Effect of microstructure of superalloy guide plate on its surface wear resistance

NASA Astrophysics Data System (ADS)

Zhou, Jianbo; Zhang, Xizhen

2018-03-01

The microstructure had been observed for guide plate, the guide plate be made of casting for groove controlling of hot rolled seamless tube, be produced for the production of 1600 seamless steel pipe,which cause obvious surface deformation and can not be normally produced. The alloy elements in matrix and precipitate phase of the guide plate were analyzed with the help of EDS. The results show that the wear resistance of the guide plate is directly affected by the fact that the guide plate is unable to form typical carbides, it shows that the formation of typical carbide strengthening plays an important role in improving the surface wear resistance of the guide plate.

Thin-layer chromatography and colorimetric analysis of multi-component explosive mixtures

DOEpatents

Pagoria, Philip F.; Mitchell, Alexander R.; Whipple, Richard E.; Carman, M. Leslie

2014-08-26

A thin-layer chromatography method for detection and identification of common military and peroxide explosives in samples includes the steps of provide a reverse-phase thin-layer chromatography plate; prepare the plate by marking spots on which to deposit the samples by touching the plate with a marker; spot one micro liter of a first standard onto one of the spots, spot one micro liter of a second standard onto another of the spots, and spot samples onto other of spots producing a spotted plate; add eluent to a developing chamber; add the spotted plate to the developing chamber; remove the spotted plate from the developing chamber producing a developed plate; place the developed plate in an ultraviolet light box; add a visualization agent to a dip tank; dip the developed plate in the dip tank and remove the developed plate quickly; and detect explosives by viewing said developed plate.

Axial dispersion, holdup and slip velocity of dispersed phase in a pulsed sieve plate extraction column by radiotracer residence time distribution analysis.

PubMed

Din, Ghiyas Ud; Chughtai, Imran Rafiq; Inayat, Mansoor Hameed; Khan, Iqbal Hussain

2008-12-01

Axial dispersion, holdup and slip velocity of dispersed phase have been investigated for a range of dispersed and continuous phase superficial velocities in a pulsed sieve plate extraction column using radiotracer residence time distribution (RTD) analysis. Axial dispersion model (ADM) was used to simulate the hydrodynamics of the system. It has been observed that increase in dispersed phase superficial velocity results in a decrease in its axial dispersion and increase in its slip velocity while its holdup increases till a maximum asymptotic value is achieved. An increase in superficial velocity of continuous phase increases the axial dispersion and holdup of dispersed phase until a maximum value is obtained, while slip velocity of dispersed phase is found to decrease in the beginning and then it increases with increase in superficial velocity of continuous phase.

Poly-arginine and arginine-rich peptides are neuroprotective in stroke models

PubMed Central

Meloni, Bruno P; Brookes, Laura M; Clark, Vince W; Cross, Jane L; Edwards, Adam B; Anderton, Ryan S; Hopkins, Richard M; Hoffmann, Katrin; Knuckey, Neville W

2015-01-01

Using cortical neuronal cultures and glutamic acid excitotoxicity and oxygen-glucose deprivation (OGD) stroke models, we demonstrated that poly-arginine and arginine-rich cell-penetrating peptides (CPPs), are highly neuroprotective, with efficacy increasing with increasing arginine content, have the capacity to reduce glutamic acid-induced neuronal calcium influx and require heparan sulfate preotoglycan-mediated endocytosis to induce a neuroprotective effect. Furthermore, neuroprotection could be induced with immediate peptide treatment or treatment up to 2 to 4 hours before glutamic acid excitotoxicity or OGD, and with poly-arginine-9 (R9) when administered intravenously after stroke onset in a rat model. In contrast, the JNKI-1 peptide when fused to the (non-arginine) kFGF CPP, which does not rely on endocytosis for uptake, was not neuroprotective in the glutamic acid model; the kFGF peptide was also ineffective. Similarly, positively charged poly-lysine-10 (K10) and R9 fused to the negatively charged poly-glutamic acid-9 (E9) peptide (R9/E9) displayed minimal neuroprotection after excitotoxicity. These results indicate that peptide positive charge and arginine residues are critical for neuroprotection, and have led us to hypothesize that peptide-induced endocytic internalization of ion channels is a potential mechanism of action. The findings also question the mode of action of different neuroprotective peptides fused to arginine-rich CPPs. PMID:25669902

A quality by design approach using artificial intelligence techniques to control the critical quality attributes of ramipril tablets manufactured by wet granulation.

PubMed

Aksu, Buket; Paradkar, Anant; de Matas, Marcel; Özer, Özgen; Güneri, Tamer; York, Peter

2013-02-01

Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

31P Solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

PubMed Central

Desai, Pinaki R.; Cormier, Ashley R.; Shah, Punit P.; Patlolla, Ram R.; Paravastu, Anant K.; Singh, Mandip

2013-01-01

The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11 and YKA) through skin intercellular lipids using 31P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, sections (0–60, 61–120 and 121–180 µm) were collected and analyzed for 31P NMR signal. The concentration dependent shift of 0, 25, 50, 100 and 200 mg/ml of TAT on skin layers, diffusion of TAT, R8, R11 and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using 31P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in 31P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180 µm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, 31P solid-state NMR can be used to track CPP penetration into different skin layers. PMID:23702274

Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo

PubMed Central

EL Andaloussi, Samir; Lehto, Taavi; Mäger, Imre; Rosenthal-Aizman, Katri; Oprea, Iulian I.; Simonson, Oscar E.; Sork, Helena; Ezzat, Kariem; Copolovici, Dana M.; Kurrikoff, Kaido; Viola, Joana R.; Zaghloul, Eman M.; Sillard, Rannar; Johansson, Henrik J.; Said Hassane, Fatouma; Guterstam, Peter; Suhorutšenko, Julia; Moreno, Pedro M. D.; Oskolkov, Nikita; Hälldin, Jonas; Tedebark, Ulf; Metspalu, Andres; Lebleu, Bernard; Lehtiö, Janne; Smith, C. I. Edvard; Langel, Ülo

2011-01-01

While small interfering RNAs (siRNAs) have been rapidly appreciated to silence genes, efficient and non-toxic vectors for primary cells and for systemic in vivo delivery are lacking. Several siRNA-delivery vehicles, including cell-penetrating peptides (CPPs), have been developed but their utility is often restricted by entrapment following endocytosis. Hence, developing CPPs that promote endosomal escape is a prerequisite for successful siRNA implementation. We here present a novel CPP, PepFect 6 (PF6), comprising the previously reported stearyl-TP10 peptide, having pH titratable trifluoromethylquinoline moieties covalently incorporated to facilitate endosomal release. Stable PF6/siRNA nanoparticles enter entire cell populations and rapidly promote endosomal escape, resulting in robust RNAi responses in various cell types (including primary cells), with minimal associated transcriptomic or proteomic changes. Furthermore, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by serum proteins. Finally, these nanoparticles promote strong RNAi responses in different organs following systemic delivery in mice without any associated toxicity. Strikingly, similar knockdown in liver is achieved by PF6/siRNA nanoparticles and siRNA injected by hydrodynamic infusion, a golden standard technique for liver transfection. These results imply that the peptide, in addition to having utility for RNAi screens in vitro, displays therapeutic potential. PMID:21245043

Evidence of structural invariance across three groups of Meehlian schizotypes

PubMed Central

Chan, Raymond CK; Gooding, Diane C; Shi, Hai-song; Geng, Fu-lei; Xie, Dong-jie; Yang, Zhuo-Ya; Liu, Wen-hua; Wang, Yi; Yan, Chao; Shi, Chuan; Lui, Simon SY; Cheung, Eric FC

2016-01-01

According to Meehl’s model of schizotypy, there is a latent personality organization associated with the diathesis for schizophrenia that can be identified in several ways. We sought to examine the structural invariance of four Chapman psychosis–proneness scales (CPPS) across three groups of putative schizotypes, namely, clinically-, biologically-, and psychometrically-identified schizotypes. We examined the factor structure of the Perceptual Aberration (PER), Magical Ideation (MIS), Revised Social Anhedonia (RSAS), and Revised Physical Anhedonia (RPAS) scales in 196 schizophrenia patients, 197 non-psychotic first-degree relatives, and 1,724 non-clinical young adults. The confirmatory factor analyses indicated that the best-fitting model was one in which there is a two-factor model with negative schizotypy (RSAS and RPAS) and positive schizotypy (PER and MIS). All three samples fit the model well, with Comparative Fit Indices>0.95 and Tucker Lewis Indices>0.90. The root mean square error of approximations were all small (P values⩽0.01). We also observed that for both anhedonia scales, the groups’ mean scale scores varied in the hypothesized direction, as predicted by Meehl’s model of schizotypy. All three Chinese samples, namely, the patients (clinical schizotypes), relatives (biologically-identified schizotypes), and non-clinical young adults (containing psychometrically-identified schizotypes) showed the same factorial structure. This finding supports the suitability of the CPPS for cross-cultural and/or genetic investigations of schizotypy. PMID:27336057

Method of ultrasonic measurement of texture

DOEpatents

Thompson, R. Bruce; Smith, John F.; Lee, Seung S.; Li, Yan

1993-10-12

A method for measuring texture of metal plates or sheets using non-destructive ultrasonic investigation includes measuring the velocity of ultrasonic energy waves in lower order plate modes in one or more directions, and measuring phase velocity dispersion of higher order modes of the plate or sheet if needed. Texture or preferred grain orientation can be derived from these measurements with improves reliability and accuracy. The method can be utilized in production on moving metal plate or sheet.

Semi-automatic for ultrasonic measurement of texture

DOEpatents

Thompson, R. Bruce; Smith, John F.; Lee, Seung S.; Li, Yan

1990-02-13

A method for measuring texture of metal plates or sheets using non-destructive ultrasonic investigation includes measuring the velocity of ultrasonic energy waves in lower order plate modes in one or more directions, and measuring phase velocity dispersion of higher order modes of the plate or sheet if needed. Texture or preferred grain orientation can be derived from these measurements with improved reliability and accuracy. The method can be utilized in production on moving metal plate or sheet.

Method of ultrasonic measurement of texture

DOEpatents

Thompson, R.B.; Smith, J.F.; Lee, S.S.; Taejon Ch'ungmam; Yan Li.

1993-10-12

A method for measuring texture of metal plates or sheets using non-destructive ultrasonic investigation includes measuring the velocity of ultrasonic energy waves in lower order plate modes in one or more directions, and measuring phase velocity dispersion of higher order modes of the plate or sheet if needed. Texture or preferred grain orientation can be derived from these measurements with improves reliability and accuracy. The method can be utilized in production on moving metal plate or sheet. 9 figures.

Semi-automatic for ultrasonic measurement of texture

DOEpatents

Thompson, R.B.; Smith, J.F.; Lee, S.S.; Li, Y.

1990-02-13

A method for measuring texture of metal plates or sheets using non-destructive ultrasonic investigation includes measuring the velocity of ultrasonic energy waves in lower order plate modes in one or more directions, and measuring phase velocity dispersion of higher order modes of the plate or sheet if needed. Texture or preferred grain orientation can be derived from these measurements with improved reliability and accuracy. The method can be utilized in production on moving metal plate or sheet. 9 figs.

Controls on the rheological properties of peridotite at a palaeosubduction interface: A transect across the base of the Oman-UAE ophiolite

NASA Astrophysics Data System (ADS)

Ambrose, Tyler K.; Wallis, David; Hansen, Lars N.; Waters, Dave J.; Searle, Michael P.

2018-06-01

Studies of experimentally deformed rocks and small-scale natural shear zones have demonstrated that volumetrically minor phases can control strain localisation by limiting grain growth and promoting grain-size sensitive deformation mechanisms. These small-scale studies are often used to infer a critical role for minor phases in the development of plate boundaries. However, the role of minor phases in strain localisation at an actual plate boundary remains to be tested by direct observation. In order to test the hypothesis that minor phases control strain localisation at plate boundaries, we conducted microstructural analyses of peridotite samples collected along a ∼1 km transect across the base of the Oman-United Arab Emirates (UAE) ophiolite. The base of the ophiolite is marked by the Semail thrust, which represents the now exhumed contact between subducted oceanic crust and the overlying mantle wedge. As such, the base of the ophiolite provides the opportunity to directly examine a former plate boundary. Our results demonstrate that the mean olivine grain size is inversely proportional to the abundance of minor phases (primarily orthopyroxene, as well as clinopyroxene, hornblende, and spinel), consistent with suppression of grain growth by grain-boundary pinning. Our results also reveal that mean olivine grain size is proportional to CPO strength (both of which generally decrease towards the metamorphic sole), suggesting that the fraction of strain produced by different deformation mechanisms varied spatially. Experimentally-derived flow laws indicate that under the inferred deformation conditions, the viscosity of olivine was grain-size sensitive. As such, grain size, and thereby the abundance of minor phases, influenced viscosity during subduction-related deformation along the base of the mantle wedge. We calculate an order of magnitude decrease in the viscosity of olivine towards the base of the ophiolite, which suggests strain was localised near the subduction interface. Our data indicate that this rheological weakening was primarily the result of more abundant minor phases near the base of the ophiolite. Our interpretations are consistent with those of previous studies on experimentally deformed rocks and smaller-scale natural shear zones that indicate minor phases can exert the primary control on strain localisation. However, our study demonstrates for the first time that minor phases can control strain localisation at the scales relevant to a major plate boundary.

Method of increasing the phase stability and the compressive yield strength of uranium-1 to 3 wt. % zirconium alloy

DOEpatents

Anderson, Robert C.

1986-01-01

A uranium-1 to 3 wt. % zirconium alloy characterized by high strength, high ductility and stable microstructure is fabricated by an improved thermal mechanical process. A homogenous ingot of the alloy which has been reduced in thickness of at least 50% in the two-step forging operation, rolled into a plate with a 75% reduction and then heated in vacuum at a temperature of about 750.degree. to 850.degree. C. and then quenched in water is subjected to further thermal-mechanical operation steps to increase the compressive yield strength approximately 30%, stabilize the microstructure, and decrease the variations in mechanical properties throughout the plate is provided. These thermal-mechanical steps are achieved by cold rolling the quenched plate to reduce the thickness thereof about 8 to 12%, aging the cold rolled plate at a first temperature of about 325.degree. to 375.degree. C. for five to six hours and then aging the plate at a higher temperature ranging from 480.degree. to 500.degree. C. for five to six hours prior to cooling the billet to ambient conditions and sizing the billet or plate into articles provides the desired increase in mechanical properties and phase stability throughout the plate.

A Mach-Zehnder interferometer based on orbital angular momentum for improved vortex coronagraph efficiency

NASA Astrophysics Data System (ADS)

Piron, P.; Delacroix, C.; Huby, E.; Mawet, D.; Karlsson, M.; Ruane, G.; Habraken, S.; Absil, O.; Surdej, J.

2015-09-01

The Annular Groove Phase Mask (AGPM) is a vectorial vortex phase mask. It acts as a half-wave plate with a radial fast axis orientation operating in the mid infrared domain. When placed at the focus of a telescope element provides a continuous helical phase ramp for an on axis sources, which creates the orbital angular momentum. Thanks to that phase, the intensity of the central source is canceled by a down-stream pupil stop, while the off axis sources are not affected. However due to experimental conditions the nulling is hardly perfect. To improve the null, a Mach-Zehnder interferometer containing Dove prisms differently oriented can be proposed to sort out light based on its orbital angular momentum (OAM). Thanks to the differential rotation of the beam, a π phase shift is achieved for the on axis light affected by a non zero OAM. Therefore the contrast between the star and its faint companion is enhanced. Nevertheless, due the Dove prisms birefringence, the performance of the interferometer is relatively poor. To solve this problem, we propose to add a birefringent wave-plate in each arm to compensate this birefringence. In this paper, we will develop the mathematical model of the wave front using the Jones formalism. The performance of the interferometer is at first computed for the simple version without the birefringent plate. Then the effect of the birefringent plate is be mathematically described and the performance is re-computed.

Hydrodynamics of bacterial colonies: Phase diagrams

NASA Astrophysics Data System (ADS)

Lega, J.; Passot, T.

2004-09-01

We present numerical simulations of a recent hydrodynamic model describing the growth of bacterial colonies on agar plates. We show that this model is able to qualitatively reproduce experimentally observed phase diagrams, which relate a colony shape to the initial quantity of nutrients on the plate and the initial wetness of the agar. We also discuss the principal features resulting from the interplay between hydrodynamic motions and colony growth, as described by our model.

Low Energy Consumption Hydraulic Techniques

DTIC Science & Technology

1988-08-30

usually at welds . 1-15 SECTION II PHASE I - ADVANCED AIRCRAFT HYDRAULIC SYSTEM SELECTION Phase I included Task 1 selection of the aircraft and definition...face was bronze plated. The bearings were 52100 tool steel and the pistons were M50 tool steel. The shoe faces were 4140 with bronze plate and the back...o Magnet assembly o Coil assembly DDV Force Motor - -- ,..._(First Stage) oeMain Control Valve __(Second Sae Main Control Valve LVDT Figure 282 Direct

An optical system with aberrations on diffraction integrals written in terms of a generalized ABCD matrix

NASA Astrophysics Data System (ADS)

Zhao, Chaoying; Tan, Weihan

2008-12-01

: In this paper, we consider the transformation of a ray beam as it passes through an optical system containing a glass plate with parallel surfaces inclined to the optical axis at the Brewster’s angle, by investigating the effects of the optical system on amplitude and phase distributions. By applying generalized matrix optics and diffraction integrals and considering the influence of a quarter of a wavelength of aberration on the transmitted amplitude and phase distributions at the focus of a de-collimating lens, we find that the central peak amplitude descends from 1.0 to 0.8 and the phase distortion is less than π/2. The general feature of the amplitude distribution shows an elongation along the y-axis perpendicular to the optical axis in the direction of tilt of the inclined plate, and conforms to the inclination direction of the glass plate.

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

Aoki, Sadao; Namikawa, Tadahiro; Hoshino, Masato

A Zernike-type phase contrast hard X-ray microscope was constructed at the Photon Factory BL3C2 (KEK). A white beam from a bending magnet was monochromatized by a silicon double crystal monochromator. Monochromatic parallel X-ray beam illuminated a sample, and transmitted and diffracted X-ray beams were imaged by a Fresnel zone plate (FZP) which had the outer zone width of 100 nm. A phase plate made of a thin aluminum foil with a pinhole was set at the back focal plane of the FZP. The phase plate modulated the diffraction beam from the FZP, whereas a direct beam passed through the pinhole.more » The resolution of the microscope was measured by observing a tantalum test pattern at an X-ray energy of 9 keV. A 100nm line-and-space pattern could be resolved. X-ray montage pictures of growing eggs of artemia (plankton) were obtained.« less

LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Measurement of optical absorption in polycrystalline CVD diamond plates by the phase photothermal method at a wavelength of 10.6 μm

NASA Astrophysics Data System (ADS)

Luk'yanov, A. Yu; Ral'chenko, Viktor G.; Khomich, A. V.; Serdtsev, E. V.; Volkov, P. V.; Savel'ev, A. V.; Konov, Vitalii I.

2008-12-01

A highly-efficient phase photothermal method is developed for quantitative measurements of the small optical absorption coefficient in thin plates made of highly transparent materials in which bulk losses significantly exceed surface losses. The bulk absorption coefficient at 10.6 μm is estimated in polycrystalline diamond plates grown from the vapour phase (a CVD diamond). The results are compared with those for natural and synthetic diamond single crystals and with the concentrations of nitrogen and hydrogen impurities. The absorption coefficient of the best samples of the CVD diamond did not exceed 0.06 cm-1, which, taking into account the high thermal conductivity of the CVD diamond (1800-2200 W mK-1 at room temperature), makes this material attractive for fabricating output windows of high-power CO2 lasers, especially for manufacturing large-size optics.

Near wall effects on flexible splitter plate behind a cylinder

NASA Astrophysics Data System (ADS)

Venkat Narayanan, K.; Vengadesan, S.; Murali, K.

2017-11-01

Vortex induced vibrations(VIV) of a rigid circular cylinder with a flexible plate attached to its rear end, close to the plane wall is numerically studied for Re = 200. Amplitude modulations were observed in the response of the flexible plate at the ground distance of G/D=0.5. Numerical simulations were conducted for a range of reduced velocities Ur(3,4,5 and 6), which appropriately captures the synchronization range of VIV of the structure. At Ur=3 there is no significant amplitude modulation. As Ur is increased further, the modulation appears. The modulation appears symmetric about the peak amplitude for successive cycles at Ur=4. The phase plots of lift coefficient CL and plate tip displacement revealed the change in sign of energy transfer between the plate and the wake. Amplitude modulation is reflected in the interaction of shed vortices and the plane wall. Shed vortices are convected parallel to the wall when the amplitude of the plate rises to its local maximum during modulation. During the growth and damping phase of the amplitudes in each modulation cycle, the vortex shedding is observed to be oblique towards the wall.

Method for preparing surfaces of metal composites having a brittle phase for plating. [Patent application

DOEpatents

Coates, C.W.; Wilson, T.J.

1982-05-19

The present invention is directed to a method for preparing surfaces of two-phase metal composites having relatively brittle and malleable components for plating with corrosion-resistant material. In practice of the present invention, the surfaces of the composite are etched to remove a major portion or fraction of the brittle component. The etched surface is then peened with particulates for breaking the brittle component from the surfaces and for spreading or smearing the malleable component over the surfaces. The peened surface is then chemically cleaned of residual traces of the brittle component to which the corrosion-resistant material may be plated thereon in an adherent manner.

Method for measuring retardation of infrared wave-plate by modulated-polarized visible light

NASA Astrophysics Data System (ADS)

Zhang, Ying; Song, Feijun

2012-11-01

A new method for precisely measuring the optical phase retardation of wave-plates in the infrared spectral region is presented by using modulated-polarized visible light. An electro-optic modulator is used to accurately determine the zero point by the frequency-doubled signal of the Modulated-polarized light. A Babinet-Soleil compensator is employed to make the phase delay compensation. Based on this method, an instrument is set up to measure the retardations of the infrared wave-plates with visible region laser. Measurement results with high accuracy and sound repetition are obtained by simple calculation. Its measurement precision is less than and repetitive precision is within 0.3%.

License plate recognition (phase B).

DOT National Transportation Integrated Search

2010-06-01

License Plate Recognition (LPR) technology has been used for off-line automobile enforcement purposes. The technology has seen mixed success with correct reading rate as high as 60 to 80% depending on the specific application and environment. This li...

Anomalous heat transport and condensation in convection of cryogenic helium

PubMed Central

Urban, Pavel; Schmoranzer, David; Hanzelka, Pavel; Sreenivasan, Katepalli R.; Skrbek, Ladislav

2013-01-01

When a hot body A is thermally connected to a cold body B, the textbook knowledge is that heat flows from A to B. Here, we describe the opposite case in which heat flows from a colder but constantly heated body B to a hotter but constantly cooled body A through a two-phase liquid–vapor system. Specifically, we provide experimental evidence that heat flows through liquid and vapor phases of cryogenic helium from the constantly heated, but cooler, bottom plate of a Rayleigh–Bénard convection cell to its hotter, but constantly cooled, top plate. The bottom plate is heated uniformly, and the top plate is cooled by heat exchange with liquid helium maintained at 4.2 K. Additionally, for certain experimental conditions, a rain of helium droplets is detected by small sensors placed in the cell at about one-half of its height. PMID:23576759

Failure of composite plates under static biaxial planar loading

NASA Technical Reports Server (NTRS)

Waas, Anthony M.; Khamseh, Amir R.

1992-01-01

The project involved detailed investigations into the failure mechanisms in composite plates as a function of hole size (holes centrally located in the plates) under static loading. There were two phases to the project, the first dealing with uniaxial loads along the fiber direction, and the second dealing with coplanar biaxial loading. Results for the uniaxial tests have been reported and published previously, thus this report will place emphasis on the second phase of the project, namely the biaxial tests. The composite plates used in the biaxial loading experiments, as well as the uniaxial, were composed of a single ply unidirectional graphite/epoxy prepreg sandwiched between two layers of transparent thermoplastic. This setup enabled us to examine the failure initiation and propagation modes nondestructively, during the test. Currently, similar tests and analysis of results are in progress for graphite/epoxy cruciform shaped flat laminates. The results obtained from these tests will be available at a later time.

Llinas’ Phase Reset Mechanism Delays the Onset of Chaos in Shark and Dolphin Wall Turbulence

DTIC Science & Technology

2014-02-10

eruption due to plate tectonics . (The plate becomes locally thin and is unable to prevent the high-pressure hot magma from erupting.) The vorticity...flat plate value. The spacing between riblet peaks s+= 10 is used unless noted. KM gives the "strength" of the riblets, where the terms "weak" and...exhibit spanwise variations in skin friction coefficients and integral boundary layer properties, even in flat plate experiments where great care has

Nondestructive testing of CFRP plates by Lamb waves

NASA Astrophysics Data System (ADS)

Tsushima, Satoshi; Fukiage, Norio; Ono, Masao

1993-03-01

Nondestructive testing based on low frequency Lamb waves was used to analyze the thickness of plates, the delamination, the fiber contents, and the wave velocities in composite laminates. The thickness of plates was predicted and the delamination was detected using the relationship between the phase velocities of Lamb waves and the product of frequency and plate thickness. The fiber content was predicted from the stationary waves, and the wave velocity propagating at an angle to the fiber direction was calculated using the Young's modulus.

Spiraling Light with Magnetic Metamaterial Quarter-Wave Turbines.

PubMed

Zeng, Jinwei; Luk, Ting S; Gao, Jie; Yang, Xiaodong

2017-09-19

Miniaturized quarter-wave plate devices empower spin to orbital angular momentum conversion and vector polarization formation, which serve as bridges connecting conventional optical beam and structured light. Enabling the manipulability of additional dimensions as the complex polarization and phase of light, quarter-wave plate devices are essential for exploring a plethora of applications based on orbital angular momentum or vector polarization, such as optical sensing, holography, and communication. Here we propose and demonstrate the magnetic metamaterial quarter-wave turbines at visible wavelength to produce radially and azimuthally polarized vector vortices from circularly polarized incident beam. The magnetic metamaterials function excellently as quarter-wave plates at single wavelength and maintain the quarter-wave phase retardation in broadband, while the turbine blades consist of multiple polar sections, each of which contains homogeneously oriented magnetic metamaterial gratings near azimuthal or radial directions to effectively convert circular polarization to linear polarization and induce phase shift under Pancharatnum-Berry's phase principle. The perspective concept of multiple polar sections of magnetic metamaterials can extend to other analogous designs in the strongly coupled nanostructures to accomplish many types of light phase-polarization manipulation and structured light conversion in the desired manner.

Electron paramagnetic resonance field-modulation eddy-current analysis of silver-plated graphite resonators

NASA Astrophysics Data System (ADS)

Mett, Richard R.; Anderson, James R.; Sidabras, Jason W.; Hyde, James S.

2005-09-01

Magnetic field modulation is often introduced into a cylindrical TE011 electron paramagnetic resonance (EPR) cavity through silver plating over a nonconductive substrate. The plating thickness must be many times the skin depth of the rf and smaller than the skin depth of the modulation. We derive a parameter that quantifies the modulation field penetration and find that it also depends on resonator dimensions. Design criteria based on this parameter are presented graphically. This parameter is then used to predict the behavior of eddy currents in substrates of moderate conductivity, such as graphite. The conductivity of the graphite permits improved plating uniformity and permits use of electric discharge machining (EDM) techniques to make the resonator. EDM offers precision tolerances of 0.005 mm and is suitable for small, complicated shapes that are difficult to machine by other methods. Analytic predictions of the modulation penetration are compared with the results of finite-element simulations. Simulated magnetic field modulation uniformity and penetration are shown for several elemental coils and structures including the plated graphite TE011 cavity. Fabrication and experimental testing of the structure are discussed. Spatial inhomogeneity of the modulation phase is also investigated by computer simulation. We find that the modulation phase is uniform to within 1% over the TE011 cavity. Structures of lower symmetry have increased phase nonuniformity.

Broadband Achromatic Phase Shifter for a Nulling Interferometer

NASA Technical Reports Server (NTRS)

Bolcar, Matthew R.; Lyon, Richard G.

2011-01-01

Nulling interferometry is a technique for imaging exoplanets in which light from the parent star is suppressed using destructive interference. Light from the star is divided into two beams and a phase shift of radians is introduced into one of the beams. When the beams are recombined, they destructively interfere to produce a deep null. For monochromatic light, this is implemented by introducing an optical path difference (OPD) between the two beams equal to lambda/2, where lambda is the wavelength of the light. For broadband light, however, a different phase shift will be introduced at each wavelength and the two beams will not effectively null when recombined. Various techniques have been devised to introduce an achromatic phase shift a phase shift that is uniform across a particular bandwidth. One popular technique is to use a series of dispersive elements to introduce a wavelength-dependent optical path in one or both of the arms of the interferometer. By intelligently choosing the number, material and thickness of a series of glass plates, a nearly uniform, arbitrary phase shift can be introduced between two arms of an interferometer. There are several constraints that make choosing the number, type, and thickness of materials a difficult problem, such as the size of the bandwidth to be nulled. Several solutions have been found for bandwidths on the order of 20 to 30 percent (Delta(lambda)/lambda(sub c)) in the mid-infrared region. However, uniform phase shifts over a larger bandwidth in the visible regime between 480 to 960 nm (67 percent) remain difficult to obtain at the tolerances necessary for exoplanet detection. A configuration of 10 dispersive glass plates was developed to be used as an achromatic phase shifter in nulling interferometry. Five glass plates were placed in each arm of the interferometer and an additional vacuum distance was also included in the second arm of the interferometer. This configuration creates a phase shift of pi radians with an average error of 5.97 x 10(exp -8) radians and standard deviation of 3.07 x 10(exp -4) radians. To reduce ghost reflections and interference effects from neighboring elements, the glass plates are tilted such that the beam does not strike each plate at normal incidence. Reflections will therefore walk out of the system and not contribute to the intensity when the beams are recombined. Tilting the glass plates, however, introduces several other problems that must be mitigated: (1) the polarization of a beam changes when refracted at an interface at non-normal incidence; (2) the beam experiences lateral chromatic spread as it traverses multiple glass plates; (3) at each surface, wavelength- dependent intensity losses will occur due to reflection. For a fixed angle of incidence, each of these effects must be balanced between each arm of the interferometer in order to ensure a deep null. The solution was found using a nonlinear optimization routine that minimized an objective function relating phase shift, intensity difference, chromatic beam spread, and polarization difference to the desired parameters: glass plate material and thickness. In addition to providing a uniform, broadband phase shift, the configuration achieves an average difference in intensity transmission between the two arms of the interferometer of 0.016 percent with a standard deviation of 3.64 x 10(exp -4) percent, an average difference in polarization between the two arms of the interferometer of 5.47 x 10(exp -5) percent with a standard deviation of 1.57 x 10(exp -6) percent, and an average chromatic beam shift between the two arms of the interferometer of -47.53 microns with a wavelength-by-wavelength spread of 0.389 microns.

Shed Vortex Structure and Phase-Averaged Velocity Statistics in Symmetric/Asymmetric Turbulent Flat Plate Wakes

NASA Technical Reports Server (NTRS)

Rai, Man Mohan

2017-01-01

The near wake of a flat plate is investigated via direct numerical simulations (DNS). Many earlier experimental investigations have used thin plates with sharp trailing edges and turbulent boundary layers to create the wake. This results in large theta divided by D (sub TE) values (theta is the boundary layer momentum thickness towards the end of the plate and D (sub TE) is the trailing edge thickness). In the present study the emphasis is on relatively thick plates with circular trailing edges (CTE) resulting in theta divided by D values less than one (D is the plate thickness and the diameter of the CTE), and vigorous vortex shedding. The Reynolds numbers based on the plate length and D are 1.255 x 10 (sup 6) and 10,000, respectively. Two cases are computed; one with turbulent boundary layers on both the upper and lower surfaces of the plate (statistically the same, symmetric wake, Case TT) and, a second with turbulent and laminar boundary layers on the upper and lower surfaces, respectively (asymmetric case, Case TL). The data and understanding obtained is of considerable engineering interest, particularly in turbomachinery where the pressure side of an airfoil can remain laminar or transitional because of a favorable pressure gradient and the suction side is turbulent. Shed-vortex structure and phase-averaged velocity statistics obtained in the two cases are compared here. The upper negative shed vortices in Case TL (turbulent separating boundary layer) are weaker than the lower positive ones (laminar separating boundary layer) at inception (a factor 1.27 weaker in terms of peak phase-averaged spanwise vorticity at first appearance of a peak). The upper vortices weaken rapidly as they travel downstream. A second feature of interest in Case TL is a considerable increase in the peak phase-averaged, streamwise normal intensity (random component) with increasing streamwise distance (x divided by D) that occurs nears the positive vortex cores. This behavior is observed for a few diameters in the near wake. This is counter to Case TT where the peak value essentially decreases with increasing x divided by D. Both these effects are examined in detail and the important contributors are identified.

Two-dimensional noncontact transportation of small objects in air using flexural vibration of a plate.

PubMed

Kashima, Ryota; Koyama, Daisuke; Matsukawa, Mami

2015-12-01

This paper investigates a two-dimensional ultrasonic manipulation technique for small objects in air. The ultrasonic levitation system consists of a rectangular vibrating plate with four ultrasonic transducers and a reflector. The configuration of the vibrator, the resonant frequency, and the positions of the four transducers with step horns were determined from finite element analysis such that an intense acoustic standing-wave field could be generated between the plates. A lattice flexural vibration mode with a wavelength of 28.3 mm was excited on the prototype plate at 24.6 kHz. Small objects could get trapped in air along the horizontal nodal plane of the standing wave. By controlling the driving phase difference between the transducers, trapped objects could be transported without contact in a two-dimensional plane. When the phase difference was changed from 0° to 720°, the distance moved by a small particle in the orthogonal direction was approximately 29 mm, which corresponds with the wavelength of the flexural vibration on the vibrating plate.

Improvement of a stability-indicating method by Quality-by-Design versus Quality-by-Testing: a case of a learning process.

PubMed

Hubert, C; Lebrun, P; Houari, S; Ziemons, E; Rozet, E; Hubert, Ph

2014-01-01

The understanding of the method is a major concern when developing a stability-indicating method and even more so when dealing with impurity assays from complex matrices. In the presented case study, a Quality-by-Design approach was applied in order to optimize a routinely used method. An analytical issue occurring at the last stage of a long-term stability study involving unexpected impurities perturbing the monitoring of characterized impurities needed to be resolved. A compliant Quality-by-Design (QbD) methodology based on a Design of Experiments (DoE) approach was evaluated within the framework of a Liquid Chromatography (LC) method. This approach allows the investigation of Critical Process Parameters (CPPs), which have an impact on Critical Quality Attributes (CQAs) and, consequently, on LC selectivity. Using polynomial regression response modeling as well as Monte Carlo simulations for error propagation, Design Space (DS) was computed in order to determine robust working conditions for the developed stability-indicating method. This QbD compliant development was conducted in two phases allowing the use of the Design Space knowledge acquired during the first phase to define the experimental domain of the second phase, which constitutes a learning process. The selected working condition was then fully validated using accuracy profiles based on statistical tolerance intervals in order to evaluate the reliability of the results generated by this LC/ESI-MS stability-indicating method. A comparison was made between the traditional Quality-by-Testing (QbT) approach and the QbD strategy, highlighting the benefit of this QbD strategy in the case of an unexpected impurities issue. On this basis, the advantages of a systematic use of the QbD methodology were discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Cretaceous to present kinematics of the Indian, African and Seychelles plates

NASA Astrophysics Data System (ADS)

Eagles, Graeme; Hoang, Ha H.

2014-01-01

An iterative inverse model of seafloor spreading data from the Mascarene and Madagascar basins and the flanks of the Carlsberg Ridge describes a continuous history of Indian-African Plate divergence since 84 Ma. Visual-fit modelling of conjugate magnetic anomaly data from near the Seychelles platform and Laxmi Ridge documents rapid rotation of a Seychelles Plate about a nearby Euler pole in Palaeocene times. As the Euler pole migrated during this rotation, the Amirante Trench on the western side of the plate accommodated first convergence and later divergence with the African Plate. The unusual present-day morphology of the Amirante Trench and neighbouring Amirante Banks can be related to crustal thickening by thrusting and folding during the convergent phase and the subsequent development of a spreading centre with a median valley during the divergent phase. The model fits FZ trends in the north Arabian and east Somali basins, suggesting that they formed in India-Africa Plate divergence. Seafloor fabric in and between the basins shows that they initially hosted a segmented spreading ridge that accommodated slow plate divergence until 71-69 Ma, and that upon arrival of the Deccan-Réunion plume and an increase to faster plate divergence rates in the period 69-65 Ma, segments of the ridge lengthened and propagated. Ridge propagation into the Indian continental margin led first to the formation of the Laxmi Basin, which accompanied extensive volcanism onshore at the Deccan Traps and offshore at the Saurashtra High and Somnath Ridge. A second propagation episode initiated the ancestral Carlsberg Ridge at which Seychelles-India and India-Africa Plate motions were accommodated. With the completion of this propagation, the plate boundaries in the Mascarene Basin were abandoned. Seafloor spreading between this time and the present has been accommodated solely at the Carlsberg Ridge.

Extracting and focusing of surface plasmon polaritons inside finite asymmetric metal/insulator/metal structure at apex of optical fiber by subwavelength holes

NASA Astrophysics Data System (ADS)

Oshikane, Yasushi; Murai, Kensuke; Nakano, Motohiro

2013-09-01

We have been studied a finite asymmetric metal-insulator-metal (MIM) structure on glass plate for near-future visible light communication (VLC) system with white LED illuminations in the living space (DOI: 10.1117/12.929201). The metal layers are vacuum-evaporated thin silver (Ag) films (around 50 nm and 200 nm, respectively), and the insulator layer (around 150 nm) is composed of magnesium fluoride (MgF2). A characteristic narrow band filtering of the MIM structure at visible region might cause a confinement of intense surface plasmon polaritons (SPPs) at specific monochromatic frequency inside a subwavelength insulator layer of the MIM structure. Central wavelength and depth of such absorption dip in flat spectral reflectance curve is controlled by changing thicknesses of both insulator and thinner metal layers. On the other hand, we have proposed a twin-hole pass-through wave guide for SPPs in thick Ag film (DOI: 10.1117/12.863587). At that time, the twin-hole converted a incoming plane light wave into a pair of channel plasmon polaritons (CPPs), and united them at rear surface of the Ag film. This research is having an eye to extract, guide, and focus the SPPs through a thicker metal layer of the MIM with FIBed subwavelength pass-through holes. The expected outcome is a creation of noble, monochromatic, and tunable fiber probe for scanning near-field optical microscopes (SNOMs) with intense white light sources. Basic experimental and FEM simulation results will be presented.

Delamination Detection Using Guided Wave Phased Arrays

NASA Technical Reports Server (NTRS)

Tian, Zhenhua; Yu, Lingyu; Leckey, Cara

2016-01-01

This paper presents a method for detecting multiple delaminations in composite laminates using non-contact phased arrays. The phased arrays are implemented with a non-contact scanning laser Doppler vibrometer (SLDV). The array imaging algorithm is performed in the frequency domain where both the guided wave dispersion effect and direction dependent wave properties are considered. By using the non-contact SLDV array with a frequency domain imaging algorithm, an intensity image of the composite plate can be generated for delamination detection. For the proof of concept, a laboratory test is performed using a non-contact phased array to detect two delaminations (created through quasi-static impact test) at different locations in a composite plate. Using the non-contact phased array and frequency domain imaging, the two impact-induced delaminations are successfully detected. This study shows that the non-contact phased array method is a potentially effective method for rapid delamination inspection in large composite structures.

Phase 2 of the array automated assembly task for the low cost silicon solar array project

NASA Technical Reports Server (NTRS)

Petersen, R. C.

1980-01-01

Studies were conducted on several fundamental aspects of electroless nickel/solder metallization for silicon solar cells. A process, which precedes the electroless nickel plating with several steps of palladium plating and heat treatment, was compared directly with single step electroless nickel plating. Work was directed toward answering specific questions concerning the effect of silicon surface oxide on nickel plating, effects of thermal stresses on the metallization, sintering of nickel plated on silicon, and effects of exposure to the plating solution on solar cell characteristics. The process was found to be extremely lengthy and cumbersome, and was also found to produce a product virtually identical to that produced by single step electroless nickel plating, as shown by adhesion tests and electrical characteristics of cells under illumination.

Method for preparing surfaces of metal composites having a brittle phase for plating

DOEpatents

Coates, Cameron W.; Wilson, Thomas J.

1984-01-01

The present invention is directed to a method for preparing surfaces of two-phase metal composites having relatively brittle and malleable components for plating with corrosion-resistant material. In practice of the present invention, the surfaces of the composites are etched to remove a major portion or fraction of the brittle component. The etched surface is then peened with particulates for breaking the brittle component from the surfaces and for spreading or smearing the malleable component over the surfaces. The peened surface is then chemically cleaned of residual traces of the brittle component so as to provide a surface of essentially the malleable component to which the corrosion-resistant material may be plated thereon in an adherent manner.

TIME CALIBRATED OSCILLOSCOPE SWEEP CIRCUIT

DOEpatents

Smith, V.L.; Carstensen, H.K.

1959-11-24

An improved time calibrated sweep circuit is presented, which extends the range of usefulness of conventional oscilloscopes as utilized for time calibrated display applications in accordance with U. S. Patent No. 2,832,002. Principal novelty resides in the provision of a pair of separate signal paths, each of which is phase and amplitude adjustable, to connect a high-frequency calibration oscillator to the output of a sawtooth generator also connected to the respective horizontal deflection plates of an oscilloscope cathode ray tube. The amplitude and phase of the calibration oscillator signals in the two signal paths are adjusted to balance out feedthrough currents capacitively coupled at high frequencies of the calibration oscillator from each horizontal deflection plate to the vertical plates of the cathode ray tube.

Design of continuous surface-relief phase plates by surface-based simulated annealing to achieve control of focal-plane irradiance

NASA Astrophysics Data System (ADS)

Lin, Y.; Kessler, T. J.; Lawrence, G. N.

1996-10-01

High-performance phase plates are of vital concern for controlling the far-field irradiance of laser-fusion systems. Several designs for solving this difficult problem have been reported in Optics Letters [e. g., S. N. Dixit et al., Opt. Lett. 19, 417 (1994)]. We report a surface-based form of simulated annealing that significantly improves the irradiance control while eliminating the high-scatter problems that have plagued other methods.

Phase measurements of EUV mask defects

DOE PAGES

Claus, Rene A.; Wang, Yow-Gwo; Wojdyla, Antoine; ...

2015-02-22

Extreme Ultraviolet (EUV) Lithography mask defects were examined on the actinic mask imaging system, SHARP, at Lawrence Berkeley National Laboratory. Also, a quantitative phase retrieval algorithm based on the Weak Object Transfer Function was applied to the measured through-focus aerial images to examine the amplitude and phase of the defects. The accuracy of the algorithm was demonstrated by comparing the results of measurements using a phase contrast zone plate and a standard zone plate. Using partially coherent illumination to measure frequencies that would otherwise fall outside the numerical aperture (NA), it was shown that some defects are smaller than themore » conventional resolution of the microscope. We found that the programmed defects of various sizes were measured and shown to have both an amplitude and a phase component that the algorithm is able to recover.« less

The Moho discontinuity beneath Taiwan orogenic zone inferred from receiver function analysis

NASA Astrophysics Data System (ADS)

Chang, H.; Chen, C.; Liang, W.

2013-12-01

We determine the depth variations of the Moho discontinuity beneath Taiwan from receiver function analysis. Taiwan is a young (~6.5 Ma) orogenic zone as a consequence of oblique collision between the Philippine Sea Plate and the Eurasian Plate. In northeastern Taiwan, the Philippine Sea Plate subducts northwestward under the Eurasian Plate along the Ryukyu Trench; in southern Taiwan, the Eurasian Plate subducts eastward beneath the Philippine Sea Plate along the Manila Trench. Recent tomographic models of Taiwan reveal P-wave velocity variations of the lithospheric structure that provide important constraints on the orogenic processes in this region. However, the depth variations of the Moho discontinuity, a key observation for better understanding crustal deformation, remain elusive. In this study, we aim to delineate the Moho depth variations by analyzing seismic converted phases indicative of the presence of discontinuity structure. We analyze waveform data from teleseismic events recorded at the Broadband Array in Taiwan for Seismology (BATS). Preliminary results of receiver functions beneath BATS stations in eastern Taiwan show that more than one converted phase (P-to-S) are likely present in crustal depths, suggesting possible multiple crustal layering, which may complicate the detection of the Moho. We further carry out synthetic experiments to explore possible crustal structures that reconcile our observations.

An East to West Mineralogical Trend in Mars Exploration Rover Spirit Moessbauer Spectra of Home Plate

NASA Technical Reports Server (NTRS)

Schroder, C.; Di, K.; Morris, R. V.; Klingelhofer, G.; Li, R.

2008-01-01

Home Plate is a light-toned plateau approx.90 m in diameter within the Inner Basin of the Columbia Hills in Gusev crater on Mars. It is the most extensive exposure of layered bedrock encountered by Spirit to date, and it is composed of clastic rocks of moderately altered alkali basalt composition, enriched in some highly volatile elements. Textural observations suggest an explosive origin and geochemical observations favor volcanism, probably a hydrovolcanic explosion [1]. Since it first arrived at Home Plate on sol 744, Spirit has circumnavigated the plateau (Fig. 1) and is now, since sol 1410, resting at its Winter Haven 3 location at the north end of Home Plate. Results: The MER Moessbauer spectrometers determine Fe oxidation states, identify Fe-bearing mineral phases and quantify the distribution of Fe among oxidation states and mineral phases [2]. Moessbauer spectra of Home Plate bedrock were obtained in five different locations from nine different targets (Fig. 1): Barnhill Ace, Posey Manager, and James Cool Papa Bell Stars at the northwest side of Home Plate; Pesapallo, June Emerson, and Elizabeth Emery on the east side; Texas Chili on the south side; Pecan Pie on the west side; and Chanute on the north side.

The microstructure of the surface layer of magnesium laser alloyed with aluminum and silicon

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

Dziadoń, Andrzej

2016-08-15

The surface layer under analysis was formed as a result of diffusion bonding of a thin AlSi20 plate to a magnesium substrate followed by laser melting. Depending on the process parameters, the laser beam melted the AlSi20 plate only or the AlSi20 plate and a layer of the magnesium surface adjacent to it. Two types of microstructure of the remelted layer were thus analyzed. If the melting zone was limited to the AlSi20 plate, the microstructure of the surface layer was typical of a rapidly solidified hypereutectic Al–Si alloy. Since, however, the liquid AlSi20 reacted with the magnesium substrate, themore » following intermetallic phases formed: Al{sub 3}Mg{sub 2}, Mg{sub 17}Al{sub 12} and Mg{sub 2}Si. The microstructure of the modified surface layer of magnesium was examined using optical, scanning electron and transmission electron microscopy. The analysis of the surface properties of the laser modified magnesium revealed that the thin layer has a microstructure of a rapidly solidified Al–Si alloy offering good protection against corrosion. By contrast, the surface layer containing particles of intermetallic phases was more resistant to abrasion but had lower corrosion resistance than the silumin type layer. - Highlights: •A CO{sub 2} laser was used for surface alloying of Mg with AlSi20. •Before alloying, an AlSi20 plate was diffusion bonded with the Mg substrate. •The process parameters affected the alloyed layer microstructure and properties. •With melting limited to AlSi20, the layer had a structure of rapidly solidified AlSi20. •Mg–Al and Mg–Si phases were present when both the substrate and the plate were melted.« less

Effect of Ag additions on the lengthening rate of Ω plates and formation of σ phase in Al-Cu-Mg alloys during thermal exposure

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

Zhou, Yaru; Liu, Zhiyi, E-mail: liuzhiyi@csu.edu.c

Effect of Ag additions on the mechanical properties and microstructures of the peak-aged Al-Cu-Mg alloys during prolonged thermal exposure at 150 °C, was investigated by tensile testing, conventional transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). The results showed that after exposure for 500 h, > 85% of the peak strength remained. Microstructure observations indicated that increasing the Ag content from 0.14 to 0.57% promoted the precipitation of a fine and uniform Ω phase and suppressed the formation of the θ′ phase, leading to a notable improvement of the strength properties and thermal stability of the studied alloys.more » Quantitative TEM analysis showed that the coarsening of Ω phase was predominated by plate lengthening rather than thickening, while its lengthening rate was independent of various Ag additions during exposure at 150 °C. In addition, an increase of Ag also facilitated the formation of a cubic σ phase, which was further supported by STEM results. - Highlights: •Increasing Ag improved strength properties and thermal stability of the alloys. •After exposure for 500 h, > 85% of the peak strength remained. •The lengthening rate of Ω plates remained constant as Ag increased at 150 °C. •Increasing Ag content facilitated the formation of σ phase.« less

Mean grain size detection of DP590 steel plate using a corrected method with electromagnetic acoustic resonance.

PubMed

Wang, Bin; Wang, Xiaokai; Hua, Lin; Li, Juanjuan; Xiang, Qing

2017-04-01

Electromagnetic acoustic resonance (EMAR) is a considerable method to determine the mean grain size of the metal material with a high precision. The basic ultrasonic attenuation theory used for the mean grain size detection of EMAR is come from the single phase theory. In this paper, the EMAR testing was carried out based on the ultrasonic attenuation theory. The detection results show that the double peaks phenomenon occurs in the EMAR testing of DP590 steel plate. The dual phase structure of DP590 steel is the inducement of the double peaks phenomenon in the EMAR testing. In reaction to the phenomenon, a corrected method with EMAR was put forward to detect the mean grain size of dual phase steel. Compared with the traditional attenuation evaluation method and the uncorrected method with EMAR, the corrected method with EMAR shows great effectiveness and superiority for the mean grain size detection of DP590 steel plate. Copyright © 2016. Published by Elsevier B.V.

Chronic Obstructive Pulmonary Disease: official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care.

PubMed

Koblizek, Vladimir; Chlumsky, Jan; Zindr, Vladimir; Neumannova, Katerina; Zatloukal, Jakub; Zak, Jaroslav; Sedlak, Vratislav; Kocianova, Jana; Zatloukal, Jaromir; Hejduk, Karel; Pracharova, Sarka

2013-06-01

COPD is a global concern. Currently, several sets of guidelines, statements and strategies to managing COPD exist around the world. The Czech Pneumological and Phthisiological Society (CPPS) has commissioned an Expert group to draft recommended guidelines for the management of stable COPD. Subsequent revisions were further discussed at the National Consensus Conference (NCC). Reviewers' comments contributed to the establishment of the document's final version. The hallmark of the novel approach to COPD is the integrated evaluation of the patient's lung functions, symptoms, exacerbations and identifications of clinical phenotype(s). The CPPS defines 6 clinically relevant phenotypes: frequent exacerbator, COPD-asthma overlap, COPD-bronchiectasis overlap, emphysematic phenotype, bronchitic phenotype and pulmonary cachexia phenotype. Treatment recommendations can be divided into four steps. 1(st) step = Risk exposure elimination: reduction of smoking and environmental tobacco smoke (ETS), decrease of home and occupational exposure risks. 2(nd) step = Standard treatment: inhaled bronchodilators, regular physical activity, pulmonary rehabilitation, education, inhalation training, comorbidity treatment, vaccination. 3(rd) step = Phenotype-specific therapy: PDE4i, ICS+LABA, LVRS, BVR, AAT augmentation, physiotherapy, mucolytic, ABT. 4(th) step = Care for respiratory insufficiency and terminal COPD: LTOT, lung transplantation, high intensity-NIV and palliative care. Optimal treatment of COPD patients requires an individualised, multidisciplinary approach to the patient's symptoms, clinical phenotypes, needs and wishes. The new Czech COPD guideline reflects and covers these requirements.

Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

PubMed

Moulton, H M; Fletcher, S; Neuman, B W; McClorey, G; Stein, D A; Abes, S; Wilton, S D; Buchmeier, M J; Lebleu, B; Iversen, P L

2007-08-01

The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.

A quality by design (QbD) study on enoxaparin sodium loaded polymeric microspheres for colon-specific delivery.

PubMed

Hales, Dana; Vlase, Laurian; Porav, Sebastian Alin; Bodoki, Andreea; Barbu-Tudoran, Lucian; Achim, Marcela; Tomuță, Ioan

2017-03-30

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of enoxaparin sodium microspheres for colon-specific delivery. The Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified. A central composite experimental design was used in order to develop the design space of microspheres for colon-specific delivery that have the desired Quality Target Product Profile (QTPP). The CPPs studied were Eudragit® FS-30D/Eudragit® RS-PO ratio, poly(vinyl alcohol) (PVA) concentration and sodium chloride (NaCl) concentration. The encapsulation efficiency increased with NaCl concentration increase, the percentages of enoxaparin sodium reaching 94% for some formulations. Increasing the ratio Eudragit® FS-30D/Eudragit® RS-PO ensured a relatively complete release of enoxaparin sodium in the environment simulating the colonic pH. Based on these results, the optimum conditions were decided and the optimum formulation was prepared. The results obtained for the latter in terms of in vitro enoxaparin sodium release were good, the microparticles releasing only 9.42% enoxaparin sodium in acidic environment and 15.16% in the medium which simulated duodenal pH, but allowing the release of up to 89.24% in the medium which simulated colonic pH. The in vitro release profile of enoxaparin sodium was close to the ideal one, therefore the system was successfully designed using QbD approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Interactions between Membranes and "Metaphilic" Polypeptide Architectures with Diverse Side-Chain Populations.

PubMed

Lee, Michelle W; Han, Ming; Bossa, Guilherme Volpe; Snell, Carly; Song, Ziyuan; Tang, Haoyu; Yin, Lichen; Cheng, Jianjun; May, Sylvio; Luijten, Erik; Wong, Gerard C L

2017-03-28

At physiological conditions, most proteins or peptides can fold into relatively stable structures that present on their molecular surfaces specific chemical patterns partially smeared out by thermal fluctuations. These nanoscopically defined patterns of charge, hydrogen bonding, and/or hydrophobicity, along with their elasticity and shape stability (folded proteins have Young's moduli of ∼1 × 10 8 Pa), largely determine and limit the interactions of these molecules, such as molecular recognition and allosteric regulation. In this work, we show that the membrane-permeating activity of antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) can be significantly enhanced using prototypical peptides with "molten" surfaces: metaphilic peptides with quasi-liquid surfaces and adaptable shapes. These metaphilic peptides have a bottlebrush-like architecture consisting of a rigid helical core decorated with mobile side chains that are terminated by cationic or hydrophobic groups. Computer simulations show that these flexible side chains can undergo significant rearrangement in response to different environments, giving rise to adaptable surface chemistry of the peptide. This quality makes it possible to control their hydrophobicity over a broad range while maintaining water solubility, unlike many AMPs and CPPs. Thus, we are able to show how the activity of these peptides is amplified by hydrophobicity and cationic charge, and rationalize these results using a quantitative mean-field theory. Computer simulations show that the shape-changing properties of the peptides and the resultant adaptive presentation of chemistry play a key enabling role in their interactions with membranes.

Use of vancomycin silica stationary phase in packed capillary electrochromatography: III. enantiomeric separation of basic compounds with the polar organic mobile phase.

PubMed

Fanali, Salvatore; Catarcini, Paolo; Quaglia, Maria Giovanna

2002-02-01

The separation of basic compounds into their enantiomers was achieved using capillary electrochromatography in 50 or 75 microm inner diameter (ID) fused-silica capillaries packed with silica a stationary phase derivatized with vancomycin and mobile phases composed of mixtures of polar organic solvents containing 13 mM ammonium acetate. Enantiomer resolution, electroosmotic flow, and the number of theoretical plates were strongly influenced by the type and concentration of the organic solvent. Mobile phases composed of 13 mM ammonium acetate dissolved in mixtures of acetonitrile/methanol, ethanol, n-propanol, or isopropanol were tested and the highest enantioresolutions were achieved using the first mobile phase, allowing the separation of almost all investigated enantiomers (9 from 11 basic compounds). The use of capillaries with different ID (50 and 75 microm ID) packed with the same chiral stationary phase revealed that a higher number of theoretical plates and higher enantioresolution was achieved with the tube with lowest ID.

Effects of H3O+, OH-, \\text{O}_{2}^{-} , \\text{NO}_{\\text{x}}^{-} and NO x for Escherichia coli inactivation in atmospheric pressure DC corona discharges

NASA Astrophysics Data System (ADS)

Sekimoto, Kanako; Gonda, Rena; Takayama, Mitsuo

2015-08-01

The effects of ionic and neutral species such as H3O+, OH-, \\text{O}2- , \\text{NO}x- (x = 2, 3), and NO x on Escherichia coli (E. coli) inactivation in gas and liquid phases was investigated using atmospheric pressure DC corona discharges with point-to-plane electrodes. The above chemical species as well as OH and O3 were selectively irradiated onto E. coli suspensions on agar plates using a needle angle of 45° with respect to the plates, airflow, and a grid plate. Irradiation with the positive ion H3O+ did not inactivate E. coli, while the negative ions OH-/\\text{O}2- resulted in bactericidal inactivation, in both gas and liquid phases. In contrast, the negative ions \\text{NO}x- and neutral species NO x in the gas phase had quite strong bactericidal effects on E. coli compared to those species in the liquid phase. These results suggest that liquid-phase HNO3, formed primarily via the reaction of gas-phase \\text{NO}x- and NO x with H2O in agar, has only a weak inactivation effect on E. coli. Furthermore, using naphthylethylenediamine spectrophotometry, the threshold amount of gas-phase \\text{NO}x- and NO x for E. coli inactivation was determined to be  ≈1.3   ×   10-9 mol mm-1.

Two-dimensional thermal modeling associated with subduction of the Philippine Sea plate in southern Kyushu, Japan

NASA Astrophysics Data System (ADS)

Suenaga, Nobuaki; Yoshioka, Shoichi; Matsumoto, Takumi; Ji, Yingfeng

2018-01-01

In Hyuga-nada, southern Kyushu in southwest Japan, afterslip events were found in association with the two large interplate earthquakes, which occurred on October 19 and December 3, 1996. In Kyushu, low-frequency earthquakes (LFEs) and tectonic tremors are not common, but a considerable concentration of tectonic tremors is observed beneath the Pacific coast of the Miyazaki prefecture. To investigate the generation mechanisms of these seismic events, we performed 2-D box-type time-dependent thermal modeling in southern Kyushu. As a result, the temperature range of the upper surface of the subducting Philippine Sea (PHS) plate, where the afterslip occurred, reached approximately 300 to 350 °C. The temperatures where the tectonic tremors occurred ranged from 450 to 650 °C in the mantle wedge corner. We also estimated the spatial distribution of water content within the subducting PHS plate, using phase diagrams of hydrous mid-ocean ridge basalt (MORB) and ultramafic rock. Then, we found that no characteristic phase transformations accompany the dehydration of the subducting PHS plate in the afterslip region, but phase transformation from lawsonite blueschist to lawsonite eclogite is expected within the oceanic crust of the PHS plate just below the active region of the tectonic tremors. Our estimated water content distribution is consistent with the VP/VS ratio calculated from the seismic tomography. Therefore, we conclude that the occurrence of the afterslip is controlled by the temperature condition at the plate boundary, and occurs near the down-dip limit of the seismogenic zone. On the other hand, determining the major factors leading to the occurrence of the tectonic tremors is difficult, we estimated the temperature in the mantle wedge is ranging from 450 °C to 650 °C, and dehydration of 1.0 wt% would be expected from the subducting PHS plate near the active region of the tectonic tremors.

Battery plate containing filler with conductive coating

NASA Technical Reports Server (NTRS)

Rowlette, John J. (Inventor)

1986-01-01

The plate (10) comprises a matrix or binder resin phase (12) in which is dispersed particulate, conductive tin oxide such as tin oxide coated glass fibers (14). A monopolar plate (11) is prepared by coating a layer (18) of electrolytically active material onto a surface of the plate (10). Tin oxide is prevented from reduction by coating a surface of the plate (10) with a conductive, impervious layer resistant to reduction such as a thin film (22) of lead adhered to the plate with a layer (21) of conductive adhesive. The plate (10) can be formed by casting a molten dispersion from mixer (36) onto a sheet (30) of lead foil or by passing an assembly of a sheet (41) of resin, a sheet (43) of fiberglass and a sheet (45) of lead between the nip of heated rollers (48, 50).

Battery plate containing filler with conductive coating

NASA Technical Reports Server (NTRS)

Rowlette, John J. (Inventor)

1985-01-01

The plate (10) comprises a matrix or binder resin phase (12) in which is dispersed particulate, conductive tin oxide such as tin oxide coated glass fibers (14). A monopolar plate (11) is prepared by coating a layer (18) of electrolytically active material onto a surface of the plate (10). Tin oxide is prevented from reduction by coating a surface of the plate (10) with a conductive, impervious layer resistant to reduction such as a thin film (22) of lead adhered to the plate with a layer (21) of conductive adhesive. The plate (10) can be formed by casting a molten dispersion from mixer (36) onto a sheet (30) of lead foil or by passing an assembly of a sheet (41) of resin, a sheet (43) of fiberglass and a sheet (45) of lead between the nip of heated rollers (48, 50).

Using chaotic forcing to detect damage in a structure

USGS Publications Warehouse

Moniz, L.; Nichols, J.; Trickey, S.; Seaver, M.; Pecora, D.; Pecora, L.

2005-01-01

In this work we develop a numerical test for Holder continuity and apply it and another test for continuity to the difficult problem of detecting damage in structures. We subject a thin metal plate with incremental damage to the plate changes, its filtering properties, and therefore the phase space trajectories of the response chaotic excitation of various bandwidths. Damage to the plate changes its filtering properties and therefore the phase space of the response. Because the data are multivariate (the plate is instrumented with multiple sensors) we use a singular value decomposition of the set of the output time series to reduce the embedding dimension of the response time series. We use two geometric tests to compare an attractor reconstructed from data from an undamaged structure to that reconstructed from data from a damaged structure. These two tests translate to testing for both generalized and differentiable synchronization between responses. We show loss of synchronization of responses with damage to the structure. ?? 2005 American Institute of Physics.

Using chaotic forcing to detect damage in a structure.

USGS Publications Warehouse

Moniz, L.; Nichols, J.; Trickey, S.; Seaver, M.; Pecora, D.; Pecora, L.

2005-01-01

In this work we develop a numerical test for Holder continuity and apply it and another test for continuity to the difficult problem of detecting damage in structures. We subject a thin metal plate with incremental damage to the plate changes, its filtering properties, and therefore the phase space trajectories of the response chaotic excitation of various bandwidths. Damage to the plate changes its filtering properties and therefore the phase space of the response. Because the data are multivariate (the plate is instrumented with multiple sensors) we use a singular value decomposition of the set of the output time series to reduce the embedding dimension of the response time series. We use two geometric tests to compare an attractor reconstructed from data from an undamaged structure to that reconstructed from data from a damaged structure. These two tests translate to testing for both generalized and differentiable synchronization between responses. We show loss of synchronization of responses with damage to the structure.

Three-dimensional couette flow of dusty fluid with heat transfer in the presence of magnetic field

NASA Astrophysics Data System (ADS)

Gayathri, R.; Govindarajan, A.; Sasikala, R.

2018-04-01

This paper is focused on the mathematical modelling of three-dimensional couette flow and heat transfer of a dusty fluid between two infinite horizontal parallel porous flat plates in the presence of an induced magnetic field. The problem is formulated using a continuum two-phase model and the resulting equations are solved analytically. The lower plate is stationary while the upper plate is undergoing uniform motion in its plane. These plates are, respectively subjected to transverse exponential injection and its corresponding removal by constant suction. Due to this type of injection velocity, the flow becomes three dimensional. The closed-form expressions for velocity and temperature fields of both the fluid and dust phase are obtained by solving the governing partial differentiation equations using the perturbation method. A selective set of graphical results is presented and discussed to show interesting features of the problem. It is found that the velocity profiles of both fluid and dust particles decrease due to the increase of (magnetic parameter) Hartmann number.

Neutron diffraction measurement of residual stresses, dislocation density and texture in Zr-bonded U-10Mo “mini” fuel foils and plates

DOE PAGES

Brown, Donald William; Okuniewski, Maria A.; Sisneros, Thomas A.; ...

2016-12-01

Here, Al clad U-10Mo fuel plates are being considered for conversion of several research reactors from high-enriched to low-enriched U fuel. Neutron diffraction measurements of the textures, residual phase stresses, and dislocation densities in the individual phases of the mini-foils throughout several processing steps and following hot-isostatic pressing to the Al cladding, have been completed. Recovery and recrystallization of the bare U-10Mo fuel foil, as indicated by the dislocation density and texture, are observed depending on the state of the material prior to annealing and the duration and temperature of the annealing process. In general, the cladding procedure significantly reducesmore » the dislocation density, but the final state of the clad plate, both texture and dislocation density, depends strongly on the final processing step of the fuel foil. In contrast, the residual stress state of the final plate is dominated by the thermal expansion mismatch of the constituent materials.« less

Testing Single Phase IGBT H-Bridge Switch Plates for the High Voltage Converter Modulator at the Spallation Neutron Source

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

Peplov, Vladimir V; Anderson, David E; Solley, Dennis J

2014-01-01

Three IGBT H-bridge switching networks are used in each High Voltage Converter Modulator (HVCM) system at the Spallation Neutron Source (SNS) to generate drive currents to three boost transformer primaries switching between positive and negative bus voltages at 20 kHz. Every switch plate assembly is tested before installing it into an operational HVCM. A Single Phase Test Stand has been built for this purpose, and it is used for adjustment, measurement and testing of different configurations of switch plates. This paper will present a description of the Test Stand configuration and discuss the results of testing switch plates with twomore » different types of IGBT gate drivers currently in use on the HVCM systems. Comparison of timing characteristics of the original and new drivers and the resulting performance reinforces the necessity to replace the original H-bridge network drivers with the upgraded units.« less

Neutron diffraction measurement of residual stresses, dislocation density and texture in Zr-bonded U-10Mo “mini” fuel foils and plates

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

Brown, Donald William; Okuniewski, Maria A.; Sisneros, Thomas A.

Here, Al clad U-10Mo fuel plates are being considered for conversion of several research reactors from high-enriched to low-enriched U fuel. Neutron diffraction measurements of the textures, residual phase stresses, and dislocation densities in the individual phases of the mini-foils throughout several processing steps and following hot-isostatic pressing to the Al cladding, have been completed. Recovery and recrystallization of the bare U-10Mo fuel foil, as indicated by the dislocation density and texture, are observed depending on the state of the material prior to annealing and the duration and temperature of the annealing process. In general, the cladding procedure significantly reducesmore » the dislocation density, but the final state of the clad plate, both texture and dislocation density, depends strongly on the final processing step of the fuel foil. In contrast, the residual stress state of the final plate is dominated by the thermal expansion mismatch of the constituent materials.« less

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

Claus, Rene A.; Wang, Yow-Gwo; Wojdyla, Antoine

Extreme Ultraviolet (EUV) Lithography mask defects were examined on the actinic mask imaging system, SHARP, at Lawrence Berkeley National Laboratory. Also, a quantitative phase retrieval algorithm based on the Weak Object Transfer Function was applied to the measured through-focus aerial images to examine the amplitude and phase of the defects. The accuracy of the algorithm was demonstrated by comparing the results of measurements using a phase contrast zone plate and a standard zone plate. Using partially coherent illumination to measure frequencies that would otherwise fall outside the numerical aperture (NA), it was shown that some defects are smaller than themore » conventional resolution of the microscope. We found that the programmed defects of various sizes were measured and shown to have both an amplitude and a phase component that the algorithm is able to recover.« less

Nonviral Vectors for Gene Delivery

NASA Astrophysics Data System (ADS)

Baoum, Abdulgader Ahmed

2011-12-01

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was also explored. Positively charged CPPs were complexed with pDNA or siRNA, which resulted in 'loose' (˜1 micron) particles. These were then condensed into small nanoparticles by using calcium, which formed "soft" crosslinks by interacting with both phosphates on nucleic acids and amines on CPPs. An optimal amount of CaCl2 produced stable, ˜100 nm complexes that exhibited higher transfection efficiency and gene silencing than PEI polyplexes. CPPs also displayed negligible cytotoxicity up to 5 mg/mL. Biophysical studies of the pDNA structure within complexes suggested that pDNA within CPP complexes (condensed with calcium) had similar structure, but enhanced thermal stability compared to PEI complexes. Thus, CPP complexes emerged as simple, attractive candidates for future studies on nonviral gene delivery in vivo.

Phase decomposition of γ-U (bcc) in U-10 wt% Mo fuel alloy during hot isostatic pressing of monolithic fuel plate

NASA Astrophysics Data System (ADS)

Park, Y.; Eriksson, N.; Newell, R.; Keiser, D. D.; Sohn, Y. H.

2016-11-01

Eutectoid decomposition of γ-phase (cI2) into α-phase (oC4) and γ‧-phase (tI6) during the hot isostatic pressing (HIP) of the U-10 wt% Mo (U10Mo) alloy was investigated using monolithic fuel plate samples consisting of U10Mo fuel alloy, Zr diffusion barrier and AA6061 cladding. The decomposition of the γ-phase was observed because the HIP process is carried out near the eutectoid temperature, 555 °C. Initially, a cellular structure, consisting of γ‧-phase surrounded by α-phase, developed from the destabilization of the γ-phase. The cellular structure further developed into an alternating lamellar structure of α- and γ‧-phases. Using scanning electron microscopy and transmission electron microscopy, qualitative and quantitative microstructural analyses were carried out to identify the phase constituents, and elucidate the microstructural development based on time-temperature-transformation diagram of the U10Mo alloy. The destabilization of γ -phase into α- and γ‧-phases would be minimized when HIP process was carried out with rapid ramping/cooling rate and dwell temperature higher than 560 °C.

Improving Plating by Use of Intense Acoustic Beams

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Denofrio, Charles

2003-01-01

An improved method of selective plating of metals and possibly other materials involves the use of directed high-intensity acoustic beams. The beams, typically in the ultrasonic frequency range, can be generated by fixed-focus transducers (see figure) or by phased arrays of transducers excited, variously, by continuous waves, tone bursts, or single pulses. The nonlinear effects produced by these beams are used to alter plating processes in ways that are advantageous.

Variable thickness double-refracting plate

DOEpatents

Hadeishi, Tetsuo

1976-01-01

This invention provides an A.C., cyclic, current-controlled, phase retardation plate that uses a magnetic clamp to produce stress birefringence. It was developed for an Isotope-Zeeman Atomic Absorption Spectrometer that uses polarization modulation to effect automatic background correction in atomic absorption trace-element measurements. To this end, the phase retardation plate of the invention is a variable thickness, photoelastic, double-refracting plate that is alternately stressed and released by the magnetic clamp selectively to modulate specific components selected from the group consisting of circularly and plane polarized Zeeman components that are produced in a dc magnetic field so that they correspond respectively to Zeeman reference and transmission-probe absorption components. The polarization modulation changes the phase of these polarized Zeeman components, designated as .sigma. reference and .pi. absorption components, so that every half cycle the components change from a transmission mode to a mode in which the .pi. component is blocked and the .sigma. components are transmitted. Thus, the Zeeman absorption component, which corresponds in amplitude to the amount of the trace element to be measured in a sample, is alternately transmitted and blocked by a linear polarizer, while the circularly polarized reference components are continuously transmitted thereby. The result is a sinusoidally varying output light amplitude whose average corresponds to the amount of the trace element present in the sample.

Deformation induced dynamic recrystallization and precipitation strengthening in an Mg−Zn−Mn alloy processed by high strain rate rolling

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

Jiang, Jimiao; Song, Min

2016-11-15

The microstructure of a high strain-rate rolled Mg−Zn−Mn alloy was investigated by transmission electron microscopy to understand the relationship between the microstructure and mechanical properties. The results indicate that: (1) a bimodal microstructure consisting of the fine dynamic recrystallized grains and the largely deformed grains was formed; (2) a large number of dynamic precipitates including plate-like MgZn{sub 2} phase, spherical MgZn{sub 2} phase and spherical Mn particles distribute uniformly in the grains; (3) the major facets of many plate-like MgZn{sub 2} precipitates deviated several to tens of degrees (3°–30°) from the matrix basal plane. It has been shown that themore » high strength of the alloy is attributed to the formation of the bimodal microstructure, dynamic precipitation, and the interaction between the dislocations and the dynamic precipitates. - Highlights: •A bimodal microstructure was formed in a high strain-rate rolled Mg−Zn−Mn alloy. •Plate-like MgZn{sub 2}, spherical MgZn{sub 2} and spherical Mn phases were observed. •The major facet of the plate-like MgZn{sub 2} deviated from the matrix basal plane.« less

The propagation of Lamb waves in multilayered plates: phase-velocity measurement

NASA Astrophysics Data System (ADS)

Grondel, Sébastien; Assaad, Jamal; Delebarre, Christophe; Blanquet, Pierrick; Moulin, Emmanuel

1999-05-01

Owing to the dispersive nature and complexity of the Lamb waves generated in a composite plate, the measurement of the phase velocities by using classical methods is complicated. This paper describes a measurement method based upon the spectrum-analysis technique, which allows one to overcome these problems. The technique consists of using the fast Fourier transform to compute the spatial power-density spectrum. Additionally, weighted functions are used to increase the probability of detecting the various propagation modes. Experimental Lamb-wave dispersion curves of multilayered plates are successfully compared with the analytical ones. This technique is expected to be a useful way to design composite parts integrating ultrasonic transducers in the field of health monitoring. Indeed, Lamb waves and particularly their velocities are very sensitive to defects.

High-Temperature Cast Aluminum for Efficient Engines

NASA Astrophysics Data System (ADS)

Bobel, Andrew C.

Accurate thermodynamic databases are the foundation of predictive microstructure and property models. An initial assessment of the commercially available Thermo-Calc TCAL2 database and the proprietary aluminum database of QuesTek demonstrated a large degree of deviation with respect to equilibrium precipitate phase prediction in the compositional region of interest when compared to 3-D atom probe tomography (3DAPT) and transmission electron microscopy (TEM) experimental results. New compositional measurements of the Q-phase (Al-Cu-Mg-Si phase) led to a remodeling of the Q-phase thermodynamic description in the CALPHAD databases which has produced significant improvements in the phase prediction capabilities of the thermodynamic model. Due to the unique morphologies of strengthening precipitate phases commonly utilized in high-strength cast aluminum alloys, the development of new microstructural evolution models to describe both rod and plate particle growth was critical for accurate mechanistic strength models which rely heavily on precipitate size and shape. Particle size measurements through both 3DAPT and TEM experiments were used in conjunction with literature results of many alloy compositions to develop a physical growth model for the independent prediction of rod radii and rod length evolution. In addition a machine learning (ML) model was developed for the independent prediction of plate thickness and plate diameter evolution as a function of alloy composition, aging temperature, and aging time. The developed models are then compared with physical growth laws developed for spheres and modified for ellipsoidal morphology effects. Analysis of the effect of particle morphology on strength enhancement has been undertaken by modification of the Orowan-Ashby equation for 〈110〉 alpha-Al oriented finite rods in addition to an appropriate version for similarly oriented plates. A mechanistic strengthening model was developed for cast aluminum alloys containing both rod and plate-like precipitates. The model accurately accounts for the temperature dependence of particle nucleation and growth, solid solution strengthening, Si eutectic strength, and base aluminum yield strength. Strengthening model predictions of tensile yield strength are in excellent agreement with experimental observations over a wide range of aluminum alloy systems, aging temperatures, and test conditions. The developed models enable the prediction of the required particle morphology and volume fraction necessary to achieve target property goals in the design of future aluminum alloys. The effect of partitioning elements to the Q-phase was also considered for the potential to control the nucleation rate, reduce coarsening, and control the evolution of particle morphology. Elements were selected based on density functional theory (DFT) calculations showing the prevalence of certain elements to partition to the Q-phase. 3DAPT experiments were performed on Q-phase containing wrought alloys with these additions and show segregation of certain elements to the Q-phase with relative agreement to DFT predictions.

Negative group velocity Lamb waves on plates and applications to the scattering of sound by shells

NASA Astrophysics Data System (ADS)

Marston, Philip L.

2003-05-01

Symmetric Lamb waves on plates exhibit anomalies for certain regions of frequency. The phase velocity appears to be double-valued [M. F. Werby and H. Überall, J. Acoust. Soc. Am. 111, 2686-2691 (2002)] with one of the branches having a negative group velocity relative to the corresponding phase velocity. The classification of the symmetric plate modes for frequencies appearing to have a double-valued phase velocity is reviewed here. The complication of a double-valued velocity is avoided by examining mode orthogonality and the complex wave-number spectra. Various authors have noted an enhancement in the backscattering of sound by elastic shells in water that occurs for frequencies where symmetric leaky Lamb waves (generalized to case of a shell) have contra-directed group and phase velocities. The ray diagram for negative group velocity contributions to the scattering by shells [G. Kaduchak, D. H. Hughes, and P. L. Marston, J. Acoust. Soc. Am. 96, 3704-3714 (1994)] is unusual since for this type of mode the energy on the shell flows in the opposite direction of the wave vector. Circumnavigation of the shell is not required for the leaky ray to be backward directed.

Evaluation of stationary phases packed with superficially porous particles for the analysis of pharmaceutical compounds using supercritical fluid chromatography.

PubMed

Perrenoud, Alexandre Grand-Guillaume; Farrell, William P; Aurigemma, Christine M; Aurigemma, Nicole C; Fekete, Szabolcs; Guillarme, Davy

2014-09-19

Superficially porous particles (SPP), or core shell particles, which consist of a non-porous silica core surrounded by a thin shell of porous silica, have gained popularity as a solid support for chromatography over the last decade. In the present study, five unbonded silica, one diol, and two ethylpyridine (2-ethyl and 4-ethyl) SPP columns were evaluated under SFC conditions using two mixtures, one with 17 drug-like compounds and the other one with 7 drug-like basic compounds. Three of the SPP phases, SunShell™ 2-ethylpyridine (2-EP), Poroshell™ HILIC, and Ascentis(®) Express HILIC, exhibited superior performances relative to the others (reduced theoretical plate height (hmin) values of 1.9-2.5 for neutral compounds). When accounting for both achievable plate count and permeability of the support using kinetic plot evaluation, the Cortecs™ HILIC 1.6μm and Ascentis(®) Express HILIC 2.7μm phases were found to be the best choices among tested SPPs to reach efficiencies up to 30,000 plates in the minimum amount of time. For desired efficiencies ranging from 30,000 to 60,000 plates, the SunShell™ 2-EP 2.6μm column clearly outperformed all other SPPs. With the addition of a mobile phase additive such as 10mM ammonium formate, which was required to elute the basic components with sharp peaks, the Poroshell™ HILIC, SunShell™ Diol and SunShell™ 2-EP phases represent the most orthogonal SPP columns with the highest peak capacities. This study demonstrates the obvious benefits of using columns packed with SPP on current SFC instrumentation. Copyright © 2014 Elsevier B.V. All rights reserved.

Friction-Stir Welding - Heavy Inclusions in Bi-metallic welds of Al 2219/2195

NASA Technical Reports Server (NTRS)

Rietz, Ward W., Jr.

2008-01-01

Heavy Inclusions (HI) were detected for the first time by radiographic examination in aluminum alloy 2219forging/2195plate (advancing/retreating side) Friction Sir Welds (FSW) for the Space Shuttle External Tank (ET) Program. Radiographic HI indications appear as either small (approx.0.005"-0.025") individual particles or clusters of small particles. Initial work was performed to verify that the HI was not foreign material or caused by FSW pin tool debris. That and subsequent elemental analysis determined that the HI were large agglomerations of Al2Cu (theta phase), which is the strengthening precipitate in Al2219. A literature search on that subject determined that the agglomeration of phase has also been found in Al2219 bead on plate FSW [Ref. 1]. Since this was detected in ET space flight hardware, an investigative study of the effect of agglomerated theta phase particles in FSW Al2219f/2195p was performed. Numerous panels of various lengths were welded per ET weld procedures and radiographically inspected to determine if any HI was detected. Areas that had HI were sampled for room temperature and cyclic cryogenic (-423F) tensile testing and determined no significant adverse affect on mechanical properties when compared to test specimens without HI and historical data. Fracture surface examination using the Scanning Electron Microscope (SEM) revealed smaller phase agglomerations undetectable by radiographic inspection dispersed throughout the Al2219f/2195p FSW. This indicates that phase agglomeration is inherent to the Al2219f/2195p FSW process and only rarely creates agglomerations large enough to be detected by radiography. HI has not been observed in FSW of plate to plate material for either Al2219 or AL2195.

Thin-plate spline analysis of mandibular growth.

PubMed

Franchi, L; Baccetti, T; McNamara, J A

2001-04-01

The analysis of mandibular growth changes around the pubertal spurt in humans has several important implications for the diagnosis and orthopedic correction of skeletal disharmonies. The purpose of this study was to evaluate mandibular shape and size growth changes around the pubertal spurt in a longitudinal sample of subjects with normal occlusion by means of an appropriate morphometric technique (thin-plate spline analysis). Ten mandibular landmarks were identified on lateral cephalograms of 29 subjects at 6 different developmental phases. The 6 phases corresponded to 6 different maturational stages in cervical vertebrae during accelerative and decelerative phases of the pubertal growth curve of the mandible. Differences in shape between average mandibular configurations at the 6 developmental stages were visualized by means of thin-plate spline analysis and subjected to permutation test. Centroid size was used as the measure of the geometric size of each mandibular specimen. Differences in size at the 6 developmental phases were tested statistically. The results of graphical analysis indicated a statistically significant change in mandibular shape only for the growth interval from stage 3 to stage 4 in cervical vertebral maturation. Significant increases in centroid size were found at all developmental phases, with evidence of a prepubertal minimum and of a pubertal maximum. The existence of a pubertal peak in human mandibular growth, therefore, is confirmed by thin-plate spline analysis. Significant morphological changes in the mandible during the growth interval from stage 3 to stage 4 in cervical vertebral maturation may be described as an upward-forward direction of condylar growth determining an overall "shrinkage" of the mandibular configuration along the measurement of total mandibular length. This biological mechanism is particularly efficient in compensating for major increments in mandibular size at the adolescent spurt.

ASURA (PHB2) Is Required for Kinetochore Assembly and Subsequent Chromosome Congression

PubMed Central

Lee, Mei Hann; Lin, Linyen; Equilibrina, Ilma; Uchiyama, Susumu; Matsunaga, Sachihiro; Fukui, Kiichi

2011-01-01

ASURA (PHB2) knockdown has been known to cause premature loss of sister chromatid cohesion, and disrupt the localization of several outer plate proteins to the kinetochore. As a result, cells are arrested at mitotic phase and chromosomes fail to congress to the metaphase plate. In this study, we further clarified the mechanism underlying ASURA function on chromosome congression. Interestingly, ASURA is not specifically localized at the kinetochore during mitotic phase, unlike other kinetochore proteins which construct the kinetochore. Electron microscopy (EM) observation showed that ASURA is required for proper kinetochore formation. By the partial depletion of ASURA, kinetochore maturation is impaired, and kinetochores showing fibrillar balls without a well-defined outer plates are often observed. Moreover, even when the outer plates of kinetochores are constructed, most showed structures stretched and/or distended from the centromere, which resembled premature kinetochores at prometaphase, indicating that the constructed kinetochore plates are less rigid against tension derived from kinetochore microtubule pulling forces. We concluded that ASURA is an essential protein for complete kinetochore development, although ASURA is not being integrated to the kinetochore. These results highlight the uniqueness of ASURA as a kinetochore protein. PMID:22282585

Thermal residual stress evaluation based on phase-shift lateral shearing interferometry

NASA Astrophysics Data System (ADS)

Dai, Xiangjun; Yun, Hai; Shao, Xinxing; Wang, Yanxia; Zhang, Donghuan; Yang, Fujun; He, Xiaoyuan

2018-06-01

An interesting phase-shift lateral shearing interferometry system was proposed to evaluate the thermal residual stress distribution in transparent specimen. The phase-shift interferograms was generated by moving a parallel plane plate. Based on analyzing the fringes deflected by deformation and refractive index change, the stress distribution can be obtained. To verify the validity of the proposed method, a typical experiment was elaborately designed to determine thermal residual stresses of a transparent PMMA plate subjected to the flame of a lighter. The sum of in-plane stress distribution was demonstrated. The experimental data were compared with values measured by digital gradient sensing method. Comparison of the results reveals the effectiveness and feasibility of the proposed method.

Methods and devices for measuring orbital angular momentum states of electrons

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

McMorran, Benjamin J.; Harvey, Tyler R.

A device for measuring electron orbital angular momentum states in an electron microscope includes the following components aligned sequentially in the following order along an electron beam axis: a phase unwrapper (U) that is a first electrostatic refractive optical element comprising an electrode and a conductive plate, where the electrode is aligned perpendicular to the conductive plate; a first electron lens system (L1); a phase corrector (C) that is a second electrostatic refractive optical element comprising an array of electrodes with alternating electrostatic bias; and a second electron lens system (L2). The phase unwrapper may be a needle electrode ormore » knife edge electrode.« less

Design of an electrostatic phase shifting device for biological transmission electron microscopy.

PubMed

Koeck, Philip J B

2018-04-01

I suggest an electrostatic phase plate designed to broaden the contrast transfer function of a transmission electron microscope operated close to Scherzer defocus primarily in the low resolution direction. At higher defocus the low frequency behavior is equal to that close to Scherzer defocus, but CTF-correction becomes necessary to extend image interpretation to higher resolution. One simple realization of the phase plate consists of two ring shaped electrodes symmetrically surrounding the central beam. Since no physical components come into contact with the central beam and charge on the electrodes is controlled by an external voltage supply, problems with uncontrolled charging are expected to be reduced. Copyright © 2018 Elsevier B.V. All rights reserved.

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Franco, Juan Va; Turk, Tarek; Jung, Jae Hung; Xiao, Yu-Tian; Iakhno, Stanislav; Garrote, Virginia; Vietto, Valeria

2018-01-26

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture reduces prostatitis symptoms in an appreciable number of participants compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference in adverse events (moderate QoE). It probably also decreases prostatitis symptoms compared with standard medical therapy in an appreciable number of participants (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2. Circumcision: (one study, 713 participants) based on short-term follow-up, early circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD -3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a greater incidence of adverse events compared with control (a waiting list to be circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants) based on short-term follow-up, we are uncertain of the effects of the use of an electromagnetic chair on prostatitis symptoms. It may be associated with a greater incidence of adverse events compared with sham procedure (low to very low QoE).4. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a greater improvement in prostatitis symptoms in an appreciable number of participants compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events.5. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events.7. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE).8. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events.9. Other interventions: there is uncertainty about the effects of other interventions included in this review. We found no information regarding psychological support or prostatic surgery. Some of the interventions can decrease prostatitis symptoms in an appreciable number without a greater incidence of adverse events. The QoE was mostly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

The stability of thermodynamically metastable phases in a Zr-Sn-Nb-Mo alloy: Effects of alloying elements, morphology and applied stress/strain

NASA Astrophysics Data System (ADS)

Yu, Hongbing; Yao, Zhongwen; Daymond, Mark R.

2017-09-01

In this paper, a dual phase Zr-Sn-Nb-Mb alloy was studied with TEM after thermal treatment and high-temperature tensile deformation. Plate and pressure tube material, manufactured through different processing routes, were used in this study. The overall average concentrations of Mo and Nb in the β phase are higher in the pressure tube than in the plate. It was revealed that these concentrations have significant effects on the subsequent stability of the β and ω phases as well as on the precipitation behavior of the α phase from the β phase. That is, the higher the concentrations, the more stable the β and ω phases are, and hence there is a reduced tendency for precipitation of α phase. Aging treatments cause the transformation of athermal ω to isothermal ω, as expected. The most striking finding is the product of the decomposition of the isothermal ω particles during aging treatment is determined as not being α phase, even though the structure of it is, as-yet, not fully determined. The non-uniform morphology of the β grains in the plate material provides us a unique opportunity to investigate the effects of morphology on the aging response of the β phase. It was found that thin β filaments suppress the precipitation of isothermal ω particles but enhance the precipitation of α phase at α/β interfaces. The effect of the Burgers orientation relationship between α and β grains on the precipitation of the α phase at the α/β interface is discussed. Applied high-temperature stress/strain has been found to enhance the decomposition of isothermal ω phase but suppress α precipitation inside the β grains. The suppression of α precipitation by applied stress/strain is discussed in terms of the ω assisted α precipitation. Implications of these findings for the in-service application of the alloy are discussed.

Laser heterodyne surface profiler

DOEpatents

Sommargren, G.E.

1980-06-16

A method and apparatus are disclosed for testing the deviation of the face of an object from a flat smooth surface using a beam of coherent light of two plane-polarized components, one of a frequency constantly greater than the other by a fixed amount to produce a difference frequency with a constant phase to be used as a reference, and splitting the beam into its two components. The separate components are directed onto spaced apart points on the face of the object to be tested for smoothness while the face of the object is rotated on an axis normal to one point, thereby passing the other component over a circular track on the face of the object. The two components are recombined after reflection to produce a reflected frequency difference of a phase proportional to the difference in path length of one component reflected from one point to the other component reflected from the other point. The phase of the reflected frequency difference is compared with the reference phase to produce a signal proportional to the deviation of the height of the surface along the circular track with respect to the fixed point at the center, thereby to produce a signal that is plotted as a profile of the surface along the circular track. The phase detector includes a quarter-wave plate to convert the components of the reference beam into circularly polarized components, a half-wave plate to shift the phase of the circularly polarized components, and a polarizer to produce a signal of a shifted phase for comparison with the phase of the frequency difference of the reflected components detected through a second polarizer. Rotation of the half-wave plate can be used for phase adjustment over a full 360/sup 0/ range.

Partial Arc Curvilinear Direct Drive Servomotor

NASA Technical Reports Server (NTRS)

Sun, Xiuhong (Inventor)

2014-01-01

A partial arc servomotor assembly having a curvilinear U-channel with two parallel rare earth permanent magnet plates facing each other and a pivoted ironless three phase coil armature winding moves between the plates. An encoder read head is fixed to a mounting plate above the coil armature winding and a curvilinear encoder scale is curved to be co-axis with the curvilinear U-channel permanent magnet track formed by the permanent magnet plates. Driven by a set of miniaturized power electronics devices closely looped with a positioning feedback encoder, the angular position and velocity of the pivoted payload is programmable and precisely controlled.

Design of continuous surface-relief phase plates by surface-based simulated annealing to achieve control of focal-plane irradiance

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

Lin, Y.; Kessler, T.J.; Lawrence, G.N.

1996-10-01

High-performance phase plates are of vital concern for controlling the far-field irradiance of laser-fusion systems. Several designs for solving this difficult problem have been reported in {ital Optics} {ital Letters} [e.g., S. N. Dixit {ital et} {ital al}., Opt. Lett. {bold 19}, 417 (1994)]. We report a surface-based form of simulated annealing that significantly improves the irradiance control while eliminating the high-scatter problems that have plagued other methods. {copyright} {ital 1996 Optical Society of America.}

Volume holographic elements in Kodak 131 plates processed with SHSG method

NASA Astrophysics Data System (ADS)

Collados, Manuel V.; Atencia, Jesus; Lopez, Ana M.; Quintanilla, Manuel M.

2001-08-01

A SHSG procedure to register volume phase holograms in Kodak 131 plates is presented. We analyze the influence on the diffraction efficiency of the developing step and the temperature of the bleaching bath of usual SHSG processes. Applying a simple 12 steps process to form phase transmission holograms developing with D-19, bleaching with R-10 at 70 degrees C and removing the sensitizing dyes that remain in the emulsion with a diluted methanol bath after the fixation step, we obtain relative efficiencies of 100 percent and effective efficiencies of 70 percent.

Influence of obliquely subducting slab on Pacific-North America shear motion inferred from seismic anisotropy along the Queen Charlotte margin

NASA Astrophysics Data System (ADS)

Cao, L.; Kao, H.; Wang, K.; Wang, Z.

2016-12-01

Haida Gwaii is located along the transpressive Queen Charlotte margin between the Pacific (PA) and North America (NA) plates. The highly oblique relative plate motion is partitioned, with the strike-slip component accommodated by the Queen Charlotte Fault (QCF) and the convergent component by a thrust fault offshore. To understand how the presence of a obliquely subducting slab influences shear deformation of the plate boundary, we investigate mantle anisotropy by analyzing shear-wave splitting of teleseismic SKS phases recorded at 17 seismic stations in and around Haida Gwaii. We used the MFAST program to determine the polarization direction of the fast wave (φ) and the delay time (δt) between the fast and slow phases. The fast directions derived from stations on Haida Gwaii and two stations to the north on the Alaska Panhandle are predominantly margin-parallel (NNW). However, away from the plate boundary, the fast direction transitions to WSW-trending, very oblique or perpendicular to the plate boundary. Because the average delay time of 0.6-2.45 s is much larger than values based on an associated local S phase splitting analysis in the same study area, it is reasonable to infer that most of the anisotropy from our SKS analysis originates from the upper mantle and is associated with lattice-preferred orientation of anisotropic minerals. The margin-parallel fast direction within about 100 km of the QCF (average φ = -40º and δt = 1.2 s) is likely induced by the PA-NA shear motion. The roughly margin-normal fast directions farther away, although more scatterd, are consistent with that previously observed in the NA continent and are attributed to the absolute motion of the NA plate. However, the transition between the two regimes based on our SKS analysis appears to be gradual, suggesting that the plate boundary shear influences a much broader region at mantle depths than would be inferred from the surface trace of the QCF. We think this is due to the presence of a subducted portion of the Pacific plate. Because the slab travels mostly in the strike direction, it is expected to induce margin-parallel shear deformation of the mantle material. This result has importance implications to the geodynamics of transpressive plate margins.

Topological valley transport of plate-mode waves in a homogenous thin plate with periodic stubbed surface

NASA Astrophysics Data System (ADS)

Chen, Jiu-Jiu; Huo, Shao-Yong; Geng, Zhi-Guo; Huang, Hong-Bo; Zhu, Xue-Feng

2017-11-01

The study for exotic topological effects of sound has attracted uprising interests in fundamental physics and practical applications. Based on the concept of valley pseudospin, we demonstrate the topological valley transport of plate-mode waves in a homogenous thin plate with periodic stubbed surface, where a deterministic two-fold Dirac degeneracy is form by two plate modes. We show that the topological property can be controlled by the height of stubs deposited on the plate. By adjusting the relative heights of adjacent stubs, the valley vortex chirality and band inversion are induced, giving rise to a phononic analog of valley Hall phase transition. We further numerically demonstrate the valley states of plate-mode waves with robust topological protection. Our results provide a new route to design unconventional elastic topological insulators and will significantly broaden its practical application in the engineering field.

Evaluation of the base/subgrade soil under repeated loading : phase II, in-box and ALF cyclic plate load tests.

DOT National Transportation Integrated Search

2012-03-01

This research study aims at evaluating the performance of base and subgrade soil in flexible pavements under repeated loading test conditions. For this purpose, an indoor cyclic plate load testing equipment was developed and used to conduct a series ...

Industrial Processes to Reduce Generation of Hazardous Waste at DoD facilities. Phase 3 Report. Summary of Projects of Excellence Workshops

DTIC Science & Technology

1985-12-01

cation impurities from the plating solution and anodes to oxidize trivalent chromium to hexavalent chromium . Hexa- . valent chromium ions remain on the...corrosion, or to improve its engineering properties (harlness, durability, solderability, or frictional characteristics). Chromium ic used principally...facturing consists of machining the worn part or stripping a portion of the old plate, overplating it with a thick layer of chromium (hard chrome plating

Porous Structures in Stacked, Crumpled and Pillared Graphene-Based 3D Materials.

PubMed

Guo, Fei; Creighton, Megan; Chen, Yantao; Hurt, Robert; Külaots, Indrek

2014-01-01

Graphene, an atomically thin material with the theoretical surface area of 2600 m 2 g -1 , has great potential in the fields of catalysis, separation, and gas storage if properly assembled into functional 3D materials at large scale. In ideal non-interacting ensembles of non-porous multilayer graphene plates, the surface area can be adequately estimated using the simple geometric law ~ 2600 m 2 g -1 /N, where N is the number of graphene sheets per plate. Some processing operations, however, lead to secondary plate-plate stacking, folding, crumpling or pillaring, which give rise to more complex structures. Here we show that bulk samples of multilayer graphene plates stack in an irregular fashion that preserves the 2600/N surface area and creates regular slot-like pores with sizes that are multiples of the unit plate thickness. In contrast, graphene oxide deposits into films with massive area loss (2600 to 40 m 2 g -1 ) due to nearly perfect alignment and stacking during the drying process. Pillaring graphene oxide sheets by co-deposition of colloidal-phase particle-based spacers has the potential to partially restore the large monolayer surface. Surface areas as high as 1000 m 2 g -1 are demonstrated here through colloidal-phase deposition of graphene oxide with water-dispersible aryl-sulfonated ultrafine carbon black as a pillaring agent.

Topography of the overriding plate during progressive subduction: A dynamic model to explain forearc subsidence

NASA Astrophysics Data System (ADS)

Chen, Z.; Schellart, W. P.; Duarte, J. C.; Strak, V.

2017-12-01

Topography that forms at the free top surface of the lithosphere contains important information about the dynamics of the tectonic plates and the sub-lithospheric mantle. Investigating topography around subduction zones can provide quantitative and conceptual insights into the interaction between the plates, the slabs, mantle flow, and the associated stresses. To achieve this, geodynamic modelling can be an effective tool. In this study, we used techniques of stereoscopic photogrammetry and Particle Image Velocimetry to monitor simultaneously the topography of the overriding plate and the velocity field of the subduction-induced mantle flow occurring in the mantle wedge. Model results show that the overriding plate topography is characterized by an area of forearc topographic subsidence, with a magnitude scaling to 1.44-3.97 km in nature, and a transient local topographic high located between the forearc depression and the trench. These topographic features rapidly develop during the slab sinking phase and gradually decrease during the slab rollback phase. We propose that these topographic transient features predominantly result from the variation of the vertical component of the trench suction along the subduction zone interface, which is minimum near the trench and maximum near the tip of the mantle wedge and is caused by the gradual slab steepening during the initial transient slab sinking phase. The downward mantle flow in the nose of the mantle wedge plays a minor role in the formation of the forearc subsidence. Our findings provide a new mechanism for the formation of forearc topographic subsidence, which has been commonly observed at natural subduction zones.

Measuring of temperatures of phase objects using a point-diffraction interferometer plate made with the thermocavitation process

NASA Astrophysics Data System (ADS)

Aguilar, Juan C.; Berriel-Valdos, L. R.; Aguilar, J. Felix; Mejia-Romero, S.

An optical system formed by four point-diffraction interferometers is used for measuring the refractive index distribution of a phase object. The phase of the object is assumed enough smooth to be computed in terms of the Radon Transform and it is processed with a tomographic iterative algorithm. Then, the associated refractive index distribution is calculated. To recovery the phase from the inteferograms we use the Kreis method, which is useful for interferograms having only few fringes. As an application of our technique, the temperature distribution of a candle flame is retrieved, this was made with the aid of the Gladstone-Dale equation. We also describe the process of manufacturing the point-diffraction interferometer (PDI) plates. These were made by means of the thermocavitation process. The obtained three dimensional distribution of temperature is presented.

Method and apparatus for acoustic plate mode liquid-solid phase transition detection

DOEpatents

Blair, Dianna S.; Freye, Gregory C.; Hughes, Robert C.; Martin, Stephen J.; Ricco, Antonio J.

1993-01-01

A method and apparatus for sensing a liquid-solid phase transition event is provided which comprises an acoustic plate mode detecting element placed in contact with a liquid or solid material which generates a high-frequency acoustic wave that is attenuated to an extent based on the physical state of the material is contact with the detecting element. The attenuation caused by the material in contact with the acoustic plate mode detecting element is used to determine the physical state of the material being detected. The method and device are particularly suited for detecting conditions such as the icing and deicing of wings of an aircraft. In another aspect of the present invention, a method is provided wherein the adhesion of a solid material to the detecting element can be measured using the apparatus of the invention.

Retrieval of the thickness and refractive index dispersion of parallel plate from a single interferogram recorded in both spectral and angular domains

NASA Astrophysics Data System (ADS)

Dong, Jingtao; Lu, Rongsheng

2018-04-01

The principle of retrieving the thickness and refractive index dispersion of a parallel glass plate is reported based on single interferogram recording and phase analysis. With the parallel plate illuminated by a convergent light sheet, the transmitted light interfering in both spectral and angular domains is recorded. The phase recovered from the single interferogram by Fourier analysis is used to retrieve the thickness and refractive index dispersion without periodic ambiguity. Experimental results of an optical substrate standard show that the accuracy of refractive index dispersion is less than 2.5 × 10-5 and the relative uncertainty of thickness is 6 × 10-5 (3σ). This method is confirmed to be robust against the intensity noises, indicating the capability of stable and accurate measurement.

Crystallographic study of Si and ZrN coated U-Mo atomised particles and of their interaction with al under thermal annealing

NASA Astrophysics Data System (ADS)

Zweifel, T.; Palancher, H.; Leenaers, A.; Bonnin, A.; Honkimaki, V.; Tucoulou, R.; Van Den Berghe, S.; Jungwirth, R.; Charollais, F.; Petry, W.

2013-11-01

A new type of high density fuel is needed for the conversion of research and test reactors from high to lower enriched uranium. The most promising one is a dispersion of atomized uranium-molybdenum (U-Mo) particles in an Al matrix. However, during in-pile irradiation the growth of an interaction layer between the U-Mo and the Al matrix strongly limits the fuel's performance. To improve the in-pile behaviour, the U-Mo particles can be coated with protective layers. The SELENIUM (Surface Engineering of Low ENrIched Uranium-Molybdenum) fuel development project consists of the production, irradiation and post-irradiation examination of 2 flat, full-size dispersion fuel plates containing respectively Si and ZrN coated U-Mo atomized powder dispersed in a pure Al matrix. In this paper X-ray diffraction analyses of the Si and ZrN layers after deposition, fuel plate manufacturing and thermal annealing are reported. It was found for the U-Mo particles coated with ZrN (thickness 1 μm), that the layer is crystalline, and exhibits lower density than the theoretical one. Fuel plate manufacturing does not strongly influence these crystallographic features. For the U-Mo particles coated with Si (thickness 0.6 μm), the measurements of the as received material suggest an amorphous state of the deposited layer. Fuel plate manufacturing strongly modifies its composition: Si reacts with the U-Mo particles and the Al matrix to grow U(Al, Si)3 and U3Si5 phases. Finally both coatings have shown excellent performances under thermal treatment by limiting drastically the U-Mo/Al interdiffusion. U(Al,Si)3 with two lattice parameters (4.16 Å and 4.21 Å), A distorted U3Si5 phase. Note that these phases were not present in the U-Mo(Si) powders. These phases are usually found in the Silicon rich diffusion layer (SiRDL) obtained in dispersed fuels (as-manufactured U-Mo/Al(Si) fuel plates [12,3] or annealed UMo(Si)/Al fuel rods [40]) as well as in diffusion couples (U-Mo/Al(Si7) [37-39] or U-Mo/Si [41]). This analysis is furthermore in full agreement with the SEM/EDX characterisations which have highlighted the growth of a SiRDL in these U-Mo(Si)/Al_P fuel plates [30]. However it must be stressed that the amount of these U(Al,Si)3 and U3Si5 crystalline phases (about 0.3 wt%) is lower than the one obtained for fuel plates containing 4-6 wt% Si in the matrix [12]. It equals to the SiRDL amount measured in the IRIS4_2.1%Si fuel plate. Using these HE-XRD measurements, the Si concentration in SiRDLs is evaluated to 51 at%. This value is somewhat higher than when measured by EDX: it has been estimated to 40 at% in [30]. U2Mo and α"-U phase for compacts annealed at 340 °C, U2Mo and α'-U phase for compacts annealed at 450 °C [43], gamma;-U-Mo and α'-U for compacts annealed at 550 °C. These results obtained on compacts are in good agreement with previous works performed on U-8Mo ingots (see Fig. 9A) -even if some differences in the α-U phase structure must be mentioned - and in very close agreement with recent studies on thermally annealed U-Mo/Al fuel plates. Indeed destabilisation products found in this work are identical to those identified after fuel plate annealing at 550 °C [25] and 450 °C [43]. Moreover this work helps establishing that destabilisation products are U2Mo and α"-U at lower temperatures (below 450 °C). This was first demonstrated on fuel plates annealed at 425 °C for more than 50 h [43] and this is confirmed here with the analysis of the compacts annealed at 340 °C during 130 days. Note finally that whatever the presence of a coating, destabilisation ratios are very close in compacts annealed in the same conditions (see Fig. 9B) and that destabilisation ratios show the expected increase between 2 and 4 h annealing at 550 °C. The non-annealed U-Mo(Si)/Al compact has been lost during fabrication.

Design for the optical retardation in broadband zero-order half-wave plates.

PubMed

Liu, Jin; Cai, Yi; Chen, Hongyi; Zeng, Xuanke; Zou, Da; Xu, Shixiang

2011-04-25

This paper presents a novel design for broadband zero-order half-wave plates to eliminate the first-order or up to second-order wavelength-dependent birefringent phase retardation (BPR) with 2 or 3 different birefringent materials. The residual BPRs of the plates increase monotonously with the wavelength deviation from a selected wavelength, so the plates are applicable to the broadband light pulses which gather most of the light energy around their central wavelengths. The model chooses the materials by the birefringent dispersion coefficient and evaluates the performances of the plates by the weighted average of the absolute value of residual BPR in order to emphasize the contributions of the incident spectral components whose possess higher energies.

Growth kinetics and microstructural evolution during hot isostatic pressing of U-10 wt.% Mo monolithic fuel plate in AA6061 cladding with Zr diffusion barrier

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

Y. Park; J. Yoo; K. Huang

2014-04-01

Phase constituents and microstructure changes in RERTR fuel plate assemblies as functions of temperature and duration of hot-isostatic pressing (HIP) during fabrication were examined. The HIP process was carried out as functions of temperature (520, 540, 560 and 580 °C for 90 min) and time (45–345 min at 560 °C) to bond 6061 Al-alloy to the Zr diffusion barrier that had been co-rolled with U-10 wt.% Mo (U10Mo) fuel monolith prior to the HIP process. Scanning and transmission electron microscopies were employed to examine the phase constituents, microstructure and layer thickness of interaction products from interdiffusion. At the interface betweenmore » the U10Mo and Zr, following the co-rolling, the UZr2 phase was observed to develop adjacent to Zr, and the a-U phase was found between the UZr2 and U10Mo, while the Mo2Zr was found as precipitates mostly within the a-U phase. The phase constituents and thickness of the interaction layer at the U10Mo-Zr interface remained unchanged regardless of HIP processing variation. Observable growth due to HIP was only observed for the (Al,Si)3Zr phase found at the Zr/AA6061 interface, however, with a large activation energy of 457 ± 28 kJ/mole. Thus, HIP can be carried to improve the adhesion quality of fuel plate without concern for the excessive growth of the interaction layer, particularly at the U10Mo-Zr interface with the a-U, Mo2Zr, and UZr2 phases.« less

Growth kinetics and microstructural evolution during hot isostatic pressing of U-10 wt.% Mo monolithic fuel plate in AA6061 cladding with Zr diffusion barrier

NASA Astrophysics Data System (ADS)

Park, Y.; Yoo, J.; Huang, K.; Keiser, D. D.; Jue, J. F.; Rabin, B.; Moore, G.; Sohn, Y. H.

2014-04-01

Phase constituents and microstructure changes in RERTR fuel plate assemblies as functions of temperature and duration of hot-isostatic pressing (HIP) during fabrication were examined. The HIP process was carried out as functions of temperature (520, 540, 560 and 580 °C for 90 min) and time (45-345 min at 560 °C) to bond 6061 Al-alloy to the Zr diffusion barrier that had been co-rolled with U-10 wt.% Mo (U10Mo) fuel monolith prior to the HIP process. Scanning and transmission electron microscopies were employed to examine the phase constituents, microstructure and layer thickness of interaction products from interdiffusion. At the interface between the U10Mo and Zr, following the co-rolling, the UZr2 phase was observed to develop adjacent to Zr, and the α-U phase was found between the UZr2 and U10Mo, while the Mo2Zr was found as precipitates mostly within the α-U phase. The phase constituents and thickness of the interaction layer at the U10Mo-Zr interface remained unchanged regardless of HIP processing variation. Observable growth due to HIP was only observed for the (Al,Si)3Zr phase found at the Zr/AA6061 interface, however, with a large activation energy of 457 ± 28 kJ/mole. Thus, HIP can be carried to improve the adhesion quality of fuel plate without concern for the excessive growth of the interaction layer, particularly at the U10Mo-Zr interface with the α-U, Mo2Zr, and UZr2 phases.

Highly intense monocycle terahertz vortex generation by utilizing a Tsurupica spiral phase plate

PubMed Central

Miyamoto, Katsuhiko; Kang, Bong Joo; Kim, Won Tae; Sasaki, Yuta; Niinomi, Hiromasa; Suizu, Koji; Rotermund, Fabian; Omatsu, Takashige

2016-01-01

Optical vortex, possessing an annular intensity profile and an orbital angular momentum (characterized by an integer termed a topological charge) associated with a helical wavefront, has attracted great attention for diverse applications due to its unique properties. In particular for terahertz (THz) frequency range, several approaches for THz vortex generation, including molded phase plates consisting of metal slit antennas, achromatic polarization elements and binary-diffractive optical elements, have been recently proposed, however, they are typically designed for a specific frequency. Here, we demonstrate highly intense broadband monocycle vortex generation near 0.6 THz by utilizing a polymeric Tsurupica spiral phase plate in combination with tilted-pulse-front optical rectification in a prism-cut LiNbO3 crystal. A maximum peak power of 2.3 MW was obtained for THz vortex output with an expected topological charge of 1.15. Furthermore, we applied the highly intense THz vortex beam for studying unique nonlinear behaviors in bilayer graphene towards the development of nonlinear super-resolution THz microscopy and imaging system. PMID:27966595

Generation of fractional acoustic vortex with a discrete Archimedean spiral structure plate

NASA Astrophysics Data System (ADS)

Jia, Yu-Rou; Wei, Qi; Wu, Da-Jian; Xu, Zheng; Liu, Xiao-Jun

2018-04-01

Artificial structure plates engraved with discrete Archimedean spiral slits have been well designed to achieve fractional acoustic vortices (FAVs). The phase and pressure field distributions of FAVs are investigated theoretically and demonstrated numerically. It is found that the phase singularities relating to the integer and fractional parts of the topological charge (TC) result in dark spots in the upper half of the pressure field profile and a low-intensity stripe in the lower half of the pressure field profile, respectively. The dynamic progress of the FAV is also discussed in detail as TC increases from 1 to 2. With increasing TC from 1 to 1.5, the splitting of the phase singularity leads to the deviation of the phase of the FAV from the integer case and hence a new phase singularity occurs. As TC m increases from 1.5 to 2, two phase singularities of the FAV approach together and finally merge as a new central phase singularity. We further perform an experiment based on the Schlieren method to demonstrate the generation of the FAV.

Development of flat-plate solar plate collector: Evaporator

NASA Astrophysics Data System (ADS)

Abramzon, B.; Yaron, I.

1981-11-01

In the present study the thermal performance of a flat plate solar collector is analyzed theoretically for the case in which the working fluid may undergo a phase change within the tubes of the collector. In addition to the common domestic applications, such a collector - evaporator may be used as a generator of vapors for the production of mechanical or electrical energy, e.g., solar water pumps, solar power stations, etc., as well as for solar - powered absorption refrigeration machines, distillation installations, etc.

Guided Lamb wave based 2-D spiral phased array for structural health monitoring of thin panel structures

NASA Astrophysics Data System (ADS)

Yoo, Byungseok

2011-12-01

In almost all industries of mechanical, aerospace, and civil engineering fields, structural health monitoring (SHM) technology is essentially required for providing the reliable information of structural integrity of safety-critical structures, which can help reduce the risk of unexpected and sometimes catastrophic failures, and also offer cost-effective inspection and maintenance of the structures. State of the art SHM research on structural damage diagnosis is focused on developing global and real-time technologies to identify the existence, location, extent, and type of damage. In order to detect and monitor the structural damage in plate-like structures, SHM technology based on guided Lamb wave (GLW) interrogation is becoming more attractive due to its potential benefits such as large inspection area coverage in short time, simple inspection mechanism, and sensitivity to small damage. However, the GLW method has a few critical issues such as dispersion nature, mode conversion and separation, and multiple-mode existence. Phased array technique widely used in all aspects of civil, military, science, and medical industry fields may be employed to resolve the drawbacks of the GLW method. The GLW-based phased array approach is able to effectively examine and analyze complicated structural vibration responses in thin plate structures. Because the phased sensor array operates as a spatial filter for the GLW signals, the array signal processing method can enhance a desired signal component at a specific direction while eliminating other signal components from other directions. This dissertation presents the development, the experimental validation, and the damage detection applications of an innovative signal processing algorithm based on two-dimensional (2-D) spiral phased array in conjunction with the GLW interrogation technique. It starts with general backgrounds of SHM and the associated technology including the GLW interrogation method. Then, it is focused on the fundamentals of the GLW-based phased array approach and the development of an innovative signal processing algorithm associated with the 2-D spiral phased sensor array. The SHM approach based on array responses determined by the proposed phased array algorithm implementation is addressed. The experimental validation of the GLW-based 2-D spiral phased array technology and the associated damage detection applications to thin isotropic plate and anisotropic composite plate structures are presented.

Performance optimization of plate heat exchangers with chevron plates

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

Muley, A.; Manglik, R.M.

1999-07-01

The enhanced heat transfer performance of a chevron plate heat exchanger (PHE) is evaluated employing (1) energy-conservation based performance evaluation criteria (PECs), and (2) the second-law based minimization of entropy generation principle. Single-phase laminar and turbulent flow convection for three different chevron-plate arrangements are considered. The influence of plate surface corrugation characteristics and their stack arrangements on the heat exchanger's thermal-hydraulic performance is delineated. Based on the different figures of merit, the results show that the extent of heat transfer enhancement increases with flow Re and chevron angle {beta} in laminar flow, but it diminishes with increasing Re in turbulentmore » flows. With up to 2.9 times higher Q, 48% lower A, and entropy generation number N{sub s,a} {lt} 1, relative to an equivalent flat-plate pack, chevron plates are found to be especially suitable in the low to medium flow rates range (20 {le} Re {le} 2,000). Also, there appears to be no significant advantage of using a mixed-plate over a symmetric-plate arrangement.« less

Phase composition and fine structure of 0.18C-1Cr-3Ni-1Mo-Fe steel after plasma-electrolytic treatment

NASA Astrophysics Data System (ADS)

Popova, Natalya; Bayatanova, Lyayla; Nikonenko, Elena; Skakov, Mazhyn; Kozlov, Eduard

2017-01-01

The paper presents the transmission electron microscopy (TEM) investigation of 0.18C-1Cr-3Mn-1Mo- Fe steel specimens to study phase transitions and modification of fine structure after plasma-electrolytic treatment (carbonitriding at 850°C during 5 min). TEM investigations involve two points: on the specimen surface and at ˜40 µm distance from it. The experiments show that the structure in the original state is a mixture consisting of ferrite and perlite grains. Carbonitriding results in a considerable modification of the quality and quantity of steel structure. Thus, on the surface, α-phase is represented by lamellar martensite, while at ˜40 µm depth - by massive and lamellar martensite tempered at low and high temperatures. Moreover, on the subsurface of the martensite plates' boundaries retained austenite layers are observed, while inside plates the particles of alloyed cementite, carbonitrides of M23(C,N)6, M2C0.61N0.39, M6,2C3,5N0,3, M(C,N)2, Cr12Fe32Mo7Ni7 types, and β-graphite are present. In the specimen at the depth of ˜40 µm, retained austenite layers are observed on the boundaries of martensite laths and plates, while inside plates only the particles of alloyed cementite and M23(C,N)6 carbonitride are formed.

Topical Treatment of Cutaneous Leishmaniasis W/WR279396 Phase II Study. Addendum

DTIC Science & Technology

2006-07-01

France) g. Tape so seal plates h. Sterile flat-bottom 96-well plates i. Inverted microscope with trail (France) j . Cryomarkers 2. Check list 2...Subinvestigators: Nathalie Messaoud Amor Zaâtour Abdelkarim El Fahem Nabil Haj Hmida OBJECTIVE To collaborate with the monitoring visit SUNDAY 19/02

Optimization of the Ethanol Recycling Reflux Extraction Process for Saponins Using a Design Space Approach

PubMed Central

Gong, Xingchu; Zhang, Ying; Pan, Jianyang; Qu, Haibin

2014-01-01

A solvent recycling reflux extraction process for Panax notoginseng was optimized using a design space approach to improve the batch-to-batch consistency of the extract. Saponin yields, total saponin purity, and pigment yield were defined as the process critical quality attributes (CQAs). Ethanol content, extraction time, and the ratio of the recycling ethanol flow rate and initial solvent volume in the extraction tank (RES) were identified as the critical process parameters (CPPs) via quantitative risk assessment. Box-Behnken design experiments were performed. Quadratic models between CPPs and process CQAs were developed, with determination coefficients higher than 0.88. As the ethanol concentration decreases, saponin yields first increase and then decrease. A longer extraction time leads to higher yields of the ginsenosides Rb1 and Rd. The total saponin purity increases as the ethanol concentration increases. The pigment yield increases as the ethanol concentration decreases or extraction time increases. The design space was calculated using a Monte-Carlo simulation method with an acceptable probability of 0.90. Normal operation ranges to attain process CQA criteria with a probability of more than 0.914 are recommended as follows: ethanol content of 79–82%, extraction time of 6.1–7.1 h, and RES of 0.039–0.040 min−1. Most of the results of the verification experiments agreed well with the predictions. The verification experiment results showed that the selection of proper operating ethanol content, extraction time, and RES within the design space can ensure that the CQA criteria are met. PMID:25470598

Birth-death models and coalescent point processes: the shape and probability of reconstructed phylogenies.

PubMed

Lambert, Amaury; Stadler, Tanja

2013-12-01

Forward-in-time models of diversification (i.e., speciation and extinction) produce phylogenetic trees that grow "vertically" as time goes by. Pruning the extinct lineages out of such trees leads to natural models for reconstructed trees (i.e., phylogenies of extant species). Alternatively, reconstructed trees can be modelled by coalescent point processes (CPPs), where trees grow "horizontally" by the sequential addition of vertical edges. Each new edge starts at some random speciation time and ends at the present time; speciation times are drawn from the same distribution independently. CPPs lead to extremely fast computation of tree likelihoods and simulation of reconstructed trees. Their topology always follows the uniform distribution on ranked tree shapes (URT). We characterize which forward-in-time models lead to URT reconstructed trees and among these, which lead to CPP reconstructed trees. We show that for any "asymmetric" diversification model in which speciation rates only depend on time and extinction rates only depend on time and on a non-heritable trait (e.g., age), the reconstructed tree is CPP, even if extant species are incompletely sampled. If rates additionally depend on the number of species, the reconstructed tree is (only) URT (but not CPP). We characterize the common distribution of speciation times in the CPP description, and discuss incomplete species sampling as well as three special model cases in detail: (1) the extinction rate does not depend on a trait; (2) rates do not depend on time; (3) mass extinctions may happen additionally at certain points in the past. Copyright © 2013 Elsevier Inc. All rights reserved.

Engineering of an inhalable DDA/TDB liposomal adjuvant: a quality-by-design approach towards optimization of the spray drying process.

PubMed

Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle; Nielsen, Hanne Mørck; Rantanen, Jukka; Foged, Camilla

2013-11-01

The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB). A quality by design (QbD) approach was applied to identify and link critical process parameters (CPPs) of the spray drying process to critical quality attributes (CQAs) using risk assessment and design of experiments (DoE), followed by identification of an optimal operating space (OOS). A central composite face-centered design was carried out followed by multiple linear regression analysis. Four CQAs were identified; the mass median aerodynamic diameter (MMAD), the liposome stability (size) during processing, the moisture content and the yield. Five CPPs (drying airflow, feed flow rate, feedstock concentration, atomizing airflow and outlet temperature) were identified and tested in a systematic way. The MMAD and the yield were successfully modeled. For the liposome size stability, the ratio between the size after and before spray drying was modeled successfully. The model for the residual moisture content was poor, although, the moisture content was below 3% in the entire design space. Finally, the OOS was drafted from the constructed models for the spray drying of trehalose stabilized DDA/TDB liposomes. The QbD approach for the spray drying process should include a careful consideration of the quality target product profile. This approach implementing risk assessment and DoE was successfully applied to optimize the spray drying of an inhalable DDA/TDB liposomal adjuvant designed for pulmonary vaccination.

Nose-to-Brain Delivery of Peptide Drugs Enhanced by Coadministration of Cell-penetrating Peptides: Therapeutic Potential for Dementia.

PubMed

Kamei, Noriyasu

2017-01-01

Recent reports suggest that peptide drugs such as insulin have the potential to serve as therapeutics in neurodegenerative diseases such as Alzheimer's disease. However, the transport of these drugs to the therapeutic target, the brain, is significantly hindered by the blood-brain barrier (BBB). Intranasal administration appears to be an ideal solution for drug delivery to the brain, bypassing the BBB, however the entry of peptide drugs into neuronal and epithelial cells in the olfactory mucosa remains low. In this study, we therefore examined whether intranasal coadministration of cell-penetrating peptides (CPPs) could improve nose-to-brain drug transport. In both mice and rats, we found that direct transport of insulin into the brain was significantly facilitated when coadministered with amphipathic CPP penetratin, and eventually insulin reached the deeper regions of the brain such as the hippocampus. In the mouse line senescence-accelerated mouse prone-8 (SAMP8), spatial learning tests demonstrated that long-term intranasal coadministration of insulin with penetratin improved mild memory loss in the early stages of dementia. In contrast, the severe cognitive dysfunction in the aged SAMP8 mice was preserved despite intranasal coadministration of insulin with penetratin. The immunohistological examination of the hippocampus suggested that enhanced nose-to-brain delivery of insulin had a partial neuroprotective effect but unexpectedly increased amyloid β plaque deposition. In conclusion, intranasal coadministration of insulin with CPPs has the potential to serve as a therapeutic for mild cognitive dysfunction. To identify suitable pharmacotherapy for dementia with severe pathology, further studies of nose-to-brain delivery of molecularly appropriate biopharmaceuticals are necessary.

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

PubMed

Abes, Saïd; Moulton, Hong M; Clair, Philippe; Prevot, Paul; Youngblood, Derek S; Wu, Rebecca P; Iversen, Patrick L; Lebleu, Bernard

2006-12-01

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.

Generation of GFP Native Protein for Detection of Its Intracellular Uptake by Cell-Penetrating Peptides.

PubMed

Kadkhodayan, S; Sadat, S M; Irani, S; Fotouhi, F; Bolhassani, A

2016-01-01

Different types of lipid- and polymer-based vectors have been developed to deliver proteins into cells, but these methods showed relatively poor efficiency. Recently, a group of short, highly basic peptides known as cell-penetrating peptides (CPPs) were used to carry polypeptides and proteins into cells. In this study, expression and purification of GFP protein was performed using the prokaryotic pET expression system. We used two amphipathic CPPs (Pep-1 and CADY-2) as a novel delivery system to transfer the GFP protein into cells. The morphological features of the CPP/GFP complexes were studied by scanning electron microscopy (SEM), Zetasizer, and SDS-PAGE. The efficiency of GFP transfection using Pep-1 and CADY-2 peptides and TurboFect reagent was compared with FITC-antibody protein control delivered by these transfection vehicles in the HEK-293T cell line. SEM data confirmed formation of discrete nanoparticles with a diameter of below 300 nm. Moreover, formation of the complexes was detected using SDS-PAGE as two individual bands, indicating non-covalent interaction. The size and homogeneity of Pep-1/GFP and CADY-2/GFP complexes were dependent on the ratio of peptide/cargo formulations, and responsible for their biological efficiency. The cells transfected by Pep-1/GFP and CADY-2/GFP complexes at a molar ratio of 20 : 1 demonstrated spreading green regions using fluorescent microscopy. Flow cytometry results showed that the transfection efficiency of Pep-based nanoparticles was similar to CADY-based nanoparticles and comparable with TurboFect-protein complexes. These data open an efficient way for future therapeutic purposes.

A standard for terminology in chronic pelvic pain syndromes: A report from the chronic pelvic pain working group of the international continence society.

PubMed

Doggweiler, Regula; Whitmore, Kristene E; Meijlink, Jane M; Drake, Marcus J; Frawley, Helena; Nordling, Jørgen; Hanno, Philip; Fraser, Matthew O; Homma, Yukio; Garrido, Gustavo; Gomes, Mario J; Elneil, Sohier; van de Merwe, Joop P; Lin, Alex T L; Tomoe, Hikaru

2017-04-01

Terms used in the field of chronic pelvic pain (CPP) are poorly defined and often confusing. An International Continence Society (ICS) Standard for Terminology in chronic pelvic pain syndromes (CPPS) has been developed with the aim of improving diagnosis and treatment of patients affected by chronic pelvic pain syndromes. The standard aims to facilitate research, enhance therapy development and support healthcare delivery, for healthcare providers, and patients. This document looks at the whole person and all the domains (organ systems) in a systematic way. A dedicated working group (WG) was instituted by the ICS Standardisation Steering Committee according to published procedures. The WG extracted information from existing relevant guidelines, consensus documents, and scientific publications. Medline and other databases were searched in relation to each chronic pelvic pain domain from 1980 to 2014. Existing ICS Standards for terminology were utilized where appropriate to ensure transparency, accessibility, flexibility, and evolution. Consensus was based on majority agreement. The multidisciplinary CPPS Standard reports updated consensus terminology in nine domains; lower urinary tract, female genital, male genital, gastrointestinal, musculoskeletal, neurological aspects, psychological aspects, sexual aspects, and comorbidities. Each is described in terms of symptoms, signs and further evaluation. The document presents preferred terms and definitions for symptoms, signs, and evaluation (diagnostic work-up) of female and male patients with chronic pelvic pain syndromes, serving as a platform for ongoing development in this field. Neurourol. Urodynam. 36:984-1008, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Process analytical technology (PAT) in insect and mammalian cell culture processes: dielectric spectroscopy and focused beam reflectance measurement (FBRM).

PubMed

Druzinec, Damir; Weiss, Katja; Elseberg, Christiane; Salzig, Denise; Kraume, Matthias; Pörtner, Ralf; Czermak, Peter

2014-01-01

Modern bioprocesses demand for a careful definition of the critical process parameters (CPPs) already during the early stages of process development in order to ensure high-quality products and satisfactory yields. In this context, online monitoring tools can be applied to recognize unfavorable changes of CPPs during the production processes and to allow for early interventions in order to prevent losses of production batches due to quality issues. Process analytical technologies such as the dielectric spectroscopy or focused beam reflectance measurement (FBRM) are possible online monitoring tools, which can be applied to monitor cell growth as well as morphological changes. Since the dielectric spectroscopy only captures cells with intact cell membranes, even information about dead cells with ruptured or leaking cell membranes can be derived. The following chapter describes the application of dielectric spectroscopy on various virus-infected and non-infected cell lines with respect to adherent as well as suspension cultures in common stirred tank reactors. The adherent mammalian cell lines Vero (African green monkey kidney cells) and hMSC-TERT (telomerase-immortalized human mesenchymal stem cells) are thereby cultured on microcarrier, which provide the required growth surface and allow the cultivation of these cells even in dynamic culture systems. In turn, the insect-derived cell lines S2 and Sf21 are used as examples for cells typically cultured in suspension. Moreover, the FBRM technology as a further monitoring tool for cell culture applications has been included in this chapter using the example of Drosophila S2 insect cells.

The propagation characteristics of the plate modes of acoustic emission waves in thin aluminum plates and thin graphite/epoxy composite plates and tubes. Ph.D. Thesis - Johns Hopkins Univ., 1991

NASA Technical Reports Server (NTRS)

Prosser, William H.

1991-01-01

Acoustic emission was interpreted as modes of vibration in plates. Classical plate theory was used to predict dispersion curves for the two fundamental modes and to calculate the shapes of flexural waveforms produced by vertical step function loading. There was good agreement between theoretical and experimental results for aluminum. Composite materials required the use of a higher order plate theory (Reissner-Mindlin) to get good agreement with the measured velocities. Four composite plates with different laminate stacking sequences were studied. The dispersion curves were determined from phase spectra of the time dependent waveforms. Plate modes were shown to be useful for determining the direction of source motion. Aluminum plates were loaded by breaking a pencil lead against their surface. By machining slots at angles to the plane of a plate, the direction in which the force acted was varied. Changing the source motion direction produced regular variations in the waveforms. To demonstrate applicability beyond simple plates, waveforms produced by lead breaks on a thin walled composite tube were also shown to be interpretable as plate modes. The tube design was based on the type of struts proposed for Space Station Freedom's trussed structures.

A one-dimensional heat transfer model for parallel-plate thermoacoustic heat exchangers.

PubMed

de Jong, J A; Wijnant, Y H; de Boer, A

2014-03-01

A one-dimensional (1D) laminar oscillating flow heat transfer model is derived and applied to parallel-plate thermoacoustic heat exchangers. The model can be used to estimate the heat transfer from the solid wall to the acoustic medium, which is required for the heat input/output of thermoacoustic systems. The model is implementable in existing (quasi-)1D thermoacoustic codes, such as DeltaEC. Examples of generated results show good agreement with literature results. The model allows for arbitrary wave phasing; however, it is shown that the wave phasing does not significantly influence the heat transfer.

Adaptive optical system for writing large holographic optical elements

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

Tyutchev, M.V.; Kalyashov, E.V.; Pavlov, A.P.

1994-11-01

This paper formulates the requirements imposed on systems for correcting the phase-difference distribution of recording waves over the field of a large-diameter photographic plate ({le}1.5 m) when writing holographic optical elements (HOEs). A technique is proposed for writing large HOEs, based on the use of an adaptive phase-correction optical system of the first type, controlled by the self-diffraction signal from a latent image. The technique is implemented by writing HOEs on photographic plates with an effective diameter of 0.7 m on As{sub 2}S{sub 3} layers. 13 refs., 4 figs.

Measurement of the complex transmittance of large optical elements with Ptychographical Iterative Engine.

PubMed

Wang, Hai-Yan; Liu, Cheng; Veetil, Suhas P; Pan, Xing-Chen; Zhu, Jian-Qiang

2014-01-27

Wavefront control is a significant parameter in inertial confinement fusion (ICF). The complex transmittance of large optical elements which are often used in ICF is obtained by computing the phase difference of the illuminating and transmitting fields using Ptychographical Iterative Engine (PIE). This can accurately and effectively measure the transmittance of large optical elements with irregular surface profiles, which are otherwise not measurable using commonly used interferometric techniques due to a lack of standard reference plate. Experiments are done with a Continue Phase Plate (CPP) to illustrate the feasibility of this method.

Abrupt plate acceleration through oblique rifting: Geodynamic aspects of Gulf of California evolution

NASA Astrophysics Data System (ADS)

Brune, S.

2016-12-01

The Gulf of California formed by oblique divergence across the Pacific-North America plate boundary. This presentation combines numerical forward modeling and plate tectonic reconstructions in order to address 2 important aspects of rift dynamics: (1) Plate motions during continental rifting are decisively controlled by the non-linear decay of rift strength. This conclusion is based on a recent plate-kinematic analysis of post-Pangea rift systems (Central Atlantic, South Atlantic, Iberia/Newfoundland, Australia/Antarctica, North Atlantic, South China Sea). In all cases, continental rifting starts with a slow phase followed by an abrupt acceleration within a few My introducing a fast rift phase. Numerical forward modeling with force boundary conditions shows that the two-phase velocity behavior and the rapid speed-up during rifting are intrinsic features of continental rupture that can be robustly inferred for different crust and mantle rheologies. (2) Rift strength depends on the obliquity of the rift system: the force required to maintain a given rift velocity can be computed from simple analytical and more realistic numerical models alike, and both modeling approaches demonstrate that less force is required to perpetuate oblique extension. The reason is that plastic yielding requires a smaller plate boundary force when extension is oblique to the rift trend. Comparing strike slip and pure extension end-member scenarios, it can be shown that about 50% less force is required to deform the lithosphere under strike-slip. This result implies that rift systems involving significant obliquity are mechanically preferred. These two aspects shed new light on the underlying geodynamic causes of Gulf of California rift history. Continental extension is thought to have started in Late Eocene/Oligocene times as part of the southern Basin and Range Province and evolved in a protracted history at low extension rate (≤15 mm/yr). However, with a direction change in Baja California microplate motion 13-6 My ago, plate divergence drastically increased its obliquity, which reduced the rifts mechanical resistance to extension. This effective loss of rift strength sparked an acceleration of the Gulf of California rift and ultimately enabled today's divergence velocities of more than 45 mm/yr.

Deformational History and Rotation of the Leeward Antilles Island Arc: Results of the BOLIVAR Project

NASA Astrophysics Data System (ADS)

Beardsley, A. G.; Avé Lallemant, H. G.

2005-12-01

The Leeward Antilles island arc is located offshore northern Venezuela and includes Aruba, Curaçao, and Bonaire (ABCs). The ABCs trend WNW-ESE parallel to the obliquely convergent Caribbean-South American plate boundary zone. Field work on the ABCs has provided new structural data supporting a minimum of 90° clockwise rotation of the islands within the diffuse plate boundary zone. Analysis of faulting, bedding, and cleavages suggest three phases of deformation (D1-D3). The oldest phase of deformation, D1, is characterized by northeast trending normal faults, northwest trending fold axes and cleavages, and northeast striking dextral strike-slip faults. East striking sinstral strike-slip faults are rare. The second phase of deformation, D2, is represented by west-northwest trending thrust faults, north-northeast striking normal faults, northwest trending dextral strike-slip faults, and northeast striking sinstral strike-slip faults. Finally, the youngest phase of deformation, D3, is characterized by northeast striking thrust faults, northwest striking normal faults, east-west dextral strike-slip faults, and north-northwest sinstral strike-slip faults. Quartz and calcite veins were also studied on the ABCs. Cross-cutting relationships in outcrop suggest three phases of veining (V1-V3). The oldest veins, V1, trend northeastward; V2 veins trend northward; and the youngest veins, V3, trend northwestward. Additionally, joints were measured on the ABCs. On Bonaire and Curaçao, joints trend approximately northeast while joints on Aruba are almost random with a slight preference for west-northwest. Fluid inclusion analysis of quartz and calcite veins provides additional information about the pressure and temperature conditions of the deformation phases. Preliminary results from the earliest veins (V1) show a single deformational event on Aruba and Bonaire. On Bonaire, they exhibit both hydrostatic and lithostatic pressure conditions. This new data supports three stages of deformation accompanied by rotation of the ABCs. The structures identified suggest a clockwise rotation of the principal stress orientation since the Late Cretaceous. D1 deformation and rotation occurred at the southeastern Caribbean plate margin beginning approximately 73 Ma on Aruba. Arc-parallel strike-slip motion rotated the islands clockwise 90° Internal deformation features of the island blocks are consistent with an obliquely convergent plate boundary. D2 deformation is characterized by clockwise block rotation facilitated by dextral strike-slip faults defining the northern and southern boundaries of the diffuse plate boundary zone. Most likely, D2 correlates to the Eocene change in plate motions due to convergence between North and South America, approximately 55 Ma. The youngest phase of deformation and rotation, D3, happens along the arcuate South Caribbean Deformed Belt. Since approximately 25 Ma, rotation and development of northwest trending pull-apart basins between the ABCs progressed. Northeastward motion of the Maracaibo block may also contribute to recent rotation of the island arc.

Zernike phase-contrast electron cryotomography applied to marine cyanobacteria infected with cyanophages.

PubMed

Dai, Wei; Fu, Caroline; Khant, Htet A; Ludtke, Steven J; Schmid, Michael F; Chiu, Wah

2014-11-01

Advances in electron cryotomography have provided new opportunities to visualize the internal 3D structures of a bacterium. An electron microscope equipped with Zernike phase-contrast optics produces images with markedly increased contrast compared with images obtained by conventional electron microscopy. Here we describe a protocol to apply Zernike phase plate technology for acquiring electron tomographic tilt series of cyanophage-infected cyanobacterial cells embedded in ice, without staining or chemical fixation. We detail the procedures for aligning and assessing phase plates for data collection, and methods for obtaining 3D structures of cyanophage assembly intermediates in the host by subtomogram alignment, classification and averaging. Acquiring three or four tomographic tilt series takes ∼12 h on a JEM2200FS electron microscope. We expect this time requirement to decrease substantially as the technique matures. The time required for annotation and subtomogram averaging varies widely depending on the project goals and data volume.

Enhanced microlithography using coated objectives and image duplication

NASA Astrophysics Data System (ADS)

Erdelyi, Miklos; Bor, Zsolt; Szabo, Gabor; Tittel, Frank K.

1998-06-01

Two processes were investigated theoretically using both a scalar wave optics model and a microlithography simulation tool (Solid-C). The first method introduces a phase- transmission filter into the exit pupil plane. The results of both the scalar optics calculation (aerial image) and the Solid-C simulation (resist image) show that the final image profile is optimum, when the exit pupil plane filter is divided into two zones with the inner zone having a phase retardation of (pi) rad with respect to the outer one and the ratio of the radii of the zones is 0.3. Using this optimized filter for the fabrication of isolated contact holes, the focus-exposure process window increases significantly, and the depth of focus (DOF) can be enhanced by a factor of 1.5 to 2. The second technique enhances the DOF of the aerial image by means of a birefringent plate inserted between the projection lens and the wafer. As the shift in focus introduced by the plate strongly depends on the refractive index, two focal points will appear when using a birefringent plate instead of an isotropic plate: the first one is created by the ordinary, and the second one is created by the extraordinary ray. The distance between these images can be controlled by the thickness of the plate. The results of the calculations show that application of a thin but strongly birefringent material is a better candidate than using a slightly birefringent but thick plate, since aberrations proportional to the thickness can cause undesirable effects.

Comparison of theoretical and experimental determination of the flexing of scratch drive actuator plates

NASA Astrophysics Data System (ADS)

Li, Lijie; Brown, James G.; Uttamchandani, Deepak G.

2002-09-01

The scratch drive actuator (SDA) is a key element in microelectromechanical System (MEMS) technology. The actuator can be designed to travel very long distance with precise step size. Various articles describe the characteristics of scratch drive actuators.3, 6, 8 The MEMS designer needs models of SDA in order to incorporate them into their Microsystems applications. The objective of our effort is to develop models for SDA when it is in the working state. In this paper, a suspended SDA plate actuated by electrostatic force is analyzed. A mathematical model is established based on electrostatic coupled mechanical theory. Two phases have been calculated because the plate will contact the bottom surface due to the electrostatic force. One phase is named non-contact mode, and another is named contact mode. From these two models, the relationship between applied voltage and contact distance has been obtained. The geometrical model of bending plate is established to determine the relationship between contact distance and step size. Therefore we can use those two results to obtain the result of step size versus applied voltage that we expect. Finally, couple-field electro-mechanical simulation has been done by commercial software IntelliSuite. We assume that the dimension of SDA plate and bushing are fixed. All the material properties are from JDSU Cronos MUMPs. A Veeco NT1000 surface profiling tool has been used to investigate the bending of SDA plate. The results of experimental and theoretical are compared.

Water-induced ethanol dewetting transition.

PubMed

Ren, Xiuping; Zhou, Bo; Wang, Chunlei

2012-07-14

The dewetting transitions of two hydrophobic plates immersed in pure water, aqueous ethanol solutions with concentrations from 25% to 90%, and pure ethanol were investigated by molecular dynamics simulations, where the dewetting transition was analogous to a first-order phase transition from liquid to vapor. It was found that the dewetting transitions occurred except that in the pure ethanol system. Although the ethanol molecules prefer to locate in the vicinity of the two plates, the inter-plate region is unfavorable for water molecules, due to losing more than one hydrogen bond. Moreover, each inter-plate water molecule forms hydrogen bonds on average with about two ethanol molecules. These intermolecular hydrogen bonds cause water and ethanol to cooperatively fill or exit the inter-plate region. Thus, water molecules play a more important role in the inter-plate filling/empty process, and induce the ethanol dewetting transition. Our results provide insight into the effect of water on the ethanol dewetting phenomena.

Industrialization of the mirror plate coatings for the ATHENA mission

NASA Astrophysics Data System (ADS)

Massahi, S.; Christensen, F. E.; Ferreira, D. D. M.; Shortt, B.; Collon, M.; Sforzini, J.; Landgraf, B.; Hinze, F.; Aulhorn, S.; Biedermann, R.

2017-08-01

In the frame of the development of the Advanced Telescope for High-ENergy Astrophysics (Athena) mission, currently in phase A, ESA is continuing to mature the optics technology and the associated mass production techniques. These efforts are driven by the programmatic and technical requirement of reaching TRL 6 prior to proposing the mission for formal adoption (planned for 2020). A critical part of the current phase A preparation activities is addressing the industrialization of the Silicon Pore Optics mirror plates coating. This include the transfer of the well-established coating processes and techniques, performed at DTU Space, to an industrial scale facility suitable for coating the more than 100,000 mirror plates required for Athena. In this paper, we explain the considerations for the planned coating facility including, requirement specification, equipment and supplier selection, preparing the coating facility for the deposition equipment, designing and fabrication.

The Influence of Finite-size Sources in Acousto-ultrasonics

NASA Technical Reports Server (NTRS)

Pavlakovic, Brian N.; Rose, Joseph L.

1994-01-01

This work explores the effects that the finite normal axisymmetric traction loading of an infinite isotropic plate has on wave propagation in acousto-ultrasonics (AU), in which guided waves are created using two normal incidence transducers. Although the work also addresses the effects of the transducer pressure distribution and pulse shape, this thesis concentrates on two main questions: how does the transducer's diameter control the phase velocity and frequency spectrum of the response, and how does the plate thickness relate to the plate's excitability? The mathematics of the time-harmonic solution and the physical principles and the practical considerations for AU wave generation are explained. Transient sources are modeled by the linear superposition of the time-harmonic solutions found using the Hankel transform and they are then compared to experimental data to provide insight into the relation between the size of the transducer and the preferred phase velocity.

Fabrication of nanocrystalline surface composite layer on Cu plate under ball collisions.

PubMed

Romankov, S; Park, Y C; Yoon, J M

2014-10-01

It was demonstrated that the severe plastic deformation of a surface induced by repeated ball collisions can be effectively used for fabrication of the nanocrystalline surface composite layers. The Cu disk was fixed at the top of a vibration chamber and ball treated. Al, Zr, Ni, Co and Fe were introduced into a Cu plate as contaminants from the grinding media one after the other by 15-min ball treatment. The composite structure was formed as a result of mechanical intermixing of the components. The particle size in as-fabricated layer ranged from 2 nm to 20 nm, with average values of about 7 nm. As-fabricated layer contained non-equilibrium multicomponent solid solution based on FCC Cu crystal structure, Zr-based phase, nanosized steel debris and amorphous phase. The hardness of the as-fabricated composite was almost ten times that of the initial Cu plate.

Structure and properties of TiSiCN coatings with different bias voltages by arc ion plating

NASA Astrophysics Data System (ADS)

Xie, Xinming; Li, Jinlong; Dong, Minpeng; Zhang, Henghua; Wang, Liping

2018-03-01

TiSiCN coatings were deposited on 316 L steel using the multi-arc ion plating system. All the coatings had the same total thickness of approximately 1.6 µm. The TiSiCN coatings were deposited under the mixture constant flow of N2 and C2H2 but varying bias. Information about structures, composition and properties were characterized by scanning electron microscope, x-ray diffraction, x-ray photoelectron spectroscopy, nanoindentation and ball-on-plate wear tests. The results show that all of the coatings consist of a TiCN nano-crystal phase and an Si3N4 amorphous phase. With an increase in the bias, the film becomes denser and exhibits better tribological behavior and mechanical properties. Moreover, the bonding strength between the coatings and the substrate increased and the resistance to thermal shock intensified when the coatings were made at a higher bias voltage.

Qualitative and semiquantitative Fourier transformation using a noncoherent system.

PubMed

Rogers, G L

1979-09-15

A number of authors have pointed out that a system of zone plates combined with a diffuse source, transparent input, lens, and focusing screen will display on the output screen the Fourier transform of the input. Strictly speaking, the transform normally displayed is the cosine transform, and the bipolar output is superimposed on a dc gray level to give a positive-only intensity variation. By phase-shifting one zone plate the sine transform is obtained. Temporal modulation is possible. It is also possible to redesign the system to accept a diffusely reflecting input at the cost of introducing a phase gradient in the output. Results are given of the sine and cosine transforms of a small circular aperture. As expected, the sine transform is a uniform gray. Both transforms show unwanted artifacts beyond 0.1 rad off-axis. An analysis shows this is due to unwanted circularly symmetrical moire patterns between the zone plates.

Phononic Crystal Tunable via Ferroelectric Phase Transition

NASA Astrophysics Data System (ADS)

Xu, Chaowei; Cai, Feiyan; Xie, Shuhong; Li, Fei; Sun, Rong; Fu, Xianzhu; Xiong, Rengen; Zhang, Yi; Zheng, Hairong; Li, Jiangyu

2015-09-01

Phononic crystals (PCs) consisting of periodic materials with different acoustic properties have potential applications in functional devices. To realize more smart functions, it is desirable to actively control the properties of PCs on demand, ideally within the same fabricated system. Here, we report a tunable PC made of Ba0.7Sr0.3Ti O3 (BST) ceramics, wherein a 20-K temperature change near room temperature results in a 20% frequency shift in the transmission spectra induced by a ferroelectric phase transition. The tunability phenomenon is attributed to the structure-induced resonant excitation of A0 and A1 Lamb modes that exist intrinsically in the uniform BST plate, while these Lamb modes are sensitive to the elastic properties of the plate and can be modulated by temperature in a BST plate around the Curie temperature. The study finds opportunities for creating tunable PCs and enables smart temperature-tuned devices such as the Lamb wave filter or sensor.

Tunable terahertz wave-plate based on dual-frequency liquid crystal controlled by alternating electric field.

PubMed

Yu, Jian-Ping; Chen, Sai; Fan, Fei; Cheng, Jie-Rong; Xu, Shi-Tong; Wang, Xiang-Hui; Chang, Sheng-Jiang

2018-01-22

In this work, the optically anisotropic property of dual-frequency liquid crystals (DFLC) in terahertz (THz) regime has been experimentally investigated, which indicates that the refractive index and birefringence of DFLC can be continuously modulated by both the alternating frequency and intensity of the alternating electric field. This tunability originates from the rotation of DFLC molecules induced by alternating electric fields. The results show that by modulating the alternating frequency from 1 kHz to 100 kHz under 30 kV/m electric field, the 600 μm thickness DFLC cell can play as a tunable quarter-wave plate above 0.68 THz, or a half-wave plate above 1.33 THz. Besides, it can be viewed as a tunable THz phase shifter from 0 to π. Therefore, due to its novel tuning mechanism, DFLC will be of great significance in dynamic manipulating on THz phase and polarization.

Numerical Simulation of Stationary AC Tungsten Inert Gas Welding of Aluminum Plate in Consideration of Oxide Layer Cleaning

NASA Astrophysics Data System (ADS)

Tashiro, Shinichi; Tanaka, Manabu

An unified numerical simulation model of AC TIG welding of the aluminum plate considering energy balance among the electrode, the arc and the base metal and employing an analytical model for calculating cleaning rate of the oxide layer has been developed for investigating heat transport properties and weld pool formation process in AC TIG welding of aluminum plate. As a result of this simulation, it was shown that although the heat flux from the arc onto the base metal increases in EN (Electrode Negative) phase due to the electron condensation, that in EP (Electrode Positive) phase conversely decreases because mainly of cooling caused by the electron emission. Furthermore, the validity of the simulation model was confirmed by comparing to experimental results such as the arc voltage, the area of cleaning zone and the shape of weld pool.

Robotic printing and drug testing of 384-well tumor spheroids.

PubMed

Ham, Stephanie L; Thakuri, Pradip S; Tavana, Hossein

2015-08-01

A major impediment to anti-cancer drug development is the lack of a reliable and inexpensive tumor model to test the efficacy of candidate compounds. This need has emerged due to the insufficiency of widely-used monolayer cultures to predict drug efficacy in vivo. Spheroids, 3D compact clusters of cancer cells, mimic important characteristics of tumors and provide a tissue analog for drug testing. Here we present a novel spheroid formation microtechnology that is simple to use and allows high throughput drug screening in 384-microwell plates. This approach is based on a polymeric aqueous two-phase system. The denser aqueous phase is mixed with cancer cells at a desired density. Using a robotic liquid handler, a drop of this cell suspension is dispensed into each well of a 384-microwell plate containing the second, immersion aqueous phase. Cancer cells remain contained in the drop, which rests on the well bottom, and form a spheroid during incubation. The use of liquid handling robotics ensures precise dispensing of a single drop, resulting in a single spheroid per well and homogenously sized spheroids within each plate. We confirmed the consistency of production of spheroids and demonstrated their biological relevance to tumors. A proof of concept study with spheroids of triple negative breast cancer cells treated with a standard chemotherapeutic compound, doxorubicin, showed the potential of this method for drug testing. This spheroid culture microtechnology presents key advantages over existing methods such as the ease of drug and viability reagent addition, ability to analyze spheroids without transferring them to a new plate, and the elimination of the need for specialized plates or devices to form spheroids. Incorporating this technology in anti-cancer drug development pipeline will help examine the efficacy of drug candidates more effectively and expedite discovery of novel drugs.

Moisture Determination of Nuts and Dry Fruits using a Capacitance Sensor

USDA-ARS?s Scientific Manuscript database

Impedance (Z), and phase angle (') of a cylindrical parallel-plate capacitor with in-shell peanuts between the plates was measured earlier, using a CI meter (Chari’s Impedance meter), at 1 and 5 MHz . Capacitance C, was derived from Z and ', and using the C, ', and Z values of a set of peanuts whos...

Sensing the Moisture Content of Dry Cherries - A Rapid and Nondestructive Method

USDA-ARS?s Scientific Manuscript database

Impedance (Z), and phase angle (') of a parallel-plate capacitor with a single cherry fruit between the plates was measured using a CI meter (Chari’s Impedance meter), at 1 and 9 MHz . Capacitance C, was derived from Z and ', and using the C, ', and Z values of a set of cherries whose moisture cont...

Mass flow rate measurements in gas-liquid flows by means of a venturi or orifice plate coupled to a void fraction sensor

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

Oliveira, Jorge Luiz Goes; Passos, Julio Cesar; Verschaeren, Ruud

Two-phase flow measurements were carried out using a resistive void fraction meter coupled to a venturi or orifice plate. The measurement system used to estimate the liquid and gas mass flow rates was evaluated using an air-water experimental facility. Experiments included upward vertical and horizontal flow, annular, bubbly, churn and slug patterns, void fraction ranging from 2% to 85%, water flow rate up to 4000 kg/h, air flow rate up to 50 kg/h, and quality up to almost 10%. The fractional root mean square (RMS) deviation of the two-phase mass flow rate in upward vertical flow through a venturi platemore » is 6.8% using the correlation of Chisholm (D. Chisholm, Pressure gradients during the flow of incompressible two-phase mixtures through pipes, venturis and orifice plates, British Chemical Engineering 12 (9) (1967) 454-457). For the orifice plate, the RMS deviation of the vertical flow is 5.5% using the correlation of Zhang et al. (H.J. Zhang, W.T. Yue, Z.Y. Huang, Investigation of oil-air two-phase mass flow rate measurement using venturi and void fraction sensor, Journal of Zhejiang University Science 6A (6) (2005) 601-606). The results show that the flow direction has no significant influence on the meters in relation to the pressure drop in the experimental operation range. Quality and slip ratio analyses were also performed. The results show a mean slip ratio lower than 1.1, when bubbly and slug flow patterns are encountered for mean void fractions lower than 70%. (author)« less

Fabrication of Achromatic Infrared Wave Plate by Direct Imprinting Process on Chalcogenide Glass

NASA Astrophysics Data System (ADS)

Yamada, Itsunari; Yamashita, Naoto; Tani, Kunihiko; Einishi, Toshihiko; Saito, Mitsunori; Fukumi, Kouhei; Nishii, Junji

2012-07-01

An achromatic infrared wave plate was fabricated by forming a subwavelength grating on the chalcogenide glass using direct imprint lithography. A low toxic chalcogenide glass (Sb-Ge-Sn-S system) substrate was imprinted with a grating of 1.63-µm depth, a fill factor of 0.7, and 3-µm period using glassy carbon as a mold at 253 °C and 3.8 MPa. Phase retardation of the element reached around 30° at 8.5-10.5 µm wavelengths, and the transmittance exceeded that of a flat substrate over 8 µm wavelength. Fabrication of the mid-infrared wave plate is thereby less expensive than that of conventional crystalline wave plates.

National Dam Safety Program. Little Bear Lake Dam (MO 30533), Mississippi - Kaskaskia - St. Louis Basin, Cape Girardeau County, Missouri. Phase I Inspection Report.

DTIC Science & Technology

1980-10-01

16 7.2 Remedial Measures 17 APPENDIX A - MAPS Plate A-1 Vicinity Topography Plate A-2 Location Map Plate A-3 Seismic Map APPENDIX B - PHOTOGRAPHS...reservoir surface area, and elvton-storage data were developed from the USGS Cape Girardeau, Missouri 7-1/2 minute topographic quadrangle map . The...project file. CA -18- APPENDIX A MAPS II ./ \\v 14,.. MITE LSRIES ILUOOtS HC Scal in eetVICIITYTOPOGRAPHY Contur Itoral -10’MO 30533

Industrial Processes to Reduce Generation of Hazardous Waste at DoD Facilities. Phase I Report. Evaluation of 40 Case Studies.

DTIC Science & Technology

1985-02-15

utilizes a cathode contained within a membrane module to selectively precipitate trivalent chromium and other cations from the plating solution...Cadmium Plating at Lockheed, Case No. 6 5-6 5.4.2 LICON Chromium Recovery at Pensacola NARF, Case No. 9 5-7 iii CONTENTS (continued) Page 5.4.3 LICON... Chromium Recovery at Charleston NYS, Case No. 12 5-9 5.4.4 Innovative Chromium Plating at Pensacola NARF, Case No. 10 5-10 5.4.5 Steam Condensate

Cadmium Alternatives for High-Strength Steel JTP. Phase 2

DTIC Science & Technology

2007-01-24

Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 U.S. AIR FORCE Project Overview Objective Assess DoD- selected cadmium alternatives in...focused) – Phase III (fatigue testing focused) • Down- selection of candidates for further testing after each phase of testing is complete (Phases I...Laboratories – Mr. John Marshall U.S. AIR FORCE Phase I Overview and Selection Process – Traditional plating (primary coatings): • Sputtered Aluminum

Study of polarization properties of fiber-optics probes with use of a binary phase plate.

PubMed

Alferov, S V; Khonina, S N; Karpeev, S V

2014-04-01

We conduct a theoretical and experimental study of the distribution of the electric field components in the sharp focal domain when rotating a zone plate with a π-phase jump placed in the focused beam. Comparing the theoretical and experimental results for several kinds of near-field probes, an analysis of the polarization sensitivity of different types of metal-coated aperture probes is conducted. It is demonstrated that with increasing diameter of the non-metal-coated tip part there occurs an essential redistribution of sensitivity in favor of the transverse electric field components and an increase of the probe's energy throughput.

Time-alternating method based on single-sideband holography with half-zone-plate processing for the enlargement of viewing zones.

PubMed

Mishina, T; Okano, F; Yuyama, I

1999-06-10

The single-sideband method of holography, as is well known, cuts off beams that come from conjugate images for holograms produced in the Fraunhofer region and from objects with no phase components. The single-sideband method with half-zone-plate processing is also effective in the Fresnel region for beams from an object that has phase components. However, this method restricts the viewing zone to a narrow range. We propose a method to improve this restriction by time-alternating switching of hologram patterns and a spatial filter set on the focal plane of a reconstruction lens.

Oxidation of ammonium sulfite by a multi-needle-to-plate gas phase pulsed corona discharge reactor

NASA Astrophysics Data System (ADS)

Ren, Hua; Lu, Na; Shang, Kefeng; Li, Jie; Wu, Yan

2013-03-01

The oxidation of ammonium sulfite in the ammonia-based flue gas desulfurization (FGD) process was investigated in a multi-needle-to-plate gas phase pulsed corona discharge reactor in this paper. The effect of several parameters, including capacitance and peak pulse voltage of discharge system, electrode gap and bubbling gas flow rate on the oxidation rate of ammonium sulfite was reviewed. The oxidation rate of ammonium sulfite could reach 47.2% at the capacitance, the peak pulse voltage, electrode gap and bubbling gas flow rate equal to 2 nF, -24.6 k V, 35 mm and 4 L min-1 within treatment time of 40 min The experimental results indicate that the gas phase pulsed discharge system with a multi-needle-to-plate electrode can oxide the ammonium sulfite. The oxidation rate increased with the applied capacitance and peak pulse voltage and decreased with the electrode gap. As the bubbling gas flow rate increased, the oxidation rate increased first and then tended to reach a stationary value. These results would be important for the process optimization of the (NH4)2SO3 to (NH4)2SO4 oxidation.

Evidence of lower-mantle slab penetration phases in plate motions.

PubMed

Goes, Saskia; Capitanio, Fabio A; Morra, Gabriele

2008-02-21

It is well accepted that subduction of the cold lithosphere is a crucial component of the Earth's plate tectonic style of mantle convection. But whether and how subducting plates penetrate into the lower mantle is the subject of continuing debate, which has substantial implications for the chemical and thermal evolution of the mantle. Here we identify lower-mantle slab penetration events by comparing Cenozoic plate motions at the Earth's main subduction zones with motions predicted by fully dynamic models of the upper-mantle phase of subduction, driven solely by downgoing plate density. Whereas subduction of older, intrinsically denser, lithosphere occurs at rates consistent with the model, younger lithosphere (of ages less than about 60 Myr) often subducts up to two times faster, while trench motions are very low. We conclude that the most likely explanation is that older lithosphere, subducting under significant trench retreat, tends to lie down flat above the transition to the high-viscosity lower mantle, whereas younger lithosphere, which is less able to drive trench retreat and deforms more readily, buckles and thickens. Slab thickening enhances buoyancy (volume times density) and thereby Stokes sinking velocity, thus facilitating fast lower-mantle penetration. Such an interpretation is consistent with seismic images of the distribution of subducted material in upper and lower mantle. Thus we identify a direct expression of time-dependent flow between the upper and lower mantle.

Understanding the solidification and microstructure evolution during CSC-MIG welding of Fe–Cr–B-based alloy

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

Sorour, A.A., E-mail: ahmad.sorour@mail.mcgill.ca; Chromik, R.R., E-mail: richard.chromik@mcgill.ca; Gauvin, R., E-mail: raynald.gauvin@mcgill.ca

2013-12-15

The present is a study of the solidification and microstructure of Fe–28.2%Cr–3.8%B–1.5%Si–1.5%Mn (wt.%) alloy deposited onto a 1020 plain carbon steel substrate using the controlled short-circuit metal inert gas welding process. The as-solidified alloy was a metal matrix composite with a hypereutectic microstructure. Thermodynamic calculation based on the Scheil–Gulliver model showed that a primary (Cr,Fe){sub 2}B phase formed first during solidification, followed by an eutectic formation of the (Cr,Fe){sub 2}B phase and a body-centered cubic Fe-based solid solution matrix, which contained Cr, Mn and Si. Microstructure analysis confirmed the formation of these phases and showed that the shape of themore » (Cr,Fe){sub 2}B phase was irregular plate. As the welding heat input increased, the weld dilution increased and thus the volume fraction of the (Cr,Fe){sub 2}B plates decreased while other microstructural characteristics were similar. - Highlights: • We deposit Fe–Cr–B-based alloy onto plain carbon steel using the CSC-MIG process. • We model the solidification behavior using thermodynamic calculation. • As deposited alloy consists of (Cr,Fe){sub 2}B plates embedded in Fe-based matrix. • We study the effect of the welding heat input on the microstructure.« less

Microstructure and Mechanical Properties of Stainless Steel/Brass Joints Brazed by Sn-Electroplated Ag Brazing Filler Metals

NASA Astrophysics Data System (ADS)

Wang, Xingxing; Peng, Jin; Cui, Datian

2018-05-01

To develop a high-Sn-content AgCuZnSn brazing filler metal, the BAg50CuZn was used as the base filler metal and a Sn layer was electroplated upon it. Then, the 304 stainless steel and the H62 brass were induction-brazed with the Sn-plated brazing filler metals. The microstructures of the joints were examined with an optical microscope, a scanning electron microscope and an x-ray diffractometer. The corresponding mechanical properties were obtained with a universal tensile testing machine. The results indicated that the induction brazed joints consisted of the Ag phase, the Cu phase and the CuZn phase. When the content of Sn in the Sn-plated Ag brazing filler metal was 6.0 or 7.2 wt.%, the Cu5Zn8, the Cu41Sn11 and the Ag3Sn phases appeared in the brazed joint. The tensile strength of the joints brazed with the Sn-plated filler metal was higher compared to the joints with the base filler metal. When the content of Sn was 6.0 wt.%, the highest tensile strength of the joint reached to 395 MPa. The joint fractures presented a brittle mode, mixed with a low amount of ductile fracture, when the content of Sn exceeded 6.0 wt.%.

A computational investigation of the phase behavior and capillary sublimation of water confined between nanoscale hydrophobic plates

NASA Astrophysics Data System (ADS)

Ferguson, Andrew L.; Giovambattista, Nicolás; Rossky, Peter J.; Panagiotopoulos, Athanassios Z.; Debenedetti, Pablo G.

2012-10-01

Thin films of water under nanoscopic confinement are prevalent in natural and manufactured materials. To investigate the equilibrium and dynamic behavior of water in such environments, we perform molecular dynamics simulations of water confined between atomistically detailed hydrophobic plates at T = 298 K for pressures (-0.1) ⩽ P ⩽ 1.0 GPa and plate separations of 0.40 ⩽ d ⩽ 0.80 nm. From these simulations, we construct an expanded P-d phase diagram for confined water, and identify and characterize a previously unreported confined monolayer ice morphology. We also study the decompression-induced sublimation of bilayer ice in a d = 0.6 nm slit, employing principal component analysis to synthesize low-dimensional embeddings of the drying trajectories and develop insight into the sublimation mechanism. Drying is observed to proceed by the nucleation of a bridging vapor cavity at one corner of the crystalline slab, followed by expansion of the cavity along two edges of the plates, and the subsequent recession of the remaining promontory of bilayer crystal into the bulk fluid. Our findings have implications for the understanding of diverse phenomena in materials science, nanofluidics, and protein folding and aggregation.

A practical technique for quantifying the performance of acoustic emission systems on plate-like structures.

PubMed

Scholey, J J; Wilcox, P D; Wisnom, M R; Friswell, M I

2009-06-01

A model for quantifying the performance of acoustic emission (AE) systems on plate-like structures is presented. Employing a linear transfer function approach the model is applicable to both isotropic and anisotropic materials. The model requires several inputs including source waveforms, phase velocity and attenuation. It is recognised that these variables may not be readily available, thus efficient measurement techniques are presented for obtaining phase velocity and attenuation in a form that can be exploited directly in the model. Inspired by previously documented methods, the application of these techniques is examined and some important implications for propagation characterisation in plates are discussed. Example measurements are made on isotropic and anisotropic plates and, where possible, comparisons with numerical solutions are made. By inputting experimentally obtained data into the model, quantitative system metrics are examined for different threshold values and sensor locations. By producing plots describing areas of hit success and source location error, the ability to measure the performance of different AE system configurations is demonstrated. This quantitative approach will help to place AE testing on a more solid foundation, underpinning its use in industrial AE applications.

Translation of an Object Using Phase-Controlled Sound Sources in Acoustic Levitation

NASA Astrophysics Data System (ADS)

Matsui, Takayasu; Ohdaira, Etsuzo; Masuzawa, Nobuyoshi; Ide, Masao

1995-05-01

Acoustic levitation is used for positioning materials in the development of new materials in space where there is no gravity. This technique is applicable to materials for which electromagnetic force cannot be used. If the levitation point of the materials can be controlled freely in this application, possibilities of new applications will be extended. In this paper we report on an experimental study on controlling the levitation point of the object in an acoustic levitation system. The system fabricated and tested in this study has two sound sources with vibrating plates facing each other. Translation of the object can be achieved by controlling the phase of the energizing electrical signal for one of the sound sources. It was found that the levitation point can be moved smoothly in proportion to the phase difference between the vibrating plates.

Experimental constraints and theoretical bases for microstructural damage in plate boundary shear zones

NASA Astrophysics Data System (ADS)

Skemer, P. A.; Cross, A. J.; Bercovici, D.

2016-12-01

(Ultra)mylonites from plate boundary shear zones are characterized by severe grain-size reduction and well-mixed mineral phases. The evolution from relatively undeformed tectonite protoliths to highly deformed (ultra)mylonites via the formation of new grain and phase boundaries is described as microstructural `damage.' Microstructural damage is important for two reasons: grain-size reduction is thought to result in significant rheological weakening, while phase mixing inhibits mechanical recovery and preserves the zone of weakness to be reactivated repeatedly throughout the tectonic cycle. Grain-size reduction by dynamic recrystallization has been studied extensively in both geologic and engineered materials, yet the progressive mixing of mineral phases during high pressure/temperature shear - the other essential element of damage or mylonitization - is not well understood. In this contribution we present new experimental results and theory related to two distinct phase mixing processes. First, we describe high strain torsion experiments on calcite and anhydrite mixtures and a simple geometric mixing model related to the stretching and thinning of monophase domains. Second, we describe a grain-switching mechanism that is driven by the surface-tension driven migration of newly formed interphase triple junctions. Unlike dynamic recrystallization, which occurs at relatively small strains, both phase mixing mechanisms described here appear to require extremely large strains, a prediction that is consistent with geologic observations. These data suggest that ductile shear zones experience long, transient intervals of microstructural evolution during which rheology is not at steady state. Microstructural damage may be interpreted as the product of several interconnected physical processes, which are collectively essential to the preservation of long-lived, Earth-like plate tectonics.

Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy.

PubMed

Vasconcelos, Luís; Lehto, Tõnis; Madani, Fatemeh; Radoi, Vlad; Hällbrink, Mattias; Vukojević, Vladana; Langel, Ülo

2018-02-01

Peptides able to translocate cell membranes while carrying macromolecular cargo, as cell-penetrating peptides (CPPs), can contribute to the field of drug delivery by enabling the transport of otherwise membrane impermeable molecules. Formation of non-covalent complexes between amphipathic peptides and oligonucleotides is driven by electrostatic and hydrophobic interactions. Here we investigate and quantify the coexistence of distinct molecular species in multiple equilibria, namely peptide monomer, peptide self-aggregates and peptide/oligonucleotide complexes. As a model for the complexes, we used a stearylated peptide from the PepFect family, PF14 and siRNA. PF14 has a cationic part and a lipid part, resembling some characteristics of cationic lipids. Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) were used to detect distinct molecular entities in solution and at the plasma membrane of live cells. For that, we labeled the peptide with carboxyrhodamine 6G and the siRNA with Cyanine 5. We were able to detect fluorescent entities with diffusional properties characteristic of the peptide monomer as well as of peptide aggregates and peptide/oligonucleotide complexes. Strategies to avoid peptide adsorption to solid surfaces and self-aggregation were developed and allowed successful FCS measurements in solution and at the plasma membrane. The ratio between the detected molecular species was found to vary with pH, peptide concentration and the proximity to the plasma membrane. The present results suggest that the diverse cellular uptake mechanisms, often reported for amphipathic CPPs, might result from the synergistic effect of peptide monomers, self-aggregates and cargo complexes, distributed unevenly at the plasma membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic bacterial prostatitis and chronic pelvic pain syndrome.

PubMed

Bowen, Diana K; Dielubanza, Elodi; Schaeffer, Anthony J

2015-08-27

Chronic prostatitis can cause pain and urinary symptoms, and can occur either with an active infection (chronic bacterial prostatitis [CBP]) or with only pain and no evidence of bacterial causation (chronic pelvic pain syndrome [CPPS]). Bacterial prostatitis is characterised by recurrent urinary tract infections or infection in the prostate with the same bacterial strain, which often results from urinary tract instrumentation. However, the cause and natural history of CPPS are unknown and not associated with active infection. We conducted a systematic overview and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 131 studies. After deduplication and removal of conference abstracts, 67 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 51 studies and the further review of 16 full publications. Of the 16 full articles evaluated, three systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for 14 PICO combinations. In this systematic overview, we categorised the efficacy for 12 interventions based on information relating to the effectiveness and safety of 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, quercetin, sitz baths, transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP).

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

PubMed

Lin, Li; Zhu, Bao-Ping; Cai, Liang

2017-06-01

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.

PubMed

Tudzynski, P; Hölter, K; Correia, T; Arntz, C; Grammel, N; Keller, U

1999-02-01

A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that catalyzes the first specific step in the biosynthesis of ergot alkaloids, was cloned from a strain of Claviceps purpurea that produces alkaloids in axenic culture. The derived gene product (CPD1) shows only 70% similarity to the corresponding gene previously isolated from Claviceps strain ATCC 26245, which is likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most probably represents the first C. purpurea gene coding for an enzymatic step of the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene named cpps1, which codes for a 356-kDa polypeptide showing significant similarity to fungal modular peptide synthetases. The protein contains three amino acid-activating modules, and in the second module a sequence is found which matches that of an internal peptide (17 amino acids in length) obtained from a tryptic digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome walking revealed the presence of additional genes upstream of cpd1 which are probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase), and a second putative oxidoreductase gene, cpox2, is closely linked to it in inverse orientation. RT-PCR experiments confirm that all four genes are expressed under conditions of peptide alkaloid biosynthesis. These results strongly suggest that at least some genes of ergot alkaloid biosynthesis in C. purpurea are clustered, opening the way for a detailed molecular genetic analysis of the pathway.

Direct cytosolic delivery of cargoes in vivo by a chimera consisting of D- and L-arginine residues.

PubMed

Ma, Yan; Gong, Cheng; Ma, Yilong; Fan, Fengkai; Luo, Meijie; Yang, Fei; Zhang, Yu-Hui

2012-09-10

The ability of cell-penetrating peptides (CPPs) to deliver a range of membrane-impermeable molecules into living cells makes them attractive potential vehicles for therapeutics. However, in vivo, the efficiency of CPP delivery to the cytosol remains unsatisfactory owing to endosomal entrapment and/or systemic toxicity, which severely restrict their bioavailability and efficacy in in vivo applications. In this study, we developed a series of novel chimeras consisting of various numbers of d- and l-arginine residues and investigated their cellular uptake behaviors and systemic toxicities. We demonstrated that the intracellular distribution, uptake efficiency, and systemic toxicity of these oligoarginines were all significantly affected by the number of d-arginine residues in the peptide sequence. We also found that a hybrid peptide, (rR)(3)R(2), possessed low systemic toxicity, high uptake efficiency, and, remarkably, achieved efficient cytosolic delivery not only in cultured cells but also in living tissue cells in mice after intravenous injection, implying that this heterogeneous motif might have promising applications in the delivery of cargoes of small sizes directed to cytosolic targets in vivo. Our studies into the uptake mechanism of (rR)(3)R(2) indicate that its cellular uptake was not affected by pharmacological or physical inhibitors of endocytosis but by the elimination of the membrane potential, suggesting that (rR)(3)R(2) does not enter the cells via endocytosis but rather through direct membrane translocation driven by the membrane potential. The results here might provide useful guidelines for the design and application of CPPs in drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Perceptual structure of adductor spasmodic dysphonia and its acoustic correlates.

PubMed

Cannito, Michael P; Doiuchi, Maki; Murry, Thomas; Woodson, Gayle E

2012-11-01

To examine the perceptual structure of voice attributes in adductor spasmodic dysphonia (ADSD) before and after botulinum toxin treatment and identify acoustic correlates of underlying perceptual factors. Reliability of perceptual judgments is considered in detail. Pre- and posttreatment trial with comparison to healthy controls, using single-blind randomized listener judgments of voice qualities, as well as retrospective comparison with acoustic measurements. Oral readings were recorded from 42 ADSD speakers before and after treatment as well as from their age- and sex-matched controls. Experienced judges listened to speech samples and rated attributes of overall voice quality, breathiness, roughness, and brokenness, using computer-implemented visual analog scaling. Data were adjusted for regression to the mean and submitted to principal components factor analysis. Acoustic waveforms, extracted from the reading samples, were analyzed and measurements correlated with perceptual factor scores. Four reliable perceptual variables of ADSD voice were effectively reduced to two underlying factors that corresponded to hyperadduction, most strongly associated with roughness, and hypoadduction, most strongly associated with breathiness. After treatment, the hyperadduction factor improved, whereas the hypoadduction factor worsened. Statistically significant (P<0.01) correlations were observed between perceived roughness and four acoustic measures, whereas breathiness correlated with aperiodicity and cepstral peak prominence (CPPs). This study supported a two-factor model of ADSD, suggesting perceptual characterization by both hyperadduction and hypoadduction before and after treatment. Responses of the factors to treatment were consistent with previous research. Correlations among perceptual and acoustic variables suggested that multiple acoustic features contributed to the overall impression of roughness. Although CPPs appears to be a partial correlate of perceived breathiness, a physical basis of this percept remained less clear. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Digital micromirror device as amplitude diffuser for multiple-plane phase retrieval

NASA Astrophysics Data System (ADS)

Abregana, Timothy Joseph T.; Hermosa, Nathaniel P.; Almoro, Percival F.

2017-06-01

Previous implementations of the phase diffuser used in the multiple-plane phase retrieval method included a diffuser glass plate with fixed optical properties or a programmable yet expensive spatial light modulator. Here a model for phase retrieval based on a digital micromirror device as amplitude diffuser is presented. The technique offers programmable, convenient and low-cost amplitude diffuser for a non-stagnating iterative phase retrieval. The technique is demonstrated in the reconstructions of smooth object wavefronts.

Electroplated Fe-Co-Ni films prepared from deep-eutectic-solvent-based plating baths

NASA Astrophysics Data System (ADS)

Yanai, Takeshi; Shiraishi, Kotaro; Akiyoshi, Toshiki; Azuma, Keita; Watanabe, Yoshimasa; Ohgai, Takeshi; Morimura, Takao; Nakano, Masaki; Fukunaga, Hirotoshi

2016-05-01

We fabricated soft magnetic films from DES-based plating baths, and investigated magnetic properties of the plated films. The plating baths were obtained by stirring the mixture of choline chloride, ethylene glycol, FeCl2 ṡ 4H2O, NiCl2 ṡ 6H2O and CoCl2 ṡ 6H2O. The composition of the electroplated film depended on the amount of the reagent in the plating bath, and we consequently obtained the films with various composition. The current efficiency of the plating process shows high values (> 88 %) in the wide composition range. The soft magnetic films with low coercivity were obtained at the Fe compositions of ≈ 30 at.% and > 80 at.%, and we found that low coercivity could be realized by the control of the film composition. We also found that the Fe-rich films prepared from DES-based plating bath have some advantages as a soft magnetic phase for a nanocomposite magnet due to their high saturation magnetization and very fine crystal structure.

Plate mode velocities in graphite/epoxy plates

NASA Technical Reports Server (NTRS)

Prosser, W. H.; Gorman, M. R.

1994-01-01

Measurements of the velocities of the extensional and flexural plate modes were made along three directions of propagation in four graphite/epoxy composite plates. The acoustic signals were generated by simulated acoustic emission events (pencil lead breaks or Hsu-Neilson sources) and detected by by broadband ultrasonic transducers. The first arrival of the extensional plate mode, which is nondispersive at low frequencies, was measured at a number of different distances from the source along the propagation direction of interest. The velocity was determined by plotting the distance versus arrival time and computing its slope. Because of the large dispersion of the flexural mode, a Fourier phase velocity technique was used to characterize this mode. The velocity was measured up to a frequency of 160 kHz. Theoretical predictions of the velocities of these modes were also made and compared with experimental observations. Classical plate theory yields good agreement with the measured extensional velocities. For predictions of the dispersion of the flexural mode, Mindlin plates theory, which includes the effects of shear deformation and rotatory inertia was shown to give better agreement with the experimental measurements.

Achromatic half-wave plate for submillimeter instruments in cosmic microwave background astronomy: modeling and simulation.

PubMed

Savini, Giorgio; Pisano, Giampaolo; Ade, Peter A R

2006-12-10

We adopted an existing formalism and modified it to simulate, with high precision, the transmission, reflection, and absorption of multiple-plate birefringent devices as a function of frequency. To validate the model, we use it to compare the measured properties of an achromatic five-plate device with a broadband antireflection coating to expectations derived from the material optical constants and its geometric configuration. The half-wave plate presented here is observed to perform well with a phase shift variation of < 2 degrees from the ideal 180 degrees over a bandwidth of Deltav/v approximately 1 at millimeter wavelengths. This formalism represents a powerful design tool for birefringent polarization modulators and enables its optical properties to be specified with high accuracy.

Approaches for Achieving Broadband Achromatic Phase Shifts for Visible Nulling Coronagraphy

NASA Technical Reports Server (NTRS)

Bolcar, Matthew R.; Lyon, Richard G.

2012-01-01

Visible nulling coronagraphy is one of the few approaches to the direct detection and characterization of Jovian and Terrestrial exoplanets that works with segmented aperture telescopes. Jovian and Terrestrial planets require at least 10(exp -9) and 10(exp -10) image plane contrasts, respectively, within the spectral bandpass and thus require a nearly achromatic pi-phase difference between the arms of the interferometer. An achromatic pi-phase shift can be achieved by several techniques, including sequential angled thick glass plates of varying dispersive materials, distributed thin-film multilayer coatings, and techniques that leverage the polarization-dependent phase shift of total-internal reflections. Herein we describe two such techniques: sequential thick glass plates and Fresnel rhomb prisms. A viable technique must achieve the achromatic phase shift while simultaneously minimizing the intensity difference, chromatic beam spread and polarization variation between each arm. In this paper we describe the above techniques and report on efforts to design, model, fabricate, align the trades associated with each technique that will lead to an implementations of the most promising one in Goddard's Visible Nulling Coronagraph (VNC).

Zernike Phase Contrast Electron Cryo-Tomography Applied to Marine Cyanobacteria Infected with Cyanophages

PubMed Central

Dai, Wei; Fu, Caroline; Khant, Htet A.; Ludtke, Steven J.; Schmid, Michael F.; Chiu, Wah

2015-01-01

Advances in electron cryo-tomography have provided a new opportunity to visualize the internal 3D structures of a bacterium. An electron microscope equipped with Zernike phase contrast optics produces images with dramatically increased contrast compared to images obtained by conventional electron microscopy. Here we describe a protocol to apply Zernike phase plate technology for acquiring electron tomographic tilt series of cyanophage-infected cyanobacterial cells embedded in ice, without staining or chemical fixation. We detail the procedures for aligning and assessing phase plates for data collection, and methods to obtain 3D structures of cyanophage assembly intermediates in the host, by subtomogram alignment, classification and averaging. Acquiring three to four tomographic tilt series takes approximately 12 h on a JEM2200FS electron microscope. We expect this time requirement to decrease substantially as the technique matures. Time required for annotation and subtomogram averaging varies widely depending on the project goals and data volume. PMID:25321408

Rayleigh phase velocities in the upper mantle of the Pacific-North American plate boundary in southern California

NASA Astrophysics Data System (ADS)

Escobar, L.; Weeraratne, D. S.; Kohler, M. D.

2013-05-01

The Pacific-North America plate boundary, located in Southern California, presents an opportunity to study a unique tectonic process that has been shaping the plate tectonic setting of the western North American and Mexican Pacific margin since the Miocene. This is one of the few locations where the interaction between a migrating oceanic spreading center and a subduction zone can be studied. The rapid subduction of the Farallon plate outpaced the spreading rate of the East Pacific Rise rift system causing it to be subducted beneath southern California and northern Mexico 30 Ma years ago. The details of microplate capture, reorganization, and lithospheric deformation on both the Pacific and North American side of this boundary is not well understood, but may have important implications for fault activity, stresses, and earthquake hazard analysis both onshore and offshore. We use Rayleigh waves recorded by an array of 34 ocean bottom seismometers deployed offshore southern California for a 12 month duration from August 2010 to 2011. Our array recorded teleseismic earthquakes at distances ranging from 30° to 120° with good signal-to-noise ratios for magnitudes Mw ≥ 5.9. The events exhibit good azimuthal distribution and enable us to solve simultaneously for Rayleigh wave phase velocities and azimuthal anisotropy. Fewer events occur at NE back-azimuths due to the lack of seismicity in central North America. We consider seismic periods between 18 - 90 seconds. The inversion technique considers non-great circle path propagation by representing the arriving wave field as two interfering plane waves. This takes advantage of statistical averaging of a large number of paths that travel offshore southern California and northern Mexico allowing for improved resolution and parameterization of lateral seismic velocity variations at lithospheric and sublithospheric depths. We present phase velocity results for periods sampling mantle structure down to 150 km depth along the west coast margin. With this study, we seek to understand the strength and deformation of the Pacific oceanic lithosphere resulting from plate convergence and subduction beneath Southern California 30 Ma as well as translational stresses present today. We also test for predictions of several geodynamic models which describe the kinematic mantle flow that accompanies plate motion within this area including passive mantle drag due to Pacific plate motion and toroidal flow in the western U.S. region that may extend offshore.

A simple agar plate preparation for effective transfer of Ureaplasma colonies onto nitrocellulose membranes for colony immunoblotting.

PubMed

Zimmerman, Carl-Ulrich R; Stiedl, Thomas; Spergser, Joachim; Rosengarten, Renate

2014-09-01

A simple method for preparing agar plates is presented, which allows an efficient transfer of Ureaplasma colonies to nitrocellulose membranes for subsequent immunological detection. This simple and reproducible procedure was used to demonstrate antigenic variation in the phase-variable mba-locus of Ureaplasma parvum serovar 3. Copyright © 2014 Elsevier B.V. All rights reserved.

The Effects of Applied Stress and Sensitization on the Passive Film Stability of Al-Mg Alloys

DTIC Science & Technology

2013-06-01

and residual tensile and compressive stresses impact the passive layer film and the material’s electrochemistry. Sample plates of AA5083 were...electrochemistry. Sample plates of AA5083 were sensitized to different levels to promote the formation of intergranular β phase (Al3Mg2). The...41  A.  MATERIAL PROCESSING: FABRICATION AND APPLIED STRESSES OF TEST SAMPLES

Resonant Interaction of a Rectangular Jet with a Flat-Plate

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.; Fagan, A. F.; Clem, M. M.; Brown, C. A.

2014-01-01

A resonant interaction between a large aspect ratio rectangular jet and a flat-plate is addressed in this experimental study. The plate is placed parallel to but away from the direct path of the jet. At high subsonic conditions and for certain relative locations of the plate, the resonance accompanied by an audible tone is encountered. The trends of the tone frequency variation exhibit some similarities to, but also marked differences from, corresponding trends of the well-known edge-tone phenomenon. Under the resonant condition flow visualization indicates a periodic flapping motion of the jet column. Phase-averaged Mach number data obtained near the plate's trailing edge illustrate that the jet cross-section goes through large contortions within the period of the tone. Farther downstream a clear 'axis switching' takes place. These results suggest that the assumption of two-dimensionality should be viewed with caution in any analysis of the flow.

Reaction process of {alpha} {yields} {gamma} massive transformation in Ti-rich TiAl alloy

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

Kumagai, T.; Abe, E.; Nakamura, M.

1995-08-01

Reaction sequence of the massive transformation from the high-temperature {alpha}-Ti phase to the {gamma}-TiAl phase ({gamma}{sub m}) in a Ti-48at.% Al alloy has been examined in terms of optical and transmission electron microscopes. Both transformed and untransformed regions were macroscopically observed in the sample quenched from the high-temperature {alpha} phase field, when the sample was held there for a extended period of time prior to quenching. The transformed region consists of randomly oriented fine {gamma} single phase grains, in which many thermal anti-phase domains (TAPDs), together with a number of stacking faults were observed. In contrast, the untransformed region comprisesmore » extremely fine lamellae of the {gamma} and {alpha}{sub 2}-Ti{sub 3}Al phases, and the {gamma} plates were found to run through the TAPDs caused by {alpha} {yields} {alpha}{sub 2} ordering. Subsequent aging at 1,273 K causes the microstructure change in the untransformed region from {alpha}{sub 2}/{gamma} lamellae to {gamma}/{gamma} lamellae spontaneously and expands the {gamma}{sub m} region. These observations suggest that the {alpha} {yields} {gamma}{sub m} transformation proceeds through formation of fine {gamma} plates.« less

The Anisotropic Structure of South China Sea: Using OBS Data to Constrain Mantle Flow

NASA Astrophysics Data System (ADS)

Li, L.; Xue, M.; Yang, T.; Liu, C.; Hua, Q.; Xia, S.; Huang, H.; Le, B. M.; Huo, D.; Pan, M.

2015-12-01

The dynamic mechanism of the formation of South China Sea (SCS) has been debated for decades. The anisotropic structure can provide useful insight into the complex evolution of SCS by indicating its mantle flow direction and strength. In this study, we employ shear wave splitting methods on two half-year seismic data collected from 10 and 6 passive source Ocean Bottom Seismometers (OBS) respectively. These OBSs were deployed along both sides of the extinct ridge in the central basin of SCS by Tongji University in 2012 and 2013 respectively, which were then successfully recovered in 2013 and 2015 respectively. Through processing and inspecting the global and regional earthquakes (with local events being processing) of the 2012 dataset, measurements are made for 2 global events and 24 regional events at 5 OBSs using the tangential energy minimization, the smallest eigenvalue minimization, as well as the correlation methods. We also implement cluster analysis on the splitting results obtained for different time windows as well as filtered at different frequency bands. For teleseismic core phases like SKS and PKS, we find the fast polarization direction beneath the central basin is approximately NE-SW, nearly parallel to the extinct ridge in the central basin of SCS. Whereas for regional events, the splitting analysis on S, PS and ScS phases shows much more complicated fast directions as the ray path varies for different phases. The fast directions observed can be divided into three groups: (1) for the events from the Eurasia plate, a gradual rotation of the fast polarization direction from NNE-SSW to NEE-SWW along the path from the inner Eurasia plate to the central SCS is observed, implying the mantle flow is controlled by the India-Eurasia collision; (2) for the events located at the junction of Pacific plate and Philippine plate, the dominant fast direction is NW-SE, almost perpendicular to Ryukyu Trench as well as sub-parallel to the absolute direction of Philippine plate; (3) for the events occurred in the SE direction near the Philippine Fault zone, the observed NE-SW fast direction is sub-parallel to the subduction direction of the Philippine plate.

Experimental study of turbulent flow heat transfer and pressure drop in a plate heat exchanger with chevron plates

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

Muley, A.; Manglik, R.M.

1997-07-01

Experimental data for isothermal pressure drop and heat transfer in single-phase water flows in a plate heat exchanger (PHE) with chevron plates are presented. A single-pass, U-type, counterflow PHE, with three different chevron plate arrangements is employed: two symmetric plate arrangements with {beta} = 30/30{degree} and 60/60{degree}, and a mixed-plate arrangement with {beta} = 30/60{degree}. With water flow rates in the turbulent flow regime (600 < Re < 10{sup 4} and 2 < Pr < 6), effects of the chevron corrugation inclination angle {beta} on Nu and f characteristics of the PHE are investigated. As {beta} increases and compared tomore » a flat-plate pack, up to 2 to 5 times higher Nu are obtained; the concomitant f, however, are 13 to 44 times higher. Based on the experimental data for Re {le} 1,000, predictive correlations of the form Nu = C{sub 1}{beta} Re{sup p1({beta})} Pr{sup 1/3} ({mu}/{mu}{sub w}){sup 0.14} and f = C{sub 2}{beta} Re{sup p2({beta})} are devised. Also, at constant pumping power and depending upon {beta}, the heat transfer is found to be enhanced over 1.8 times that in equivalent flat-plate channels.« less

Looking for Plate Tectonics in all the wrong fluids

NASA Astrophysics Data System (ADS)

Davaille, Anne

2017-04-01

Ever since the theory of Plate Tectonics in the 1960's, the dream of the geomodeler has been to generate plate tectonics self-consistently from thermal convection in the laboratory. By selfconsistenly, I mean that the configuration of the plate boundaries is in no way specified a priori, so that the plates develop and are wholly consumed without intervention from the modeler. The reciepe is simple : put a well-chosen fluid in a fishtank heated from below and cooled from above, wait and see. But the « well-chosen » is the difficult part... and the interesting one. Plate tectonics is occuring on Earth because of the characteristics of the lithosphere rheology. The latter are complex to estimate as they depend on temperature, pressure, phase, water content, chemistry, strain rate, memory and scale. As a result, the ingredients necessary for plate tectonics are still debated, and it would be useful to find an analog fluid who could reproduce plate tectonics in the laboratory. I have therefore spent the last 25 years to try out fluids, and I shall present a number of failures to generate plate tectonics using polymers, colloids, ketchup, milk, chocolate, sugar, oils. To understand why they failed is important to narrow down the « well-chosen » fluid.

An Experimental Investigation of the Flow Structure of Supersonic Impinging Jets

NASA Technical Reports Server (NTRS)

Henderson, Brenda; Bridges, James; Wernet, Mark

2002-01-01

An experimental investigation into the jet structure associated with sound production by a supersonic impinging jet is presented. Large plate impinging tones are investigated for a nozzle pressure ratio (NPR) of 4 and nozzle-to-plate spacings between 1 and 5 nozzle exit diameters, where NPR is equal to the ratio of the stagnation pressure to the pressure at the nozzle lip. Results from phase-locked shadowgraph and phase-averaged digital particle image velocimetry (DPIV) studies indicate that, during the oscillation cycle, the Mach disk oscillates axially, a well defined recirculation zone is created in the subsonic impingement region and moves toward the plate, and the compression and expansion regions in the outer supersonic flow move downstream, Sound appears to be generated in the wall jet at approximately 2.6R from the jet axis, where R is the nozzle exit radius. The oscillatory motion in the wall jet is the result of the periodic fluid motion in the near wall region.

Analytical Round Robin for Elastic-Plastic Analysis of Surface Cracked Plates, Phase II Results

NASA Technical Reports Server (NTRS)

Allen, P. A.; Wells, D. N.

2017-01-01

The second phase of an analytical round robin for the elastic-plastic analysis of surface cracks in flat plates was conducted under the auspices of ASTM Interlaboratory Study 732. The interlaboratory study (ILS) had 10 participants with a broad range of expertise and experience, and experimental results from a surface crack tension test in 4142 steel plate loaded well into the elastic-plastic regime provided the basis for the study. The participants were asked to evaluate a surface crack tension test according to the version of the surface crack initiation toughness testing standard published at the time of the ILS, E2899-13. Data were provided to each participant that represent the fundamental information that would be provided by a mechanical test laboratory prior to evaluating the test result. Overall, the participant’s test analysis results were in good agreement and constructive feedback was received that has resulted in an improved published version of the standard E2899-15.

An ultrathin terahertz quarter-wave plate using planar babinet-inverted metasurface.

PubMed

Wang, Dacheng; Gu, Yinghong; Gong, Yandong; Qiu, Cheng-Wei; Hong, Minghui

2015-05-04

Metamaterials promise an exotic approach to artificially manipulate the polarization state of electromagnetic waves and boost the design of polarimetric devices for sensitive detection, imaging and wireless communication. Here, we present the design and experimental demonstration of an ultrathin (0.29λ) terahertz quarter-wave plate based on planar babinet-inverted metasurface. The quarter-wave plate consisting of arrays of asymmetric cross apertures reveals a high transmission of 0.545 with 90 degrees phase delay at 0.870 THz. The calculated ellipticity indicates a high degree of polarization conversion from linear to circular polarization. With respect to different incident polarization angles, left-handed circular polarized light, right-handed circular polarized light and elliptically polarized light can be created by this novel design. An analytical model is applied to describe transmitted amplitude, phase delay and ellipticitiy, which are in good agreement with the measured and simulated results. The planar babinet-inverted metasurface with the analytical model opens up avenues for new functional terahertz devices design.

Facile synthesis of Co3O4 hexagonal plates by flux method

NASA Astrophysics Data System (ADS)

Han, Ji-Long; Meng, Qing-Fen; Gao, Sheng-Li

2018-01-01

Using a novel flux method, a hexagonal plate of Co3O4 was directly synthesized. In this method, CoCl2·6H2O, NaOH, and the cosolvent H3BO3 were heated to 750 °C for 2 h in a corundum crucible. The products were characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and high-resolution transmission electron microscope (HRTEM). Furthermore, XRD studies indicated that the product consisted of a cubic phase of Co3O4, and the phase existed in a completely crystalline form. Then, SEM results indicated that these hexagonal plates tiered up and they had diameters in the range of 2-10 μm. According to the results of SAED and HRTEM analyses, the interlayer spacing was about 0.24 nm, which corresponds to the interlayer distance of (3 1 1) crystal plane of cubic Co3O4.

X-ray ptychography using randomized zone plates

DOE PAGES

Morrison, G. R.; Zhang, F.; Robinson, Ian K.; ...

2018-05-31

We have developed a randomized grating condenser zone plate (GCZP) that provides a μm-scale probe for use in x-ray ptychography. This delivers a significantly better x-ray throughput than probes defined by pinhole apertures, while providing a clearly-defined level of phase diversity to the illumination on the sample, and helping to reduce the dynamic range of the detected signal by spreading the zero-order light over an extended area of the detector. The first use of this novel x-ray optical element has been demonstrated successfully for both amplitude and phase contrast imaging using soft x-rays on the TwinMic beamline at the Elettramore » synchrotron.« less

X-ray ptychography using randomized zone plates

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

Morrison, G. R.; Zhang, F.; Robinson, Ian K.

We have developed a randomized grating condenser zone plate (GCZP) that provides a μm-scale probe for use in x-ray ptychography. This delivers a significantly better x-ray throughput than probes defined by pinhole apertures, while providing a clearly-defined level of phase diversity to the illumination on the sample, and helping to reduce the dynamic range of the detected signal by spreading the zero-order light over an extended area of the detector. The first use of this novel x-ray optical element has been demonstrated successfully for both amplitude and phase contrast imaging using soft x-rays on the TwinMic beamline at the Elettramore » synchrotron.« less

Insight into collision zone dynamics from topography: numerical modelling results and observations

NASA Astrophysics Data System (ADS)

Bottrill, A. D.; van Hunen, J.; Allen, M. B.

2012-11-01

Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs) basin on the overriding plate after initial collision. This "collisional mantle dynamic basin" (CMDB) is caused by slab steepening drawing, material away from the base of the overriding plate. Also, during this initial collision phase, surface uplift is predicted on the overriding plate between the suture zone and the CMDB, due to the subduction of buoyant continental material and its isostatic compensation. After slab detachment, redistribution of stresses and underplating of the overriding plate cause the uplift to spread further into the overriding plate. This topographic evolution fits the stratigraphy found on the overriding plate of the Arabia-Eurasia collision zone in Iran and south east Turkey. The sedimentary record from the overriding plate contains Upper Oligocene-Lower Miocene marine carbonates deposited between terrestrial clastic sedimentary rocks, in units such as the Qom Formation and its lateral equivalents. This stratigraphy shows that during the Late Oligocene-Early Miocene the surface of the overriding plate sank below sea level before rising back above sea level, without major compressional deformation recorded in the same area. Our modelled topography changes fit well with this observed uplift and subsidence.

Seismic anisotropy of western Mexico and northeastern Tibet

NASA Astrophysics Data System (ADS)

Leon-Soto, Gerardo

In this dissertation, characteristics of upper mantle anisotropy, using shear wave splitting techniques, for two distinct tectonic provinces are presented. In the first part, in western Mexico, the Rivera and Cocos plates subduct beneath the North America plate constituting a young subduction setting where plate fragmentation and capture is occurring today. We characterize the upper mantle anisotropy from SKS and local S phases from the data collected by the MARS experiment (MApping the Rivera Subduction zone) and by two stations of the Mexican Servicio Sismologico National. SKS shear-wave splitting parameters indicate that the fast directions of the split SKS waves for the stations that lie on the central and southern Jalisco block are approximately trench normal. Fast polarizations of these phases also follow the convergence direction between the Rivera Plate and Jalisco block with respect to the North America plate. S-wave splitting from slab events show a small averaged delay time of about 0.2 sec for the upper 60 km of the crust and mantle. Therefore, the main source of anisotropy must reside on the entrained mantle below the young and thin Rivera Plate. Trench-oblique fast SKS split directions are observed in the western edge of the Rivera Plate and western parts of the Cocos slab. The curved pattern of fast SKS split directions in the western Jalisco block and the Rivera-Cocos gap indicate 3-D toroidal mantle flow, around the northwestern edge of the Rivera slab and Rivera- Cocos gap. This behavior profoundly affects finite strain field in the northwestern edge of the Rivera slab and the mantle wedge. The shear wave splitting results support the idea that the Rivera and Cocos plates not only moved in a down-dip direction but also have recently rolled back towards the trench and the Colima rift is intimately related to the tearing between the Rivera and Cocos plates. In the second study, the tectonic enviroment of the northeastern Tibetan plateau is considered. Shear wave splitting measurements using teleseismic SKS and SKKS phases recorded by the ASCENT (A Seismic Collaborative Experiment in Northeastern Tibet) and INDEPTH-IV (International Deep Profiling of Tibet and the Himalaya, Phase IV) experiments reveal significant anisotropy in north-eastern Tibet with a large delay time of up 2.2 sec, indicating that anisotropy exists in both the lithospheric and asthenospheric mantle. The coherence between fast polarization directions of split core phases and the left-lateral slip on eastern-striking, southeastern-striking and southern-striking faults in eastern Tibet as well as the surface velocity calculated from GPS data support the idea that left-lateral shear strain is the predominant cause of the orientation of the upper mantle petrofabrics. The left-lateral motion can be best understood as a manifestation of north-striking right-lateral simple shear exerted by the eastern edge of the underthrusting Indian plate as it penetrates into Eurasia, as well as the bending of the Eastern Himalayan Syntaxis (EHS) by the foundering Burma-Andaman-Sumatra slab. Two plausible competing models are proposed for the flow of asthenosphere. In the first, the deforming lithosphere gliding over the passive asthenosphere induces flow of the asthenosphere. In the second, the asthenosphere beneath northeastern Tibet is flowing eastward in an asthenosphere channel that lies between the Ordos plateau and Sichuan basin, and around the EHS as it is being compressed between the advancing Indian continental lithosphere and the thick Tarim and Qaidam lithospheres to the north. Delay times from stations in the EHS have a maximum of 1.3 sec suggesting that although most anisotropy is residing in the lithosphere, some may be associated with flow of the asthenosphere. The retreating Burma slab induces flow that is toroidal and located exclusively around the northern edge of the slab. The curved fast directions of split shear waves for stations in the EHS are consistent with the toroidal flow pattern as well as the rotational deformation of the overlying lithosphere. It is suggested that the foundering Burma plate may also play an important role in bending the EHS in the late Cenozoic time.

LCP crystallization and X-ray diffraction analysis of VcmN, a MATE transporter from Vibrio cholerae

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

Kusakizako, Tsukasa; Tanaka, Yoshiki; Hipolito, Christopher J.

A V. cholerae MATE transporter was crystallized using the lipidic cubic phase (LCP) method. X-ray diffraction data sets were collected from single crystals obtained in a sandwich plate and a sitting-drop plate to resolutions of 2.5 and 2.2 Å, respectively. Multidrug and toxic compound extrusion (MATE) transporters, one of the multidrug exporter families, efflux xenobiotics towards the extracellular side of the membrane. Since MATE transporters expressed in bacterial pathogens contribute to multidrug resistance, they are important therapeutic targets. Here, a MATE-transporter homologue from Vibrio cholerae, VcmN, was overexpressed in Escherichia coli, purified and crystallized in lipidic cubic phase (LCP). X-raymore » diffraction data were collected to 2.5 Å resolution from a single crystal obtained in a sandwich plate. The crystal belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 52.3, b = 93.7, c = 100.2 Å. As a result of further LCP crystallization trials, crystals of larger size were obtained using sitting-drop plates. X-ray diffraction data were collected to 2.2 Å resolution from a single crystal obtained in a sitting-drop plate. The crystal belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 61.9, b = 91.8, c = 100.9 Å. The present work provides valuable insights into the atomic resolution structure determination of membrane transporters.« less

Wavefront measurements of phase plates combining a point-diffraction interferometer and a Hartmann-Shack sensor.

PubMed

Bueno, Juan M; Acosta, Eva; Schwarz, Christina; Artal, Pablo

2010-01-20

A dual setup composed of a point diffraction interferometer (PDI) and a Hartmann-Shack (HS) wavefront sensor was built to compare the estimates of wavefront aberrations provided by the two different and complementary techniques when applied to different phase plates. Results show that under the same experimental and fitting conditions both techniques provide similar information concerning the wavefront aberration map. When taking into account all Zernike terms up to 6th order, the maximum difference in root-mean-square wavefront error was 0.08 microm, and this reduced up to 0.03 microm when excluding lower-order terms. The effects of the pupil size and the order of the Zernike expansion used to reconstruct the wavefront were evaluated. The combination of the two techniques can accurately measure complicated phase profiles, combining the robustness of the HS and the higher resolution and dynamic range of the PDI.

All-dielectric reflective half-wave plate metasurface based on the anisotropic excitation of electric and magnetic dipole resonances.

PubMed

Ma, Zhijie; Hanham, Stephen M; Gong, Yandong; Hong, Minghui

2018-02-15

We present an all-dielectric metasurface that simultaneously supports electric and magnetic dipole resonances for orthogonal polarizations. At resonances, the metasurface reflects the incident light with nearly perfect efficiency and provides a phase difference of π in the two axes, making a low-loss half-wave plate in reflection mode. The polarization handedness of the incident circularly polarized light is preserved after reflection; this is different from either a pure electric mirror or magnetic mirror. With the features of high reflection and circular polarization conservation, the metamirror is an ideal platform for the geometric phase-based gradient metasurface functioning in reflection mode. Anomalous reflection with the planar meta-mirror is demonstrated as a proof of concept. The proposed meta-mirror can be a good alternative to plasmonic metasurfaces for future compact and high-efficiency metadevices for polarization and phase manipulation in reflection mode.

Giant self-biased converse magnetoelectric effect in multiferroic heterostructure with single-phase magnetostrictive materials

NASA Astrophysics Data System (ADS)

Zhang, Jitao; Li, Ping; Wen, Yumei; He, Wei; Yang, Aichao; Wang, Decai; Yang, Chao; Lu, Caijiang

2014-10-01

Giant self-biased converse magnetoelectric (CME) effects with obvious hysteretic behaviors are systematically investigated in two-phase SmFe2/PZT [Pb(Zr1-x, Tix)O3] multiferroic laminates at room temperature. Taking advantage of the huge anisotropic field of SmFe2 plate, large remnant CME coupling is provoked by this field instead of permanent magnets to bias the laminate. Consequently, bitable magnetization status switching is realized through a smaller ac voltage far below the electric coercive field in the absence of magnetic bias field. Experiments demonstrate that a large remnant CME coefficient (αCME) of 0.007 mG/V is achieved, exhibiting ˜50 times higher CME coefficient than the previous laminate composite multi-phase magnetostrictive plates. These results provide promising applications for realization of high-density magnetoelectric random access memories (MERAMs) devices with lower energy consumption.

Topography of the Overriding Plate During Progressive Subduction: A Dynamic Model to Explain Forearc Subsidence

NASA Astrophysics Data System (ADS)

Chen, Zhihao; Schellart, Wouter P.; Duarte, João. C.; Strak, Vincent

2017-10-01

Overriding plate topography provides constraints on subduction zone geodynamics. We investigate its evolution using fully dynamic laboratory models of subduction with techniques of stereoscopic photogrammetry and particle image velocimetry. Model results show that the topography is characterized by an area of forearc dynamic subsidence, with a magnitude scaling to 1.44-3.97 km in nature, and a local topographic high between the forearc subsided region and the trench. These topographic features rapidly develop during the slab free-sinking phase and gradually decrease during the steady state slab rollback phase. We propose that they result from the variation of the vertical component of the trench suction force along the subduction zone interface, which gradually increases with depth and results from the gradual slab steepening during the initial transient slab sinking phase. The downward mantle flow in the nose of the mantle wedge plays a minor role in driving forearc subsidence.

Measurement of the topological charge and index of vortex vector optical fields with a space-variant half-wave plate.

PubMed

Liu, Gui-Geng; Wang, Ke; Lee, Yun-Han; Wang, Dan; Li, Ping-Ping; Gou, Fangwang; Li, Yongnan; Tu, Chenghou; Wu, Shin-Tson; Wang, Hui-Tian

2018-02-15

Vortex vector optical fields (VVOFs) refer to a kind of vector optical field with an azimuth-variant polarization and a helical phase, simultaneously. Such a VVOF is defined by the topological index of the polarization singularity and the topological charge of the phase vortex. We present a simple method to measure the topological charge and index of VVOFs by using a space-variant half-wave plate (SV-HWP). The geometric phase grating of the SV-HWP diffracts a VVOF into ±1 orders with orthogonally left- and right-handed circular polarizations. By inserting a polarizer behind the SV-HWP, the two circular polarization states project into the linear polarization and then interfere with each other to form the interference pattern, which enables the direct measurement of the topological charge and index of VVOFs.

Transmission electron microscopy investigation of interfaces in a two-phase TiAl alloy

NASA Astrophysics Data System (ADS)

Mahon, G. J.; Howe, J. M.

1990-06-01

The atomic structures of the γ/α2 and γ/γT interfaces in a TiAl alloy were investigated using conventional and high-resolution transmission electron microscopy (TEM) in order to understand the growth mechanisms and deformation behavior of the two-phase alloy. The results show that the α2 plates grow from the γ phase by the migration of a/6<112> partial dislocation ledges across the faces and that the γ/α2 interface usually contains closely spaced arrays of interfacial dislocations. Deformation twins cut through both γ twin boundaries and α2 plates during deformation, although slip of twinning c slocations through α2 appears to be a difficult process. Both the γ/α2 and γ/γT interfaces can be imaged and modeled at the atomic level, although slight crystal and/or beam tilt can complicate image interpretation.

Apparatus for monitoring two-phase flow

DOEpatents

Sheppard, John D.; Tong, Long S.

1977-03-01

A method and apparatus for monitoring two-phase flow is provided that is particularly related to the monitoring of transient two-phase (liquid-vapor) flow rates such as may occur during a pressurized water reactor core blow-down. The present invention essentially comprises the use of flanged wire screens or similar devices, such as perforated plates, to produce certain desirable effects in the flow regime for monitoring purposes. One desirable effect is a measurable and reproducible pressure drop across the screen. The pressure drop can be characterized for various known flow rates and then used to monitor nonhomogeneous flow regimes. Another useful effect of the use of screens or plates in nonhomogeneous flow is that such apparatus tends to create a uniformly dispersed flow regime in the immediate downstream vicinity. This is a desirable effect because it usually increases the accuracy of flow rate measurements determined by conventional methods.

Method and apparatus for monitoring two-phase flow. [PWR

DOEpatents

Sheppard, J.D.; Tong, L.S.

1975-12-19

A method and apparatus for monitoring two-phase flow is provided that is particularly related to the monitoring of transient two-phase (liquid-vapor) flow rates such as may occur during a pressurized water reactor core blow-down. The present invention essentially comprises the use of flanged wire screens or similar devices, such as perforated plates, to produce certain desirable effects in the flow regime for monitoring purposes. One desirable effect is a measurable and reproducible pressure drop across the screen. The pressure drop can be characterized for various known flow rates and then used to monitor nonhomogeneous flow regimes. Another useful effect of the use of screens or plates in nonhomogeneous flow is that such apparatus tends to create a uniformly dispersed flow regime in the immediate downstream vicinity. This is a desirable effect because it usually increases the accuracy of flow rate measurements determined by conventional methods.

Measurement of elastic and thermal properties of composite materials using digital speckle pattern interferometry

NASA Astrophysics Data System (ADS)

Kumar, Manoj; Khan, Gufran S.; Shakher, Chandra

2015-08-01

In the present work, application of digital speckle pattern interferometry (DSPI) was applied for the measurement of mechanical/elastic and thermal properties of fibre reinforced plastics (FRP). Digital speckle pattern interferometric technique was used to characterize the material constants (Poisson's ratio and Young's modulus) of the composite material. Poisson ratio based on plate bending and Young's modulus based on plate vibration of material are measured by using DSPI. In addition to this, the coefficient of thermal expansion of composite material is also measured. To study the thermal strain analysis, a single DSPI fringe pattern is used to extract the phase information by using Riesz transform and the monogenic signal. The phase extraction from a single DSPI fringe pattern by using Riesz transform does not require a phase-shifting system or spatial carrier. The elastic and thermal parameters obtained from DSPI are in close agreement with the theoretical predictions available in literature.

Ultra-thin optical vortex phase plate based on the metasurface and the angular momentum transformation

NASA Astrophysics Data System (ADS)

Wang, Wei; Li, Yan; Guo, Zhongyi; Li, Rongzhen; Zhang, Jingran; Zhang, Anjun; Qu, Shiliang

2015-04-01

The ultra-thin optical vortex phase plate (VPP) has been designed and investigated based on the metasurface of the metal rectangular split-ring resonators (MRSRRs) array. The circularly polarized incident light can convert into corresponding cross-polarization transmission light, and the phase and the amplitude of cross-polarization transmission light can be simultaneously governed by modulating two arms of the MRSRR. The MRSRR has been arranged in a special order for forming an ultra-thin optical VPP that can covert a plane wave into a vortex beam with a variety of the topological charges, and the transformation between spin angular momentum (SAM) and orbital angular momentum (OAM) has been discussed in detail. The multi-spectral characteristics of the VPP have also been investigated, and the operating bandwidth of the designed VPP is 190 nm (in the range of 710-900 nm), which enable a potential implication for integrated optics and vortex optics.

Visualization and quantification of capillary drainage in the pore space of laminated sandstone by a porous plate method using differential imaging X-ray microtomography

NASA Astrophysics Data System (ADS)

Lin, Qingyang; Bijeljic, Branko; Rieke, Holger; Blunt, Martin J.

2017-08-01

The experimental determination of capillary pressure drainage curves at the pore scale is of vital importance for the mapping of reservoir fluid distribution. To fully characterize capillary drainage in a complex pore space, we design a differential imaging-based porous plate (DIPP) method using X-ray microtomography. For an exemplar mm-scale laminated sandstone microcore with a porous plate, we quantify the displacement from resolvable macropores and subresolution micropores. Nitrogen (N2) was injected as the nonwetting phase at a constant pressure while the porous plate prevented its escape. The measured porosity and capillary pressure at the imaged saturations agree well with helium measurements and experiments on larger core samples, while providing a pore-scale explanation of the fluid distribution. We observed that the majority of the brine was displaced by N2 in macropores at low capillary pressures, followed by a further brine displacement in micropores when capillary pressure increases. Furthermore, we were able to discern that brine predominantly remained within the subresolution micropores, such as regions of fine lamination. The capillary pressure curve for pressures ranging from 0 to 1151 kPa is provided from the image analysis compares well with the conventional porous plate method for a cm-scale core but was conducted over a period of 10 days rather than up to few months with the conventional porous plate method. Overall, we demonstrate the capability of our method to provide quantitative information on two-phase saturation in heterogeneous core samples for a wide range of capillary pressures even at scales smaller than the micro-CT resolution.

The lithosphere-asthenosphere boundary beneath the South Island of New Zealand

NASA Astrophysics Data System (ADS)

Hua, Junlin; Fischer, Karen M.; Savage, Martha K.

2018-02-01

Lithosphere-asthenosphere boundary (LAB) properties beneath the South Island of New Zealand have been imaged by Sp receiver function common-conversion point stacking. In this transpressional boundary between the Australian and Pacific plates, dextral offset on the Alpine fault and convergence have occurred for the past 20 My, with the Alpine fault now bounded by Australian plate subduction to the south and Pacific plate subduction to the north. Using data from onland seismometers, especially the 29 broadband stations of the New Zealand permanent seismic network (GeoNet), we obtained 24,971 individual receiver functions by extended-time multi-taper deconvolution, and mapped them to three-dimensional space using a Fresnel zone approximation. Pervasive strong positive Sp phases are observed in the LAB depth range indicated by surface wave tomography. These phases are interpreted as conversions from a velocity decrease across the LAB. In the central South Island, the LAB is observed to be deeper and broader to the northwest of the Alpine fault. The deeper LAB to the northwest of the Alpine fault is consistent with models in which oceanic lithosphere attached to the Australian plate was partially subducted, or models in which the Pacific lithosphere has been underthrust northwest past the Alpine fault. Further north, a zone of thin lithosphere with a strong and vertically localized LAB velocity gradient occurs to the northwest of the fault, juxtaposed against a region of anomalously weak LAB conversions to the southeast of the fault. This structure could be explained by lithospheric blocks with contrasting LAB properties that meet beneath the Alpine fault, or by the effects of Pacific plate subduction. The observed variations in LAB properties indicate strong modification of the LAB by the interplay of convergence and strike-slip deformation along and across this transpressional plate boundary.