Tactical Defenses Against Systematic Variation in Wind Tunnel Testing
NASA Technical Reports Server (NTRS)
DeLoach, Richard
2002-01-01
This paper examines the role of unexplained systematic variation on the reproducibility of wind tunnel test results. Sample means and variances estimated in the presence of systematic variations are shown to be susceptible to bias errors that are generally non-reproducible functions of those variations. Unless certain precautions are taken to defend against the effects of systematic variation, it is shown that experimental results can be difficult to duplicate and of dubious value for predicting system response with the highest precision or accuracy that could otherwise be achieved. Results are reported from an experiment designed to estimate how frequently systematic variations are in play in a representative wind tunnel experiment. These results suggest that significant systematic variation occurs frequently enough to cast doubts on the common assumption that sample observations can be reliably assumed to be independent. The consequences of ignoring correlation among observations induced by systematic variation are considered in some detail. Experimental tactics are described that defend against systematic variation. The effectiveness of these tactics is illustrated through computational experiments and real wind tunnel experimental results. Some tutorial information describes how to analyze experimental results that have been obtained using such quality assurance tactics.
Postmarketing surveillance: perspectives of a journal editor.
Gelenberg, A J
1993-01-01
In the absence of a systematic monitoring program for drugs newly approved by the Food and Drug Administration (FDA), reports in clinical journals provide a legitimate forum for disseminating information about unexpected pharmacologic events. A journal editor bears the responsibility for publishing educated clinical observations that meet standards of scientific rigor while not giving premature credibility to chance and dubious reports of side effects of new drugs. Often this responsibility involves overcoming the fear of bad publicity and withstanding pressures from pharmaceutical companies to print only positive information about new products. Published preliminary observations may contribute to the problem of product liability, but they also generate testable hypotheses and healthy debate. If hypotheses later prove to be incorrect, they can be refuted by systematic studies and clarified in reviews and editorials. Our goal of effective education will be reached not by self-censorship but by scientific openness.
A two-step automatic sleep stage classification method with dubious range detection.
Sousa, Teresa; Cruz, Aniana; Khalighi, Sirvan; Pires, Gabriel; Nunes, Urbano
2015-04-01
The limitations of the current systems of automatic sleep stage classification (ASSC) are essentially related to the similarities between epochs from different sleep stages and the subjects' variability. Several studies have already identified the situations with the highest likelihood of misclassification in sleep scoring. Here, we took advantage of such information to develop an ASSC system based on knowledge of subjects' variability of some indicators that characterize sleep stages and on the American Academy of Sleep Medicine (AASM) rules. An ASSC system consisting of a two-step classifier is proposed. In the first step, epochs are classified using support vector machines (SVMs) spread into different nodes of a decision tree. In the post-processing step, the epochs suspected of misclassification (dubious classification) are tagged, and a new classification is suggested. Identification and correction are based on the AASM rules, and on misclassifications most commonly found/reported in automatic sleep staging. Six electroencephalographic and two electrooculographic channels were used to classify wake, non-rapid eye movement (NREM) sleep--N1, N2 and N3, and rapid eye movement (REM) sleep. The proposed system was tested in a dataset of 14 clinical polysomnographic records of subjects suspected of apnea disorders. Wake and REM epochs not falling in the dubious range, are classified with accuracy levels compatible with the requirements for clinical applications. The suggested correction assigned to the epochs that are tagged as dubious enhances the global results of all sleep stages. This approach provides reliable sleep staging results for non-dubious epochs. Copyright © 2015 Elsevier Ltd. All rights reserved.
Schmidt, Joachim; Hoffmann, Hannes; Michalik, Peter
2016-02-22
The first eyeless beetle known from Baltic amber, Trechus eoanophthalmus sp. n., is described and imaged using light microscopy and X-ray micro-computed tomography. Based on external characters, the new species is most similar to species of the Palaearctic Trechus sensu stricto clade and seems to be closely related to the Baltic amber fossil T. balticus Schmidt & Faille, 2015. Due to the poor conservation of the internal parts of the body, no information on the genital characters can be provided. Therefore, the systematic position of this fossil within the megadiverse genus Trechus remains dubious. The occurrence of the blind and flightless T. eoanophthalmus sp. n. in the Baltic amber forests supports a previous hypothesis that these forests were located in an area partly characterised by mountainous habitats with temperate climatic conditions.
Simou, Effie; Koutsogeorgou, Eleni
2014-04-01
Due to the current economic crisis in Greece, effects on health and healthcare have been reported. The aim of this study was to present a systematic overview of the consequences that the financial crisis has had for health and healthcare in Greece. Systematic literature review was conducted in order to identify articles that were published from January 2009 to March 2013 and explicitly referred to the effects of economic crisis on health or healthcare, in Greece. Data extraction and synthesis was performed with the use of thematic analysis. Thirty-nine studies were considered for further analyses. Various existing and potential relevant effects were identified, including reductions in public health expenditure and changes in healthcare services and the pharmaceutical market, with an increasing number of admissions in public healthcare sector, and efficiency and organizational-related issues being evident, overall. Indications were found for post-crisis deterioration of public health with increasing rates of mental health, suicides, and epidemics, and deterioration of self-rated health. The recent efforts to reform the Greek National Health System have been focusing mainly on short-term effects by reducing expenditure, while the measures imposed seem to have dubious long-term consequences for Greek public health and healthcare. Copyright © 2014 The Authos. Published by Elsevier Ireland Ltd.. All rights reserved.
Que, Ting-zhi; Zhao, Shu-min; Li, Cheng-tao
2010-08-01
Determination strategies for half sibling sharing a same mother were investigated through the detection of autosomal and X-chromosomal STR (X-STR) loci and polymorphisms on hypervariable (HV) region of mitochondrial DNA (mtDNA). Genomic DNA were extracted from blood stain samples of the 3 full siblings and one dubious half sibling sharing the same mother with them. Fifteen autosomal STR loci were genotyped by Sinofiler kit, and 19 X-STR loci were genotyped by Mentype Argus X-8 kit and 16 plex in-house system. Polymorphisms of mtDNA HV-I and HV-II were also detected with sequencing technology. Full sibling relationship between the dubious half sibling and each of the 3 full siblings were excluded based on the results of autosomal STR genotyping and calculation of full sibling index (FSI) and half sibling index (HIS). Results of sequencing for mtDNA HV-I and HV-II showed that all of the 4 samples came from a same maternal line. X-STR genotyping results determined that the dubious half sibling shared a same mother with the 3 full siblings. It is reliable to combine three different genotyping technologies including autosomal STR, X-STR and sequencing of mtDNA HV-I and HV-II for determination of half sibling sharing a same mother.
On the Viability of Conspiratorial Beliefs
Grimes, David Robert
2016-01-01
Conspiratorial ideation is the tendency of individuals to believe that events and power relations are secretly manipulated by certain clandestine groups and organisations. Many of these ostensibly explanatory conjectures are non-falsifiable, lacking in evidence or demonstrably false, yet public acceptance remains high. Efforts to convince the general public of the validity of medical and scientific findings can be hampered by such narratives, which can create the impression of doubt or disagreement in areas where the science is well established. Conversely, historical examples of exposed conspiracies do exist and it may be difficult for people to differentiate between reasonable and dubious assertions. In this work, we establish a simple mathematical model for conspiracies involving multiple actors with time, which yields failure probability for any given conspiracy. Parameters for the model are estimated from literature examples of known scandals, and the factors influencing conspiracy success and failure are explored. The model is also used to estimate the likelihood of claims from some commonly-held conspiratorial beliefs; these are namely that the moon-landings were faked, climate-change is a hoax, vaccination is dangerous and that a cure for cancer is being suppressed by vested interests. Simulations of these claims predict that intrinsic failure would be imminent even with the most generous estimates for the secret-keeping ability of active participants—the results of this model suggest that large conspiracies (≥1000 agents) quickly become untenable and prone to failure. The theory presented here might be useful in counteracting the potentially deleterious consequences of bogus and anti-science narratives, and examining the hypothetical conditions under which sustainable conspiracy might be possible. PMID:26812482
Government Classification: An Overview.
ERIC Educational Resources Information Center
Brown, Karen M.
Classification of government documents (confidential, secret, top secret) is a system used by the executive branch to, in part, protect national security and foreign policy interests. The systematic use of classification markings with precise definitions was established during World War I, and since 1936 major changes in classification have…
InGen Inconsistencies: The "Dinosaurs" Of Jurassic Park May Not Be What The Corporation Claims
NASA Astrophysics Data System (ADS)
Haupt, R. J.; Traer, M. M.
2017-12-01
InGen has made and continues to make dubious claims about proprietary technology developed to clone non-avian dinosaurs for exhibition within their "Jurassic Park." Notably, there are several inconsistencies between their claims for how their technology works and what has been observed within the park. Here we investigate several of these inconsistencies in the hopes that it will push for increased transparency between corporations and academia. First, we highlight a disconnect between supposedly Jurassic amber used for dinosaur DNA extraction and the overwhelming presence of Late Cretaceous dinosaurs within the park. Further, InGen's mining operations only publicly operate in Jurassic-aged formations of the Dominican Republic, which clashes with the presence of Velociraptor and Gallimimus, known only from Mongolia. Second, the park contains seemingly full-grown adult specimens despite InGen's claims that they first successfully cloned a prehistoric animal in 1984, though there is no publicly available information as to what animal this was. That the park was nearly ready to open by 1993 precludes the presence of fully mature dinosaurs and suggests that InGen might be misrepresenting their technologies. Third, we must point out that fossil DNA denatures to the point of uselessness within thousands, not millions, of years. Additionally, the use of anuran DNA to fill in gaps from fossil dinosaurian DNA is a dubious choice given that more closely related organisms are available. Either there is an unexplained reason for this choice, or little attention has been paid to dinosaurian phylogeny by InGen geneticists. Finally, rumors of a secret InGen project to produce a dinosaur not currently known to paleontologists suggests one of two things: they were able to find DNA from a dinosaur previously unknown in the fossil record, which is highly plausible if their techniques are valid, or that InGen is able to artificially manipulate DNA to a degree far beyond what other biotech companies have been able to do at present. These inconsistencies suggest that the actual technological assets developed by InGen might be slightly, or even significantly, different than what their promotional materials claim, and that paleontologists should be wary of using these animals as study organisms to test paleontological hypotheses.
2011-07-01
sciences and philosophies are based on dubious premises or are in fact pseudosciences. Modern military theory was heavily influenced by empiricism and...determinism. Empiricism is described as a logical process based on pursuing knowledge through observation and experiments. One can make sensible
Critical review of expert system validation in transportation
DOT National Transportation Integrated Search
1997-01-01
Expert system validationthat is, testing systems to ascertain whether they achieve acceptable performance levelshas with few exceptions been ad hoc, informal, and of dubious value. Very few efforts have been made in this regard in the transport...
L'Erario, Ines; Frezzolini, Alessandra; Ruggiero, Barbara; De Pità, Ornella; Emma, Francesco; Gianviti, Alessandra
2011-01-01
Lupus nephritis (LN) may represent a diagnostic problem, particularly in pediatric patients that present with typical histological lesions but do not fulfill the American Rheumatism Association (ARA) criteria for the diagnosis of systemic lupus erythematosus (SLE). Based on the well-described deposition of immunoglobulins (Ig) and complement at the dermoepithelial junction in SLE, we hypothesized that skin biopsies may help in the diagnosis of LN. To test this hypothesis, we carried out a pilot study, performing a skin biopsy in 22 patients with LN and 13 patients with lupus-like lesions, regardless of the time elapsed from onset of renal disease. The latter group of patients was further divided into a purely renal group, designated as isolated full-house nephropathy (FHN), and a dubious cases group, presenting with additional clinical and biological features consistent with SLE but insufficient for diagnosing SLE. None of the 6 isolated FHN patients had positive skin immunofluorescence. Conversely, 5/7 patients in the dubious cases group (p<0.02) and 13/22 in the LN group (p<0.002) had positive staining for C1q, and 5/7 patients in the dubious cases group (p<0.02) and 16/22 patients in the LN group (p<0.001) had positive staining for IgM. No correlation was observed with the time elapsed from the initial diagnosis. These data suggest that skin biopsies may help distinguishing LN from isolated FHN. In addition, they identify an intermediate group of patients with evidence of systemic involvement despite the absence of a sufficient number of ARA criteria to be labeled as SLE.
ERIC Educational Resources Information Center
Nyberg, David; Farber, Paul
1986-01-01
Teachers are in the awkward position of exercising authority, yet have dubious control over the conditions within which they do so. The ideal teacher role is authority exercised in good faith and a commitment to the burdens and uncertainties of educational authority. (CB)
Heringer, Lindolfo Carlos; de Oliveira, Matheus Fernandes; Rotta, José Marcus; Botelho, Ricardo Vieira
2016-01-01
Background: Recurrent or residual pituitary adenomas previously treated by transsphenoidal surgery are not uncommon. There are no strongly established guidelines to perform treatment of such cases. The objective of this study is to elucidate the effect of transsphenoidal reoperation in residual or recurrent pituitary adenomas. Methods: We made a systematic review of the literature to elucidate this effect through electronic search in MEDLINE/PubMed and Cochrane Central database. PRISMA statement was used as a basis for this systematic review and analysis of the risk of bias was made according to the Grading of Recommendations, Assessment, Development and Evaluation recommendations. Results: In this review, fifteen studies were finally pooled analyzed. Although remission rates (RRs) and follow-up periods varied widely, from 149 patients with growth hormone-secreting tumors the mean RR was 44.5%, from 273 patients with adrenocorticotropic hormone-secreting tumors the mean RR was 55.5% and among 173 patients with nonsecreting tumors, RR was 76.1%. There was significant higher RR in nonsecreting tumors. Mean follow-up was 32.1 months. No difference was found between microscopic and endoscopic techniques. Conclusions: A second transsphenoidal surgery is accompanied by a chance of remission in approximately half of cases with secreting tumors. In nonsecreting ones, success is higher. PMID:26958420
Muscedere, John; Rewa, Oleksa; McKechnie, Kyle; Jiang, Xuran; Laporta, Denny; Heyland, Daren K
2011-08-01
Aspiration of secretions containing bacterial pathogens into the lower respiratory tract is the main cause of ventilator-associated pneumonia. Endotracheal tubes with subglottic secretion drainage can potentially reduce this and, therefore, the incidence of ventilator-associated pneumonia. New evidence on subglottic secretion drainage as a preventive measure for ventilator-associated pneumonia has been recently published and to consider the evidence in totality, we conducted an updated systematic review and meta-analysis. We searched computerized databases, reference lists, and personal files. We included randomized clinical trials of mechanically ventilated patients comparing standard endotracheal tubes to those with subglottic secretion drainage and reporting on the occurrence of ventilator-associated pneumonia. Studies were meta-analyzed for the primary outcome of ventilator-associated pneumonia and secondary clinical outcomes. We identified 13 randomized clinical trials that met the inclusion criteria with a total of 2442 randomized patients. Of the 13 studies, 12 reported a reduction in ventilator-associated pneumonia rates in the subglottic secretion drainage arm; in meta-analysis, the overall risk ratio for ventilator-associated pneumonia was 0.55 (95% confidence interval, 0.46-0.66; p < .00001) with no heterogeneity (I = 0%). The use of subglottic secretion drainage was associated with reduced intensive care unit length of stay (-1.52 days; 95% confidence interval, -2.94 to -0.11; p = .03); decreased duration of mechanically ventilated (-1.08 days; 95% confidence interval, -2.04 to -0.12; p = .03), and increased time to first episode of ventilator-associated pneumonia (2.66 days; 95% confidence interval, 1.06-4.26; p = .001). There was no effect on adverse events or on hospital or intensive care unit mortality. In those at risk for ventilator-associated pneumonia, the use of endotracheal tubes with subglottic secretion drainage is effective for the prevention of ventilator-associated pneumonia and may be associated with reduced duration of mechanical ventilation and intensive care unit length of stay.
Alternatives to Drug Treatment for Hyperactivity.
ERIC Educational Resources Information Center
Den Houtter, Kathryn
1980-01-01
Results from recent studies on the effectiveness of Ritalin for "hyperactivity" show that this treatment is dubious at best. This article presents an alternative treatment approach, placing emphasis on devising an appropriate learning situation that meets the needs of the so-called hyperactive child. (Author)
The Future of Education's Liberal Consensus.
ERIC Educational Resources Information Center
Finn, Chester E., Jr.
1980-01-01
The liberal consensus that has shaped national education policy is seen as succumbing to dubious ideas and undesirable practices. Issues discussed include: educational equity, equality and quality; measures of educational achievement; accountability; "need" and ability; statism and monoply, pluralism and diversity; federal role; and…
U.S. Broadcast Deregulation: A Case of Dubious Evidence.
ERIC Educational Resources Information Center
Levin, Harry J.
1986-01-01
Reviews the empirical evidence cited by the FCC in favor of increasing the allowable number of radio and TV stations owned by one group. Argues FCC was biased in favor of deregulation despite weighty evidence indicating continued need for regulation. (MS)
A comprehensive review on privacy preserving data mining.
Aldeen, Yousra Abdul Alsahib S; Salleh, Mazleena; Razzaque, Mohammad Abdur
2015-01-01
Preservation of privacy in data mining has emerged as an absolute prerequisite for exchanging confidential information in terms of data analysis, validation, and publishing. Ever-escalating internet phishing posed severe threat on widespread propagation of sensitive information over the web. Conversely, the dubious feelings and contentions mediated unwillingness of various information providers towards the reliability protection of data from disclosure often results utter rejection in data sharing or incorrect information sharing. This article provides a panoramic overview on new perspective and systematic interpretation of a list published literatures via their meticulous organization in subcategories. The fundamental notions of the existing privacy preserving data mining methods, their merits, and shortcomings are presented. The current privacy preserving data mining techniques are classified based on distortion, association rule, hide association rule, taxonomy, clustering, associative classification, outsourced data mining, distributed, and k-anonymity, where their notable advantages and disadvantages are emphasized. This careful scrutiny reveals the past development, present research challenges, future trends, the gaps and weaknesses. Further significant enhancements for more robust privacy protection and preservation are affirmed to be mandatory.
Smeraglia, Francesco; Mariconda, Massimo; Balato, Giovanni; Di Donato, Sigismondo Luca; Criscuolo, Giovanni; Maffulli, Nicola
2018-06-01
Trapeziometacarpal arthritis is a common and disabling condition. There is no evidence in the literature of superiority of one surgical procedure over others. Several prosthetic implants have been introduced to preserve joint mobility. We searched the on Medline (PubMed), Web of Science and Scopus databases using the combined keywords 'artelon', 'thumb', 'carpometacarpal', 'trapeziometacarpal' and 'rhizoarthrosis'; 11 studies were identified. The use of Artelon implant is not recommended because of its high revision rate and worse outcomes compared to conventional techniques. Inert materials subjected to compressive and shearing forces could produce debris and subsequent inflammatory response. There is debate in the published scientific literature regarding the role of preoperative antibiotic profilaxis and post-surgery inflammatory response. Standard techniques such as trapeziectomy alone or combined with interposition or suspensionplasty offer effective treatment for thumb basal joint arthritis. Several prosthetic implants show promising results in terms of pain relief and functional request, but there is a need of long-term randomized controlled trials to demonstrate their equivalence, and eventually superiority, compared to standard techniques.
Computational and Experimental Analysis of the Secretome of Methylococcus capsulatus (Bath)
Indrelid, Stine; Mathiesen, Geir; Jacobsen, Morten; Lea, Tor; Kleiveland, Charlotte R.
2014-01-01
The Gram-negative methanotroph Methylococcus capsulatus (Bath) was recently demonstrated to abrogate inflammation in a murine model of inflammatory bowel disease, suggesting interactions with cells involved in maintaining mucosal homeostasis and emphasizing the importance of understanding the many properties of M. capsulatus. Secreted proteins determine how bacteria may interact with their environment, and a comprehensive knowledge of such proteins is therefore vital to understand bacterial physiology and behavior. The aim of this study was to systematically analyze protein secretion in M. capsulatus (Bath) by identifying the secretion systems present and the respective secreted substrates. Computational analysis revealed that in addition to previously recognized type II secretion systems and a type VII secretion system, a type Vb (two-partner) secretion system and putative type I secretion systems are present in M. capsulatus (Bath). In silico analysis suggests that the diverse secretion systems in M.capsulatus transport proteins likely to be involved in adhesion, colonization, nutrient acquisition and homeostasis maintenance. Results of the computational analysis was verified and extended by an experimental approach showing that in addition an uncharacterized protein and putative moonlighting proteins are released to the medium during exponential growth of M. capsulatus (Bath). PMID:25479164
A dubious success: The NGO campaign against GMOs
Paarlberg, Robert
2014-01-01
Genetically engineered agricultural crops are widely grown for animal feed (yellow corn, soybean meal) and for industrial purposes (such as cotton for fabric, or yellow corn for ethanol), but almost nobody grows GMO food staple crops. The only GMO food staple crop planted anywhere is white maize, and only in one country – the Republic of South Africa. It has been two decades now since GMO crops were first planted commercially, yet it is still not legal anywhere to plant GMO wheat or GMO rice. When it comes to GMO food crops, anti-GMO campaigners have thus won a remarkable yet dubious victory. They have not prevented rich countries from using GMO animal feed or GMO cotton, yet farmers and consumers in poor countries need increased productivity for food crops, not animal feed or industrial crops. Today's de facto global ban on GMO food crops therefore looks suspiciously like an outcome designed by the rich and for the rich, with little regard for the interests of the poor. PMID:25437241
A dubious success: the NGO campaign against GMOs.
Paarlberg, Robert
2014-07-03
Genetically engineered agricultural crops are widely grown for animal feed (yellow corn, soybean meal) and for industrial purposes (such as cotton for fabric, or yellow corn for ethanol), but almost nobody grows GMO food staple crops. The only GMO food staple crop planted anywhere is white maize, and only in one country--the Republic of South Africa. It has been two decades now since GMO crops were first planted commercially, yet it is still not legal anywhere to plant GMO wheat or GMO rice. When it comes to GMO food crops, anti-GMO campaigners have thus won a remarkable yet dubious victory. They have not prevented rich countries from using GMO animal feed or GMO cotton, yet farmers and consumers in poor countries need increased productivity for food crops, not animal feed or industrial crops. Today's de facto global ban on GMO food crops therefore looks suspiciously like an outcome designed by the rich and for the rich, with little regard for the interests of the poor.
Marine Pollution and the Law of the Sea
ERIC Educational Resources Information Center
Paterson, Arthur E., III
1975-01-01
Despite a rising tide of contamination, effective controls of marine pollution appear dubious because of conflicting national and economic interests. Since countries can not agree on problems such as national sovereignty, dispute settlement, jurisdiction over oil on the Continental Shelf and international seabed sources, marine pollution will…
How Much Is a President Worth?
ERIC Educational Resources Information Center
Trachtenberg, Stephen Joel
2007-01-01
Finding an appropriate policy for setting presidents' pay is elusive, given the dubious nature of salary comparisons. In this article, the author suggests that trustees should determine the president's worth by considering the institution's interests, the limited talent pool, and the multiple demands of the job. He contends that institutions…
Holding Aesthetics and Ideology in Tension
ERIC Educational Resources Information Center
Duncum, Paul
2008-01-01
Studying imagery, irrespective of the kind, must focus equally upon its aesthetic attractiveness, its sensory lures, and its oftentimes dubious social ideology. The terms "aesthetic" and "ideology" are addressed as problematic and are defined in current, ordinary language terms: aesthetics as visual appearances and their effects and ideology as a…
A Dubious Distinction? The BA versus the BS in Psychology
ERIC Educational Resources Information Center
Pfund, Rory A.; Norcross, John C.; Hailstorks, Robin; Aiken, Leona S.; Stamm, Karen E.; Christidis, Peggy
2016-01-01
Previous studies have documented small differences between the bachelor of arts (BA) and the bachelor of science (BS) psychology degrees in their general education core requirements, particularly mathematics and science courses. But are there differences between the BA and BS degrees within the psychology curriculum? Using data from the…
US Policies toward Tehran: Redefining Counterproliferation for the Twenty-First Century
2011-01-01
latent weapons power, purposefully not constructing an explicit, fully weaponized arsenal, but rather cultivating and maintaining a hedged nuclear...decisively dropping the popular but empirically dubious assump tion that Iran’s primary intent is to put mushroom clouds over Tel Aviv and Washington as
1989-11-15
independence but we have, after all, achieved success. We are in a position about which we could only dream not too long ago. We have achieved this without... lucidity and intelligibility, and they reflect the strength of the author’s convictions, even if these are at times dubious or even sound objectionable
European Security & Russia: A Workshop at CNAC, 13 April 2001
2001-07-01
Agricultural Policy , a dubious prospect. A half-hearted US commitment to Europe would be another ingredi- ent for continued drift. US withdrawal might... Agricultural Policy , had the responsibility for guaran- teeing European security throughout the Cold War. The prospective members ofboth NATO and the EU in
ERIC Educational Resources Information Center
Walton, Gerald
2006-01-01
The province of British Columbia has a dubious history where support for lesbian, gay, bisexual, and transgendered (LGBT) issues in education is concerned. Most notable is the Surrey School Board's decision in 1997 to ban three picture books for children that depict families with two moms or two dads. The North Vancouver School Board has also…
Leasure, A Renee; Stirlen, Joan; Lu, Shu Hua
2012-01-01
Ventilator-associated pneumonia (VAP) is a subset of hospital-acquired pneumonias and is a serious, sometimes fatal, complication in patients who need mechanical ventilation. In addition, pay-for-performance initiative has placed increased emphasis on preventing nosocomial infections including VAP. Facilities may not be reimbursed for costs associated with prevalence infections. This article presents a review and meta-analysis of the prevention of VAP through the aspiration of subglottic secretion.
ERIC Educational Resources Information Center
Hiers, Richard H.
2002-01-01
Analyzes the origins of recent federal appellate decisions' divergence from the Supreme Court's identification of teachers' or faculty's academic freedom as "a special concern of the First Amendment." Suggests ways in which academic freedom might better be accorded its rightful importance within the framework of current Supreme Court…
Failure to Learn from Failure: Evaluating Computer Systems in Medicine
Grann, Richard P.
1980-01-01
Evaluation of ADP systems in medicine frequently becomes mired in problems of tenuous cost measurement, of proving illusory cost savings, of false precision, and of dubious discounting methods, while giving only superficial treatment to non-dollar benefits. It would frequently be more advantageous to study non-dollar impacts with greater care and rigor.
The Dubious Promise of Educational Technologies: Historical Patterns and Future Challenges
ERIC Educational Resources Information Center
Cuban, Larry; Jandric, Petar
2015-01-01
In this article, Larry Cuban discusses his ideas about the topic of this Special Issue of E-learning and Digital Media "Networked Realms and Hoped-For Futures: A Trans-Generational Dialogue" with one of its co-editors, Petar Jandric. The conversation explores the historical relationships between education and information and…
News Coverage as the Contagion of Terrorism: Dangerous Charges Backed by Dubious Science.
ERIC Educational Resources Information Center
Picard, Robert G.
The literature implicating the media as responsible for the contagion of terrorist violence has grown rapidly, but, under scrutiny, it appears to contain no credible supporting evidence and fails to establish a cause-effect relationship. Some students of terrorism have borrowed conclusions from the literature about the effects of televised…
ERIC Educational Resources Information Center
Allen, Craig M.
A number of flight accidents in recent years have made the use of helicopters in news coverage controversial. Radio or television reporters are sometimes asked to fly under unsafe conditions simply because competing stations have sent up their reporters. Although pilots have the right to refuse to fly if they feel conditions are dubious, they too…
Achieving Success in Obtaining Grant Funding as a Research Scholar
ERIC Educational Resources Information Center
Cherubini, Lorenzo
2014-01-01
The process of writing successful grant proposals has received not so dubious attention in the last several decades. This article provides contextual significance resulting from a review of literature spanning 1975 to 2013. I identify essential vocabulary stemming from the literature review to familiarize the reader with the terminology associated…
Student Rights and Freedoms: Toward Implementation Models.
ERIC Educational Resources Information Center
Collins, Charles C.
Faculty, administration, and the board of trustees are dubious champions of student rights and freedoms. Without reliable protectors within the academic community, students have the options of securing their rights and freedoms by (1) the exercise of raw power, (2) finding a means to participate in the decision making process, or (3) seeking…
Initial Teacher Certification Testing in Massachusetts: A Case of the Tail Wagging the Dog.
ERIC Educational Resources Information Center
Flippo, Rona F.; Riccards, Michael P.
2000-01-01
An evaluation of the Massachusetts Educator Certification Test has revealed unforeseen, counterproductive consequences. Teacher preparation colleges are adjusting curricular emphases to teach to a test of dubious validity and are inadvertently excluding substantial portions of enrollees to boost test scores. Minorities are failing at higher rates.…
Some Esoteric Aspects of SEM that Its Practitioners Should Want to Know
ERIC Educational Resources Information Center
Rozeboom, William W.
2009-01-01
The topic of this article is the interpretation of structural equation modeling (SEM) solutions. Its purpose is to augment structural modeling's metatheoretic resources while enhancing awareness of how problematic is the causal significance of SEM-parameter solutions. Part I focuses on the nonuniqueness and consequent dubious interpretability of…
Spreading Chaos: The Role of Popularizations in the Diffusion of Scientific Ideas
ERIC Educational Resources Information Center
Paul, Danette
2004-01-01
Scientific popularizations are generally considered translations (often dubious ones) of scientific research for a lay audience. This study explores the role popularizations play within scientific discourse, specifically in the development of chaos theory. The methods included a review of the popular and the semipopular books on chaos theory from…
ERIC Educational Resources Information Center
Belz, Herman
2012-01-01
The part played by Sally Hemings in the life of Thomas Jefferson has been regarded as provocatively dubious since political enemy James Callender claimed in 1802 that Jefferson was the father of several of Hemings's children. Historian Merrill Peterson, observing that paternity is hard to prove, wrote in 1960 that no concrete evidence was ever…
One principle and a fourth fallacy of disability studies
Harris, J.
2002-01-01
This brief paper shows that the idea of benefits to the subject compensating for the harms of disability is at best self defeating and at worst sinister. Equally benefits to third parties while real are dubious as compensating factors. This shows that disabilities are just that, a net loss and not a net gain.
A Double Standard and Dubious Ethics in Determining Quality Teaching
ERIC Educational Resources Information Center
Reardon, R. Martin
2016-01-01
"Double Standard" was created by the actors who appeared in the accompanying video in spring 2014, as part fulfillment of the requirements for a master's-level class highlighting ethics in education for future educational administrators. A double standard comes into focus as an incoming middle school principal establishes procedures she…
Better data, better planning: the College of Emergency Medicine sentinel sites project.
Moulton, Chris; Mann, Clifford; Tempest, Michelle
2014-11-01
This article describes the College of Emergency Medicine's initial attempt to gather high quality data from its own 'sentinel sites' rather than relying on more comprehensive national data of dubious quality. Such information is essential to inform and guide the planning of urgent and emergency care services in the future.
Focusing Our Aim: Strengthening Faculty Commitment to Community Engagement
ERIC Educational Resources Information Center
Butin, Dan W.
2007-01-01
While many speak strongly about community engagement, few are able or willing to develop sustained and consequential programs and practices that further it. Many faculty are, in fact, dubious about an educational reform that appears too a-theoretical, too co-curricular, too much like yet another under-financed fad. In this article, the author…
ERIC Educational Resources Information Center
Ali, Radwan; Katz, Irvin R.
2010-01-01
Today's information and communications technology (ICT) provides unprecedented amounts of information to organizations and their employees. This overabundance challenges workers, placing an increasing premium on skills of sifting through information of sometimes dubious quality, integrating information critically, and producing well-reasoned…
Corporate corruption of science--the case of chromium(VI).
Egilman, David; Scout
2006-01-01
Corporate infiltration of a panel convened to set standards for chromium(VI) in California, buttressed by the engineered production of dubious "scientific" literature advancing industry's goal, succeeded in skewing the panel's decision to protect industry profits rather than public health. This situation demonstrates the insidious and effective influence of industry on the regulatory process.
Coggins, M H; Pynchon, M R
1998-01-01
The Mental Health Liaison Program developed and used by the Secret Service is presented as a model for comprehensive, multidimensional interactions between law enforcement and mental health systems, with particular focus on assessing and preventing violent behavior. The structure of the program pairs consultants--psychologists and psychiatrists--with Secret Service field offices to provide (a) consultation regarding risk assessment and case management of individuals who threaten or display inappropriate interest in the President or other protectees; (b) training for agents on risk assessment, mental illness, and mental health care issues; and (c) liaison activities between the Secret Service and the mental health community. Practical benefits to the Secret Service are discussed to encourage more systematic use of broad based psychological and psychiatric consultation to law enforcement, with a goal of enhanced intersystem communication and collaboration. The need for program evaluation and outcome research is discussed in the context of applying the model to improve other mental health and law enforcement systems interactions.
Choong, Wai-Kok; Lih, Tung-Shing Mamie; Chen, Yu-Ju; Sung, Ting-Yi
2017-12-01
To confirm the existence of missing proteins, we need to identify at least two unique peptides with length of 9-40 amino acids of a missing protein in bottom-up mass-spectrometry-based proteomic experiments. However, an identified unique peptide of the missing protein, even identified with high level of confidence, could possibly coincide with a peptide of a commonly observed protein due to isobaric substitutions, mass modifications, alternative splice isoforms, or single amino acid variants (SAAVs). Besides unique peptides of missing proteins, identified variant peptides (SAAV-containing peptides) could also alternatively map to peptides of other proteins due to the aforementioned issues. Therefore, we conducted a thorough comparative analysis on data sets in PeptideAtlas Tiered Human Integrated Search Proteome (THISP, 2017-03 release), including neXtProt (2017-01 release), to systematically investigate the possibility of unique peptides in missing proteins (PE2-4), unique peptides in dubious proteins, and variant peptides affected by isobaric substitutions, causing doubtful identification results. In this study, we considered 11 isobaric substitutions. From our analysis, we found <5% of the unique peptides of missing proteins and >6% of variant peptides became shared with peptides of PE1 proteins after isobaric substitutions.
Borovička, J; Oborník, M; Stříbrný, J; Noordeloos, M E; Parra Sánchez, L A; Gryndler, M
2015-06-01
Five Psilocybe species with unresolved systematic position (P. atrobrunnea, P. laetissima, P. medullosa, P. pelliculosa, and P. silvatica) were investigated using four molecular markers (EF1-α, ITS, LSU, and IGS). Phylogenetic analysis revealed that with the exception of P. laetissima, which is now rightfully classified in the genus Leratiomyces, all investigated species belong to Psilocybe sect. Psilocybe. For the first time, psychotropic compounds psilocin and psilocybin were detected in P. medullosa using gas chromatography-mass spectrometry. On the contrary, neither psilocin, nor psilocybin was detected in P. atrobrunnea and negative results were also obtained from mycelia grown in vitro on tryptamine/tryptophan-amended media. These results strongly suggest that biosynthesis of these alkaloids was lost in P. atrobrunnea. With the exception of minor differences detected in EF1-α marker, all sequences of American and European collections of P. atrobrunnea were identical. On the other hand, a thorough nomenclatural study revealed that the name P. atrobrunnea must be considered dubious; the oldest available candidate name, P. fuscofulva, was therefore adopted. The molecular data suggests that morphologically identical American P. silvatica and European P. medullosa likely represent distinct species; epitypes of both taxa were therefore designated.
DBSecSys: a database of Burkholderia mallei secretion systems.
Memišević, Vesna; Kumar, Kamal; Cheng, Li; Zavaljevski, Nela; DeShazer, David; Wallqvist, Anders; Reifman, Jaques
2014-07-16
Bacterial pathogenicity represents a major public health concern worldwide. Secretion systems are a key component of bacterial pathogenicity, as they provide the means for bacterial proteins to penetrate host-cell membranes and insert themselves directly into the host cells' cytosol. Burkholderia mallei is a Gram-negative bacterium that uses multiple secretion systems during its host infection life cycle. To date, the identities of secretion system proteins for B. mallei are not well known, and their pathogenic mechanisms of action and host factors are largely uncharacterized. We present the Database of Burkholderia malleiSecretion Systems (DBSecSys), a compilation of manually curated and computationally predicted bacterial secretion system proteins and their host factors. Currently, DBSecSys contains comprehensive experimentally and computationally derived information about B. mallei strain ATCC 23344. The database includes 143 B. mallei proteins associated with five secretion systems, their 1,635 human and murine interacting targets, and the corresponding 2,400 host-B. mallei interactions. The database also includes information about 10 pathogenic mechanisms of action for B. mallei secretion system proteins inferred from the available literature. Additionally, DBSecSys provides details about 42 virulence attenuation experiments for 27 B. mallei secretion system proteins. Users interact with DBSecSys through a Web interface that allows for data browsing, querying, visualizing, and downloading. DBSecSys provides a comprehensive, systematically organized resource of experimental and computational data associated with B. mallei secretion systems. It provides the unique ability to study secretion systems not only through characterization of their corresponding pathogen proteins, but also through characterization of their host-interacting partners.The database is available at https://applications.bhsai.org/dbsecsys.
Propagating native plants at the National Tropical Botanical Garden
Diane Ragone
2002-01-01
Hawaii has the dubious distinction of being the extinction capital of the United States with close to 30 percent of native plant species listed as endangered. The National Tropical Botanical Garden has been a leader in efforts to propagate and conserve native Hawaiian plants with close to 800 species collected for ex situ conservation since 1990....
Comments on the papers recently published by M.M. Khandpekar et al.
NASA Astrophysics Data System (ADS)
Petrosyan, A. M.; Ghazaryan, V. V.; Fleck, M.
2011-09-01
It is argued that the existence of the new compounds of glycine recently reported by M.M. Khandpekar et al. (Optics Commun. 284(2011) 1583 and Optics Commun. 284(2011) 1578) is dubious. We argue that these compounds are not what the authors propose. In addition, two more similar cases are indicated.
British Values and British Identity: Muddles, Mixtures, and Ways Ahead
ERIC Educational Resources Information Center
Richardson, Robin
2015-01-01
In the final eleven months of its five-year term, the Coalition Government placed much emphasis in the education system on what it called fundamental British values (FBV). The phrase had its origins in counter-terrorism strategies that were of dubious validity both conceptually and operationally, and the trigger for its introduction into the…
Dewey and Video Games: From Education through Occupations to Education through Simulations
ERIC Educational Resources Information Center
Waddington, David I.
2015-01-01
Critics like Leonard Waks argue that video games are, at best, a dubious substitute for the rich classroom experiences that John Dewey wished to create and that, at worst, they are profoundly miseducative. Using the example of "Fate of the World," a climate change simulation game, David Waddington addresses these concerns through a…
Silent Echoes: A Young Author Rewrites the Rules to Transitioning
ERIC Educational Resources Information Center
Stephens, Aaron Notarianni
2008-01-01
This article describes Sarah, a young woman with autism from Frederick, Maryland, who made a choice to forgo traditional employment options for people with disabilities and to pursue the seemingly improbable option of becoming an author. Becoming a successful writer can be a dubious prospect for people without disabilities. And yet with talent,…
The Trial of Margaret Macomber: A Classroom Exercise in Fact-Finding and Literary Analysis.
ERIC Educational Resources Information Center
Diguette, Richard
1998-01-01
Describes how one professor uses a classroom trial (based on Hemingway's short story "The Short Happy Life of Francis Macomber") to prepare students for writing analytical essays about the story by teaching them to interrogate the text and by helping to cure the weaknesses of text-reticence and dubious deduction. (SR)
The Dubious Benefits of Multi-Level Modeling
ERIC Educational Resources Information Center
Gorard, Stephen
2007-01-01
This paper presents an argument against the wider adoption of complex forms of data analysis, using multi-level modeling (MLM) as an extended case study. MLM was devised to overcome some deficiencies in existing datasets, such as the bias caused by clustering. The paper suggests that MLM has an unclear theoretical and empirical basis, has not led…
The Politics of Teaching of Indigenous Traditions in Aotearoa/New Zealand
ERIC Educational Resources Information Center
Wiseman, Wendy A.
2015-01-01
Reflecting on two study abroad trips to New Zealand in 2005 and 2007, I suggest in this essay that it is possible to mitigate the risk of (American or European) students recapitulating imperial attitudes through development of a rigorous curriculum focusing on the legacies of colonialism, institutional racism, and the somewhat dubious phenomenon…
The Bell Curve Wars. Race, Intelligence, and the Future of America.
ERIC Educational Resources Information Center
Fraser, Steven, Ed.
"The Bell Curve" by Richard J. Herrnstein and Charles Murray has generated enormous debate as a result of its claim that there is a connection between race and intelligence. The essays of this collection respond to "The Bell Curve" in various ways. Taken together, the following offer an antidote to a work of dubious premises…
ERIC Educational Resources Information Center
Corwin, Ronald G.
The preoccupation with choice between public and private schools offered under voucher programs obscures the greater problem of a lack of variety in the present educational system. If providing a greater variety of school structures and improving the educational system is the objective, competition between the public and private sectors will not…
Islamic Fatalism and the Clash of Civilizations: An Appraisal of a Contentious and Dubious Theory
ERIC Educational Resources Information Center
Acevedo, Gabriel A.
2008-01-01
This paper will address the question of Islamic fatalism. Survey data will be used to assess Samuel P. Huntington's controversial "Clash of Civilizations" thesis and its emphasis on fatalism as an inherent characteristic of Islamic religion. The concept of fatalism is expanded and theorized as a function of both structural and…
The Dubious Utility of the Value-Added Concept in Higher Education: The Case of Accounting
ERIC Educational Resources Information Center
Yunker, J.A.
2005-01-01
Using data on CPA exam pass rates and various institutional variables, this research examines the potential usefulness of the value-added concept in accounting higher education. For a sample of 548 US colleges and universities, predicted pass rates were computed from regression equations relating observed pass rates to institutional variables. The…
The Concept of Quality in Cambodian Teacher Training: A Philosophical Ethnography
ERIC Educational Resources Information Center
Stanfill, Enoch M.
2016-01-01
Research shows that quality teachers are the single most significant influence on the quality of education available to students. This recognition of the importance of quality teachers on quality education is reflected in goal 6 of the EFA: Quality Education. EFA proxies for quality, however, are dubious measures of the concept......What does the…
Schaal, René; Kupfahl, Claudio; Buchheidt, Dieter; Neumaier, Michael; Findeisen, Peter
2007-11-01
Reliable and early diagnosis of life-threatening invasive mycoses in neutropenic patients caused by fungi of the Aspergillus species remains challenging because current clinical diagnostic tools lack in sensitivity and/or specificity. During invasive growth a variety of fungal proteases are secreted into the bloodstream and protease profiling with reporter peptides might improve diagnosis of invasive aspergillosis in serum specimens. To characterise the specific protease activity of Aspergillus fumigatus and Aspergillus niger we analyzed Aspergillus culture supernatants, human serum and the mixture of both. A systematic screening for optimised protease substrates was performed using a random peptide library consisting of 360 synthetic peptides featuring fluorescence resonance energy transfer (FRET). We could identify numerous peptides that are selectively cleaved by fungus-specific proteases. These reporter peptides might be feasible for future protease profiling of serum specimens to improve diagnosis and monitoring of invasive aspergillosis.
Device-independent secret-key-rate analysis for quantum repeaters
NASA Astrophysics Data System (ADS)
Holz, Timo; Kampermann, Hermann; Bruß, Dagmar
2018-01-01
The device-independent approach to quantum key distribution (QKD) aims to establish a secret key between two or more parties with untrusted devices, potentially under full control of a quantum adversary. The performance of a QKD protocol can be quantified by the secret key rate, which can be lower bounded via the violation of an appropriate Bell inequality in a setup with untrusted devices. We study secret key rates in the device-independent scenario for different quantum repeater setups and compare them to their device-dependent analogon. The quantum repeater setups under consideration are the original protocol by Briegel et al. [Phys. Rev. Lett. 81, 5932 (1998), 10.1103/PhysRevLett.81.5932] and the hybrid quantum repeater protocol by van Loock et al. [Phys. Rev. Lett. 96, 240501 (2006), 10.1103/PhysRevLett.96.240501]. For a given repeater scheme and a given QKD protocol, the secret key rate depends on a variety of parameters, such as the gate quality or the detector efficiency. We systematically analyze the impact of these parameters and suggest optimized strategies.
Stengel, Dirk; Bauwens, Kai; Ekkernkamp, Axel; Cramer, Jörg
2005-03-01
The reputation of total ankle arthroplasty for treating end-stage ankle arthritis of different origin is dubious. Newer generation meniscal-bearing prostheses may have overcome the known problems with earlier implants. There is, however, no systematic approach to the available scientific evidence allowing for a critical appraisal of their benefits and risks. We conducted a systematic review meta-analysis of studies exploring the efficacy of three-component total ankle prostheses. We demanded a minimum sample size of 20 subjects, at least 1 year of follow-up, and a clinically relevant study endpoint (for example, results of ankle scoring, ranges of motion [ROM], complications, and survival rates). We identified citations by electronic medical databases and a manual search. We made no restrictions for language. We used an eight-point quality scale to appraise methodological standards, and modeled outcomes by random-effects meta-regression analysis. Eighteen of 1830 citations including 1086 patients fulfilled our eligibility criteria. Studies met a median of four quality items (interquartile range 2-5). Outcome estimates did not depend on methodological quality. There was no evidence of strong heterogeneity or publication bias. With standardized 100-point ankle and hindfoot scores, formal data pooling was possible for 10 trials (n =497), showing a mean improvement of 45.2 points (95% confidence interval [CI] 39.3-51.1). Overall ROM improved slightly (6.3 degrees, 95%CI 2.2-10.5 degrees ). Weighted complication rates ranged from 1.6% (deep infections) to 14.7% (impingement). Secondary surgery had to be performed in 12.5%, whereas secondary arthrodesis was necessary in 6.3%. The weighted 5-year prosthesis survival rate averaged 90.6%. Ankle arthroplasty improves pain and joint mobility in end-stage ankle arthritis. Its performance in comparison to the current reference standard (that is, ankle fusion) remains to be defined in a properly designed randomized trial.
Building Paths to the Middle Class: Innovations in Career and Technical Education
ERIC Educational Resources Information Center
Kelly, Andrew P.; James, Kevin J.; Lautzenheiser, Daniel K.; Deane, KC; Columbus, Rooney
2015-01-01
There is currently more focus than ever on the importance of earning a college degree. At the same time, many students and parents are dubious that America's expensive, one-size-fits-all higher education system can adequately educate students for an ever more diverse and sophisticated world of work. There are other educational options that are…
Teachers Undefeated: How Global Education Reform Has Failed to Crush the Spirit of Educators
ERIC Educational Resources Information Center
Berry, Jon
2016-01-01
"Teachers Undefeated" is about how teachers continue to do the best for their students. They do so despite clumsy interventions from governments who have no idea how difficult they have made school life. They do so despite the fact that they are pressurized into producing dubious outcomes and are over-scrutinized in every aspect of their…
ERIC Educational Resources Information Center
Cohen, Albert; Orzech, David
This project explored the feasibility for vocational rehabilitation of a perplexing group of patients awaiting separation from a state mental hospital. The patients were of dubious employability. The design was a series of sequential stages through which the 98 workshop participants passed, with attrition taking place at each stage. The program…
Parent Attitudes Toward the Virginia Beach Year-Round School Pilot Project. Final Report.
ERIC Educational Resources Information Center
Schlechty, Phillip C.
Part of the Virginia Beach year-round school program evaluation, this final report contains a detailed analysis of parental attitudes, beliefs, and perceptions. The data leads to the following conclusions: a majority (53.3 percent) of parents are dubious or negative toward the 45-15 pilot project; a slight majority of parents in the pilot schools…
Another Look at Plagiarism in the Digital Age: Is It Time to Turn in My Badge?
ERIC Educational Resources Information Center
Colvin, Benie B.
2007-01-01
In this article, the author talks about plagiarism in the digital age and how plagiarism challenges teachers in their relationship with students. With a growing body of digital commentary and the looming dominance of electronic writing, current professional consensus in the plagiarism dilemma appears dubious and the slope gets more slippery every…
ERIC Educational Resources Information Center
Kovacs, Philip E.; Christie, H. K.
2008-01-01
Int his essay, the authors identify and problematize the claims and activities of four think tanks supported by contributions from the Bill and Melinda Gates Foundation. Kovacs and Christie attempt to show that these contributions support scholars and research of dubious quality, engage in political science abuse, and perpetuate discourses and…
Janet Klein; Andrea Williams; John Menke
2013-01-01
The Marin Municipal Water District's (MMWD) 7487 ha Mt. Tamalpais watershed in Marin County, California has the dubious distinction of being one of the earliest and most extensive areas impacted by Phytophthora ramorum in California. Rapid die off of tanoaks (Notholithocarpus densiflorus (Hook. & Arn.) Manos, Cannon...
ERIC Educational Resources Information Center
Wood, Richard E.
Second language instruction in the U.S. and Europe is in difficulties. The choice of a second language is artibrary and the motivation dubious. In Europe and now also in the U.S., attention has turned to the planned interlanguage Esperanto, which offers a maximally regularized structure, is considered "easy" by learners, and has the…
ERIC Educational Resources Information Center
Reppert, James E.
An instructor uses a unique instructional paradigm in his MCOM 1003/Introduction to Mass Communication course at Southern Arkansas University (SAU) in a unit on media and politics. According to his students, one of the most popular learning strategies is the use of original edited videos that focus on dubious practices by some media professionals.…
A Review on Bradykinin-Related Peptides Isolated from Amphibian Skin Secretion
Xi, Xinping; Li, Bin; Chen, Tianbao; Kwok, Hang Fai
2015-01-01
Amphibian skin secretion has great potential for drug discovery and contributes hundreds of bioactive peptides including bradykinin-related peptides (BRPs). More than 50 BRPs have been reported in the last two decades arising from the skin secretion of amphibian species. They belong to the families Ascaphidae (1 species), Bombinatoridae (3 species), Hylidae (9 speices) and Ranidae (25 species). This paper presents the diversity of structural characteristics of BRPs with N-terminal, C-terminal extension and amino acid substitution. The further comparison of cDNA-encoded prepropeptides between the different species and families demonstrated that there are various forms of kininogen precursors to release BRPs and they constitute important evidence in amphibian evolution. The pharmacological activities of isolated BRPs exhibited unclear structure–function relationships, and therefore the scope for drug discovery and development is limited. However, their diversity shows new insights into biotechnological applications and, as a result, comprehensive and systematic studies of the physiological and pharmacological activities of BRPs from amphibian skin secretion are needed in the future. PMID:25793726
Public Debt: Private Asset. Government Debt and Its Role in the Economy.
ERIC Educational Resources Information Center
Schilling, Tim
In 1981, the United States reached a dubious economic milestone--the federal debt surpassed one trillion dollars for the first time. It took more than 200 years to build up that much debt. The federal debt doubled to two trillion by 1986, hit the three trillion level in 1990, and stands at an estimated five-and-a-half trillion for 1998. Just as…
Biopsy guided by dermoscopy in cutaneous pigmented lesion - Case report*
Bomm, Lislaine; Benez, Marcela Duarte Villela; Maceira, Juan Manuel Piñeiro; Succi, Isabel Cristina Brasil; Scotelaro, Maria de Fatima Guimarães
2013-01-01
It may be clinically difficult to differentiate early-stage melanoma from benign tumors, specially pigmented seborrheic keratosis. Dermoscopy can help; however, the findings are not always conclusive. Therefore, histopathology may be necessary for a correct diagnosis. We describe a melanocytic lesion with dubious clinic and dermoscopic findings. An incisional biopsy of a suspicious area, guided by dermoscopy, was performed to clarify the findings. PMID:23539018
CrossTalk. The Journal of Defense Software Engineering. Volume 26, Number 5
2013-10-01
to a backend domain managed by the cyber criminal. Mobile bots can perform piggybacking on legitimate applications and steal data by controlling...technology infrastructure for managing identities, interfaces (web and/or mobile ), and agreements with service providers. The necessary capabilities and...platforms of unknown or dubious origin, global access by mobile (and largely insecure) devices, eroded trust boundaries, and the possibility of malevolent
Can and Should the United States Preserve A Military Capability for Revolutionary Conflict
1972-01-01
unexpected interventions (Korea, Cambodia) and the inherent uncertainties of international relations render dubious any firm prediction that no president in...superpowers or pose a direct military threat. The United States has a strong interest in forestalling any transformation of internal revolts into... internal security assistance (training and advice) draw the United States relentlessly into direct and costly military intervention (deployment of
ERIC Educational Resources Information Center
Maconachie, Roy; Binns, Tony
2007-01-01
Sierra Leone is currently emerging from a brutal civil war that lasted most of the 1990s, and now has the dubious distinction of being ranked among the world's poorest countries. As thousands of displaced people move back to their villages, a large proportion of the predominantly farm-based rural population are growing food crops for the first…
ERIC Educational Resources Information Center
Wildavsky, Ben
2011-01-01
In the past year, for-profit higher education providers have been thrust into the spotlight. The fastest growing postsecondary sector has come under unprecedented scrutiny from policymakers, regulators, and the media. Critics have zeroed in on a range of concerns, from perceived dubious recruiting tactics and overblown promises about students'…
On the Historical and Conceptual Foundations of a Community Psychology of Social Transformation.
Gokani, Ravi; Walsh, Richard T G
2017-06-01
We examine historical and conceptual literature in community psychology in order to understand the field's potential to be the socially transformative subdiscipline of psychology to which it aspires. By reviewing papers from two prominent journals and other literature, we conclude that the claim that community psychology is well-suited to social transformation, because it is a product of Sixties' radicalism and is theoretically equipped, is untenable. Systematic accounts of the subdiscipline's origins suggest that the transformative aspirations of current community psychologists do not correspond to the subdiscipline's reformist past. Furthermore, in analyzing three related concepts currently employed in the field-social justice, power, and praxis-we show that each suffers from conceptual ambiguity and a restricted political scope. These conceptual flaws, coupled with community psychology's historical inclination toward social reform, inhibit the possibility of contributing to radical social transformation. We conclude that neither questionable historical claims nor ambiguous and politically dubious concepts support a community psychology of social transformation. We offer solutions for the historical and conceptual problems we identify and, as a broader solution to the problem of engaging in socially transformative work, propose that community psychologists should seek direct political engagement in solidarity with other citizens as fellow citizens not as psychologists. © Society for Community Research and Action 2017.
Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state.
Adiputra, Yohanes; Chen, Shao-Liang
2015-05-20
The objective was to delineate the current knowledge of fractional flow reserve (FFR) in terms of definition, features, clinical applications, and pitfalls of measurement of FFR. We searched database for primary studies published in English. The database of National Library of Medicine (NLM), MEDLINE, and PubMed up to July 2014 was used to conduct a search using the keyword term "FFR". The articles about the definition, features, clinical application, and pitfalls of measurement of FFR were identified, retrieved, and reviewed. Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes. FFR is a valuable tool to determine the functional significance of coronary stenosis. It combines physiological and anatomical information, and can be followed immediately by percutaneous coronary intervention (PCI) if necessary. The technique of FFR measurement can be performed easily, rapidly, and safely in the catheterization laboratory. By systematic use of FFR in dubious stenosis and multi-vessel disease, PCI can be made an even more effective and better treatment than it is currently. The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory.
Sachdev, Rishibha; Kappes-Horn, Karin; Paulsen, Lydia; Duernberger, Yvonne; Pleschka, Catharina; Denner, Philip; Kundu, Bishwajit; Reimann, Jens; Vorberg, Ina
2018-03-15
Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line. We find that increased MsntPP protein levels induce ER stress. MstnPP metabolites were predominantly retained within the endoplasmic reticulum (ER), also evident in sIBM histology. MstnPP cleavage products formed insoluble high molecular weight aggregates, a process that was aggravated by experimental ER stress. Importantly, ER stress also impaired secretion of mature myostatin. Reduced secretion and aggregation of MstnPP metabolites were not simply caused by overexpression, as both events were also observed in wildtype cells under ER stress. It is tempting to speculate that reduced circulating myostatin growth factor could be one explanation for the poor clinical efficacy of drugs targeting the myostatin pathway in sIBM.
Global Pursuits: The Underground Railroad
ERIC Educational Resources Information Center
School Arts: The Art Education Magazine for Teachers, 2004
2004-01-01
This brief article describes Charles T. Webber's oil on canvas painting, "The Underground Railroad, 1893." The subject of this painting is the Underground Railroad, which today has become an American legend. The Underground Railroad was not a systematic means of transportation, but rather a secretive process that allowed fugitive slaves…
ERIC Educational Resources Information Center
Cauce, Ana M.; And Others
Most of the research on the assessment of the intelligence of Latinos in the United States appears to be based on some possibly erroneous or at least dubious assumptions. Among these are the following: (1) the assumption of bilinguality; (2) the assumption of equal proficiency in the English language; (3) the assumption of the equivalence of…
ERIC Educational Resources Information Center
Takayama, Keita
2007-01-01
There are three notable aspects to the recent crisis discourse in Japanese education. First, it is highly questionable whether the current state of Japanese education is deserving of a sensationalist label. Japanese scholars who were dubious of the crisis claim pointed to its highly ideological nature and to the lack of reliable longitudinal data…
Technology Transfer: A Compilation of Varied Approaches to the Management of Innovation.
1982-12-01
Objectives. Risk. Technical interest. Social pressure. In Phase Two of the data review, the student-annotated articles were re-ordered by chapter...Type Plans--A. J. Geare Chapter 12. Willingness 71. The Absorption Rate of Ideas--G. Gallup 72. Innovacion -Resisting and Innovation-Producing...their questionable impact on social institu- tions. While technology has been clearly beneficial to many people, it has been of dubious value in
Entering dubious realms: Grover Krantz, science, and Sasquatch.
Regal, Brian
2009-01-01
Physical anthropologist Grover Krantz (1931-2002) spent his career arguing that the anomalous North American primate called Sasquatch was a living animal. He attempted to prove the creature's existence by applying to the problem the techniques of physical anthropology: methodologies and theoretical models that were outside the experience of the amateur enthusiasts who dominated the field of anomalous primate studies. For his efforts, he was dismissed or ignored by academics who viewed the Sasquatch, also commonly called Bigfoot, as at best a relic of folklore and at worst a hoax, and Krantz's project as having dubious value. Krantz also received a negative reaction from amateur Sasquatch researchers, some of whom threatened and abused him. His career is best situated therefore as part of the discussion about the historical relationship between amateur naturalists and professional scientists. The literature on this relationship articulates a combining/displacement process: when a knowledge domain that has potential for contributions to science is created by amateurs, it will eventually combine with and then be taken over by professionals, with the result that amateur leadership is displaced. This paper contributes to that discussion by showing the process at work in Krantz's failed attempt to legitimize Bigfoot research by removing it from the amateur sphere and repositioning it in the professional world of anthropology.
Rubinelli, Sara; Nakamoto, Kent; Schulz, Peter J
2008-01-01
There is an ongoing global debate over the potential benefits and risks of allowing direct-to-consumer advertising of prescription medicines (DTCA). The core of this debate concerns the identification of DTCA either as a beneficial procedure to be promoted or as a damaging procedure to be abolished. Economic data on DTCA suggest that this form of advertising has an impact on consumers. Based on this premise, we explore the use of argumentation theory to inquire into the reasons for this success. In particular, by combining perspectives from argumentation theory and marketing research this paper aims to test the hypothesis of whether DTCA presents information framed in potentially misleading, but persuasive, argumentative structures. We highlight and discuss the results of two studies designed to assess whether readers perceive DTCA as argumentative and, if so, which explicit and implicit elements provide groundings for the inference that consumers draw from the ads. The analysis highlights the presence in DTCA of dubious arguments (fallacies and distracting claims) that may go unnoticed. Also, it illustrates the nature of readers' wrong assumptions that arise independently from the contents of the ads. These factors seem to influence the level of the self-perceived persuasiveness of DTCA.
The dubious assessment of gay, lesbian, and bisexual adolescents of add health.
Savin-Williams, Ritch C; Joyner, Kara
2014-04-01
In this essay, we argue that researchers who base their investigations of nonheterosexuality derived from reports of romantic attractions of adolescent participants from Wave 1 of Add Health must account for their disappearance in future waves of data collection. The high prevalence of Wave 1 youth with either both-sex or same-sex romantic attractions was initially striking and unexpected. Subsequent data from Add Health indicated that this prevalence sharply declined over time such that over 70 % of these Wave 1 adolescents identified as exclusively heterosexual as Wave 4 young adults. Three explanations are proposed to account for the high prevalence rate and the temporal inconsistency: (1) gay adolescents going into the closet during their young adult years; (2) confusion regarding the use and meaning of romantic attraction as a proxy for sexual orientation; and (3) the existence of mischievous adolescents who played a "jokester" role by reporting same-sex attraction when none was present. Relying on Add Health data, we dismissed the first explanation as highly unlikely and found support for the other two. Importantly, these "dubious" gay, lesbian, and bisexual adolescents may have led researchers to erroneously conclude from the data that sexual-minority youth are more problematic than heterosexual youth in terms of physical, mental, and social health.
Lee, Kai-Hui; Chiu, Pei-Ling
2013-10-01
Conventional visual cryptography (VC) suffers from a pixel-expansion problem, or an uncontrollable display quality problem for recovered images, and lacks a general approach to construct visual secret sharing schemes for general access structures. We propose a general and systematic approach to address these issues without sophisticated codebook design. This approach can be used for binary secret images in non-computer-aided decryption environments. To avoid pixel expansion, we design a set of column vectors to encrypt secret pixels rather than using the conventional VC-based approach. We begin by formulating a mathematic model for the VC construction problem to find the column vectors for the optimal VC construction, after which we develop a simulated-annealing-based algorithm to solve the problem. The experimental results show that the display quality of the recovered image is superior to that of previous papers.
Determining the Localization of Carbohydrate Active Enzymes Within Gram-Negative Bacteria.
McLean, Richard; Inglis, G Douglas; Mosimann, Steven C; Uwiera, Richard R E; Abbott, D Wade
2017-01-01
Investigating the subcellular location of secreted proteins is valuable for illuminating their biological function. Although several bioinformatics programs currently exist to predict the destination of a trafficked protein using its signal peptide sequence, these programs have limited accuracy and often require experimental validation. Here, we present a systematic method to fractionate gram-negative cells and characterize the subcellular localization of secreted carbohydrate active enzymes (CAZymes). This method involves four parallel approaches that reveal the relative abundance of protein within the cytoplasm, periplasm, outer membrane, and extracellular environment. Cytoplasmic and periplasmic proteins are fractionated by lysis and osmotic shock, respectively. Outer membrane bound proteins are determined by comparing cells before and after exoproteolytic digestion. Extracellularly secreted proteins are collected from the media and concentrated. These four different fractionations can then be probed for the presence and quantity of target proteins using immunochemical methods such as Western blots and ELISAs, or enzyme activity assays.
Shotgun proteomics of Aspergillus niger microsomes upon D-xylose induction.
Ferreira de Oliveira, José Miguel P; van Passel, Mark W J; Schaap, Peter J; de Graaff, Leo H
2010-07-01
Protein secretion plays an eminent role in cell maintenance and adaptation to the extracellular environment of microorganisms. Although protein secretion is an extremely efficient process in filamentous fungi, the mechanisms underlying protein secretion have remained largely uncharacterized in these organisms. In this study, we analyzed the effects of the d-xylose induction of cellulase and hemicellulase enzyme secretion on the protein composition of secretory organelles in Aspergillus niger. We aimed to systematically identify the components involved in the secretion of these enzymes via mass spectrometry of enriched subcellular microsomal fractions. Under each condition, fractions enriched for secretory organelles were processed for tandem mass spectrometry, resulting in the identification of peptides that originate from 1,081 proteins, 254 of which-many of them hypothetical proteins-were predicted to play direct roles in the secretory pathway. d-Xylose induction led to an increase in specific small GTPases known to be associated with polarized growth, exocytosis, and endocytosis. Moreover, the endoplasmic-reticulum-associated degradation (ERAD) components Cdc48 and all 14 of the 20S proteasomal subunits were recruited to the secretory organelles. In conclusion, induction of extracellular enzymes results in specific changes in the secretory subproteome of A. niger, and the most prominent change found in this study was the recruitment of the 20S proteasomal subunits to the secretory organelles.
ERIC Educational Resources Information Center
Parthasarthy, K.; Balasaravanan, T.
India has made considerable progress toward universal primary education but has the dubious distinction of having the highest illiteracy rates in the world. Stringent endeavors are being made at the national, state, and district levels to eradicate illiteracy through mass approaches and programs. Extension is recognized as the third dimension of…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burns, G.
This bibliography, updated from an earlier 1947 printing, is divided into 18 separate areas. It will allow the reader to identify books and recent journal and magazine articles on the panoply of nuclear issues. It assumed that better information enables more-effective involvement in the effort to secure real peace, and not the dubious peace achieved through nuclear terror.
The Elephant in the Room: Confronting Ideology and Armed Groups
2010-12-01
World Public Opinion.org, April 24, 2007, http://www.fcnl.org/ pdfs /middle_east/muslim_public_opinion_ pipa.pdf, 21–22. 41 Michael Mousseau...gigantic world conspiracy of probably Satanic origins.59 The term “Patriot movement” (which Neiwert uses because its members use the term for...characterized by a dubious interpretation of the Protestant Bible and the U.S. Constitution. While the bombing by Timothy McVeigh of the Murrah Federal
Chen, Po Ting; Chao, Yun-Peng
2006-10-01
By systematic investigation, glutamate and a mixture of metal ions were identified as factors limiting the production of nattokinase in Bacillus subtilis. Consequently, in medium supplemented with these materials, the recombinant strain secreted 4 times more nattokinase (260 mg l(-1)) than when grown in the unsupplemented medium.
Unemployment as a chronic stressor: A systematic review of cortisol studies.
Sumner, Rachel C; Gallagher, Stephen
2017-03-01
Unemployment is a type of chronic stressor that impacts human health. The reasons for how the stress of unemployment affect health is still a matter of discussion. One of the pathways from chronic stress to ill health is mediated by cortisol, and so we set out to compile extant data on how its secretion is affected by unemployment. A systematic literature search was conducted to establish the cortisol dysregulatory effects of this stressor. Only studies that specifically examined the effects of unemployment on cortisol excretion, and were written in English were included. Ten reports were obtained and synthesised to determine the severity and complexity of the effect of unemployment on cortisol secretion. The resulting combined evidence is mixed in terms of degree or dynamic of relationship. The differences between the cumulate findings of the studies can be understood in the context of the lack of both standardised methodology and an absence of consensus on unemployment definition. We propose existing methodologies may be strengthened by acknowledging and accounting for the individual characteristics that may be relevant to the stress experience of unemployment.
Secretome analysis of diarrhea-inducing strains of Escherichia coli
Nirujogi, Raja Sekhar; Muthusamy, Babylakshmi; Kim, Min-Sik; Sathe, Gajanan J.; Lakshmi, P.T.V.; Kovbasnjuk, Olga N.; Prasad, T.S. Keshava; Wade, Mary; Jabbour, Rabih E.
2017-01-01
Secreted proteins constitute a major part of virulence factors that are responsible for pathogenesis caused by Gram-negative bacteria. Enterohemorrhagic Escherichia coli, O157:H7, is the major pathogen often causing outbreaks. However, studies have reported that the significant outbreaks caused by non-O157:H7 E. coli strains, also known as “Big-Six” serogroup strains, are increasing. There is no systematic study describing differential secreted proteins from these non-O157:H7 E. coli strains. In this study, we carried out MS-based differential secretome analysis using tandem mass tags labeling strategy of non-O157:H7 E. coli strains, O103, O111, O121, O145, O26, and O45. We identified 1241 proteins, of which 565 proteins were predicted to be secreted. We also found that 68 proteins were enriched in type III secretion system and several of them were differentially expressed across the strains. Additionally, we identified several strain-specific secreted proteins that could be used for developing potential markers for the identification and strain-level differentiation. To our knowledge, this study is the first comparative proteomic study on secretome of E. coli Big-Six serogroup and the several of these strain-specific secreted proteins can be further studied to develop potential markers for identification and strain-level differentiation. Moreover, the results of this study can be utilized in several applications, including food safety, diagnostics of E. coli outbreaks, and detection and identification of bio threats in biodefense. PMID:28070933
Technology for Director Dubious: Evaluation and Decision in Public Contexts
1977-08-01
Utilities at six Nuclear Waste Disposal Sites v . . . ".. . Acknowledgment h., Preparation of this report and conceptual work on the place of decision...cannot necessarily be related to public decisions without a great deal of intermediate work ." On the question of measuring values, Mr. Coates seems to...is addressed to the first of the two key problems that Mr. Coates identified: the problem of uncer- tainty. The work that I will be reporting comes
Nielson, Kristy A; Correro, Anthony N
2017-10-01
The Deese-Roediger-McDermott (DRM) paradigm examines false memory by introducing words associated with a non-presented 'critical lure' as memoranda, which typically causes the lures to be remembered as frequently as studied words. Our prior work has shown enhanced veridical memory and reduced misinformation effects when arousal is induced after learning (i.e., during memory consolidation). These effects have not been examined in the DRM task, or with signal detection analysis, which can elucidate the mechanisms underlying memory alterations. Thus, 130 subjects studied and then immediately recalled six DRM lists, one after another, and then watched a 3-min arousing (n=61) or neutral (n=69) video. Recognition tested 70min later showed that arousal induced after learning led to better delayed discrimination of studied words from (a) critical lures, and (b) other non-presented 'weak associates.' Furthermore, arousal reduced liberal response bias (i.e., the tendency toward accepting dubious information) for studied words relative to all foils, including critical lures and 'weak associates.' Thus, arousal induced after learning effectively increased the distinction between signal and noise by enhancing access to verbatim information and reducing endorsement of dubious information. These findings provide important insights into the cognitive mechanisms by which arousal modulates early memory consolidation processes. Copyright © 2017 Elsevier Inc. All rights reserved.
Kardum-Skelin, Ika
2011-09-01
Clinical cytology is an interdisciplinary medical diagnostic profession that integrates clinical, laboratory and analytical fields along with final cytologist's expert opinion. Cytology involves nonaggressive, minimally invasive and simple for use procedures that are fully acceptable for the patient. Cytology offers rapid orientation, while in combination with additional technologies on cytologic smear analysis (cytochemistry, immunocytochemistry for cell marker analysis, computer image analysis) or sophisticated methods on cytologic samples (flow cytometry, molecular and cytogenetic analysis) it plays a major role in the diagnosis, subtyping and prognosis of malignant tumors. Ten rules for successful performance in cytology are as follows: 1) due knowledge of overall cytology (general cytologist); 2) inclusion in all stages of cytologic sample manipulation from sampling through reporting; 3) due knowledge of additional technologies to provide appropriate interpretation and/or rational advice in dubious cases; 4) to preserve dignity of the profession because every profession has its advantages, shortcomings and limitations; 5) to insist on quality control of the performance, individual cytologists and cytology team; 6) knowledge transfer to young professionals; 7) assisting fellow professionals in dubious cases irrespective of the time needed and fee because it implies helping the patient and the profession itself; 8) experience exchange with other related professionals to upgrade mutual understanding; 9) to prefer the interest of the profession over one's own interest; and 10) to love cytology.
Golovatch, Sergei; Stoev, Pavel
2013-01-01
The Philippine fauna of the family Paradoxosomatidae is reviewed and shown to comprise only 12 certain species (+ one dubious), definitely only a fraction of the real diversity to be expected from such a large tropical archipelago. Two new combinations are proposed: Euphyodesmusphilippina (Nguyen Duc & Sierwald, 2010), comb. n. ex Desmoxytes Chamberlin, 1923, and Luzonomorphapolilloensis (San Juan & Lit, 2010), comb. n. ex Prionopeltis Pocock, 1895. The first representative of the large, basically Papuan genus Eustrongylosoma Silvestri, 1896 is described from Luzon, Philippines: Eustrongylosomapenevi sp. n. It differs from the other congeners in certain details of gonopod structure, as well as by the particularly long legs. Based on a restudy of the types of Strongylosomaluzoniense Peters, 1864, from Luzon, the species is shown to be a new senior subjective synonym of Helicorthomorphaorthogona (Silvestri, 1898), syn. n. This formally results also in Helicorthomorphaluzoniensis (Peters, 1864), comb. n. Anoplodesmusanthracinus Pocock, 1895 is illustrated and briefly redescribed, based on material from State Pulau Penang, Malaysia, which represents the first formal record of the species in that country. This species is also new to the fauna of Sri Lanka. A review of the Anoplodesmus species reported from Sri Lanka, nearly all of them dubious, is presented.
Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state
Adiputra, Yohanes; Chen, Shao-Liang
2015-01-01
Objective: The objective was to delineate the current knowledge of fractional flow reserve (FFR) in terms of definition, features, clinical applications, and pitfalls of measurement of FFR. Data Sources: We searched database for primary studies published in English. The database of National Library of Medicine (NLM), MEDLINE, and PubMed up to July 2014 was used to conduct a search using the keyword term “FFR”. Study Selection: The articles about the definition, features, clinical application, and pitfalls of measurement of FFR were identified, retrieved, and reviewed. Results: Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes. Conclusions: FFR is a valuable tool to determine the functional significance of coronary stenosis. It combines physiological and anatomical information, and can be followed immediately by percutaneous coronary intervention (PCI) if necessary. The technique of FFR measurement can be performed easily, rapidly, and safely in the catheterization laboratory. By systematic use of FFR in dubious stenosis and multi-vessel disease, PCI can be made an even more effective and better treatment than it is currently. The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory. PMID:25963364
Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris.
Avril, Marion; Hathaway, Marianne J; Cartwright, Megan M; Gose, Severin O; Narum, David L; Smith, Joseph D
2009-06-29
VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL) domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. From a total of 42 different VAR2CSA constructs, 15 proteins (36%) were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development.
Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris
Avril, Marion; Hathaway, Marianne J; Cartwright, Megan M; Gose, Severin O; Narum, David L; Smith, Joseph D
2009-01-01
Background VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL) domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. Methods VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. Results From a total of 42 different VAR2CSA constructs, 15 proteins (36%) were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. Conclusion These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development. PMID:19563628
Shotgun Proteomics of Aspergillus niger Microsomes upon d-Xylose Induction▿ †
de Oliveira, José Miguel P. Ferreira; van Passel, Mark W. J.; Schaap, Peter J.; de Graaff, Leo H.
2010-01-01
Protein secretion plays an eminent role in cell maintenance and adaptation to the extracellular environment of microorganisms. Although protein secretion is an extremely efficient process in filamentous fungi, the mechanisms underlying protein secretion have remained largely uncharacterized in these organisms. In this study, we analyzed the effects of the d-xylose induction of cellulase and hemicellulase enzyme secretion on the protein composition of secretory organelles in Aspergillus niger. We aimed to systematically identify the components involved in the secretion of these enzymes via mass spectrometry of enriched subcellular microsomal fractions. Under each condition, fractions enriched for secretory organelles were processed for tandem mass spectrometry, resulting in the identification of peptides that originate from 1,081 proteins, 254 of which—many of them hypothetical proteins—were predicted to play direct roles in the secretory pathway. d-Xylose induction led to an increase in specific small GTPases known to be associated with polarized growth, exocytosis, and endocytosis. Moreover, the endoplasmic-reticulum-associated degradation (ERAD) components Cdc48 and all 14 of the 20S proteasomal subunits were recruited to the secretory organelles. In conclusion, induction of extracellular enzymes results in specific changes in the secretory subproteome of A. niger, and the most prominent change found in this study was the recruitment of the 20S proteasomal subunits to the secretory organelles. PMID:20453123
Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan
Kaplan, Joshua M.
2008-01-01
Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling. PMID:19043554
Design considerations to enhance the safety of patient compartments in ambulance transporters.
Byran, Eyal; Gilad, Issachar
2012-01-01
The safety of the interior of ambulances is dubious and, in the event of sudden impact during emergency transport, potentially perilous to patients they carry. The workplace ergonomics of the interior of the passenger cabin is lacking. This article discusses an improved ergonomic interior design based on study findings, observations and subjective perception. It suggests design aspects and safety concepts aimed at increasing the safety of patients and paramedic staff inside the ambulance as a mobile workstation.
Effects of NO-modulating agents on the development of acute painful reaction in rats.
Dyuizen, I V; Lamash, N E
2008-08-01
Painful reaction of rats to intraperitoneal injections of L-arginine, Nw-nitro-L-arginine, and agmatine was studied on the model of formalin-induced inflammation. All drugs exhibited a dubious effect on the patterns of nociceptive behavior depending on the phase of painful reaction. The dynamics of nitrate/nitrite content in animal blood and serum indicated the presence of NO-dependent and NO-independent components in the mechanisms of pharmacological effects of these drugs.
Physiotherapy Secretion Removal Techniques in People With Spinal Cord Injury: A Systematic Review
Reid, W. Darlene; Brown, Jennifer A; Konnyu, Kristin J; Rurak, Jennifer M.E; Sakakibara, Brodie M
2010-01-01
Objective: To address whether secretion removal techniques increase airway clearance in people with chronic spinal cord injury (SCI). Data Sources and Study Selection: MEDLINE/PubMed, CINAHL, EMBASE, and PsycINFO were searched from inception to May 2009 for population keywords (spinal cord injury, paraplegia, tetraplegia, quadriplegia) paired with secretion removal–related interventions and outcomes. Inclusion criteria for articles were a research study, irrespective of design, that examined secretion removal in people with chronic SCI published in English. Review Methods: Two reviewers determined whether articles met the inclusion criteria, abstracted information, and performed a quality assessment using PEDro or Downs and Black criteria. Studies were then given a level of evidence based on a modified Sackett scale. Results: Of 2,416 abstracts and titles retrieved, 24 met the inclusion criteria. Subjects were young (mean, 31 years) and 84% were male. Most evidence was level 4 or 5 and only 2 studies were randomized controlled trials. Three reports described outcomes for secretion removal techniques in addition to cough, whereas most articles examined the immediate effects of various components of cough. Studies examining insufflation combined with manual assisted cough provided the most consistent, high-level evidence. Compelling recent evidence supports the use of respiratory muscle training or electrical stimulation of the expiratory muscles to facilitate airway clearance in people with SCI. Conclusion: Evidence supporting the use of secretion removal techniques in SCI, while positive, is limited and mostly of low level. Treatments that increase respiratory muscle force show promise as effective airway clearance techniques. PMID:21061895
Critical review of a new volcanic eruption chronology
NASA Astrophysics Data System (ADS)
Neuhäuser, Dagmar L.; Neuhäuser, Ralph
2016-04-01
Sigl. et al. (2015, Nature) present historical evidence for 32 volcanic eruptions to evaluate their new polar ice core 10-Be chronology - 24 are dated within three years of sulfur layers in polar ice. Most of them can be interpreted as weather phenomena (Babylonia: disk of sun like moon, reported for only one day, e.g. extinction due to clouds), Chinese sunspot reports (pellet, black vapor, etc.), solar eclipses, normal ice-halos and coronae (ring, bow, etc.), one aurora (redness), red suns due to mist drops in wet fog or fire-smoke, etc. Volcanic dust may facilitate detections of sunspots and formation of Bishop's ring, but tend to inhibit ice-halos, which are otherwise often reported in chronicles. We are left with three reports possibly indicating volcanic eruptions, namely fulfilling genuine criteria for atmospheric disturbances due to volcanic dust, e.g. bluish or faint sun, orange sky, or fainting of stars for months (BCE 208, 44-42, and 32). Among the volcanic eruptions used to fix the chronology (CE 536, 626, 939, 1257), the reports cited for the 930s deal only with 1-2 days, at least one reports an eclipse. In the new chronology, there is a sulfur detection eight years after the Vesuvius eruption, but none in CE 79. It may appear surprising that, from BCE 500 to 1, all five northern sulfur peaks labeled in figure 2 in Sigl et al. are systematically later by 2-4 years than the (corresponding?) southern peaks, while all five southern peaks from CE 100 to 600 labeled in figure 2 are systematically later by 1-4 years than the (corresponding?) northern peaks. Furthermore, in most of their six strongest volcanic eruptions, temperatures decreased years before their sulfur dating - correlated with weak solar activity as seen in radiocarbon, so that volcanic climate forcing appears dubious here. Also, their 10-Be peaks at CE 775 and 994 are neither significant nor certain in dating.
Araujo, Thaís L S; Zeidler, Julianna D; Oliveira, Percíllia V S; Dias, Matheus H; Armelin, Hugo A; Laurindo, Francisco R M
2017-02-01
Extracellular protein disulfide isomerase (PDIA1) pool mediates thrombosis and vascular remodeling, however its externalization mechanisms remain unclear. We performed systematic pharmacological screening of secretory pathways affecting extracellular PDIA1 in endothelial cells (EC). We identified cell-surface (csPDIA1) and secreted non-particulated PDIA1 pools in EC. Such Golgi bypass also occurred for secreted PDIA1 in EC at baseline or after PMA, thrombin or ATP stimulation. Inhibitors of Type I, II and III unconventional routes, secretory lysosomes and recycling endosomes, including syntaxin-12 deletion, did not impair EC PDIA1 externalization. This suggests predominantly Golgi-independent unconventional secretory route(s), which were GRASP55-independent. Also, these data reinforce a vesicular-type traffic for PDIA1. We further showed that PDIA1 traffic is ATP-independent, while actin or tubulin cytoskeletal disruption markedly increased EC PDIA1 secretion. Clathrin inhibition enhanced extracellular soluble PDIA1, suggesting dynamic cycling. Externalized PDIA1 represents <2% of intracellular PDIA1. PDIA1 was robustly secreted by physiological levels of arterial laminar shear in EC and supported alpha 5 integrin thiol oxidation. Such results help clarify signaling and homeostatic mechanisms involved in multiple (patho)physiological extracellular PDIA1 functions. Copyright © 2016 Elsevier Inc. All rights reserved.
CRYOPRESERVATION EFFECTS ON RECOMBINANT MYOBLASTS ENCAPSULATED IN ADHESIVE ALGINATE HYDROGELS
Ahmad, Hajira F.; Sambanis, Athanassios
2013-01-01
Cell encapsulation in hydrogels is widely used in tissue engineering applications, including encapsulation of islets or other insulin-secreting cells in pancreatic substitutes. Use of adhesive, bio-functionalized hydrogels is receiving increasing attention, as cell-matrix interactions in 3-D can be important for various cell processes. With pancreatic substitutes, studies have indicated benefits of 3-D adhesion on the viability and/or function of insulin-secreting cells. As long-term storage of microencapsulated cells is critical for their clinical translation, cryopreservation of cells in hydrogels is actively being investigated. Previous studies have examined the cryopreservation response of cells encapsulated in non-adhesive hydrogels using conventional freezing and/or vitrification (ice-free cryopreservation), however, none have systematically compared the two cryopreservation methods with cells encapsulated within an adhesive 3-D environment. The latter would be significant, as evidence suggests adhesion influences cellular response to cryopreservation. Thus, the objective of this study was to determine the response to conventional freezing and vitrification of insulin-secreting cells encapsulated in an adhesive biomimetic hydrogel. Recombinant insulin-secreting C2C12 myoblasts were encapsulated in oxidized RGD-alginate and cultured 1 or 4 days post-encapsulation, cryopreserved, and assessed up to 3 days post-warming for metabolic activity and insulin secretion, and one day post-warming for cell morphology. Besides certain transient differences of the vitrified group relative to the Fresh control, both conventional freezing and vitrification maintained metabolism, secretion and morphology of the recombinant C2C12 cells. Thus, due to a simpler procedure and slightly superior results, conventional freezing is recommended over vitrification for the cryopreservation of C2C12 cells in oxidized RGD-modified alginate. PMID:23499987
Pournourmohammadi, Shirin; Grimaldi, Mariagrazia; Stridh, Malin H; Lavallard, Vanessa; Waagepetersen, Helle S; Wollheim, Claes B; Maechler, Pierre
2017-07-01
Glucose homeostasis is determined by insulin secretion from the ß-cells in pancreatic islets and by glucose uptake in skeletal muscle and other insulin target tissues. While glutamate dehydrogenase (GDH) senses mitochondrial energy supply and regulates insulin secretion, its role in the muscle has not been elucidated. Here we investigated the possible interplay between GDH and the cytosolic energy sensing enzyme 5'-AMP kinase (AMPK), in both isolated islets and myotubes from mice and humans. The green tea polyphenol epigallocatechin-3-gallate (EGCG) was used to inhibit GDH. Insulin secretion was reduced by EGCG upon glucose stimulation and blocked in response to glutamine combined with the allosteric GDH activator BCH (2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid). Insulin secretion was similarly decreased in islets of mice with ß-cell-targeted deletion of GDH (ßGlud1 -/- ). EGCG did not further reduce insulin secretion in the mutant islets, validating its specificity. In human islets, EGCG attenuated both basal and nutrient-stimulated insulin secretion. Glutamine/BCH-induced lowering of AMPK phosphorylation did not operate in ßGlud1 -/- islets and was similarly prevented by EGCG in control islets, while high glucose systematically inactivated AMPK. In mouse C2C12 myotubes, like in islets, the inhibition of AMPK following GDH activation with glutamine/BCH was reversed by EGCG. Stimulation of GDH in primary human myotubes caused lowering of insulin-induced 2-deoxy-glucose uptake, partially counteracted by EGCG. Thus, mitochondrial energy provision through anaplerotic input via GDH influences the activity of the cytosolic energy sensor AMPK. EGCG may be useful in obesity by resensitizing insulin-resistant muscle while blunting hypersecretion of insulin in hypermetabolic states. Copyright © 2017 Elsevier Ltd. All rights reserved.
O'Neill, T J; Sargeant, J M; Poljak, Z
2014-12-01
Q fever in humans and coxiellosis in livestock are both caused by Coxiella burnetii. The public health importance of vaccination against C. burnetii shedding from sheep and goats was evaluated using systematic review and meta-analysis to provide evidence for policy direction to prevent potential zoonotic spread. Publications reporting shedding of C. burnetii in vaginal and uterine secretions, milk, placenta and faeces were included. A single observational (one goat) and seven experimental (four goat and three sheep) vaccine studies were included in the review. No relevant publications on other interventions were identified. Random effects meta-analyses were performed for the risk of shedding in individuals in the control and vaccinated groups and for the mean difference in the level of bacterial shedding in sheep and goats stratified by age and previous exposure status. Limited data were available for further analytic evaluation. From the pooled analysis, an inactivated phase I vaccine significantly reduced the risk of shedding from uterine (RR = 0.10; 95%CI 0.05-0.20) secretions in previously sensitized goats. Individual studies reported significant risk reduction in milk (RR = 0.03; 95%CI 0.01-0.26), vaginal secretions (RR = 0.40; 95%CI 0.22-0.75) and faeces (RR = 0.79; 95%CI 0.63-0.97) from naïve goats. The pooled mean levels of bacteria shed from placental [mean difference (MD = -5.24 Log10 ; 95%CI -6.75 to -3.7)] and vaginal (MD = -1.78 Log10 ; 95%CI -2.19 to -1.38) routes were significantly decreased in vaccinated naïve goats compared with controls. Shedding through all other routes from vaccinated goats was not significantly different than shedding from control goats. No effect of vaccination was found on the risk of shedding or the mean level of shedding in vaccinated sheep compared with control sheep. Our conclusions are based on a limited amount of data with variable risk of systematic error. © 2013 Blackwell Verlag GmbH.
Wu, Minfeng; Deng, Yu; Li, Su; Chen, Yu; Guo, Dongjie; Jin, Xingxiu; Xu, Qi; Li, Bin; Li, Fulun
2018-05-08
Psoriasis is a chronic inflammatory cutaneous disease characterized by clinical manifestations of erythema and white scales. The pathogenesis of psoriasis is not yet clear. Despite a combination of hormonal therapy and physiotherapy used in Western medicine, the condition often relapses after withdrawal of drugs. Traditional Chinese medicine (TCM) has therapeutic features and may be a clinically effective formula by regulating unbalanced immune systems, such as by targeting interleukins. In this paper, we review recent research about how Chinese medicine immunoregulates psoriasis via interleukins, and systematically summarizes the related mechanisms. There are three common pathways leading to psoriasis: (1) Th17 cells secrete IL-17, which is stimulated by IL-23; (2) Th1 cells secrete IL-21, TNF-[Formula: see text] and IFN-[Formula: see text], with the help of Th17 cells; (3) Th22 cells secrete IL-22 under the stimulation of Th17 cells. Clinical and experiment data indicate that TCM could modify psoriasis by antagonizing or regulating interleukin and IL-23/IL-17 axis to inhibit the main pathways.
Gorlani, A; Hulsik, D Lutje; Adams, H; Vriend, G; Hermans, P; Verrips, T
2012-01-01
Variable domains of llama heavy-chain antibodies (VHH) are becoming a potent tool for a wide range of biotechnological and medical applications. Because of structural features typical of their single-domain nature, they are relatively easy to produce in lower eukaryotes, but it is not uncommon that some molecules have poor secretion efficiency. We therefore set out to study the production yield of VHH. We computationally identified five key residues that are crucial for folding and secretion, and we validated their importance with systematic site-directed mutations. The observation that all key residues were localised in the V segment, in proximity of the J segment of VHH, led us to study the importance of J segment in secretion efficiency. Intriguingly, we found that the use of specific J segments in VHH could strongly influence the production yield. Sequence analysis and expression experiments strongly suggested that interactions with chaperones, especially with the J segment, are a crucial aspect of the production yield of VHH.
Cancer articles in weekly magazines: useful media to deliver cancer information to the public?
Nagata, Masayoshi; Takita, Morihito; Kishi, Yukiko; Kodama, Yuko; Matsumura, Tomoko; Murashige, Naoko; Homma, Yukio; Kami, Masahiro
2013-04-01
Japanese weekly magazines, which have a circulation of over 2 700 000, play important roles in communicating with the public. They offer a wide range of information, entertainment, gossip, politics and economics, and often include articles on cancer. However, cancer articles in magazines have not been systematically analyzed. We investigated cancer-related articles and advertisements in six major Japanese weekly magazines to demonstrate trends in public interest regarding cancer. The total number of articles assessed from July 2009 to December 2010 was 36 914, of which 696 (1.9%) were cancer articles. The total number of advertisements was 21 718, of which 340 (1.6%) were related to cancer. The number of cancer articles demonstrated an upward trend during the study period. Articles focused on lung (n = 145) and urogenital cancer (n = 122). The most common content comprised therapies and diagnosis (n = 340) and case reports on individual patients (n = 160). After a famous Japanese comedian revealed his prostate cancer diagnosis, the number of articles on prostate cancer increased from 2.0 to 6.6 per month. Immunotherapy including some dubious folk therapies was the most frequently reported cancer therapy in articles and advertisements (30.4%). A small group of oncologists were repeatedly referred to in comment sources; 35.6% of comments were presented by only five doctors. Cancer articles in weekly magazines are common paper media for providing cancer information to the public. However, the information provided might place emphasis on unestablished treatments or biased opinions.
The Intermediate Range Nuclear Forces (INF) Negotiations and Treaty: An Historical Case Study.
1989-09-01
Level Lobbying for SALT," Time, 114: 37-36 (22 October 1979). 38. Hoyle , Russ. "Andropov’s Ultimatum," Time, 122: 70- 71 (7 November 1983). 39. Hoyle ...Russ. "Concession or Propaganda?," Time, 121: 28-29 (16 May 1983). 40. Hoyle , Russ. "Listening to the Allies," Time, 121: 26 (7 February 1983). 41...Disarmament and Global Security: A Search For Alternatives. Boulder CO: Westview Press, Inc., 1984. 44. Kaplan, Fred M. "Dubious Specter: A Skeptical Look at
Dr. William O. Coffee and his absorption cure for cataract.
Ferry, A P
1989-08-01
Dr. William O. Coffee was an ophthalmologist who conducted an office and mail-order practice in the Midwest from the 1880s until 1927. His main stock in trade was a self-discovered absorption cure for a variety of ocular diseases, with particular emphasis on the medical cure of cataracts. Dr. Coffee's career was a checkered one, marked by dubious credentials, exuberant self-promotion, unlikely and exaggerated claims of medical successes, plagiarism, and rejection by the medical "establishment." Certain parallels may be drawn between his activities and some currently observed practices in ophthalmology.
NASA Astrophysics Data System (ADS)
James, Jessica
2008-04-01
Riccardo Rebonato is a man with a clear and deep understanding of the most complex elements of the financial markets. His first book, Interest Rate Option Models, was one of the earliest proper mathematical texts on the complexities of "interest rate options" - investment tools in which the pay-offs depend on the future level of interest rates - and it is still relevant today. But is he the right person to write a book, without equations, about the fundamental problems underlying risk management in the markets? Before I opened Plight of the Fortune Tellers I have to confess to being dubious.
Xu, Qi; Knoshaug, Eric P.; Wang, Wei; ...
2017-07-24
Lipomyces starkeyi is one of the leading lipid-producing microorganisms reported to date; its genetic transformation was only recently reported. Our aim is to engineer L. starkeyi to serve in consolidated bioprocessing (CBP) to produce lipid or fatty acid-related biofuels directly from abundant and low-cost lignocellulosic substrates. To evaluate L. starkeyi in this role, we first conducted a genome analysis, which revealed the absence of key endo- and exocellulases in this yeast, prompting us to select and screen four signal peptides for their suitability for the overexpression and secretion of cellulase genes. To compensate for the cellulase deficiency, we chose twomore » prominent cellulases, Trichoderma reesei endoglucanase II (EG II) and a chimeric cellobiohydrolase I (TeTrCBH I) formed by fusion of the catalytic domain from Talaromyces emersonii CBH I with the linker peptide and cellulose-binding domain from T. reesei CBH I. The systematically tested signal peptides included three peptides from native L. starkeyi and one from Yarrowia lipolytica. We found that all four signal peptides permitted secretion of active EG II. We also determined that three of these signal peptides worked for expression of the chimeric CBH I; suggesting that our design criteria for selecting these signal peptides was effective. Encouragingly, the Y. lipolytica signal peptide was able to efficiently guide secretion of the chimeric TeTrCBH I protein from L. starkeyi. The purified chimeric TeTrCBH I showed high activity against the cellulose in pretreated corn stover and the purified EG II showed high endocellulase activity measured by the CELLG3 (Megazyme) method. Our results suggest that L. starkeyi is capable of expressing and secreting core fungal cellulases. Moreover, the purified EG II and chimeric TeTrCBH I displayed significant and potentially useful enzymatic activities, demonstrating that engineered L. starkeyi has the potential to function as an oleaginous CBP strain for biofuel production. Lastly, the effectiveness of the tested secretion signals will also benefit future secretion of other heterologous proteins in L. starkeyi and, given the effectiveness of the cross-genus secretion signal, possibly other oleaginous yeasts as well.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Qi; Knoshaug, Eric P.; Wang, Wei
Lipomyces starkeyi is one of the leading lipid-producing microorganisms reported to date; its genetic transformation was only recently reported. Our aim is to engineer L. starkeyi to serve in consolidated bioprocessing (CBP) to produce lipid or fatty acid-related biofuels directly from abundant and low-cost lignocellulosic substrates. To evaluate L. starkeyi in this role, we first conducted a genome analysis, which revealed the absence of key endo- and exocellulases in this yeast, prompting us to select and screen four signal peptides for their suitability for the overexpression and secretion of cellulase genes. To compensate for the cellulase deficiency, we chose twomore » prominent cellulases, Trichoderma reesei endoglucanase II (EG II) and a chimeric cellobiohydrolase I (TeTrCBH I) formed by fusion of the catalytic domain from Talaromyces emersonii CBH I with the linker peptide and cellulose-binding domain from T. reesei CBH I. The systematically tested signal peptides included three peptides from native L. starkeyi and one from Yarrowia lipolytica. We found that all four signal peptides permitted secretion of active EG II. We also determined that three of these signal peptides worked for expression of the chimeric CBH I; suggesting that our design criteria for selecting these signal peptides was effective. Encouragingly, the Y. lipolytica signal peptide was able to efficiently guide secretion of the chimeric TeTrCBH I protein from L. starkeyi. The purified chimeric TeTrCBH I showed high activity against the cellulose in pretreated corn stover and the purified EG II showed high endocellulase activity measured by the CELLG3 (Megazyme) method. Our results suggest that L. starkeyi is capable of expressing and secreting core fungal cellulases. Moreover, the purified EG II and chimeric TeTrCBH I displayed significant and potentially useful enzymatic activities, demonstrating that engineered L. starkeyi has the potential to function as an oleaginous CBP strain for biofuel production. Lastly, the effectiveness of the tested secretion signals will also benefit future secretion of other heterologous proteins in L. starkeyi and, given the effectiveness of the cross-genus secretion signal, possibly other oleaginous yeasts as well.« less
Xu, Qi; Knoshaug, Eric P; Wang, Wei; Alahuhta, Markus; Baker, John O; Yang, Shihui; Vander Wall, Todd; Decker, Stephen R; Himmel, Michael E; Zhang, Min; Wei, Hui
2017-07-24
Lipomyces starkeyi is one of the leading lipid-producing microorganisms reported to date; its genetic transformation was only recently reported. Our aim is to engineer L. starkeyi to serve in consolidated bioprocessing (CBP) to produce lipid or fatty acid-related biofuels directly from abundant and low-cost lignocellulosic substrates. To evaluate L. starkeyi in this role, we first conducted a genome analysis, which revealed the absence of key endo- and exocellulases in this yeast, prompting us to select and screen four signal peptides for their suitability for the overexpression and secretion of cellulase genes. To compensate for the cellulase deficiency, we chose two prominent cellulases, Trichoderma reesei endoglucanase II (EG II) and a chimeric cellobiohydrolase I (TeTrCBH I) formed by fusion of the catalytic domain from Talaromyces emersonii CBH I with the linker peptide and cellulose-binding domain from T. reesei CBH I. The systematically tested signal peptides included three peptides from native L. starkeyi and one from Yarrowia lipolytica. We found that all four signal peptides permitted secretion of active EG II. We also determined that three of these signal peptides worked for expression of the chimeric CBH I; suggesting that our design criteria for selecting these signal peptides was effective. Encouragingly, the Y. lipolytica signal peptide was able to efficiently guide secretion of the chimeric TeTrCBH I protein from L. starkeyi. The purified chimeric TeTrCBH I showed high activity against the cellulose in pretreated corn stover and the purified EG II showed high endocellulase activity measured by the CELLG3 (Megazyme) method. Our results suggest that L. starkeyi is capable of expressing and secreting core fungal cellulases. Moreover, the purified EG II and chimeric TeTrCBH I displayed significant and potentially useful enzymatic activities, demonstrating that engineered L. starkeyi has the potential to function as an oleaginous CBP strain for biofuel production. The effectiveness of the tested secretion signals will also benefit future secretion of other heterologous proteins in L. starkeyi and, given the effectiveness of the cross-genus secretion signal, possibly other oleaginous yeasts as well.
Systematic review: Helicobacter pylori infection and impaired drug absorption.
Lahner, E; Annibale, B; Delle Fave, G
2009-02-15
Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.
Human Rhinovirus 16 Causes Golgi Apparatus Fragmentation without Blocking Protein Secretion
Mousnier, Aurelie; Swieboda, Dawid; Pinto, Anaïs; Guedán, Anabel; Rogers, Andrew V.; Walton, Ross; Johnston, Sebastian L.
2014-01-01
ABSTRACT The replication of picornaviruses has been described to cause fragmentation of the Golgi apparatus that blocks the secretory pathway. The inhibition of major histocompatibility complex class I upregulation and cytokine, chemokine and interferon secretion may have important implications for host defense. Previous studies have shown that disruption of the secretory pathway can be replicated by expression of individual nonstructural proteins; however the situation with different serotypes of human rhinovirus (HRV) is unclear. The expression of 3A protein from HRV14 or HRV2 did not cause Golgi apparatus disruption or a block in secretion, whereas other studies showed that infection of cells with HRV1A did cause Golgi apparatus disruption which was replicated by the expression of 3A. HRV16 is the serotype most widely used in clinical HRV challenge studies; consequently, to address the issue of Golgi apparatus disruption for HRV16, we have systematically and quantitatively examined the effect of HRV16 on both Golgi apparatus fragmentation and protein secretion in HeLa cells. First, we expressed each individual nonstructural protein and examined their cellular localization and their disruption of endoplasmic reticulum and Golgi apparatus architecture. We quantified their effects on the secretory pathway by measuring secretion of the reporter protein Gaussia luciferase. Finally, we examined the same outcomes following infection of cells with live virus. We demonstrate that expression of HRV16 3A and 3AB and, to a lesser extent, 2B caused dispersal of the Golgi structure, and these three nonstructural proteins also inhibited protein secretion. The infection of cells with HRV16 also caused significant Golgi apparatus dispersal; however, this did not result in the inhibition of protein secretion. IMPORTANCE The ability of replicating picornaviruses to influence the function of the secretory pathway has important implications for host defense. However, there appear to be differences between different members of the family and inconsistent results when comparing infection with live virus to expression of individual nonstructural proteins. We demonstrate that individual nonstructural HRV16 proteins, when expressed in HeLa cells, can both fragment the Golgi apparatus and block secretion, whereas viral infection fragments the Golgi apparatus without blocking secretion. This has major implications for how we interpret mechanistic evidence derived from the expression of single viral proteins. PMID:25100828
[Mucus secreting tumors of the appendix. Report of 22 cases].
Beyrouti, Mohamed Issam; Gharbi, Ahmed; Abid, Mohamed; Beyrouti, Ramez; Kharrat, Madiha; Gargouri, Faouzi; Gharbi, Walid; Tafech, Issam; Affes, Najmeddine; Khebir, Abdelmajid; Sellami, Abdelhafidh
2004-12-01
The retrospective study presented in this article was realized on a series of 22 cases of mucus secreting tumor of the appendix compiled among 8373 appendicectomies. The clinical picture was dominated by an appendiceal syndrome (73%). The diagnosis was made pre or peroperatively in 10 cases and it was only with to the systematic anatomopathologic exam that 12 other cases were discovered. The histological study of the appendectomy piece showed a retention mucocele (12 cases), a mucosal hyperplasia (8 cases) and a cystadenoma (2 cases). For 5 patients, the diagnosis of peritoneal pseudomyxoma (4 cases) or extraperitoneal (1 case) was retained. All the patients underwent an appendicectomy, associated to an evacuation of the peritoneal gelatinous ascites for 5 patients among whom two underwent in more an omentectomie. Two cases of recurrence were recorded 5 months later.
Karaarslan, Numan; Yilmaz, Ibrahim; Akgun, Feride Sinem; Caliskan, Tezcan; Ozbek, Hanefi; Ates, Ozkan
2018-04-09
This study discusses the management of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH), developed after subarachnoid hemorrhage, in a comparative manner in light of the literature. Without country or language restrictions, articles with high evidential value found in electronic databases were compared to our patients' data. After the literature review, three articles were included for systematic evaluation. Desmopressin was applied to the patients for the treatment of hyponatremia, volume contraction, and negative sodium balance caused by SIADH. However, it was not used for preventing re-bleeding. To prevent the development of this complication (SIADH), the use of desmopressin, an analogue of vasopressin, is important in routine clinical practice.
The use of prisoners as sources of organs--an ethically dubious practice.
Caplan, Arthur
2011-10-01
The movement to try to close the ever-widening gap between demand and supply of organs has recently arrived at the prison gate. While there is enthusiasm for using executed prisoners as sources of organs, there are both practical barriers and moral concerns that make it unlikely that proposals to use prisoners will or should gain traction. Prisoners are generally not healthy enough to be a safe source of organs, execution makes the procurement of viable organs difficult, and organ donation post-execution ties the medical profession too closely to the act of execution.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Payne, F.W.
1988-01-01
Our energy industry has gone through the dynamic restructuring. The changes taking place in the energy industry will affect the pocketbooks, thus the lives, of every American, at every level. The geopolitical/militaristic intrigues which surround the international oil segment of this industry must be left to the dubious talents of others. But as motivators, planners, and executors of the powerful changes which are restructuring the other aspects of our industry, the author believes the American people share grave responsibilities. The author defines the scope, the meaning, the results of these changes, and applies the new techniques and technologies they provide.
Unruly democracy and the privileges of public intimacy: (same) sex spousal hiring in academia.
Nadeau, Chantal
2005-01-01
Within the context of a discussion of lesbian academic couples there is something to be said about the (dis)pleasures and profits of a heteronormative practice such as spousal hiring and how much this privilege reveals the broader systemic discrimination vis-à-vis sexual and gender claims in our academic institutions. Two issues emerge from its (questionable) application: (1) How a privilege such as spousal hiring intersects with institutional policies concerning sexual diversity; and in light of this, (2)Why queer or lesbian couples shouldn't embrace dubious spousal hiring incentives.
Cossidae of the Socotra Archipelago (Yemen)
Borth, Robert; Ivinskis, Povilas; Saldaitis, Aidas; Yakovlev, Roman
2011-01-01
Abstract The faunistic composition of the family Cossidae (Lepidoptera) of the Socotra Archipelago is revised. Five species are recognized, including two new species (Mormogystia brandstetteri and Meharia hackeri), and dubious identifications and records are discussed. Adults and genitalia are illustrated and bionomic details, DNA barcodes and a synonymic checklist for Socotran cossids are provided. A review of their distribution reveals that at least 80 percent of Socotra’s cossids are unique to the archipelago, which is renowned for its endemism. A checklist listing all the species from generas Meharia, Mormogystia, Aethalopteryx, Azygophleps, as well as the synonymy and distribution is provided. PMID:21998527
The endocrine pharmacology of testosterone therapy in men
NASA Astrophysics Data System (ADS)
Oettel, Michael
The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.
Buhren, Bettina Alexandra; Martinez, Cynthia; Schrumpf, Holger; Gasis, Marcia; Grether-Beck, Susanne; Krutmann, Jean
2013-01-01
Through bioinformatics analyses of a human gene expression database representing 105 different tissues and cell types, we identified 687 skin-associated genes that are selectively and highly expressed in human skin. Over 50 of these represent uncharacterized genes not previously associated with skin and include a subset that encode novel secreted and plasma membrane proteins. The high levels of skin-associated expression for eight of these novel therapeutic target genes were confirmed by semi-quantitative real time PCR, western blot and immunohistochemical analyses of normal skin and skin-derived cell lines. Four of these are expressed specifically by epidermal keratinocytes; two that encode G-protein-coupled receptors (GPR87 and GPR115), and two that encode secreted proteins (WFDC5 and SERPINB7). Further analyses using cytokine-activated and terminally differentiated human primary keratinocytes or a panel of common inflammatory, autoimmune or malignant skin diseases revealed distinct patterns of regulation as well as disease associations that point to important roles in cutaneous homeostasis and disease. Some of these novel uncharacterized skin genes may represent potential biomarkers or drug targets for the development of future diagnostics or therapeutics. PMID:23840300
Crosstalk between the heart and peripheral organs in heart failure
Jahng, James Won Suk; Song, Erfei; Sweeney, Gary
2016-01-01
Mediators from peripheral tissues can influence the development and progression of heart failure (HF). For example, in obesity, an altered profile of adipokines secreted from adipose tissue increases the incidence of myocardial infarction (MI). Less appreciated is that heart remodeling releases cardiokines, which can strongly impact various peripheral tissues. Inflammation, and, in particular, activation of the nucleotide-binding oligomerization domain-like receptors with pyrin domain (NLRP3) inflammasome are likely to have a central role in cardiac remodeling and mediating crosstalk with other organs. Activation of the NLRP3 inflammasome in response to cardiac injury induces the production and secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18. In addition to having local effects in the myocardium, these pro-inflammatory cytokines are released into circulation and cause remodeling in the spleen, kidney, skeletal muscle and adipose tissue. The collective effects of various cardiokines on peripheral organs depend on the degree and duration of myocardial injury, with systematic inflammation and peripheral tissue damage observed as HF progresses. In this article, we review mechanisms regulating myocardial inflammation in HF and the role of factors secreted by the heart in communication with peripheral tissues. PMID:26964833
The kisspeptin-GnRH pathway in human reproductive health and disease
Skorupskaite, Karolina; George, Jyothis T; Anderson, Richard A
2014-01-01
BACKGROUND The discovery of kisspeptin as key central regulator of GnRH secretion has led to a new level of understanding of the neuroendocrine regulation of human reproduction. The related discovery of the kisspeptin-neurokinin B-dynorphin (KNDy) pathway in the last decade has further strengthened our understanding of the modulation of GnRH secretion by endocrine, metabolic and environmental inputs. In this review, we summarize current understanding of the physiological roles of these novel neuropeptides, and discuss the clinical relevance of these discoveries and their potential translational applications. METHODS A systematic literature search was performed using PUBMED for all English language articles up to January 2014. In addition, the reference lists of all relevant original research articles and reviews were examined. This review focuses mainly on published human studies but also draws on relevant animal data. RESULTS Kisspeptin is a principal regulator of the secretion of gonadotrophins, and through this key role it is critical for the onset of puberty, the regulation of sex steroid-mediated feedback and the control of adult fertility. Although there is some sexual dimorphism, both neuroanatomically and functionally, these functions are apparent in both men and women. Kisspeptin acts upstream of GnRH and, following paracrine stimulatory and inhibitory inputs from neurokinin B and dynorphin (KNDy neuropeptides), signals directly to GnRH neurones to control pulsatile GnRH release. When administered to humans in different isoforms, routes and doses, kisspeptin robustly stimulates LH secretion and LH pulse frequency. Manipulation of the KNDy system is currently the focus of translational research with the possibility of future clinical application to regulate LH pulsatility, increasing gonadal sex steroid secretion in reproductive disorders characterized by decreased LH pulsatility, including hypothalamic amenorrhoea and hypogonadotropic hypogonadism. Conversely there may be scope to reduce the activity of the KNDy system to reduce LH secretion where hypersecretion of LH adds to the phenotype, such as in polycystic ovary syndrome. CONCLUSIONS Kisspeptin is a recently discovered neuromodulator that controls GnRH secretion mediating endocrine and metabolic inputs to the regulation of human reproduction. Manipulation of kisspeptin signalling has the potential for novel therapies in patients with pathologically low or high LH pulsatility. PMID:24615662
Glynn, Eric; Thompson, Benjamin; Vadrevu, Suryakiran; Lu, Shusheng; Kennedy, Robert T.; Ha, Joon; Sherman, Arthur
2016-01-01
Mouse islets exhibit glucose-dependent oscillations in electrical activity, intracellular Ca2+ and insulin secretion. We developed a mathematical model in which a left shift in glucose threshold helps compensate for insulin resistance. To test this experimentally, we exposed isolated mouse islets to varying glucose concentrations overnight and monitored their glucose sensitivity the next day by measuring intracellular Ca2+, electrical activity, and insulin secretion. Glucose sensitivity of all oscillation modes was increased when overnight glucose was greater than 2.8mM. To determine whether threshold shifts were a direct effect of glucose or involved secreted insulin, the KATP opener diazoxide (Dz) was coapplied with glucose to inhibit insulin secretion. The addition of Dz or the insulin receptor antagonist s961 increased islet glucose sensitivity, whereas the KATP blocker tolbutamide tended to reduce it. This suggests insulin and glucose have opposing actions on the islet glucose threshold. To test the hypothesis that the threshold shifts were due to changes in plasma membrane KATP channels, we measured cell KATP conductance, which was confirmed to be reduced by high glucose pretreatment and further reduced by Dz. Finally, treatment of INS-1 cells with glucose and Dz overnight reduced high affinity sulfonylurea receptor (SUR1) trafficking to the plasma membrane vs glucose alone, consistent with insulin increasing KATP conductance by altering channel number. The results support a role for metabolically regulated KATP channels in the maintenance of glucose homeostasis. PMID:26697721
Advanced Fingerprint Analysis Project Fingerprint Constituents
DOE Office of Scientific and Technical Information (OSTI.GOV)
GM Mong; CE Petersen; TRW Clauss
The work described in this report was focused on generating fundamental data on fingerprint components which will be used to develop advanced forensic techniques to enhance fluorescent detection, and visualization of latent fingerprints. Chemical components of sweat gland secretions are well documented in the medical literature and many chemical techniques are available to develop latent prints, but there have been no systematic forensic studies of fingerprint sweat components or of the chemical and physical changes these substances undergo over time.
Early Pleistocene 40Ar/39Ar ages for Bapang Formation hominins, Central Jawa, Indonesia
Larick, Roy; Ciochon, Russell L.; Zaim, Yahdi; Sudijono; Suminto; Rizal, Yan; Aziz, Fachroel; Reagan, Mark; Heizler, Matthew
2001-01-01
The Sangiran dome is the primary stratigraphic window for the Plio-Pleistocene deposits of the Solo basin of Central Jawa. The dome has yielded nearly 80 Homo erectus fossils, around 50 of which have known findspots. With a hornblende 40Ar/39Ar plateau age of 1.66 ± 0.04 mega-annum (Ma) reportedly associated with two fossils [Swisher, C.C., III, Curtis, G. H., Jacob, T., Getty, A. G., Suprijo, A. & Widiasmoro (1994) Science 263, 1118–1121), the dome offers evidence that early Homo dispersed to East Asia during the earliest Pleistocene. Unfortunately, the hornblende pumice was sampled at Jokotingkir Hill, a central locality with complex lithostratigraphic deformation and dubious specimen provenance. To address the antiquity of Sangiran H. erectus more systematically, we investigate the sedimentary framework and hornblende 40Ar/39Ar age for volcanic deposits in the southeast quadrant of the dome. In this sector, Bapang (Kabuh) sediments have their largest exposure, least deformation, and most complete tephrostratigraphy. At five locations, we identify a sequence of sedimentary cycles in which H. erectus fossils are associated with epiclastic pumice. From sampled pumice, eight hornblende separates produced 40Ar/39Ar plateau ages ranging from 1.51 ± 0.08 Ma at the Bapang/Sangiran Formation contact, to 1.02 ± 0.06 Ma, at a point above the hominin-bearing sequence. The chronological sequence of 40Ar/39Ar ages follows stratigraphic order across the southeast quadrant. An intermediate level yielding four nearly complete crania has an age of about 1.25 Ma. PMID:11309488
Early Pleistocene 40Ar/39Ar ages for Bapang Formation hominins, Central Jawa, Indonesia.
Larick, R; Ciochon, R L; Zaim, Y; Sudijono; Suminto; Rizal, Y; Aziz, F; Reagan, M; Heizler, M
2001-04-24
The Sangiran dome is the primary stratigraphic window for the Plio-Pleistocene deposits of the Solo basin of Central Jawa. The dome has yielded nearly 80 Homo erectus fossils, around 50 of which have known findspots. With a hornblende (40)Ar/(39)Ar plateau age of 1.66 +/- 0.04 mega-annum (Ma) reportedly associated with two fossils [Swisher, C.C., III, Curtis, G. H., Jacob, T., Getty, A. G., Suprijo, A. & Widiasmoro (1994) Science 263, 1118-1121), the dome offers evidence that early Homo dispersed to East Asia during the earliest Pleistocene. Unfortunately, the hornblende pumice was sampled at Jokotingkir Hill, a central locality with complex lithostratigraphic deformation and dubious specimen provenance. To address the antiquity of Sangiran H. erectus more systematically, we investigate the sedimentary framework and hornblende (40)Ar/(39)Ar age for volcanic deposits in the southeast quadrant of the dome. In this sector, Bapang (Kabuh) sediments have their largest exposure, least deformation, and most complete tephrostratigraphy. At five locations, we identify a sequence of sedimentary cycles in which H. erectus fossils are associated with epiclastic pumice. From sampled pumice, eight hornblende separates produced (40)Ar/(39)Ar plateau ages ranging from 1.51 +/- 0.08 Ma at the Bapang/Sangiran Formation contact, to 1.02 +/- 0.06 Ma, at a point above the hominin-bearing sequence. The chronological sequence of (40)Ar/(39)Ar ages follows stratigraphic order across the southeast quadrant. An intermediate level yielding four nearly complete crania has an age of about 1.25 Ma.
Remagnetization in Some Transitional Flows
NASA Astrophysics Data System (ADS)
Valet, J. P.; Carlut, J. H.; Vella, J.; Le Goff, M.; Soler, V.
2016-12-01
Very large directional variations of magnetization have been reported in several lava flows recording a geomagnetic reversal. Such behavior could reflect real geomagnetic changes or be caused by artifacts due to post-emplacement alteration and/or non-ideal magnetic behavior. More recently, a high resolution paleomagnetic record from sediments pleads also for an extremely rapid reversal process during the last reversal (Sagnotti et al., 2014). Assuming that the geomagnetic field would have moved by tens of degrees during cooling of moderate thickness lava flows implies brief episodes of rapid changes by a few degrees per day that are difficult to reconcile with the rate of liquid motions at the core surface. Systematical mineralogical bias is a most likely explanation to promote such behavior as recently reconsidered by Coe et al., 2014 for the rapid field changes recorded at Steens Mountain. We resampled two lava flows at La Palma island (Canarias) that are sandwiched between reverse polarity and normal polarity flows associated with the last geomagnetic reversal. The results show an evolution of the magnetization direction from top to bottom. Hysteresis, coercivity and thermomagnetic parameters do not show important variations and no correlation with the amplitude of the deviations could be established. Thermal demagnetization experiments conducted using continuous demagnetization (TRIAXE method) did not allow the detection of dubious behavior. Experimental evidences finally indicate that critical thermal activation of some of the magnetic grains during the moderate baking by the above flow may be responsible for the directional swing. Microscopic observations indicate poor exsolution, which suggest a link between Ti-rich magnetite and thermoviscous remagnetization.
Body donations today and tomorrow: What is best practice and why?
Riederer, Beat M
2016-01-01
There is considerable agreement that the use of human bodies for teaching and research remains important, yet not all universities use dissection to teach human gross anatomy. The concept of body donation has evolved over centuries and there are still considerable discrepancies among countries regarding the means by which human bodies are acquired and used for education and research. Many countries have well-established donation programs and use body dissection to teach most if not all human gross anatomy. In contrast, there are countries without donation programs that use unclaimed bodies or perhaps a few donated bodies instead. In several countries, use of cadavers for dissection is unthinkable for cultural or religious reasons. Against this background, successful donation programs are highlighted in the present review, emphasizing those aspects of the programs that make them successful. Looking to the future, we consider what best practice could look like and how the use of unclaimed bodies for anatomy teaching could be replaced. From an ethical point of view, countries that depend upon unclaimed bodies of dubious provenance are encouraged to use these reports and adopt strategies for developing successful donation programs. In many countries, the act of body donation has been guided by laws and ethical frameworks and has evolved alongside the needs for medical knowledge and for improved teaching of human anatomy. There will also be a future need for human bodies to ensure optimal pre- and post-graduate training and for use in biomedical research. Good body donation practice should be adopted wherever possible, moving away from the use of unclaimed bodies of dubious provenance and adopting strategies to favor the establishment of successful donation programs. © 2015 Wiley Periodicals, Inc.
'Resuscitation' of extremely preterm and/or low-birth-weight infants - time to 'call it'?
O'Donnell, Colm P F
2008-01-01
Since ancient times, various methods have been used to revive apparently stillborn infants; many were of dubious efficacy and had the potential to cause harm. Based largely on studies of acutely asphyxiated term animal models, clinical assessment and positive pressure ventilation have become the cornerstones of neonatal resuscitation over the last 40 years. Over the last 25 years, care of extremely preterm infants in the delivery room has evolved from a policy of indifference to one of increasingly aggressive support. The survival of these infants has improved considerably in recent years; this has not, however, necessarily been due to more aggressive resuscitation. Urban myths have evolved that all extremely preterm infants died before they were intubated, and that all such infants need to immediately intubated or they will quickly die. This has never been true. Clinical assessment of infants at birth is subjective. Also, many techniques used to support preterm infants at birth have not been well studied and there is evidence that they may be harmful. It may thus be argued that many of our well-intentioned resuscitation interventions are of dubious efficacy and have the potential to cause harm. 'Resuscitation' is an emotive term which means 'restoration of life'. Death, thankfully, is a rare presentation in the delivery room. Therefore, concerning neonatal 'resuscitation', it is time to 'call it' something else. This will allow us to dispassionately distinguish preterm infants who are dead, or nearly dead, from those who are merely at high risk of parenchymal lung disease. We may then be able to refine our interventions and determine what methods of support benefit these infants most. (c) 2008 S. Karger AG, Basel.
The good, the bad and the dubious: VHELIBS, a validation helper for ligands and binding sites
2013-01-01
Background Many Protein Data Bank (PDB) users assume that the deposited structural models are of high quality but forget that these models are derived from the interpretation of experimental data. The accuracy of atom coordinates is not homogeneous between models or throughout the same model. To avoid basing a research project on a flawed model, we present a tool for assessing the quality of ligands and binding sites in crystallographic models from the PDB. Results The Validation HElper for LIgands and Binding Sites (VHELIBS) is software that aims to ease the validation of binding site and ligand coordinates for non-crystallographers (i.e., users with little or no crystallography knowledge). Using a convenient graphical user interface, it allows one to check how ligand and binding site coordinates fit to the electron density map. VHELIBS can use models from either the PDB or the PDB_REDO databank of re-refined and re-built crystallographic models. The user can specify threshold values for a series of properties related to the fit of coordinates to electron density (Real Space R, Real Space Correlation Coefficient and average occupancy are used by default). VHELIBS will automatically classify residues and ligands as Good, Dubious or Bad based on the specified limits. The user is also able to visually check the quality of the fit of residues and ligands to the electron density map and reclassify them if needed. Conclusions VHELIBS allows inexperienced users to examine the binding site and the ligand coordinates in relation to the experimental data. This is an important step to evaluate models for their fitness for drug discovery purposes such as structure-based pharmacophore development and protein-ligand docking experiments. PMID:23895374
Sustainable business makes dollars and sense.
Fields, Scott
2002-01-01
The last decade has marked a radical change in the business of sustainability, say environmental activists and industrialists alike. On the wane are "greenwashing" campaigns in which corporations promote dubious environmental accomplishments to draw attention away from environmentally damaging practices. On the rise are corporate investments in sustainability programs, new types of environmental markets, and public demand for green products and investments. Once an afterthought, an annoyance, or a nonentity, sustainability is now often a focal point for businesses. No longer thought of as a business cost, environmentally benign practices are now viewed as a competitive advantage as companies seek to win both stockholders and customers. PMID:11882490
Food allergy--fact or fiction: a review.
Finn, R
1992-01-01
Food sensitivity is a common condition presenting with various clinical syndromes including migraine, urticaria, gluten enteropathy, Crohn's disease and irritable bowel syndrome. It is a heterogeneous condition affecting different organ systems and is also aetiologically diverse with subgroups due to allergy, pharmacological reactions, enzyme deficiencies and psychological causes. Clinical acceptance of food sensitivity has been delayed by the use of dubious diagnostic techniques by a minority of practitioners and the lack of laboratory diagnostic tests, but several double blind studies have now fully validated the existence of food sensitivity syndromes. More widespread recognition of food sensitivity would be cost effective for the National Health Service. PMID:1433127
Policy folklists and evolutionary theory
O’Neill, Barry
2014-01-01
Policy folklists present a set of alleged historical facts seen as relevant to some social issue. Although the validity of these folklists is dubious, leaders and writers circulate them in the media, variants arise, and the lists continue on, sometimes for decades. Folklists are repeated because their messages are appealing and their users are credible. Because folklists are on the record, we can examine their origins and changes. This report draws an analogy with evolutionary theory and suggests that biological mechanisms of self-repair, boundary maintenance, plasticity, speciation, and predation have significant interpretations for folklists, and clarify how the lists win the credence of otherwise skeptical people. PMID:25024210
Collective action and individual choice: rethinking how we regulate narcotics and antibiotics.
Anomaly, Jonny
2013-12-01
Governments across the globe have squandered treasure and imprisoned millions of their own citizens by criminalising the use and sale of recreational drugs. But use of these drugs has remained relatively constant, and the primary victims are the users themselves. Meanwhile, antimicrobial drugs that once had the power to cure infections are losing their ability to do so, compromising the health of people around the world. The thesis of this essay is that policymakers should stop wasting resources trying to fight an unwinnable and morally dubious war against recreational drug users, and start shifting their attention to the serious threat posed by our collective misuse of antibiotics.
Biochemical and genetic analysis of the yeast proteome with a movable ORF collection
Gelperin, Daniel M.; White, Michael A.; Wilkinson, Martha L.; Kon, Yoshiko; Kung, Li A.; Wise, Kevin J.; Lopez-Hoyo, Nelson; Jiang, Lixia; Piccirillo, Stacy; Yu, Haiyuan; Gerstein, Mark; Dumont, Mark E.; Phizicky, Eric M.; Snyder, Michael; Grayhack, Elizabeth J.
2005-01-01
Functional analysis of the proteome is an essential part of genomic research. To facilitate different proteomic approaches, a MORF (moveable ORF) library of 5854 yeast expression plasmids was constructed, each expressing a sequence-verified ORF as a C-terminal ORF fusion protein, under regulated control. Analysis of 5573 MORFs demonstrates that nearly all verified ORFs are expressed, suggests the authenticity of 48 ORFs characterized as dubious, and implicates specific processes including cytoskeletal organization and transcriptional control in growth inhibition caused by overexpression. Global analysis of glycosylated proteins identifies 109 new confirmed N-linked and 345 candidate glycoproteins, nearly doubling the known yeast glycome. PMID:16322557
Climate change: evidence of human causes and arguments for emissions reduction.
Baum, Seth D; Haqq-Misra, Jacob D; Karmosky, Chris
2012-06-01
In a recent editorial, Raymond Spier expresses skepticism over claims that climate change is driven by human actions and that humanity should act to avoid climate change. This paper responds to this skepticism as part of a broader review of the science and ethics of climate change. While much remains uncertain about the climate, research indicates that observed temperature increases are human-driven. Although opinions vary regarding what should be done, prominent arguments against action are based on dubious factual and ethical positions. Thus, the skepticisms in the recent editorial are unwarranted. This does not diminish the general merits of skeptical intellectual inquiry.
NASA Astrophysics Data System (ADS)
Heatwole, Harold; Lillywhite, Harvey; Grech, Alana
2016-09-01
Recent, more accurate delineation of the distributions of sea kraits and prior dubious use of proxy temperatures and mean values in correlative studies requires re-assessment of the relationships of temperature and salinity as determinants of the size of the geographic ranges of sea kraits. Correcting the sizes of geographic ranges resolved the paradox of lack of correspondence of size of range with degree of terrestrialism, but did not form a definitive test of the theory. Recent ecological, physiological, and behavioural studies provide an example of the kind of approach likely to either validate or refute present theory.
Efficacy vs. effectiveness research in psychotherapy: implications for clinical hypnosis.
Amundson, Jon K; Alladin, Assen; Eamon, Gill
2003-07-01
Empirically supported therapy (EST) has become a major focus and trend for mental health practice. When hypnosis is involved, this may mean satisfying a standard that is entirely too narrow in its emphasis. In this article "efficacy"-based research in clinical practice is contrasted with "effectiveness" -focused research, and they are discussed from the perspective of hypnosis. When clinicians can consider trans-theoretical factors as well as those that are treatment-enhancing, possibilities for improved treatment outcome increase. The "effectiveness" perspective also serves as a counter point for hypnosis in contrast with the dubious efficacy-based gold standard currently proposed for therapy in general, and hypnosis in particular.
Sustainable business makes dollars and sense.
Fields, Scott
2002-03-01
The last decade has marked a radical change in the business of sustainability, say environmental activists and industrialists alike. On the wane are "greenwashing" campaigns in which corporations promote dubious environmental accomplishments to draw attention away from environmentally damaging practices. On the rise are corporate investments in sustainability programs, new types of environmental markets, and public demand for green products and investments. Once an afterthought, an annoyance, or a nonentity, sustainability is now often a focal point for businesses. No longer thought of as a business cost, environmentally benign practices are now viewed as a competitive advantage as companies seek to win both stockholders and customers.
Gu, Yanyan; Zheng, Jiayi; Feng, Jun; Cao, Mingfeng; Gao, Weixia; Quan, Yufen; Dang, Yulei; Wang, Yi; Wang, Shufang; Song, Cunjiang
2017-05-01
Levan is a functional homopolymer of fructose with considerable applications in food, pharmaceutical and cosmetic industries. To improve the levan production in Bacillus amyloliquefaciens, the regulatory elements of sacB (encoding levansucrase) expression and levansucrase secretion were optimized. Four heterologous promoters were evaluated for sacB expression, and the Pgrac promoter led to the highest level for both sacB transcription and levansucrase enzyme activity. The levan production in the corresponding recombinant strain ΔLP-pHTPgrac reached 30.5 g/L, which was 114% higher than that of the control strain NK-ΔLP. In a further step, eight signal peptides were investigated (with Pgrac as the promoter for sacB expression) for their effects on the levansucrase secretion and levan production. The signal peptide yncM was identified as the optimal one, with a secretion efficiency of approximately 90%, and the levan production in the corresponding recombinant strain ΔLP-Y reached 37.4 g/L, which was 161% higher when compared with the control strains NK-ΔLP. Finally, fed-batch fermentation was carried out in 5-L bioreactors for levan production using the recombinant strain ΔLP-Y. A final levan concentration of 102 g/L was achieved, which is very close to the ever reported highest levan production level from the literature. To our best knowledge, this is the first report of the improvement of levan production through metabolic optimization for sacB expression and levansucrase secretion. The results from this study provided essential insights for systematically metabolic engineering of microbial cell factories for enhanced biochemical production.
Metabolomic analysis of pancreatic β-cell insulin release in response to glucose.
Huang, Mei; Joseph, Jamie W
2012-01-01
Defining the key metabolic pathways that are important for fuel-regulated insulin secretion is critical to providing a complete picture of how nutrients regulate insulin secretion. We have performed a detailed metabolomics study of the clonal β-cell line 832/13 using a gas chromatography-mass spectrometer (GC-MS) to investigate potential coupling factors that link metabolic pathways to insulin secretion. Mid-polar and polar metabolites, extracted from the 832/13 β-cells, were derivatized and then run on a GC/MS to identify and quantify metabolite concentrations. Three hundred fifty-five out of 527 chromatographic peaks could be identified as metabolites by our metabolomic platform. These identified metabolites allowed us to perform a systematic analysis of key pathways involved in glucose-stimulated insulin secretion (GSIS). Of these metabolites, 41 were consistently identified as biomarker for GSIS by orthogonal partial least-squares (OPLS). Most of the identified metabolites are from common metabolic pathways including glycolytic, sorbitol-aldose reductase pathway, pentose phosphate pathway, and the TCA cycle suggesting these pathways play an important role in GSIS. Lipids and related products were also shown to contribute to the clustering of high glucose sample groups. Amino acids lysine, tyrosine, alanine and serine were upregulated by glucose whereas aspartic acid was downregulated by glucose suggesting these amino acids might play a key role in GSIS. In summary, a coordinated signaling cascade elicited by glucose metabolism in pancreatic β-cells is revealed by our metabolomics platform providing a new conceptual framework for future research and/or drug discovery.
The kisspeptin-GnRH pathway in human reproductive health and disease.
Skorupskaite, Karolina; George, Jyothis T; Anderson, Richard A
2014-01-01
The discovery of kisspeptin as key central regulator of GnRH secretion has led to a new level of understanding of the neuroendocrine regulation of human reproduction. The related discovery of the kisspeptin-neurokinin B-dynorphin (KNDy) pathway in the last decade has further strengthened our understanding of the modulation of GnRH secretion by endocrine, metabolic and environmental inputs. In this review, we summarize current understanding of the physiological roles of these novel neuropeptides, and discuss the clinical relevance of these discoveries and their potential translational applications. A systematic literature search was performed using PUBMED for all English language articles up to January 2014. In addition, the reference lists of all relevant original research articles and reviews were examined. This review focuses mainly on published human studies but also draws on relevant animal data. Kisspeptin is a principal regulator of the secretion of gonadotrophins, and through this key role it is critical for the onset of puberty, the regulation of sex steroid-mediated feedback and the control of adult fertility. Although there is some sexual dimorphism, both neuroanatomically and functionally, these functions are apparent in both men and women. Kisspeptin acts upstream of GnRH and, following paracrine stimulatory and inhibitory inputs from neurokinin B and dynorphin (KNDy neuropeptides), signals directly to GnRH neurones to control pulsatile GnRH release. When administered to humans in different isoforms, routes and doses, kisspeptin robustly stimulates LH secretion and LH pulse frequency. Manipulation of the KNDy system is currently the focus of translational research with the possibility of future clinical application to regulate LH pulsatility, increasing gonadal sex steroid secretion in reproductive disorders characterized by decreased LH pulsatility, including hypothalamic amenorrhoea and hypogonadotropic hypogonadism. Conversely there may be scope to reduce the activity of the KNDy system to reduce LH secretion where hypersecretion of LH adds to the phenotype, such as in polycystic ovary syndrome. Kisspeptin is a recently discovered neuromodulator that controls GnRH secretion mediating endocrine and metabolic inputs to the regulation of human reproduction. Manipulation of kisspeptin signalling has the potential for novel therapies in patients with pathologically low or high LH pulsatility. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
Wang, Lei; Zhou, Mei; McClelland, Ann; Reilly, Aislinn; Chen, Tianbao; Gagliardo, Ron; Walker, Brian; Shaw, Chris
2008-10-01
By integrating systematic peptidome and transcriptome studies of the defensive skin secretion of the Central American red-eyed leaf frog, Agalychnis callidryas, we have identified novel members of three previously described antimicrobial peptide families, a 27-mer dermaseptin-related peptide (designated DRP-AC4), a 33-mer adenoregulin-related peptide (designated ARP-AC1) and most unusually, a 27-mer caerin-related peptide (designated CRP-AC1). While dermaseptin and adenoregulin were originally isolated from phyllomedusine leaf frogs, the caerins, until now, had only been described in Australian frogs of the genus, Litoria. Both the dermaseptin and adenoregulin were C-terminally amidated and lacked the C-terminal tripeptide of the biosynthetic precursor sequence. In contrast, the caerin-related peptide, unlike the majority of Litoria analogs, was not C-terminally amidated. The present data emphasize the need for structural characterization of mature peptides to ensure that unexpected precursor cleavages and/or post-translational modifications do not produce mature peptides that differ in structure to those predicted from cloned biosynthetic precursor cDNA. Additionally, systematic study of the secretory peptidome can produce unexpected results such as the CRP described here that may have phylogenetic implications. It is thus of the utmost importance in the functional evaluation of novel peptides that the primary structure of the mature peptide is unequivocally established -- something that is often facilitated by cloning biosynthetic precursor cDNAs but obviously not reliable using such data alone.
Smelov, Vitaly; Thomas, Pierre; Ouburg, Sander; Morré, Servaas A
2017-09-29
A reliable overview of data on the prevalence of Chlamydia trachomatis (CT) in Russia is lacking and needed. All the available data on CT prevalence were analyzed in a systematic literature review on CT prevalence in Russia, strengthened with data from the multicenter study among 1263 people in the second-largest Russian megalopolis, St. Petersburg, testing for CT DNA in urethral, anal, cervical and prostate samples. A total of 10 articles met the inclusion criteria. The overall average prevalence of genital CT infections in Russian populations ranged from 2.9% to 33%. Risk factors included being symptomatic (P = 0.004; in men P < 0.001), being younger than 30 years (P = 0.001) and being a man who has sex with men (MSM) (P = 0.0084). Main limitations included the lack of studies in MSM. CT prevalence was higher in the groups where urethral and prostate secretion samples were pooled (5.2%-7.3% vs 3.2% in the urethra only). The data on CT prevalence in a range of Russian populations are analyzed and reported. Prostate secretions represent an additional sampling material for the study of CT infection in men. CT detection in some settings in St. Petersburg yielded levels of reliability comparable with internationally available tests. The initiation of screening programs for Chlamydia infections in Russia should be considered. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Imparato, Beatriz A; Antoniazzi, Marta M; Rodrigues, Miguel T; Jared, Carlos
2007-07-01
Many lizards have epidermal glands in the cloacal or femoral region with semiochemical function related to sexual behavior and/or territorial demarcation. Externally, these glands are recognized as a row of pores, opening individually in the center of a modified scale. In many species the pores are used as systematic characters. They form a glandular cord or, in some species, a row of glandular beads below the dermis, and are connected to the exterior through the ducts, which continuously liberate a solid secretion. Dead cells, desquamated from the secretory epithelium, constitute the secretion, known as "a secretion plug." The present work focuses on the morphology of the femoral glands of the teiid lizard Ameiva ameiva, correlating it to the way in which the secretion is deposited in the environment. The results here obtained are compared to those available for other lizards and amphisbaenians. We observed that the diameter of the glandular pores did not show significant differences between males and females. The glands comprise germinative and secretory cells, which pass through at least three stages of differentiation, during which an accumulation of cytoplasmic granules, with a glycoprotein content, occurs. The cells eventually die and desquamate from the secretory epithelium, forming a secretory plug mostly constituted by juxtaposed nonfragmented secretory cells. Because of the arrangement of the rosette-like scales surrounding the femoral pores, we suggest that when the animal is in a resting position, with its femoral regions touching the ground, these scales may be involved in the breakage of their respective plugs, depositing tiny portions on the substrate. In this manner, it seems that the method for signal dispersion in this species involves specifically adapted structures and does not simply involve the chance breakage of the plug, as the gland secretes it. Signal dispersion must also be intimately associated with the animal's movement within its territory.
Links between early child maltreatment, mental disorders, and cortisol secretion anomalies.
Bronsard, Guillaume; Auquier, Pascal; Boyer, Laurent
2016-11-01
Early child maltreatment has been widely associated with the development of mental disorders in both childhood and adulthood. However, such association cannot be systematically established, as only few factors are observed regularly, such as high prevalence of comorbidities and externalized disorders. Similarly, the association between early abuse and cortisol secretion anomalies has been well-documented. Whereas early hypercortisolism followed by hypocortisolism was often described, the results proved inconsistent and at times contradictory. The physiopathological mechanisms are quite complex and varied, including mixed neurotoxicity and stress response anomalies, linked to circadian rhythm disturbances. One of the difficulties inherent to research on this topic is to better define maltreatment in childhood. Studying children's groups at risk of maltreatment, such as children followed by juvenile justice or in child welfare systems, could be a very good tool, provided that social, judiciary, and mental health professionals are able to work together and implement common research objectives. Copyright © 2017 Elsevier Ltd. All rights reserved.
Bledsoe, Bryan E
2015-02-01
The evidence is quite clear that ITH in the prehospital setting is of dubious benefit. But what is the harm in continuing the practice? Well, prehospital ITH most likely takes away from more beneficial therapies such as high-quality CPR, rapid defibrillation, recognition of ST-segment elevation myocardial infarction (STEMI), and similar essential treatments. Several studies have shown prehospital ITH, in many cases, delays hospital transport. When the initial studies of ITH were released, I was immediately on the ITH bandwagon. Interestingly, the American Heart Association (AHA) has never recommended prehospital ITH. Even the position paper on ITH by the National Association of EMS Physicians (NAEMSP) was cautious, saying, "A lack of evidence on induced hypothermia in the prehospital setting currently precludes recommending this treatment modality as standard of care for all emergency medical services (EMS) patients resuscitated from cardiac arrest. A systematic review of ITH recently published states, "In cardiac arrest, the initiation of therapeutic hypothermia in the out-of-hospital environment has not been shown to improve neurologic outcomes, although studies to date have been limited. We now know that caution Fxercised by the AHA and preMSP was appropriate. One medmy mentors in residency and ays said, "Never be the first- Univtor to prescribe a new drug or of Mlast doctor to prescribe an old is th" Lik" many things in EMS, EMS tms something that was put in Practe with good intent but lim- scientific evidence. We now P ITH is probably not a good ice and it is time to abandon it. However, we should still carry chilled IV fluids for hyperthermia, excited delirium and to main- tainormothermia in patients in cardiac arrest where transport times are long.
Ingicco, Thomas; Balzeau, Antoine; Callou, Cécile; Fitriana, Yuliana Sulistya
2011-10-01
The debate over the taxonomic position and affinities of Trachypithecus auratus has been ongoing since its identification by E. Geoffroy Saint-Hilaire in 1812. The type specimen of this species is housed in Muséum national d'Histoire naturelle in Paris (MNHN-ZM 2005-912). This point is debated due to the complex and fluctuating taxonomy of Southeast Asian Colobinae (Brandon-Jones et al.: Int J Primatol 25 (2004) 97-164) and to the fact that this individual is represented by a mounted skeleton. By means of 3D medical imaging methodologies we describe for the first time the cranial anatomy of the specimen MNHN-ZM 2005-912 and compare it with other Trachypithecus species, in order to test the molecular systematic hypotheses for affinities among the T. auratus-T. cristatus group. We ascertain the taxonomic attribution of this individual to the species Trachypithecus auratus species. The most diagnostic characters shared by the type specimen and Trachypithecus auratus compared to other species of Trachypithecus are the rounded orbits and the straight facial profile. We then try to clarify the inconsistencies concerning the geographical provenance of the type. The island of Java appears to be the most probable locality from a cluster analysis based on linear morphometry. After this approach and a discriminant analysis, a northeastern Javanese provenance of this specimen, as proposed by Brandon-Jones et al. (Int J Primatol 25 (2004) 97-164) is dubious. Finally we provide 3D models of the skull and the endocast, and a list of cranial landmark coordinates of the holotype for future research. Copyright © 2011 Wiley-Liss, Inc.
Fake news portrayals of stem cells and stem cell research.
Marcon, Alessandro R; Murdoch, Blake; Caulfield, Timothy
2017-10-01
This study examines how stem cells and stem cell research are portrayed on websites deemed to be purveyors of distorted and dubious information. Content analysis was conducted on 224 articles from 2015 to 2016, compiled by searching with the keywords 'stem cell(s)' on a list of websites flagged for containing either 'fake' or 'junk science' news. Articles contained various exaggerated positive and negative claims about stem cells and stem cell science, health and science related conspiracy theories, and statements promoting fear and mistrust of conventional medicine. Findings demonstrate the existence of organized misinformation networks, which may lead the public away from accurate information and facilitate a polarization of public discourse.
The Hong Kong/AAO/Strasbourg Hα (HASH) Planetary Nebula Database
NASA Astrophysics Data System (ADS)
Bojičić, Ivan S.; Parker, Quentin A.; Frew, David J.
2017-10-01
The Hong Kong/AAO/Strasbourg Hα (HASH) planetary nebula database is an online research platform providing free and easy access to the largest and most comprehensive catalogue of known Galactic PNe and a repository of observational data (imaging and spectroscopy) for these and related astronomical objects. The main motivation for creating this system is resolving some of long standing problems in the field e.g. problems with mimics and dubious and/or misidentifications, errors in observational data and consolidation of the widely scattered data-sets. This facility allows researchers quick and easy access to the archived and new observational data and creating and sharing of non-redundant PN samples and catalogues.
Rounded atelectasis of the lung: A pictorial review
Sobocińska, Magdalena; Sobociński, Bartosz; Jarzemska, Agnieszka; Serafin, Zbigniew
2014-01-01
Summary Rounded atelectasis of the lung is well described in medical literature, but still difficult to diagnose. Since lesions give no clinical symptoms in patients, radiologists are often the first to recognize the round lesion in an X-ray picture or a CT scan. Rounded atelectasis is an atypical form of lung collapse that usually occurs adjacent to scarred pleura and can be mistaken for lung cancer. Patients with rounded atelectasis have a history of asbestos exposure or pleural effusion due to various causes. When characteristic imaging findings are present, the diagnosis is rarely dubious and no further investigation is necessary. However, differential diagnosis of rounded atelectasis poses a challenge to pulmonary specialists and radiologists. PMID:25045412
Editor’s message: Groundwater modeling fantasies - Part 2, down to earth
Voss, Clifford I.
2011-01-01
Simplicity is the final achievement. After one has played a vast quantity of notes and more notes, it is simplicity that emerges as the crowning reward of art. (Frédéric Chopin, a musician and composer, quoted in If Not God, Then What? by Fost 2007)Despite the dubious developments discussed in part 1 of this Editor’s Message (Voss 2011), groundwater modeling really does represent the state of the art in hydrogeology, and groundwater modeling is in fact one of our most powerful tools for enhancing hydrogeologic understanding and for informing management of subsurface resources, at least when in the hands of competent hydrologists.
The use of total simulator training in transitioning air-carrier pilots: A field evaluation
NASA Technical Reports Server (NTRS)
Randle, R. J., Jr.; Tanner, T. A.; Hamerman, J. A.; Showalter, T. H.
1981-01-01
A field study was conducted in which the performance of air carrier transitioning pilots who had landing training in a landing maneuver approved simulator was compared with the performance of pilots who had landing training in the aircraft. Forty-eight trainees transitioning to the B-727 aircraft and eighty-seven trainees transitioning to the DC-10 were included in the study. The study results in terms of both objectively measured performance indicants and observer and check-pilot ratings did not demonstrate a clear distinction between the two training groups. The results suggest that, for these highly skilled transitioning pilots, a separate training module in the aircraft may be of dubious value.
STS-32 Columbia, OV-102, liftoff from KSC LC Pad 39A is reflected in waterway
1990-01-09
STS032-S-069 (9 Jan. 1990) --- The space shuttle Columbia, with a five member crew aboard, lifts off for the ninth time as STS-32 begins a 10-day mission in Earth orbit. Leaving from Launch Pad 39A at 7:34:59:98 a.m. EST, in this horizontal (cropped 70mm) frame, Columbia is seen reflected in nearby marsh waters some 24 hours after dubious weather at the return-to-launch site (RTLS) had cancelled a scheduled launch. Onboard the spacecraft were astronauts Daniel C. Brandenstein, James D. Wetherbee, Bonnie J. Dunbar, G. David Low and Marsha S. Ivins. Photo credit: NASA
Holtz-Eakin, Douglas; Ramlet, Michael J
2010-06-01
The federal government faces a daunting fiscal outlook, which makes the budgetary impact of the Patient Protection and Affordable Care Act even more important. The official Congressional Budget Office (CBO) analysis indicates modest deficit reduction over the next ten years and beyond. We examine the underpinnings of the CBO's projection and conclude that it is built on a shaky foundation of omitted costs, premiums shifted from other entitlements, and politically dubious spending cuts and revenue increases. A more comprehensive and realistic projection suggests that the new reform law will raise the deficit by more than $500 billion during the first ten years and by nearly $1.5 trillion in the following decade.
Targets to treat androgen excess in polycystic ovary syndrome.
Luque-Ramírez, Manuel; Escobar-Morreale, Héctor Francisco
2015-01-01
The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects.
Moodley, Yoshan; Uhr, Markus; Stamer, Christiana; Vauterin, Marc; Suerbaum, Sebastian; Achtman, Mark
2010-01-01
The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI–carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown. PMID:20808891
Characterization and Comprehensive Proteome Profiling of Exosomes Secreted by Hepatocytes
Conde-Vancells, Javier; Rodriguez-Suarez, Eva; Embade, Nieves; Gil, David; Matthiesen, Rune; Valle, Mikel; Elortza, Felix; Lu, Shelly C.; Mato, Jose M.; Falcon-Perez, Juan M.
2009-01-01
Synopsis Exosomes constitute a discrete population of nanometer-sized (30-150 nm) vesicles formed in endocytic compartments and released to the extracellular environment by different cell types. In this work we demonstrated by electron microscopic, western blotting and proteomic analyses that primary hepatocytes secrete exosome-like vesicles containing proteins involved in metabolizing lipoproteins, endogenous compounds as well as xenobiotics. These new findings contribute to improve our knowledge about biology's hepatocyte and may have important diagnostic, prognosis and therapeutic implications in liver diseases Exosomes represent a discrete population of vesicles that are secreted from various cell types to the extracellular media. Their protein and lipid composition are a consequence of sorting events at the level of the multivesicular body, a central organelle which integrates endocytic and secretory pathways. Characterization of exosomes from different biological samples has shown the presence of common as well as cell-type specific proteins. Remarkably, the protein content of the exosomes is modified upon pathological or stress conditions. Hepatocytes play a central role in the body response to stress metabolizing potentially harmful endogenous substances as well as xenobiotics. In the present study we described and characterized for first time exosome secretion in non-tumoral hepatocytes, and using a systematic proteomic approach, we establish the first extensive proteome of a hepatocyte-derived exosome population which should be useful in furthering our understanding of the hepatic function and in the identification of components that may serve as biomarkers for hepatic alterations. Our analysis identifies a significant number of proteins previously described among exosomes derived from others cell types as well as proteins involved in metabolizing lipoproteins, endogenous compounds and xenobiotics, not previously described in exosomes. Furthermore, we demonstrated that exosomal membrane proteins can constitute an interesting tool to express non-exosomal proteins into exosomes with therapeutic purposes. PMID:19367702
Olbermann, Patrick; Josenhans, Christine; Moodley, Yoshan; Uhr, Markus; Stamer, Christiana; Vauterin, Marc; Suerbaum, Sebastian; Achtman, Mark; Linz, Bodo
2010-08-19
The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI-carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown.
Briceno, Vanessa; Zaidi, Hasan A; Doucette, Joanne A; Onomichi, Kaho B; Alreshidi, Amer; Mekary, Rania A; Smith, Timothy R
2017-05-01
Growth hormone-secreting pituitary adenomas in adults can result in severe craniofacial disfigurement and potentially fatal medical complications. Surgical resection leading to remission of the disease is dependent on complete surgical resection of the tumor. Lesions that invade the cavernous sinus may not be safely accessible via an endonasal transsphenoidal surgery (TSS), and the rates of biochemical remission of patients with residual disease vary widely in the literature. We conducted a meta-analysis to examine the prevalence of biochemical remission after TSS among patients with growth hormone-secreting pituitary adenomas with and without cavernous sinus invasion. Embase, PubMed, and Cochrane Library databases were searched for relevant publications. Fourteen studies with 972 patients with biochemically confirmed growth hormone-secreting pituitary adenomas were included in the meta-analysis. The overall remission prevalence under a fixed-effect model was 47.6% (95% CI = 40.8-54.4%) for patients with invasive macroadenomas (I 2 = 74.6%, p < 0.01); 76.4% (95% CI = 72.2-80.1%) for patients with non-invasive macroadenomas (I 2 = 59.6%, p = 0.03); and 74.2% (95% CI = 66.3-80.7%) for patients with non-invasive microadenomas (I 2 = 36.4, p = 0.10). The significant difference among the three groups resulted from the difference between patients with or without cavernous sinus invasion (p = 0.01) and not from the size of adenomas among those without cavernous sinus invasion (p = 0.66). The prevalence of biochemical remission in patients with cavernous sinus invasion was lower than in patients without cavernous sinus invasion after TSS for acromegaly.
Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo
Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.
2016-01-01
Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433
Lallemand, Mathilde; Login, Frédéric H; Guschinskaya, Natalia; Pineau, Camille; Effantin, Géraldine; Robert, Xavier; Shevchik, Vladimir E
2013-01-01
The type II secretion system (T2SS) is a multiprotein nanomachine that transports folded proteins across the outer membrane of gram-negative bacteria. The molecular mechanisms that govern the secretion process remain poorly understood. The inner membrane components GspC, GspL and GspM possess a single transmembrane segment (TMS) and a large periplasmic region and they are thought to form a platform of unknown function. Here, using two-hybrid and pull-down assays we performed a systematic mapping of the GspC/GspL/GspM interaction regions in the plant pathogen Dickeya dadantii. We found that the TMS of these components interact with each other, implying a complex interaction network within the inner membrane. We also showed that the periplasmic, ferredoxin-like, domains of GspL and GspM drive homo- and heterodimerizations of these proteins. Disulfide bonding analyses revealed that the respective domain interfaces include the equivalent secondary-structure elements, suggesting alternating interactions of the periplasmic domains, L/L and M/M versus L/M. Finally, we found that displacements of the periplasmic GspM domain mediate coordinated shifts or rotations of the cognate TMS. These data suggest a plausible mechanism for signal transmission between the periplasmic and the cytoplasmic portions of the T2SS machine.
Guschinskaya, Natalia; Pineau, Camille; Effantin, Géraldine; Robert, Xavier; Shevchik, Vladimir E.
2013-01-01
The type II secretion system (T2SS) is a multiprotein nanomachine that transports folded proteins across the outer membrane of gram-negative bacteria. The molecular mechanisms that govern the secretion process remain poorly understood. The inner membrane components GspC, GspL and GspM possess a single transmembrane segment (TMS) and a large periplasmic region and they are thought to form a platform of unknown function. Here, using two-hybrid and pull-down assays we performed a systematic mapping of the GspC/GspL/GspM interaction regions in the plant pathogen Dickeya dadantii. We found that the TMS of these components interact with each other, implying a complex interaction network within the inner membrane. We also showed that the periplasmic, ferredoxin-like, domains of GspL and GspM drive homo- and heterodimerizations of these proteins. Disulfide bonding analyses revealed that the respective domain interfaces include the equivalent secondary-structure elements, suggesting alternating interactions of the periplasmic domains, L/L and M/M versus L/M. Finally, we found that displacements of the periplasmic GspM domain mediate coordinated shifts or rotations of the cognate TMS. These data suggest a plausible mechanism for signal transmission between the periplasmic and the cytoplasmic portions of the T2SS machine. PMID:24223969
Lakowitz, Antonia; Godard, Thibault; Biedendieck, Rebekka; Krull, Rainer
2018-05-01
Bio-pharmaceuticals like antibodies, hormones and growth factors represent about one-fifth of commercial pharmaceuticals. Host candidates of growing interest for recombinant production of these proteins are strains of the genus Bacillus, long being established for biotechnological production of homologous and heterologous proteins. Bacillus strains benefit from development of efficient expression systems in the last decades and emerge as major industrial workhorses for recombinant proteins due to easy cultivation, non-pathogenicity and their ability to secrete recombinant proteins directly into extracellular medium allowing cost-effective downstream processing. Their broad product portfolio of pharmaceutically relevant recombinant proteins described in research include antibody fragments, growth factors, interferons and interleukins, insulin, penicillin G acylase, streptavidin and different kinases produced in various cultivation systems like microtiter plates, shake flasks and bioreactor systems in batch, fed-batch and continuous mode. To further improve production and secretion performance of Bacillus, bottlenecks and limiting factors concerning proteases, chaperones, secretion machinery or feedback mechanisms can be identified on different cell levels from genomics and transcriptomics via proteomics to metabolomics and fluxomics. For systematical identification of recurring patterns characteristic of given regulatory systems and key genetic targets, systems biology and omics-technology provide suitable and promising approaches, pushing Bacillus further towards industrial application for recombinant pharmaceutical protein production. Copyright © 2017. Published by Elsevier B.V.
Complementary and Alternative Medicine for Management of Premature Ejaculation: A Systematic Review.
Cooper, Katy; Martyn-St James, Marrissa; Kaltenthaler, Eva; Dickinson, Kath; Cantrell, Anna; Ren, Shijie; Wylie, Kevan; Frodsham, Leila; Hood, Catherine
2017-03-01
Premature ejaculation (PE) is defined as ejaculation within 1 minute (lifelong PE) or 3 minutes (acquired PE), inability to delay ejaculation, and negative personal consequences. Management includes behavioral and pharmacologic approaches. To systematically review effectiveness, safety, and robustness of evidence for complementary and alternative medicine in managing PE. Nine databases including Medline were searched through September 2015. Randomized controlled trials evaluating complementary and alternative medicine for PE were included. Studies were included if they reported on intravaginal ejaculatory latency time (IELT) and/or another validated PE measurement. Adverse effects were summarized. Ten randomized controlled trials were included. Two assessed acupuncture, five assessed Chinese herbal medicine, one assessed Ayurvedic herbal medicine, and two assessed topical "severance secret" cream. Risk of bias was unclear in all studies because of unclear allocation concealment or blinding, and only five studies reported stopwatch-measured IELT. Acupuncture slightly increased IELT over placebo in one study (mean difference [MD] = 0.55 minute, P = .001). In another study, Ayurvedic herbal medicine slightly increased IELT over placebo (MD = 0.80 minute, P = .001). Topical severance secret cream increased IELT over placebo in two studies (MD = 8.60 minutes, P < .001), although inclusion criteria were broad (IELT < 3 minutes). Three studies comparing Chinese herbal medicine with selective serotonin reuptake inhibitors (SSRIs) favored SSRIs (MD = 1.01 minutes, P = .02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies; MD = 1.92 minutes, P < .00001) and over Chinese medicine alone (two studies; MD = 2.52 minutes, P < .00001). Adverse effects were not consistently assessed but where reported were generally mild. There is preliminary evidence for the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical severance secret cream in improving IELT and other outcomes. However, results are based on clinically heterogeneous studies of unclear quality. There are sparse data on adverse effects or potential for drug interactions. Further well-conducted randomized controlled trials would be valuable. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
T3SEdb: data warehousing of virulence effectors secreted by the bacterial Type III Secretion System.
Tay, Daniel Ming Ming; Govindarajan, Kunde Ramamoorthy; Khan, Asif M; Ong, Terenze Yao Rui; Samad, Hanif M; Soh, Wei Wei; Tong, Minyan; Zhang, Fan; Tan, Tin Wee
2010-10-15
Effectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and therefore the identification of these effectors is important in understanding virulence. However, the effectors display high level of sequence diversity, therefore making the identification a difficult process. There is a need to collate and annotate existing effector sequences in public databases to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes that can be validated by a smaller number of key experiments. Herein, we present T3SEdb http://effectors.bic.nus.edu.sg/T3SEdb, a specialized database of annotated T3SS effector (T3SE) sequences containing 1089 records from 46 bacterial species compiled from the literature and public protein databases. Procedures have been defined for i) comprehensive annotation of experimental status of effectors, ii) submission and curation review of records by users of the database, and iii) the regular update of T3SEdb existing and new records. Keyword fielded and sequence searches (BLAST, regular expression) are supported for both experimentally verified and hypothetical T3SEs. More than 171 clusters of T3SEs were detected based on sequence identity comparisons (intra-cluster difference up to ~60%). Owing to this high level of sequence diversity of T3SEs, the T3SEdb provides a large number of experimentally known effector sequences with wide species representation for creation of effector predictors. We created a reliable effector prediction tool, integrated into the database, to demonstrate the application of the database for such endeavours. T3SEdb is the first specialised database reported for T3SS effectors, enriched with manual annotations that facilitated systematic construction of a reliable prediction model for identification of novel effectors. The T3SEdb represents a platform for inclusion of additional annotations of metadata for future developments of sophisticated effector prediction models for screening and selection of putative novel effectors from bacterial genomes/proteomes that can be validated by a small number of key experiments.
Kolb, Hildegard; Snowden, Austyn; Stevens, Elaine
2018-03-01
To identify effective treatments and risk factors associated with death rattle in adults at the end of life. The presence of noisy, pooled respiratory tract secretions is among the most common symptoms in dying patients around the world. It is unknown if "death rattle" distresses patients, but it can distress relatives and clinicians. Treatments appear unsatisfactory, so prophylaxis would be ideal if possible. Quantitative systematic review and narrative summary following Cochrane Collaboration guidelines. CINAHL, MEDLINE, Health Source Nursing and Web of Science were searched for international literature in any language published from 1993 - 2016 using MeSH headings and iterative interchangeable terms for "death rattle". Randomized controlled trials were appraised using the Cochrane Collaboration's tool for assessing risk of bias. Non-randomized studies were assessed using ROBINS-I tool for assessing risk of bias in non-randomized studies of interventions. Instances of treatment and risk were extracted and relevant key findings extracted in line with Cochrane methods. Five randomized trials and 23 non-randomized studies were analysed. No pharmacological or non-pharmacological treatment was found superior to placebo. There was a weak association between lung or brain metastases and presence of death rattle, but otherwise inconsistent empirical support for a range of potential risk factors. Clinicians have no clear evidence to follow in either treating death rattle or preventing it occurring. However, several risk factors look promising candidates for prospective analysis, so this review concludes with clear recommendations for further research. © 2018 John Wiley & Sons Ltd.
Barczak, Amy K; Avraham, Roi; Singh, Shantanu; Luo, Samantha S; Zhang, Wei Ran; Bray, Mark-Anthony; Hinman, Amelia E; Thompson, Matthew; Nietupski, Raymond M; Golas, Aaron; Montgomery, Paul; Fitzgerald, Michael; Smith, Roger S; White, Dylan W; Tischler, Anna D; Carpenter, Anne E; Hung, Deborah T
2017-05-01
A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is the capacity to survive within host macrophages. Although several factors required for this survival have been identified, a comprehensive knowledge of such factors and how they work together to manipulate the host environment to benefit bacterial survival are not well understood. To systematically identify Mtb factors required for intracellular growth, we screened an arrayed, non-redundant Mtb transposon mutant library by high-content imaging to characterize the mutant-macrophage interaction. Based on a combination of imaging features, we identified mutants impaired for intracellular survival. We then characterized the phenotype of infection with each mutant by profiling the induced macrophage cytokine response. Taking a systems-level approach to understanding the biology of identified mutants, we performed a multiparametric analysis combining pathogen and host phenotypes to predict functional relationships between mutants based on clustering. Strikingly, mutants defective in two well-known virulence factors, the ESX-1 protein secretion system and the virulence lipid phthiocerol dimycocerosate (PDIM), clustered together. Building upon the shared phenotype of loss of the macrophage type I interferon (IFN) response to infection, we found that PDIM production and export are required for coordinated secretion of ESX-1-substrates, for phagosomal permeabilization, and for downstream induction of the type I IFN response. Multiparametric clustering also identified two novel genes that are required for PDIM production and induction of the type I IFN response. Thus, multiparametric analysis combining host and pathogen infection phenotypes can be used to identify novel functional relationships between genes that play a role in infection.
Emerging spectra of singular correlation matrices under small power-map deformations
NASA Astrophysics Data System (ADS)
Vinayak; Schäfer, Rudi; Seligman, Thomas H.
2013-09-01
Correlation matrices are a standard tool in the analysis of the time evolution of complex systems in general and financial markets in particular. Yet most analysis assume stationarity of the underlying time series. This tends to be an assumption of varying and often dubious validity. The validity of the assumption improves as shorter time series are used. If many time series are used, this implies an analysis of highly singular correlation matrices. We attack this problem by using the so-called power map, which was introduced to reduce noise. Its nonlinearity breaks the degeneracy of the zero eigenvalues and we analyze the sensitivity of the so-emerging spectra to correlations. This sensitivity will be demonstrated for uncorrelated and correlated Wishart ensembles.
What Instills Trust? A Qualitative Study of Phishing
NASA Astrophysics Data System (ADS)
Jakobsson, Markus; Tsow, Alex; Shah, Ankur; Blevis, Eli; Lim, Youn-Kyung
This paper reports the highlights of a user study which gauges reactions to a variety of common "trust indicators" - such as logos, third party endorsements, and padlock icons - over a selection of authentic and phishing stimuli. In the course of the think-aloud protocol, participants revealed different sensitivities to email messages and web pages. Our principal result is the analysis of what makes phishing emails and web pages appear authentic. This is not only of interest from a pure scientific point of view, but can also guide the design of legitimate material to avoid unnecessary risks. A second result of ours are observations of what makes legitimate content appear dubious to consumers. This is a result with obvious applications to online advertising.
Emerging spectra of singular correlation matrices under small power-map deformations.
Vinayak; Schäfer, Rudi; Seligman, Thomas H
2013-09-01
Correlation matrices are a standard tool in the analysis of the time evolution of complex systems in general and financial markets in particular. Yet most analysis assume stationarity of the underlying time series. This tends to be an assumption of varying and often dubious validity. The validity of the assumption improves as shorter time series are used. If many time series are used, this implies an analysis of highly singular correlation matrices. We attack this problem by using the so-called power map, which was introduced to reduce noise. Its nonlinearity breaks the degeneracy of the zero eigenvalues and we analyze the sensitivity of the so-emerging spectra to correlations. This sensitivity will be demonstrated for uncorrelated and correlated Wishart ensembles.
Majchrowicz, M
1995-05-01
The kombucha (or Manchurian) mushroom has numerous claims of "significant" health improvements, yet there is no research or any basic evidence to back up the claims. According to folklore, the kombucha is a super immune booster that can fight many ailments, including AIDS, cancer, arthritis, constipation, and more. However, there is concern about the safety of kombucha, which is not really a mushroom but a yeast culture. Since the culture must grow at room temperature for seven to ten days, contamination and growth of other organisms can take place. The tea's original ingredients include caffeine and large amounts of sugar. These may account for the increased energy some individuals have claimed. Some stories state miraculous results. Other accounts mention no improvement in general well-being.
Improving Public Perception of Behavior Analysis.
Freedman, David H
2016-05-01
The potential impact of behavior analysis is limited by the public's dim awareness of the field. The mass media rarely cover behavior analysis, other than to echo inaccurate negative stereotypes about control and punishment. The media instead play up appealing but less-evidence-based approaches to problems, a key example being the touting of dubious diets over behavioral approaches to losing excess weight. These sorts of claims distort or skirt scientific evidence, undercutting the fidelity of behavior analysis to scientific rigor. Strategies for better connecting behavior analysis with the public might include reframing the field's techniques and principles in friendlier, more resonant form; pushing direct outcome comparisons between behavior analysis and its rivals in simple terms; and playing up the "warm and fuzzy" side of behavior analysis.
Reflections on the self state dream.
Slap, J W; Trunnell, E E
1987-04-01
Self psychologists contend that patients with narcissistic personality disorders have dreams which cannot be understood in terms of current psychoanalytic dream theory and that these dreams, called self state dreams, have a different origin and structure. The manifest content of these dreams is said to reveal the reactions of healthy sectors of the psyche to disturbing changes in the condition of the self. Self psychologists are said to be able to understand these dreams directly, without the patients' associations, as portrayals of the dreamers' dread of threats to the integrity of the self. The authors raise questions about these contentions. They conclude that the self state dream will remain a dubious concept until a more extensive psychology of dreaming is provided by self psychologists.
STS-32 crewmembers wave as they leave KSC O&C Bldg for launch pad
1990-01-09
STS032-S-056 (20 Jan 1990) --- STS-32 Columbia, Orbiter Vehicle (OV) 102, crewmembers depart the Kennedy Space Center (KSC) Operations and Checkout (O and C) Building enroute to KSC Launch Complex (LC) Pad 39A. Dubious weather at the return-to-launch site (RTLS) caused postponement of yesterday's planned launch. From left to right are Mission Specialist (MS) G. David Low, MS Marsha S. Ivins, MS Bonnie J. Dunbar, Pilot James D. Wetherbee, and Commander Daniel C. Brandenstein. All crewmembers are wearing launch and entry suits (LESs) and Low, Ivins, and Wetherbee wave to spectators as they head to the transportation van. Following the crew are astronaut Michael L. Coats (left) and NASA/JSC manager Donald R. Puddy.
Medical management of frailty: confessions of a gnostic.
Rockwood, K
1997-10-15
Geriatric Medicine is concerned chiefly with the care of frail elderly people, especially when they become ill. Physicians face special challenges in dealing with such patients, who tend to have multiple interacting medical and social problems, impaired function, altered pharmacokinetics and pharmacodynamics, atypical disease presentations and to be affected by polypharmacy. The joy of geriatrics is in systematically meeting each of these challenges, but the techniques that geriatricians use to do so must not be kept secret. More must be done to encourage all physicians to use these techniques in caring for frail elderly people who are ill.
Medical management of frailty: confessions of a gnostic
Rockwood, K
1997-01-01
Geriatric Medicine is concerned chiefly with the care of frail elderly people, especially when they become ill. Physicians face special challenges in dealing with such patients, who tend to have multiple interacting medical and social problems, impaired function, altered pharmacokinetics and pharmacodynamics, atypical disease presentations and to be affected by polypharmacy. The joy of geriatrics is in systematically meeting each of these challenges, but the techniques that geriatricians use to do so must not be kept secret. More must be done to encourage all physicians to use these techniques in caring for frail elderly people who are ill. PMID:9347779
Interorgan Communication Pathways in Physiology: Focus on Drosophila
Droujinine, Ilia A.; Perrimon, Norbert
2017-01-01
Studies in mammals and Drosophila have demonstrated the existence and significance of secreted factors involved in communication between distal organs. In this review, primarily focusing on Drosophila, we examine the known interorgan communication factors and their functions, physiological inducers, and integration in regulating physiology. Moreover, we describe how organ-sensing screens in Drosophila can systematically identify novel conserved interorgan communication factors. Finally, we discuss how interorgan communication enabled and evolved as a result of specialization of organs. Together, we anticipate that future studies will establish a model for metazoan interorgan communication network (ICN) and how it is deregulated in disease. PMID:27732790
Interorgan Communication Pathways in Physiology: Focus on Drosophila.
Droujinine, Ilia A; Perrimon, Norbert
2016-11-23
Studies in mammals and Drosophila have demonstrated the existence and significance of secreted factors involved in communication between distal organs. In this review, primarily focusing on Drosophila, we examine the known interorgan communication factors and their functions, physiological inducers, and integration in regulating physiology. Moreover, we describe how organ-sensing screens in Drosophila can systematically identify novel conserved interorgan communication factors. Finally, we discuss how interorgan communication enabled and evolved as a result of specialization of organs. Together, we anticipate that future studies will establish a model for metazoan interorgan communication network (ICN) and how it is deregulated in disease.
Proteomics of filamentous fungi.
Kim, Yonghyun; Nandakumar, M P; Marten, Mark R
2007-09-01
Proteomic analysis, defined here as the global assessment of cellular proteins expressed in a particular biological state, is a powerful tool that can provide a systematic understanding of events at the molecular level. Proteomic studies of filamentous fungi have only recently begun to appear in the literature, despite the prevalence of these organisms in the biotechnology industry, and their importance as both human and plant pathogens. Here, we review recent publications that have used a proteomic approach to develop a better understanding of filamentous fungi, highlighting sample preparation methods and whole-cell cytoplasmic proteomics, as well as subproteomics of cell envelope, mitochondrial and secreted proteins.
A Bacillus megaterium System for the Production of Recombinant Proteins and Protein Complexes.
Biedendieck, Rebekka
2016-01-01
For many years the Gram-positive bacterium Bacillus megaterium has been used for the production and secretion of recombinant proteins. For this purpose it was systematically optimized. Plasmids with different inducible promoter systems, with different compatible origins, with small tags for protein purification and with various specific signals for protein secretion were combined with genetically improved host strains. Finally, the development of appropriate cultivation conditions for the production strains established this organism as a bacterial cell factory even for large proteins. Along with the overproduction of individual proteins the organism is now also used for the simultaneous coproduction of up to 14 recombinant proteins, multiple subsequently interacting or forming protein complexes. Some of these recombinant strains are successfully used for bioconversion or the biosynthesis of valuable components including vitamins. The titers in the g per liter scale for the intra- and extracellular recombinant protein production prove the high potential of B. megaterium for industrial applications. It is currently further enhanced for the production of recombinant proteins and multi-subunit protein complexes using directed genetic engineering approaches based on transcriptome, proteome, metabolome and fluxome data.
Zhou, Bo O; Ding, Lei; Morrison, Sean J
2015-01-01
Hematopoietic stem cells (HSCs) are maintained by a perivascular niche in bone marrow but it is unclear whether the niche is reciprocally regulated by HSCs. Here, we systematically assessed the expression and function of Angiopoietin-1 (Angpt1) in bone marrow. Angpt1 was not expressed by osteoblasts. Angpt1 was most highly expressed by HSCs, and at lower levels by c-kit+ hematopoietic progenitors, megakaryocytes, and Leptin Receptor+ (LepR+) stromal cells. Global conditional deletion of Angpt1, or deletion from osteoblasts, LepR+ cells, Nes-cre-expressing cells, megakaryocytes, endothelial cells or hematopoietic cells in normal mice did not affect hematopoiesis, HSC maintenance, or HSC quiescence. Deletion of Angpt1 from hematopoietic cells and LepR+ cells had little effect on vasculature or HSC frequency under steady-state conditions but accelerated vascular and hematopoietic recovery after irradiation while increasing vascular leakiness. Hematopoietic stem/progenitor cells and LepR+ stromal cells regulate niche regeneration by secreting Angpt1, reducing vascular leakiness but slowing niche recovery. DOI: http://dx.doi.org/10.7554/eLife.05521.001 PMID:25821987
Identification of two integration sites in favor of transgene expression in Trichoderma reesei.
Qin, Lina; Jiang, Xianzhang; Dong, Zhiyang; Huang, Jianzhong; Chen, Xiuzhen
2018-01-01
The ascomycete fungus Trichoderma reesei was widely used as a biotechnological workhorse for production of cellulases and recombinant proteins due to its large capacity of protein secretion. Transgenesis by random integration of a gene of interest (GOI) into the genome of T. reesei can generate series of strains that express different levels of the indicated transgene. The insertion site of the GOI plays an important role in the ultimate production of the targeted proteins. However, so far no systematic studies have been made to identify transgene integration loci for optimal expression of the GOI in T. reesei . Currently, only the locus of exocellobiohydrolases I encoding gene ( cbh1) is widely used as a promising integration site to lead to high expression level of the GOI. No additional sites associated with efficient gene expression have been characterized. To search for gene integration sites that benefit for the secreted expression of GOI, the food-and-mouth disease virus 2A protein was applied for co-expression of an Aspergillus niger lipA gene and Discosoma sp. DsRed1 gene in T. reesei, by random integration of the expression cassette into the genome. We demonstrated that the fluorescent intensity of RFP (red fluorescent protein) inside of the cell was well correlated with the secreted lipase yields, based on which, we successfully developed a high-throughput screening method to screen strains with relatively higher secreted expression of the GOI (in this study, lipase). The copy number and the insertion sites of the transgene were investigated among the selected highly expressed strains. Eventually, in addition to cbh1 gene locus, two other genome insertion loci that efficiently facilitate gene expression in T. reesei were identified. We have successfully developed a high-throughput screening method to screen strains with optimal expression of the indicated secreted proteins in T. reesei . Moreover, we identified two optimal genome loci for transgene expression, which could provide new approach to modulate gene expression levels while retaining the indicated promoter and culture conditions.
Skoczinski, Pia; Volkenborn, Kristina; Fulton, Alexander; Bhadauriya, Anuseema; Nutschel, Christina; Gohlke, Holger; Knapp, Andreas; Jaeger, Karl-Erich
2017-09-25
Bacillus subtilis produces and secretes proteins in amounts of up to 20 g/l under optimal conditions. However, protein production can be challenging if transcription and cotranslational secretion are negatively affected, or the target protein is degraded by extracellular proteases. This study aims at elucidating the influence of a target protein on its own production by a systematic mutational analysis of the homologous B. subtilis model protein lipase A (LipA). We have covered the full natural diversity of single amino acid substitutions at 155 positions of LipA by site saturation mutagenesis excluding only highly conserved residues and qualitatively and quantitatively screened about 30,000 clones for extracellular LipA production. Identified variants with beneficial effects on production were sequenced and analyzed regarding B. subtilis growth behavior, extracellular lipase activity and amount as well as changes in lipase transcript levels. In total, 26 LipA variants were identified showing an up to twofold increase in either amount or activity of extracellular lipase. These variants harbor single amino acid or codon substitutions that did not substantially affect B. subtilis growth. Subsequent exemplary combination of beneficial single amino acid substitutions revealed an additive effect solely at the level of extracellular lipase amount; however, lipase amount and activity could not be increased simultaneously. Single amino acid and codon substitutions can affect LipA secretion and production by B. subtilis. Several codon-related effects were observed that either enhance lipA transcription or promote a more efficient folding of LipA. Single amino acid substitutions could improve LipA production by increasing its secretion or stability in the culture supernatant. Our findings indicate that optimization of the expression system is not sufficient for efficient protein production in B. subtilis. The sequence of the target protein should also be considered as an optimization target for successful protein production. Our results further suggest that variants with improved properties might be identified much faster and easier if mutagenesis is prioritized towards elements that contribute to enzymatic activity or structural integrity.
Kipf, Elena; Koch, Julia; Geiger, Bettina; Erben, Johannes; Richter, Katrin; Gescher, Johannes; Zengerle, Roland; Kerzenmacher, Sven
2013-10-01
We present a systematic screening of carbon-based anode materials for microbial fuel cells with Shewanella oneidensis MR-1. Under anoxic conditions nanoporous activated carbon cloth is a superior anode material in terms of current density normalized to the projected anode area and anode volume (24.0±0.3 μA cm(-2) and 482±7 μA cm(-3) at -0.2 vs. SCE, respectively). The good performance can be attributed to the high specific surface area of the material, which is available for mediated electron transfer through self-secreted flavins. Under aerated conditions no influence of the specific surface area is observed, which we attribute to a shift from primary indirect electron transfer by mediators to direct electron transfer via adherent cells. Furthermore, we show that an aerated initial growth phase enhances the current density under subsequent anoxic conditions fivefold when compared to a similar experiment that was conducted under permanently anoxic conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.
[Use of stimulation techniques in pain treatment].
Rosted, Palle; Andersen, Claus
2006-05-15
Stimulation techniques (SB) include manipulation, acupuncture, acupressure, physiotherapy, transcutaneous electrical nerve stimulation, reflexotherapy, laser treatment and epidural stimulation technique. The purpose of this paper is to investigate the scientific evidence for these techniques. The Cochrane Library and Medline were searched for all techniques from 2000 to date. Only randomised controlled studies written in English were included. Search words were used, such as; acupuncture and neck pain, shoulder pain, etc. In total 587 papers were identified for the following diseases; headache, neck pain, shoulder pain, elbow pain, low back pain and knee pain. 415 papers were excluded, and the remaining 172 papers, a total of 20,431 patients, are the basis for this study. The effect of acupuncture and epidural stimulation technique is scientifically well-supported. For the remaining techniques, the scientific evidence is dubious.
Tierra, Tatiana De La
2004-01-01
Abstract The intensity of falling in love is expressed through sexual longing and is focused on pleasures of the body. Fresh fruits and vegetables and other elements of nature-wind, birds, foliage-form part of the setting of seduction. Being in love with another woman makes the entire world beautiful. But the lesbian paradise is eventually eclipsed by bitter realities that intrude upon the relationship-the ever-present ex-lover (still in the picture), family ties (with homophobic overtones), business connections (that imperil lesbian economic independence), and issues of commitment and honesty that eventually lead to betrayal and a bittersweet breakup. Based on correspondence originally written in Spanish, "Neurotic Love Letters" is a testament to an unfortunate fact-that all the love and lust between two women cannot always conquer dubious circumstances and harsh realities unique to lesbian relationships.
NASA Technical Reports Server (NTRS)
Kharecha, Pushker A.; Hansen, James
2013-01-01
Sovacool et al.'s analysis of our paper contains numerous errors, misinterpretations, and dubious assumptions. For instance, we make no presumption in our paper that nuclear power is the only major option to replace fossil fuels nor have we in the past, as evidenced by our other peer-reviewed publications. Furthermore, all of our results are based on complete fuel cycle analysis and are presented as mean values along with their ranges. Thus it is incorrect to claim that we single out the worst estimates for coal mortality. Contrary to Sovacool et al.'s assertions, our only bias is our belief that humanity's best chance of success for mitigating the daunting challenge of climate change is to utilize all available and proven means.
2010-01-01
Academy, the Department of the Army, or any other agency of the U.s. Government. C o M B A T I n G T E R R o R I s M C E n T E R A T W E s T...p o I n T o B j E C T I V E . R E L E V A n T . R I G o R o U s CTC SeNTiNeL Usama bin Ladin explains why he declared jihad against the United...Taliban professed today by al- Qa`ida and its Pakistan-based allies— including the Haqqani network and Tehrik- i -Taliban Pakistan (TTP)—is more a
[Management and orientation of a hand laceration].
Masmejean, Emmanuel
2013-11-01
The good management and orientation of a hand laceration by the general physician is essential. Anatomical knowledge help to judge, after examination, the opportunity for surgery exploration with local anesthesia. Serious stakes are prognostic and economics. The conclusion identifies three clinical pictures : simple superf cial wound requiring a simple clinical control 2 days follow-up, the dubious wound that need to be sent to a specialized center, and the wound requiring care in an emergency hand unit. Extremely urgent wounds are devascularization, amputation and the pressure injection . Bites and wounds on a tendon way require surgical exploration. Bandage should be as simple as possible in order to allow early motion. No antibiotic is given preventively exept for bite, open fractures and/or delay of treatment. Outpatient surgery under loca anesthesia simplifies management.
Alternative Medicine: Contagion and Cure in Karel Čapek's The White Plague.
Soloski, Alexis
Though written amid an atmosphere of unprecedented medical advance in both diagnosis and therapeutics, Karel Čapek's The White Plague takes a starkly critical stance against overconfidence in medical science and its dubious ethical orbit. This article explores Čapek's censure of those who would privilege scientific interest in disease over the holistic plight of the sufferer. Provocatively, Čapek achieves this not only via the play's content, but also-prefiguring aspects of contemporary live art practice by several decades-by placing audience members in worrying proximity to abject ill bodies. Čapek proposes a sort of theatrical homeopathy, suggesting that limited exposure to the threat of disease might spur spectators toward empathy for those who suffer and promote a healthier, more compassionate society.
Can an Inquiry Approach Improve College Student Learning in a Teaching Laboratory?
Cogan, John G.
2009-01-01
We present an inquiry-based, hands-on laboratory exercise on enzyme activity for an introductory college biology course for science majors. We measure student performance on a series of objective and subjective questions before and after completion of this exercise; we also measure performance of a similar cohort of students before and after completion of an existing, standard, “direct” exercise over the same topics. Although student performance on these questions increased significantly after completion of the inquiry exercise, it did not increase after completion of the control, standard exercise. Pressure to “cover” many complex topics as preparation for high-stakes examinations such as the Medical College Admissions Test may account for persistence of highly efficient, yet dubiously effective “cookbook” laboratory exercises in many science classes. PMID:19255136
Song, Shu-qi; Zhang, Ya-qiang
2009-12-01
The etiology, pathogenesis, and diagnostic criteria of chronic prostatitis were reviewed in this article. Based on clinical practice, the authors systematically discussed the thoughts and methods for the treatment of chronic prostatitis by integrated traditional Chinese and Western medicine. Meanwhile, advice on disputed problems in clinical study of prostatits were given, such as curative effect estimation value of the number of leukocytes in expressed prostatic secretion (EPS) and bacterial culture in EPS, the opportunity and treatment course of antibiotics, National Institutes of Health chronic prostatitis symptom index, classification of syndromes of traditional Chinese medicine (TCM), TCM symptom score, and clinical study period.
Zheng, Yadong
2013-11-01
Echinococcus species have been studied as a model to investigate parasite-host interactions. Echinococcus spp. can actively communicate dynamically with a host to facilitate infection, growth and proliferation partially via secretion of molecules, especially in terms of harmonization of host immune attacks. This review systematically outlines our current knowledge of how the Echinococcus species have evolved to adapt to their host's microenvironment. This understanding of parasite-host interplay has implications in profound appreciation of parasite plasticity and is informative in designing novel and effective tools including vaccines and drugs for the treatment of echinococcosis and other diseases. © 2013.
Makarov, Slobodan E; Bodner, Michaela; Reineke, Doris; Vujisić, Ljubodrag V; Todosijević, Marina M; Antić, Dragan Ž; Vagalinski, Boyan; Lučić, Luka R; Mitić, Bojan M; Mitov, Plamen; Anđelković, Boban D; Lucić, Sofija Pavković; Vajs, Vlatka; Tomić, Vladimir T; Raspotnig, Günther
2017-04-01
Cave animals live under highly constant ecological conditions and in permanent darkness, and many evolutionary adaptations of cave-dwellers have been triggered by their specific environment. A similar "cave effect" leading to pronounced chemical interactions under such conditions may be assumed, but the chemoecology of troglobionts is mostly unknown. We investigated the defensive chemistry of a largely cave-dwelling julid group, the controversial tribe "Typhloiulini", and we included some cave-dwelling and some endogean representatives. While chemical defense in juliform diplopods is known to be highly uniform, and mainly based on methyl- and methoxy-substituted benzoquinones, the defensive secretions of typhloiulines contained ethyl-benzoquinones and related compounds. Interestingly, ethyl-benzoquinones were found in some, but not all cave-dwelling typhloiulines, and some non-cave dwellers also contained these compounds. On the other hand, ethyl-benzoquinones were not detected in troglobiont nor in endogean typhloiuline outgroups. In order to explain the taxonomic pattern of ethyl-benzoquinone occurrence, and to unravel whether a cave-effect triggered ethyl-benzoquinone evolution, we classed the "Typhloiulini" investigated here within a phylogenetic framework of julid taxa, and traced the evolutionary history of ethyl-benzoquinones in typhloiulines in relation to cave-dwelling. The results indicated a cave-independent evolution of ethyl-substituted benzoquinones, indicating the absence of a "cave effect" on the secretions of troglobiont Typhloiulini. Ethyl-benzoquinones probably evolved early in an epi- or endogean ancestor of a clade including several, but not all Typhloiulus (basically comprising a taxonomic entity known as "Typhloiulus sensu stricto") and Serboiulus. Ethyl-benzoquinones are proposed as novel and valuable chemical characters for julid systematics.
Dubious Bargain: Trading Sleep for Leno and Letterman
Basner, Mathias; Dinges, David F.
2009-01-01
Study Objectives: Sleeping less than 7 hours daily impairs alertness and is associated with increased obesity, morbidity, and mortality; yet up to 40% of US adults do so. Population data indicate work time is the primary activity reciprocally related to sleep time in the United States. Reducing work time and its economic benefits to increase sleep time may not be feasible for most of the population. We sought to identify waking activities under discretionary control and adjacent to the sleep period that would be a more feasible source for increasing sleep time. Design/Participants: American Time Use Survey data from 21,475 respondents aged ≥ 15 years were pooled for the years 2003–2006 to explore activities in 2-hour periods prior to going to bed and past getting up on weekdays. Interventions: N/A Results: Long workers (≥ 8 hours) terminated bed time an average of 0.68 h earlier than short workers (< 8 hours, P < 0.0001) and 1.31 h earlier than respondents not working on the interview day (P < 0.001), but time of going to bed did not differ among groups (22:37 vs. 22:42 vs. 22:37, respectively, P = 0.385). Watching television was the primary activity people engaged in before going to bed, accounting for 55.6 min (46.3%) of the 2-h pre-bed period. In the morning, travel time and work time increased steadily toward the end of the post-awakening 2-h period, accounting for 14.8% and 12.3%, respectively. Conclusions: Watching television may be an important social Zeitgeber for the time of going to bed. Watching less television in the evening and postponing work start time in the morning appear to be the candidate behavioral changes for achieving additional sleep. While the timing of work may not be flexible, giving up some TV viewing in the evening should be possible to reduce chronic sleep debt and promote adequate sleep in those who need it. Citation: Basner M; Dinges DF. Dubious bargain: trading sleep for Leno and Letterman. SLEEP 2009;32(6):747–752. PMID:19544750
A systematic approach to very important person preparedness for a trauma center.
Bulson, Julie; Mattice, Connie; Bulson, Timothy
2012-01-01
Hospitals across the United States are more involved in disaster/rapid response planning than ever. This collaboration is often driven by continuing federal and state preparedness and all-hazards planning efforts that provide cooperative agreement and/or grant support. These efforts currently include programs administered by the US assistant secretary for preparedness and response, the US Centers for Disease Control and Prevention, the US Department of Defense, and the US Department of Homeland Security. Beyond legislated support or mandates, key emergency management regulations governing hospital-specific disaster planning and response activities are required of hospitals by The Joint Commission, the largest national hospital accrediting body. Despite this ongoing, heightened awareness and inclusion of health care in local and regional emergency response planning, there is 1 partnership to yet strengthen: the relationship between community trauma centers and US Secret Service staff responsible for White House travel and health care contingency plans. One Michigan hospital system designed a program that has made preevent communications and preparedness for rapid very important person response with the Secret Service as important as other local all-hazards planning; the evolution of this partnership is the focus of this article.
An unusual recruitment strategy in a mass-recruiting stingless bee, Partamona orizabaensis.
Flaig, Isabelle C; Aguilar, Ingrid; Schmitt, Thomas; Jarau, Stefan
2016-10-01
Foragers of several stingless bee species deposit attractive scent marks on solid substrates to precisely recruit nestmates to food. Interestingly, Partamona workers quickly recruit large numbers of nest mates to resources, likely even without the deposition of attractive scent marks. However, systematic studies of the recruitment system of these bees are lacking. We now studied the recruitment behavior of P. orizabaensis. Our findings show that foragers of this species can recruit large numbers of nestmates to food sources at a particular location. The precise nestmate recruitment does not rely on attractive scent marks deposited on substrates. We never observed any scent marking behavior and feeders baited with labial or mandibular gland extracts were not attractive for the bees. Chemical analyses showed that the foragers' labial gland secretions exclusively contain long chain hydrocarbons, which render their role in recruitment communication unlikely. Whether mandibular gland secretions, which contain esters and alcohols that are known as attractive pheromones in other bee species, are used to guide recruits toward food during flight, remains elusive. We conclude that Partamona's quick recruitment system that does not rely on conspicuous scent marks has evolved as a strategy against competition with sympatrically occurring and more aggressive bee species.
Wang, Shu-Xia; Zhang, Jia-Ming; Wu, Kai; Chen, Juan; Shi, Jian-Feng
2014-08-01
To investigate the pathogenic infection and its drug resistance in expressed prostatic secretion (EPS) and its correlation with serum PSA, and provide some evidence for the systematic and normalized diagnosis and treatment of prostatitis. Three EPS swabs were collected from each of the 320 prostatis patients following measurement of the serum PSA level, 1 for bacterial culture and identification, 1 for detection of Mycoplasma and drug sensitivity, and the other for examination of Chlamydia trachomatis antigen by colloidal gold immunoblot. Totally 244 strains were isolated from the 320 EPS samples, including 188 bacterial strains (dominated by Staphylococcus and sensitive to vancomycin or linezolid) and 44 Mycoplasma and Chlamydia strains (mainly Ureaplasma urealyticum and susceptible to josamycin or doxycycline). The serum PSA level was significantly higher in the pathogen-positive than in the pathogen-negative group ([6.98 +/- 0.56] microg/L vs [2.32 +/- 0.12] microg/L, P < 0.05). Prostatitis may lead to the elevation of the serum PSA level and the pathogens involved vary in their resistance to different antibacterial spectrums. Therefore, appropriate and individualized antibiotic therapy should be selected according to etiological diagnosis and the results of drug sensitivity test.
Grünbacher, André; Throm, Tanja; Seidel, Constanze; Gutt, Beatrice; Röhrig, Julian; Strunk, Timo; Vincze, Paul; Walheim, Stefan; Schimmel, Thomas; Wenzel, Wolfgang; Fischer, Reinhard
2014-01-01
Hydrophobins are amphiphilic proteins able to self-assemble at water-air interphases and are only found in filamentous fungi. In Aspergillus nidulans two hydrophobins, RodA and DewA, have been characterized, which both localize on the conidiospore surface and contribute to its hydrophobicity. RodA is the constituent protein of very regularly arranged rodlets, 10 nm in diameter. Here we analyzed four more hydrophobins, DewB-E, in A. nidulans and found that all six hydrophobins contribute to the hydrophobic surface of the conidiospores but only deletion of rodA caused loss of the rodlet structure. Analysis of the rodlets in the dewB-E deletion strains with atomic force microscopy revealed that the rodlets appeared less robust. Expression of DewA and DewB driven from the rodA promoter and secreted with the RodA secretion signal in a strain lacking RodA, restored partly the hydrophobicity. DewA and B were able to form rodlets to some extent but never reached the rodlet structure of RodA. The rodlet-lacking rodA-deletion strain opens the possibility to systematically study rodlet formation of other natural or synthetic hydrophobins.
Seidel, Constanze; Gutt, Beatrice; Röhrig, Julian; Strunk, Timo; Vincze, Paul; Walheim, Stefan; Schimmel, Thomas; Wenzel, Wolfgang; Fischer, Reinhard
2014-01-01
Hydrophobins are amphiphilic proteins able to self-assemble at water-air interphases and are only found in filamentous fungi. In Aspergillus nidulans two hydrophobins, RodA and DewA, have been characterized, which both localize on the conidiospore surface and contribute to its hydrophobicity. RodA is the constituent protein of very regularly arranged rodlets, 10 nm in diameter. Here we analyzed four more hydrophobins, DewB-E, in A. nidulans and found that all six hydrophobins contribute to the hydrophobic surface of the conidiospores but only deletion of rodA caused loss of the rodlet structure. Analysis of the rodlets in the dewB-E deletion strains with atomic force microscopy revealed that the rodlets appeared less robust. Expression of DewA and DewB driven from the rodA promoter and secreted with the RodA secretion signal in a strain lacking RodA, restored partly the hydrophobicity. DewA and B were able to form rodlets to some extent but never reached the rodlet structure of RodA. The rodlet-lacking rodA-deletion strain opens the possibility to systematically study rodlet formation of other natural or synthetic hydrophobins. PMID:24722460
Kolodinsky, Jane; Labrecque, JoAnne; Doyon, Maurice; Reynolds, Travis; Oble, Frédéric; Bellavance, François; Marquis, Marie
2008-01-01
Functional foods (FF)--foods containing nutritional supplements in addition to natural nutrients--have an increasing presence in the marketplace. Expanding on previous research, the authors investigated college students' acceptance of FF. In September--March 2004, 811 undergraduates in Canada, the United States, and France participated in the study. A self-administered questionnaire measured students' general food attitudes and beliefs as well as FF-related knowledge, attitudes, beliefs, and purchase intention. Overall, participants slightly favored FF over traditional foods. However, although most respondents associated FF with positive health benefits, many remained dubious of currently available FF information. In terms of culture and sex, the authors found small but significant divergences in FF knowledge, attitudes, and behaviors. Stronger labeling and education efforts may increase cross-cultural acceptance of FF by college students.
Air-to-air view of STS-32 Columbia, OV-102, launch
1990-01-09
STS-32 Columbia, Orbiter Vehicle (OV) 102, pierces a layer of low lying clouds as it makes its ascent to Earth orbit for a 10-day mission. In this air-to-air view, OV-102 rides atop the external tank (ET) with flames created by solid rocket boosters (SRBs) appearing directly underneath it and a long plume of exhaust smoke trailing behind it and extending to Kennedy Space Center (KSC) Launch Complex (LC) Pad 39A below. OV-102 left KSC LC Pad 39A at 7:34:59:98 am Eastern Standard Time (EST) some 24 hours after dubious weather at the return-to-landing site (RTLS) had cancelled a scheduled launch. The photo was taken by astronaut Michael L. Coats, acting chief of the Astronaut Office, from the Shuttle Training Aircraft (STA).
Foreign language affects the contribution of intentions and outcomes to moral judgment.
Geipel, Janet; Hadjichristidis, Constantinos; Surian, Luca
2016-09-01
We examine whether the use of a foreign language, as opposed to the native language, influences the relative weight intentions versus outcomes carry in moral evaluations. In Study 1, participants were presented with actions that had positive outcomes but were motivated by dubious intentions, while in Study 2 with actions that had negative outcomes but were motivated by positive intentions. Participants received the materials either in their native or a foreign language. Foreign language prompted more positive moral evaluations in Study 1 and less positive evaluations in Study 2. These results show that foreign language reduces the relative weight placed on intentions versus outcomes. We discuss several theoretical accounts that are consistent with the results such as that foreign language attenuates emotions (triggered by intentions) or it depletes cognitive resources. Copyright © 2016 Elsevier B.V. All rights reserved.
A blind squirrel finds a nut: tales from at an entrepreneurial adventure
NASA Astrophysics Data System (ADS)
Doughty, Chris
2010-03-01
When I received my PhD back in the dark days of 386 computers, fax machines, and a miserable economy it was commonly said that ``a degree in Physics is a great foundation for wide variety of non-academic career paths,'' but it was never entirely clear what those paths were. I still can't say what those paths are but can describe at least one: starting, building and ultimately exiting a small entrepreneurial business. This talk will describe at least one entrepreneurial path, where a physics background has value, where it is a liability, and what other skills the physicist needs to acquire to succeed in business. I will give a personal view of what it looks like inside a startup, lessons learned, mistakes made, and copious advice of dubious utility and value.
DangerTrack: A scoring system to detect difficult-to-assess regions.
Dolgalev, Igor; Sedlazeck, Fritz; Busby, Ben
2017-01-01
Over recent years, multiple groups have shown that a large number of structural variants, repeats, or problems with the underlying genome assembly have dramatic effects on the mapping, calling, and overall reliability of single nucleotide polymorphism calls. This project endeavored to develop an easy-to-use track for looking at structural variant and repeat regions. This track, DangerTrack, can be displayed alongside the existing Genome Reference Consortium assembly tracks to warn clinicians and biologists when variants of interest may be incorrectly called, of dubious quality, or on an insertion or copy number expansion. While mapping and variant calling can be automated, it is our opinion that when these regions are of interest to a particular clinical or research group, they warrant a careful examination, potentially involving localized reassembly. DangerTrack is available at https://github.com/DCGenomics/DangerTrack.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lellouche, P.
The Atlantic Alliance was disturbed when the Strategic Defense Initiative (SDI) was conceived and presented primarily as an American unilateral initiative, with no political or strategic consultation with the allies. It was also disturbed by the confused and contradictory objectives of SDI; i.e., its rejection of the logic of deterrence as a dangerous and unethical proposition at the same time that it reinforces the logic of mutual assured destruction (MAD). Some of the basic ambiguity is related to the technology, which remains untested. SDI's purpose is not to defend people or missiles, but to destroy weapons. The author argues thatmore » SDI threatens the survival of Europe's high tech industries and could lead to a massive transfer of NATO-related defense expenditures away from European defense and toward a defensive shield of dubious value for Europeans.« less
[Carcinogenic effect of metals].
Desurmont, M
1983-09-01
Some metals are essential oligo-elements for man. However, if the body load of these same metal derivatives becomes excessive they may be responsible for deleterious effects, particularly cytotoxic ones. Metals are divided into four categories: potent carcinogens; presumptive carcinogens with a documented cocarcinogenic effect; ascertained cocarcinogens; metals with no demonstrated carcinogenic or cocarcinogenic effect. The most common tumors induced by metals are those of the lung. Arsenic induces cancer of the lung and skin, beryllium may induce lung cancer, the effects of cobalt are dubious, cadmium can induce cancer of the lung and, above all, prostate, the role of iron is uncertain, hexavalent chrome may induce cancer of the lung and nasal fossae, nickel is responsible for cancer of lung and nasal fossae. Our understanding of metal carcinogenesis is clearly insufficient and more experimental research and epidemiologic studies addressing this subject are needed.
POST TRAUMATIC STRESS DISORDER (PTSD) IN ARAB AMERICAN REFUGEE AND RECENT IMMIGRANT WOMEN.
Kulwicki, Anahid; Ballout, Suha
2015-01-01
Routine male circumcision (RMC) has been found effective in preventing HIV infection in Africa; at the same time, incidence of HIV infection has been rising in China. Hence, RMC may be a possible means by which Chinese nationals could address increasing HIV infection rates. A focus group study was conducted to explore perceptions of RMC among mainland Chinese nationals. The results indicated that 1) 90% of participants considered RMC to be an unfamiliar and culturally sensitive topic; 2) 80% felt that being uncircumcised had not created significant health drawbacks for them or males they knew; and 3) the group believed that RMC would not be a good strategy to address rising HIV rates and were dubious about the idea of mandated RMC in China. For Chinese nationals, cultural traditions regarding RMC appear to outweigh concerns about HIV infection.
How patients stress, con, and intimidate physicians to file dubious disability reports.
Brooks, T R
1996-05-01
This study was undertaken to determine the association between health providers' stress and performances, and patients who presented with disability forms that the providers did not feel were justified. Two questionnaires were given to health-care providers at the Family Practice Clinic, Martin Luther King/Drew Medical Center, Los Angeles, California. One questionnaire assessed the level of stress they suffered from, and a second questionnaire assessed how these types of patients may affect their general performance. The data suggested that the performance of providers was definitely affected by hostile, demanding, threatening, and malingering patients. The students, residents, nurses, and clinic administrative staff were all affected. Third-year medical students and foreign-trained doctors appeared not to be affected as much, probably because of a lack of knowledge about the "system" or because they preferred not to "rock the boat".
Soft ferromagnetic properties of Ni44Fe6Mn32Al18 doped Co partially
NASA Astrophysics Data System (ADS)
Notonegoro, Hamdan Akbar; Kurniawan, Budhy; Kurniawan, Candra; Manaf, Azwar
2017-01-01
Research in finding suitable magnetocaloric material around room temperature made ferromagnetic (FM) (Ni-Mn)-based Heusler alloys receive considerable attention as a potential candidate for the magnetic refrigerator. This compound are associated with the shape-memory effect, magnetic superelasticity, and more others magneto-functional properties. The compounds were prepared by vacuum arc melter (VAM) under argon atmosphere which sintering and annealing process were running with quartz cube in vacuum condition. A small amount of coercivity value at σ = 0 in the hysteresis curve occurred whereas magnetization of the sample in various temperature does not reach saturation. The Currie temperature Tc of the sample was obtained at 358 K. Nevertheless, this is dubious value because at T = 300 K the curves had swooped down. Additional measurements necessary to taken as a comparison to verify this value.
Wurdack, Kenneth J.; Farfan-Rios, William
2017-01-01
Abstract Incadendron esseri K.Wurdack & Farfan, gen. & sp. nov., from the wet sub-Andean cordilleras of Ecuador (Cordillera del Cóndor) and Peru (Cusco, Oxapampa) is described and illustrated. This recently discovered large canopy tree with a narrow elevational range presents an unusual combination of rare morphological characters in Hippomaneae including mucilage-secreting sheathing stipules, conduplicate ptyxis, and large, woody fruits. The broader significance of these characters in Hippomaneae is discussed. The morphology and anatomy of Incadendron were investigated, highlighting its fruit similarities with Guiana Shield endemic Senefelderopsis, and the systematics value of ptyxis variation, which remains poorly studied for the family. PMID:29033661
Xiang, Jie; Zhou, Mei; Wu, Yuxin; Chen, Tianbao; Shaw, Chris; Wang, Lei
2017-10-31
Bombinin and bombinin H are two antimicrobial peptide (AMP) families initially discovered from the skin secretion of Bombina that share the same biosynthetic precursor-encoding cDNAs, but have different structures and physicochemical properties. Insight into their possible existing relationship lead us to perform the combination investigations into their anti-infectious activities. In this work, we report the molecular cloning and functional characterization of two novel AMPs belonging to bombinin and bombinin H families from secretions of Bombina orientalis Their mature peptides (BHL-bombinin and bombinin HL), coded by single ORF, were chemically synthesized along with an analogue peptide that replaced L-leucine with D-leucine from the second position of the N-terminus (bombinin HD). CD analysis revealed that all of them displayed well-defined α-helical structures in membrane mimicking environments. Furthermore, BHL-bombinin displayed broad-spectrum bactericidal activities on a wide range of microorganisms, while bombinin H only exhibited a mildly bacteriostatic effect on the Gram-positive bacteria Staphylococcus aureus The combination potency of BHL-bombinin with either bombinin HL or bombinin HD showed the synergistic inhibition activities against S. aureus (fractional inhibitory concentration index (FICI): 0.375). A synergistic effect has also been observed between bombinin H and ampicillin, which was further systematically evaluated and confirmed by in vitro time-killing investigations. Haemolytic and cytotoxic examinations exhibited a highly synergistic selectivity and low cytotoxicity on mammalian cells of these three peptides. Taken together, the discovery of the potent synergistic effect of AMPs in a single biosynthetic precursor with superior functional selectivity provides a promising strategy to combat multidrug-resistant pathogens in clinical therapy. © 2017 The Author(s).
Diverse secreted effectors are required for Salmonella persistence in a mouse infection model.
Kidwai, Afshan S; Mushamiri, Ivy; Niemann, George S; Brown, Roslyn N; Adkins, Joshua N; Heffron, Fred
2013-01-01
Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.
Cui, Ju; Pang, Jing; Lin, Ya-Jun; Gong, Huan; Wang, Zhen-He; Li, Yun-Xuan; Li, Jin; Wang, Zai; Jiang, Ping; Dai, Da-Peng; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei
2017-06-01
Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion of Kif5b aggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on an HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down-regulation of key thermogenic gene expression. In conclusion, selective deletion of Kif5b in adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity. © FASEB.
Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kidwai, Afshan S.; Mushamiri, Ivy T.; Niemann, George
Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 moremore » strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.« less
Red junglefowl have individual body odors.
Karlsson, Anna-Carin; Jensen, Per; Elgland, Mathias; Laur, Katriann; Fyrner, Timmy; Konradsson, Peter; Laska, Matthias
2010-05-01
Olfaction may play an important role in regulating bird behavior, and has been suggested to be involved in feather-pecking. We investigated possible differences in the body odors of red junglefowl females by using an automated olfactometer which assessed the ability of trained mice to discriminate between the odors of uropygial gland secretions (the main carrier of potential individual odors in chickens) of six feather-pecked and six non-pecked birds. All mice were clearly able to discriminate between all individual red junglefowl odors, showing that each bird has an individual body odor. We analyzed whether it was more difficult to discriminate between the odors of two feather-pecked, or two non-pecked birds, than it was to discriminate between the odors of two randomly selected birds. This was not the case, suggesting that feather-pecked birds did not share a common odor signature. Analyses using gas chromatography and mass spectrometry showed that the composition of aliphatic carboxylic acids in uropygial gland secretions differed consistently between individuals. However, chemical composition did not vary according to feather-pecking status. We conclude that red junglefowl have individual body odors which appear to be largely based on differences in the relative abundance of aliphatic carboxylic acids, but there is no evidence of systematic differences between the body odors of pecked and non-pecked birds.
Clinical Effects of Thai Herbal Compress: A Systematic Review and Meta-Analysis
Dhippayom, Teerapon; Kongkaew, Chuenjid; Chaiyakunapruk, Nathorn; Dilokthornsakul, Piyameth; Sruamsiri, Rosarin; Saokaew, Surasak; Chuthaputti, Anchalee
2015-01-01
Objective. To determine the clinical effects of Thai herbal compress. Methods. International and Thai databases were searched from inception through September 2014. Comparative clinical studies investigating herbal compress for any indications were included. Outcomes of interest included level of pain, difficulties in performing activities, and time from delivery to milk secretion. Mean changes of the outcomes from baseline were compared between herbal compress and comparators by calculating mean difference. Results. A total of 13 studies which involved 778 patients were selected from 369 articles identified. The overall effects of Thai herbal compress on reducing osteoarthritis (OA) and muscle pain were not different from those of nonsteroidal anti-inflammatory drugs, knee exercise, and hot compress. However, the reduction of OA pain in the herbal compress group tended to be higher than that of any comparators (weighted mean difference 0.419; 95% CI −0.004, 0.842) with moderate heterogeneity (I 2 = 58.3%, P = 0.048). When compared with usual care, herbal compress provided significantly less time from delivery to milk secretion in postpartum mothers (mean difference −394.425 minutes; 95% CI −620.084, −168.766). Conclusion. Thai herbal compress may be considered as an alternative for osteoarthritis and muscle pain and could also be used as a treatment of choice to induce lactation. PMID:25861373
The effects of Ramadan fasting on the health and function of the eye.
Javadi, Mohammad Ali; Assadi, Mahsan; Einollahi, Bahram; Rabei, Hossein Mohammad; Afarid, Mehrdad; Assadi, Majid
2014-08-01
Ramadan fasting may alter a variety of physiological parameters which by themselves influence ocular system. Here, we review the effects of Ramadan fasting on the health and function of the eye. Literature records in PubMed/MEDLINE, Web of Science, EMBASE, Google Scholar, and Iran Medex databases as well as proceedings of related meetings from January 1986 to March 2014 were systematically reviewed. The search key words was based on the terms "Ramadan Fasting," "Ramadan," "Islamic Fasting," "Fasting in Ramadan" accompanied with one of the eye, tear drop, myopia, intraocular pressure (IOP), tear break up time, basal tear secretion, refractive error, and visual acuity. Predawn water loading and dehydration in the evening are shown to increase and decrease IOP and tear secretion, respectively. Ocular blood flow is changed in Ramadan fasting, and patients with ocular vein occlusion may experience more frequent attacks. There are no or minimal fluctuations in visual acuity and refractive errors, but most of them are decompensated after Ramadan. Although the influence of fasting in different eye parameters is evaluated in several studies, there are no or only limited studies conducted on patients suffering from glaucoma, damage to ophthalmic vasculature, tear dysfunction, and minimal visual acuity. Such studies are required to make a definite decision before fasting is declared harmless to these patients.
Rendering justice in witch trials: the case of the val de Lièpvre.
Simon, Maryse
2011-01-01
The borderland of the val de Lièpvre, with lands in Alsace and in the Duchy of Lorraine, and divided by religion and language, offers a rich collection of sources for the history of witchcraft persecution. The territory sharply reveals what was undoubtedly characteristic of witchcraft trials more widely. The crime of witchcraft was considered abominable before the Christian community and God, and its prosecution justified abandoning many of the safeguards and constraints in legal procedure, whether restrictions on the use of torture, the reliance on dubious testimony or even denial of advocacy to the witches. The action of the judges was nonetheless, as they understood it, the rendering of true justice, by punishing the culprits with a harshness that would expiate their crimes before the community and preserve them from damnation in the face of God's judgment.
NASA Technical Reports Server (NTRS)
Nuth, J. A., III
1981-01-01
Steady state vibrational populations of SiO and CO in dilute black body radiation fields were calculated as a function of total pressure, kinetic temperature and chemical composition of the gas. Approximate calculations for polyatomic molecules are presented. Vibrational disequilibrium becomes increasingly significant as total pressure and radiation density decrease. Many regions of postulated grain formation are found to be far from thermal equilibrium before the onset of nucleation. Calculations based upon classical nucleation theory or equilibrium thermodynamics are expected to be of dubious value in such regions. Laboratory measurements of the extinction of small iron and magnetite grains were made from 195 nm to 830 nm and found to be consistent with predictions based upon published optical constants. This implies that small iron particles are not responsible for the 220 nm interstellar extinction features. Additional measurements are discussed.
Stahnisch, Frank W
2016-01-01
Research in biological psychiatry during the first half of the 20 th century was based upon a wide range of interrelated disciplines, including neurology, neuroanatomy, neuropathology, and experimental biology. The work of German-American psychiatrist and neurologist Lothar B. Kalinowsky (1899-1992) is taken here as an example of how such fields could be combined to produce a highly innovative and multidimensional research program in clinical neuroscience. Kalinowsky functioned exceptionally well in both scientific and clinical cultures despite the marked contextual differences between the Charité in Berlin and his later workplace in New York's Columbia Medical School. The innovative ideas exemplified by Kalinowsky's efforts, however, sometimes amounted to a dubious advantage for émigré clinical neuroscientists: they easily led to incommensurable scientific views, and sometimes even resulted in the marginalization of the innovator from existing research programs.
Use of nutritional supplements in sports: risks, knowledge, and behavioural-related factors.
Molinero, O; Márquez, S
2009-01-01
A large number of recreational and elite athletes use nutritional supplements in hopes of improving performance. These aids can be costly and potentially harmful, and the advertised ergogenic gains are often based on little or no scientific evidence. Due to the lack of regulation of the dietary supplement industry, an abundance of supplement products of dubious value, content, and quality are now available around the world. Many supplement products contain substances that are prohibited in sport or that have been associated with significant morbidity and mortality. For athletes, lack of knowledge or misinformation has been established despite numerous sources of information being available, and the reasons for, and implications of, unsupervised and unrestricted supplement use require further attention. In addition to the necessity of an appropriate regulation of dietary supplements, nutritional education and scientifically sound guidance for athletes is required. Intervention and prevention efforts should be particularly targeted to adolescents.
Construction and preliminary validation of the Barcelona Immigration Stress Scale.
Tomás-Sábado, Joaquín; Qureshi, Adil; Antonin, Montserrat; Collazos, Francisco
2007-06-01
In the study of mental health and migration, an increasing number of researchers have shifted the focus away from the concept of acculturation towards the stress present in the migratory experience. The bulk of research on acculturative stress has been carried out in the United States, and thus the definition and measurement of the construct has been predicated on that cultural and demographic context, which is of dubious applicability in Europe in general, and Spain in particular. Further, some scales have focused on international students, which down-played the importance of the migratory process, because it deals with a special subset of people who are not formally immigrating. The Barcelona Immigration Stress Scale was developed to measure acculturative stress appropriate to immigrants in Spain, using expert and focus group review and has 42 items. The scale shows acceptable internal validity, and, consistent with other scales, suggests that immigration stress is a complex construct.
Morgellons: contested illness, diagnostic compromise and medicalisation.
Fair, Brian
2010-05-01
The case of Morgellons illustrates how the emergence of a new medically contested illness intersected with and impacted on the diagnostic processes of an existing uncontested psychiatric condition, Delusional Parasitosis (DP). More specifically, the sociopolitical processes at play in the contested illness, Morgellons, dubiously reflect patient empowerment, as well the resilience and power of medical jurisdiction. This research offers insights into the contested illness and medicalisation literatures, and aims to bridge these two approaches towards the relationship between patient empowerment and medical authority, which I do through the notion of doctor-patient compromise. The data for this research come from a comprehensive qualitative analysis of Morgellons discourse through four key sources: the pro-Morgellons website Morgellons.org; the anti-Morgellons website Morgellonswatch.com; the popular media's portrayal of Morgellons; and the DP and Morgellons articles published in peer-reviewed medical journals, as made available on PubMed.
Characterization of redox conditions in groundwater contaminant plumes
NASA Astrophysics Data System (ADS)
Christensen, Thomas H.; Bjerg, Poul L.; Banwart, Steven A.; Jakobsen, Rasmus; Heron, Gorm; Albrechtsen, Hans-Jørgen
2000-10-01
Evaluation of redox conditions in groundwater pollution plumes is often a prerequisite for understanding the behaviour of the pollutants in the plume and for selecting remediation approaches. Measuring of redox conditions in pollution plumes is, however, a fairly recent issue and yet relative few cases have been reported. No standardised or generally accepted approach exists. Slow electrode kinetics and the common lack of internal equilibrium of redox processes in pollution plumes make, with a few exceptions, direct electrochemical measurement and rigorous interpretation of redox potentials dubious, if not erroneous. Several other approaches have been used in addressing redox conditions in pollution plumes: redox-sensitive compounds in groundwater samples, hydrogen concentrations in groundwater, concentrations of volatile fatty acids in groundwater, sediment characteristics and microbial tools, such as MPN counts, PLFA biomarkers and redox bioassays. This paper reviews the principles behind the different approaches, summarizes methods used and evaluates the approaches based on the experience from the reported applications.
Kasturirangan, Rajesh
2008-01-01
Philosophers as well lay people often think of beliefs as psychological states with dubious epistemic properties. Beliefs are conceptualized as unregulated conceptual structures, for the most part hypothetical and often fanciful or deluded. Thinking and reasoning on the other hand are seen as rational activities regulated by rules and governed by norms. Computational modeling of the mind has focused on rule-governed behavior, ultimately trying to reduce them to rules of logic. What if thinking is less like reasoning and more like believing? I argue that the classical model of thought as rational is mistaken and that thinking is fundamentally constituted by believing. This new approach forces us to re-evaluate classical epistemic concepts like "truth", "justification" etc. Furthermore, if thinking is believing, then it is not clear how thoughts can be modeled computationally. We need new mathematical ideas to model thought, ideas that are quite different from traditional logic-based mathematical structures.
NASA Astrophysics Data System (ADS)
Šuber, Daniel
In recent years, a group of social scientists have credited Wilhelm Dilthey with the status of a "classical sociological theorist" (Bakker 1999) and a key figure with regard to the establishment of the social sciences since the last decades of the nineteenth century.1 Such evaluations stand in distinct contrast to Dilthey's reputation as a firm critic of sociology on the one hand and his dubious standing within his proper field, philosophy, on the other, where he is perceived as a failed epistemologist. Generally, his influence on social and cultural science is associated with his notion of Erleben and understanding as fundamental categories for the interpretive sciences and their unique relatedness to their particular subject. On the basis of this starting point, he eventually established a division between Verstehen and Erklären and, correspondingly, human and natural sciences.
Kim, Scott Y. H.; Wall, Ian F.; Stanczyk, Aimee; Vries, Raymond De
2010-01-01
In a Liberal Democracy, Policy Decisions regarding ethical controversies, including those in research ethics, should incorporate the opinions of its citizens. Eliciting informed and well-considered ethical opinions can be challenging. The issues may not be widely familiar and they may involve complex scientific, legal, historical, and ethical dimensions. Traditional surveys risk eliciting superficial and uninformed opinions that may be of dubious quality for policy formation. We argue that the theory and practice of deliberative democracy (DD) is especially useful in overcoming such inadequacies. We explain DD theory and practice, discuss the rationale for using DD methods in research ethics, and illustrate in depth the use of a DD method for a long-standing research ethics controversy involving research based on surrogate consent. The potential pitfalls of DD and the means of minimizing them as well as future research directions are also discussed. PMID:19919315
Computational Fact Checking from Knowledge Networks
Ciampaglia, Giovanni Luca; Shiralkar, Prashant; Rocha, Luis M.; Bollen, Johan; Menczer, Filippo; Flammini, Alessandro
2015-01-01
Traditional fact checking by expert journalists cannot keep up with the enormous volume of information that is now generated online. Computational fact checking may significantly enhance our ability to evaluate the veracity of dubious information. Here we show that the complexities of human fact checking can be approximated quite well by finding the shortest path between concept nodes under properly defined semantic proximity metrics on knowledge graphs. Framed as a network problem this approach is feasible with efficient computational techniques. We evaluate this approach by examining tens of thousands of claims related to history, entertainment, geography, and biographical information using a public knowledge graph extracted from Wikipedia. Statements independently known to be true consistently receive higher support via our method than do false ones. These findings represent a significant step toward scalable computational fact-checking methods that may one day mitigate the spread of harmful misinformation. PMID:26083336
Breaking Binaries? Biomedicine and Serostatus Borderlands among Couples with Mixed HIV Status.
Persson, Asha; Newman, Christy E; Ellard, Jeanne
2017-01-01
With recent breakthroughs in HIV treatment and prevention, the meanings of HIV-positivity and HIV-negativity are changing at biomedical and community levels. We explore how binary constructions of HIV serostatus identities are giving way to something more complex that brings both welcome possibilities and potential concerns. We draw on research with couples with mixed HIV status to argue that, in the context of lived experiences, serostatus identities have always been more ambiguous than allowed for in HIV discourse. However, their supposed dichotomous quality seems even more dubious now in view of contemporary biomedical technologies. Invoking the anthropological concept of "borderlands," we consider how biomedicine is generating more diverse serostatus identities, widening the options for how to live with HIV, and eroding the stigmatizing serostatus binary that has haunted the epidemic. But we also ask whether this emerging borderland, and its "normalizing" tendencies, is concomitantly giving rise to new and troubling binaries.
Current-Current Interactions, Dynamical Symmetry - and Quantum Chromodynamics.
NASA Astrophysics Data System (ADS)
Neuenschwander, Dwight Edward, Jr.
Quantum Chromodynamics with massive gluons (gluon mass (TBOND) xm(,p)) in a contact-interaction limit called CQCD (strong coupling g (--->) (INFIN); x (--->) (INFIN)), despite its non-renormalizability and lack of hope of confinement, is nevertheless interesting for at least two reasons. (1) Some authors have suggested a relation between 4-Fermi and Yang-Mills theories. If g/x('2) << 1, then CQCD is not merely a 4-Fermi interaction, but includes 4, 6, 8, ...-Fermi non-Abelian contact interactions. (2) With the possibility of infrared slavery, perturbative evaluation of QCD in the infrared is a dubious practice. However, if g('2)/x('2) << 1 in CQCD, then the simplest 4-Fermi interaction is dominant, and CQCD admits perturbative treatment, but only in the infrared. With the dominant interaction, a dynamical Nambu-Goldstone realization of chiral symmetry -breaking (XSB) is found. Although in QCD the relation between confinement and XSB is controversial, XSB occurs in CQCD provided confinement is sacrificed.
A dubious defense of 'after-birth abortion': A reply to Räsänen.
Kaczor, Christopher
2018-02-01
Scholars have offered various critiques of Alberto Giubilini and Francesca Minerva's controversial article, 'After-birth abortion: Why should the baby live?' My book The Ethics of Abortion: Women's Rights, Human Life, and the Question of Justice presents four such critiques. First, Giubilini and Minerva argue from the deeply controversial to the even more controversial. Second, they presuppose a false view of personal identity called body-self dualism. Third, their view cannot secure human equality. And fourth, their account of harm cannot account for harm found in some cases of murder. In the article, 'Pro-life arguments against infanticide and why they are not convincing', J. Räsänen examines and finds wanting these four critiques. This essay responds to Räsänen's defense of infanticide and argues that his responses to the four objections fail. © 2017 John Wiley & Sons Ltd.
Alexis Carrel: genius, innovator and ideologist.
Dutkowski, P; de Rougemont, O; Clavien, P-A
2008-10-01
Alexis Carrel was a Frenchman from Lyon, who gained fame at the Rockefeller Institute in New York at the beginning of the 20th century. He was the first to demonstrate that arteriovenous anastomoses were possible. Alexis Carrel was awarded the Nobel Prize for his contributions to vascular surgery and transplantation in 1912. He was a versatile scientist, who made numerous discoveries from the design of an antiseptic solution to treat injuries during the First World War to tissue culture and engineering, and organ preservation, making him the father of solid organ transplantation. Together, with the famous aviator and engineer Charles Lindbergh, they were the first scientists capable of keeping an entire organ alive outside of the body, using a perfusion machine. Due to his many dubious ideas and his association with fascism in the 1930s and during the Second World War, many of his scientific achievements have been forgotten today and taken for granted.
Ethics and forensic psychiatry: translating principles into practice.
Appelbaum, Paul S
2008-01-01
Twenty-five years ago, Alan Stone expressed his skepticism that forensic psychiatry could be practiced ethically. His remarks have proven a useful goad to the field, focusing attention on the importance of an ethics framework for forensic practice. But Stone remains dubious that any system of ethics--including the "Standard Position" on which he focuses his critique--could be of much value in practice. In contrast, I suggest that Stone's pessimism is not well founded. Immanent in forensic practice itself is a reasonable set of ethics principles, based on truth-telling and respect for persons. Psychiatrists can offer reliable and valid testimony, while resisting seduction into an advocacy role. Indeed, with new structured approaches to assessment, the potential utility of forensic testimony is probably greater than ever. Though problematic behavior still exists, forensic psychiatry offers the factual background and interpretive context to allow legal decision-makers to make better choices than they otherwise would.
Kim, Scott Y H; Wall, Ian F; Stanczyk, Aimee; De Vries, Raymond
2009-12-01
In a liberal democracy, policy decisions regarding ethical controversies, including those in research ethics, should incorporate the opinions of its citizens. Eliciting informed and well-considered ethical opinions can be challenging. The issues may not be widely familiar and they may involve complex scientific, legal, historical, and ethical dimensions. Traditional surveys risk eliciting superficial and uninformed opinions that may be of dubious quality for policy formation. We argue that the theory and practice of deliberative democracy (DD) is especially useful in overcoming such inadequacies. We explain DD theory and practice, discuss the rationale for using DD methods in research ethics, and illustrate in depth the use of a DD method for a longstanding research ethics controversy involving research based on surrogate consent. The potential pitfalls of DD and the means of minimizing them as well as future research directions are also discussed.
Bharti, Himender; Guénard, Benoit; Bharti, Meenakshi; Economo, Evan P.
2016-01-01
Abstract As one of the 17 megadiverse countries of the world and with four biodiversity hotspots represented in its borders, India is home to an impressive diversity of life forms. However, much work remains to document and catalogue the species of India and their geographic distributions, especially for diverse invertebrate groups. In the present study, a comprehensive and critical list of Indian ant species is provided with up-to-date state-wise distribution. A total of 828 valid species and subspecies names belonging to 100 genera are listed from India. Potential erroneous data, misidentifications and dubious distributional records that may exist in the literature are also identified. The present exhaustive listing of Indian ants will provide a holistic view about diversity and distribution and will also help to identify major undersampled areas where future sampling and taxonomic efforts should be directed. PMID:26877665
Exploring the Legacies of Filmed Patient Narratives
Robert, Glenn; Maben, Jill
2015-01-01
We trace the legacies of filmed patient narratives that were edited and screened to encourage engagement with a participatory quality improvement project in an acute hospital setting in England. Using Gabriel’s theory of “narrative contract,” we examine the initial success of the films in establishing common grounds for participatory project and later, and more varied, interpretations of the films. Over time, the films were interpreted by staff as either useful sources of learning by critical reflection, dubious (invalid or unreliable) representations of patient experience, or as “closed” items available as auditable evidence of completed quality improvement work. We find these interpretations of the films to be shaped by the effect of social distance, the differential outcomes of project work, and changing organizational agendas. We consider the wider conditions of patient narrative as a form of quality improvement knowledge with immediate potency and fragile or fluid legitimacy over time. PMID:25576480
Legal issues in the development and use of clinical practice guidelines.
Gevers, S
2001-01-01
Over the last ten years, the development and dissemination of practice guidelines has increased at a rapid pace. From a legal point of view, it should always be made clear whether a guideline has been developed to improve the quality of care and is based on medical evidence and professional experience, or whether other concerns and considerations (organisational, financial) did prevail. Guidelines should not simply be imposed on health professionals; that would result in a standardisation of care that does no justice to individual patient needs and preferences. Patients have the right to be informed about reasonable and realistic treatment alternatives, even if they are not included in the guideline. Using cost effectiveness analysis in guideline development can help to reduce care of dubious effectiveness. But if cost considerations are used as a reason to limit effective medical care, the guidelines in question need political legitimation.
NASA Technical Reports Server (NTRS)
Rose, F. G.
1983-01-01
Modeled temperature data from a one-dimensional, time-dependent, initial value, planetary boundary layer model for 16 separate model runs with varying initial values of moisture availability are applied, by the use of a regression equation, to longwave infrared GOES satellite data to infer moisture availability over a regional area in the central U.S. This was done for several days during the summers of 1978 and 1980 where a large gradient in the antecedent precipitation index (API) represented the boundary between a drought area and a region of near normal precipitation. Correlations between satellite derived moisture availability and API were found to exist. Errors from the presence of clouds, water vapor and other spatial inhomogeneities made the use of the measurement for anything except the relative degree of moisture availability dubious.
NASA Technical Reports Server (NTRS)
Powers, Sheryll Goecke
1994-01-01
Being a woman in engineering, and in particular, being the woman with the dubious distinction of having the most years at Dryden, gives the author a long-term perspective on the women who worked in the engineering field and their working environment. The working environment for the women was influenced by two main factors. One factor was the Dryden's growth of 14 persons (2 of them women) at the end of 1946 to the present size. The other factor was the need for programming knowledge when the digital computers came into use. Women have been involved with flight research at Dryden since the days of the first transonic and supersonic airplanes. This paper uses available records, along with memory, to document the number of women in engineering at Dryden, to comment about observed trends, and to make personal observations.
Seven Simple Secrets: What the Best Teachers Know and Do!
ERIC Educational Resources Information Center
Breaux, Annette L.; Whitaker, Todd
2006-01-01
Implementing the secrets presented in this book will change your life both in and out of the classroom. But most importantly, implementing these secrets will enhance the lives of every student you teach. The following are contained in this book: Secret One: The Secret of Planning; Secret Two: The Secret of Classroom Management; Secret Three: The…
Genetic variants and the risk of gestational diabetes mellitus: a systematic review.
Zhang, Cuilin; Bao, Wei; Rong, Ying; Yang, Huixia; Bowers, Katherine; Yeung, Edwina; Kiely, Michele
2013-01-01
Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies. Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity. Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P < 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P = 0.002) per T allele of rs12255372. In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
Will They or Won't They? Secret Telling in Interpersonal Interactions.
Kowalski, Robin Marie; Morgan, Chad Alan; Whittaker, Elizabeth; Zaremba, Brittany; Frazee, Laura; Dean, Jessica
2015-01-01
This study investigated predictors of within-gender secret telling. Eighty-eight participants were exposed to either a "positive" or a "negative" secret about another individual. Just under 20% of participants told the secret. Conscientiousness, secret condition, empathy, and the conscientiousness by secret condition interaction had effects on the rate of secret telling, χ(2) (5,82) = 17.78, p = .003, AIC = 80.60. Conscientiousness had a negative effect on secret telling among participants that told the "negative" secret.
Trade secrets in life science and pharmaceutical companies.
Nealey, Tara; Daignault, Ronald M; Cai, Yu
2014-11-20
Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through "improper means" is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today's interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees' careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
Trade Secrets in Life Science and Pharmaceutical Companies
Nealey, Tara; Daignault, Ronald M.; Cai, Yu
2015-01-01
Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through “improper means” is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today’s interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees’ careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. PMID:25414378
1982-04-01
the secret . In each, we shall consider * the plausible interpretations of the utterance "Do you know the secret ?" Setting 1: If S knows the secret and...believes that H doesn’t know the secret , then "Do you know the secret ?" is probably an offer to tell H the secret . Setting 2: If S doesn’t know the ... secret and believes that H does know the secret then "Do you know the
Molecular Mechanism of Pancreatic and Salivary Glands Fluid and HCO3− Secretion
Lee, Min Goo; Ohana, Ehud; Park, Hyun Woo; Yang, Dongki; Muallem, Shmuel
2013-01-01
Fluid and HCO3− secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO3− secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren’s syndrome and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO3− secretion, in particular by secretory glands. Fluid and HCO3− secretion by secretory glands is a two step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl− and secrete HCO3−. The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete small amount of NaCl-rich fluid, while the duct absorbs the Cl− and secretes HCO3− and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO3− secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that contains high concentrations of Na+ and Cl− and fluid secretion is mediated by active Cl− secretion. The salivary glands duct absorbs both the Na+ and Cl− and secretes K+ and HCO3−. In this review, we focus on the molecular mechanism of fluid and HCO3− secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and point the differences to meet glands specific secretions. PMID:22298651
Airway clearance techniques in neuromuscular disorders: A state of the art review.
Chatwin, Michelle; Toussaint, Michel; Gonçalves, Miguel R; Sheers, Nicole; Mellies, Uwe; Gonzales-Bermejo, Jesus; Sancho, Jesus; Fauroux, Brigitte; Andersen, Tiina; Hov, Brit; Nygren-Bonnier, Malin; Lacombe, Matthieu; Pernet, Kurt; Kampelmacher, Mike; Devaux, Christian; Kinnett, Kathy; Sheehan, Daniel; Rao, Fabrizio; Villanova, Marcello; Berlowitz, David; Morrow, Brenda M
2018-03-01
This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
32 CFR 154.77 - Reporting requirements.
Code of Federal Regulations, 2010 CFR
2010-07-01
... took the action, using the enclosed format: (1) Number of Top Secret, Secret, and Confidential clearances issued; (2) Number of Top Secret, Secret, and Confidential clearances denied; (3) Number of Top...) Total number of personnel holding a clearance for Top Secret, Secret, Confidential and Sensitive...
Code of Federal Regulations, 2010 CFR
2010-07-01
... Security Policy Board. (b) Requirements for physical protection—(1) Top Secret. Top Secret information... of the alarm annunciation. (2) Secret. Secret information shall be stored in the same manner as Top.... Confidential information shall be stored in the same manner as prescribed for Top Secret or Secret information...
Cheng, Yali; Avis, Tyler J; Bolduc, Sébastien; Zhao, Yingyi; Anguenot, Raphaël; Neveu, Bertrand; Labbé, Caroline; Belzile, François; Bélanger, Richard R
2008-12-01
Secretion of recombinant proteins aims to reproduce the correct posttranslational modifications of the expressed protein while simplifying its recovery. In this study, secretion signal sequences from an abundantly secreted 34-kDa protein (P34) from Pseudozyma flocculosa were cloned. The efficiency of these sequences in the secretion of recombinant green fluorescent protein (GFP) was investigated in two Pseudozyma species and compared with other secretion signal sequences, from S. cerevisiae and Pseudozyma spp. The results indicate that various secretion signal sequences were functional and that the P34 signal peptide was the most effective secretion signal sequence in both P. flocculosa and P. antarctica. The cells correctly processed the secretion signal sequences, including P34 signal peptide, and mature GFP was recovered from the culture medium. This is the first report of functional secretion signal sequences in P. flocculosa. These sequences can be used to test the secretion of other recombinant proteins and for studying the secretion pathway in P. flocculosa and P. antarctica.
A new potential secretion pathway for recombinant proteins in Bacillus subtilis.
Wang, Guangqiang; Xia, Yongjun; Gu, Zhennan; Zhang, Hao; Chen, Yong Q; Chen, Haiqin; Ai, Lianzhong; Chen, Wei
2015-11-10
Secretion of cytoplasmic expressed proteins into growth media has significant advantages. Due to the lack of an outer membrane, Bacillus subtilis is considered as a desirable 'cell factory' for the secretion of recombinant proteins. However, bottlenecks in the classical pathway for the secretion of recombinant proteins limit its use on a wide scale. In this study, we attempted to use four typical non-classically secreted proteins as signals to export three recombinant model proteins to the culture medium. All four non-classically secreted proteins can direct the export of the intrinsically disordered nucleoskeletal-like protein (Nsp). Two of them can guide the secretion of alkaline phosphatase (PhoA). One can lead the secretion of the thermostable β-galactosidase BgaB, which cannot be secreted with the aid of typical Sec-dependent signal peptides. Our results show that the non-classically secreted proteins lead the recombinant proteins to the culture medium, and thus non-classical protein secretion pathways can be exploited as a novel secretion pathway for recombinant proteins.
Computing on quantum shared secrets
NASA Astrophysics Data System (ADS)
Ouyang, Yingkai; Tan, Si-Hui; Zhao, Liming; Fitzsimons, Joseph F.
2017-11-01
A (k ,n )-threshold secret-sharing scheme allows for a string to be split into n shares in such a way that any subset of at least k shares suffices to recover the secret string, but such that any subset of at most k -1 shares contains no information about the secret. Quantum secret-sharing schemes extend this idea to the sharing of quantum states. Here we propose a method of performing computation securely on quantum shared secrets. We introduce a (n ,n )-quantum secret sharing scheme together with a set of algorithms that allow quantum circuits to be evaluated securely on the shared secret without the need to decode the secret. We consider a multipartite setting, with each participant holding a share of the secret. We show that if there exists at least one honest participant, no group of dishonest participants can recover any information about the shared secret, independent of their deviations from the algorithm.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Je Min, E-mail: jemin@knu.ac.kr; Department of Horticultural Science, Kyungpook National University, Daegu; Lee, Sang-Jik
Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function inmore » fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.« less
29 CFR 14.20 - Dissemination to individuals and firms outside the executive branch.
Code of Federal Regulations, 2010 CFR
2010-07-01
... following guidelines: (a) Top Secret information. All requests for Top Secret information by an individual... Confidential, Secret, or Top Secret information, a report providing all available details must be immediately... outside the United States. All requests from outside the United States for Top Secret, Secret or...
Byun, Hyunjong; Park, Jiyeon; Kim, Sun Chang; Ahn, Jung Hoon
2017-12-01
Efficient protein production for industrial and academic purposes often involves engineering microorganisms to produce and secrete target proteins into the culture. Pseudomonas fluorescens has a TliDEF ATP-binding cassette transporter, a type I secretion system, which recognizes C-terminal LARD3 signal sequence of thermostable lipase TliA. Many proteins are secreted by TliDEF in vivo when recombined with LARD3, but there are still others that cannot be secreted by TliDEF even when LARD3 is attached. However, the factors that determine whether or not a recombinant protein can be secreted through TliDEF are still unknown. Here, we recombined LARD3 with several proteins and examined their secretion through TliDEF. We found that the proteins secreted via LARD3 are highly negatively charged with highly-acidic isoelectric points (pI) lower than 5.5. Attaching oligo-aspartate to lower the pI of negatively-charged recombinant proteins improved their secretion, and attaching oligo-arginine to negatively-charged proteins blocked their secretion by LARD3. In addition, negatively supercharged green fluorescent protein (GFP) showed improved secretion, whereas positively supercharged GFP did not secrete. These results disclosed that proteins' acidic pI and net negative charge are major factors that determine their secretion through TliDEF. Homology modeling for TliDEF revealed that TliD dimer forms evolutionarily-conserved positively-charged clusters in its pore and substrate entrance site, which also partially explains the pI dependence of the TliDEF-dependent secretions. In conclusion, lowering the isoelectric point improved LARD3-mediated protein secretion, both widening the range of protein targets for efficient production via secretion and signifying an important aspect of ABC transporter-mediated secretions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
The Classification of E-Authentication Protocols for Targeted Applicability
2009-12-01
that the secret is only known to the Claimant and either the Verifier or Relying Party (V/RP), and serves as a form of identifier to the... secret against unauthorized observation. The protection of the secret is critical to prevent potential impersonation attacks. The secret is usually...confident that the Claimant is who he claims, if he is able to prove possession of this secret. 1. Symmetric vs. Asymmetric Secret The secret used by
Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist
Wang, Kaiyu; Gan, Longjie; Jiang, Li; Zhang, Xianhui; Yang, Xiangyue; Chen, Min
2015-01-01
Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (Kd = 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a “double-hit” mouse model of SEB-induced TSS, established via sensitization with d-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS. PMID:25624325
40 CFR 370.64 - What information can I claim as trade secret or confidential?
Code of Federal Regulations, 2011 CFR
2011-07-01
... secret or confidential? 370.64 Section 370.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... secret or confidential? (a) Trade secrets. You may be able to withhold the name of a specific chemical... trade secret. The requirements for withholding trade secret information are set forth in EPCRA section...
40 CFR 370.64 - What information can I claim as trade secret or confidential?
Code of Federal Regulations, 2010 CFR
2010-07-01
... secret or confidential? 370.64 Section 370.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... secret or confidential? (a) Trade secrets. You may be able to withhold the name of a specific chemical... trade secret. The requirements for withholding trade secret information are set forth in EPCRA section...
40 CFR 370.64 - What information can I claim as trade secret or confidential?
Code of Federal Regulations, 2012 CFR
2012-07-01
... secret or confidential? 370.64 Section 370.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... secret or confidential? (a) Trade secrets. You may be able to withhold the name of a specific chemical... trade secret. The requirements for withholding trade secret information are set forth in EPCRA section...
40 CFR 370.64 - What information can I claim as trade secret or confidential?
Code of Federal Regulations, 2013 CFR
2013-07-01
... secret or confidential? 370.64 Section 370.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... secret or confidential? (a) Trade secrets. You may be able to withhold the name of a specific chemical... trade secret. The requirements for withholding trade secret information are set forth in EPCRA section...
40 CFR 370.64 - What information can I claim as trade secret or confidential?
Code of Federal Regulations, 2014 CFR
2014-07-01
... secret or confidential? 370.64 Section 370.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... secret or confidential? (a) Trade secrets. You may be able to withhold the name of a specific chemical... trade secret. The requirements for withholding trade secret information are set forth in EPCRA section...
Venegas-Moreno, Eva; Vazquez-Borrego, Mari C; Dios, Elena; Gros-Herguido, Noelia; Flores-Martinez, Alvaro; Rivero-Cortés, Esther; Madrazo-Atutxa, Ainara; Japón, Miguel A; Luque, Raúl M; Castaño, Justo P; Cano, David A; Soto-Moreno, Alfonso
2018-03-01
Acromegaly is a hormonal disorder resulting from excessive growth hormone (GH) secretion frequently produced by pituitary adenomas and consequent increase in insulin-like growth factor 1 (IGF-I). Elevated GH and IGF-I levels result in a wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Somatostatin analogues (SSAs) form the basis of medical therapy for acromegaly and are currently used as first-line treatment or as second-line therapy in patients undergoing unsuccessful surgery. However, a considerable percentage of patients do not respond to SSAs treatment. Somatostatin receptors (SSTR1-5) and dopamine receptors (DRD1-5) subtypes play critical roles in the regulation of hormone secretion. These receptors are considered important pharmacological targets to inhibit hormone oversecretion. It has been proposed that decreased expression of SSTRs may be associated with poor response to SSAs. Here, we systematically examine SSTRs and DRDs expression in human somatotroph adenomas by quantitative PCR. We observed an association between the response to SSAs treatment and DRD4, DRD5, SSTR1 and SSTR2 expression. We also examined SSTR expression by immunohistochemistry and found that the immunohistochemical detection of SSTR2 in particular might be a good predictor of response to SSAs. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
The effects of Ramadan fasting on the health and function of the eye
Javadi, Mohammad Ali; Assadi, Mahsan; Einollahi, Bahram; Rabei, Hossein Mohammad; Afarid, Mehrdad; Assadi, Majid
2014-01-01
Background: Ramadan fasting may alter a variety of physiological parameters which by themselves influence ocular system. Here, we review the effects of Ramadan fasting on the health and function of the eye. Materials and Methods: Literature records in PubMed/MEDLINE, Web of Science, EMBASE, Google Scholar, and Iran Medex databases as well as proceedings of related meetings from January 1986 to March 2014 were systematically reviewed. The search key words was based on the terms “Ramadan Fasting,” “Ramadan,” “Islamic Fasting,” “Fasting in Ramadan” accompanied with one of the eye, tear drop, myopia, intraocular pressure (IOP), tear break up time, basal tear secretion, refractive error, and visual acuity. Results: Predawn water loading and dehydration in the evening are shown to increase and decrease IOP and tear secretion, respectively. Ocular blood flow is changed in Ramadan fasting, and patients with ocular vein occlusion may experience more frequent attacks. There are no or minimal fluctuations in visual acuity and refractive errors, but most of them are decompensated after Ramadan. Conclusion: Although the influence of fasting in different eye parameters is evaluated in several studies, there are no or only limited studies conducted on patients suffering from glaucoma, damage to ophthalmic vasculature, tear dysfunction, and minimal visual acuity. Such studies are required to make a definite decision before fasting is declared harmless to these patients. PMID:25422666
Wu, Yuantai; Janetopoulos, Chris
2013-01-01
While GABA has been suggested to regulate spore encapsulation in the social amoeba Dictyostelium discoideum, the metabolic profile and other potential functions of GABA during development remain unclear. In this study, we investigated the homeostasis of GABA metabolism by disrupting genes related to GABA metabolism and signaling. Extracellular levels of GABA are tightly regulated during early development, and GABA is generated by the glutamate decarboxylase, GadB, during growth and in early development. However, overexpression of the prespore-specific homologue, GadA, in the presence of GadB reduces production of extracellular GABA. Perturbation of extracellular GABA levels delays the process of aggregation. Cytosolic GABA is degraded by the GABA transaminase, GabT, in the mitochondria. Disruption of a putative vesicular GABA transporter (vGAT) homologue DdvGAT reduces secreted GABA. We identified the GABAB receptor-like family member GrlB as the major GABA receptor during early development, and either disruption or overexpression of GrlB delays aggregation. This delay is likely the result of an abolished pre-starvation response and late expression of several “early” developmental genes. Distinct genes are employed for GABA generation during sporulation. During sporulation, GadA alone is required for generating GABA and DdvGAT is likely responsible for GABA secretion. GrlE but not GrlB is the GABA receptor during late development. PMID:23548898
Gao, Wen; Yin, Jun; Bao, Lichen; Wang, Qun; Hou, Shan; Yue, Yali; Yao, Wenbing; Gao, Xiangdong
2018-05-18
Escherichia coli extracellular expression systems have a number of advantages over other systems, such as lower pyrogen levels and a simple purification process. Various approaches, such as the generation of leaky mutants via chromosomal engineering, have been explored for this expression system. However, extracellular protein yields in leaky mutants are relatively low compared to that in intracellular expression systems and therefore need to be improved. In this work, we describe the construction, characterization, and mechanism of enhanced extracellular expression in Escherichia coli. On the basis of the localizations, functions, and transcription levels of cell envelope proteins, we systematically elucidated the effects of multiple gene deletions on cell growth and extracellular expression using modified CRISPR/Cas9-based genome editing and a FlAsH labeling assay. High extracellular yields of heterologous proteins of different sizes were obtained by screening multiple gene mutations. The enhancement of extracellular secretion was associated with the derepression of translation and translocation. This work utilized universal methods in the design of extracellular expression systems for genes not directly associated with protein synthesis that were used to generate strains with higher protein expression capability. We anticipate that extracellular expression systems may help to shed light on the poorly understood aspects of these secretion processes as well as to further assist in the construction of engineered prokaryotic cells for efficient extracellular production of heterologous proteins.
Micha, Renata; Wu, Jason H. Y.; de Oliveira Otto, Marcia C.; Mozaffarian, Dariush
2016-01-01
Background Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis. Methods and Findings We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias. Conclusions This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity. PMID:27434027
Sun, Hongxin; Niisato, Naomi; Nishio, Kyosuke; Hamilton, Kirk L.; Marunaka, Yoshinori
2014-01-01
Epithelial Cl− secretion plays important roles in water secretion preventing bacterial/viral infection and regulation of body fluid. We previously suggested that quercetin would be a useful compound for maintaining epithelial Cl− secretion at a moderate level irrespective of cAMP-induced stimulation. However, we need a compound that stimulates epithelial Cl− secretion even under cAMP-stimulated conditions, since in some cases epithelial Cl− secretion is not large enough even under cAMP-stimulated conditions. We demonstrated that quercetin and myricetin, flavonoids, stimulated epithelial Cl− secretion under basal conditions in epithelial A6 cells. We used forskolin, which activates adenylyl cyclase increasing cytosolic cAMP concentrations, to study the effects of quercetin and myricetin on cAMP-stimulated epithelial Cl− secretion. In the presence of forskolin, quercetin diminished epithelial Cl− secretion to a level similar to that with quercetin alone without forskolin. Conversely, myricetin further stimulated epithelial Cl− secretion even under forskolin-stimulated conditions. This suggests that the action of myricetin is via a cAMP-independent pathway. Therefore, myricetin may be a potentially useful compound to increase epithelial Cl− secretion under cAMP-stimulated conditions. In conclusion, myricetin would be a useful compound for prevention from bacterial/viral infection even under conditions that the amount of water secretion driven by cAMP-stimulated epithelial Cl− secretion is insufficient. PMID:24818160
Comparison of Western and Asian Guidelines Concerning the Management of Colon Cancer.
Pellino, Gianluca; Warren, Oliver; Mills, Sarah; Rasheed, Shahnawaz; Tekkis, Paris P; Kontovounisios, Christos
2018-02-01
Guidelines are important to standardize treatments and optimize outcomes. Several societies have published authoritative guidelines for patients with colon cancer, and a certain degree of variation can be predicted. This study aims to compare Western and Asian guidelines for the management of colon cancer. A literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies published between 2010 and 2017 by the online resources from the official Web sites of the societies/panels. Sources included guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network. Only full-text studies and the latest guidelines dealing with colon cancer were included. Studies and guidelines were separately assessed by 2 authors, who independently identified discrepancies and areas for further research. These were discussed and agreed with by all the authors. The recommendations of the guidelines of each society were compared, seeking discrepancies and potential areas for improvement. Endoscopic techniques for the management of early colon cancer are discussed in detail in the Asian guidelines. Asian guidelines advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in selected T2 patients, whereas such an approach is still under investigation in Western countries. Only US guidelines describe neoadjuvant chemotherapy and radiotherapy. All the guidelines recommend adjuvant treatment in selected stage II patients, but agreement exists that this is performed without solid evidence, because better outcomes are hypothesized based on studies including stage III or stage II/III patients. The role of cytoreductive surgery with intra-abdominal chemotherapy is dubious, and European guidelines only recommend it in the setting of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal disease. Only US guidelines include a patient advocate in the drafting panel. Bias may have arisen from country-specific socioeconomic and cultural issues, and from the latest available updates. Surgical approaches to colon cancer differ significantly among Western and Asian guidelines, reflecting different concepts of treatment. The role of adjuvant treatment in node-negative disease and quality-of-life assessment need further research.
YscU/FlhB of Yersinia pseudotuberculosis Harbors a C-terminal Type III Secretion Signal*
Login, Frédéric H.; Wolf-Watz, Hans
2015-01-01
All type III secretion systems (T3SS) harbor a member of the YscU/FlhB family of proteins that is characterized by an auto-proteolytic process that occurs at a conserved cytoplasmic NPTH motif. We have previously demonstrated that YscUCC, the C-terminal peptide generated by auto-proteolysis of Yersinia pseudotuberculosis YscU, is secreted by the T3SS when bacteria are grown in Ca2+-depleted medium at 37 °C. Here, we investigated the secretion of this early T3S-substrate and showed that YscUCC encompasses a specific C-terminal T3S signal within the 15 last residues (U15). U15 promoted C-terminal secretion of reporter proteins like GST and YopE lacking its native secretion signal. Similar to the “classical” N-terminal secretion signal, U15 interacted with the ATPase YscN. Although U15 is critical for YscUCC secretion, deletion of the C-terminal secretion signal of YscUCC did neither affect Yop secretion nor Yop translocation. However, these deletions resulted in increased secretion of YscF, the needle subunit. Thus, these results suggest that YscU via its C-terminal secretion signal is involved in regulation of the YscF secretion. PMID:26338709
Prediabetes in Pediatric Recipients of Liver Transplant: Mechanism and Risk Factors.
Perito, Emily R; Lustig, Robert H; Rosenthal, Philip
2017-03-01
To investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths. This was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL). Corrected insulin response (CIR) was calculated as measure of insulin secretion, corrected for glucose (CIR 30 , CIR 60 , CIR 120 ). Subjects were aged 8.1-30.0 years and 1.1-24.7 years post-transplant; 44% had prediabetes-27% IGT, 14% IFG, and 3% both. IGT was characterized by insulin hyposecretion, with lower CIR 60 and CIR 120 in IGT than subjects with normal glucose tolerance. Subjects with tacrolimus trough >6 µg/mL at study visit had lower CIR 120 than those with trough ≤6 µg/mL and those off calcineurin-inhibitors. Mean of tacrolimus troughs preceding the study visit, years since transplant, and rejection episodes were not associated significantly with lower CIR. CIR suppression by tacrolimus was most pronounced >6 years from transplant. Overweight/obese subjects and adolescents who retained normal glucose tolerance had greater CIR than those who were IGT. IGT after pediatric liver transplant is driven by inadequate insulin secretion. It is quite common but not detectable with fasting laboratory values-the screening recommended by current guidelines. Calcineurin inhibitors suppress insulin secretion in these patients in a dose-dependent manner. Given the recent focus on long-term outcomes and immunosuppression withdrawal in these children, longitudinal studies are warranted to investigate whether IGT is reversible with calcineurin inhibitor minimization. Copyright © 2016 Elsevier Inc. All rights reserved.
Matroids and quantum-secret-sharing schemes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sarvepalli, Pradeep; Raussendorf, Robert
A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previousmore » work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.« less
YscU/FlhB of Yersinia pseudotuberculosis Harbors a C-terminal Type III Secretion Signal.
Login, Frédéric H; Wolf-Watz, Hans
2015-10-23
All type III secretion systems (T3SS) harbor a member of the YscU/FlhB family of proteins that is characterized by an auto-proteolytic process that occurs at a conserved cytoplasmic NPTH motif. We have previously demonstrated that YscUCC, the C-terminal peptide generated by auto-proteolysis of Yersinia pseudotuberculosis YscU, is secreted by the T3SS when bacteria are grown in Ca(2+)-depleted medium at 37 °C. Here, we investigated the secretion of this early T3S-substrate and showed that YscUCC encompasses a specific C-terminal T3S signal within the 15 last residues (U15). U15 promoted C-terminal secretion of reporter proteins like GST and YopE lacking its native secretion signal. Similar to the "classical" N-terminal secretion signal, U15 interacted with the ATPase YscN. Although U15 is critical for YscUCC secretion, deletion of the C-terminal secretion signal of YscUCC did neither affect Yop secretion nor Yop translocation. However, these deletions resulted in increased secretion of YscF, the needle subunit. Thus, these results suggest that YscU via its C-terminal secretion signal is involved in regulation of the YscF secretion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Autocrine effect of Zn²⁺ on the glucose-stimulated insulin secretion.
Slepchenko, Kira G; Daniels, Nigel A; Guo, Aili; Li, Yang V
2015-09-01
It is well known that zinc (Zn(2+)) is required for the process of insulin biosynthesis and the maturation of insulin secretory granules in pancreatic beta (β)-cells, and that changes in Zn(2+) levels in the pancreas have been found to be associated with diabetes. Glucose-stimulation causes a rapid co-secretion of Zn(2+) and insulin with similar kinetics. However, we do not know whether Zn(2+) regulates insulin availability and secretion. Here we investigated the effect of Zn(2+) on glucose-stimulated insulin secretion (GSIS) in isolated mouse pancreatic islets. Whereas Zn(2+) alone (control) had no effect on the basal secretion of insulin, it significantly inhibited GSIS. The application of CaEDTA, by removing the secreted Zn(2+) from the extracellular milieu of the islets, resulted in significantly increased GSIS, suggesting an overall inhibitory role of secreted Zn(2+) on GSIS. The inhibitory action of Zn(2+) was mostly mediated through the activities of KATP/Ca(2+) channels. Furthermore, during brief paired-pulse glucose-stimulated Zn(2+) secretion (GSZS), Zn(2+) secretion following the second pulse was significantly attenuated, probably by the secreted endogenous Zn(2+) after the first pulse. Such an inhibition on Zn(2+) secretion following the second pulse was completely reversed by Zn(2+) chelation, suggesting a negative feedback mechanism, in which the initial glucose-stimulated Zn(2+) release inhibits subsequent Zn(2+) secretion, subsequently inhibiting insulin co-secretion as well. Taken together, these data suggest a negative feedback mechanism on GSZS and GSIS by Zn(2+) secreted from β-cells, and the co-secreted Zn(2+) may act as an autocrine inhibitory modulator.
10 CFR 1045.17 - Classification levels.
Code of Federal Regulations, 2010 CFR
2010-01-01
...) Top Secret. The Director of Classification shall classify RD information Top Secret if it is vital to... exceptionally grave damage to the national security. Examples of RD information that warrant Top Secret... comprehensive to warrant designation as Top Secret. Examples of RD information that warrant Secret...
Hepp, Christof; Maier, Berenike
2017-10-01
Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. Bacteria employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.
Salmonella-secreted Virulence Factors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heffron, Fred; Niemann, George; Yoon, Hyunjin
In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellentmore » reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.« less
Verifiable Secret Redistribution
2001-10-01
but they are not trusted with secret. Thus, we require a protocol for redistribution without reconstruction of the secret . We also require...verification that the new shareholders have valid shares (ones that can be used to reconstruct the secret ). We present a new protocol to perform non...secret to shareholders in Shamir’s (m,n) threshold scheme (one in which we require m of n shares to reconstruct the secret ), and wish to redistribute the
Unitary reconstruction of secret for stabilizer-based quantum secret sharing
NASA Astrophysics Data System (ADS)
Matsumoto, Ryutaroh
2017-08-01
We propose a unitary procedure to reconstruct quantum secret for a quantum secret sharing scheme constructed from stabilizer quantum error-correcting codes. Erasure correcting procedures for stabilizer codes need to add missing shares for reconstruction of quantum secret, while unitary reconstruction procedures for certain class of quantum secret sharing are known to work without adding missing shares. The proposed procedure also works without adding missing shares.
Solís, Stella M; Zini, Lucía M; González, Valeria V; Ferrucci, María S
2017-11-01
We investigated the morphology and structure of the floral nectary in 11 Neotropical genera belonging to the subfamilies Dodonaeoideae and Paullinioideae (Sapindaceae) from southern South America representing three tribes (Dodonaeaeae, Paullinieae, and Melicocceae), in relation to other floral traits in species with contrasting morphological flower characteristics. Nectary organization was analyzed under light, stereoscopic, and scanning electron microscopes; Diplokeleba floribunda N.E. Br. was also observed using transmission electron microscopy. Our comparative data may contribute to the understanding of floral nectary evolution and systematic value in this family. The nectaries were studied in both staminate and pistillate flowers. All the floral nectaries are typical of Sapindaceae: extrastaminal, receptacular, structured, and persistent. The anatomical analysis revealed a differentiated secretory parenchyma and an inner non-secretory parenchyma; the nectary is supplied by phloem traces and, less frequently, by phloem and xylem traces. Nectar is secreted through nectarostomata of anomocytic type. The anatomical analysis showed the absence of nectary in the three morphs of Dodonaea viscosa flowers. Nectary ultrastructure is described in D. floribunda. In this species, the change in nectary color is related to progressive accumulation of anthocyanins during the functional phase. We found relatively small variation in the nectary structural characteristics compared with large variation in nectary morphology. The latter aspect agreed with the main infrafamilial groupings revealed by recent phylogenetic studies, so it is of current valuable systematic importance for Sapindaceae. In representatives of Paullinieae, the reduction of the floral nectary to 4-2 posterior lobes should be interpreted as a derived character state.
Li, Ling-Wei; Wong, Hai Ming; Sun, Ling; Wen, Yi Feng; McGrath, Colman P
2015-11-01
The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2-18-y-old participants were included. An initial search identified 4191 papers; 278 potentially effective studies (k = 0.82) and 16 effective studies (k = 0.83) were included after screening. The mean quality of evidence among the studies was 20.3, according to the Strengthening the Reporting of Observational studies in Epidemiology checklist (k = 0.79). Meta-analyses showed that obesity (measured by body mass index) was significantly associated with visible plaque index (OR: 4.75; 95% CI: 2.42, 9.34), bleeding on probing (OR: 5.41; 95% CI: 2.75, 10.63), subgingival calculus (OR: 3.07; 95% CI: 1.10, 8.62), probing depth (OR: 14.15; 95% CI: 5.10, 39.25) and flow rate of salivary secretion (standardized mean difference: -0.89; 95% CI: -1.18, -0.61). However, various results were reported in the effective studies that were not included in meta-analyses. In conclusion, obesity is associated with some signs of periodontal disease in children and adolescents. Further studies with a comprehensive prospective cohort design and more potential variables are recommended. © 2015 American Society for Nutrition.
Li, Ling-Wei; Wong, Hai Ming; Sun, Ling; Wen, Yi Feng; McGrath, Colman P
2015-01-01
The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2–18-y-old participants were included. An initial search identified 4191 papers; 278 potentially effective studies (k = 0.82) and 16 effective studies (k = 0.83) were included after screening. The mean quality of evidence among the studies was 20.3, according to the Strengthening the Reporting of Observational studies in Epidemiology checklist (k = 0.79). Meta-analyses showed that obesity (measured by body mass index) was significantly associated with visible plaque index (OR: 4.75; 95% CI: 2.42, 9.34), bleeding on probing (OR: 5.41; 95% CI: 2.75, 10.63), subgingival calculus (OR: 3.07; 95% CI: 1.10, 8.62), probing depth (OR: 14.15; 95% CI: 5.10, 39.25) and flow rate of salivary secretion (standardized mean difference: −0.89; 95% CI: −1.18, −0.61). However, various results were reported in the effective studies that were not included in meta-analyses. In conclusion, obesity is associated with some signs of periodontal disease in children and adolescents. Further studies with a comprehensive prospective cohort design and more potential variables are recommended. PMID:26567204
Niu, Shu-Fen; Chung, Min-Huey; Chen, Chiung-Hua; Hegney, Desley; O'Brien, Anthony; Chou, Kuei-Ru
2011-03-01
Disrupted circadian rhythm, especially working night duty together with irregular sleep patterns, sleep deprivation, and fatigue, creates an occupational health risk associated with diminished vigilance and work performance. This study reviewed the effect of shift rotations on employee cortisol profile, sleep quality, fatigue, and attention level. Researchers conducted a systematic review of relevant articles published between 1996 and 2008 that were listed on the following databases: SCOPUS, OVID, Blackwell Science, EBSCO Host, PsycINFO, Cochrane Controlled Trials Register, and CEPS. A total of 28 articles were included in the review. Previous research into the effects of shift work on cortisol profiles, sleep quality, fatigue, and attention used data assessed at evidence Levels II to IV. Our systematic review confirmed a conflict between sleep-wake cycle and light-dark cycle in night work. Consequences of circadian rhythm disturbance include disruption of sleep, decreased vigilance, general feeling of malaise, and decreased mental efficiency. Shift workers who sleep during the day (day sleepers) experience cortisol secretion increases, which diminish the healing power of sleep and enjoy 1 to 4 hours less sleep on average than night sleepers. Sleep debt accumulation results in chronic fatigue. Prolonged fatigue and inadequate recovery result in decreased work performance and more incidents. Rotation from day shift to night shift and its effect on shift workers was a special focus of the articles retained for review. Disturbed circadian rhythm in humans has been associated with a variety of mental and physical disorders and may negatively impact on work safety, performance, and productivity.
Megli, Christina J.
2013-01-01
Type IV pili are important for microcolony formation, biofilm formation, twitching motility, and attachment. We and others have shown that type IV pili are important for protein secretion across the outer membrane, similar to type II secretion systems. This study explored the relationship between protein secretion and pilus formation in Vibrio cholerae. The toxin-coregulated pilus (TCP), a type IV pilus required for V. cholerae pathogenesis, is necessary for the secretion of the colonization factor TcpF (T. J. Kirn, N. Bose, and R. K. Taylor, Mol. Microbiol. 49:81–92, 2003). This phenomenon is not unique to V. cholerae; secreted virulence factors that are dependent on the presence of components of the type IV pilus biogenesis apparatus for secretion have been reported with Dichelobacter nodosus (R. M. Kennan, O. P. Dhungyel, R. J. Whittington, J. R. Egerton, and J. I. Rood, J. Bacteriol. 183:4451–4458, 2001) and Francisella tularensis (A. J. Hager et al., Mol. Microbiol. 62:227–237, 2006). Using site-directed mutagenesis, we demonstrated that the secretion of TcpF is dependent on the presence of selected amino acid R groups at position five. We were unable to find other secretion determinants, suggesting that Y5 is the major secretion determinant within TcpF. We also report that proteins secreted in a type IV pilus biogenesis apparatus-dependent manner have a YXS motif within the first 15 amino acids following the Sec cleavage site. The YXS motif is not present in proteins secreted by type II secretion systems, indicating that this is unique to type IV pilus-mediated secretion. Moreover, we show that TcpF interacts with the pilin TcpA, suggesting that these proteins are secreted by the type IV pilus biogenesis system. These data provide a starting point for understanding how type IV pili can mediate secretion of virulence factors important for bacterial pathogenesis. PMID:23564177
The Utility of Free Software for Gravity and Magnetic Advanced Data Processing
NASA Astrophysics Data System (ADS)
Grandis, Hendra; Dahrin, Darharta
2017-04-01
The lack of computational tools, i.e. software, often hinders the proper teaching and application of geophysical data processing in academic institutions in Indonesia. Although there are academic licensing options for commercial software, such options are still way beyond the financial capability of some academic institutions. Academic community members (both lecturers and students) are supposed to be creative and resourceful to overcome such situation. Therefore, capability for writing computer programs or codes is a necessity. However, there are also many computer programs and even software that are freely available on the internet. Generally, the utility of the freely distributed software is limited for demonstration only or for visualizing and exchanging data. The paper discusses the utility of Geosoft’s Oasis Montaj Viewer along with USGS GX programs that are available for free. Useful gravity and magnetic advanced data processing (i.e. gradient calculation, spectral analysis etc.) can be performed “correctly” without any approximation that sometimes leads to dubious results and interpretation.
NASA Astrophysics Data System (ADS)
Walder, Joseph S.
I have read the recent Forum commentaries describing disgruntlement with particular anonymous reviews (1 July 2003 and 29 July 2003 issues), and nodded sympathetically. After all, who among us has not felt, at one time or another, that a reviewer badly misunderstood our contribution to the scientific literature or our grant proposal? But each of these recent Forum contributors in fact committed the elementary logical error of invoking anecdotal evidence to prove a point. I doubt that any of these correspondents would accept scientific claims based on anecdotes. Yet somehow they believe that anecdotes form a sufficient basis for claiming that anonymous reviewing is inherently a nasty business. These correspondents further employed the dubious rhetorical device of contrasting their own self-defined, high ethical standards with those of their adversaries, whom they variously described as rude, hostile, vindictive, lazy, cowardly, selfish, bigoted against women and minorities, and attired in “the costume of crooks.” The parallel with the discourse of political argument is hard to miss.
CerÍaco, Luis M P; Marques, Mariana P; Bauer, Aaron M
2018-02-26
Five problematic cases regarding the presence of reptile taxa on the island of São Tomé (Gulf of Guinea) are reviewed. These cases deal with 1) the past presence of crocodilians in the island, 2) the putative type locality of Dipsas pulverulenta Fischer, 1856, 3) the dubious presence of a mamba (genus Dendroaspis) on the island, 4) an erroneous reference to the presence of Gastropyxis smaragdina, and 5) two specimens (Psammophis lineatus and Psammophis elegans) from Carl Weiss collection, currently deposited in the Zoological Museum of Hamburg and wrongly labelled as being from São Tomé island. A provisional checklist to the terrestrial herpetofauna of the three oceanic islands of the Gulf of Guinea-São Tomé, Príncipe and Annobon-is presented in order to clarify the current numbers of the endemics of each island, as well as to review and present current research.
Commercialism, choice and consumer protection: regulation of complementary medicines in Australia.
Harvey, Ken J; Korczak, Viola S; Marron, Loretta J; Newgreen, David B
2008-01-07
Controls on the supply and promotion of complementary medicines in Australia are weak. We used weight-loss products as an example to compare the regulation in Australia of listed complementary medicines and registered pharmaceutical products. Complementary medicines are listed without evaluation for efficacy, while conventional pharmaceutical products are registered after evaluation for quality, safety and efficacy. From 1996 to 2006, over 1000 "weight-loss" products were listed on the Australian Register of Therapeutic Goods; most contained multiple unevaluated ingredients (herbs, vitamins, minerals) of dubious efficacy. Over the same period, 10 conventional medicines were registered; each contained one evaluated ingredient of proven efficacy. The number of listed weight-loss products (and complaints about their promotion) is increasing. These appear to be a direct consequence of the decision not to evaluate listed products for efficacy and the lower fees for listing a product, compared with registration. Complaint procedures (now overloaded) are no substitute for adequate regulation at the time of market entry. Regulatory reform of listed and homoeopathic products is required.
Adams, Mary; Robert, Glenn; Maben, Jill
2015-09-01
We trace the legacies of filmed patient narratives that were edited and screened to encourage engagement with a participatory quality improvement project in an acute hospital setting in England. Using Gabriel's theory of "narrative contract," we examine the initial success of the films in establishing common grounds for participatory project and later, and more varied, interpretations of the films. Over time, the films were interpreted by staff as either useful sources of learning by critical reflection, dubious (invalid or unreliable) representations of patient experience, or as "closed" items available as auditable evidence of completed quality improvement work. We find these interpretations of the films to be shaped by the effect of social distance, the differential outcomes of project work, and changing organizational agendas. We consider the wider conditions of patient narrative as a form of quality improvement knowledge with immediate potency and fragile or fluid legitimacy over time. © The Author(s) 2015.
Current-current interactions, dynamical symmetry-breaking, and quantum chromodynamics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Neuenschwander, D.E. Jr.
1983-01-01
Quantum Chromodynamics with massive gluons (gluon mass triple bond xm/sub p/) in a contact-interaction limit called CQCD (strong coupling g..-->..infinity; x..-->..infinity), despite its non-renormalizability and lack of hope of confinement, is nevertheless interesting for at least two reasons. Some authors have suggested a relation between 4-Fermi and Yang-Mills theories. If g/x/sup 2/ much less than 1, then CQCD is not merely a 4-Fermi interaction, but includes 4,6,8 etc-Fermi non-Abelian contact interactions. With possibility of infrared slavery, perturbative evaluation of QCD in the infrared is a dubious practice. However, if g/sup 2//x/sup 2/ much less than 1 in CQCD, then themore » simplest 4-Fermi interaction is dominant, and CQCD admits perturbative treatment, but only in the infrared. With the dominant interaction, a dynamical Nambu-Goldstone realization of chiral symmetry-breaking (XSB) is found. Although in QCD the relation between confinement and XSB is controversial, XSB occurs in CQCD provided confinement is sacrificed.« less
Rabies Prevention and Management of Cats in the Context of Trap, Neuter, Vaccinate, Release Programs
Roebling, Allison D.; Johnson, Dana; Blanton, Jesse D.; Levin, Michael; Slate, Dennis; Fenwick, George; Rupprecht, Charles E.
2016-01-01
Summary Domestic cats are an important part of many Americans’ lives, but effective control of the 60–100 million feral cats living throughout the country remains problematic. Although Trap-Neuter-Vaccinate-Return (TNVR) programs are growing in popularity as alternatives to euthanizing feral cats, their ability to adequately address disease threats and population growth within managed cat colonies is dubious. Rabies transmission via feral cats is a particular concern as demonstrated by the significant proportion of rabies postexposure prophylaxis associated with exposures involving cats. Moreover, TNVR has not been shown to reliably reduce feral cat colony populations because of low implementation rates, inconsistent maintenance, and immigration of unsterilized cats into colonies. For these reasons, TNVR programs are not effective methods for reducing public health concerns or for controlling feral cat populations. Instead, responsible pet ownership, universal rabies vaccination of pets, and removal of strays remain integral components to control rabies and other diseases. PMID:23859607
Rabies prevention and management of cats in the context of trap-neuter-vaccinate-release programmes.
Roebling, A D; Johnson, D; Blanton, J D; Levin, M; Slate, D; Fenwick, G; Rupprecht, C E
2014-06-01
Domestic cats are an important part of many Americans' lives, but effective control of the 60-100 million feral cats living throughout the country remains problematic. Although trap-neuter-vaccinate-return (TNVR) programmes are growing in popularity as alternatives to euthanizing feral cats, their ability to adequately address disease threats and population growth within managed cat colonies is dubious. Rabies transmission via feral cats is a particular concern as demonstrated by the significant proportion of rabies post-exposure prophylaxis associated with exposures involving cats. Moreover, TNVR has not been shown to reliably reduce feral cat colony populations because of low implementation rates, inconsistent maintenance and immigration of unsterilized cats into colonies. For these reasons, TNVR programmes are not effective methods for reducing public health concerns or for controlling feral cat populations. Instead, responsible pet ownership, universal rabies vaccination of pets and removal of strays remain integral components to control rabies and other diseases. © 2013 Blackwell Verlag GmbH.
Complex mediascapes, complex realities: critically engaging with biotechnology debates in Ghana.
Rock, Joeva
2018-01-01
The recent increase in research and commercialization of genetically modified (GM) crops in Africa has resulted in considerable and understandable interest from farmers, scholars, and practitioners. However, messy situations are often hard to critically engage in from afar, and the recent article published by Braimah et al. [(2017). Debated agronomy: Public discourse and the future of biotechnology policy in Ghana. Global Bioethics . doi:10.1080/11287462.2016.1261604] presents certain claims that further obfuscate - rather than clarify - an already complex landscape. In this commentary I first seek to clarify particular details of the Ghanaian "GMO" (as GM crops are colloquially called in Ghana) story with particular focus on certain actors and their stances. Next, I highlight some methodological shortcomings of Debated Agronomy and correct certain dubious quotations and claims. Finally, I suggest a more ethnographically and discourse-focused methodology to gain much needed insight into how Ghanaians are actively molding, contesting, and questioning GM discourse, funding, and use.
Primordial Black Holes from First Principles (Overview)
NASA Astrophysics Data System (ADS)
Lam, Casey; Bloomfield, Jolyon; Moss, Zander; Russell, Megan; Face, Stephen; Guth, Alan
2017-01-01
Given a power spectrum from inflation, our goal is to calculate, from first principles, the number density and mass spectrum of primordial black holes that form in the early universe. Previously, these have been calculated using the Press- Schechter formalism and some demonstrably dubious rules of thumb regarding predictions of black hole collapse. Instead, we use Monte Carlo integration methods to sample field configurations from a power spectrum combined with numerical relativity simulations to obtain a more accurate picture of primordial black hole formation. We demonstrate how this can be applied for both Gaussian perturbations and the more interesting (for primordial black holes) theory of hybrid inflation. One of the tools that we employ is a variant of the BBKS formalism for computing the statistics of density peaks in the early universe. We discuss the issue of overcounting due to subpeaks that can arise from this approach (the ``cloud-in-cloud'' problem). MIT UROP Office- Paul E. Gray (1954) Endowed Fund.
Measurements of the Free-Stream Fluctuations above a Turbulent Boundary Layer
NASA Technical Reports Server (NTRS)
Wood, D. H.; Westphal, R. V.
1988-01-01
In this paper an investigation of the velocity fluctuations in the free stream above an incompressible turbulent boundary layer developing at constant pressure is described. It is assumed that the fluctuations receive contributions from three statistically independent sources: (1) one-dimensional unsteadiness, (2) free-stream turbulence, and (3) the irrotational motion induced by the turbulent boundary layer. Measurements were made in a wind tunnel with a root-mean-square level of the axial velocity fluctuations of about 0.2%. All three velocity components were measured using an X-wire probe. The unsteadiness was determined from the spanwise covariance of the axial velocity fluctuations, measured using two single-wire probes. The results show that it is possible to separate the contributions to the rms level of the velocity fluctuations without resorting to the dubious technique of high-pass filtering. This separation could be extended to the spectral densities of the contributions if measurements of sufficient accuracy were available.
Measurements of the free stream fluctuations above a turbulent boundary layer
NASA Technical Reports Server (NTRS)
Wood, David H.; Westphal, Russell V.
1987-01-01
This paper investigates the velocity fluctuations in the free stream above an incompressible turbulent boundary layer developing at constant pressure. It is assumed that the fluctuations receive contributions from three statistically independent sources: (1) one-dimensional unsteadiness, (2) free stream turbulence, and (3) the potential motion induced by the turbulent boundary layer. Measurements were made in a wind tunnel with a root-mean-square level of the axial velocity fluctuations of about 0.2 percent. All three velocity components were measured using an X-wire probe. The unsteadiness was determined from the spanwise covariance of the axial velocity, measured using two single wire probes. The results show that it is possible to separate the contributions to the r.m.s. level of the velocity fluctuations, without resorting to the dubious technique of high-pass filtering. The separation could be extended to the spectral densities of the contributions, if measurements of sufficient accuracy were available. The Appendix provides a general guide for the measurement of small free stream fluctuation levels.
Eidecker, Judith; Glöckner-Rist, Angelika; Gerlach, Alexander L
2010-08-01
The Social Interaction and Anxiety Scale (SIAS) is widely used to assess social interaction anxiety. Yet its dimensional structure is still not well-defined. Especially, the conceptual pertinence of three negatively keyed items has been challenged. In this study, dimensionality of the answers of a student sample to a German SIAS version was first analyzed exploratorily. Subsequently, we tested confirmatorily several measurement models specifying different SIAS dimensions, and investigated how these relate to extraversion. The most reasonable model was cross-validated relying on data from healthy controls and social phobia sufferers. All analyses involved methods suited for an adequate handling of ordinal data. The findings confirm that three negatively keyed items are dubious indicators of social interaction anxiety. Thus, only the remaining 17 items should be used for this purpose in future studies. Analyses of their psychometric properties show, in addition, that they apparently tap three different facets of social interaction anxiety. (c) 2010 Elsevier Ltd. All rights reserved.
Mulder, Mark T
2012-01-01
Present patterns of residential segregation have been proven to have antecedents in the so-called white flight of the 1950s, 1960s, and 1970s. Close scrutiny of this social phenomenon has yielded results that indicate complicated impetuses and call into question sweeping assumptions about white flight. A case study of seven congregations from a denomination called the Christian Reformed Church in North America (CRC) who left the Englewood and Roseland neighborhoods of Chicago during the juncture in question further reveals the dubious role of religious practices and arrangements in the out-migration of white evangelical Christians. By utilizing church histories, council minutes, and field interviews, it became readily apparent that the departure of the members of these congregations found sanction within the hierarchical apparatus (or lack thereof) of the church. The response of these CRC congregations exemplified how the political structures (congregational polity) and social networks of a particular denomination could allow for an almost seamless process of white flight.
Cognitive techniques and language: A return to behavioral origins.
Froján Parga, María X; Núñez de Prado Gordillo, Miguel; de Pascual Verdú, Ricardo
2017-08-01
the main purpose of this study is to offer an alternative explanatory account of the functioning of cognitive techniques that is based on the principles of associative learning and highlights their verbal nature. The traditional accounts are questioned and analyzed in the light of the situation of psychology in the 1970s. conceptual analysis is employed to revise the concepts of language, cognition and behavior. Several operant- and Pavlovian-based approaches to these phenomena are presented, while particular emphasis is given to Mowrer’s (1954) approach and Ryle (1949) and Wittgenstein’s (1953) philosophical contributions to the field. several logical problems are found in regard to the theoretical foundations of cognitive techniques. A combination of both operant and Pavlovian paradigms based on the above-mentioned approaches is offered as an alternative explanatory account of cognitive techniques. This new approach could overcome the conceptual fragilities of the cognitive standpoint and its dependence upon constructs of dubious logical and scientific validity.
Evapotranspiration from forage grass replacing native vegetation in the Gila River valley of Arizona
Leppanen, O.E.
1981-01-01
Estimates of evapotranspiration from an area of forage grass, which had been planted to replace native vegetation of little economic value, were made daily for a 363-day period in 1969 and 1970. The measurement site was located in the Gila River valley in east-central Arizona. The forage, panigrass (Panicum antidotale Retz.), grew from seed during the early summer of 1969 and after winterkill, regrew in 1970. Daily evapotranspiration estimates, which were based on energy budget measurements, ranged from a maximum of 9.2 millimeters to small amounts of condensation. Two daily values of substantial condensation (0.9 and 0.4 millimeter) were of dubious quality, but were retained in the record. The annual evapotranspiration was 989 millimeters, of which about 332 millimeters came from precipitation at the site. The water table fluctuated between 210 and 280 centimeters below land surface. However, the measurement site was near a wash, so that undocumented, shallower subterranean flows may have occurred. (USGS)
Complex mediascapes, complex realities: critically engaging with biotechnology debates in Ghana
2018-01-01
ABSTRACT The recent increase in research and commercialization of genetically modified (GM) crops in Africa has resulted in considerable and understandable interest from farmers, scholars, and practitioners. However, messy situations are often hard to critically engage in from afar, and the recent article published by Braimah et al. [(2017). Debated agronomy: Public discourse and the future of biotechnology policy in Ghana. Global Bioethics. doi:10.1080/11287462.2016.1261604] presents certain claims that further obfuscate – rather than clarify – an already complex landscape. In this commentary I first seek to clarify particular details of the Ghanaian “GMO” (as GM crops are colloquially called in Ghana) story with particular focus on certain actors and their stances. Next, I highlight some methodological shortcomings of Debated Agronomy and correct certain dubious quotations and claims. Finally, I suggest a more ethnographically and discourse-focused methodology to gain much needed insight into how Ghanaians are actively molding, contesting, and questioning GM discourse, funding, and use. PMID:29887770
Cappella, Annalisa; Amadasi, Alberto; Castoldi, Elisa; Mazzarelli, Debora; Gaudio, Daniel; Cattaneo, Cristina
2014-11-01
The distinction between perimortem and postmortem fractures is an important challenge for forensic anthropology. Such a crucial task is presently based on macro-morphological criteria widely accepted in the scientific community. However, several limits affect these parameters which have not yet been investigated thoroughly. This study aims at highlighting the pitfalls and errors in evaluating perimortem or postmortem fractures. Two trained forensic anthropologists were asked to classify 210 fractures of known origin in four skeletons (three victims of blunt force trauma and one natural death) as perimortem, postmortem, or dubious, twice in 6 months in order to assess intraobserver error also. Results show large errors, ranging from 14.8 to 37% for perimortem fractures and from 5.5 to 14.8% for postmortem ones; more than 80% of errors concerned trabecular bone. This supports the need for more objective and reliable criteria for a correct assessment of peri- and postmortem bone fractures. © 2014 American Academy of Forensic Sciences.
The meaning of the 2006 Nobel Peace Prize. Microcredit evangelism, health, and social policy.
Bond, Patrick
2007-01-01
The awarding of the 2006 Nobel Peace Prize to Muhammad Yunus, founder of the Grameen Bank, provides an opportunity to consider the use and abuse of microfinancing, especially because credit continues to be touted as a poverty-reduction strategy associated with health education and health care financing strategies. Not only is the Grameen diagnosis of poverty dubious, but many structural problems also plague the model, ranging from financial accounting to market failures. In Southern Africa, to illustrate, microcredit schemes for peasants and small farmers have been attempted for more than 70 years, on the basis that modem capitalism and peasant/informal system gaps can be bridged by an expanded financial system. The results have been disappointing. A critical reading of political economy posits an organic linkage between the "developed" and "underdeveloped" economies that is typically not mitigated by capitalist financial markets, but instead is often exacerbated. When applied to health and social policy, microcredit evangelism becomes especially dangerous.
Immobile Trace Element Discrimination of Near-cogenetic Eruptions
NASA Astrophysics Data System (ADS)
Villa, I. M.
2015-12-01
A chemical diagram to discriminate individual magma batches in composite plutonic/volcanic complexes is proposed here: x = Y/Al, y = Zr/Ti. Both ratios are stable during weathering and low-grade metamorphism. Y/Al only depends on fractional crystallization of garnet, xenotime and monazite during magmatogenesis and the degree of partial melting. This already distinguishes individual magmas. Zr/Ti is modified by other phases (rutile, titanite, zircon, ilmenite, biotite, etc) that neither accommodate nor fractionate trivalent cations and provides a totally independent perspective on magmatogenesis. The Y/Al-Zr/Ti plot has no relation to tectonic setting (convergent, rift, intraplate, etc) and is not designed to distinguish lines of descent (calc-alkaline, transitional, etc). Instead, it can discriminate at a very fine scale lavas that share a common regional origin and are therefore confused in classic tectonic discrimination plots. Disentangling individual magma batches is inaccessible to global modeling but important to chronostratigraphers. Application to two well studied examples, Adamello (Alps) and North Anatolia, reproduces known consanguinity and rejects a few dubious ones.
The central dogma, "GMO" and defective epistemology.
Tagliabue, Giovanni
2017-10-02
The expression "Genetically Modified Organisms" was coined to indicate a group of agricultural products (mostly crops and vegetables), modified through direct DNA recombination in order to obtain useful phenotypic traits or to inhibit undesirable characteristics. But the border between rDNA ("GMO") and other biotech methods is blurred. Moreover, the ill-assorted group is frequently charged with having peculiar, negative characteristics: many activists, part of the public and a few social science scholars think that "GMOs" are all dubious, even inherently dangerous. However, theoretical justifications of this alleged problematic nature which is supposed to be necessarily linked to the "splicing" of DNA, only when applied to agricultural products, are missing: the only text which tries to go in depth on the subject, an article by biologist Barry Commoner, takes aim at the wrong target, misunderstanding the Central Dogma. "GMO" is a term that has no clear reference, let alone in a detrimental sense. The only attempt to give it epistemological dignity fails.
In the search for extraterrestrial life
NASA Technical Reports Server (NTRS)
Ponnamperuma, C.
1972-01-01
The study of stellar, planetary and galactic evolution leads to the conclusion that the phenomenon of life must be coursing through the universe. It is estimated, by means of telescopic sampling, that there are billions of stars capable of having those photochemical reactions necessary for the origin of life. One approach in the search for other life would be to deploy men and instruments in spacecraft. Radio contact with other civilizations is another approach. Finally, the question might be approached by considering life as an inevitable consequence of the evolution of matter. A survey of Martian characteristics shows the possibility of life there to be dubious. The possibility of life in other parts of the galaxy is supported by a fundamental conclusion of living matter that all organisms have a common chemical ancestry. The experiment of Urey and Miller, wherein four amino acids were obtained by subjecting a mixture of methane, ammonia, and water to an electric arc, is believed to duplicate the initial organic syntheses which led to the emergence of life on earth.
Towards the responsible conduct of scientific research: is ethics education enough?
Novossiolova, Tatyana; Sture, Judi
2012-01-01
Much of the discourse on ‘beyond the laboratory door’ biosecurity to date has focused on the need to raise awareness among the scientific community of the risks posed by the rapid advancement of biotechnology in recent decades. While education is undoubtedly important, a growing body of evidence suggests that ethics education does not necessarily translate into ethical behaviour. This trend has already been reported in clinical settings, where research has highlighted doctors’ own reports of ethically dubious practices and challenges when confronted with moral dilemmas in their everyday work. The purpose of this paper is to critically evaluate the practical value of ethics education and show why it is an essential, although insufficient, measure for promoting a culture of responsible conduct of research. We conclude by highlighting the importance of continuing professional development as a way of maintaining life scientists’ engagement with biosecurity issues and supporting them in active roles in the effective implementation of the Biological and Toxin Weapons Convention (BWC). PMID:22606762
5 CFR 1312.27 - Top secret control.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...
5 CFR 1312.27 - Top secret control.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...
30 CFR 47.81 - Provisions for withholding trade secrets.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name...
18 CFR 401.75 - Protection of trade secrets; Confidential information.
Code of Federal Regulations, 2010 CFR
2010-04-01
... secrets; Confidential information. 401.75 Section 401.75 Conservation of Power and Water Resources... to Decisions of the Executive Director in Water Qualtity Cases § 401.75 Protection of trade secrets; Confidential information. No person shall be required in such report to divulge trade secrets or secret...
5 CFR 1312.27 - Top secret control.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...
30 CFR 47.81 - Provisions for withholding trade secrets.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name...
30 CFR 47.81 - Provisions for withholding trade secrets.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name...
5 CFR 1312.27 - Top secret control.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...
30 CFR 47.81 - Provisions for withholding trade secrets.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Provisions for withholding trade secrets. 47.81... TRAINING HAZARD COMMUNICATION (HazCom) Trade Secret Hazardous Chemical § 47.81 Provisions for withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the name...
18 CFR 401.75 - Protection of trade secrets; Confidential information.
Code of Federal Regulations, 2012 CFR
2012-04-01
... secrets; Confidential information. 401.75 Section 401.75 Conservation of Power and Water Resources... to Decisions of the Executive Director in Water Qualtity Cases § 401.75 Protection of trade secrets; Confidential information. No person shall be required in such report to divulge trade secrets or secret...
18 CFR 401.75 - Protection of trade secrets; Confidential information.
Code of Federal Regulations, 2014 CFR
2014-04-01
... secrets; Confidential information. 401.75 Section 401.75 Conservation of Power and Water Resources... to Decisions of the Executive Director in Water Qualtity Cases § 401.75 Protection of trade secrets; Confidential information. No person shall be required in such report to divulge trade secrets or secret...
18 CFR 401.75 - Protection of trade secrets; Confidential information.
Code of Federal Regulations, 2013 CFR
2013-04-01
... secrets; Confidential information. 401.75 Section 401.75 Conservation of Power and Water Resources... to Decisions of the Executive Director in Water Qualtity Cases § 401.75 Protection of trade secrets; Confidential information. No person shall be required in such report to divulge trade secrets or secret...
5 CFR 1312.27 - Top secret control.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...
Mechanisms of bicarbonate secretion: lessons from the airways.
Bridges, Robert J
2012-08-01
Early studies showed that airway cells secrete HCO(3)(-) in response to cAMP-mediated agonists and HCO(3)(-) secretion was impaired in cystic fibrosis (CF). Studies with Calu-3 cells, an airway serous model with high expression of CFTR, also show the secretion of HCO(3)(-) when cells are stimulated with cAMP-mediated agonists. Activation of basolateral membrane hIK-1 K(+) channels inhibits HCO(3)(-) secretion and stimulates Cl(-) secretion. CFTR mediates the exit of both HCO(3)(-) and Cl(-) across the apical membrane. Entry of HCO(3)(-) on a basolateral membrane NBC or Cl(-) on the NKCC determines which anion is secreted. Switching between these two secreted anions is determined by the activity of hIK-1 K(+) channels.
Semiquantum secret sharing using entangled states
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li Qin; Department of Computer Science, Sun Yat-sen University, Guangzhou 510006; Department of Mathematics, Hong Kong Baptist University, Kowloon
Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but onemore » of them cannot. The presented protocols are also shown to be secure against eavesdropping.« less
Hoopoes color their eggs with antimicrobial uropygial secretions
NASA Astrophysics Data System (ADS)
Soler, Juan J.; Martín-Vivaldi, M.; Peralta-Sánchez, J. M.; Arco, L.; Juárez-García-Pelayo, N.
2014-09-01
Uropygial gland secretions are used as cosmetics by some species of birds to color and enhance properties of feathers and teguments, which may signal individual quality. Uropygial secretions also reach eggshells during incubation and, therefore, may influence the coloration of birds' eggs, a trait that has attracted the attention of evolutionary biologists for more than one century. The color of hoopoe eggs typically changes along incubation, from bluish-gray to greenish-brown. Here, we test experimentally the hypothesis that dark uropygial secretion of females is responsible for such drastic color change. Moreover, since uropygial secretion of hoopoes has antimicrobial properties, we also explore the association between color and antimicrobial activity of the uropygial secretion of females. We found that eggs stayed bluish-gray in nests where female access to the uropygial secretion was experimentally blocked. Furthermore, experimental eggs that were maintained in incubators and manually smeared with uropygial secretion experienced similar color changes that naturally incubated eggs did, while control eggs that were not in contact with the secretions did not experience such color changes. All these results strongly support the hypothesis that female hoopoes use their uropygial gland secretion to color the eggs. Moreover, saturation of the uropygial secretion was associated with antimicrobial activity against Bacillus licheniformis. Given the known antimicrobial potential of uropygial secretions of birds, this finding opens the possibility that in scenarios of sexual selection, hoopoes in particular and birds in general signal antimicrobial properties of their uropygial secretion by mean of changes in egg coloration along incubation.
Case, R. M.; Scratcherd, T.
1974-01-01
1. The secretion of sodium, potassium and lithium has been studied in the isolated cat pancreas, perfused with bicarbonate buffered saline solutions of varying composition and osmolality, and stimulated maximally with secretin. 2. Under isosmolal conditions, when perfusate sodium chloride was replaced by sucrose, sodium secretion and potassium secretion were directly related to perfusate sodium concentration, [Na]p. 3. When osmolality was varied by increasing or decreasing perfusate sodium chloride concentration, the secretion of sodium and of potassium were maximal at [Na]p of about 120 and 80 mM respectively. 4. At a given [Na]p, sodium secretion was greater under hypo-osmolal conditions than under isosmolal conditions. 5. When potassium concentration was varied over the range 0-130 mM under isosmolal conditions, by adjusting perfusate NaCl concentration, the secretion of potassium and of sodium were maximal at [K]p of about 50 and 10 mM respectively. Water flux was maximal at a [K]p of 10-15 mM. The concentration of potassium in the secretion was almost identical with that in the perfusate over the whole concentration range. 6. Replacement of perfusate sodium by lithium reduced the volume of secretion, though a small secretion was maintained even in the complete absence of sodium. The concentration of lithium in the secretion was generally slightly greater than that in the perfusate. 7. Omission of potassium from the perfusate reduced secretion by about 65%. Rubidium was a complete substitute for potassium; caesium was not. 8. Energy for secretion is derived largely from oxidative phosphorylation. Secretion was reduced by more than 90% under anaerobic conditions and in the presence of dinitrophenol or cyanide. Removal of glucose from the perfusate reduced secretion by more than 50% within 30 min; lactate was a complete substitute for glucose. 9. Ouabain, ethacrinic acid and frusimide, known inhibitors of Na+, K+-ATPase activity, all inhibited pancreatic electrolyte secretion. 10. The observations are interpreted with reference to the nature of active transport processes involved in pancreatic electrolyte secretion. PMID:4281836
75 FR 735 - Original Classification Authority
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-05
... classify information originally as ``Top Secret'' or ``Secret'': TOP SECRET Executive Office of the... Space Administration The Director, Information Security Oversight Office SECRET Executive Office of the...
Diverse C-Terminal Sequences Involved in Flavobacterium johnsoniae Protein Secretion
Kulkarni, Surashree S.; Zhu, Yongtao; Brendel, Colton J.
2017-01-01
ABSTRACT Flavobacterium johnsoniae and many related bacteria secrete proteins across the outer membrane using the type IX secretion system (T9SS). Proteins secreted by T9SSs have amino-terminal signal peptides for export across the cytoplasmic membrane by the Sec system and carboxy-terminal domains (CTDs) targeting them for secretion across the outer membrane by the T9SS. Most but not all T9SS CTDs belong to the family TIGR04183 (type A CTDs). We functionally characterized diverse CTDs for secretion by the F. johnsoniae T9SS. Attachment of the CTDs from F. johnsoniae RemA, AmyB, and ChiA to the foreign superfolder green fluorescent protein (sfGFP) that had a signal peptide at the amino terminus resulted in secretion across the outer membrane. In each case, approximately 80 to 100 amino acids from the extreme carboxy termini were needed for efficient secretion. Several type A CTDs from distantly related members of the phylum Bacteroidetes functioned in F. johnsoniae, supporting the secretion of sfGFP by the F. johnsoniae T9SS. F. johnsoniae SprB requires the T9SS for secretion but lacks a type A CTD. It has a conserved C-terminal domain belonging to the family TIGR04131, which we refer to as a type B CTD. The CTD of SprB was required for its secretion, but attachment of C-terminal regions of SprB of up to 1,182 amino acids to sfGFP failed to result in secretion. Additional features outside the C-terminal region of SprB may be required for its secretion. IMPORTANCE Type IX protein secretion systems (T9SSs) are common in but limited to members of the phylum Bacteroidetes. Most proteins that are secreted by T9SSs have conserved carboxy-terminal domains that belong to the protein domain family TIGR04183 (type A CTDs) or TIGR04131 (type B CTDs). Here, we identify features of T9SS CTDs of F. johnsoniae that are required for protein secretion and demonstrate that type A CTDs from distantly related members of the phylum function with the F. johnsoniae T9SS to secrete the foreign protein sfGFP. In contrast, type B CTDs failed to target sfGFP for secretion, suggesting a more complex association with the T9SS. PMID:28396348
Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.
2011-01-01
To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844
An Image Secret Sharing Method
2006-07-01
the secret image in lossless manner and (2) any or fewer image shares cannot get sufficient information to reveal the ... secret image. It is an effective, reliable and secure method to prevent the secret image from being lost, stolen or corrupted. In comparison with...other image secret sharing methods, this approach’s advantages are its large compression rate on the size of the image shares, its strong protection of the secret image and its ability for real-time
Fändriks, L; Stage, L
1986-12-01
Chloralosed cats were acutely vagotomized, their splanchnic nerves cut and the adrenal glands ligated. The gastric lumen was perfused with isotonic NaCl and gastric motility was monitored as changes in hydrostatic pressure within the perfusion circuit. Gastric secretion of H+ and HCO3- were calculated from continuous measurements of pH and PCO2. Methodological tests ex vivo showed good accuracy of the estimations. Recovery of H+ after HCl instillation into the stomach in vivo was almost complete, while HCO3- recovery after NaHCO3 instillations was 85-95%. Pentagastrin (10 micrograms kg-1 h-1 i.v.) stimulated gastric contractile activity and increased gastric H+ secretion 30-fold, while HCO3- secretion decreased somewhat. Carbachol (4 micrograms kg-1 h-1) induced gastric contractions and increased H+ secretion by 400% and HCO3- output by 100-130%. Electrical stimulation of the cut vagal nerves (10 Hz for 10 min) induced well known gastric motor responses and increased gastric H+ secretion 20-fold preceded by a transient doubling of HCO3- secretion. Omeprazole, a selective inhibitor of gastric H+ secretion, decreased the vagally induced H+ secretion, while recorded gastric HCO3- secretion was clearly enhanced. In conclusion, the technique permits simultaneous recordings of rapid alterations of gastric motility and H+ and HCO3- secretions. However, HCO3- secretion was modestly underestimated, probably due to mucosal CO2 absorption.
Khawaja, A M; Liu, Y C; Rogers, D F
1999-01-01
Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism. Copyright 1999 Academic Press.
31 CFR 401.1 - Secret Service agents authorized to make seizures.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in the...
30 CFR 47.81 - Provisions for withholding trade secrets.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Provisions for withholding trade secrets. 47.81... withholding trade secrets. (a) Operators may withhold the identity of a trade secret chemical, including the... trade secret, (2) Identifies the chemical in a way that it can be referred to without disclosing the...
31 CFR 401.1 - Secret Service agents authorized to make seizures.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in the...
31 CFR 401.1 - Secret Service agents authorized to make seizures.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in the...
31 CFR Appendix D to Subpart C of... - United States Secret Service
Code of Federal Regulations, 2010 CFR
2010-07-01
... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false United States Secret Service D... Secret Service 1. In general. This appendix applies to the United States Secret Service. It sets forth... requests for notification and access to records and accountings of disclosures for the United States Secret...
31 CFR Appendix D to Subpart C of... - United States Secret Service
Code of Federal Regulations, 2011 CFR
2011-07-01
... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false United States Secret Service D... Secret Service 1. In general. This appendix applies to the United States Secret Service. It sets forth... requests for notification and access to records and accountings of disclosures for the United States Secret...
31 CFR 401.1 - Secret Service agents authorized to make seizures.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in the...
31 CFR Appendix D to Subpart C of... - United States Secret Service
Code of Federal Regulations, 2012 CFR
2012-07-01
... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false United States Secret Service D... Secret Service 1. In general. This appendix applies to the United States Secret Service. It sets forth... requests for notification and access to records and accountings of disclosures for the United States Secret...
31 CFR 401.1 - Secret Service agents authorized to make seizures.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in the...
31 CFR Appendix D to Subpart C of... - United States Secret Service
Code of Federal Regulations, 2013 CFR
2013-07-01
... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false United States Secret Service D... Secret Service 1. In general. This appendix applies to the United States Secret Service. It sets forth... requests for notification and access to records and accountings of disclosures for the United States Secret...
31 CFR Appendix D to Subpart C of... - United States Secret Service
Code of Federal Regulations, 2014 CFR
2014-07-01
... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false United States Secret Service D... Secret Service 1. In general. This appendix applies to the United States Secret Service. It sets forth... requests for notification and access to records and accountings of disclosures for the United States Secret...
Authentication Without Secrets
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pierson, Lyndon G.; Robertson, Perry J.
This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integritymore » of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.« less
Investment in secreted enzymes during nutrient-limited growth is utility dependent.
Cezairliyan, Brent; Ausubel, Frederick M
2017-09-12
Pathogenic bacteria secrete toxins and degradative enzymes that facilitate their growth by liberating nutrients from the environment. To understand bacterial growth under nutrient-limited conditions, we studied resource allocation between cellular and secreted components by the pathogenic bacterium Pseudomonas aeruginosa during growth on a protein substrate that requires extracellular digestion by secreted proteases. We identified a quantitative relationship between the rate of increase of cellular biomass under nutrient-limiting growth conditions and the rate of increase in investment in secreted proteases. Production of secreted proteases is stimulated by secreted signals that convey information about the utility of secreted proteins during nutrient-limited growth. Growth modeling using this relationship recapitulated the observed kinetics of bacterial growth on a protein substrate. The proposed regulatory strategy suggests a rationale for quorum-sensing-dependent stimulation of the production of secreted enzymes whereby investment in secreted enzymes occurs in proportion to the utility they confer. Our model provides a framework that can be applied toward understanding bacterial growth in many environments where growth rate is limited by the availability of nutrients.
Berghuis, A. M. Sofie; Koffijberg, Hendrik; Prakash, Jai; Terstappen, Leon W. M. M.; IJzerman, Maarten J.
2017-01-01
Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence. PMID:28208771
Pheochromocytoma in Urologic Practice
Waingankar, Nikhil; Bratslavsky, Gennady; Jimenez, Camilo; Russo, Paul; Kutikov, Alexander
2016-01-01
Context Pheochromocytoma is regularly encountered in urological practice and requires a thoughtful and careful clinical approach. Objective To review clinical aspects of management of pheochromocytoma in urologic practice. Evidence Acquisition A systematic review of English-language literature was performed through year 2015 using the Medline database. Manuscripts were selected with consensus of the coauthors and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Evidence Synthesis Findings and recommendations of the evaluated manuscripts are discussed with an emphasis on the description of presentation, diagnosis, evaluation, and perioperative care. Conclusion In addition to surgical expertise, appropriate management of pheochromocytoma in urologic practice requires nuanced understanding of pathophysiology, genetics, and endocrinological principles. When skillfully managed, the vast majority of patients with pheochromocytoma should expect an excellent prognosis. Patient Summary In this article we review the clinical approach to patients with pheochromocytoma, a tumor that stems from the innermost part of the adrenal gland and that often secretes excessive amounts of powerful hormones such as noradrenaline and adrenaline. Significant expertise is required to appropriately manage patients with these tumors. Take Home Message In addition to surgical expertise, appropriate management of pheochromocytoma in urologic practice requires nuanced understanding of pathophysiology, genetics, and endocrinological principles. When skillfully managed, vast majority of patients with pheochromocytoma should expect an excellent prognosis. PMID:28078330
A sampling design framework for monitoring secretive marshbirds
Johnson, D.H.; Gibbs, J.P.; Herzog, M.; Lor, S.; Niemuth, N.D.; Ribic, C.A.; Seamans, M.; Shaffer, T.L.; Shriver, W.G.; Stehman, S.V.; Thompson, W.L.
2009-01-01
A framework for a sampling plan for monitoring marshbird populations in the contiguous 48 states is proposed here. The sampling universe is the breeding habitat (i.e. wetlands) potentially used by marshbirds. Selection protocols would be implemented within each of large geographical strata, such as Bird Conservation Regions. Site selection will be done using a two-stage cluster sample. Primary sampling units (PSUs) would be land areas, such as legal townships, and would be selected by a procedure such as systematic sampling. Secondary sampling units (SSUs) will be wetlands or portions of wetlands in the PSUs. SSUs will be selected by a randomized spatially balanced procedure. For analysis, the use of a variety of methods as a means of increasing confidence in conclusions that may be reached is encouraged. Additional effort will be required to work out details and implement the plan.
Deciphering Interplay between Salmonella Invasion Effectors
Koronakis, Vassilis
2008-01-01
Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction. PMID:18389058
Hormones and immune function: implications of aging.
Arlt, Wiebke; Hewison, Martin
2004-08-01
Aging is associated with a decline in immunity described as immunosenescence. This is paralleled by a decline in the production of several hormones, as typically illustrated by the menopausal loss of ovarian oestrogen production. However, other hormonal changes that occur with aging and that potentially impact on immune function include the release of the pineal gland hormone melatonin and pituitary growth hormone, adrenal production of dehydroepiandrosterone and tissue-specific availability of active vitamin D. It remains to be established whether hormonal changes with aging actually contribute to immunosenescence and this area is at the interface of fact and fiction, clearly inviting systematic research efforts. As a step in this direction, the present review summarizes established facts on the physiology of secretion and function of hormones that, in most cases, decline with aging and that are likely to affect the immune system.
EVpedia: A community web resource for prokaryotic and eukaryotic extracellular vesicles research.
Kim, Dae-Kyum; Lee, Jaewook; Simpson, Richard J; Lötvall, Jan; Gho, Yong Song
2015-04-01
For cell-to-cell communication, all living cells including archaea, bacteria, and eukaryotes secrete nano-sized membrane vesicles into the extracellular space. These extracellular vesicles harbor specific subsets of proteins, mRNAs, miRNAs, lipids, and metabolites that represent their cellular status. These vesicle-specific cargos are considered as novel diagnostic biomarkers as well as therapeutic targets. With the advancement in high-throughput technologies on multiomics studies and improvements in bioinformatics approaches, a huge number of vesicular proteins, mRNAs, miRNAs, lipids, and metabolites have been identified, and our understanding of these complex extracellular organelles has considerably increased during these past years. In this review, we highlight EVpedia (http://evpedia.info), a community web portal for systematic analyses of prokaryotic and eukaryotic extracellular vesicles research. Copyright © 2015 Elsevier Ltd. All rights reserved.
[Constipation in patients with diabetes mellitus].
Rossol, Siegbert
2007-11-01
Up to 60% of the patients with diabetes mellitus suffer from gastrointestinal tract symptoms that arise pathogenetically from a disturbance of the autonomous nervous system. Patient age, disease duration and poor control of diabetes mellitus correlate positively with the presence of gastrointestinal symptoms. Chronic constipation, in addition to diarrhoea, gall bladder dysfunction and incontinence, is increasingly regarded as a serious problem and for the first time, is now considered in the current guidelines of the professional societies. Modern diagnosis and treatment facilitate systematic control of the symptoms. Treatment necessitates long-term intake of laxatives, proper diabetes control and other accompanying general measures such as adequate amounts of liquids, dietary fibre and exercise. Motility and secretion-stimulating, osmotically active or locally applied laxatives are used. Slow transit constipation, which is typically observed in diabetics, can be best controlled with polyethylene glycol, bisacodyl or sodium picosulphate.
Wang, Yong; Lee, Dongyoung; Zhang, Lisa; Jeon, Hyojin; Mendoza-Elias, Joshua E.; Harvat, Tricia A.; Hassan, Sarah Z.; Zhou, Amanda; Eddington, David T.; Oberholzer, José
2012-01-01
Reliable long-term cell culture in microfluidic system is limited by air bubble formation and accumulation. In this study, we developed a bubble removal system capable of both trapping and discharging air bubbles in a consistent and reliable manner. Combined with PDMS (Polydimethylsiloxane) hydrophilic surface treatment and vacuum filling, a microfluidic perifusion system equipped with the bubble trap was successfully applied for long-term culture of mouse pancreatic islets with no bubble formation and no flow interruption. In addition to demonstrating normal cell viability and islet morphology, post-cultured islets exhibited normal insulin secretion kinetics, intracellular calcium signaling, and changes in mitochondrial potentials in response to glucose challenge. This design could be easily adapted by other microfluidic systems due to its simple design, ease of fabrication, and portability. PMID:22252566
Rhizoid differentiation of Spirogyra is regulated by substratum.
Ikegaya, Hisato; Sonobe, Seiji; Murakami, Kohei; Shimmen, Teruo
2008-11-01
Some species of Spirogyra can anchor to substratum with rod- or rosette-shaped rhizoid (hapteron). The rhizoid differentiation can be induced by cutting algal filaments in a laboratory. Requirement of contact stimulation for rhizoid differentiation has been reported (Nagata in Plant Cell Physiol 14:531-541, 1973a). However, the control mechanism of rhizoid morphology has not been elucidated. When cut filaments were incubated on the glass surface, start of tip growth, secretion of lectin-binding material and callose synthesis were observed. In the absence of contact to the glass surface, none of above phenomena was induced. Systematic analysis showed that rosette-shaped rhizoid was formed only on the hydrophobic substratum. On the hydrophobic substratum, both Bandeiraea (Griffonia) simplicifolia lectin and jacalin strongly stained the rhizoids. On the hydrophilic substratum, however, only Bandeiraea (Griffonia) simplicifolia lectin strongly stained the rhizoids.
Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof.
Lucas, Michael L
2010-04-01
For almost 40 years, one of the principal causes of diarrhoeal disease has been thought to be fluid secretion emanating from the epithelial cells of the small and large intestine. Given the extremely large fluid losses seen in cholera, where secretion can be up to several litres per day, this seems a plausible hypothesis. The enterocyte (epithelial cell) secretion hypothesis rapidly displaced all other alternatives, such as vasodilatation coupled with enhanced paracellular permeability. An essential mechanism underlying enterocyte secretion has always been assumed to be electrogenic chloride secretion, leading to a localized osmotic imbalance at the mucosal surface of the enterocytes that causes fluid entry into the lumen by osmosis. The chloride secretion basis for enterotoxin-deranged secretion is assumed to be measurable by changes in electrical currents and by altered transport of chloride ion. These can be detected after the small intestine is exposed to a heat-stable enterotoxin (STa) produced by Escherichia coli. However, in vivo, when the recovered volume technique is used, STa is found not to be secretory. The heat-stable enterotoxin is therefore a test case toxin, because the complex techniques used to demonstrate enterocyte secretion after STa exposure show apparent secretion, while the simplest technique based on fluid recovery and genuinely measuring the mass transport of fluid does not. This review scrutinizes the nature of the evidence put forward for enterocyte secretion and reaches the conclusion that there is no evidence for it. Debilitating secretion undoubtedly does take place in severe diarrhoeal disease, but secretion from enterocytes is unlikely to be the cause.
Fan, Wei; Xu, Jia-Meng; Lou, He-Qiang; Xiao, Chuan; Chen, Wei-Wei; Yang, Jian-Li
2016-01-01
Grain amaranth (Amaranthus hypochondriacus L.) is abundant in oxalate and can secrete oxalate under aluminium (Al) stress. However, the features of Al-induced secretion of organic acid anions (OA) and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH) together with quantitative real-time PCR (qRT-PCR) was used to identify up-regulated genes that are potentially involved in OA secretion. The results showed that grain amaranth roots secrete both oxalate and citrate in response to Al stress. The secretion pattern, however, differs between oxalate and citrate. Neither lanthanum chloride (La) nor cadmium chloride (Cd) induced OA secretion. A total of 84 genes were identified as up-regulated by Al, in which six genes were considered as being potentially involved in OA secretion. The expression pattern of a gene belonging to multidrug and toxic compound extrusion (MATE) family, AhMATE1, was in close agreement with that of citrate secretion. The expression of a gene encoding tonoplast dicarboxylate transporter and four genes encoding ATP-binding cassette transporters was differentially regulated by Al stress, but the expression pattern was not correlated well with that of oxalate secretion. Our results not only reveal the secretion pattern of oxalate and citrate from grain amaranth roots under Al stress, but also provide some genetic information that will be useful for further characterization of genes involved in Al toxicity and tolerance mechanisms. PMID:27144562
Fan, Wei; Xu, Jia-Meng; Lou, He-Qiang; Xiao, Chuan; Chen, Wei-Wei; Yang, Jian-Li
2016-04-30
Grain amaranth (Amaranthus hypochondriacus L.) is abundant in oxalate and can secrete oxalate under aluminium (Al) stress. However, the features of Al-induced secretion of organic acid anions (OA) and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH) together with quantitative real-time PCR (qRT-PCR) was used to identify up-regulated genes that are potentially involved in OA secretion. The results showed that grain amaranth roots secrete both oxalate and citrate in response to Al stress. The secretion pattern, however, differs between oxalate and citrate. Neither lanthanum chloride (La) nor cadmium chloride (Cd) induced OA secretion. A total of 84 genes were identified as up-regulated by Al, in which six genes were considered as being potentially involved in OA secretion. The expression pattern of a gene belonging to multidrug and toxic compound extrusion (MATE) family, AhMATE1, was in close agreement with that of citrate secretion. The expression of a gene encoding tonoplast dicarboxylate transporter and four genes encoding ATP-binding cassette transporters was differentially regulated by Al stress, but the expression pattern was not correlated well with that of oxalate secretion. Our results not only reveal the secretion pattern of oxalate and citrate from grain amaranth roots under Al stress, but also provide some genetic information that will be useful for further characterization of genes involved in Al toxicity and tolerance mechanisms.
Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P
2007-08-01
Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.
Air Force UAV’s: The Secret History
2010-07-01
iA Mitchell Institute Study i Air Force UAVs The Secret History A Mitchell Institute Study July 2010 By Thomas P. Ehrhard Report Documentation Page...DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Air Force UAVs The Secret History 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c... The Secret History 2 Air Force UAVs: The Secret History2 air Force uaVs: The secret history Has any airplane in the past decade captured the public
Hawken, P A R; Luckins, N; Tilbrook, A; Fiol, C; Martin, G B; Blache, D
2013-01-01
We investigated the effect of genetic selection for temperament on the way that stressors affect the behaviour and the adrenal and reproductive axes of sheep. We tested three hypotheses: (i) isolation would increase cortisol secretion and decrease luteinising hormone (LH) secretion more in nervous sheep than in calm sheep; (ii) isolation combined with simulated human presence would increase cortisol secretion and decrease LH secretion more in nervous sheep than in calm sheep and (iii) isolation combined with stressors that were not specific to the selection process (i.e. non-selection stressors) would increase cortisol secretion and decrease LH secretion equally in calm and nervous sheep. Isolation alone increased cortisol secretion and decreased LH secretion in nervous sheep but not in calm sheep. Compared to calm sheep, nervous sheep were more agitated during the first 2 h of isolation but not during the second 2 h of isolation. Exposure to non-selection stressors increased cortisol secretion, decreased LH pulse amplitude and the mean plasma concentrations of LH in both calm and nervous sheep. We conclude that genetic selection for temperament affects the behavioural expression of the stress response and the secretion of adrenal and reproductive hormones during isolation, but has less impact on their reactivity to non-selection stressors.
Bernard, J; Jeannesson, P; Thiernesse, N; Zagury, D; Ternynck, T; Avrameas, S
1979-01-01
Mice were injected in their hind footpads with peroxidase (PO) emulsified in Freund's complete adjuvant. The development of cells secreting anti-peroxidase antibody (Ab) and cells secreting immunoglobulins (Ig) were detected in the draining popliteal lymph nodes in the subsequent 35 days, using local haemolysis plaque assay with sheep red cell blood cells coated with either PO or anti-mouse Ig antibody. Plaque-forming cells (PFC) were isolated from the centre of plaques by micromanipulation and after appropriate treatment, were examined by electron microscopy for their intracellular Ab content and in corporation of [3H]-thymidine. Four subpopulations of Ig secreting cells were distinguished: (1) cells secreting Ig without Ab function and not containing intracellular Ab detectable between days 5 and 20; (2) cells secreting Ig without Ab function but containing Ab appearing on day 6 and present throughout the immune response; (3) cells secreting Ab and containing Ab; (4) cells secreting Ab, but without detectable intracellular Ab. These last subpopulations appeared on day 7 and were found in all subsequent assays. The analysis of the kinetics of these subpopulations suggest that cells secreting Ig without Ab function might be precursors of Ab secreting cells. Images Figure 2a Figure 2b Figure 4 PMID:374259
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Trade secrets and commercial or financial... secrets and commercial or financial information which is privileged or confidential. (a) A trade secret... either innovation or substantial effort. There must be a direct relationship between the trade secret and...
Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places
ERIC Educational Resources Information Center
Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth
2014-01-01
In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Trade secrets and commercial or financial... secrets and commercial or financial information which is privileged or confidential. (a) A trade secret... either innovation or substantial effort. There must be a direct relationship between the trade secret and...
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Trade secrets and commercial or financial... secrets and commercial or financial information which is privileged or confidential. (a) A trade secret... either innovation or substantial effort. There must be a direct relationship between the trade secret and...
31 CFR Appendix D to Subpart A of... - United States Secret Service
Code of Federal Regulations, 2010 CFR
2010-07-01
... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false United States Secret Service D...—United States Secret Service 1. In general. This appendix applies to the United States Secret Service. 2. Public reading room. The United States Secret Service will provide a room on an ad hoc basis when...
31 CFR Appendix D to Subpart A of... - United States Secret Service
Code of Federal Regulations, 2011 CFR
2011-07-01
... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false United States Secret Service D...—United States Secret Service 1. In general. This appendix applies to the United States Secret Service. 2. Public reading room. The United States Secret Service will provide a room on an ad hoc basis when...
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Trade secrets and commercial or financial... secrets and commercial or financial information which is privileged or confidential. (a) A trade secret... either innovation or substantial effort. There must be a direct relationship between the trade secret and...
31 CFR Appendix D to Subpart A of... - United States Secret Service
Code of Federal Regulations, 2013 CFR
2013-07-01
... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false United States Secret Service D...—United States Secret Service 1. In general. This appendix applies to the United States Secret Service. 2. Public reading room. The United States Secret Service will provide a room on an ad hoc basis when...
31 CFR Appendix D to Subpart A of... - United States Secret Service
Code of Federal Regulations, 2012 CFR
2012-07-01
... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false United States Secret Service D...—United States Secret Service 1. In general. This appendix applies to the United States Secret Service. 2. Public reading room. The United States Secret Service will provide a room on an ad hoc basis when...
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Trade secrets and commercial or financial... secrets and commercial or financial information which is privileged or confidential. (a) A trade secret... either innovation or substantial effort. There must be a direct relationship between the trade secret and...
31 CFR Appendix D to Subpart A of... - United States Secret Service
Code of Federal Regulations, 2014 CFR
2014-07-01
... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false United States Secret Service D...—United States Secret Service 1. In general. This appendix applies to the United States Secret Service. 2. Public reading room. The United States Secret Service will provide a room on an ad hoc basis when...
41 CFR 105-62.102 - Authority to originally classify.
Code of Federal Regulations, 2012 CFR
2012-01-01
... originally classify. (a) Top secret, secret, and confidential. The authority to originally classify information as Top Secret, Secret, or Confidential may be exercised only by the Administrator and is delegable...
41 CFR 105-62.102 - Authority to originally classify.
Code of Federal Regulations, 2010 CFR
2010-07-01
... originally classify. (a) Top secret, secret, and confidential. The authority to originally classify information as Top Secret, Secret, or Confidential may be exercised only by the Administrator and is delegable...
NASA Astrophysics Data System (ADS)
Wang, Xiao-Jun; An, Long-Xi; Yu, Xu-Tao; Zhang, Zai-Chen
2017-10-01
A multilayer quantum secret sharing protocol based on GHZ state is proposed. Alice has the secret carried by quantum state and wants to distribute this secret to multiple agent nodes in the network. In this protocol, the secret is transmitted and shared layer by layer from root Alice to layered agents. The number of agents in each layer is a geometric sequence with a specific common ratio. By sharing GHZ maximally entangled states and making generalized Bell basis measurement, one qubit state can be distributed to multiparty agents and the secret is shared. Only when all agents at the last layer cooperate together, the secret can be recovered. Compared with other protocols based on the entangled state, this protocol adopts layered construction so that secret can be distributed to more agents with fewer particles GHZ state. This quantum secret sharing protocol can be used in wireless network to ensure the security of information delivery.
Létoffé, S; Wandersman, C
1992-01-01
Protease B from Erwinia chrysanthemi was shown previously to have a C-terminal secretion signal located downstream of a domain that contains six glycine-rich repeats. This domain is conserved in all known bacterial proteins secreted by the signal peptide-independent pathway. The role of these repeats in the secretion process is controversial. We compared the secretion processes of various heterologous polypeptides fused either directly to the signal or separated from it by the glycine-rich domain. Although the repeats are not involved in the secretion of small truncated protease B carboxy-terminal peptides, they are required for the secretion of higher-molecular-weight fusion proteins. Secretion efficiency was also dependent on the size of the passenger polypeptide. Images PMID:1629152
[Secret remedies in France until abolition in 1926].
Warolin, Christian
2002-01-01
Secret remedies are preparations or medicines whose composition is not disclosed by the inventor in order to protect his invention or to deceive the public. Secret remedies have always existed. From time immemorial the communities of apothecaries in Paris or in the provinces were opposed to quack doctors or healers who sold inactive mixtures. The 1352 Royal Edict forbade preparations of secret remedies. However, in the 17th century secret remedies were authorized through commission letters or warrants. In the 18th century regulations were implemented to control secret trade. The famous 11 April 1803 Law called the Germinal Law banned the sale of secret remedies but its severity was softened through successive decrees based on divergent interpretations of the regulations. The final banning of secret remedies was pronounced by a decree on 13 July 1926.
Soldani, G; Del Tacca, M; Bambini, G; Polloni, A; Bernardini, C; Martinotti, E; Martino, E
1982-01-01
The effects of GnRH on gastric secretion and gastrin release from dogs provided with gastric fistulae and Heidenhain pouches have been investigated. A transient yet significant inhibition of pentagastrin-stimulated secretion from gastric fistulae was observed, while secretion from Heidenhain pouches was unchanged. The maximal inhibitory effect of GnRH on both acid and pepsin secretion stimulated by 2-deoxy-D-glucose was obtained from gastric fistulae. On the contrary, GnRH failed to affect either acid secretion stimulated by bethanechol or acid secretion and gastrin release induced by bombesin. The present results indicate that GnRH possesses an inhibitory action on gastric secretion from the vagally innervated stomach of the dog. The most likely inhibitory mechanism seems to be represented by a decrease of the vagal activity.
Abu-Basha, E A; Yibchok-Anun, S; Hopper, D L; Hsu, W H
1999-11-01
The study purpose was to investigate the direct effect of amitraz, a formamidine insecticide/acaricide, and its active metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas. Amitraz and BTS 27271 (0.01, 0.1, 1, and 10 micromol/L) inhibited insulin secretion in a concentration-dependent manner. Amitraz increased glucagon secretion at 10 micromol/L, whereas BTS 27271 increased glucagon secretion at 1 and 10 micromol/L. Amitraz- and BTS 27271-induced decreases in insulin secretion and increases in glucagon secretion were not abolished during the 10-minute washout period. During the arginine treatment, both amitraz and BTS 27271 groups (0.1, 1, and 10 micromol/L) had lower insulin secretion and higher glucagon secretion than the control group. Idazoxan, an alpha2A/2D-adrenergic receptor (AR) antagonist, prevented the inhibitory effect of amitraz on insulin secretion in a concentration-dependent manner, but prazosin, an alpha1- and alpha2B/2C-AR antagonist, failed to antagonize the effect of amitraz. These results demonstrate that (1) amitraz and BTS 27271 inhibit insulin and stimulate glucagon secretion from the perfused rat pancreas, (2) amitraz inhibits insulin secretion by activation of alpha2D-ARs, since rats have alpha2D- but not alpha2A-ARs, and (3) amitraz and BTS 27271 may have a high binding affinity to the alpha2D-ARs of pancreatic islets.
Ning, Xiaojun; Luckenbaugh, Laurie; Liu, Kuancheng; Bruss, Volker; Sureau, Camille; Hu, Jianming
2018-05-09
During the morphogenesis of hepatitis B virus (HBV), an enveloped virus, two types of virions are secreted: (1) a minor population of complete virions containing a mature nucleocapsid with the characteristic, partially double-stranded, relaxed circular DNA genome and (2) a major population containing an empty capsid with no DNA or RNA (empty virions). Secretion of both types of virions requires interactions between the HBV capsid or core protein (HBc) and the viral surface or envelope proteins. We have studied the requirements from both HBc and envelope proteins for empty virion secretion, in comparison with those for secretion of complete virions. Substitutions within the N-terminal domain of HBc that block secretion of DNA-containing virions reduced but did not prevent secretion of empty virions. The HBc C-terminal domain was not essential for empty virion secretion. Among the three viral envelope proteins, the smallest, S, alone was sufficient for empty virion secretion at a basal level. The largest protein, L, essential for complete virion secretion, was not required for, but could stimulate empty virion secretion. Also, substitutions in L that eliminate secretion of complete virions reduced but did not eliminate empty virion secretion. S mutations that block secretion of the hepatitis D virus (HDV), an HBV satellite, did not block secretion of either empty or complete HBV virions. Together, these results indicate that both common and distinct signals on empty capsids vs. mature nucleocapsids interact with the S and L proteins during the formation of complete vs. empty virions. IMPORTANCE Hepatitis B virus (HBV) is a major cause of severe liver diseases including cirrhosis and cancer. In addition to the complete infectious virion particle, which contains an outer envelope layer and an interior capsid that, in turn, encloses a DNA genome, HBV infected cells also secrete non-infectious, incomplete viral particles in large excess over the complete virions. In particular, the empty (or genome-free) virion share with the complete virion the outer envelope and interior capsid but contain no genome. We have carried out a comparative study on the capsid and envelope requirements for the secretion of these two types of virion particles and uncovered both shared and distinct determinants on the capsid and envelope for their secretion. These results provide new information on HBV morphogenesis, and have implications for efforts to develop empty HBV virions as a novel biomarker and a new generation of HBV vaccine. Copyright © 2018 American Society for Microbiology.
Extracellular secretion of recombinant proteins
Linger, Jeffrey G.; Darzins, Aldis
2014-07-22
Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.
Mechanophysical Stimulations of Mucin Secretion in Cultures of Nasal Epithelial Cells
Even-Tzur Davidovich, Nurit; Kloog, Yoel; Wolf, Michael; Elad, David
2011-01-01
Nasal epithelial cells secret mucins and are exposed in vivo to airflow-induced mechanophysical stresses, including wall shear stress (WSS), temperature, and humidity. In this work, human nasal epithelial cells cultured under air-liquid interface conditions were subjected to fields of airflow-induced oscillatory WSS at different temperature and humidity conditions. Changes in mucin secretion due to WSS were measured and the role of the cytoskeleton in mucin secretion was explored. Mucin secretion significantly increased in response to WSS in a magnitude-dependent manner with respect to static cultures and independently of the airflow temperature and humidity. In static cultures, mucin secretion decreased at high humidity with or without elevation of the temperature with respect to cultures at a comfortable climate. In cultures exposed to WSS, mucin secretion increased at high temperature with respect to cultures at comfortable climate conditions. The polymerization of actin microfilaments was shown to increase mucin secretion under WSS, whereas the dynamics of microtubule polymerization did not affect secretion. In conclusion, the data in this study show that mucin secretion is sensitive to oscillatory WSS as well as high temperature and humidity conditions. PMID:21689518
Effect of alpha 2-adrenoceptor agonists on gastric pepsin and acid secretion in the rat.
Tazi-Saad, K.; Chariot, J.; Del Tacca, M.; Rozé, C.
1992-01-01
1. The purpose of the present study was to analyze the effects of the alpha 2-adrenoceptor agonists clonidine, guanabenz, detomidine and medetomidine on pepsin secretion in conscious rats provided with gastric chronic fistula and to compare this with acid secretion. 2. Basal interdigestive gastric secretion, which is mainly neurally driven in the rat, and the secretion directly stimulated by the two main stimulants of chief cells, cholecystokinin octapeptide (CCK8) and methacholine, were studied. 3. Basal secretion of pepsin and acid was inhibited by all four drugs with comparable EC50S. 4. CCK-stimulated pepsin and acid secretion was less sensitive than basal pepsin and acid secretion to alpha 2-adrenoceptor inhibition. 5. Methacholine-stimulated pepsin and acid secretion was not changed by clonidine and guanabenz; methacholine-stimulated acid was even marginally increased by clonidine. 6. These results do not favour the presence of alpha 2-receptors on chief cells in the rat stomach. They rather suggest that pepsin inhibition by alpha 2-adrenoceptor agonists is indirect and due to central or peripheral inhibition of the discharge of nerve fibres activating pepsin secretion. PMID:1356566
Efficient multiparty quantum-secret-sharing schemes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xiao Li; Deng Fuguo; Key Laboratory for Quantum Information and Measurements, MOE, Beijing 100084
In this work, we generalize the quantum-secret-sharing scheme of Hillery, Buzek, and Berthiaume [Phys. Rev. A 59, 1829 (1999)] into arbitrary multiparties. Explicit expressions for the shared secret bit is given. It is shown that in the Hillery-Buzek-Berthiaume quantum-secret-sharing scheme the secret information is shared in the parity of binary strings formed by the measured outcomes of the participants. In addition, we have increased the efficiency of the quantum-secret-sharing scheme by generalizing two techniques from quantum key distribution. The favored-measuring-basis quantum-secret-sharing scheme is developed from the Lo-Chau-Ardehali technique [H. K. Lo, H. F. Chau, and M. Ardehali, e-print quant-ph/0011056] wheremore » all the participants choose their measuring-basis asymmetrically, and the measuring-basis-encrypted quantum-secret-sharing scheme is developed from the Hwang-Koh-Han technique [W. Y. Hwang, I. G. Koh, and Y. D. Han, Phys. Lett. A 244, 489 (1998)] where all participants choose their measuring basis according to a control key. Both schemes are asymptotically 100% in efficiency, hence nearly all the Greenberger-Horne-Zeilinger states in a quantum-secret-sharing process are used to generate shared secret information.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahren, B.
The thyroid gland is known to harbor cholinergic and VIPergic nerves. In the present study, the influences of cholinergic stimulation by carbachol, cholinergic blockade by methylatropine and stimulation with various VIP sequences on basal, TSH-induced and VIP-induced thyroid hormone secretion were investigated in vivo in mice. The mice were pretreated with /sup 125/I and thyroxine; the subsequent release of /sup 125/I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was inhibited by both carbachol and methylatropine. Furthermore, TSH-induced radioiodine secretion was inhibited already by a low dose of carbachol. Moreover, a high dose ofmore » carbachol could inhibit VIP-induced radioiodine secretion. Methylatropine did not influence TSH- or VIP-stimulated radioiodine secretion, but counteracted the inhibitory action of carbachol on TSH- and VIP-induced radioiodine release. In addition, contrary to VIP, six various synthesized VIP fragments had no effect on basal or stimulated radioiodine release. It is concluded that basal thyroid hormone secretion is inhibited by both cholinergic activation and blockade. Furthermore, TSH-induced thyroid hormone secretion is more sensitive to inhibition with cholinergic stimulation than is VIP-induced thyroid hormone secretion. In addition, the VIP stimulation of thyroid hormone secretion seems to require the full VIP sequence.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Coleman, R.A.; Haynes, E.B.; Sand, T.M.
1987-05-01
The development of the liver's ability to coordinately express the synthesis and secretion of the two major components of very low density lipoproteins (VLDL): triacylglycerol (TG) and apolipoprotein B (apo B) was examined in cultured hepatocytes obtained from fetal, suckling and adult rats. Hepatocytes from fetal and suckling rats synthesized and secreted TG at rates lower than that displayed by adult cells. When TG synthesis was equalized by adding oleic acid to the culture medium, fetal cells still secreted only 39% as much TG as did adult cells. To determine the basis for the apparent defect in VLDL assembly/secretion displayedmore » by fetal cells, the synthesis and secretion of (TVS)methionine-labeled apo B was quantified by immunoprecipitation. Although adult and fetal cells synthesized and secreted large molecular weight apo B at similar rates, the synthesis and secretion of small molecular weight apo B was 2-fold greater in adult cells. These data suggest that the ability to assemble/secrete VLDL triacylglycerol varies in parallel with the developmental expression of small molecular weight apo B. Furthermore, these studies show the usefulness of the cultured rat hepatocyte model for examining the ontogeny and regulation of VLDL assembly/secretion.« less
Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells
Cavet, M E; West, M; Simmons, N L
1997-01-01
Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para-amino hippurate, probenecid (10 mM), taurocholate (100 μM) or bromosulphophthalein (100 μM). Similarly tetraethylammonium and N-′methylnicotinamide (10 mM) were without effect. Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4′-diisothiocyanostilbene-2-2′-disulphonic acid (DIDS, 400 μM). Net secretion of ciprofloxacin was partially inhibited by 100 μM verapamil, whilst net secretion of the P-glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti-P-glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretion in Caco-2 epithelia, and was not itself secreted by the P-glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl− or K+ in the bathing media. The substrate specificity of the ciprofloxacin secretory transport in Caco-2 epithelia is distinct from both the renal organic anion and cation transport. A role for P-glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco-2 epithelia. PMID:9283689
Barreto, Savio G; Woods, Charmaine M; Carati, Colin J; Schloithe, Ann C; Jaya, Surendra R; Toouli, James; Saccone, Gino T P
2009-08-01
Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10(-12) M to 10(-7) M), carbachol (10(-6) M), or caerulein (10(-10) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), hexamethonium (10(-5) M), or diazoxide (10(-7) M and 10(-4) M) for 30 min followed by incubation with caerulein (10(-10) M) alone or combined with galanin (10(-12) M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10(-6) M and 10(-10) M, respectively. Galanin (10(-12) M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by approximately 80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release.
Overlooked Short Toxin-Like Proteins: A Shortcut to Drug Design
Linial, Michal
2017-01-01
Short stable peptides have huge potential for novel therapies and biosimilars. Cysteine-rich short proteins are characterized by multiple disulfide bridges in a compact structure. Many of these metazoan proteins are processed, folded, and secreted as soluble stable folds. These properties are shared by both marine and terrestrial animal toxins. These stable short proteins are promising sources for new drug development. We developed ClanTox (classifier of animal toxins) to identify toxin-like proteins (TOLIPs) using machine learning models trained on a large-scale proteomic database. Insects proteomes provide a rich source for protein innovations. Therefore, we seek overlooked toxin-like proteins from insects (coined iTOLIPs). Out of 4180 short (<75 amino acids) secreted proteins, 379 were predicted as iTOLIPs with high confidence, with as many as 30% of the genes marked as uncharacterized. Based on bioinformatics, structure modeling, and data-mining methods, we found that the most significant group of predicted iTOLIPs carry antimicrobial activity. Among the top predicted sequences were 120 termicin genes from termites with antifungal properties. Structural variations of insect antimicrobial peptides illustrate the similarity to a short version of the defensin fold with antifungal specificity. We also identified 9 proteins that strongly resemble ion channel inhibitors from scorpion and conus toxins. Furthermore, we assigned functional fold to numerous uncharacterized iTOLIPs. We conclude that a systematic approach for finding iTOLIPs provides a rich source of peptides for drug design and innovative therapeutic discoveries. PMID:29109389
Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.
Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia
2017-10-01
Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.
Comparative multi-omics systems analysis of Escherichia coli strains B and K-12.
Yoon, Sung Ho; Han, Mee-Jung; Jeong, Haeyoung; Lee, Choong Hoon; Xia, Xiao-Xia; Lee, Dae-Hee; Shim, Ji Hoon; Lee, Sang Yup; Oh, Tae Kwang; Kim, Jihyun F
2012-05-25
Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced. We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions. This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts.
Comparative multi-omics systems analysis of Escherichia coli strains B and K-12
2012-01-01
Background Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced. Results We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions. Conclusions This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts. PMID:22632713
Role of oncogene 24p3 neutrophil gelatinase-associated lipocalin (NGAL) in digestive system cancers.
Michalak, Łukasz; Bulska, Magdalena; Kudłacz, Katarzyna; Szcześniak, Piotr
2016-01-04
Neutrophil gelatinase-associated lipocalin, known also as 24p3 lipocalin, lipocalin-2 or uterocalin (in mouse), is a small secretory protein binding small molecular weight ligands which takes part in numerous processes including apoptosis induction in leukocytes, iron transport, smell, and prostaglandins and retinol transport [19]. It was discovered in activated neutrophils as a covalent peptide associated with human gelatinase neutrophils [7]. Neutrophil lipocalin is secreted physiologically in the digestive system, respiratory tract, renal tubular cells, liver or immunity system. Systematic (circulated in plasma) neutrophil gelatinase come from multiple sources; it may be synthesized in the liver, secreted from activated neutrophils or macrophages, or derive from atherosclerosis or inflammatory endothelial cells [17]. NGAL is stored secondarily in granulates with lactoferrin, calprotectin or MAC-1, which take part in neutrophils' action and migration [13,19]. NGAL participates in acute and chronic inflammation (production of NGAL is indicated by factors conducive to cancer progression) [13,21]. NGAL levels increase in inflammatory or endothelial damage. NGAL level is measured in blood or urine. It is known as a kidney failure factor [7,20]. NGAL is therefore one of the most promising new generation biomarkers in clinical nephrology [6]. The role of NGAL in digestive system neoplasms has not been explored in detail. However, overexpression of this marker was proved in neoplasms such as esophageal carcinoma, stomach cancer, pancreatic cancer or colon cancer, which may indicate an association between concentration and neoplasm [3].
Duellman, Tyler; Warren, Christopher; Yang, Jay
2014-01-01
Microribonucleic acids (miRNAs) work with exquisite specificity and are able to distinguish a target from a non-target based on a single nucleotide mismatch in the core nucleotide domain. We questioned whether miRNA regulation of gene expression could occur in a single nucleotide polymorphism (SNP)-specific manner, manifesting as a post-transcriptional control of expression of genetic polymorphisms. In our recent study of the functional consequences of matrix metalloproteinase (MMP)-9 SNPs, we discovered that expression of a coding exon SNP in the pro-domain of the protein resulted in a profound decrease in the secreted protein. This missense SNP results in the N38S amino acid change and a loss of an N-glycosylation site. A systematic study demonstrated that the loss of secreted protein was due not to the loss of an N-glycosylation site, but rather an SNP-specific targeting by miR-671-3p and miR-657. Bioinformatics analysis identified 41 SNP-specific miRNA targeting MMP-9 SNPs, mostly in the coding exon and an extension of the analysis to chromosome 20, where the MMP-9 gene is located, suggesting that SNP-specific miRNAs targeting the coding exon are prevalent. This selective post-transcriptional regulation of a target messenger RNA harboring genetic polymorphisms by miRNAs offers an SNP-dependent post-transcriptional regulatory mechanism, allowing for polymorphic-specific differential gene regulation. PMID:24627221
Wang, Ya-Qiong; Liang, Zhi-Tao; Li, Qin; Yang, Hua; Chen, Hu-Biao; Zhao, Zhong-Zhen; Li, Ping
2011-03-01
The light microscope has been successfully used in identification of Chinese herbal medicines (CHMs) for more than a century. However, positive identification is not always possible. Given the popularity of fluorescence microscopy in bioanalysis, researchers dedicated to finding new ways to identify CHMs more effectively are now turning to fluorescence microscopy for authentication purposes. Some studies on distinguishing confused species from the same genus and on exploring distributions of chemicals in tissues of CHMs by fluorescence microscopy have been reported; however, no systematic investigations on fluorescent characteristics of powdered CHMs have been reported. Here, 46 samples of 16 CHMs were investigated. Specifically, the mechanical tissues including stone cells and fibers, the conducting tissues including three types of vessels, and ergastic substances including crystals of calcium oxalate and secretions, in various powdered CHMs were investigated by both light microscope and fluorescence microscope. The results showed many microscopic features emit fluorescence that makes them easily observed, even against complex backgrounds. Under the fluorescence microscope, different microscopic features from the same powdered CHM or some same features from different powdered CHMs emitted the different fluorescence, making this information very helpful for the authentication of CHMs in powder form. Moreover, secretions with unique chemical profiles from different powdered CHMs showed different fluorescent characteristics. Hence, fluorescence microscopy could be a useful additional method for the authentication of powdered CHMs if the fluorescent characteristics of specific CHMs are known. Copyright © 2010 Wiley-Liss, Inc.
Co-regulation of Primary Mouse Hepatocyte Viability and Function by Oxygen and Matrix
Buck, Lorenna D.; Inman, S. Walker; Rusyn, Ivan; Griffith, Linda G.
2014-01-01
Although oxygen and extracellular matrix cues both influence differentiation state and metabolic function of primary rat and human hepatocytes, relatively little is known about how these factors together regulate behaviors of primary mouse hepatocytes in culture. To determine the effects of pericellular oxygen tension on hepatocellular function, we employed 2 methods of altering oxygen concentration in the local cellular microenvironment of cells cultured in the presence or absence of an extracellular matrix (Matrigel) supplement. By systematically altering medium depth and gas phase oxygen tension, we created multiple oxygen regimes (hypoxic, normoxic, and hyperoxic) and measured the local oxygen concentrations in the pericellular environment using custom-designed oxygen microprobes. From these measurements of oxygen concentrations, we derived values of oxygen consumption rates under a spectrum of environmental contexts, thus providing the first reported estimates of these values for primary mouse hepatocytes. Oxygen tension and matrix microenvironment were found to synergistically regulate hepatocellular survival and function as assessed using quantitative image analysis for cells stained with vital dyes, and assessment of secretion of albumin. Hepatocellular viability was affected only at strongly hypoxic conditions. Surprisingly, albumin secretion rates were greatest at a moderately supra-physiological oxygen concentration, and this effect was mitigated at still greater supra-physiological concentrations. Matrigel enhanced the effects of oxygen on retention of function. This study underscores the importance of carefully controlling cell density, medium depth and gas phase oxygen, as the effects of these parameters on local pericellular oxygen tension and subsequent hepatocellular function are profound. PMID:24222008
Bicarbonate secretion by rabbit cortical collecting tubules in vitro.
McKinney, T D; Burg, M B
1978-06-01
We previously reported that rabbit renal cortical collecting tubules can secrete bicarbonate in vitro (i.e., there can be net transport from bath to lumen, causing the concentration in the lumen to increase). Net bicarbonate secretion was observed most often when rabbits had been pretreated with NaHCO(3) and were excreting alkaline urine before being killed for experiments. The purpose of the present studies was to elucidate the mechanism involved by testing the effects of ion substitutions and drugs on collecting tubules that were secreting bicarbonate. Acetazolamide inhibited net bicarbonate secretion, suggesting that the process is dependent upon carbonic anhydrase. Net bicarbonate secretion also decreased when sodium in the perfusate and bath was replaced by choline, but not when chloride was replaced by nitrate or methylsulfate. Ouabain had no significant effect. Amiloride caused net bicarbonate secretion to increase. The rate of net secretion did not correlate with transepithelial voltage. The results are compared to those in turtle urinary bladders that also secrete bicarbonate. There are no direct contradictions between the results in the two tissues, i.e., in turtle bladders acetazolamide also inhibited bicarbonate secretion and ouabain had no effect. Nevertheless, it seems unlikely that net secretion of bicarbonate by collecting tubules involves specific exchange for chloride, as has been proposed for turtle bladders, because replacement of chloride by other anions did not inhibit bicarbonate secretion by collecting tubules. It was previously shown that the collecting tubules in vitro also may absorb bicarbonate, especially when the rabbits have been treated with NH(4)Cl and are excreting acid urine before being killed. The effects of drugs on net bicarbonate secretion found in the present studies are compared to their previously reported effects on net bicarbonate absorption and the possibility is discussed that bicarbonate absorption and secretion are independent processes, as was previously proposed for turtle bladders.
Bicarbonate Secretion by Rabbit Cortical Collecting Tubules in Vitro
McKinney, Thurman D.; Burg, Maurice B.
1978-01-01
We previously reported that rabbit renal cortical collecting tubules can secrete bicarbonate in vitro (i.e., there can be net transport from bath to lumen, causing the concentration in the lumen to increase). Net bicarbonate secretion was observed most often when rabbits had been pretreated with NaHCO3 and were excreting alkaline urine before being killed for experiments. The purpose of the present studies was to elucidate the mechanism involved by testing the effects of ion substitutions and drugs on collecting tubules that were secreting bicarbonate. Acetazolamide inhibited net bicarbonate secretion, suggesting that the process is dependent upon carbonic anhydrase. Net bicarbonate secretion also decreased when sodium in the perfusate and bath was replaced by choline, but not when chloride was replaced by nitrate or methylsulfate. Ouabain had no significant effect. Amiloride caused net bicarbonate secretion to increase. The rate of net secretion did not correlate with transepithelial voltage. The results are compared to those in turtle urinary bladders that also secrete bicarbonate. There are no direct contradictions between the results in the two tissues, i.e., in turtle bladders acetazolamide also inhibited bicarbonate secretion and ouabain had no effect. Nevertheless, it seems unlikely that net secretion of bicarbonate by collecting tubules involves specific exchange for chloride, as has been proposed for turtle bladders, because replacement of chloride by other anions did not inhibit bicarbonate secretion by collecting tubules. It was previously shown that the collecting tubules in vitro also may absorb bicarbonate, especially when the rabbits have been treated with NH4Cl and are excreting acid urine before being killed. The effects of drugs on net bicarbonate secretion found in the present studies are compared to their previously reported effects on net bicarbonate absorption and the possibility is discussed that bicarbonate absorption and secretion are independent processes, as was previously proposed for turtle bladders. PMID:659604
Regulation of Retinoschisin Secretion in Weri-Rb1 Cells by the F-Actin and Microtubule Cytoskeleton
Kitamura, Eiko; Gribanova, Yekaterina E.; Farber, Debora B.
2011-01-01
Retinoschisin is encoded by the gene responsible for X-linked retinoschisis (XLRS), an early onset macular degeneration that results in a splitting of the inner layers of the retina and severe loss in vision. Retinoschisin is predominantly expressed and secreted from photoreceptor cells as a homo-oligomer protein; it then associates with the surface of retinal cells and maintains the retina cellular architecture. Many missense mutations in the XLRS1 gene are known to cause intracellular retention of retinoschisin, indicating that the secretion process of the protein is a critical step for its normal function in the retina. However, the molecular mechanisms underlying retinoschisin's secretion remain to be fully elucidated. In this study, we investigated the role of the F-actin cytoskeleton in the secretion of retinoschisin by treating Weri-Rb1 cells, which are known to secrete retinoschisin, with cytochalasin D, jasplakinolide, Y-27632, and dibutyryl cGMP. Our results show that cytochalasin D and jasplakinolide inhibit retinoschisin secretion, whereas Y-27632 and dibutyryl cGMP enhance secretion causing F-actin alterations. We also demonstrate that high concentrations of taxol, which hyperpolymerizes microtubules, inhibit retinoschisin secretion. Our data suggest that retinoschisin secretion is regulated by the F-actin cytoskeleton, that cGMP or inhibition of ROCK alters F-actin structure enhancing the secretion, and that the microtubule cytoskeleton is also involved in this process. PMID:21738583
The enteric nervous system modulates mammalian duodenal mucosal bicarbonate secretion.
Hogan, D L; Yao, B; Steinbach, J H; Isenberg, J I
1993-08-01
Interaction of the enteric nerves in regulating mammalian duodenal mucosal bicarbonate secretion is not well understood. The purpose of the present experiments was to evaluate the role of the enteric nervous system on bicarbonate secretion from rabbit duodenal mucosa in vitro. Proximal duodenum from male New Zealand White rabbits was stripped of seromuscular layers, mounted in Ussing chambers, and studied under short-circuited conditions. Effects of electrical field stimulation, vasoactive intestinal polypeptide (VIP), carbachol, prostaglandin E2 (PGE2), dibutyryl-cyclic adenosine monophosphate (db-cAMP), and the neurotoxin tetrodotoxin (TTX) and muscarinic blockade by atropine were studied. Electrical field stimulation significantly (P < 0.01) stimulated bicarbonate secretion, short-circuit current (Isc), and electrical potential difference (PD) that was sensitive to both TTX and atropine. VIP-stimulated bicarbonate secretion was significantly inhibited by TTX (-73%), yet Isc and PD remained unchanged. Atropine decreased VIP-induced bicarbonate secretion (-69%) and Isc (-43%). Carbachol-stimulated bicarbonate secretion, Isc, and PD were abolished by atropine, whereas TTX was without affect. Neither TTX nor atropine had a significant effect on PGE2 or db-cAMP-stimulated bicarbonate secretion. These results suggest that (1) enteric nerve stimulation activates an acetylcholine receptor that in turn stimulates duodenal epithelial bicarbonate secretion; (2) VIP stimulates bicarbonate secretion, in large part, via the enteric nervous system; and (3) PGE2 and cAMP stimulate bicarbonate secretion independent of the enteric nervous system.
Proteases induce secretion of collagenase and plasminogen activator by fibroblasts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Werb, Z.; Aggeler, J.
1978-04-01
We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continuedmore » presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.« less
The semantics of secrecy: young children's classification of secret content.
Anagnostaki, Lida; Wright, Michael J; Bourchier-Sutton, Alison J
2010-01-01
The authors explored whether young children can distinguish potential secrets from nonsecrets by their content, as can older children, adolescents, and adults. Ninety children, 4, 5, and 6 years old, rated the secrecy of items from an adult-validated list of personal information about an age- and gender-appropriate puppet. Two factors of the children's data corresponded to the adult categories of nonsecrets and secrets, and a third factor corresponded to surprises. All ages rated surprises as significantly more secret than nonsecret items; however, the surprise items contained linguistic cues to secrecy. A tendency to rate nonsecrets as secret decreased with age, but only the 6-year-olds rated secrets other than surprises as significantly more secret than nonsecrets. Thus, children acquire the implicit rules defining secret content from a somewhat later age than that reported for the cognitive or behavioral capacities for secrecy.
ERIC Educational Resources Information Center
Paxman, Christina G.
2013-01-01
The exploration of secrets summons the adage that ''what someone doesn't know won't hurt them.'' While this phrase implies that keeping secrets can be advantageous, it also foreshadows another consideration: secrets have the propensity to hurt others (Caughlin, Scott, Miller, & Hefner, 2009). Despite this, the act…
Lindeberg, Magdalen; Boyd, Carol M.; Keen, Noel T.; Collmer, Alan
1998-01-01
The type II secretion system (main terminal branch of the general secretion pathway) is used by diverse gram-negative bacteria to secrete extracellular proteins. Proteins secreted by this pathway are synthesized with an N-terminal signal peptide which is removed upon translocation across the inner membrane, but the signals which target the mature proteins for secretion across the outer membrane are unknown. The plant pathogens Erwinia chrysanthemi and Erwinia carotovora secrete several isozymes of pectate lyase (Pel) by the out-encoded type II pathway. However, these two bacteria cannot secrete Pels encoded by heterologously expressed pel genes from the other species, suggesting the existence of species-specific secretion signals within these proteins. The functional cluster of E. chrysanthemi out genes carried on cosmid pCPP2006 enables Escherichia coli to secrete E. chrysanthemi, but not E. carotovora, Pels. We exploited the high sequence similarity between E. chrysanthemi PelC and E. carotovora Pel1 to construct 15 hybrid proteins in which different regions of PelC were replaced with homologous sequences from Pel1. The differential secretion of these hybrid proteins by E. coli(pCPP2006) revealed M118 to D175 and V215 to C329 as regions required for species-specific secretion of PelC. We propose that the primary targeting signal is contained within the external loops formed by G274 to C329 but is dependent on residues in M118 to D170 and V215 to G274 for proper positioning. PMID:9515910
Engineering Signal Peptides for Enhanced Protein Secretion from Lactococcus lactis
Ng, Daphne T. W.
2013-01-01
Lactococcus lactis is an attractive vehicle for biotechnological production of proteins and clinical delivery of therapeutics. In many such applications using this host, it is desirable to maximize secretion of recombinant proteins into the extracellular space, which is typically achieved by using the native signal peptide from a major secreted lactococcal protein, Usp45. In order to further increase protein secretion from L. lactis, inherent limitations of the Usp45 signal peptide (Usp45sp) must be elucidated. Here, we performed extensive mutagenesis on Usp45sp to probe the effects of both the mRNA sequence (silent mutations) and the peptide sequence (amino acid substitutions) on secretion. We screened signal peptides based on their resulting secretion levels of Staphylococcus aureus nuclease and further evaluated them for secretion of Bacillus subtilis α-amylase. Silent mutations alone gave an increase of up to 16% in the secretion of α-amylase through a mechanism consistent with relaxed mRNA folding around the ribosome binding site and enhanced translation. Targeted amino acid mutagenesis in Usp45sp, combined with additional silent mutations from the best clone in the initial screen, yielded an increase of up to 51% in maximum secretion of α-amylase while maintaining secretion at lower induction levels. The best sequence from our screen preserves the tripartite structure of the native signal peptide but increases the positive charge of the n-region. Our study presents the first example of an engineered L. lactis signal peptide with a higher secretion yield than Usp45sp and, more generally, provides strategies for further enhancing protein secretion in bacterial hosts. PMID:23124224
Engineering signal peptides for enhanced protein secretion from Lactococcus lactis.
Ng, Daphne T W; Sarkar, Casim A
2013-01-01
Lactococcus lactis is an attractive vehicle for biotechnological production of proteins and clinical delivery of therapeutics. In many such applications using this host, it is desirable to maximize secretion of recombinant proteins into the extracellular space, which is typically achieved by using the native signal peptide from a major secreted lactococcal protein, Usp45. In order to further increase protein secretion from L. lactis, inherent limitations of the Usp45 signal peptide (Usp45sp) must be elucidated. Here, we performed extensive mutagenesis on Usp45sp to probe the effects of both the mRNA sequence (silent mutations) and the peptide sequence (amino acid substitutions) on secretion. We screened signal peptides based on their resulting secretion levels of Staphylococcus aureus nuclease and further evaluated them for secretion of Bacillus subtilis α-amylase. Silent mutations alone gave an increase of up to 16% in the secretion of α-amylase through a mechanism consistent with relaxed mRNA folding around the ribosome binding site and enhanced translation. Targeted amino acid mutagenesis in Usp45sp, combined with additional silent mutations from the best clone in the initial screen, yielded an increase of up to 51% in maximum secretion of α-amylase while maintaining secretion at lower induction levels. The best sequence from our screen preserves the tripartite structure of the native signal peptide but increases the positive charge of the n-region. Our study presents the first example of an engineered L. lactis signal peptide with a higher secretion yield than Usp45sp and, more generally, provides strategies for further enhancing protein secretion in bacterial hosts.
Social and cognitive factors associated with children’s secret-keeping for a parent
Gordon, Heidi M.; Lyon, Thomas D.; Lee, Kang
2014-01-01
This study examined children’s secret-keeping for a parent and its relationship to trust, theory of mind, secrecy endorsement, and executive functioning (EF). Children (N = 107) between 4 and 12 years of age participated in a procedure wherein parents broke a toy and asked children to promise secrecy. Responses to open-ended and direct questions were examined. Overall, secret-keeping increased with age and promising to keep the secret was related to fewer disclosures in open-ended questioning. Children who kept the secret in direct questioning exhibited greater trust and better parental ratings of EF than children who disclosed the secret. Findings highlight the importance of both social and cognitive factors in secret-keeping development. PMID:25291258
10 CFR 709.3 - Covered persons subject to a CI evaluation and polygraph.
Code of Federal Regulations, 2010 CFR
2010-01-01
... routine access to Top Secret Restricted Data; (5) With regular and routine access to Top Secret National... and non-routine basis to Top Secret Restricted Data or Top Secret National Security Information or the...
Secrets and Misperceptions: The Creation of Self-Fulfilling Illusions
Cowan, Sarah K.
2015-01-01
This study examines who hears what secrets, comparing two similar secrets-one that is highly stigmatized and one that is less so. Using a unique survey representative of American adults and intake forms from a medical clinic, I document marked differences in who hears these secrets. People who are sympathetic to the stigmatizing secret are more likely to hear of it than those who may react negatively. This is a consequence of people not just selectively disclosing their own secrets but selectively sharing others’ as well. As a result, people in the same social network will be exposed to and influenced by different information about those they know and hence experience that network differently. When people effectively exist in networks tailored by others not to offend, then the information they hear tends to be that of which they already approve. Were they to hear secrets they disapproved of, then their attitudes might change, but they are less likely to hear those secrets. As such, the patterns of secret hearing contribute to a stasis in public opinion. PMID:26082932
Quantum secret sharing with qudit graph states
DOE Office of Scientific and Technical Information (OSTI.GOV)
Keet, Adrian; Fortescue, Ben; Sanders, Barry C.
We present a unified formalism for threshold quantum secret sharing using graph states of systems with prime dimension. We construct protocols for three varieties of secret sharing: with classical and quantum secrets shared between parties over both classical and quantum channels.
Deposition of anal-sac secretions by captive wolves (Canis lupus)
Asa, C.S.; Peterson, E.K.; Seal, U.S.; Mech, L.D.
1985-01-01
Deposition of anal-sac secretions by captive wolves was investigated by a labelling technique using protein-bound iodine125 and food dye. Wolves deposited secretions on some but not all scats. Adult males, especially the alpha male, deposited anal-sac secretions more frequently while defecating than did females or juveniles. Secretions sometimes also were deposited independently of defecation, suggesting a dual role in communication by these substances.
Security of a kind of quantum secret sharing with entangled states.
Wang, Tian-Yin; Liu, Ying-Zhao; Wei, Chun-Yan; Cai, Xiao-Qiu; Ma, Jian-Feng
2017-05-30
We present a new collusion attack to a kind of quantum secret sharing schemes with entangled states. Using this attack, an unauthorized set of agents can gain access to the shared secret without the others' cooperation. Furthermore, we establish a general model for this kind of quantum secret sharing schemes and then give some necessary conditions to design a secure quantum secret sharing scheme under this model.
Secretion of Ipa proteins by Shigella flexneri: inducer molecules and kinetics of activation.
Bahrani, F K; Sansonetti, P J; Parsot, C
1997-01-01
The type III Mxi-Spa secretion machinery of Shigella flexneri is responsible for secretion of Ipa proteins, which are involved in the entry of bacteria into epithelial cells. Ipa proteins accumulate within bacteria growing in laboratory media, and their secretion is activated upon contact of bacteria with eukaryotic cells. In this study, we have identified a group of chemical compounds, including Congo red, Evans blue, and direct orange, which are able to induce secretion of Ipa proteins by bacteria suspended in phosphate-buffered saline. Parameters of kinetics of activation of Ipa secretion by Congo red were determined by measuring by enzyme-linked immunosorbent assay the amount of IpaC secreted and by investigating the increase in susceptibility of Ipa proteins to proteinase K degradation. Ipa secretion occurred at 37 degrees C, was obtained with 5 to 10 microM Congo red, and was complete within 30 min. In addition, activation of Ipa secretion by Congo red was observed with bacteria harvested throughout the exponential phase of growth but not with bacteria in the stationary phase. The interactions of Congo red and Congo red-related compounds with the Mxi-Spa secretion apparatus might be specific hydrophobic interactions similar to those involved in binding of Congo red to amyloid proteins. PMID:9316999
Chahal, Sabreen; Wei, Peter; Moua, Pachai; Park, Sung Pil James; Kwon, Janet; Patel, Arth; Vu, Anthony T; Catolico, Jason A; Tsai, Yu Fang Tina; Shaheen, Nadia; Chu, Tiffany T; Tam, Vivian; Khan, Zill-E-Huma; Joo, Hyun Henry; Xue, Liang; Lin-Cereghino, Joan; Tsai, Jerry W; Lin-Cereghino, Geoff P
2017-01-20
The methylotrophic yeast Pichia pastoris has been used extensively for expressing recombinant proteins because it combines the ease of genetic manipulation, the ability to provide complex posttranslational modifications and the capacity for efficient protein secretion. The most successful and commonly used secretion signal leader in Pichia pastoris has been the alpha mating factor (MATα) prepro secretion signal. However, limitations exist as some proteins cannot be secreted efficiently, leading to strategies to enhance secretion efficiency by modifying the secretion signal leader. Based on a Jpred secondary structure prediction and knob-socket modeling of tertiary structure, numerous deletions and duplications of the MATα prepro leader were engineered to evaluate the correlation between predicted secondary structure and the secretion level of the reporters horseradish peroxidase (HRP) and Candida antarctica lipase B. In addition, circular dichroism analyses were completed for the wild type and several mutant pro-peptides to evaluate actual differences in secondary structure. The results lead to a new model of MATα pro-peptide signal leader, which suggests that the N and C-termini of MATα pro-peptide need to be presented in a specific orientation for proper interaction with the cellular secretion machinery and for efficient protein secretion. Copyright © 2016 Elsevier B.V. All rights reserved.
Secretory NaCl and volume flow in renal tubules.
Beyenbach, K W
1986-05-01
This review attempts to give a retrospective survey of the available evidence concerning the secretion of NaCl and fluid in renal tubules of the vertebrate kidney. In the absence of glomerular filtration, epithelial secretory mechanisms, which to this date have not been elucidated, are responsible for the renal excretion of NaCl and water in aglomerular fish. However, proximal tubules isolated from glomerular fish kidneys of the flounder, killifish, and the shark also have the capacity to secrete NaCl and fluid. In shark proximal tubules, fluid secretion appears to be driven via secondary active transport of Cl. In another marine vertebrate, the sea snake, secretion of Na (presumably NaCl) and fluid is observed in freshwater-adapted and water-loaded animals. Proximal tubules of mammals can be made to secrete NaCl in vitro together with secretion of aryl acids. An epithelial cell line derived from dog kidney exhibits secondary active secretion of Cl when stimulated with catecholamines. Tubular secretion of NaCl and fluid may serve a variety of renal functions, all of which are considered here. The occurrence of NaCl and fluid secretion in glomerular proximal tubules of teleosts, elasmobranchs, and reptiles and in mammalian renal tissue cultures suggests that the genetic potential for NaCl secretion is present in every vertebrate kidney.
Cushing's disease: current medical therapies and molecular insights guiding future therapies.
Lau, Darryl; Rutledge, Caleb; Aghi, Manish K
2015-02-01
OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.
A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion
Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko
2014-11-06
Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components thatmore » form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yokawa, Satoru; School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650; Suzuki, Takahiro
We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion. From immunochemical analyses, PGCG-GLase stably expressed in clonal αTC1.6 cells was correctly processed and released by secretory granules. Luminescence signals of the secreted PGCG-GLase frommore » the stable cells were visualized by video-rate bioluminescence microscopy. The video images showed an increase in glucagon secretion from clustered cells in response to stimulation by KCl. The secretory events were observed frequently at the intercellular contact regions. Thus, the localization and frequency of glucagon secretion might be regulated by cell-cell adhesion. - Highlights: • The fused protein of proglucagon to Gaussia luciferase was used as a reporter. • The fusion protein was highly expressed using a preferred human-codon optimized gene. • Glucagon secretion stimulated by depolarization was determined by luminescence. • Glucagon secretion in α cells was visualized by bioluminescence imaging. • Glucagon secretion sites were localized in the intercellular contact regions.« less
De Coi, Niccolò; Feuermann, Marc; Schmid-Siegert, Emanuel; Băguţ, Elena-Tatiana; Mignon, Bernard; Waridel, Patrice; Peter, Corinne; Pradervand, Sylvain
2016-01-01
ABSTRACT Dermatophytes are the most common agents of superficial mycoses in humans and animals. The aim of the present investigation was to systematically identify the extracellular, possibly secreted, proteins that are putative virulence factors and antigenic molecules of dermatophytes. A complete gene expression profile of Arthroderma benhamiae was obtained during infection of its natural host (guinea pig) using RNA sequencing (RNA-seq) technology. This profile was completed with those of the fungus cultivated in vitro in two media containing either keratin or soy meal protein as the sole source of nitrogen and in Sabouraud medium. More than 60% of transcripts deduced from RNA-seq data differ from those previously deposited for A. benhamiae. Using these RNA-seq data along with an automatic gene annotation procedure, followed by manual curation, we produced a new annotation of the A. benhamiae genome. This annotation comprised 7,405 coding sequences (CDSs), among which only 2,662 were identical to the currently available annotation, 383 were newly identified, and 15 secreted proteins were manually corrected. The expression profile of genes encoding proteins with a signal peptide in infected guinea pigs was found to be very different from that during in vitro growth when using keratin as the substrate. Especially, the sets of the 12 most highly expressed genes encoding proteases with a signal sequence had only the putative vacuolar aspartic protease gene PEP2 in common, during infection and in keratin medium. The most upregulated gene encoding a secreted protease during infection was that encoding subtilisin SUB6, which is a known major allergen in the related dermatophyte Trichophyton rubrum. IMPORTANCE Dermatophytoses (ringworm, jock itch, athlete’s foot, and nail infections) are the most common fungal infections, but their virulence mechanisms are poorly understood. Combining transcriptomic data obtained from growth under various culture conditions with data obtained during infection led to a significantly improved genome annotation. About 65% of the protein-encoding genes predicted with our protocol did not match the existing annotation for A. benhamiae. Comparing gene expression during infection on guinea pigs with keratin degradation in vitro, which is supposed to mimic the host environment, revealed the critical importance of using real in vivo conditions for investigating virulence mechanisms. The analysis of genes expressed in vivo, encoding cell surface and secreted proteins, particularly proteases, led to the identification of new allergen and virulence factor candidates. PMID:27822542
Lake, J R; Licko, V; Van Dyke, R W; Scharschmidt, B F
1985-01-01
In these studies, we have used several approaches to systematically explore the contribution of transcellular vesicular transport (transcytosis) to the blood-to-bile movement of inert fluid-phase markers of widely varying molecular weight. First, under steady-state conditions, the perfused rat liver secreted even large markers in appreciable amounts. The bile-to-plasma (B/P) ratio of these different markers, including microperoxidase (B/P ratio = 0.06; mol wt = 1,879), insulin (B/P ratio = 0.09, mol wt = 5,000), horseradish peroxidase (B/P ratio = 0.04, mol wt = 40,000), and dextran (B/P ratio = 0.09, mol wt = 70,000), exhibited no clear ordering based on size alone, and when dextrans of two different sizes (40,000 and 70,000 mol wt) were studied simultaneously, the relative amounts of the two dextran species in bile were the same as in perfusate. Taurocholate administration produced a 71% increase in bile flow but little or no (0-20%) increase in the output of horseradish peroxidase, microperoxidase, inulin, and dextran. Second, under nonsteady-state conditions in which the appearance in or disappearance from bile of selected markers was studied after their abrupt addition to or removal from perfusate, erythritol reached a B/P ratio of 1 within 2 min. Microperoxidase and dextran appeared in bile only after a lag period of approximately 12 min and then slowly approached maximal values, whereas sucrose exhibited kinetically intermediate behavior. A similar pattern was observed after removal of greater than 95% of the marker from the perfusate. Erythritol rapidly reapproached a B/P ratio of 1, whereas the B/P ratio for sucrose, dextran, and microperoxidase fell much more slowly and exceeded 1 for a full 30 min after perfusate washout. Finally, electron microscopy and fluorescence microscopy of cultured hepatocytes demonstrated the presence of horseradish peroxidase and fluorescein-dextran, respectively, in intracellular vesicles, and fractionation of perfused liver homogenates revealed that at least 35-50% of sucrose, inulin, and dextran was associated with subcellular organelles. Collectively, these observations are most compatible with a transcytosis pathway that contributes minimally to the secretion of erythritol, but accounts for a substantial fraction of sucrose secretion and virtually all (greater than 95%) of the blood-to-bile transport of microperoxidase and larger markers. These findings have important implications with respect to current concepts of canalicular bile formation as well as with respect to the conventional use of solutes such as sucrose as markers of canalicular or paracellular pathway permeability. Images PMID:2411761
Tran, Van Du T; De Coi, Niccolò; Feuermann, Marc; Schmid-Siegert, Emanuel; Băguţ, Elena-Tatiana; Mignon, Bernard; Waridel, Patrice; Peter, Corinne; Pradervand, Sylvain; Pagni, Marco; Monod, Michel
2016-01-01
Dermatophytes are the most common agents of superficial mycoses in humans and animals. The aim of the present investigation was to systematically identify the extracellular, possibly secreted, proteins that are putative virulence factors and antigenic molecules of dermatophytes. A complete gene expression profile of Arthroderma benhamiae was obtained during infection of its natural host (guinea pig) using RNA sequencing (RNA-seq) technology. This profile was completed with those of the fungus cultivated in vitro in two media containing either keratin or soy meal protein as the sole source of nitrogen and in Sabouraud medium. More than 60% of transcripts deduced from RNA-seq data differ from those previously deposited for A. benhamiae . Using these RNA-seq data along with an automatic gene annotation procedure, followed by manual curation, we produced a new annotation of the A. benhamiae genome. This annotation comprised 7,405 coding sequences (CDSs), among which only 2,662 were identical to the currently available annotation, 383 were newly identified, and 15 secreted proteins were manually corrected. The expression profile of genes encoding proteins with a signal peptide in infected guinea pigs was found to be very different from that during in vitro growth when using keratin as the substrate. Especially, the sets of the 12 most highly expressed genes encoding proteases with a signal sequence had only the putative vacuolar aspartic protease gene PEP2 in common, during infection and in keratin medium. The most upregulated gene encoding a secreted protease during infection was that encoding subtilisin SUB6, which is a known major allergen in the related dermatophyte Trichophyton rubrum . IMPORTANCE Dermatophytoses (ringworm, jock itch, athlete's foot, and nail infections) are the most common fungal infections, but their virulence mechanisms are poorly understood. Combining transcriptomic data obtained from growth under various culture conditions with data obtained during infection led to a significantly improved genome annotation. About 65% of the protein-encoding genes predicted with our protocol did not match the existing annotation for A. benhamiae . Comparing gene expression during infection on guinea pigs with keratin degradation in vitro , which is supposed to mimic the host environment, revealed the critical importance of using real in vivo conditions for investigating virulence mechanisms. The analysis of genes expressed in vivo , encoding cell surface and secreted proteins, particularly proteases, led to the identification of new allergen and virulence factor candidates.
Code of Federal Regulations, 2011 CFR
2011-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... part which constitute the temporary residence of the President or other person protected by the Secret...
Code of Federal Regulations, 2010 CFR
2010-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... part which constitute the temporary residence of the President or other person protected by the Secret...
Code of Federal Regulations, 2013 CFR
2013-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... part which constitute the temporary residence of the President or other person protected by the Secret...
Code of Federal Regulations, 2014 CFR
2014-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... part which constitute the temporary residence of the President or other person protected by the Secret...
Code of Federal Regulations, 2012 CFR
2012-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... part which constitute the temporary residence of the President or other person protected by the Secret...
6 CFR 7.20 - Classification and declassification authority.
Code of Federal Regulations, 2010 CFR
2010-01-01
.... (a) Top Secret original classification authority may only be exercised by the Secretary of Homeland... up to and including Top Secret. No official who is delegated Top Secret original classification... Secret and Confidential original classification authority to other officials determined to have frequent...
32 CFR 2001.46 - Transmission.
Code of Federal Regulations, 2010 CFR
2010-07-01
... between the U.S., Puerto Rico, or a U.S. possession or trust territory. (1) Top Secret. Top Secret... an authorized government agency courier service; a designated courier or escort with Top Secret clearance; electronic means over approved communications systems. Under no circumstances will Top Secret...
32 CFR 147.19 - The three standards.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) The investigation standard for“Q” access authorizations and for access to top secret (including top secret Special Access Programs) and Sensitive Compartmented Information; (c) The reinvestigation standard... authorizations and for access to confidential and secret (including all secret-level Special Access Programs not...
Normal and abnormal secretion by haemopoietic cells
STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M
2001-01-01
The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687
The immune system in children with malnutrition--a systematic review.
Rytter, Maren Johanne Heilskov; Kolte, Lilian; Briend, André; Friis, Henrik; Christensen, Vibeke Brix
2014-01-01
Malnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed. To review the scientific literature about immune function in children with malnutrition. A systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1-60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition. The literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied. The immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.
Liang, John J; Oelkers, Peter; Guo, Cuiying; Chu, Pi-Chun; Dixon, Joseph L; Ginsberg, Henry N; Sturley, Stephen L
2004-10-22
The relative importance of each core lipid in the assembly and secretion of very low density lipoproteins (VLDL) has been of interest over the past decade. The isolation of genes encoding diacylglycerol acyltransferase (DGAT) and acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) provided the opportunity to investigate the effects of isolated increases in triglycerides (TG) or cholesteryl esters (CE) on apolipoprotein B (apoB) lipoprotein biogenesis. Overexpression of human DGAT1 in rat hepatoma McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of TG. These effects were associated with decreased intracellular degradation and increased secretion of newly synthesized apoB as VLDL. Similarly, overexpression of human ACAT1 or ACAT2 in McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of CE. This led to decreased intracellular degradation and increased secretion of VLDL apoB. Overexpression of ACAT2 had a significantly greater impact upon assembly and secretion of VLDL from liver cells than did overexpression of ACAT1. The addition of oleic acid (OA) to media resulted in a further increase in VLDL secretion from cells expressing DGAT1, ACAT1, or ACAT2. VLDL secreted from DGAT1-expressing cells incubated in OA had a higher TG:CE ratio than VLDL secreted from ACAT1- and ACAT2-expressing cells treated with OA. These studies indicate that increasing DGAT1, ACAT1, or ACAT2 expression in McA-RH7777 cells stimulates the assembly and secretion of VLDL from liver cells and that the core composition of the secreted VLDL reflects the enzymatic activity that is elevated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Samudrala, Ram; Heffron, Fred; McDermott, Jason E.
2009-04-24
The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, aftermore » eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.« less
Vitamin E Secretion by Caco-2 Monolayers to APOA1, but Not to HDL, Is Vitamer Selective12
Nicod, Nathalie; Parker, Robert S.
2013-01-01
The aim of this study was to characterize the pathways of basolateral secretion of common dietary tocopherols from polarized Caco-2 monolayers, a model of intestinal absorption. Given differences in structure and physical properties, we hypothesized that secretion may differ between different forms of vitamin E, thus potentially contribute to the selectivity seen in vivo. Monolayers were incubated apically and simultaneously with 10 μmol/L α-, γ-, and δ-tocopherol (1:1:1) in lipid micelles. Treatment with the microsomal triglyceride transfer protein inhibitor BMS201038 revealed that the triglyceride-rich particle secretory pathway (apolipoprotein B–dependent pathway) accounted for ∼80% of total tocopherol secretion, without selectivity among the three forms of vitamin E. Apolipoprotein B–independent secretion of tocopherols (and cholesterol) was greatly enhanced by the liver X receptor agonist T0901317. T0901317 induced ATP-binding cassette transporter A1 (ABCA1) protein expression and basolateral secretion of tocopherols to apolipoprotein A1. ABCA1-dependent secretion demonstrated vitamer selectivity such that efficiency of secretion of α- and γ-tocopherols exceeded that of δ-tocopherol. Basal addition of HDL stimulated vitamin E secretion but without selectivity among the three forms, whereas LDL had no effect. Basal addition of scavenger receptor class B member I (SR-BI) blocking antibody, which inhibits the interaction between SR-BI and HDL, increased basal accumulation of all tocopherols, demonstrating a role for SR-BI in cellular re-uptake of secreted vitamin E. These findings demonstrated that vitamin E and cholesterol utilize common pathways of secretion and that secretion via the ABCA1 pathway favors certain forms of vitamin E. PMID:23946344
A Phytase-Based Reporter System for Identification of Functional Secretion Signals in Bifidobacteria
Osswald, Annika; Westermann, Christina; Sun, Zhongke; Riedel, Christian U.
2015-01-01
Health-promoting effects have been attributed to a number of Bifidobacterium sp. strains. These effects as well as the ability to colonise the host depend on secreted proteins. Moreover, rational design of protein secretion systems bears the potential for the generation of novel probiotic bifidobacteria with improved health-promoting or therapeutic properties. To date, there is only very limited data on secretion signals of bifidobacteria available. Using in silico analysis, we demonstrate that all bifidobacteria encode the major components of Sec-dependent secretion machineries but only B. longum strains harbour Tat protein translocation systems. A reporter plasmid for secretion signals in bifidobacteria was established by fusing the coding sequence of the signal peptide of a sialidase of Bifidobacterium bifidum S17 to the phytase gene appA of E. coli. The recombinant strain showed increased phytase activity in spent culture supernatants and reduced phytase levels in crude extracts compared to the control indicating efficient phytase secretion. The reporter plasmid was used to screen seven predicted signal peptides in B. bifidum S17 and B. longum E18. The tested signal peptides differed substantially in their efficacy to mediate protein secretion in different host strains. An efficient signal peptide was used for expression and secretion of a therapeutically relevant protein in B. bifidum S17. Expression of a secreted cytosine deaminase led to a 100-fold reduced sensitivity of B. bifidum S17 to 5-fluorocytosine compared to the non-secreted cytosine deaminase suggesting efficient conversion of 5-fluorocytosine to the cytotoxic cancer drug 5-fluorouracil by cytosine deaminase occurred outside the bacterial cell. Selection of appropriate signal peptides for defined protein secretion might improve therapeutic efficacy as well as probiotic properties of bifidobacteria. PMID:26086721
DOE Office of Scientific and Technical Information (OSTI.GOV)
Werb, Z.
1978-01-01
The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1 to 1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contast, secretion of lysozyme was not affectedmore » by glucocorticoids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1 to 10 nM) similar to those that half-saturated the specific glucocorticoid receptors. At high concentrations of dexamethasone (100 to 1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (>95%) than the secretion of elastase (60 to 80%).Progesterone alone had no effect on secretion, but blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1 to 100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone.« less
Lu, Jin Fang; Wang, Wei Na; Wang, Gai Ling; Zhang, He; Zhou, Ying; Gao, Zhi Peng; Nie, Pin; Xie, Hai Xia
2016-01-01
The type III secretion system (T3SS) of Edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. The orf13 gene (escE) of E. tarda is located 84 nucleotides (nt) upstream of esrC in the T3SS gene cluster. We found that EscE is secreted and translocated in a T3SS-dependent manner and that amino acids 2 to 15 in the N terminus were required for a completely functional T3SS in E. tarda. Deletion of escE abolished the secretion of T3SS translocators, as well as the secretion and translocation of T3SS effectors, but did not influence their intracellular protein levels in E. tarda. Complementation of the escE mutant with a secretion-incompetent EscE derivative restored the secretion of translocators and effectors. Interestingly, the effectors that were secreted and translocated were positively correlated with the EscE protein level in E. tarda. The escE mutant was attenuated in the blue gourami fish infection model, as its 50% lethal dose (LD50) increased to 4 times that of the wild type. The survival rate of the escE mutant-strain-infected fish was 69%, which was much higher than that of the fish infected with the wild-type bacteria (6%). Overall, EscE represents a secreted T3SS regulator that controls effector injection and translocator secretion, thus contributing to E. tarda pathogenesis in fish. The homology of EscE within the T3SSs of other bacterial species suggests that the mechanism of secretion and translocation control used by E. tarda may be commonly used by other bacterial pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Monks, Jenifer; Dzieciatkowska, Monika; Bales, Elise S; Orlicky, David J; Wright, Richard M; McManaman, James L
2016-10-15
Xanthine oxidoreductase (XOR) modulates milk lipid secretion and lactation initiation. XOR is required for butyrophilin1a1 clustering in the membrane during milk lipid secretion. XOR mediates apical membrane reorganization during milk lipid secretion. Loss of XOR delays milk fat globule secretion. XOR loss alters the proteome of milk fat globules. Apocrine secretion is utilized by epithelial cells of exocrine glands. These cells bud off membrane-bound particles into the lumen of the gland, losing a portion of the cytoplasm in the secretion product. The lactating mammary gland secretes milk lipid by this mechanism, and xanthine oxidoreductase (XOR) has long been thought to be functionally important. We generated mammary-specific XOR knockout (MGKO) mice, expecting lactation to fail. Histology of the knockout glands showed very large lipid droplets enclosed in the mammary alveolar cells, but milk analysis showed that these large globules were secreted. Butyrophilin, a membrane protein known to bind to XOR, was clustered at the point of contact of the cytoplasmic lipid droplet with the apical plasma membrane, in the wild-type gland but not in the knockout, suggesting that XOR mediates 'docking' to this membrane. Secreted milk fat globules were isolated from mouse milk of wild-type and XOR MGKO dams, and subjected to LC-MS/MS for analysis of protein component. Proteomic results showed that loss of XOR leads to an increase in cytoplasmic, cytoskeletal, Golgi apparatus and lipid metabolism proteins associated with the secreted milk fat globule. Association of XOR with the lipid droplet results in membrane docking and more efficient retention of cytoplasmic components by the secretory cell. Loss of XOR then results in a reversion to a more rudimentary, less efficient, apocrine secretion mechanism, but does not prevent milk fat globule secretion. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
The Physical Burdens of Secrecy
ERIC Educational Resources Information Center
Slepian, Michael L.; Masicampo, E. J.; Toosi, Negin R.; Ambady, Nalini
2012-01-01
The present work examined whether secrets are experienced as physical burdens, thereby influencing perception and action. Four studies examined the behavior of people who harbored important secrets, such as secrets concerning infidelity and sexual orientation. People who recalled, were preoccupied with, or suppressed an important secret estimated…
10 CFR 1016.34 - Accountability for Secret Restricted Data.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 10 Energy 4 2012-01-01 2012-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall maintain...
Code of Federal Regulations, 2011 CFR
2011-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... persons protected by the Secret Service shall be that property which each designates for protection by the...
10 CFR 1016.34 - Accountability for Secret Restricted Data.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 10 Energy 4 2014-01-01 2014-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall maintain...
10 CFR 1016.34 - Accountability for Secret Restricted Data.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 10 Energy 4 2013-01-01 2013-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall maintain...
Code of Federal Regulations, 2012 CFR
2012-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... persons protected by the Secret Service shall be that property which each designates for protection by the...
10 CFR 1016.34 - Accountability for Secret Restricted Data.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 10 Energy 4 2010-01-01 2010-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall maintain...
Code of Federal Regulations, 2013 CFR
2013-07-01
... and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE, DEPARTMENT... SECRET SERVICE AND TEMPORARY OFFICES OF THE PRESIDENT AND STAFF, OR OTHER PERSON PROTECTED BY THE SECRET... persons protected by the Secret Service shall be that property which each designates for protection by the...
10 CFR 1016.34 - Accountability for Secret Restricted Data.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 10 Energy 4 2011-01-01 2011-01-01 false Accountability for Secret Restricted Data. 1016.34 Section... Information § 1016.34 Accountability for Secret Restricted Data. Each permittee possessing documents containing Secret Restricted Data shall establish a document accountability procedure and shall maintain...
32 CFR 2800.4 - General information.
Code of Federal Regulations, 2010 CFR
2010-07-01
... STATES SECURITY PROCEDURES § 2800.4 General information. (a) Staff Security Officer/Top Secret Control... Staff Security Officer will serve as Top Secret Control Officer and Assistant Top Secret Control Officer... responsible for the overall supervision of the Top Secret Control program. They will maintain positive control...
14 CFR 1203.203 - Degree of protection.
Code of Federal Regulations, 2010 CFR
2010-01-01
... classified documents or materials except as expressly provided by statute or by NASA Directives. (1) Top Secret. Top Secret is the designation applied to information or material the unauthorized disclosure of... security. (2) Secret. Secret is the designation applied to information or material the unauthorized...
41 CFR 105-62.102 - Authority to originally classify.
Code of Federal Regulations, 2013 CFR
2013-07-01
... originally classify. (a) Top secret, secret, and confidential. The authority to originally classify information as Top Secret, Secret, or Confidential may be exercised only by the Administrator and is delegable... classification authority. Delegations of original classification authority are limited to the minimum number...
41 CFR 105-62.102 - Authority to originally classify.
Code of Federal Regulations, 2011 CFR
2011-01-01
... originally classify. (a) Top secret, secret, and confidential. The authority to originally classify information as Top Secret, Secret, or Confidential may be exercised only by the Administrator and is delegable... classification authority. Delegations of original classification authority are limited to the minimum number...
41 CFR 105-62.102 - Authority to originally classify.
Code of Federal Regulations, 2014 CFR
2014-01-01
... originally classify. (a) Top secret, secret, and confidential. The authority to originally classify information as Top Secret, Secret, or Confidential may be exercised only by the Administrator and is delegable... classification authority. Delegations of original classification authority are limited to the minimum number...
Exosome secretion affects social motility in Trypanosoma brucei
Shaked, Hadassa; Arvatz, Gil; Tkacz, Itai Dov; Binder, Lior; Waldman Ben-Asher, Hiba; Okalang, Uthman; Chikne, Vaibhav; Cohen-Chalamish, Smadar; Michaeli, Shulamit
2017-01-01
Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites. PMID:28257521
Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells.
Almaça, Joana; Molina, Judith; Menegaz, Danusa; Pronin, Alexey N; Tamayo, Alejandro; Slepak, Vladlen; Berggren, Per-Olof; Caicedo, Alejandro
2016-12-20
In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via 5-HT 1F receptors and inhibits glucagon secretion. Without serotonergic input, alpha cells lose their ability to regulate glucagon secretion in response to changes in glucose concentration, suggesting that diminished serotonergic control of alpha cells can cause glucose blindness and the uncontrolled glucagon secretion associated with diabetes. Supporting this model, pharmacological activation of 5-HT 1F receptors reduces glucagon secretion and has hypoglycemic effects in diabetic mice. Thus, modulation of serotonin signaling in the islet represents a drug intervention opportunity. Published by Elsevier Inc.
Novel Threshold Changeable Secret Sharing Schemes Based on Polynomial Interpolation
Li, Mingchu; Guo, Cheng; Choo, Kim-Kwang Raymond; Ren, Yizhi
2016-01-01
After any distribution of secret sharing shadows in a threshold changeable secret sharing scheme, the threshold may need to be adjusted to deal with changes in the security policy and adversary structure. For example, when employees leave the organization, it is not realistic to expect departing employees to ensure the security of their secret shadows. Therefore, in 2012, Zhang et al. proposed (t → t′, n) and ({t1, t2,⋯, tN}, n) threshold changeable secret sharing schemes. However, their schemes suffer from a number of limitations such as strict limit on the threshold values, large storage space requirement for secret shadows, and significant computation for constructing and recovering polynomials. To address these limitations, we propose two improved dealer-free threshold changeable secret sharing schemes. In our schemes, we construct polynomials to update secret shadows, and use two-variable one-way function to resist collusion attacks and secure the information stored by the combiner. We then demonstrate our schemes can adjust the threshold safely. PMID:27792784
Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H
1984-08-01
The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.
Novel Threshold Changeable Secret Sharing Schemes Based on Polynomial Interpolation.
Yuan, Lifeng; Li, Mingchu; Guo, Cheng; Choo, Kim-Kwang Raymond; Ren, Yizhi
2016-01-01
After any distribution of secret sharing shadows in a threshold changeable secret sharing scheme, the threshold may need to be adjusted to deal with changes in the security policy and adversary structure. For example, when employees leave the organization, it is not realistic to expect departing employees to ensure the security of their secret shadows. Therefore, in 2012, Zhang et al. proposed (t → t', n) and ({t1, t2,⋯, tN}, n) threshold changeable secret sharing schemes. However, their schemes suffer from a number of limitations such as strict limit on the threshold values, large storage space requirement for secret shadows, and significant computation for constructing and recovering polynomials. To address these limitations, we propose two improved dealer-free threshold changeable secret sharing schemes. In our schemes, we construct polynomials to update secret shadows, and use two-variable one-way function to resist collusion attacks and secure the information stored by the combiner. We then demonstrate our schemes can adjust the threshold safely.
Imai, Saki; Kusakabe, Takahiro; Xu, Jian; Li, Zhiqing; Shirai, Shintaro; Mon, Hiroaki; Morokuma, Daisuke; Lee, Jae Man
2015-11-01
Baculovirus expression vector system (BEVS) is widely used for production of recombinant eukaryotic proteins in insect larvae or cultured cells. BEVS has advantages over bacterial expression system in producing post-translationally modified secreted proteins. However, for some unknown reason, it is very difficult for insects to secrete sufficiently for certain proteins of interest. To understand the reasons why insect cells fail to secrete some kinds of recombinant proteins, we here employed three mammalian proteins as targets, EPO, HGF, and Wnt3A, with different secretion levels in BEVS and investigated their mRNA transcriptions from the viral genome, subcellular localizations, and interactions with silkworm ER chaperones. Moreover, we observed that no significantly influence on the secretion amounts of all three proteins when depleting or overexpressing most endogenous ER chaperone genes in cultured silkworm cells. However, among all detected ER chaperones, the depletion of BiP severely decreased the recombinant protein secretion in BEVS, indicating the possible central role of Bip in silkworm secretion pathway.
Beaudoin, M; Carey, M C; Small, D M
1975-01-01
Bile salts play a major role in bile formation and biliary lipid secretion. Sodium taurodihydrofusidate (TDHF), a derivative of the antibiotic fusidic acid, closely resembles bile salts in terms of structure, micellar characteristics, and capacity ot solubilize otherwise insolbule lipids. We have therefore studied the biliary secretion of this bile salt analogue and its influence on bile formation and biliary lipid secretion in primates. Alert, unanesthetized female rhesus monkeys prepared with a total biliary fistula were allowed to reach a steady bile salt secretion rate before each study. In three animals (group I),[14C]TDHF was infused intravenously. Most of the compound was secreted rapidly in bile chemically unchanged. The biliary secretion of this drug produced a twofold increase in bile flow; however, the bile salt output was markedly reduced during the infusion. In spite of this reduction, the phospholipid output remained essentially unchanged whereas the cholesterol output increased almost twofold. In five other animals (group II), the effect of TDHF on the bile salt secretion was further investigated by an intravenous infusion of [14C]taurocholate followed by a combined infusion of [14C]taurocholate and TDHF. When TDHF was added to the infusate, a reduction in the [14C]taurocholate output and a progressive rise in the plasma [14C]taurocholate concentration were observed in each animal. An analysis of the data in both groups indicates that (a) the most likely explanation to account for the decreased bile salt output is that the bile salt analogue, TDHF, interfered with bile salt secretion into the biliary canaliculi; (b) TDHF induces a greater secretion of biliary water than was observed with bile salts, an effect consistent with a stimulation of the bile salt-independent canalicular flow; (c) at similar 3alpha-hydroxysteroid secretion rates TDHF caused a significant increase in cholesterol secretion compared to that induced by bile salt. This finding suggests that TDHF affects cholesterol metabolism or secretion in a way distinct from bile salts. Thus, the solubilization of biliary lipids in mixed micelles, although essential, is only one of the factors which determine their secretion into bile. PMID:811689
Steingoetter, Andreas; Sauter, Matthias; Curcic, Jelena; Liu, Dian; Menne, Dieter; Fried, Michael; Fox, Mark; Schwizer, Werner
2015-09-02
Postprandial accumulation of gastric secretions in the proximal stomach above the meal adjacent to the esophagogastric junction (EGJ), referred to as the 'acid pocket', has been proposed as a pathophysiological factor in gastro-esophageal reflux disease (GERD) and as a target for GERD treatment. This study assessed the effect of proton pump inhibitor (PPI) therapy on the volume, distribution and acidity of gastric secretions in GERD and healthy subjects (HS). A randomized, double blind, cross-over study in 12 HS and 12 GERD patients pre-treated with 40 mg pantoprazole (PPI) or placebo b.i.d. was performed. Postprandial secretion volume (SV), formation of a secretion layer and contact between the layer and the EGJ were quantified by Magnetic Resonance Imaging (MRI). Multi-channel pH-monitoring assessed intragastric pH. A distinct layer of undiluted acid secretion was present on top of gastric contents in almost all participants on and off high-dose acid suppression. PPI reduced SV (193 ml to 100 ml, in HS, 227 ml to 94 ml in GERD; p < 0.01) and thickness of the acid layer (26 mm to 7 mm, 36 mm to 9 mm respectively, p < 0.01). No differences in secretion volume or layer thickness were observed between groups; however, off treatment, contact time between the secretion layer and EGJ was 2.6 times longer in GERD compared to HS (p = 0.012). This was not the case on PPI. MRI can visualize and quantify the volume and distribution dynamics of gastric secretions that form a layer in the proximal stomach after ingestion of a liquid meal. The secretion volume and the secretion layer on top of gastric contents is similar in GERD patients and HS; however contact between the layer of undiluted secretion and the EGJ is prolonged in patients. High dose PPI reduced secretion volume by about 50% and reduced contact time between secretion and EGJ towards normal levels. NCT01212614.
[Exo- and endosecretive digestive glands of enzymes as modulators of secretion].
Korot'ko, G F
2010-01-01
Enzymes, exosecreted by the digestive glands plays not only a role of the hydrolases, but also an informational and modulating role in the urgent adaptation of the enzyme secretion to the structure and properties of the luminal content of the gastrointestinal tract. Endosecreted enzymes in the blood not only inform about enzymatic condition of the hydrolase-producing glands and duct system, but also plays an informational and modulating role by the inhibition of the secretion of the same enzymes, and by the stimulation of the secretion of the heteronymic enzyme, defines a parity of their secretion and recretion, integrates enzyme secretion of the pancreas and gastric glands.
Cao, Haojie; van Heel, Auke J; Ahmed, Hifza; Mols, Maarten; Kuipers, Oscar P
2017-04-04
Bacillus subtilis is widely used as a cell factory for numerous heterologous proteins of commercial value and medical interest. To explore the possibility of further enhancing the secretion potential of this model bacterium, a library of engineered strains with modified cell surface components was constructed, and the corresponding influences on protein secretion were investigated by analyzing the secretion of α-amylase variants with either low-, neutral- or high- isoelectric points (pI). Relative to the wild-type strain, the presence of overall anionic membrane phospholipids (phosphatidylglycerol and cardiolipin) increased dramatically in the PssA-, ClsA- and double KO mutants, which resulted in an up to 47% higher secretion of α-amylase. Additionally, we demonstrated that the appropriate net charge of secreted targets (AmyTS-23, AmyBs and AmyBm) was beneficial for secretion efficiency as well. In B. subtilis, the characteristics of cell membrane phospholipid bilayer and the pIs of heterologous α-amylases appear to be important for their secretion efficiency. These two factors can be engineered to reduce the electrostatic interaction between each other during the secretion process, which finally leads to a better secretion yield of α-amylases.
Optical properties of the uropygial gland secretion: no evidence for UV cosmetics in birds
NASA Astrophysics Data System (ADS)
Delhey, Kaspar; Peters, Anne; Biedermann, Peter H. W.; Kempenaers, Bart
2008-10-01
Ultraviolet (UV) reflectance of the plumage is common in birds and plays an important role in sexual signalling. Recently, it has been proposed that birds are able to modify plumage UV reflectance by the application of uropygial gland secretion. Based on a survey of the optical properties of this secretion from 51 species belonging to 12 avian orders, we show that two main types of uropygial secretions exist, one predominantly found in passerines and one in non-passerines, both reducing relative UV reflectance of a white background (Teflon™ tape). We quantified how each type of secretion (exemplified by blue tit and mallard) affected feather UV reflectance. Both secretions reduced overall brightness and relative UV reflectance of white mallard feathers but hardly affected the reflectance of UV/blue blue tit crown feathers. According to models of avian colour vision, changes in reflectance due to application of the secretion were at or below the discrimination threshold of most birds. We conclude that the uropygial secretion is unlikely to play a major role in modifying plumage UV reflectance. However, the optical properties of the uropygial secretion may have been selected to interfere as little as possible with visual signaling through plumage reflectance.
Effects and Mechanisms of Tastants on the Gustatory-Salivary Reflex in Human Minor Salivary Glands.
Satoh-Kuriwada, Shizuko; Shoji, Noriaki; Miyake, Hiroyuki; Watanabe, Chiyo; Sasano, Takashi
2018-01-01
The effects and mechanisms of tastes on labial minor salivary gland (LMSG) secretion were investigated in 59 healthy individuals. Stimulation with each of the five basic tastes (i.e., sweet, salty, sour, bitter, and umami) onto the tongue induced LMSG secretion in a dose-dependent manner. Umami and sour tastes evoked greater secretion than did the other tastes. A synergistic effect of umami on LMSG secretion was recognized: a much greater increase in secretion was observed by a mixed solution of monosodium glutamate and inosine 5'-monophosphate than by each separate stimulation. Blood flow (BF) in the nearby labial mucosa also increased following stimulation by each taste except bitter. The BF change and LMSG secretion in each participant showed a significant positive correlation with all tastes, including bitter. Administration of cevimeline hydrochloride hydrate to the labial mucosa evoked a significant increase in both LMSG secretion and BF, while adrenaline, atropine, and pirenzepine decreased LMSG secretion and BF. The change in LMSG secretion and BF induced by each autonomic agent was significantly correlated in each participant. These results indicate that basic tastes can induce the gustatory-salivary reflex in human LMSGs and that parasympathetic regulation is involved in this mechanism.
Yoshimura, Yuri; Kasuya, Eiiti
2013-01-01
The roles played by nonfatal secretions of adult anurans in the avoidance of predation remain unknown. The adult Wrinkled frog (Rana rugosa) has warty skin with the odorous mucus secretion that is not fatal to the snake Elaphe quadrivirgata. We fed R. rugosa or Fejervarya limnocharis, which resembles R. rugosa in appearance and has mucus secretion, to snakes and compared the snakes’ responses to the frogs. Compared to F. limnocharis, R. rugosa was less frequently bitten or swallowed by snakes. The snakes that bit R. rugosa spat out the frogs and showed mouth opening (gaping) behavior, while the snakes that bit F. limnocharis did not show gaping behavior. We also compared the responses of the snakes to R. rugosa and F. limnocharis secretions. We coated palatable R. japonica with secretions from R. rugosa or F. limnocharis. The frogs coated by R. rugosa secretion were less frequently bitten or swallowed than those coated by F. limnocharis secretion. We concluded that compared to different frog species of similar sizes, the adult R. rugosa was less frequently preyed upon by, and that its skin secretion was effective in avoiding predation by snakes. PMID:24278410
Yoshimura, Yuri; Kasuya, Eiiti
2013-01-01
The roles played by nonfatal secretions of adult anurans in the avoidance of predation remain unknown. The adult Wrinkled frog (Rana rugosa) has warty skin with the odorous mucus secretion that is not fatal to the snake Elaphe quadrivirgata. We fed R. rugosa or Fejervarya limnocharis, which resembles R. rugosa in appearance and has mucus secretion, to snakes and compared the snakes' responses to the frogs. Compared to F. limnocharis, R. rugosa was less frequently bitten or swallowed by snakes. The snakes that bit R. rugosa spat out the frogs and showed mouth opening (gaping) behavior, while the snakes that bit F. limnocharis did not show gaping behavior. We also compared the responses of the snakes to R. rugosa and F. limnocharis secretions. We coated palatable R. japonica with secretions from R. rugosa or F. limnocharis. The frogs coated by R. rugosa secretion were less frequently bitten or swallowed than those coated by F. limnocharis secretion. We concluded that compared to different frog species of similar sizes, the adult R. rugosa was less frequently preyed upon by, and that its skin secretion was effective in avoiding predation by snakes.
Pérez-Sotelo, Diego; Roca-Rivada, Arturo; Larrosa-García, María; Castelao, Cecilia; Baamonde, Iván; Baltar, Javier; Crujeiras, Ana Belen; Seoane, Luisa María; Casanueva, Felipe F; Pardo, María
2017-02-01
The secretion of the hepatokine alpha-2-Heremans-Schmid glycoprotein/Fetuin A, implicated in pathological processes including systemic insulin resistance, by adipose tissue has been recently described. Thus, we have recently identified its presence in white adipose tissue secretomes by mass spectrometry. However, the secretion pattern and function of adipose-derived alpha-2-Heremans-Schmid glycoprotein are poorly understood. The aim of this study is to evaluate the expression and secretion of total and active phosphorylated alpha-2-Heremans-Schmid glycoprotein by adipose tissue from visceral and subcutaneous localizations in animals at different physiological and nutritional status including anorexia and obesity. Alpha-2-Heremans-Schmid glycoprotein expression and secretion in visceral adipose tissue and subcutaneous adipose tissue explants from animals under fasting and exercise training, at pathological situations such as anorexia and obesity, and from human obese individuals were assayed by immunoblotting, quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. We reveal that visceral adipose tissue expresses and secretes more alpha-2-Heremans-Schmid glycoprotein than subcutaneous adipose tissue, and that this secretion is diminished after fasting and exercise training. Visceral adipose tissue from anorectic animals showed reduced alpha-2-Heremans-Schmid glycoprotein secretion; on the contrary, alpha-2-Heremans-Schmid glycoprotein is over-secreted by visceral adipose tissue in the occurrence of obesity. While secretion of active-PhophoSer321α2HSG by visceral adipose tissue is independent of body mass index, we found that the fraction of active-alpha-2-Heremans-Schmid glycoprotein secreted by subcutaneous adipose tissue increments significantly in situations of obesity. Functional studies show that the inhibition of adipose-derived alpha-2-Heremans-Schmid glycoprotein increases insulin sensitivity in differentiated adipocytes. In conclusion, visceral adipose tissue secretes more alpha-2-Heremans-Schmid glycoprotein than subcutaneous adipose tissue and this secretion is more sensitive to nutritional and physiological changes. The over-secretion of alpha-2-Heremans-Schmid glycoprotein by visceral adipose tissue, the increased secretion of the active phosphorylated form by subcutaneous adipose tissuein obese animals, and the adipose-derived alpha-2-Heremans-Schmid glycoprotein capacity to inhibit the insulin pathway suggest the participation of adipose-derived alpha-2-Heremans-Schmid glycoprotein in the deleterious effects of obesity.
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