Characteristics of Tularemia in Kosovo 2010

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Mr.Sc. Izet Sadiku

2011-12-01

Conclusions: In this late decade in our country, tularemia continues to be a disease that represents a healthcare problem. Glandular forms of tularemia dominate in Kosovo. Treatment with gentamicin has had good effects. Incision and drainage of the inflamed glands has shown to be a good method in accelerating the recovery of patient. Prophylaxis has to be applied for prevention of the disease.

High-risk regions and outbreak modelling of tularemia in humans.

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Desvars-Larrive, A; Liu, X; Hjertqvist, M; Sjöstedt, A; Johansson, A; Rydén, P

2017-02-01

Sweden reports large and variable numbers of human tularemia cases, but the high-risk regions are anecdotally defined and factors explaining annual variations are poorly understood. Here, high-risk regions were identified by spatial cluster analysis on disease surveillance data for 1984-2012. Negative binomial regression with five previously validated predictors (including predicted mosquito abundance and predictors based on local weather data) was used to model the annual number of tularemia cases within the high-risk regions. Seven high-risk regions were identified with annual incidences of 3·8-44 cases/100 000 inhabitants, accounting for 56·4% of the tularemia cases but only 9·3% of Sweden's population. For all high-risk regions, most cases occurred between July and September. The regression models explained the annual variation of tularemia cases within most high-risk regions and discriminated between years with and without outbreaks. In conclusion, tularemia in Sweden is concentrated in a few high-risk regions and shows high annual and seasonal variations. We present reproducible methods for identifying tularemia high-risk regions and modelling tularemia cases within these regions. The results may help health authorities to target populations at risk and lay the foundation for developing an early warning system for outbreaks.

A rare cause of abdominal lymphadenopathy--tularemia: report of two pediatric cases.

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Gülhan, Belgin; Tezer, Hasan; Kanık-Yüksek, Saliha; Kılıç, Selçuk; Senel, Emrah

2014-01-01

Tularemia caused by Francisella tularensis occurs worldwide in the northern hemisphere, with great variation in geographic and temporal occurrence. It generally presents as an acute febrile disease with the major clinical presentations including the six classic forms of tularemia: ulceroglandular, glandular, oculoglandular, oropharyngeal, typhoidal, and pneumonic. In contrast to European countries, where the ulceroglandular form is more prominent, the oropharyngeal form is the most common presentation in Turkey. We present rare cases of oropharyngeal tularemia in a 16-year-old boy and nine-year-old girl. To the best of our knowledge, these are the firstly described abdominal lymphadenopathy cases from Turkey. The second case was admitted with erythema nodosum, and abdominal lymphadenopathy was detected during the investigation. Excisional lymph node biopsy revealed abdominal tularemia. It is necessary to consider tularemia in the differential diagnosis of abdominal lymphadenopathy in tularemia regions. We also conclude that oropharyngeal tularemia can cause lymphadenopathy in any part of the gastrointestinal tract.

Ulceroglandular tularemia in a toddler in Germany after a mosquito bite.

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Hanke, Christof A; Otten, Joerg-Elard; Berner, Reinhard; Serr, Annerose; Splettstoesser, Wolf; von Schnakenburg, Christian

2009-08-01

Although tularemia is a long-known disease, its significance had diminished over the last decades in Middle Europe. However, over the past years, there is new evidence suggesting that tularemia has re-emerged in Germany. In 2007, the highest number of human cases for almost 50 years has been notified. Beside typical vectors, new ways of transmission seem to gain significance. So far, mosquito bite-transmitted tularemia has only been known from Scandinavia but not from Middle Europe. We report the first case of a 1-year-old toddler from Southwestern Germany with mosquito bite-associated ulceroglandular tularaemia. The new and interesting features of this case are the young age of the patient and the unusual transmission route. The available data suggesting changes in the epidemiology for tularemia in Germany are reviewed. This is an interesting case of infantile tularemia with a very unusual transmission route, highlighting ongoing changes in the epidemiology of tularemia in Germany.

Tularemia: Current Diagnosis and Treatment Options

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2008-04-01

for growing F. tularensis, which include cysteine blood agar, Thayer–Martin agar and cysteine heart agar with 9% heated sheep red blood cells (CHAB...SL et al. An outbreak of primary pneumonic tularemia on Martha’s Vineyard . N. Engl. J. Med. 345, 1601–1606 (2001). 86 Feldman KA, Stiles-Enos D...Julian K et al. Tularemia on Martha’s Vineyard : seroprevalence and occupational risk. Emerg. Infect. Dis. 9, 350–354 (2003). 87 Christensen DR

Cluster of ulceroglandular tularemia cases in Slovenia.

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Rojko, Tereza; Korva, Miša; Lotrič-Furlan, Stanka; Strle, Franc; Avšič-Županc, Tatjana

2016-10-01

In Slovenia, a small Central European country, where tularemia cases are very rare and mostly sporadic, six cases of ulceroglandular tularemia were recognised in 2012-2013 in patients residing in or visiting a small geographical area of <6km 2 . Epidemiological data indicated transmission by a tick bite in at least 3/6 patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

A Field Study of Plague and Tularemia in Rodents, Western Iran.

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Mostafavi, Ehsan; Shahraki, Abdolrazagh Hashemi; Japoni-Nejad, Alireza; Esmaeili, Saber; Darvish, Jamshid; Sedaghat, Mohammad Mehdi; Mohammadi, Ali; Mohammadi, Zeinolabedin; Mahmoudi, Ahmad; Pourhossein, Behzad; Ghasemi, Ahmad; Gyuranecz, Miklós; Carniel, Elisabeth

2017-04-01

Kurdistan Province in Iran is a historical focus for plague and tularemia. This study aimed at assessing the current status of these two foci by studying their rodent reservoirs. Rodents were trapped and their ectoparasites were collected. The genus and species of both rodents and ectoparasites were determined. Serological analyses of rodent blood samples were done by enzyme-linked immunosorbent assay for plague and by standard tube agglutination assay for tularemia. Rodent spleen samples were subjected to bacterial culture, microscopic examination, and real-time PCR to search for active plague or tularemia infection. During this study, 245 rodents were trapped, of which the most abundant genera were Apodemus (40%), Mus (24.49%), and Meriones (12.65%). One hundred fifty-three fleas, 37 mites, and 54 ticks were collected on these rodents. The results of all direct and indirect tests were negative for plague. Serological tests were positive for tularemia in 4.8% of trapped rodents. This study is the first report on the presence of tularemia infection in rodents in Western Iran. Since Meriones persicus is a known reservoir for plague and tularemia, and this rodent carried plague and tularemia vectors in Marivan and Sanandaj districts, there is a real potential for the occurrence of these two diseases in this region.

Performance of seven serological assays for diagnosing tularemia

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2014-01-01

Background Tularemia is a rare zoonotic disease caused by the Gram-negative bacterium Francisella tularensis. Serology is frequently the preferred diagnostic approach, because the pathogen is highly infectious and difficult to cultivate. The aim of this retrospective study was to determine the diagnostic accuracy of tularemia specific tests. Methods The Serazym®Anti-Francisella tularensis ELISA, Serion ELISA classic Francisella tularensis IgG/IgM, an in-house ELISA, the VIRapid® Tularemia immunochromatographic test, an in-house antigen microarray, and a Western Blot (WB) assay were evaluated. The diagnosis tularemia was established using a standard micro-agglutination assay. In total, 135 sera from a series of 110 consecutive tularemia patients were tested. Results The diagnostic sensitivity and diagnostic specificity of the tests were VIRapid (97.0% and 84.0%), Serion IgG (96.3% and 96.8%), Serion IgM (94.8% and 96.8%), Serazym (97.0% and 91.5%), in-house ELISA (95.6% and 76.6%), WB (93.3% and 83.0%), microarray (91.1% and 97.9%). Conclusions The diagnostic value of the commercial assays was proven, because the diagnostic accuracy was >90%. The diagnostic sensitivity of the in-house ELISA and the WB were acceptable, but the diagnostic accuracy was <90%. Interestingly, the antigen microarray test was very specific and had a very good positive predictive value. PMID:24885274

A case of typhoidal tularemia in a male Japanese farmer

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Kiwamu Nakamura

2018-06-01

Full Text Available In Japan, most tularemia cases occur after contact with hares (hunting, cooking and involve the glandular or ulceroglandular form. Here, we present a case of typhoidal tularemia in a 72-year-old Japanese male farmer who presented with fever, fatigue, and right lower abdominal pain. Computed tomography revealed intestinal wall thickening at the ascending colon, pleural effusion, and ascites. Following an initial diagnosis of bacterial enteric infection, his symptoms deteriorated after a week-long cephalosporin treatment course. The patient lived in an area endemic for scrub typhus; the antibiotic was changed to a tetracycline on suspicion of scrub typhus infection. His symptoms rapidly improved after initiation of minocycline treatment. Later, blood tests revealed marked increases in serological tests against Francisella tularensis exclusively, and the patient was diagnosed with typhoidal tularemia. Typhoidal tularemia may be characterized by any combination of general symptoms, but does not exhibit the local manifestations associated with other forms of tularemia. The patient, in this case, had no direct contact with hares or other wild animals and did not present with local manifestations of tularemia. Physicians should consider this disease, especially when tick-borne disease is suspected in the absence of local wounds, eschar, ulcers, or lymphadenopathy.

[Tularemia in Konya region, Turkey].

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Dikici, Nebahat; Ural, Onur; Sümer, Sua; Oztürk, Kayhan; Albayrak Yiğit, Ozgen; Katlanır, Eda; Keleş, Bahar

2012-04-01

Tularemia is a zoonotic infection caused by Francisella tularensis. In the recent years tularemia has become a re-emerging infection in Turkey with epidemics and also sporadic cases. Transmission occurs most often through consumption of contaminated water and food, direct contact with animals and insect/ tick bites. In this study, we evaluated clinical features and laboratory findings of 35 tularemia cases diagnosed during two outbreaks that occurred in two different villages during two different periods in Konya (located in Central Anatolia), Turkey and five sporadic cases. In both outbreaks, first (index) cases were admitted to our outpatient clinic with the complaints of cervical lympadenopathy. After diagnosis of tularemia, an organized team visited the villages to search if more cases existed. For microbiological diagnosis, blood, throat and tonsil swabs and lymph node aspirate specimens were collected from the suspected cases. Diagnostic tests (culture, serology, molecular methods) for tularemia were performed in reference center, Refik Saydam National Public Health Agency. Drinking and potable water samples from those villages were also collected by provincial health authorities. The cases (n= 14) that belonged to the first epidemics were detected in February 2010 and cases (n= 21) of the second epidemics in November- December 2010; five cases were followed as sporadic. The mean age of the 40 patients (25 females, 15 males) was 37.6 (age range: 5-80 years; five of them were pediatric group) years. The most common complaints of patients were cervical mass (90%), sore throat (63%), chills (60%) and fever (58%). The most frequently detected clinical findings were enlarged lymph nodes (n= 34, 85%), followed by tonsillitis (20%), skin lesions (15%) and conjunctivitis (8%). Most of the patients (82.5%) had been misdignosed as acute tonsillitis, suppurative lymphadenitis, tuberculous lymphadenitis and brucellosis, before their admission to our hospital and treated

Outbreaks of Tularemia in a Boreal Forest Region Depends on Mosquito Prevalence

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Rydén, Patrik; Björk, Rafael; Schäfer, Martina L.; Lundström, Jan O.; Petersén, Bodil; Lindblom, Anders; Forsman, Mats; Sjöstedt, Anders

2012-01-01

Background. We aimed to evaluate the potential association of mosquito prevalence in a boreal forest area with transmission of the bacterial disease tularemia to humans, and model the annual variation of disease using local weather data. Methods. A prediction model for mosquito abundance was built using weather and mosquito catch data. Then a negative binomial regression model based on the predicted mosquito abundance and local weather data was built to predict annual numbers of humans contracting tularemia in Dalarna County, Sweden. Results. Three hundred seventy humans were diagnosed with tularemia between 1981 and 2007, 94% of them during 7 summer outbreaks. Disease transmission was concentrated along rivers in the area. The predicted mosquito abundance was correlated (0.41, P tularemia (temporal correlation, 0.76; P tularemia in a tularemia-endemic boreal forest area of Sweden and that environmental variables can be used as risk indicators. PMID:22124130

Human tularemia in Italy. Is it a re-emerging disease?

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D'Alessandro, D; Napoli, C; Nusca, A; Bella, A; Funari, E

2015-07-01

Tularemia is a contagious infectious disease due to Francisiella tularensis that can cause serious clinical manifestations and significant mortality if untreated. Although the frequency and significance of the disease has diminished over the last decades in Central Europe, over the past few years, there is new evidence suggesting that tularemia has re-emerged worldwide. To know the real epidemiology of the disease is at the root of correct control measures. In order to evaluate whether tularemia is re-emerging in Italy, data on mortality and morbidity (obtained by the National Institute of Statistics; ISTAT), Italian cases described in the scientific literature and data concerning hospitalizations for tularemia (obtained by the National Hospital Discharge Database) were analysed. From 1979 to 2010, ISTAT reported 474 cases and no deaths. The overall number of cases obtained from the literature review was at least 31% higher than that reported by ISTAT. Moreover, the number of cases reported by ISTAT was 3·5 times smaller than hospitalized cases. In Italy tularemia is sporadic, rarely endemic and self-limiting; but, although the trend of reported tularemia does not support the hypothesis of a re-emerging disease, the study demonstrates a wide underreporting of the disease. The real frequency of the disease should be carefully investigated and taken into account in order to implement specific prevention measures.

Tularemia, a re-emerging infectious disease in Iran and neighboring countrie

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Zargar, Afsaneh; Maurin, Max; Mostafavi, Ehsan

2015-01-01

OBJECTIVES: Tularemia is a zoonotic disease transmitted by direct contact with infected animals and through arthropod bites, inhalation of contaminated aerosols, ingestion of contaminated meat or water, and skin contact with any infected material. It is widespread throughout the northern hemisphere, including Iran and its neighbors to the north, northeast, and northwest. METHODS: In this paper, the epidemiology of tularemia as a re-emerging infectious disease in the world with a focus on Iran and the neighboring countries is reviewed. RESULTS: In Iran, positive serological tests were first reported in 1973, in wildlife and domestic livestock in the northwestern and southeastern parts of the country. The first human case was reported in 1980 in the southwest of Iran, and recent studies conducted among at-risk populations in the western, southeastern, and southwestern parts of Iran revealed seroprevalences of 14.4, 6.52, and 6%, respectively. CONCLUSIONS: Several factors may explain the absence of reported tularemia cases in Iran since 1980. Tularemia may be underdiagnosed in Iran because Francisella tularensis subspecies holarctica is likely to be the major etiological agent and usually causes mild to moderately severe disease. Furthermore, tularemia is not a disease extensively studied in the medical educational system in Iran, and empirical therapy may be effective in many cases. Finally, it should be noted that laboratories capable of diagnosing tularemia have only been established in the last few years. Since both recent and older studies have consistently found tularemia antibodies in humans and animals, the surveillance of this disease should receive more attention. In particular, it would be worthwhile for clinical researchers to confirm tularemia cases more often by isolating F. tularensis from infected humans and animals. PMID:25773439

[EPIZOOTOLOGICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF TULAREMIA IN GEORGIA].

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Elashvili, E; Velijanashvili, I

2017-02-01

The appropriate data as well as archival materials about the spread of Tularemia disease have been studied over of period from 1991-2014 in Georgia in order to evaluate the current situation in Kartli lowland foci as well as the main reasons of disease agent circulation and maintenance in the study area. 54 (24.6%) out of 220 suspicious cases were laboratory confirmed during the study period. Most of confirmed cases - 32 (59.26%) have been detected in Shida Kartli focus among the old population during the outbreaks in the winter period. Tularemia causative agent has been isolated from the environmental object on 87 occasions, 50 (57.5%) of them have been found in Shida Kartli and 8 (9.2%) - in Kvemo Kartli lowland. Existence of rodents and ixodes ticks in Kartli lowland greatly supports keeping up Tularemia foci in this area. The common vectors and kind of storage of disease are considered to be different species of ixodes ticks especially D. marginatus, Haem. Punctata, Haem. Sulcata. It should be noted that reduction of intensity of Tularemia agent partially should be linked to the reduction frequency of planned and intentional researches during the last period of time.

Seroepidemiological survey of tularemia among different groups in western Iran.

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Esmaeili, Saber; Gooya, Mohammad Mehdi; Shirzadi, Mohammad Reza; Esfandiari, Behzad; Amiri, Fahimeh Bagheri; Behzadi, Manijeh Yousefi; Banafshi, Omid; Mostafavi, Ehsan

2014-01-01

The first human case of tularemia in Iran was reported in 1980 and there have been no subsequent reports of tularemia in the country. The aim of this study was to carry out a survey of tularemia among different groups in the province of Kurdistan in western Iran. The following information was collected by means of an in-house questionnaire: participant demographic characteristics, exposure to risks, and use of appropriate personal protective equipment and disinfectant in their occupation. A blood sample was collected from each participant. Sera were tested using an ELISA kit (Virion\\Serion) to detect specific IgG antibodies against Francisella tularensis. Of a total of 250 serum samples, 14.40% had anti-tularemia IgG antibodies. The highest seroprevalence was found in hunters (18%) and the lowest in health care workers (12%). Age had a significant positive association with tularemia seroprevalence (ptularemia in people exposed to foxes (hunting or eating the meat) (25%) was significantly higher than in others (8.65%) (p = 0.01). According to the findings of this study, it is highly recommended that physicians and health care workers are informed about bacteria circulating in this area. By sensitizing the health system, it is expected that some cases of the clinical disease will be reported in the near future. Similar studies in other parts of the country and on domestic and wild animals will clarify the epidemiology of tularemia in Iran. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

First Pediatric Case of Tularemia after a Coyote Bite

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Bruno B. Chomel

2016-01-01

Full Text Available Bite-transmitted tularemia is a rare event in humans and most of the cases have been associated with cat bites. We report the first pediatric case of tularemia caused by a coyote (Canis latrans bite. Coyotes can be healthy carriers of Francisella tularensis and transmit this infectious agent through a bite. Pediatricians should be aware of this risk after a carnivore bite and implement appropriate antibiotic therapy, as amoxicillin/clavulanate potassium (Augmentin may have prolonged the typical two to three days’ incubation period commonly observed for tularemia after an animal bite and was not effective in preventing clinical signs in this child. Finally, it emphasizes again the importance of early and late serum samples for appropriate serodiagnostic.

Climate Variability Reveals Complex Events for Tularemia Dynamics in Man and Mammals

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Thomas R. Palo

2005-06-01

Full Text Available Tularemia is caused by the bacterium Francisella tularensis, but the natural reservoir is unknown and environmental conditions for outbreaks in mammals and man are poorly understood. The present study analyzed the synchrony between the North Atlantic Oscillation (NAO index, the number of human cases of tularemia reported in Sweden, and the density of hares. Climate variation at a lag of 2 yr explained as a single factor ~ 27% of the variation in the number of tularemia cases over time. A low NAO index, indicating cold winters, and low water flow in rivers during the coming summer were associated with high numbers of human cases of tularemia 2 yr later. The number of mountain hares was not related to NAO or to the number of cases of tularemia. The change in mountain hare numbers was negatively associated with the number of human cases, showing the sensitivity of this species to the disease. Low turnover in water environments may at some point in time trigger a chain of events leading to increased replication of F. tularensis via unknown reservoirs and/or vectors that affect humans and mammals. A possible increase in the NAO index with a future warmer climate would not be expected to facilitate a higher frequency of tularemia outbreaks in Sweden.

Spatio-temporal dynamics of tularemia in French wildlife: 2002-2013.

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Moinet, Marie; Decors, Anouk; Mendy, Christiane; Faure, Eva; Durand, Benoit; Madani, Nora

2016-08-01

Tularemia, caused by Francisella tularensis, is endemic in France. The surveillance of this disease in wildlife is operated by the SAGIR Network and by the National Reference Laboratory for Tularemia. Wild animals found dead or dying collected by the SAGIR network are necropsied and when tularemia is suspected culture and/or PCR are performed to confirm the diagnosis. The aim of this study was to present the results of tularemia surveillance in wildlife and to investigate the spatial and temporal pattern of tularemia observed between the 2002-2003 and 2012-2013 hunting seasons in French wildlife. Fourty-one to 121 cases were collected each hunting season for a total of 693 confirmed cases and 46 additional suspected cases. The main species affected was the European Brown Hare (Lepus europaeus) but 4 rabbits (Oryctolagus cuniculus), 2 roe deer (Capreolus capreolus) and one wild boar (Sus scrofa) were also found positive. The Standard Mortality Ratio was mapped and Kulldorff's retrospective space-time scan statistic was implemented and allowed the detection of several clusters: the nationwide outbreak of 2007-2008; 2 clusters in northern and central-western France in high hare-abundance areas and another in North-eastern France where the abundance of hares is low. Our results confirm the usefulness of brown hare as a sentinel of environmental risk. Copyright © 2016 Elsevier B.V. All rights reserved.

Rabbit hunter uveitis: case report of tularemia uveitis.

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Terrada, Céline; Azza, Said; Bodaghi, Bahram; Le Hoang, Phuc; Drancourt, Michel

2016-09-01

Literature reports on ophthalmological manifestations related to tularemia, a zoonose caused by the bacterium Francisella tularensis, largely refer to Parinaud's oculoglandular syndrome, which consists of the association of conjunctivitis with preauricular lymphadenitis. In this paper, we report a case of intraocular inflammation during tularemia infection. A 52-year-old Caucasian man was diagnosed with unilateral uveitis. The uveitis was posterior, with a 2+ vitritis and a large yellowish lesion involving the macula with an overlying sub-retinal detachment, extending inferiorly, and subretinal hemorrhages. Fluorescein angiography showed a late hyperfluorescence with focal vascular leakage. Ultrasound biomicroscopy confirmed the presence of a 3.8 mm parietal granuloma with a few calcifications in the left eye. While extensive work-up eliminated any other infectious and non-infectious etiology, tularemia was diagnosed by advanced serology consisting of two-dimensional Western-immunoblotting. The patient, a hunter, recalled having killed rabbits in the days before the symptoms appeared. Uveitis was rapidly controlled following treatment with doxycycline, yet three years after initiation of the treatment, the patient still complained of loss of vision in the left eye with a central scotoma. Posterior uveitis may be an infrequent manifestation of tularemia infection, and therefore this infection should be considered in the differential diagnosis of intraocular inflammation in areas where F. tularensis is endemic.

Tuberculosis or tularemia? A molecular study in cervical lymphadenitis.

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Yıldırım, Sükrü; Turhan, Vedat; Karadenizli, Aynur; Önem, Yalçın; Karagöz, Ergenekon; Eroğlu, Cafer; Çiftçi, Faruk

2014-01-01

Over the last two to three decades there has been a marked decrease in certain bacterial infections in Turkey. One of them is tuberculosis. Of note, statistics published by the Turkish Ministry of Health (MoH) show decreasing pulmonary tuberculosis (PTB), but on the other hand, increasing extrapulmonary tuberculosis (EPTB). The most common form of EPTB is tuberculous cervical lymphadenitis (TCL). The increase in the number of TCL cases despite the decline in cases of PTB is seen as a paradoxical issue. In contrast there has been an increase in the number of oropharyngeal tularemia cases in the last decade in Turkey. The aim of this study was to draw attention to the importance of differentiating between TCL and tularemia lymphadenitis, because these diseases may have a similar histopathological appearance. Thirty-two cases diagnosed as TCL were identified from the archives of a pathology laboratory (Patomer Pathology Laboratory, Bursa, Turkey). PCR tests for Francisella tularensis and Mycobacterium tuberculosis were carried out on the paraffin tissue blocks of these cases. At the same time, statistical data on PTB and EPTB for the period 1996-2010 were retrieved from the MoH and reviewed. Statistics related to tularemia, which has been diagnosed since 1988 and has been increasing in the last 10 years, were obtained from the Department of Zoonoses of the MoH. Six out of 32 (19%) cases who had previously been diagnosed with 'casseifying granulomatous lymphadenitis consistent with tuberculosis' were found to be positive for tularemia by PCR test of the cervical lymph nodes. Oropharyngeal tularemia should be kept in mind in the differential diagnosis of cervical lymphadenitis in widespread geographic regions of the Northern Hemisphere, including the Asian continent. In particular, if granulomatous inflammation with necrosis is seen histopathologically, tularemia should be excluded before making the diagnosis of TCL. Copyright © 2013 The Authors. Published by Elsevier

[THE EPIZOOTIC AND EPIDEMIC ACTIVITY OF NATURAL TULAREMIA FOCI OF DIFFERENT LANDSCAPE EPIDEMIOLOGICAL TYPES IN 2009-2014].

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Meshcheryakova, I S; Mikhailova, T V; Demidova, T N; Kormilitsyna, M I

2016-01-01

to assess the present state of the natural tularemia foci of different landscape epidemiological types, by using individual focal areas as an example. Epizootological monitoring and epidemiological analysis were conducted in the areas of natural tularemia foci of tundra (Wrangel Island), meadow-field (Central Federal District of the Russian Federation), flood-swamp (Arkhangelsk Region, Khanty-Mansi Autonomous District), and steppe (Mongolii) types. Small mammals (organs, blood), tularemia patients' sera, and environniental objects were examined. Molecular genetic and immune serological diagnostic assays were used. The incidence of tularemia in the past decade was analyzed using the maps for the epidemiological examinations of tularemia cases and medical reports. The natural foci of tularemia were established to continue to actively operate. There were 2913 cases of tularemia in the Russian Federation in 2001 to 2014. The flood-swamp natural foci, in which there were summer transmissive tularemia outbreaks, the largest of high occurred in Khanti-Mansiysk in 2013 when a total of 1005 people fell ill, are a special epidemic hazard. Analysis of the tularemia outbreaks suggests that there is a need for continuous epizootological monitoring of the areas of natural tularemia foci for the timely prediction and prevention of epidemic complications. It is noted that there is an unfounded reduction in the scope of preventive measures, and immunoprevention in particular, and a weaker control of the antitularemia immune status in the population residing in the area of active natural foci of tularemia.

Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

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Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

2015-01-01

To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

Tularemia Outbreak Investigation in Kosovo: Case Control and Environmental Studies

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Dedushaj, Isuf; Gjini, Ardiana; Jorgensen, Tine Rikke; Cotter, Benvon; Lieftucht, Alfons; D’Ancona, Fortunato; Dennis, David T.; Kosoy, Michael A.; Mulliqi-Osmani, Gjyle; Grunow, Roland; Kalaveshi, Ariana; Gashi, Luljeta; Humolli, Isme

2002-01-01

A large outbreak of tularemia occurred in Kosovo in the early postwar period, 1999-2000. Epidemiologic and environmental investigations were conducted to identify sources of infection, modes of transmission, and household risk factors. Case and control status was verified by enzyme-linked immunosorbent assay, Western blot, and microagglutination assay. A total of 327 serologically confirmed cases of tularemia pharyngitis and cervical lymphadenitis were identified in 21 of 29 Kosovo municipalities. Matched analysis of 46 case households and 76 control households suggested that infection was transmitted through contaminated food or water and that the source of infection was rodents. Environmental circumstances in war-torn Kosovo led to epizootic rodent tularemia and its spread to resettled rural populations living under circumstances of substandard housing, hygiene, and sanitation. PMID:11749751

Molecular Investigation of Tularemia Outbreaks, Spain, 1997–2008

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Ariza-Miguel, Jaime; Johansson, Anders; Fernández-Natal, María Isabel; Martínez-Nistal, Carmen; Orduña, Antonio; Rodríguez-Ferri, Elías F.; Hernández, Marta

2014-01-01

Tularemia outbreaks occurred in northwestern Spain in 1997–1998 and 2007–2008 and affected >1,000 persons. We assessed isolates involved in these outbreaks by using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus variable number tandem repeat analysis of 16 genomic loci of Francisella tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable number tandem repeat analysis. Isolates obtained from the second tularemia outbreak had the same genotypes as isolates obtained from the first outbreak. Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002–00, which is widely distributed in countries in central and western Europe. Thus, reemergence of tularemia in Spain was not caused by the reintroduction of exotic strains, but probably by persistence of local reservoirs of infection. PMID:24750848

Tularemia in Children, Turkey, September 2009–November 2012

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Tezer, Hasan; Aykan, Hakan; Erkocoglu, Mustafa; Gülhan, Belgin; Demir, Ahmet; Kanik-Yuksek, Saliha; Tapisiz, Anil; Polat, Meltem; Kara, Soner; Devrim, Ilker; Kilic, Selcuk

2015-01-01

Tularemia, a zoonotic disease caused by Francisella tularensis, is found throughout most of the Northern Hemisphere. It is not well known and is often misdiagnosed in children. Our aim with this study was to evaluate the diagnosis, treatment, and prognosis for 100 children with tularemia in Turkey. The mean patient age was 10.1 ± 3.5 years (range 3–18 years), and most (63%) patients were male. The most common physical signs and laboratory findings were cervical lymphadenopathy (92%) and elevated erythrocyte sedimentation rate (89%). Treatment response was higher and rate of relapse lower for children 5–10 years of age than for those in other age groups. Associated with treatment failure were female sex, treatment delay of ≥16 days, and use of doxycycline. Tularemia is endemic to Turkey, and the number of cases has been increasing among children as well as adults. PMID:25529639

[Seasonal and regional distribution of tularemia cases in Amasya, Turkey].

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Yanık, Keramettin; Sarıaydın, Muzaffer; Uzun, M Önder; Çoban, Ahmet Yılmaz; Seçilmiş, Halil

2015-01-01

Tularemia have attracted attention due to increased number of cases since 2009 in Amasya region which is located at Central Blacksea Region of Turkey. The aims of this letter were to provide information about the disease, to emphasize the importance of early treatment due to the outbreak peak in our province between 2009-2012 and water chlorination in epidemic areas. A total of 250 tularemia-suspected patients (117 female, 133 male; mean age: 42 yrs) who were admitted to our hospital with the symptoms of sore throat, fever, malaise and/or presence of neck mass, from 20 different locations within last four years were included in the study. Serum samples of 73 (29.2%) patients yielded ≥ 1/160 titers with F.tularensis microagglutination test which were considered as positive. All positive cases presented with the oropharyngeal form of the disease. The year with the highest number of tularemia cases was 2010. When the regional distribution was evaluated, it was detected that positive cases have precipitated especially in the southeastern (highland area) and northeastern (lowland area) parts of Amasya (34/73; 46.6%). Majority of the tularemia cases (53/73; 72.6%) were identified in colder seasons. The number of cases in rural and urban centers have decreased after 2010. In conclusion, it is considered that the emergence of new cases is likely to persist due to the geographical characteristics of Amasya and occupational properties (livestock breeding) of the population. Therefore, the clinicians should consider tularemia in differential diagnosis of the cases originated from risky rural areas.

Piezoelectric Biosensor for a Simple Serological Diagnosis of Tularemia in Infected European Brown Hares (Lepus europaeus

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Jiří Pikula

2007-11-01

Full Text Available Piezoelectric biosensor was used for diagnosis of infection by Francisellatularensis subsp. holarctica in European brown hares. Two kinds of experiments wereperformed in this study. First, sera from experimentally infected European brown hares(Lepus europaeus were assayed by piezoelectric biosensor and the seventh day postinfection was found as the first one when statistically significant diagnosis of tularemia waspossible; all other sera collected from hares later than on day 7 following the infection werefound tularemia positive. Typing to classify the field strain of F. tularensis used for theexperimental infection was confirmed by proteome study. Second, sera from 35 Europeanbrown hare specimens sampled at hunting grounds and tested as tularemia positive by slowagglutination allowed diagnosis of tularemia by the piezoelectric biosensor. All these sera ofnaturally infected hares were found as tularemia positive, too. Efficacy of the piezoelectricbiosensor for the serological diagnosis of tularemia is discussed.

Human Cases of Tularemia in Armenia, 1996-2012.

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Melikjanyan, Syuzanna; Palayan, Karo; Vanyan, Artavazd; Avetisyan, Lilit; Bakunts, Nune; Kotanyan, Marine; Guerra, Marta

2017-09-01

A retrospective analysis was conducted of human cases and outbreaks of tularemia in the Republic of Armenia from 1996 to 2012 utilizing geographic information system software. A total of 266 human cases of tularemia were recorded in Armenia from 1996 to 2012, with yearly incidence ranging from 0 to 5.5 cases per 100,000 people. Cases predominantly affected the male population (62.8%), 11-20 year age group (37.2%), agricultural workers (49.6%), and persons residing in rural areas (93.6%). In 2003, a waterborne outbreak involving 158 cases occurred in Kotayk Marz, and in 2007, a foodborne outbreak with 17 cases occurred in Gegharkunik Marz, attributed to exposure of food products to contaminated hay. Geospatial analysis of all cases showed that the majority were associated with the steppe vegetation zone, elevations between 1,400 and 2,300 m, and the climate zone associated with dry, warm summers, and cold winters. Characterization of these environmental factors were used to develop a predictive risk model to improve surveillance and outbreak response for tularemia in Armenia.

About three cases of ulceroglandular tularemia, is this the re-emergence of Francisella tularensis in Belgium?

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Dupont, E; Van Eeckhoudt, S; Thissen, X; Ausselet, N; Fretin, D; Stefanescu, I; Glupczynski, Y; Delaere, B

2015-10-01

Tularemia is a zoonosis caused by Francisella tularensis that can be transmitted by several ways to human being and cause different clinical manifestations. We report three clinical cases of tularemia with ulceroglandular presentation in young males acquired during outdoor activities in Southern Belgium. Confirmation of the diagnosis was established by serology. Only three cases of tularemia have been reported in Belgium between 1950 and 2012 by the National Reference Laboratory CODA-CERVA (Ref Lab CODA-CERVA) but re-emergence of tularemia is established in several European countries and F. tularensis is also well known to be present in animal reservoirs and vectors in Belgium. The diagnosis of tularemia has to be considered in case of suggestive clinical presentation associated with epidemiological risk factors.

[Epizootic and epidemic manifestation of natural foci of tularemia in Moscow region (1965-2013)].

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Demidova, T N; Popov, V P; Polukhina, A N; Orlov, D S; Mescheryakova, I S; Mikhailova, T V

2015-01-01

Detection of contemporary features of tularemia focimanifestations, determination of territories of high epidemic risk in various landscape zones and creation of a map of foci territories of Moscow Region for isolation of tularemia infectious agent cultures and registered human morbidity for justified planning of prophylaxis measures. Report materials of epizootologic examinations of natural foci for 1965-2013, 156 maps of epidemiologic examination of cases of human infection with tularemia, results of studies of casting of predatory birds and dung of predatory mammals were used. Registered morbidity and isolation of tularemia infectious agent cultures from 1965 to date were applied to an electronic map of Moscow Region by sign method using modern. GIS-technologies (MapInfo 10.5 program). Electronic maps Ingit at 1:200,000 scale, as well as Google Earth program were used to search for base points. Analysis of morbidity has revealed structure change in human tularemia morbidity--an increase of the fraction of urban population and a decrease of the fraction of patients among rural inhabitants, unimmunized against this infection are mostly ill. The presence of DNA of tularemia causative agent in biological objects in the complex with serologic and bacteriological studies was shown to allow to detect flaccid epizootics even at low numbers of rodents. Cartographic reflection of registered morbidity and isolation of tularemia infectious agent cultures allowed to show territories with various degrees of epizootic activity and epidemic manifestation. Positive results of serologic and molecular-genetic studies of environmental objects gives evident on epizootic activity and constant risk of aggravation of epidemic situation for this infection.

Epidemiological and clinical characteristics and management of oropharyngeal tularemia outbreak.

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Uzun, Mustafa Önder; Yanik, Keramettin; Erdem, Müge; Kostakoglu, Ugur; Yilmaz, Gürdal; Tanriverdi Çayci, Yeliz

2015-01-01

The purpose of this study was to determine the epidemiological and clinical characteristics of patients diagnosed with tularemia and the effectiveness of the administered treatments. Patients treated in our hospital between January 2009 and March 2011 and diagnosed with tularemia were evaluated retrospectively. Patients' epidemiological and clinical characteristics, administered treatments, and posttreatment findings were recorded on patient monitoring forms. At anamnesis, 29% of patients used water from wells and 71% used water from the network supply; moreover, 48.4% had a history of contact with animals and 87.1% a history of lethargy. At physical examination, 96.8% had a mass in the neck and 90.3% had fever. Gentamycin + doxycycline therapy was administered to 45.2% of patients, while levofloxacin, gentamycin, and streptomycin were used for the other patients. After treatment, neck masses persisted in 48.4% of patients and complaints of lethargy and fever in 6.5%. Treatment of these patients was initiated once tularemia had been diagnosed, as test results were announced about 3 weeks later. Lymphadenopathy excision was performed on 19.4% of patients in whom neck mass persisted. Appropriate empiric antibiotherapy should be commenced in patients presenting with neck mass, fever, and lethargy in regions with tularemia epidemics.

The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

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Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

2018-01-01

Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

First case of severe pneumonic tularemia in an immunocompetent patient in the Netherlands

NARCIS (Netherlands)

Sigaloff, K.C.E.; Chung, P.K.; Koopmans, J.; Notermans, D.W.; Rijckevorsel, Van G.G.C.; Koene, M.; Sprengers, R.W.; Gooskens, J.; Stalenhoef, J.E.

2017-01-01

Tularemia is a zoonosis caused by different subspecies of the Gram-negative bacterium Francisella tularensis. We report the first case in the Netherlands of pneumonic tularemia caused by the F. tularensis subspecies holarctica after probable occupational inhalation of contaminated aerosols.

First case of severe pneumonic tularemia in an immunocompetent patient in the Netherlands.

NARCIS (Netherlands)

Sigaloff, K C E; Chung, P K; Koopmans, J; Notermans, D W; van Rijckevorsel, G G C; Koene, M; Sprengers, R W; Gooskens, J; Stalenhoef, J E

Tularemia is a zoonosis caused by different subspecies of the Gram-negative bacterium Francisella tularensis. We report the first case in the Netherlands of pneumonic tularemia caused by the F. tularensis subspecies holarctica after probable occupational inhalation of contaminated aerosols.

[Natural focus of tularemia on the Kerchen peninsula (Crimea)].

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Golkovskiĭ, G M; Mitsevich, G F; Khaĭtovich, A B; Alekseev, E V; Korchevskiĭ, P G

1981-10-01

The study confirming the existence of the steppe-type natural focus of tularemia on the Kerch peninsula has been carried out. For the first time the cultures of Francisella tularensis have been isolated. Voles and house mice play the main role in the circulation of the infection. The parasitic system comprises ticks (Ixodidae and Nyalomma), as well as some species of fleas. In carrying out erizootological studies for detecting tularemia in the Crimea the use of low temperature (0 degrees C) for the preservation of specimens and preparations in recommended.

Tularemia Outbreaks and Common Vole (Microtus arvalis) Irruptive Population Dynamics in Northwestern Spain, 1997-2014.

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Luque-Larena, Juan José; Mougeot, François; Roig, Dolors Vidal; Lambin, Xavier; Rodríguez-Pastor, Ruth; Rodríguez-Valín, Elena; Anda, Pedro; Escudero, Raquel

2015-09-01

During the last decades, large tularemia outbreaks in humans have coincided in time and space with population outbreaks of common voles in northwestern Spain, leading us to hypothesize that this rodent species acts as a key spillover agent of Francisella tularensis in the region. Here, we evaluate for the first time a potential link between irruptive vole numbers and human tularemia outbreaks in Spain. We compiled vole abundance estimates obtained through live-trapping monitoring studies and official reports of human tularemia cases during the period 1997-2014. We confirm a significant positive association between yearly cases of tularemia infection in humans and vole abundance. High vole densities during outbreaks (up to 1000 voles/hectare) may therefore enhance disease transmission and spillover contamination in the environment. If this ecological link is further confirmed, the apparent multiannual cyclicity of common vole outbreaks might provide a basis for forecasting the risk of tularemia outbreaks in northwestern Spain.

Tularemia and plague survey in rodents in an earthquake zone in southeastern Iran

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Gyuranecz, Miklós

2015-01-01

OBJECTIVES: Earthquakes are one the most common natural disasters that lead to increased mortality and morbidity from transmissible diseases, partially because the rodents displaced by an earthquake can lead to an increased rate of disease transmission. The aim of this study was to evaluate the prevalence of plague and tularemia in rodents in the earthquake zones in southeastern Iran. METHODS: In April 2013, a research team was dispatched to explore the possible presence of diseases in rodents displaced by a recent earthquake magnitude 7.7 around the cities of Khash and Saravan in Sistan and Baluchestan Province. Rodents were trapped near and in the earthquake zone, in a location where an outbreak of tularemia was reported in 2007. Rodent serums were tested for a serological survey using an enzyme-linked immunosorbent assay. RESULTS: In the 13 areas that were studied, nine rodents were caught over a total of 200 trap-days. Forty-eight fleas and 10 ticks were obtained from the rodents. The ticks were from the Hyalomma genus and the fleas were from the Xenopsylla genus. All the trapped rodents were Tatera indica. Serological results were negative for plague, but the serum agglutination test was positive for tularemia in one of the rodents. Tatera indica has never been previously documented to be involved in the transmission of tularemia. CONCLUSIONS: No evidence of the plague cycle was found in the rodents of the area, but evidence was found of tularemia infection in rodents, as demonstrated by a positive serological test for tularemia in one rodent. PMID:26602769

Tularemia in Germany—A Re-emerging Zoonosis

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Mirko Faber

2018-02-01

Full Text Available Tularemia, also known as “rabbit fever,” is a zoonosis caused by the facultative intracellular, gram-negative bacterium Francisella tularensis. Infection occurs through contact with infected animals (often hares, arthropod vectors (such as ticks or deer flies, inhalation of contaminated dust or through contaminated food and water. In this review, we would like to provide an overview of the current epidemiological situation in Germany using published studies and case reports, an analysis of recent surveillance data and our own experience from the laboratory diagnostics, and investigation of cases. While in Germany tularemia is a rarely reported disease, there is evidence of recent re-emergence. We also describe some peculiarities that were observed in Germany, such as a broad genetic diversity, and a recently discovered new genus of Francisella and protracted or severe clinical courses of infections with the subspecies holarctica. Because tularemia is a zoonosis, we also touch upon the situation in the animal reservoir and one-health aspects of this disease. Apparently, many pieces of the puzzle need to be found and put into place before the complex interaction between wildlife, the environment and humans are fully understood. Funding for investigations into rare diseases is scarce. Therefore, combining efforts in several countries in the framework of international projects may be necessary to advance further our understanding of this serious but also scientifically interesting disease.

Tularemia in Germany—A Re-emerging Zoonosis

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Faber, Mirko; Heuner, Klaus; Jacob, Daniela; Grunow, Roland

2018-01-01

Tularemia, also known as “rabbit fever,” is a zoonosis caused by the facultative intracellular, gram-negative bacterium Francisella tularensis. Infection occurs through contact with infected animals (often hares), arthropod vectors (such as ticks or deer flies), inhalation of contaminated dust or through contaminated food and water. In this review, we would like to provide an overview of the current epidemiological situation in Germany using published studies and case reports, an analysis of recent surveillance data and our own experience from the laboratory diagnostics, and investigation of cases. While in Germany tularemia is a rarely reported disease, there is evidence of recent re-emergence. We also describe some peculiarities that were observed in Germany, such as a broad genetic diversity, and a recently discovered new genus of Francisella and protracted or severe clinical courses of infections with the subspecies holarctica. Because tularemia is a zoonosis, we also touch upon the situation in the animal reservoir and one-health aspects of this disease. Apparently, many pieces of the puzzle need to be found and put into place before the complex interaction between wildlife, the environment and humans are fully understood. Funding for investigations into rare diseases is scarce. Therefore, combining efforts in several countries in the framework of international projects may be necessary to advance further our understanding of this serious but also scientifically interesting disease. PMID:29503812

Towards Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays.

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Nakajima, Rie; Escudero, Raquel; Molina, Douglas M; Rodríguez-Vargas, Manuela; Randall, Arlo; Jasinskas, Algis; Pablo, Jozelyn; Felgner, Philip L; AuCoin, David P; Anda, Pedro; Davies, D Huw

2016-07-01

Tularemia in humans is caused mainly by two subspecies of the Gram-negative facultative anaerobe Francisella tularensis: F. tularensis subsp. tularensis (type A) and F. tularensis subsp. holarctica (type B). The current serological test for tularemia is based on agglutination of whole organisms, and the reactive antigens are not well understood. Previously, we profiled the antibody responses in type A and B tularemia cases in the United States using a proteome microarray of 1,741 different proteins derived from the type A strain Schu S4. Fifteen dominant antigens able to detect antibodies to both types of infection were identified, although these were not validated in a different immunoassay format. Since type A and B subspecies are closely related, we hypothesized that Schu S4 antigens would also have utility for diagnosing type B tularemia caused by strains from other geographic locations. To test this, we probed the Schu S4 array with sera from 241 type B tularemia cases in Spain. Despite there being no type A strains in Spain, we confirmed the responses against some of the same potential serodiagnostic antigens reported previously, as well as determined the responses against additional potential serodiagnostic antigens. Five potential serodiagnostic antigens were evaluated on immunostrips, and two of these (FTT1696/GroEL and FTT0975/conserved hypothetical protein) discriminated between the Spanish tularemia cases and healthy controls. We conclude that antigens from the type A strain Schu S4 are suitable for detection of antibodies from patients with type B F. tularensis infections and that these can be used for the diagnosis of tularemia in a deployable format, such as the immunostrip. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[Investigation of the presence of Mycobacterium tuberculosis in the lymph node aspirates of the suspected tularemia lymphadenitis cases].

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Albayrak, Nurhan; Celebi, Bekir; Kavas, Semra; Simşek, Hülya; Kılıç, Selçuk; Sezen, Figen; Arslantürk, Ahmet

2014-01-01

Recently reports of cervical tuberculous lymphadenitis and oropharyngeal tularemia which are the most common infectious causes of granulomatous lymphadenitis, have been significantly increased in Turkey. The differentiation of cervical tuberculous lymphadenitis and oropharyngeal tularemia is usually confusing on the basis of clinical and histopathological findings. Thus, in tularemia endemic areas, the patients are more commonly evaluated in terms of tularemia lymphadenitis leaving tuberculosis out. The aim of this study was to investigate the presence of Mycobacterium tuberculosis in cervical lymph node aspirates, obtained from tularemia suspected cases. A total of 105 oropharyngeal tularemia-suspected cases which were found negative for Francisella tularensis by bacteriological (culture), molecular (PCR) and serological (microagglutination) methods, were included in the study. The samples had been previously studied at National Tularemia Reference Laboratory, Turkish Public Health Institution, between 2009-2011. The study samples were evaluated in terms of M.tuberculosis by culture and real-time PCR (rtPCR) methods in the National Tuberculosis Reference Laboratory. Both Lowenstein-Jensen (LJ) medium and liquid-based MGIT (BD, USA) automated culture system were used for mycobacterial culture. Samples that yielded mycobacterial growth were identified as M.tuberculosis by immunochromotographic test (BD, USA). The lymph node aspirates of 65 patients who were F.tularensis PCR negative but antibody positive, were used as the control group. As a result, M.tuberculosis was found to be positive in 9 (8.6%) of 105 tularemia-negative lymph node aspirates, sent to our laboratory from different geographic regions for the investigation of tularemia. Six of the M.tuberculosis positive cases were male and the age range of the patients was 26-85 years. The presence of M.tuberculosis was detected only by culture in two samples, only by rtPCR in five samples and both by culture and

Ultrasonography and contrast-enhanced CT findings of tularemia in the neck.

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Doğan, Serap; Ekinci, Afra; Demiraslan, Hayati; Ulu Kılıç, Ayşegül; Mavili, Ertuğrul; Öztürk, Mustafa; İmamoğlu, Hakan; Doğanay, Mehmet

2016-01-01

We aimed to evaluate the ultrasonography (US) and contrast-enhanced computed tomography (CECT) findings of tularemia in the neck. US and CECT findings of 58 patients with serologically proven tularemia were retrospectively evaluated. Forty-eight patients underwent US and 42 patients underwent CECT. Lymph node characteristics and parotid preauricular region involvement were analyzed using US and CECT. In addition, involvement of larynx, oropharynx, and retropharynx; presence of periorbital edema; and neck abscess formation were evaluated using CECT. Fine needle aspiration cytology (FNAC) results of enlarged lymph nodes were analyzed in 29 patients. Hypoechoic pattern, round shape, absence of hilum, and cystic necrosis were seen in most of the lymph nodes especially at level 2 and 3 on US and CECT. Matting was more commonly observed than irregular nodal border on US and CECT. Parotid preauricular region involvement was seen in 20.8% of patients on US. Oropharyngeal, retropharyngeal, laryngeal and parotid preauricular region involvement and periorbital edema were seen in 52.4%, 19.1%, 4.8%, 31%, and 9.5% of tularemia patients, respectively. Neck abscess was found in 59.5% of patients on CECT. Suppurative inflammation was the most common finding of FNAC. Tularemia should be considered in the presence of level 2 and 3 lymph nodes with cystic necrosis, matting, absence of calcification, oropharyngeal and retropharyngeal region involvement, and neck abscess, particularly in endemic areas.

MBL, P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia.

Science.gov (United States)

Somuk, Battal Tahsin; Koc, Sema; Ates, Omer; Göktas, Göksel; Soyalic, Harun; Uysal, Ismail Onder; Gurbuzler, Levent; Sapmaz, Emrah; Sezer, Saime; Eyibilen, Ahmet

2016-11-01

A significant association was found of oropharyngeal tularemia with SLC11A1 allele polymorphism (INT4 G/C) and MBL2 C + 4T (P/Q). These results indicate C allele and Q allele might be a risk factor for the development of oropharyngeal tularemia. This study aimed to investigate the relationship of SLC11A1, MBL, and P2X 7 gene polymorphism with oropharyngeal tularemia. The study included totally 120 patients who were diagnosed with oropharyngeal tularemia. Frequencies of polymorphisms in the following genes were analyzed both in the patient and control groups in the study: SLC11A1 (5'(GT) n Allele 2/3, Int4 G/C, 3' UTR, D543N G/A), MBL (MBL2 C + 4T (P/Q), and P2X 7 (-762 C/T and 1513 A/C). Among all polymorphisms that were investigated in this study, SLC11A1 gene showed a significance in the distriburtion of polymorphism allelle frequency at the INT4 region. Frequency of C allele was 54 (28%) in patients with oropharyngeal tularemia, and 31 (13%) in the control group (p = 0.006 and OR = 1.96 (1.21-3.20)). An association was detected between MBL2 C + 4T (P/Q) gene polymorphism and oropharyngeal tularemia (p tularemia in this study (p > 0.05).

Tularemia, plague, yersiniosis, and Tyzzer’s disease in wild rodents and lagomorphs in Canada: A review

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Wobeser, Gary; Campbell, G. Douglas; Dallaire, André; McBurney, Scott

2009-01-01

Information related to infection of wild rodents or lagomorphs in Canada by Francisella tularensis, Yersinia pestis, other Yersinia spp., and Clostridium piliforme was searched for this study. Reports on tularemia in humans linked to these species came from diagnostic databases, literature, wildlife health specialists, and public health agencies. Tularemia has been diagnosed in 8 species of wild rodent and 2 species in the genus Lepus in Canada. Tularemia occurred in wild animals, or in humans associated with these species, in all jurisdictions except the Yukon and Nunavut. Tularemia was diagnosed most frequently in beaver, muskrats, and snowshoe hares, and although tularemia is closely linked to cottontail rabbits in the USA, it has not been reported in cottontails in Canada. Tularemia in humans was associated with muskrats and hares more commonly than with beaver. Plague was diagnosed in bushy-tailed woodrats in British Columbia in 1988. Based on surveys, Y. pestis may occur enzootically in southern Alberta, Saskatchewan, and British Columbia. Infection with Yersinia pseudotuberculosis and Y. enterocolitica has been diagnosed in beaver, muskrats, and snowshoe hares in many provinces. Tyzzer’s disease has been diagnosed in muskrats in British Columbia, Saskatchewan, Ontario, and Quebec and in snowshoe hares in Ontario. Infection with these bacteria is likely much more frequent than indicated by diagnostic records. PMID:20190973

Comparison of experimental respiratory tularemia in three nonhuman primate species.

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Glynn, Audrey R; Alves, Derron A; Frick, Ondraya; Erwin-Cohen, Rebecca; Porter, Aimee; Norris, Sarah; Waag, David; Nalca, Aysegul

2015-04-01

Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than >30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis. Published by Elsevier Ltd.

Oropharyngeal tularemia cases admitted to a military hospital in Ankara, Turkey.

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Karakas, Ahmet; Coskun, Omer; Artuk, Cumhur; Savasci, Umit; Gul, Hanefi Cem; Mert, Gurkan; Avci, Ismail Yasar; Besirbellioglu, Bulent Ahmet; Eyigun, Can Polat

2014-08-13

This study aimed to review the possible sources of infection of 16 oropharyngeal tularemia hospital cases, and to document their epidemiological and demographical characteristics, laboratory findings, treatment methods, and treatment results. Sixteen cases from a Turkish military hospital between January 2011 and December 2012 were retrospectively evaluated. The age, sex, occupation, place of residence, symptoms, duration of symptoms, laboratory results, treatment and duration, and treatment results were recorded. Tularemia was diagnosed through tularemia-specific tests once the other conditions that may have caused lymphadenopathy were excluded. Twelve of the patients included in this study were males. The average age of the patients was 32.1 ± 17.2 years. Sore throat, fatigue, and fever were the most frequent symptoms. The mean duration of symptoms was 21.6 ± 6.9 days. All the patients had been treated for tonsillopharyngitis in primary healthcare institutions previously. However, despite the treatment, cervical lymphadenopathy had developed in these cases. Patients were given streptomycin, doxycycline, and ciprofloxacin monotherapy or in combination. Ten of the cases fully recovered, while five required surgical lymph node drainage. Spontaneous drainage occurred in the single remaining case. Turkey is considered to be an endemic country with regards to tularemia. Prompt diagnosis and proper treatment of the disease is imperative in providing cure. Since it can be potentially confused with tuberculous lymphadenitis, differential diagnosis is vital. Patients presenting with a condition of tonsillopharyngitis in endemic areas must be carefully monitored.

Evaluation of clinical and sonographic features in 55 children with tularemia.

Science.gov (United States)

Oz, Fatma; Eksioglu, Ayse; Tanır, Gonul; Bayhan, Gulsum; Metin, Özge; Teke, Turkan Aydın

2014-08-01

The aim of this study was to determine the clinical characteristics and sonographic features of lymphadenopathy (LAP) and to evaluate the treatment modalities and treatment outcomes in children with tularemia. Demographic characteristics, ultrasonographic and physical examination findings, and treatment outcomes in 55 tularemia patients (24 male and 31 female) with a mean age of 10.8 ± 4.0 years were analyzed retrospectively. Lymph node necrosis was classified in three stages based on ultrasound findings-stage 1, cortical microabscesses; stage 2, cortical and medullar abscesses; stage 3, total necrosis of the lymph node. In total, 50 (90%) of the patients had oropharyngeal, four (8%) had glandular, and one (2%) had oculoglandular tularemia. The most common symptoms were sore throat (67%) and fever (64%). LAP was the most frequently (100%) observed sign. Abscess formation was noted in 36 (65%) patients, of which seven (19%) were sonographically classified as stage 1, 20 (55%) as stage 2, and nine (26%) as stage 3. There was a statistically significant correlation between delayed treatment and stage of abscess formation in lymph nodes (p0.05). In all, nine (16%) of the patients did not respond to medical treatment, and surgical intervention was required. Tularemia should be considered in the differential diagnosis of children presenting with unexplained fever, sore throat, and cervical LAP in endemic areas. Sonographic findings may be useful in the evaluation and staging of this infection.

Differential diagnosis of cervical lymphadenitis mimicking malignancy due to tularemia: Our experiences

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Vedat Turhan

2013-01-01

Full Text Available Background: Tularemia is a disease caused by a Gram-negative coccobacillus Francisella tularensis. This bacterium may cause different types of clinical pictures owing to acquisition route and entrance site, such as ulceroglandular, oropharyngeal, glandular, pneumonic, typhoid and ocular forms. Oropharyngeal tularemia (OPT is the most common form of tularemia in some regions. OPT may cause tonsillopharyngitis followed by cervical lymphadenopathies (LAPs. Without treatment LAP may persist for several months and may mimic other diseases causing cervical LAPs. Materials and Methods: A total of six cases of OPT, five male and one female, between 21 and 31 years old, diagnosed serologically and clinically recorded in GATA Haydarpasa Training Hospital were included in this study. Detailed story including the region they lived for last 6 months, their occupation, family and neighborhood story with similar complaints were obtained. Patient data were also obtained from manually written patients files and electronical patient file system. Formalin fixed paraffin embedded tissue blocks of all biopsy material were submitted for polymerase chain reaction (PCR study for F. tularensis. Results: A total of six cases with head and neck mass following a story of tonsillopharyngitis admitted to different clinics including infectious diseases, ear-nose-throat and internal medicine in our tertiary care hospital. Physical examination revealed immobile, hard, conglomerated unilateral cervical lymphadenopathy in all cases. Histopathological examination revealed granulomatous inflammation in four cases. Acute suppurative inflammatory changes were also seen in two cases. Large necrotic areas mimicking casseifying necrosis were seen in two cases. PCR amplification of F. tularensis genom from isolated deoxyribonucleic acids was successful in five cases. Conclusion: Tularemia should be kept in mind in patients with tonsillopharyngitis not responding to penicillins and beta

Low Dose Vaccination with Attenuated Francisella tularensis Strain SchuS4 Mutants Protects against Tularemia Independent of the Route of Vaccination

Science.gov (United States)

Rockx-Brouwer, Dedeke; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Crane, Deborah D.

2012-01-01

Tularemia, caused by the Gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia. PMID:22662210

Dermatologic manifestations of tularemia: a study of 151 cases in the mid-Anatolian region of Turkey.

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Şenel, Engin; Satılmış, Özgür; Acar, Bilal

2015-01-01

Tularemia is a serious and potentially life-threatening zoonosis caused by Francisella tularensis, a highly infective, gram-negative coccobacillus. Although there are plenty of case reports and studies of tularemia outbreaks, the literature is lacking in reports on dermatologic manifestations of the disease. This study aimed to identify skin manifestations in clinical forms of tularemia. A total of 151 patients diagnosed with tularemia at Çankırı State Hospital, Çankırı, Turkey, were retrospectively examined. Dermatologic data for these patients were assessed. The most frequent clinical manifestation of tularemia was the glandular form (49.7%), followed by the oropharyngeal, ulceroglandular, and oculoglandular forms (39.1, 6.0, and 5.3%, respectively). Physical manifestations were observed in 64.5% of females and 56.9% of males. Lymphadenopathy and tonsillitis were the most frequent physical findings and were noted in 57.6 and 25.2% of patients, respectively. Erythema multiforme was found in 17 patients (11.3%), most of whom presented with the oropharyngeal and glandular forms, and was followed by ulcer (6.0%), urticaria (3.3%), erythema nodosum (2.6%), and cellulitis (0.7%). However, it should be noted that this study was retrospective and that its patient sample demonstrated four of the six clinical forms of tularemia. Patients with the oropharyngeal form of tularemia had statistically significantly more physical findings than those with other clinical forms of the disease (P < 0.001). There were statistically more skin findings in the ulceroglandular form (P < 0.001). There was no statistical correlation between serum antibody titers and cutaneous findings (P = 0.585). Although the literature reports that skin lesions are observed more frequently in women than in men, we did not find any statistically significant difference between the sexes in any type of skin lesion. © 2014 The International Society of Dermatology.

Towards an understanding of the perpetuation of the agent of tularemia

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Sam eTelford

2011-01-01

Full Text Available The epidemiology of tularemia has influenced, perhaps incorrectly skewed, our views on the ecology of the agent of tularemia. In particular, the central role of lagomorphs needs to be reexamined. Diverse observations, some incidental, and some that are more generally reproducible, have not been synthesized so that the critical elements of the perpetuation of Francisella tularensis can be identified. Developing a quantitative model of the basic reproduction number (BRN of F. tularensis may require separate treatments for Type A and Type B given the fundamental differences in their ecology.

Tularemia, an animal-borne disease

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,

1945-01-01

the disease tularemia continues to be of such importance in the United States that the Fish and Wildlife Service is constantly receiving requests for information on its nature and on the procedure recommended by field representatives of the Service in their work wiht the public. Such information is summarized in this leaflet.the information on human infections presented and the recommendations made have been endorsed by the United States Public Health Service.

Organs of BALB/c mice can be injured in course of tularemia.

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Pavlis, Oto; Kusakova, Eva; Novotny, Ladislav; Pohanka, Miroslav

2014-12-01

Francisella tularensis is a biological agent exploitable for bioterrorism and biological warfare purposes due to serious pathogenic progression and easy dissemination. Despite intensive research in the past, some adverse consequences remain unclear. One consequence of this pathogen is oxidative stress. The aim of this study was to undertake ex vivo assays for monitoring the disease in mice and increase our knowledge of the oxidative stress induced by tularemia. The mouse BALB/c model was chosen and the animals were infected by a dose 10(4) CFU of F. tularensis. After five days, the animals were euthanized. Blood immediately processed in plasma, spleen and liver were sampled from the cadavers. Oxidative stress markers, cytokines and histopathological were undertaken. There was a significant link between oxidative stress and tularemia. Particularly elevated levels of malondialdehyde and decreased levels of low molecular weight antioxidants were found in the liver and spleen of tularemia-infected animals. The histopathological findings correlated well with the oxidative stress markers. The liver and spleen were proven to be significantly at risk from the disease and an association between stress and neutrophils in the affected organs was found. The histopathology excluded risk to other organs such as the kidney and or heart. Oxidative stress plays a significant role in tularemia infection in mice and this was confirmed by the histology.

Rational design of nanomaterials for water treatment

KAUST Repository

Li, Renyuan

2015-08-26

The ever-increasing human demand for safe and clean water is gradually pushing conventional water treatment technologies to their limits and it is now a popular perception that the solutions to the existing and future water challenges will highly hinge upon the further development of nanomaterial sciences. The concept of rational design emphasizes ‘design-for-purpose’ and it necessitates a scientifically clear problem definition to initiate the nanomaterial design. The field of rational design of nanomaterials for water treatment has experienced a significant growth in the past decade and is poised to make its contribution in creating advanced next-generation water treatment technologies in the years to come. Within the water treatment context, this review offers a comprehensive and in-depth overview of the latest progress of the rational design, synthesis and applications of nanomaterials in adsorption, chemical oxidation and reduction reactions, membrane-based separation, oil/water separation, and synergistic multifunctional all-in-one nanomaterials/nanodevices. Special attention is paid on chemical concepts of the nanomaterial designs throughout the review.

The status of tularemia in Europe in a one-health context: a review.

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Hestvik, G; Warns-Petit, E; Smith, L A; Fox, N J; Uhlhorn, H; Artois, M; Hannant, D; Hutchings, M R; Mattsson, R; Yon, L; Gavier-Widen, D

2015-07-01

The bacterium Francisella tularensis causes the vector-borne zoonotic disease tularemia, and may infect a wide range of hosts including invertebrates, mammals and birds. Transmission to humans occurs through contact with infected animals or contaminated environments, or through arthropod vectors. Tularemia has a broad geographical distribution, and there is evidence which suggests local emergence or re-emergence of this disease in Europe. This review was developed to provide an update on the geographical distribution of F. tularensis in humans, wildlife, domestic animals and vector species, to identify potential public health hazards, and to characterize the epidemiology of tularemia in Europe. Information was collated on cases in humans, domestic animals and wildlife, and on reports of detection of the bacterium in arthropod vectors, from 38 European countries for the period 1992-2012. Multiple international databases on human and animal health were consulted, as well as published reports in the literature. Tularemia is a disease of complex epidemiology that is challenging to understand and therefore to control. Many aspects of this disease remain poorly understood. Better understanding is needed of the epidemiological role of animal hosts, potential vectors, mechanisms of maintenance in the different ecosystems, and routes of transmission of the disease.

An overview: tularemia and travel medicine.

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Ulu-Kilic, Aysegul; Doganay, Mehmet

2014-01-01

Tularemia is a bacterial zoonotic infection. The disease is endemic in most parts of the world, has been reported through the northern hemisphere between 30 and 71° N latitude. Francisella tularensis causes infection in a wide range of vertebrates (rodents, lagomorphs) and invertebrates (ticks, mosquitoes and other arthropods). Humans can acquire this infection through several routes including; a bite from an infected tick, deerfly or mosquito, contact with an infected animal or its dead body. It can also be spread to human by drinking contaminated water or breathing contaminated dirt or aerosol. Clinical manifestation of this disease varies depending on the biotype, inoculum and port of entry. Infection is potentially life threatening, but can effectively be treated with antibiotics. Travelers visiting rural and agricultural areas in endemic countries may be at greater risk. Appropriate clothing and use of insect repellants is essential to prevent tick borne illness. Travelers also should be aware of food and waterborne disease; avoid consuming potentially contaminated water and uncooked meat. Physicians should be aware of any clinical presentation of tularemia in the patients returning from endemic areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

[REAL TIME POLYMERASE CHAIN REACTION IN TULAREMIA LABORATORY DIAGNOSTICS].

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Kormilitsyna, M I; Mescheryakova, I S; Mikhailova, T V; Dobrovolsky, A A

2015-01-01

Enhancement of tularemia laboratory diagnostics by F. tularensis DNA determination in blood sera of patients using real time polymerase chain reaction (RT-PCR). 39 blood sera of patients obtained during transmissive epidemic outbreak of tularemia in Khanty-Mansiysk in 2013 were studied in agglutination reaction, passive hemagglutination, RT-PCR. Specific primers and fluorescent probes were used: ISFTu2F/R+ISFTu2P, Tu14GF/R+tul4-PR2. Advantages of using RT-PCR for early diagnostics of tularemia, when specific antibodies are not detected using traditional immunologic methods, were established. Use of a combination of primers and ISFTu2F/R+ISFTu2P probe allowed to detect F. tularensis DNA in 100% of sera, whereas Tul4G F/R+tul4-PR2 combination--92% of sera. The data were obtained when DNA was isolated from sera using "Proba Rapid" express method. Clinical-epidemiologic diagnosis oftularemia was confirmed by both immune-serologic and RT-PCR methods when sera were studied 3-4 weeks after the onset of the disease. RT-PCR with ISFTu2F/R primers and fluorescent probe ISFTu2P, having high sensitivity and specificity, allows to determine F. tularensis DNA in blood sera of patients at both the early stage and 3-4 weeks after the onset of the disease.

Towards a formal logic of design rationalization

DEFF Research Database (Denmark)

Galle, Per

1997-01-01

Certain extensions to standard predicate logic are proposed and used as a framework for critical logical study of patterns of inference in design reasoning. It is shown that within this framework a modal logic of design rationalization (suggested by an empirical study reported earlier) can...... be formally defined in terms of quantification over a universe of discourse of ‘relevant points of view’. Five basic principles of the extended predicate logic are listed, on the basis of which the validity of ten modal patterns of inference encountered in design rationalization is tested. The basic idea...

[THE ENVIRONMENTAL BASES AND MECHANISM FOR NATURAL OPISTHORCHIASIS FOCUS PULSATION IN THE COMBINED FOCUS OF OPISTHORCHIASIS AND TULAREMIA].

Science.gov (United States)

Ushakov, A V

2015-01-01

A cyclic change in the epizootic activity of a tularemia activity underlies the mechanism of natural opisthorchiasis focus pulsation in the combined focus of opisthorchiasis and tularemia in the ecosystem of the Konda River. This is due to mass breeding and depression in the water vole (Arvicola terrestris) population. The mass breeding is predetermined by high population reproduction constants. The rodents' potential fecundity occurs with the high capacity of lands, which is caused by the hydrological regime of rivers. The size depression is predetermined by the epizootics of tularemia. The water vole is a host of the pathogens of opisthorchiasis and tularemia. So the mass rodent breeding in the combined infection and invasion focus causes an increase in the number of real invasion sources. The epizootic of tularemia is responsible for elimination of these invasion sources and for decreases in the flow of invasion material, the infection rate of Codiella and hence the amount of their produced cercarae, the extensive and intensive indicators of fish contamination, and the intensity of an epizootic process in the opisthorchiasis focus.

Tularemia: potential role of cytopathology in differential diagnosis of cervical lymphadenitis: multicenter experience in 53 cases and literature review.

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Tuncer, Ersin; Onal, Binnur; Simsek, Gulcin; Elagoz, Sahande; Sahpaz, Ahmet; Kilic, Selcuk; Altuntas, Emine Elif; Ulu Kilic, Aysegul

2014-03-01

Tularemia is a zoonosis caused by Francisella tularensis. Tularemia outbreaks occurred in Central Anatolia during 2009 and 2011. We evaluated the clinical characteristics and cytomorphologies of fine needle aspirations (FNAs) from cervical lymph nodes in serologically confirmed tularemia cases. To our knowledge, this is the first large series concerning FNA morphology of Tularemia. FNA smears of 53 patients of the 290, diagnosed by microagglutination tests and PCR, were evaluated at three Pathology centers. FNAs were performed by cytopathologists or ear-nose-throat surgeons. Of all patients, 17 had also lymph node resections. FNAs showed the presence of suppuration and abscess. Rare epithelioid histiocytes and granulomas, seldom phagocytosed bacilli-like microorganisms were observed. On histopathology; granulomas, necrosis, and suppurative inflammation extending extracapsular areas were seen. Tularemia is endemic in certain areas of the Northern Hemisphere. The benefit from cytopathology is limited and cytological suspicion should be confirmed by serology. However FNA cytology is helpful in differential diagnosis of tularemia and other diseases presented with suppurative, granulomatous cervical lymphadenitis. It is also useful in providing the material for PCR and culture in early phase when the serology is negative and the treatment is more effective. © 2013 APMIS. Published by John Wiley & Sons Ltd.

Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants protects against tularemia independent of the route of vaccination.

Directory of Open Access Journals (Sweden)

Dedeke Rockx-Brouwer

Full Text Available Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. <100 organisms, may address this concern. Herein we describe the ability of three defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c, FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity against tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia.

Dynamics of a Tularemia Outbreak in a Closely Monitored Free-Roaming Population of Wild House Mice.

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Dobay, Akos; Pilo, Paola; Lindholm, Anna K; Origgi, Francesco; Bagheri, Homayoun C; König, Barbara

2015-01-01

Infectious disease outbreaks can be devastating because of their sudden occurrence, as well as the complexity of monitoring and controlling them. Outbreaks in wildlife are even more challenging to observe and describe, especially when small animals or secretive species are involved. Modeling such infectious disease events is relevant to investigating their dynamics and is critical for decision makers to accomplish outbreak management. Tularemia, caused by the bacterium Francisella tularensis, is a potentially lethal zoonosis. Of the few animal outbreaks that have been reported in the literature, only those affecting zoo animals have been closely monitored. Here, we report the first estimation of the basic reproduction number R0 of an outbreak in wildlife caused by F. tularensis using quantitative modeling based on a susceptible-infected-recovered framework. We applied that model to data collected during an extensive investigation of an outbreak of tularemia caused by F. tularensis subsp. holarctica (also designated as type B) in a closely monitored, free-roaming house mouse (Mus musculus domesticus) population in Switzerland. Based on our model and assumptions, the best estimated basic reproduction number R0 of the current outbreak is 1.33. Our results suggest that tularemia can cause severe outbreaks in small rodents. We also concluded that the outbreak self-exhausted in approximately three months without administrating antibiotics.

Dynamics of a Tularemia Outbreak in a Closely Monitored Free-Roaming Population of Wild House Mice.

Directory of Open Access Journals (Sweden)

Akos Dobay

Full Text Available Infectious disease outbreaks can be devastating because of their sudden occurrence, as well as the complexity of monitoring and controlling them. Outbreaks in wildlife are even more challenging to observe and describe, especially when small animals or secretive species are involved. Modeling such infectious disease events is relevant to investigating their dynamics and is critical for decision makers to accomplish outbreak management. Tularemia, caused by the bacterium Francisella tularensis, is a potentially lethal zoonosis. Of the few animal outbreaks that have been reported in the literature, only those affecting zoo animals have been closely monitored. Here, we report the first estimation of the basic reproduction number R0 of an outbreak in wildlife caused by F. tularensis using quantitative modeling based on a susceptible-infected-recovered framework. We applied that model to data collected during an extensive investigation of an outbreak of tularemia caused by F. tularensis subsp. holarctica (also designated as type B in a closely monitored, free-roaming house mouse (Mus musculus domesticus population in Switzerland. Based on our model and assumptions, the best estimated basic reproduction number R0 of the current outbreak is 1.33. Our results suggest that tularemia can cause severe outbreaks in small rodents. We also concluded that the outbreak self-exhausted in approximately three months without administrating antibiotics.

Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis

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Ruxandra Calin

2017-07-01

Full Text Available A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF therapy is reported here. The patient required prolonged treatment with doxycycline–ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment.

Study of toxic properties of prototypes of photo inactivated vaccines against tularemia and brucellosis by speckle microscopy

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Ulianova, Onega V.; Ulyanov, Sergey

2011-03-01

Testing of prototypes of vaccines against extremely dangerous diseases, such as tularemia and brucellosis has been performed using speckle-microscopy. Changes of microcirculation caused by effect of toxins at applications of suspension of photoinactivated bacteria have been studied. Toxic properties of prototypes of vaccines against tularemia and brucellosis have been analyzed.

Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis.

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Calin, Ruxandra; Caumes, Eric; Reibel, Florence; Ali Mohamed, Anzime; Brossier, Florence; Foltz, Violaine; Boussouar, Samia; Fautrel, Bruno; Maurin, Max; Katlama, Christine; Pourcher, Valérie

2017-07-01

A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF) therapy is reported here. The patient required prolonged treatment with doxycycline-ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Historical distribution and host-vector diversity of Francisella tularensis, the causative agent of tularemia, in Ukraine.

Science.gov (United States)

Hightower, Jake; Kracalik, Ian T; Vydayko, Nataliya; Goodin, Douglas; Glass, Gregory; Blackburn, Jason K

2014-10-16

Francisella tularensis, the causative agent of tularemia, is a zoonotic agent that remains across much of the northern hemisphere, where it exists in enzootic cycles. In Ukraine, tularemia has a long history that suggests a need for sustained surveillance in natural foci. To better characterize the host-vector diversity and spatial distribution of tularemia, we analyzed historical data from field collections carried out from 1941 to 2008. We analyzed the spatial-temporal distribution of bacterial isolates collected from field samples. Isolates were characterized by source and dominant land cover type. To identify environmental persistence and spatial variation in the source of isolation, we used the space-time permutation and multinomial models in SaTScan. A total of 3,086 positive isolates were taken from 1,084 geographic locations. Isolation of F. tularensis was more frequent among arthropods [n = 2,045 (66.3%)] followed by mammals [n = 619 (20.1%)], water [n = 393 (12.7%)], and farm produce [n = 29 (0.94%)], respectively. Four areas of persistent bacterial isolation were identified. Water and farm produce as sources of bacterial isolation were clustered. Our findings confirm the presence of long-standing natural foci of F. tularensis in Ukraine. Given the history of tularemia as well as its environmental persistence there exists a possibility of (re)emergence in human populations. Heterogeneity in the distribution of tularemia isolate recovery related to land cover type supports the theory of natural nidality and clusters identify areas to target potential sources of the pathogen and improve surveillance.

Epidemiology and Ecology of Tularemia in Sweden, 1984–2012

Science.gov (United States)

Desvars, Amélie; Furberg, Maria; Hjertqvist, Marika; Vidman, Linda; Sjöstedt, Anders; Rydén, Patrik

2015-01-01

The zoonotic disease tularemia is endemic in large areas of the Northern Hemisphere, but research is lacking on patterns of spatial distribution and connections with ecologic factors. To describe the spatial epidemiology of and identify ecologic risk factors for tularemia incidence in Sweden, we analyzed surveillance data collected over 29 years (1984–2012). A total of 4,830 cases were notified, of which 3,524 met all study inclusion criteria. From the first to the second half of the study period, mean incidence increased 10-fold, from 0.26/100,000 persons during 1984–1998 to 2.47/100,000 persons during 1999–2012 (ptularemia was higher than expected in the boreal and alpine ecologic regions (ptularemia in Sweden and illustrate that incidence is higher in locations near lakes and rivers. PMID:25529978

Detection of Francisella tularensis-Specific Antibodies in Patients with Tularemia by a Novel Competitive Enzyme-Linked Immunosorbent Assay

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Sharma, Neekun; Hotta, Akitoyo; Yamamoto, Yoshie; Fujita, Osamu; Uda, Akihiko; Morikawa, Shigeru; Yamada, Akio

2013-01-01

A novel competitive enzyme-linked immunosorbent assay (cELISA) was developed and evaluated for detection of antibodies against Francisella tularensis in humans. The assay is based on the ability of serum antibodies to inhibit the binding of monoclonal antibodies (MAbs) directed against F. tularensis lipopolysaccharide antigens. The assay was evaluated using serum samples of tularemia patients, inactivated F. tularensis-immunized rabbits, and F. tularensis-infected mice. Antibodies against F. tularensis were successfully detected in serum samples of tularemia patients as well as the immunized and infected animals. The cELISA method was compared to indirect ELISA (iELISA) and the commonly used microagglutination test (MA) using serum samples of 19 tularemia patients and 50 healthy individuals. The sensitivity and specificity of cELISA were 93.9 and 96.1%, respectively, in comparison to the iELISA. MA was less sensitive than cELISA with a sensitivity and specificity of only 81.8 and 98.0%, respectively. A high degree of correlation (R2 = 0.8226) was observed between cELISA and iELISA results. The novel cELISA developed in this study appears to be highly sensitive and specific for serodiagnosis of human tularemia. The potential of the MAb-based cELISA to be used in both human and animal samples emphasizes its usefulness for serological survey of tularemia among multiple animal species. PMID:23114700

Modeling Inhalational Tularemia: Deliberate Release and Public Health Response

Science.gov (United States)

Hall, Ian M.; Leach, Steve

2011-01-01

Two epidemic modeling studies of inhalational tularemia were identified in the published literature, both demonstrating the high number of potential casualties that could result from a deliberate aerosolized release of the causative agent in an urban setting. However, neither study analyzed the natural history of inhalational tularemia nor modeled the relative merits of different mitigation strategies. We first analyzed publicly available human/primate experimental data and reports of naturally acquired inhalational tularemia cases to better understand the epidemiology of the disease. We then simulated an aerosolized release of the causative agent, using airborne dispersion modeling to demonstrate the potential number of casualties and the extent of their spatial distribution. Finally, we developed a public health intervention model that compares 2 mitigation strategies: targeting antibiotics at symptomatic individuals with or without mass distribution of antibiotics to potentially infected individuals. An antibiotic stockpile that is sufficient to capture all areas where symptomatic individuals were infected is likely to save more lives than treating symptomatic individuals alone, providing antibiotics can be distributed rapidly and their uptake is high. However, with smaller stockpiles, a strategy of treating symptomatic individuals alone is likely to save many more lives than additional mass distribution of antibiotics to potentially infected individuals. The spatial distribution of symptomatic individuals is unlikely to coincide exactly with the path of the dispersion cloud if such individuals are infected near their work locations but then seek treatment close to their homes. The optimal mitigation strategy will depend critically on the size of the release relative to the stockpile level and the effectiveness of treatment relative to the speed at which antibiotics can be distributed. PMID:22044315

Tularemia without lesions in grey tree squirrels: A diagnostic challenge

Science.gov (United States)

Fifteen cases of Francisella tularenesis infection (tularemia) were identified in western grey (Sciurus griseus) and eastern grey (Sciurus carolinesis) squirrels submitted to the Washington Animal Disease Diagnostic Laboratory between 2008 and 2011. All of the squirrels originated in Washington stat...

An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis.

Science.gov (United States)

Johansson, Anders; Lärkeryd, Adrian; Widerström, Micael; Mörtberg, Sara; Myrtännäs, Kerstin; Ohrman, Caroline; Birdsell, Dawn; Keim, Paul; Wagner, David M; Forsman, Mats; Larsson, Pär

2014-12-01

The bacterium Francisella tularensis is recognized for its virulence, infectivity, genetic homogeneity, and potential as a bioterrorism agent. Outbreaks of respiratory tularemia, caused by inhalation of this bacterium, are poorly understood. Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimens. A localized outbreak of tularemia in Sweden was investigated. Sixty-seven humans contracted laboratory-verified respiratory tularemia. F. tularensis subspecies holarctica was isolated from the blood or pleural fluid of 10 individuals from July to September 2010. Using whole-genome sequencing and analysis of single-nucleotide polymorphisms (SNPs), outbreak isolates were compared with 110 archived global isolates. There were 757 SNPs among the genomes of the 10 outbreak isolates and the 25 most closely related archival isolates (all from Sweden/Finland). Whole genomes of outbreak isolates were >99.9% similar at the nucleotide level and clustered into 3 distinct genetic clades. Unexpectedly, high-sequence similarity grouped some outbreak and archival isolates that originated from patients from different geographic regions and up to 10 years apart. Outbreak and archival genomes frequently differed by only 1-3 of 1 585 229 examined nucleotides. The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespread, and apparently persisted in the environment. Multiple independent acquisitions of F. tularensis from the environment over a short time period suggest that natural outbreaks of respiratory tularemia are triggered by environmental cues. The findings additionally caution against interpreting genome sequence identity for this pathogen as proof of a direct epidemiological link. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developing and Testing Rational Models of Message Design.

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O'Keefe, Barbara J.

1992-01-01

Responds to an article in the same issue regarding research methods for conversational cognition. Argues for a noncognitive view of rational models in communication research. Sets out an analysis of the kinds of claims made by rational models of message design. Discusses the implications of this analysis for studies of the cognitive processes…

Tularemia Associated to Drinking Mountain Water Presenting with Lymphadenopathy: a Case Report

Directory of Open Access Journals (Sweden)

Hakan Sarlak

2012-04-01

Full Text Available Tularemia is a zoonotic disease that can be passed to humans via the consumption of wild animal meat or inadequately cooked contaminated drinking water. There has been an increase in the number of observed cases in recent years. The clinical picture may vary from asymptomatic disease to septic shock. Oropharyngeal type of the disease is the most common clinical form and is associated with pharyngitis, fever and cervical lymphadenopathy (LAP. Here we present a 22-year-old female patient who developed cervical LAP after tonsillopharyngitis and was diagnosed with oropharyngeal tularemia that was determined to be related to drinking mountain water. [TAF Prev Med Bull 2012; 11(2.000: 245-247

Evaluation of In-House and Commercial Serological Tests for Diagnosis of Human Tularemia

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Yanes, Hadjila; Hennebique, Aurélie; Pelloux, Isabelle; Boisset, Sandrine; Bicout, Dominique J.; Caspar, Yvan

2017-01-01

ABSTRACT Tularemia is a zoonosis caused by the bacterium Francisella tularensis. Its specific diagnosis remains based on serological methods, while F. tularensis is rarely detected in clinical samples by culture or PCR. The aim of the present study was to evaluate the performance of the Serion enzyme-linked immunosorbent assay (ELISA) classic Francisella tularensis IgG and IgM tests (Virion/Serion GmbH Institute, Würzburg, Germany) and the VIRapid tularemia immunochromatographic test (ICT) (Vircell, Granada, Spain) compared to that of the in-house microagglutination test (MAT) and indirect immunofluorescence assay (IFA) currently used at the French National Reference Center for Francisella. We evaluated 256 consecutive sera from 208 patients, including 51 confirmed and 23 probable tularemia cases, and 134 control patients not infected with F. tularensis. The IFA tests displayed 72.5% sensitivity for IgM (cutoff titer ≥80) and 74.5% for IgG (cutoff titer ≥160), and 99.3% specificity for both IgM and IgG. Using cutoffs advocated by the manufacturer, the Serion ELISAs displayed 88.2% sensitivity for IgM and 86.3% for IgG antibodies; specificity was 94.8% for IgM and 95.5% for IgG. Compared to MAT and IFA tests, the Serion ELISAs allowed earlier detection of specific antibodies (1 to 2 weeks versus 2 to 3 weeks after the onset of symptoms). The ICT sensitivity and specificity were 90% and 83.6%, respectively, when considering the cutoff advocated by the manufacturer. In conclusion, the Serion ELISAs are useful as screening tests for tularemia diagnosis, but additional confirmatory tests (such as MAT and IFA) are needed, especially in areas of low endemicity. PMID:29118164

Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

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Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

2016-10-01

Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Usefulness of a single-assay chemiluminescence test (Tularaemia VIRCLIA IgG + IgM monotest) for the diagnosis of human tularemia. Comparison of five serological tests.

Science.gov (United States)

Cubero, África; Durántez, Carlos; Almaraz, Ana; Fernández-Lago, Luis; Gutiérrez, María P; Castro, María J; Bratos, Miguel A; Simarro, María; March, Gabriel A; Orduña, Antonio

2018-04-01

The aim of this work was to ascertain the usefulness of a new commercially-available single-assay chemiluminescence test (CHT) for the diagnosis of human tularemia (Tularaemia VIRCLIA IgG + IgM monotest, Vircell, Santa Fe, Granada, Spain). A total of 773 sera from 773 patients including 364 initial sera from patients with diagnosed tularemia, patients with suspected tularemia not confirmed (100), healthy people (152), patients with serology positive to Brucella (97), patients diagnosed with other infectious diseases (30), and patients diagnosed with autoimmune diseases (30) were included. All sera were tested by CHT, "in-house" microagglutination test (MAT), immunochromatographic test (ICT) (Virapid Tularaemia, Vircell, Santa Fe Granada, Spain), and "in-house" ELISA IgG, and ELISA IgM. Of the total initial sera, 334 (sensitivity 91.8%) were positive in the CHT, 332 (sensitivity 91.2%) in the MAT, 330 (sensitivity 90.7%) in the ICT, and 328 (sensitivity 90.1%) in the ELISA IgG and ELISA IgM tests. The specificity of the CHT was 96.7%; of the MAT, 100%; of the ICT, 98.7%; and of the ELISA IgG and ELISA IgM, 97.4%. In the group of patients with serology positive to Brucella, at least 12.4% of sera were positive in tularemia tests (12.4% in ELISA IgM, 13.4% in MAT, 14.4% in ICT, and 15.5% in CHT and ELISA IgG). In conclusion, CHT presents a sensitivity and specificity in early diagnosis of human tularemia, similar to MAT, ICT, and ELISA IgG and ELISA IgM. Its single assay design allows lower costs, especially in areas of low endemicity or inter-epidemic periods.

[Seroprevalence of tularemia in risk groups of humans and animals in Van, eastern Turkey].

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Bayram, Yasemin; Özkaçmaz, Ayşe; Parlak, Mehmet; Başbuğan, Yıldıray; Kılıç, Selçuk; Güdücüoğlu, Hüseyin

2015-10-01

Tularemia has become a re-emerging zoonotic disease in Turkey recently. The aims of this study were to determine the seroprevalence of tularemia in humans and their animals living in rural risky areas of our region and to investigate the risk factors. Between January and July 2012, people living in rural areas of Van province (located at eastern part of Turkey) and their domestic animals were included in the study. The sample size was determined by using cluster sampling method like in an event with known prevalence and planned as a cross-sectional epidemiological study. Proportional random sampling method was used to determine which individuals will be included in the study. Presence of tularemia antibodies in the sera of a total 495 voluntary persons (343 female, 152 male; age range: 18-79 years, mean age: 40.61) and their 171 animals (40 cattle, 124 sheep and 7 goats) were screened by microagglutination test using safranin O-stained F.tularensis antigen (Public Health Agency of Turkey). For the evaluation of cross-reactivity between Brucella spp., tularemia positive serum samples were also tested with brucella microagglutination test. Among human and animal samples, 11.9% (59/495) and 44% (76/171) yielded positive results with the titers of ≥ 1:20 in F.tularensis microagglutination test, respectively. However, 69.5% (41/59) of human sera and 78.9% (60/76) of animal sera demonstrated equal or higher titers in the brucella test, so those sera were considered as cross-reactive. After exclusion of these sera, the seroprevalence for F.tularensis were calculated as 3.6% (18/495) for humans and 9.4% (16/171) for animals. Among the 16 animals with positive results, 12 were sheep, three were cattle and one was goat. The difference between seropositivity rates among the domestic animal species was not statistically significant (p> 0.05). In addition, no statistically significant differences were found between risk factors including insect bite, tick bite, contact with

[Evaluation of modern epizootic activity of natural tularemia foci in Voronezh region using immune-serological and molecular-genetic study of main carriers of the disease].

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Meshcheriakova, I S; Trankvilevskiĭ, D V; Kvasov, D A; Mikhaĭlova, T V; Kormilitsina, M I; Demidova, T N; Stepkin, Iu I; Zhukov, V I

2015-01-01

Improvement of monitoring and prognosis of epidemic manifestations of natural foci of tularemia on the territory of Voronezh region using immune-serological and molecular-genetic study of main carriers of the disease. 539 small mammals captured during summer period of 2011 in 4 districts of North-Eastern part of Voronezh region were studied. Animal organs were studied by serologic (search for Francisella tularensis antigens) and molecular-biologic (detection of F. tularensis DNA) methods. Tularemia antigen was detected using passive hemagglutination reaction (PHAR) with erythrocytic tularemia immunoglobulin diagnosticum. Real-time polymerase chain reaction (RT-PCR) was applied for detection of tularemia causative agent DNA. Complex study revealed epizootic activity of natural foci of tularemia in the examined territory. F. tularensis antigen and/or DNA were detected in 82 objects (15.2%). Use of RT-PCR allowed to additionally detect samples with relatively low content of F. tularensis DNA substrate, when antigen was not detected in samples. High sensitivity and specificity of the RT-PCR was ensured by inclusion of specific probes (tu14-PR2 and ISFTu2P). The results obtained give evidence on functioning and epizootic activity of natural foci of tularemia in Voronezh region that requires constant monitoring of the territory and prophylaxis measures, first of all vaccination of risk groups by live tularemia vaccine.

Transmission of tularemia from a water source by transstadial maintenance in a mosquito vector

Science.gov (United States)

Bäckman, Stina; Näslund, Jonas; Forsman, Mats; Thelaus, Johanna

2015-01-01

Mosquitoes are thought to function as mechanical vectors of Francisella tularensis subspecies holarctica (F. t. holarctica) causing tularemia in humans. We investigated the clinical relevance of transstadially maintained F. t. holarctica in mosquitoes. Aedes egypti larvae exposed to a fully virulent F. t. holarctica strain for 24 hours, were allowed to develop into adults when they were individually homogenized. Approximately 24% of the homogenates tested positive for F. t. DNA in PCR. Mice injected with the mosquito homogenates acquired tularemia within 5 days. This novel finding demonstrates the possibility of transmission of bacteria by adult mosquitoes having acquired the pathogen from their aquatic larval habitats.

Difficulty in the Clinical Diagnosis of Tularemia: Highlighting the Importance of a Physical Exam

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Rupin Kumar

2018-01-01

Full Text Available We report an 18-month-old male who presented with fever and nonspecific symptoms. He was evaluated for multiple differential diagnoses including Kawasaki disease and JIA and received treatment for them. After he was readmitted, tularemia was considered based on the physical exam finding of an ulcer on the scalp and enlarged lymph nodes. Tularemia titers were positive, and the patient was given the appropriate antibiotic and was discharged home. Follow-up of the patient showed complete resolution of symptoms. This is a case that demonstrates the importance of physical exam in identifying rare diseases presenting with common signs and symptoms.

Guest-responsive structural adaptation of a rationally-designed ...

Indian Academy of Sciences (India)

adaptability of the TB core to undergo subtle structural changes in response to the guest that is included. The structural ... we report the design, synthesis and inclusion behaviour of a novel ..... Based on a rational design, we have shown from ...

Evaluation of urban river landscape design rationality based on AHP

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Qiao Lifang

2008-12-01

Full Text Available An evaluation model for the rationality of the landscape design of urban rivers was established with the analytic hierarchy process (AHP method so as to provide a foundation for updating the landscape design of urban rivers. The evaluation system was divided into four layers, including the target layer, the comprehensive layer, the element layer, and the index layer. Each layer was made of different indices. The evaluation standards for each index were also given in this paper. This evaluation model was proved tenable through its application to the landscape design rationality evaluation of the Weihe River in Xinxiang City of Henan Province. The results show that the water quality, space, activity, facility, community, width of vegetation, sense of beauty and water content are among the most influential factors and should be considered the main basis for evaluating the rationality of the landscape design of urban rivers.

[Tularemia is spreading from north to south side of Turkey: a small outbreak in Kahramanmaras, Turkey].

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Bozkurt, İlkay; Kiliç, Selçuk

2014-07-01

Tularemia is a zoonotic disease caused by Francisella tularensis. Sporadic tularemia cases have been increasingly reported particularly from provinces located at northwest and central regions of Turkey especially during last two decades, as well as waterborne outbreaks reported from almost all regions. Transmission most often occurs through consumption of contaminated water and food, thus, oropharyngeal form is the most common clinical presentation in our country. The aim of this study was to present a small outbreak experience in Afsin, country of Kahramanmaras province located at southern part of Turkey. A total of 10 patients (5 male, 5 female; age range 2-68 years; mean age 25 years) who were admitted to Afsin State Hospital with the complaints of swollen neck between 21 October 2013-22 January 2014, were evaluated considering their clinical findings and treatment outcomes. Following the diagnosis of the first tularemia case coming from Nadir village, a field investigation was performed. All villagers were informed about the disease and water samples from the possible sources of outbreak were collected by provincial health authorities. Lymph node aspirate and serum samples were sent for culture and serologic investigation and the environmental water samples were sent for molecular analysis to the National Tularemia Reference Laboratory at Public Health Institution of Turkey. Six out of 10 patients' sera were found positive in terms of F.tularensis antibodies between the titers of 1/320-1/1280 by microagglutination test (MAT) and diagnosis of oropharyngeal tularemia was based on the clinical and serological findings. One of the patients also presented with oculoglandular form accompanying oropharyngeal form. Cultures from aspirate samples that could be obtained from only two patients yielded negative results. Three out of six patients' lymph nodes were drained surgically and one was drained by ultrasound-guided needle. In one case lymph node suppuration occured

[Tularemia in a jogger woman after the attack by a common buzzard (Buteo buteo): A "One Health" case report].

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Ehrensperger, F; Riederer, L; Friedl, A

2018-03-01

A female jogger was attacked by a common buzzard (Buteo buteo) and was scratched lightly at the back of the head. One week later she was taken ill with high fever and headache which was later diagnosed as ulcero-glandular tularemia in regional lymph nodes, caused by Francisella tularensis. Recovery was only achieved after several weeks of systemic antibiotic treatment (Gentamicin/ Ciprofloxacine). Tularemia is a well known zoonotic disease, called "rabbit fever", mainly affecting rabbits and hares, but also small rodents. Human infection occurs often following tick bites or bloodsucking insects, or in hunters or slaughterers handling infected animals. Bites by mice have also been reported as a cause of tularemia. For the first time we report this case of tularemia as a result of an attack by a bird of prey. We assume that the bird acted as a vector just carrying the F. tularensis on its claws or beak, but we cannot exclude an infection of the bird itself. Several other joggers had also been attacked by a common buzzard in the same area shortly after the above described event and one of these also became infected with F. tularensis.

Phylogeography of Francisella tularensis from Tibet, China: Evidence for an asian origin and radiation of holarctica-type Tularemia.

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Lu, Yongfeng; Yu, Yonghui; Feng, Le; Li, Yanwei; He, Jun; Zhu, Hong; Duan, Qing; Song, Lihua

2016-07-01

The geographical origin and radiation of holarctica-type tularemia, which has spread across the northern hemisphere, is open to scientific debate. Here, through phylogenetics, we show that five Tibetan Francisella tularensis isolates subsp. holarctica cluster between basal-positioned Japanese isolates and all other subspecies strains in the world, providing evidence for a previously unknown intermediate lineage next to the Japanese isolates. Importantly, identification of this new intermediate lineage complements current knowledge of tularemia epidemiology, supporting a geographical origin and radiation of the subsp. holarctica in Asia. In addition, thirteen Tibetan isolates belonging to a clade previously found only in North America and Scandinavia, further increases the diversity of holarctica strains in Asia. In summary, this study provides evidence for an Asian origin and radiation of holarctica-type tularemia. Copyright © 2016 Elsevier GmbH. All rights reserved.

Tularemia in Alaska, 1938 - 2010

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Hansen Cristina M

2011-11-01

Full Text Available Abstract Tularemia is a serious, potentially life threatening zoonotic disease. The causative agent, Francisella tularensis, is ubiquitous in the Northern hemisphere, including Alaska, where it was first isolated from a rabbit tick (Haemophysalis leporis-palustris in 1938. Since then, F. tularensis has been isolated from wildlife and humans throughout the state. Serologic surveys have found measurable antibodies with prevalence ranging from F. tularensis isolates from Alaska were analyzed using canonical SNPs and a multi-locus variable-number tandem repeats (VNTR analysis (MLVA system. The results show that both F. t. tularensis and F. t. holarctica are present in Alaska and that subtype A.I, the most virulent type, is responsible for most recently reported human clinical cases in the state.

Machine learning in the rational design of antimicrobial peptides.

Science.gov (United States)

Rondón-Villarreal, Paola; Sierra, Daniel A; Torres, Rodrigo

2014-01-01

One of the most important public health issues is the microbial and bacterial resistance to conventional antibiotics by pathogen microorganisms. In recent years, many researches have been focused on the development of new antibiotics. Among these, antimicrobial peptides (AMPs) have raised as a promising alternative to combat antibioticresistant microorganisms. For this reason, many theoretical efforts have been done in the development of new computational tools for the rational design of both better and effective AMPs. In this review, we present an overview of the rational design of AMPs using machine learning techniques and new research fields.

Rational Design of an Ultrasensitive Quorum-Sensing Switch.

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Zeng, Weiqian; Du, Pei; Lou, Qiuli; Wu, Lili; Zhang, Haoqian M; Lou, Chunbo; Wang, Hongli; Ouyang, Qi

2017-08-18

One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization. The performance of realized quorum-sensing switches was in good qualitative agreement with the computational predictions. This study provides practical principles for the rational design of genetic circuits with targeted functions.

From bricolage to BioBricks™: Synthetic biology and rational design.

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Lewens, Tim

2013-12-01

Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vaccination evokes gender-dependent protection against tularemia infection in C57BL/6Tac mice.

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Sunagar, Raju; Kumar, Sudeep; Franz, Brian J; Gosselin, Edmund J

2016-06-17

Francisella tularensis (Ft) is a Category A biothreat agent for which there currently is no FDA-approved vaccine. Thus, there is a substantial effort underway to develop an effective tularemia vaccine. While it is well established that gender can significantly impact susceptibility to primary infection, the impact of gender on vaccine efficacy is not well established. Thus, development of a successful vaccine against tularemia will require an understanding of the impact gender has on vaccine-induced protection against this organism. In this study, a role for gender in vaccine-induced protection following Ft challenge is identified for the first time. In the present study, mucosal vaccination with inactivated Ft (iFt) LVS elicited gender-based protection in C57BL/6Tac mice against respiratory challenge with Ft LVS. Specifically, vaccinated male mice were more susceptible to subsequent Ft LVS challenge. This increased susceptibility in male mice correlated with increased bacterial burden, increased tissue inflammation, and increased proinflammatory cytokine production late in post-challenge infection. In contrast, improved survival of iFt-vaccinated female mice correlated with reduced bacterial burden and enhanced levels of Ft-specific Abs in serum and broncho-alveolar lavage (BAL) fluid post-challenge. Furthermore, vaccination with a live attenuated vaccine consisting of an Ft LVS superoxide dismutase (SodB) mutant, which has proven efficacious against the highly virulent Ft SchuS4 strain, demonstrated similar gender bias in protection post-Ft SchuS4 challenge. Of particular significance is the fact that these are the first studies to demonstrate that gender differences impact disease outcome in the case of lethal respiratory tularemia following mucosal vaccination. In addition, these studies further emphasize the fact that gender differences must be a serious consideration in any future tularemia vaccine development studies. Copyright © 2016 Elsevier Ltd. All

Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease.

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Hill, Timothy M; Gilchuk, Pavlo; Cicek, Basak B; Osina, Maria A; Boyd, Kelli L; Durrant, Douglas M; Metzger, Dennis W; Khanna, Kamal M; Joyce, Sebastian

2015-06-01

The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.

Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent F. tularensis subsp. tularensis

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Jia, Qingmei; Horwitz, Marcus A.

2018-01-01

Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed “Foshay” vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals—especially mice—but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including F. tularensis. Since live attenuated—but not killed or subunit—vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies holarctica or F. novicida, or against non-respiratory challenge with virulent subsp. tularensis (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. tularensis, the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. holarctica, F. novicida, and subsp. tularensis, and heterologous vaccines developed using viral or bacterial vectors to express F. tularensis immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development—safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the

Design of 2-D rational digital filters

International Nuclear Information System (INIS)

Harris, D.B

1981-01-01

A novel 2-D rational filter design technique is presented which makes use of a reflection coefficient function (RCF) representation for the filter transfer function. The design problem is formulated in the frequency domain. A least-square error criterion is used though the usual error measure is augmented with barrier functions. These act to restrict the domain of approximation to the set of stable filters. Construction of suitable barrier functions is facilitated by the RCF characterization

Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

Directory of Open Access Journals (Sweden)

Sukalyani Banik

Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

Oropharyngeal Tularemia Outbreak Associated with Drinking Contaminated Tap Water, Turkey, July-September 2013.

Science.gov (United States)

Aktas, Dilber; Celebi, Bekir; Isik, Mehmet Emirhan; Tutus, Celal; Ozturk, Huseyin; Temel, Fehminaz; Kizilaslan, Mecit; Zhu, Bao-Ping

2015-12-01

In 2013, an oropharyngeal tularemia outbreak in Turkey affected 55 persons. Drinking tap water during the likely exposure period was significantly associated with illness (attack rate 27% vs. 11% among non-tap water drinkers). Findings showed the tap water source had been contaminated by surface water, and the chlorination device malfunctioned.

Refolding of proteins from inclusion bodies: rational design and recipes.

Science.gov (United States)

Basu, Anindya; Li, Xiang; Leong, Susanna Su Jan

2011-10-01

The need to develop protein biomanufacturing platforms that can deliver proteins quickly and cost-effectively is ever more pressing. The rapid rate at which genomes can now be sequenced demands efficient protein production platforms for gene function identification. There is a continued need for the biotech industry to deliver new and more effective protein-based drugs to address new diseases. Bacterial production platforms have the advantage of high expression yields, but insoluble expression of many proteins necessitates the development of diverse and optimised refolding-based processes. Strategies employed to eliminate insoluble expression are reviewed, where it is concluded that inclusion bodies are difficult to eliminate for various reasons. Rational design of refolding systems and recipes are therefore needed to expedite production of recombinant proteins. This review article discusses efforts towards rational design of refolding systems and recipes, which can be guided by the development of refolding screening platforms that yield both qualitative and quantitative information on the progression of a given refolding process. The new opportunities presented by light scattering technologies for developing rational protein refolding buffer systems which in turn can be used to develop new process designs armed with better monitoring and controlling functionalities are discussed. The coupling of dynamic and static light scattering methodologies for incorporation into future bioprocess designs to ensure delivery of high-quality refolded proteins at faster rates is also discussed.

Standby Gasoline Rationing Plan. Contingency gasoline rationing regulations

Energy Technology Data Exchange (ETDEWEB)

1979-02-01

The Economic Regulatory Administration issues final rules with respect to standby gasoline rationing. The plan is designed for and would be used only in the event of a severe gasoline shortage. The plan provides that eligibility for ration allotments will be primarily on the basis of motor vehicle registrations. DOE will mail government ration checks to the parties named in a national vehicle registration file to be maintained by DOE. Ration recipients may cash these checks for ration coupons at various designated coupon issuance points. Retail outlets and other suppliers will be required to redeem the ration coupons received in exchange for gasoline sold. Supplemental gas will be given to high-priority activities. A ration banking system will be established with two separate and distinct of ration accounts: retail outlets and other suppliers will open redemption accounts for the deposit of redeemed ration rights; and individuals or firms may open ration rights accounts, which will operate in much the same manner as monetary checking accounts. A white market will be permitted for the sale of transfer of ration rights. A percentage of the total ration rights to be issued will be reserved for distribution to the states as a State Ration Reserve, to be used by the states primarily for the relief of hardship. A National Ration Reserave will also be established. All sections of the Standby Gasoline Rationing Regulations are analyzed. (MCW)

Re-emergence of tularemia in Germany: Presence of Francisella tularensis in different rodent species in endemic areas

Directory of Open Access Journals (Sweden)

Pfeffer Martin

2008-11-01

Full Text Available Abstract Background Tularemia re-emerged in Germany starting in 2004 (with 39 human cases from 2004 to 2007 after over 40 years of only sporadic human infections. The reasons for this rise in case numbers are unknown as is the possible reservoir of the etiologic agent Francisella (F. tularensis. No systematic study on the reservoir situation of F. tularensis has been published for Germany so far. Methods We investigated three areas six to ten months after the initial tularemia outbreaks for the presence of F. tularensis among small mammals, ticks/fleas and water. The investigations consisted of animal live-trapping, serologic testing, screening by real-time-PCR and cultivation. Results A total of 386 small mammals were trapped. F. tularensis was detected in five different rodent species with carrier rates of 2.04, 6.94 and 10.87% per trapping area. None of the ticks or fleas (n = 432 tested positive for F. tularensis. We were able to demonstrate F. tularensis-specific DNA in one of 28 water samples taken in one of the outbreak areas. Conclusion The findings of our study stress the need for long-term surveillance of natural foci in order to get a better understanding of the reasons for the temporal and spatial patterns of tularemia in Germany.

Tularemia in the Republic of Serbia during the period from 2000-2011

Directory of Open Access Journals (Sweden)

Marić Jovan

2012-01-01

Full Text Available Tularemia is an infective disease of zoonotic character, bacterial etiology, which occurs predominantly among rodents, but also in other species of domestic and wild mammals, birds, reptiles, fish, and humans. The cause of the disease is Francisella tularensis. Due to its epidemiological-epizootiological characteristics, the cause belongs to the group of biological agents and it has been used as a biological weapon. The disease is characterized by primary local ulcerous changes on the skin and mucosa, regional lymphadenitis, expressed general septicemia, and other changes. This disease is suspected on the grounds of epizootiological data on the incidence of the disease or the deaths of rabbits, sheep, or dogs, but also humans. During the observed period of twelve years, 317 cases of infected humans were recorded in the territory of the Republic of Serbia, without any mortal outcomes. The disease was confirmed in animals in only one case (2006.. In order to ensure full success in preventing the spreading and in the curbing of tularemia it is necessary to secure cooperation among a large number of professionals, in particular those engaged in the fields of human and veterinary medicine.

Environmental Monitoring and Surveillance of Rodents and Vectors for Francisella tularensis Following Outbreaks of Human Tularemia in Georgia.

Science.gov (United States)

Elashvili, Eka; Kracalik, Ian; Burjanadze, Irma; Datukishvili, Sophio; Chanturia, Gvantsa; Tsertsvadze, Nikoloz; Beridze, Levan; Shavishvili, Merab; Dzneladze, Archil; Grdzelidze, Marina; Imnadze, Paata; Pearson, Andrew; Blackburn, Jason K

2015-10-01

Tularemia is a re-emerging bacterial zoonosis, broadly distributed across the northern hemisphere. In Georgia, there is a history of human tularemia outbreaks dating back to the 1940s. In response to outbreaks, health officials initiated long-term field surveillance and environmental monitoring. The objective of our study was to obtain information from 57 years of field surveys to identify species that play a role in the occurrence Francisella tularensis subsp. holarctica in the environment in Georgia. We collected historical data on human outbreaks, field collections, population dynamics of the common vole (Microtus arvalis), and conducted surveys on small mammals and vectors from five regions in Georgia during 1956-2012. Bacterial isolation was conducted using standard culturing techniques, and isolation rates for species were obtained for a subset of years. We used a Spearman rank correlation to test for associations between the density of the common vole and isolation rates. From 1956 through 2012, there were four recorded outbreaks of human tularemia (362 cases). A total of 465 bacterial isolates of F. tularensis subsp. holarctica were obtained from 27 species and environmental samples. The number of isolations was highest in the common vole (M. arvalis; 149 isolates; 32%) and Dermacentor marginatus ticks (132 isolates; 28%); isolation rates ranged between 0-0.91% and 0-0.47%, respectively. Population dynamics of the common vole were not correlated with the isolation rate. Given the history of tularemia re-emergence in Georgia, continued field surveys and environmental monitoring may provide an early indication of outbreak risk in humans. In conclusion, our findings provide evidence of long-standing foci of F. tularensis subsp. holarctica that are likely maintained by the common vole-tick cycle.

RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

OpenAIRE

YEŞİLADA, Akgül; ÖZKANLI, Fügen

2004-01-01

In this review, after a short introduction to definition and physiological roles of regulatory peptides, problems faced during the development of peptide drugs, studies directed to solve these problems and rational design of peptide drugs with special emphesis on peptidomimetics are mentioned

Antibodies to Both Terminal and Internal B-Cell Epitopes of Francisella tularensis O-Polysaccharide Produced by Patients with Tularemia

Science.gov (United States)

Lu, Zhaohua; Perkins, Hillary M.

2014-01-01

Francisella tularensis, the Gram-negative bacterium that causes tularemia, is considered a potential bioterrorism threat due to its low infectivity dose and the high morbidity and mortality from respiratory disease. We previously characterized two mouse monoclonal antibodies (MAbs) specific for the O-polysaccharide (O antigen [OAg]) of F. tularensis lipopolysaccharide (LPS): Ab63, which targets a terminal epitope at the nonreducing end of OAg, and Ab52, which targets a repeating internal OAg epitope. These two MAbs were protective in a mouse model of respiratory tularemia. To determine whether these epitope types are also targeted by humans, we tested the ability of each of 18 blood serum samples from 11 tularemia patients to inhibit the binding of Ab63 or Ab52 to F. tularensis LPS in a competition enzyme-linked immunosorbent assay (ELISA). Although all serum samples had Ab63- and Ab52-inhibitory activities, the ratios of Ab63 to Ab52 inhibitory potencies varied 75-fold. However, the variation was only 2.3-fold for sequential serum samples from the same patient, indicating different distributions of terminal- versus internal-binding antibodies in different individuals. Western blot analysis using class-specific anti-human Ig secondary antibodies showed that both terminal- and internal-binding OAg antibodies were of the IgG, IgM, and IgA isotypes. These results support the use of a mouse model to discover protective B-cell epitopes for tularemia vaccines or prophylactic/therapeutic antibodies, and they present a general strategy for interrogating the antibody responses of patients and vaccinees to microbial carbohydrate epitopes that have been characterized in experimental animals. PMID:24351753

A rational approach for ω-transaminase-catalyzed process design

DEFF Research Database (Denmark)

T. Gundersen, Maria; Lloyd, Richard; Tufvesson, Pär

Herein we describe a novel rational approach to the design of a ω-transaminase process such that it will fulfill criteria necessary for industrial use. By first determining the fundamental properties of the reaction system, it is possible to suggest appropriate process strategies that may be used...

Immunoproteomic analysis of the human antibody response to natural tularemia infection with Type A or Type B strains or LVS vaccination

Science.gov (United States)

Fulton, Kelly M.; Zhao, Xigeng; Petit, Mireille D.; Kilmury, Sara L.N; Wolfraim, Lawrence A.; House, Robert V.; Sjostedt, Anders; Twine, Susan M.

2011-01-01

Francisella tularensis is pathogenic for many mammalian species including humans, causing a spectrum of diseases called tularemia. The highly virulent Type A strains have associated mortality rates of up to 60% if inhaled. An attenuated live vaccine strain (LVS) is the only vaccine to show efficacy in humans, but suffers several barriers to licensure, including the absence of a correlate of protection. An immunoproteomics approach was used to survey the repertoire of antibodies in sera from individuals who had contracted tularemia during two outbreaks and individuals from two geographical areas who had been vaccinated with NDBR Lot 11 or Lot 17 LVS. These data showed a large overlap in the antibodies generated in response to tularemia infection or LVS vaccination. A total of seven proteins were observed to be reactive with 60 % or more sera from vaccinees and convalescents. A further four proteins were recognised by 30–60 % of the sera screened. These proteins have the potential to serve as markers of vaccination or candidates for subunit vaccines. PMID:21873113

Design rationalization and the logic of design: a case study

DEFF Research Database (Denmark)

Galle, Per

1996-01-01

various ‘sources of credibility’ of premises, items of general background knowledge, and several (abductive and deductive) patterns of inference which suggest a possible ‘logic of design’. Rationalization of decisions is defined, and many decisions are found not to be fully rationalized, despite...... the apparent rationality of the reasoning....

Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.

Science.gov (United States)

Yang, Liye; Li, Wenying; Huang, Yanyu; Zhou, Yangliang; Chen, Tianfeng

2015-09-01

A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MIRATE: MIps RATional dEsign Science Gateway.

Science.gov (United States)

Busato, Mirko; Distefano, Rosario; Bates, Ferdia; Karim, Kal; Bossi, Alessandra Maria; López Vilariño, José Manuel; Piletsky, Sergey; Bombieri, Nicola; Giorgetti, Alejandro

2018-06-13

Molecularly imprinted polymers (MIPs) are high affinity robust synthetic receptors, which can be optimally synthesized and manufactured more economically than their biological equivalents (i.e. antibody). In MIPs production, rational design based on molecular modeling is a commonly employed technique. This mostly aids in (i) virtual screening of functional monomers (FMs), (ii) optimization of monomer-template ratio, and (iii) selectivity analysis. We present MIRATE, an integrated science gateway for the intelligent design of MIPs. By combining and adapting multiple state-of-the-art bioinformatics tools into automated and innovative pipelines, MIRATE guides the user through the entire process of MIPs' design. The platform allows the user to fully customize each stage involved in the MIPs' design, with the main goal to support the synthesis in the wet-laboratory. MIRATE is freely accessible with no login requirement at http://mirate.di.univr.it/. All major browsers are supported.

Structure-based, rational design of T cell receptors

Directory of Open Access Journals (Sweden)

Vincent eZoete

2013-09-01

Full Text Available Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce TCR modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction pMHC. Using the well-characterized 2C TCR/SIYR/H-2K(b structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. 54% of the designed sequence replacements exhibited improved pMHC-binding as compared to the native TCR, with up to 150 fold increase in affinity, while preserving specificity. Genetically-engineered CD8+ T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity. Beyond the affinity threshold at KD < 1 μM we observed an attenuation in cellular function. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes. We have complemented the approach with a simplified rigid method to predict the TCR orientation over pMHC. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of

Rationalization of design and construction of buildings for nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Satoh, Shunsaku; Mitsumatsu, Kazuo

1987-02-01

This article presents various rationalization methods introduced in the past few years for design and construction of BWR nuclear power plant buildings. When the site for a nuclear power plant has been decided, investigation is made on various aspects of possible earthquakes, based on which anti-earthquake design for the plant site is established. The next step is to examine the displacements and stresses that may occur to various parts of the bulding from a postulated earthquake. This is normally called the earthquake response analysis and consists of calculating the behaviors of the buildings using large computers. A seismic controlled structure system has recently proposed, aiming to reduce the displacements and stresses of the building itself by controlling the flexibility of the installed seismic apparatus against the input of external loads. Lately, high strength concrete and high strength reinforcing steel bars (rebars) are being considered for practical application. If advanced computers and related accessories are utilized to the maximum, it will lead not only to efficiency in the design work but to the possibility of optimized design. For rational construction, a combined scaffolding and temporary support has been devised to reduce the time and volume of required temporary work. What have been developed for rationalization of construction work also include robots for heavy weight rebar fabrication, horizontal reed blind type rebars, portable concrete distributor, all weather environment facilities, and construction materials conveyance system. (Nogami, K.).

Rationalization of design and construction of buildings for nuclear power plants

International Nuclear Information System (INIS)

Satoh, Shunsaku; Mitsumatsu, Kazuo

1987-01-01

This article presents various rationalization methods introduced in the past few years for design and construction of BWR nuclear power plant buildings. When the site for a nuclear power plant has been decided, investigation is made on various aspects of possible earthquakes, based on which anti-earthquake design for the plant site is established. The next step is to examine the displacements and stresses that may occur to various parts of the bulding from a postulated earthquake. This is normally called the earthquake response analysis and consists of calculating the behaviors of the buildings using large computers. A seismic controlled structure system has recently proposed, aiming to reduce the displacements and stresses of the building itself by controlling the flexibility of the installed seismic apparatus against the input of external loads. Lately, high strength concrete and high strength reinforcing steel bars (rebars) are being considered for practical application. If advanced computers and related accessories are utilized to the maximum, it will lead not only to efficiency in the design work but to the possibility of optimized design. For rational construction, a combined scaffolding and temporary support has been devised to reduce the time and volume of required temporary work. What have been developed for rationalization of construction work also include robots for heavy weight rebar fabrication, horizontal reed blind type rebars, portable concrete distributor, all weather environment facilities, and construction materials conveyance system. (Nogami, K.)

On rationally supported surfaces

DEFF Research Database (Denmark)

Gravesen, Jens; Juttler, B.; Sir, Z.

2008-01-01

We analyze the class of surfaces which are equipped with rational support functions. Any rational support function can be decomposed into a symmetric (even) and an antisymmetric (odd) part. We analyze certain geometric properties of surfaces with odd and even rational support functions....... In particular it is shown that odd rational support functions correspond to those rational surfaces which can be equipped with a linear field of normal vectors, which were discussed by Sampoli et al. (Sampoli, M.L., Peternell, M., Juttler, B., 2006. Rational surfaces with linear normals and their convolutions...... with rational surfaces. Comput. Aided Geom. Design 23, 179-192). As shown recently, this class of surfaces includes non-developable quadratic triangular Bezier surface patches (Lavicka, M., Bastl, B., 2007. Rational hypersurfaces with rational convolutions. Comput. Aided Geom. Design 24, 410426; Peternell, M...

Rational assembly of nanoparticle superlattices with designed lattice symmetries

Science.gov (United States)

Gang, Oleg; Lu, Fang; Tagawa, Miho

2017-09-05

A method for lattice design via multivalent linkers (LDML) is disclosed that introduces a rationally designed symmetry of connections between particles in order to achieve control over the morphology of their assembly. The method affords the inclusion of different programmable interactions within one linker that allow an assembly of different types of particles. The designed symmetry of connections is preferably provided utilizing DNA encoding. The linkers may include fabricated "patchy" particles, DNA scaffold constructs and Y-shaped DNA linkers, anisotropic particles, which are preferably functionalized with DNA, multimeric protein-DNA complexes, and particles with finite numbers of DNA linkers.

Live Vaccine Strain Francisella tularensis is Detectable at the Inoculation Site but Not in Blood after Vaccination Against Tularemia

National Research Council Canada - National Science Library

Hepburn, Matthew J; Purcell, Bret K; Lawler, James V; Coyne, Susan R; Petitt, Patricia L; Sellers, Karen D; Norwood, David A; Ulrich, Melanie P

2006-01-01

...) for the detection of F. tularensis in human clinical samples. Methods. Blood and skin swab samples were prospectively collected from volunteers who received the LVS tularemia vaccine at baseline (negative controls...

Rational design of soft mechanical metamaterials : Independent tailoring of elastic properties with randomness

NARCIS (Netherlands)

Mirzaali Mazandarani, M.J.; Hedayati, R.; Vena, P; Vergani, L.; Strano, M.; Zadpoor, A.A.

2017-01-01

The elastic properties of mechanical metamaterials are direct functions of their topological designs. Rational design approaches based on computational models could, therefore, be used to devise topological designs that result in the desired properties. It is of particular importance to

Lipoxin A4, a 5-lipoxygenase pathway metabolite, modulates immune response during acute respiratory tularemia.

Science.gov (United States)

Singh, Anju; Rahman, Tabassum; Bartiss, Rose; Arabshahi, Alireza; Prasain, Jeevan; Barnes, Stephen; Musteata, Florin Marcel; Sellati, Timothy J

2017-02-01

Respiratory infection with Francisella tularensis (Ft) is characterized by a muted, acute host response, followed by sepsis-like syndrome that results in death. Infection with Ft establishes a principally anti-inflammatory environment that subverts host-cell death programs to facilitate pathogen replication. Although the role of cytokines has been explored extensively, the role of eicosanoids in tularemia pathogenesis is not fully understood. Given that lipoxin A 4 (LXA 4 ) has anti-inflammatory properties, we investigated whether this lipid mediator affects host responses manifested early during infection. The addition of exogenous LXA 4 inhibits PGE 2 release by Ft-infected murine monocytes in vitro and diminishes apoptotic cell death. Tularemia pathogenesis was characterized in 5‑lipoxygenase-deficient (Alox5 -/- ) mice that are incapable of generating LXA 4 Increased release of proinflammatory cytokines and chemokines, as well as increased apoptosis, was observed in Alox5 -/- mice as compared with their wild-type counterparts. Alox5 -/- mice also exhibited elevated recruitment of neutrophils during the early phase of infection and increased resistance to lethal challenge. Conversely, administration of exogenous LXA 4 to Alox5 -/- mice made them more susceptible to infection thus mimicking wild-type animals. Taken together, our results suggest that 5-LO activity is a critical regulator of immunopathology observed during the acute phase of respiratory tularemia, regulating bacterial burden and neutrophil recruitment and production of proinflammatory modulators and increasing morbidity and mortality. These studies identify a detrimental role for the 5-LO-derived lipid mediator LXA 4 in Ft-induced immunopathology. Targeting this pathway may have therapeutic benefit as an adjunct to treatment with antibiotics and conventional antimicrobial peptides, which often have limited efficacy against intracellular bacteria. © Society for Leukocyte Biology.

The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

Science.gov (United States)

Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

2017-02-01

The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Zoonotic occupational diseases in forestry workers – Lyme borreliosis, tularemia and leptospirosis in Europe

Directory of Open Access Journals (Sweden)

Stéphanie Richard

2015-02-01

Full Text Available [b]Introduction[/b]. Forestry workers and other people who come into close contact with wild animals, such as hunters, natural science researchers, game managers or mushroom/berry pickers, are at risk of contracting bacterial, parasitological or viral zoonotic diseases. Synthetic data on the incidence and prevalence of zoonotic diseases in both animals and humans in European forests do not exist. It is therefore difficult to promote appropriate preventive measures among workers or people who come into direct or indirect contact with forest animals. [b]Objectives.[/b] The objectives of this review are to synthesise existing knowledge on the prevalence of the three predominant bacterial zoonotic diseases in Europe, i.e. Lyme borreliosis, tularemia and leptospirosis, in order to draw up recommendations for occupational or public health. [b]Methods[/b]. 88 papers published between 1995–2013 (33 on Lyme borreliosis, 30 on tularemia and 25 on leptospirosis were analyzed. [b]Conclusions[/b]. The prevalences of these three zoonotic diseases are not negligible and information targeting the public is needed. Moreover, the results highlight the lack of standardised surveys among different European countries. It was also noted that epidemiological data on leptospirosis are very scarce

Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.

Directory of Open Access Journals (Sweden)

Deborah D Crane

Full Text Available Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR(+ cells, γδTCR(+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4(+ and CD8(+ cells are the primary producers of IFN-γand that γδTCR(+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection.

Does decision documentation help junior designers rationalize their decisions? A comparative multiple-case study

NARCIS (Netherlands)

Heesch, U. van; Avgeriou, P.; Tang, A.

Software architecture design is challenging, especially for junior software designers. Lacking practice and experience, junior designers need process support in order to make rational architecture decisions. In this paper, we present the results of a comparative multiple-case study conducted to find

Neutrophils: potential therapeutic targets in tularemia?

Directory of Open Access Journals (Sweden)

Lee-Ann H Allen

2013-12-01

Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

Fundamental understanding and rational design of high energy structural microbatteries

Energy Technology Data Exchange (ETDEWEB)

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; Li, Huidong; Mendoza, Sarah; Zhang, Ji-Guang; Deng, Zhiqun Daniel; Xiao, Jie

2018-01-01

Microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices and medical applications, etc. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.

Tularemia induces different biochemical responses in BALB/c mice and common voles

Directory of Open Access Journals (Sweden)

Vitula Frantisek

2009-06-01

Full Text Available Abstract Background Both BALB/c mice and common voles (Microtus arvalis are considered highly susceptible to tularemia. However, the common vole is reported to harbour Francisella tularensis in European habitats as well as to survive longer with chronic shedding of the bacterium. The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection. Methods Rodents were evaluated for differences in the total antioxidant capacity derived from low-molecular-weight antioxidants, biochemistry including lipid metabolism, tissue bacterial burdens and histopathology following experimental intraperitoneal infection with 160 colony forming units (CFU pro toto. Results Bacterial burdens in common voles started to develop later post-exposure and amounted to lower levels than in BALB/c mice. Elevation of liver function enzymes was more pronounced in mice than common voles and there were marked differences in lipid metabolism in the course of tularemia in these two species. Hypertriglyceridemia and hypercholesterolemia developed in mice, while physiologically higher levels of triglycerides and cholesterol showed a decreasing tendency in common voles. On the other hand, the total plasma antioxidant capacity gradually dropped to 81.5% in mice on day 5 post-infection, while it increased to 130% on day 6 post-infection in common voles. Significant correlations between tissue bacterial burdens and several biochemical parameters were found. Conclusion As differences in lipid metabolism and the total antioxidant capacity of highly susceptible rodent species were demonstrated, the role of triglycerides, cholesterol and antioxidants in tularemic sepsis should be further investigated.

Rational Multiparty Computation

OpenAIRE

Wallrabenstein, John Ross

2014-01-01

The field of rational cryptography considers the design of cryptographic protocols in the presence of rational agents seeking to maximize local utility functions. This departs from the standard secure multiparty computation setting, where players are assumed to be either honest or malicious. ^ We detail the construction of both a two-party and a multiparty game theoretic framework for constructing rational cryptographic protocols. Our framework specifies the utility function assumptions neces...

Designing institutions for climate change: Why rational design involves technology

Energy Technology Data Exchange (ETDEWEB)

Coninck, H. de [Energy Research Centre of the Netherlands, Petten (Netherlands)

2008-09-30

This paper aims to explore how to augment the institutional solutions offered by current political theory for addressing the unprecedented problem of climate change. Although steering directly at emission reductions in an international treaty has benefits in terms of cost-effectiveness, the paper arrives at the conclusion that considerations around technological development should be drawn into the treaty equation in order to generate sufficient reciprocity to have a politically feasible international regime. It then argues that the benefits of technology agreements for climate change mitigation may be larger than commonly assumed, as they - if properly designed - could lead to real emission reductions and provide more flexibility to reach agreement in post-2012 negotiations than proposals modelled exclusively on the Kyoto Protocol or other types of absolute emission targets. Based on rational design of international institutions for environmental governance, and attempting to take into account considerations of technological dynamics and the 'sociotechnical system', contours of a possible environmentally effective and politically feasible international climate change agreements are sketched.

Fundamental understanding and rational design of high energy structural microbatteries

International Nuclear Information System (INIS)

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; Li, Huidong; Mendoza, Sarah

2017-01-01

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

Directory of Open Access Journals (Sweden)

Charles H. Williams

2011-04-01

Full Text Available In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.

Rational Design of Semiconductor Nanostructures for Functional Subcellular Interfaces.

Science.gov (United States)

Parameswaran, Ramya; Tian, Bozhi

2018-05-15

One of the fundamental questions guiding research in the biological sciences is how cellular systems process complex physical and environmental cues and communicate with each other across multiple length scales. Importantly, aberrant signal processing in these systems can lead to diseases that can have devastating impacts on human lives. Biophysical studies in the past several decades have demonstrated that cells can respond to not only biochemical cues but also mechanical and electrical ones. Thus, the development of new materials that can both sense and modulate all of these pathways is necessary. Semiconducting nanostructures are an emerging class of discovery platforms and tools that can push the limits of our ability to modulate and sense biological behaviors for both fundamental research and clinical applications. These materials are of particular interest for interfacing with cellular systems due to their matched dimension with subcellular components (e.g., cytoskeletal filaments), and easily tunable properties in the electrical, optical and mechanical regimes. Rational design via traditional or new approaches, such as nanocasting and mesoscale chemical lithography, can allow us to control micro- and nanoscale features in nanowires to achieve new biointerfaces. Both processes endogenous to the target cell and properties of the material surface dictate the character of these interfaces. In this Account, we focus on (1) approaches for the rational design of semiconducting nanowires that exhibit unique structures for biointerfaces, (2) recent fundamental discoveries that yield robust biointerfaces at the subcellular level, (3) intracellular electrical and mechanical sensing, and (4) modulation of cellular behaviors through material topography and remote physical stimuli. In the first section, we discuss new approaches for the synthetic control of micro- and nanoscale features of these materials. In the second section, we focus on achieving biointerfaces with

Evaluation of an Immunochromatographic Test for Rapid and Reliable Serodiagnosis of Human Tularemia and Detection of Francisella tularensis-Specific Antibodies in Sera from Different Mammalian Species ▿

Science.gov (United States)

Splettstoesser, W.; Guglielmo-Viret, V.; Seibold, E.; Thullier, P.

2010-01-01

Tularemia is a highly contagious infectious zoonosis caused by the bacterial agent Francisella tularensis. Serology is still considered to be a cornerstone in tularemia diagnosis due to the low sensitivity of bacterial culture and the lack of standardization in PCR methodology for the direct identification of the pathogen. We developed a novel immunochromatographic test (ICT) to efficiently detect F. tularensis-specific antibodies in sera from humans and other mammalian species (nonhuman primate, pig, and rabbit). This new tool requires none or minimal laboratory equipment, and the results are obtained within 15 min. When compared to the method of microagglutination, which was shown to be more specific than the enzyme-linked immunosorbent assay, the ICT had a sensitivity of 98.3% (58 positive sera were tested) and a specificity of 96.5% (58 negative sera were tested) on human sera. On animal sera, the overall sensitivity was 100% (22 positive sera were tested) and specificity was also 100% (70 negative sera were tested). This rapid test preferentially detects IgG antibodies that may occur early in the course of human tularemia, but further evaluation with human sera is important to prove that the ICT can be a valuable field test to support a presumptive diagnosis of tularemia. The ICT can also be a useful tool to monitor successful vaccination with subunit vaccines or live vaccine strains containing lipopolysaccharide (e.g., LVS) and to detect seropositive individuals or animals in outbreak situations or in the context of epidemiologic surveillance programs in areas of endemicity as recently recommended by the World Health Organization. PMID:20220165

Influence of tularemia live vaccine immunization on the immediate and end-results of combined treatment of patients with endometrial carcinoma

International Nuclear Information System (INIS)

Adamyan, R.T.; Movsesyan, M.A.

1999-01-01

Early and delayed results of the combined treatment (surgery + remote gamma therapy) of patients with corpus uteri carcinoma preliminary immunized with tularemia live vaccine (TLV). It is shown that the immunization of almost all indices of delayed treatment results ay all disease stages [ru

Rational design and application of responsive α-helical peptide hydrogels

Science.gov (United States)

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-01-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2-4. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture. PMID:19543314

Geology and Design: Formal and Rational Connections

Science.gov (United States)

Eriksson, S. C.; Brewer, J.

2016-12-01

Geological forms and the manmade environment have always been inextricably linked. From the time that Upper Paleolithic man created drawings in the Lascaux Caves in the southwest of France, geology has provided a critical and dramatic spoil for human creativity. This inspiration has manifested itself in many different ways, and the history of architecture is rife with examples of geologically derived buildings. During the early 20th Century, German Expressionist art and architecture was heavily influenced by the natural and often translucent quality of minerals. Architects like Bruno Taut drew and built crystalline forms that would go on to inspire the more restrained Bauhaus movement. Even within the context of Contemporary architecture, geology has been a fertile source for inspiration. Architectural practices across the globe leverage the rationality and grounding found in geology to inform a process that is otherwise dominated by computer-driven parametric design. The connection between advanced design technology and the beautifully realized geo natural forms insures that geology will be a relevant source of architectural inspiration well into the 21st century. The sometimes hidden relationship of geology to the various sub-disciplines of Design such as Architecture, Interiors, Landscape Architecture, and Historic Preservation is explored in relation to curriculum and the practice of design. Topics such as materials, form, history, the cultural and physical landscape, natural hazards, and global design enrich and inform curriculum across the college. Commonly, these help define place-based education.

Structured morphological modeling as a framework for rational strain design of Streptomyces species

NARCIS (Netherlands)

Celler, K.; Picioreanu, C.; Van Loosdrecht, M.C.M.; Van Wezel, G.P.

2012-01-01

Successful application of a computational model for rational design of industrial Streptomyces exploitation requires a better understanding of the relationship between morphology—dictated by microbial growth, branching, fragmentation and adhesion—and product formation. Here we review the

Nucleic acids for the rational design of reaction circuits.

Science.gov (United States)

Padirac, Adrien; Fujii, Teruo; Rondelez, Yannick

2013-08-01

Nucleic acid-based circuits are rationally designed in vitro assemblies that can perform complex preencoded programs. They can be used to mimic in silico computations. Recent works emphasized the modularity and robustness of these circuits, which allow their scaling-up. Another new development has led to dynamic, time-responsive systems that can display emergent behaviors like oscillations. These are closely related to biological architectures and provide an in vitro model of in vivo information processing. Nucleic acid circuits have already been used to handle various processes for technological or biotechnological purposes. Future applications of these chemical smart systems will benefit from the rapidly growing ability to design, construct, and model nucleic acid circuits of increasing size. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rational use of water in trickle irrigation design.

Science.gov (United States)

Saad, J. C. C.; da Silva Junior, H. M.

2012-04-01

In trickle irrigation systems, the design is based on the pre-established emission uniformity (EU) which is the combined result of the equipment characteristics and its hydraulic configuration. However, this desired value of the EU may not be confirmed by the final project (in field conditions) and neither by the yield uniformity. However, the most important is to assure yield uniformity with rational use of water. The hypotheses of this research were: a) the EU of a trickle irrigation system at field conditions is equal to the emission uniformity pre-established in the design; b) EU has always the lowest value when compared with other indicators of uniformity; c) the discharge variation coefficient is not equal to production variation coefficient in the operational unit; d) the productivity variation coefficient is more dependent on water depth applied than the EU. This study aimed to evaluate the relationships among EU used in the irrigation system design, water depth applied and the final yield uniformity. The uniformity indicators evaluated were: EU, distribution uniformity (UD) and the index proposed by Barragan & Wu (2005). They were compared estimating the performance of a trickle irrigation system applied in a citrus orchard with dimensions of 400m x 600m. The design of the irrigation system was optimized by a Linear Programming model. The tree rows were leveled in the larger direction and the spacing adopted in the orchard was 7m x 4m. The manifold line was always operating on a slope condition. The sensitivity analysis involved different slopes, 0, 3, 6, 9 and 12%, and different values of emission uniformity, 60, 70, 75, 80, 85, 90 and 94%. The citrus yield uniformity was evaluated by the variation coefficient. The emission uniformity (EU) after design differed from the EU pre-established, more sharply in the initial values lower than 90%. Comparing the uniformity indexes, the EU always generated lower values when compared with the UD and with the index

An acarologic survey and Amblyomma americanum distribution map with implications for tularemia risk in Missouri

Science.gov (United States)

Brown, H.E.; Yates, K.F.; Dietrich, G.; MacMillan, K.; Graham, C.B.; Reese, S.M.; Helterbrand, Wm. S.; Nicholson, W.L.; Blount, K.; Mead, P.S.; Patrick, S.L.; Eisen, R.J.

2011-01-01

In the United States, tickborne diseases occur focally. Missouri represents a major focus of several tickborne diseases that includes spotted fever rickettsiosis, tularemia, and ehrlichiosis. Our study sought to determine the potential risk of human exposure to human-biting vector ticks in this area. We collected ticks in 79 sites in southern Missouri during June 7-10, 2009, which yielded 1,047 adult and 3,585 nymphal Amblyomma americanum, 5 adult Amblyomma maculatum, 19 adult Dermacentor variabilis, and 5 nymphal Ixodes brunneus. Logistic regression analysis showed that areas posing an elevated risk of exposure to A. americanum nymphs or adults were more likely to be classified as forested than grassland, and the probability of being classified as elevated risk increased with increasing relative humidity during the month of June (30-year average). Overall accuracy of each of the two models was greater than 70% and showed that 20% and 30% of the state were classified as elevated risk for human exposure to nymphs and adults, respectively. We also found a significant positive association between heightened acarologic risk and counties reporting tularemia cases. Our study provides an updated distribution map for A. americanum in Missouri and suggests a wide-spread risk of human exposure to A. americanum and their associated pathogens in this region. Copyright ?? 2011 by The American Society of Tropical Medicine and Hygiene.

Rational drug design paradigms: the odyssey for designing better drugs.

Science.gov (United States)

Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

2015-01-01

Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

Tularemia con afectación faríngea y ganglionar cervical

Directory of Open Access Journals (Sweden)

María Martín-Bailón

2018-05-01

Full Text Available Introducción: La tularemia es una zoonosis producida por la bacteria Francisella tularensis, la cual se encuentra principalmente en conejos y otros animales y a veces libre en el suelo o en aguas contaminadas. Se trasmite fundamentalmente a través de la picadura de garrapata aunque también puede adquirirse por contacto directo con productos animales, agua o alimentos contaminados o por aerosolización de las bacterias. En áreas geográficas con alto porcentaje de población rural en contacto con animales sigue siendo una enfermedad a tener en cuenta en el diagnóstico diferencial de síndromes adenopáticos.Caso clínico: Varón de 45 años sin antecedentes de interés que acude a Urgencias por odinofagia derecha sin fiebre y aparición de tumoración laterocervical derecha. En la exploración se objetiva ulceración y varias aftas a nivel de amígdala derecha, así como adenopatía cervical en nivel II derecho de unos 5 cm de tamaño; analítica de sangre dentro de la normalidad. Se instaura tratamiento con amoxicilina-clavulánico y antiinflamatorios, pero a los pocos días el paciente consulta de nuevo por ausencia de mejoría. Se solicita TC de cuello con contraste que muestra adenopatía abscesificada en área II derecha de 3 cm de tamaño. Serología para tularemia positiva. Se instaura tratamiento con Levofloxacino intravenoso durante 5 días y posteriormente oral durante 10 días más, con buena respuesta. Revisión del paciente a los 3 meses, estando asintomático, con negativización de la serología y desaparición de la adenopatía cervical.Discusión: Se distinguen siete formas clínicas de tularemia, siendo la ulceroganglionar responsable del 75% de los casos: consiste en  la aparición de una lesión típica cutánea o mucosa  y adenopatías mayores de 1 cm. Es frecuente la abscesificación de estas adenopatías, pudiendo fistulizar al exterior de forma espontánea. En un 25 % de los pacientes aparece una forma orofar

Technique on rationalization of using electricity and cases

International Nuclear Information System (INIS)

1988-04-01

This book deals with rationalization of using electric and cases. It is divided into four parts. The first part introduces necessity and of progression rationalization of using electric. The second part describes the technique on rationalization of using electric with management of electric energy. The third part depicts domestic cases of rationalization on using of electric such as substation and motor. The last part also introduces foreign cases of rationalization on using of electric with measure of generator circuit, design of motor, design of lighting and design of other equipment.

Rational design of the exchange-spring permanent magnet.

Science.gov (United States)

Jiang, J S; Bader, S D

2014-02-12

The development of the optimal exchange-spring permanent magnet balances exchange hardening, magnetization enhancement, and the feasibility of scalable fabrication. These requirements can be met with a rational design of the microstructural characteristics. The magnetization processes in several model exchange-spring structures with different geometries have been analyzed with both micromagnetic simulations and nucleation theory. The multilayer geometry and the soft-cylinders-in-hard-matrix geometry have the highest achievable figure of merit (BH)max, while the soft-spheres-in-hard-matrix geometry has the lowest upper limit for (BH)max. The cylindrical geometry permits the soft phase to be larger and does not require strict size control. Exchange-spring permanent magnets based on the cylindrical geometry may be amenable to scaled-up fabrication.

Rational design of the exchange-spring permanent magnet

International Nuclear Information System (INIS)

Jiang, J S; Bader, S D

2014-01-01

The development of the optimal exchange-spring permanent magnet balances exchange hardening, magnetization enhancement, and the feasibility of scalable fabrication. These requirements can be met with a rational design of the microstructural characteristics. The magnetization processes in several model exchange-spring structures with different geometries have been analyzed with both micromagnetic simulations and nucleation theory. The multilayer geometry and the soft-cylinders-in-hard-matrix geometry have the highest achievable figure of merit (BH) max , while the soft-spheres-in-hard-matrix geometry has the lowest upper limit for (BH) max . The cylindrical geometry permits the soft phase to be larger and does not require strict size control. Exchange-spring permanent magnets based on the cylindrical geometry may be amenable to scaled-up fabrication. (paper)

Does decision documentation help junior designers rationalize their decisions? A comparative multiple-case study

OpenAIRE

Heesch, U. van; Avgeriou, P.; Tang, A.

2013-01-01

Software architecture design is challenging, especially for junior software designers. Lacking practice and experience, junior designers need process support in order to make rational architecture decisions. In this paper, we present the results of a comparative multiple-case study conducted to find out if decision viewpoints from van Heesch et al. (2012, in press) can provide such a support. The case study was conducted with four teams of software engineering students working in industrial s...

Principles underlying rational design of live attenuated influenza vaccines

Science.gov (United States)

Jang, Yo Han

2012-01-01

Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

Standby Gasoline Rationing Plan

Energy Technology Data Exchange (ETDEWEB)

None

1980-06-01

The final rules adopted by the President for a Standby Gasoline Rationing Plan are presented. The plan provides that eligibility for ration allotments will be determined primarily on the basis of motor vehicle registrations, taking into account historical differences in the use of gasoline among states. The regulations also provide authority for supplemental allotments to firms so that their allotment will equal a specified percentage of gasoline use during a base period. Priority classifications, i.e., agriculture, defense, etc., are established to assure adequate gasoline supplies for designated essential services. Ration rights must be provided by end-users to their suppliers for each gallon sold. DOE will regulate the distribution of gasoline at the wholesale level according to the transfer by suppliers of redeemed ration rights and the gasoline allocation regulations. Ration rights are transferable. A ration banking system is created to facilitate transfers of ration rights. Each state will be provided with a reserve of ration rights to provide for hardship needs and to alleviate inequities. (DC)

Rationally designed synthetic protein hydrogels with predictable mechanical properties.

Science.gov (United States)

Wu, Junhua; Li, Pengfei; Dong, Chenling; Jiang, Heting; Bin Xue; Gao, Xiang; Qin, Meng; Wang, Wei; Bin Chen; Cao, Yi

2018-02-12

Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

  A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity

DEFF Research Database (Denmark)

Huebener, Nicole; Fest, Stefan; Strandsby, Anne Bystrup

2008-01-01

Therapeutic vaccination against tumor antigens without induction of autoimmunity remains a major challenge in cancer immunotherapy. Here, we show for the first time effective therapeutic vaccination followed by suppression of established spontaneous neuroblastoma metastases using a tyrosine...... show effective therapeutic vaccination against neuroblastoma with a novel rationally designed TH minigene vaccine without induction of autoimmunity providing an important baseline for future clinical application of this strategy....

Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

Science.gov (United States)

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

2016-01-01

Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

Science.gov (United States)

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

2015-12-01

Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials.

Science.gov (United States)

Zadpoor, Amir A

2017-07-25

Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials

Directory of Open Access Journals (Sweden)

Amir A. Zadpoor

2017-07-01

Full Text Available Recent advances in additive manufacturing (AM techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes.

One-pot synthesis of water soluble iron nanoparticles using rationally-designed peptides and ligand release.

Science.gov (United States)

Papst, Stefanie; Cheong, Soshan; Banholzer, Moritz J; Brimble, Margaret A; Williams, David E; Tilley, Richard D

2013-05-18

Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.

Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis

Directory of Open Access Journals (Sweden)

Anne Busch

2018-03-01

Full Text Available Francisella (F. tularensis is a highly virulent, Gram-negative bacterial pathogen and the causative agent of the zoonotic disease tularemia. Here, we generated, analyzed and characterized a high quality circular genome sequence of the F. tularensis subsp. holarctica strain 12T0050 that caused fatal tularemia in a hare. Besides the genomic structure, we focused on the analysis of oriC, unique to the Francisella genus and regulating replication in and outside hosts and the first report on genomic DNA methylation of a Francisella strain. The high quality genome was used to establish and evaluate a diagnostic whole genome sequencing pipeline. A genotyping strategy for F. tularensis was developed using various bioinformatics tools for genotyping. Additionally, whole genome sequences of F. tularensis subsp. holarctica isolates isolated in the years 2008–2015 in Germany were generated. A phylogenetic analysis allowed to determine the genetic relatedness of these isolates and confirmed the highly conserved nature of F. tularensis subsp. holarctica.

Development of a Preventive HIV Vaccine Requires Solving Inverse Problems Which Is Unattainable by Rational Vaccine Design

Directory of Open Access Journals (Sweden)

Marc H. V. Van Regenmortel

2018-01-01

Full Text Available Hypotheses and theories are essential constituents of the scientific method. Many vaccinologists are unaware that the problems they try to solve are mostly inverse problems that consist in imagining what could bring about a desired outcome. An inverse problem starts with the result and tries to guess what are the multiple causes that could have produced it. Compared to the usual direct scientific problems that start with the causes and derive or calculate the results using deductive reasoning and known mechanisms, solving an inverse problem uses a less reliable inductive approach and requires the development of a theoretical model that may have different solutions or none at all. Unsuccessful attempts to solve inverse problems in HIV vaccinology by reductionist methods, systems biology and structure-based reverse vaccinology are described. The popular strategy known as rational vaccine design is unable to solve the multiple inverse problems faced by HIV vaccine developers. The term “rational” is derived from “rational drug design” which uses the 3D structure of a biological target for designing molecules that will selectively bind to it and inhibit its biological activity. In vaccine design, however, the word “rational” simply means that the investigator is concentrating on parts of the system for which molecular information is available. The economist and Nobel laureate Herbert Simon introduced the concept of “bounded rationality” to explain why the complexity of the world economic system makes it impossible, for instance, to predict an event like the financial crash of 2007–2008. Humans always operate under unavoidable constraints such as insufficient information, a limited capacity to process huge amounts of data and a limited amount of time available to reach a decision. Such limitations always prevent us from achieving the complete understanding and optimization of a complex system that would be needed to achieve a truly

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

Science.gov (United States)

Wu, Junjun; Zhang, Xia; Zhu, Yingjie; Tan, Qinyu; He, Jiacheng; Dong, Mingsheng

2017-05-03

Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.

Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

Science.gov (United States)

García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

2017-08-01

Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Rational Emotive Education

Science.gov (United States)

Knaus, William

1977-01-01

Rational Emotive Education--an outgrowth of theories developed by Albert Ellis--is a teaching design of mental health concepts and problem-solving activities designed to help students to approach and cope with their problems through experiential learning, via a structured, thematic sequence of emotive education lessons. (MJB)

Population Genomics of Francisella tularensis subsp. holarctica and its Implication on the Eco-Epidemiology of Tularemia in Switzerland.

Science.gov (United States)

Wittwer, Matthias; Altpeter, Ekkehard; Pilo, Paola; Gygli, Sebastian M; Beuret, Christian; Foucault, Frederic; Ackermann-Gäumann, Rahel; Karrer, Urs; Jacob, Daniela; Grunow, Roland; Schürch, Nadia

2018-01-01

Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to elucidate complex disease transmission patterns, as well as resolving the phylogeny at high resolution on a micro-geographic scale. In this study, we present insights into the population structure of Francisella tularensis subsp. holarctica , the causative agent of tularemia in Switzerland. A total of 59 Fth isolates were obtained from castor bean ticks ( Ixodes ricinus) , animals and humans and a high resolution phylogeny was inferred using WGS methods. The majority of the Fth population in Switzerland belongs to the west European B.11 clade and shows an extraordinary genetic diversity underlining the old evolutionary history of the pathogen in the alpine region. Moreover, a new B.11 subclade was identified which was not described so far. The combined analysis of the epidemiological data of human tularemia cases with the whole genome sequences of the 59 isolates provide evidence that ticks play a pivotal role in transmitting Fth to humans and other vertebrates in Switzerland. This is further underlined by the correlation of disease risk estimates with climatic and ecological factors influencing the survival of ticks.

Population Genomics of Francisella tularensis subsp. holarctica and its Implication on the Eco-Epidemiology of Tularemia in Switzerland

Science.gov (United States)

Wittwer, Matthias; Altpeter, Ekkehard; Pilo, Paola; Gygli, Sebastian M.; Beuret, Christian; Foucault, Frederic; Ackermann-Gäumann, Rahel; Karrer, Urs; Jacob, Daniela; Grunow, Roland; Schürch, Nadia

2018-01-01

Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to elucidate complex disease transmission patterns, as well as resolving the phylogeny at high resolution on a micro-geographic scale. In this study, we present insights into the population structure of Francisella tularensis subsp. holarctica, the causative agent of tularemia in Switzerland. A total of 59 Fth isolates were obtained from castor bean ticks (Ixodes ricinus), animals and humans and a high resolution phylogeny was inferred using WGS methods. The majority of the Fth population in Switzerland belongs to the west European B.11 clade and shows an extraordinary genetic diversity underlining the old evolutionary history of the pathogen in the alpine region. Moreover, a new B.11 subclade was identified which was not described so far. The combined analysis of the epidemiological data of human tularemia cases with the whole genome sequences of the 59 isolates provide evidence that ticks play a pivotal role in transmitting Fth to humans and other vertebrates in Switzerland. This is further underlined by the correlation of disease risk estimates with climatic and ecological factors influencing the survival of ticks. PMID:29623260

Mouse models of aerosol-acquired tularemia caused by Francisella tularensis types A and B.

Science.gov (United States)

Fritz, David L; England, Marilyn J; Miller, Lynda; Waag, David M

2014-10-01

After preliminary assessment of virulence in AKR/J, DBA/1, BALB/c, and C57BL/6 mice, we investigated histopathologic changes in BALB/c and C57BL/6 mice infected with type A (strain SCHU S4) or type B (strain 425) Francisella tularensis by aerosol exposure. In mice exposed to type A infection, changes in histologic presentation were not apparent until day 3 after infection, when pyogranulomatous inflammation was detected in spleens and livers of BALB/c mice, and in lungs and spleens of C57BL/6 mice. Histopathologic changes were most severe and widespread in both mouse strains on day 5 after infection and seemed to completely resolve within 22 d of challenge. BALB/c mice were more resistant than C57BL/6 mice in lethal-dose calculations, but C57BL/6 mice cleared the infection more rapidly. Mice similarly challenged with type B F. tularensis also developed histopathologic signs of infection beginning on day 3. The most severe changes were noted on day 8 and were characterized by granulomatous or pyogranulomatous infiltrations of the lungs. Unlike type A infection, lesions due to type B did not resolve over time and remained 3 wk after infection. In type B, but not type A, infection we noted extensive inflammation of the heart muscle. Although no microorganisms were found in tissues of type A survivors beyond 9 d after infection, mice surviving strain 425 infection had a low level of residual infection at 3 wk after challenge. The histopathologic presentation of tularemia caused by F. tularensis types A and B in BALB/c and C57BL/6 mice bears distinct similarities to tularemia in humans.

Rational design of capillary-driven flows for paper-based microfluidics.

Science.gov (United States)

Elizalde, Emanuel; Urteaga, Raúl; Berli, Claudio L A

2015-05-21

The design of paper-based assays that integrate passive pumping requires a precise programming of the fluid transport, which has to be encoded in the geometrical shape of the substrate. This requirement becomes critical in multiple-step processes, where fluid handling must be accurate and reproducible for each operation. The present work theoretically investigates the capillary imbibition in paper-like substrates to better understand fluid transport in terms of the macroscopic geometry of the flow domain. A fluid dynamic model was derived for homogeneous porous substrates with arbitrary cross-sectional shapes, which allows one to determine the cross-sectional profile required for a prescribed fluid velocity or mass transport rate. An extension of the model to slit microchannels is also demonstrated. Calculations were validated by experiments with prototypes fabricated in our lab. The proposed method constitutes a valuable tool for the rational design of paper-based assays.

Attenuation of Vibrio fischeri quorum sensing using rationally designed polymers.

Science.gov (United States)

Piletska, Elena V; Stavroulakis, Georgios; Karim, Kal; Whitcombe, Michael J; Chianella, Iva; Sharma, Anant; Eboigbodin, Kevin E; Robinson, Gary K; Piletsky, Sergey A

2010-04-12

A first attempt to attenuate the quorum sensing (QS) of a marine heterotroph microorganism, Vibrio fischeri , using signal molecule-sequestering polymers (SSPs) is presented. A set of rationally designed polymers with affinity toward a signal molecule of V. fischeri , N-(beta-ketocaproyl)-l-homoserine lactone (3-oxo-C6-AHL) was produced. It is reported that computationally designed polymers could sequester a signal molecule of V. fischeri and prevent QS-controlled phenotypes (in this case, bioluminescence) from being up-regulated. It was proven that the attenuation of bioluminescence of V. fischeri was due to sequestration of the signal molecule by specific polymers and not due to the toxicity of polymer or nonspecific depletion of nutrients. The ability to disrupt the bacterial communication using easy to synthesize and chemically inert polymers could provide a new concept for the development of pharmaceuticals and susceptible device coatings such as catheters.

Seroprevalence of brucellosis, tularemia, and yersiniosis in wild boars (Sus scrofa) from north-eastern Germany.

Science.gov (United States)

Al Dahouk, S; Nöckler, K; Tomaso, H; Splettstoesser, W D; Jungersen, G; Riber, U; Petry, T; Hoffmann, D; Scholz, H C; Hensel, A; Neubauer, H

2005-12-01

Brucellosis and tularemia are classical zoonotic diseases transmitted from an animal reservoir to humans. Both, wildlife and domestic animals, contribute to the spreading of these zoonoses. The surveillance of the animal health status is strictly regulated for domestic animals, whereas systematic disease monitoring in wildlife does not exist. The aim of the present study was to provide data on the prevalence of anti-Brucella, anti-Francisella and anti-Yersinia antibodies in wild boars from North-Eastern Germany to assess public health risks. A total of 763 sera of wild boars from Mecklenburg-Western Pomerania hunted in 1995/1996 were tested using a commercially available Brucella suis ELISA, an in-house lipopolysaccharide (LPS)-based Francisella ELISA, and commercially available Western blot kits for the detection of anti-Francisella and anti-Yersinia antibodies. The Yersinia enterocolitica O:9 LPS is able to induce serological cross-reactions indistinguishable from brucellosis due to a similar immunodominant epitope in the Brucella O-polysaccharide. The Yersinia Western blot assay was, therefore, based on five recombinant Yersinia outer proteins which have been proved to be specific for the serodiagnosis of yersiniosis. Anti-Brucella, anti-Francisella and anti-Yersinia antibodies were detected in 22.0%, 3.1%, and 62.6% of the wild boars, respectively. The high seroprevalence of tularemia and brucellosis in wild boars indicates that natural foci of these zoonoses are present in wildlife in Germany. However, the impact of transmission of zoonotic pathogens from wildlife to livestock is unknown. Only careful and systematic monitoring will help to prevent the (re)emergence of these zoonotic diseases in domestic animals and consequently human infection.

Considerations for the rational design of a Chlamydia vaccine.

Science.gov (United States)

Liang, Steven; Bulir, David; Kaushic, Charu; Mahony, James

2017-04-03

Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Remarkable progress in vaccine research over the past six decades has led to the advancement of novel C. trachomatis vaccine candidates into clinical trials. However, many questions regarding the role of specific cellular populations and molecular mechanisms in protective immunity against human C. trachomatis genital tract infections remain unanswered. Biomarkers of vaccine induced protective immunity are elusive in humans, while a cautionary message on the translatability of data obtained from current animal models has emanated from vaccine research and development efforts against other important human pathogens. In this commentary, we highlight recent advances in Chlamydia vaccine development and discuss their implications in the context of a rational approach to the design of a human C. trachomatis vaccine.

Development of rational design technique for frame steel structure combining seismic resistance and economic performance

International Nuclear Information System (INIS)

Kato, Motoki; Morishita, Kunihiro; Shimono, Masaki; Chuman, Yasuharu; Okafuji, Takashi; Monaka, Toshiaki

2015-01-01

Anti-seismic designs have been applied to plant support steel frames for years. Today, a rational structure that further improves seismic resistance and ensures economic performance is required in response to an increase of seismic load on the assumption of predicted future massive earthquakes. For satisfying this requirement, a steel frame design method that combines a steel frame weight minimizing method, which enables economic design through simultaneous minimization of multiple steel frame materials, and a seismic response control design technology that improves seismic resistance has been established. Its application in the design of real structures has been promoted. This paper gives an overview of this design technology and presents design examples to which this design technology is applied. (author)

Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

Science.gov (United States)

Kesisoglou, Filippos; Mitra, Amitava

2015-09-01

Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

Rational design of hierarchical ZnO@Carbon nanoflower for high performance lithium ion battery anodes

Science.gov (United States)

liu, Huichao; Shi, Ludi; Li, Dongzhi; Yu, Jiali; Zhang, Han-Ming; Ullah, Shahid; Yang, Bo; Li, Cuihua; Zhu, Caizhen; Xu, Jian

2018-05-01

The rational structure design and strong interfacial bonding are crucially desired for high performance zinc oxide (ZnO)/carbon composite electrodes. In this context, micro-nano secondary structure design and strong dopamine coating strategies are adopted for the fabrication of flower-like ZnO/carbon (ZnO@C nanoflowers) composite electrodes. The results show the ZnO@C nanoflowers (2-6 μm) are assembled by hierarchical ZnO nanosheets (∼27 nm) and continuous carbon framework. The micro-nano secondary architecture can facilitate the penetration of electrolyte, shorten lithium ions diffusion length, and hinder the aggregation of the nanosheets. Moreover, the strong chemical interaction between ZnO and coating carbon layer via C-Zn bond improves structure stability as well as the electronic conductivity. As a synergistic result, when evaluated as lithium ion batteries (LIBs) anode, the ZnO@C nanoflower electrodes show high reversible capacity of ca. 1200 mA h g-1 at 0.1 A g-1 after 80 cycles. As well as good long-cycling stability (638 and 420 mA h g-1 at 1 and 5 A g-1 after 500 cycles, respectively) and excellent rate capability. Therefore, this rational design of ZnO@C nanoflowers electrode is a promising anode for high-performance LIBs.

Rational design of functional and tunable oscillating enzymatic networks

Science.gov (United States)

Semenov, Sergey N.; Wong, Albert S. Y.; van der Made, R. Martijn; Postma, Sjoerd G. J.; Groen, Joost; van Roekel, Hendrik W. H.; de Greef, Tom F. A.; Huck, Wilhelm T. S.

2015-02-01

Life is sustained by complex systems operating far from equilibrium and consisting of a multitude of enzymatic reaction networks. The operating principles of biology's regulatory networks are known, but the in vitro assembly of out-of-equilibrium enzymatic reaction networks has proved challenging, limiting the development of synthetic systems showing autonomous behaviour. Here, we present a strategy for the rational design of programmable functional reaction networks that exhibit dynamic behaviour. We demonstrate that a network built around autoactivation and delayed negative feedback of the enzyme trypsin is capable of producing sustained oscillating concentrations of active trypsin for over 65 h. Other functions, such as amplification, analog-to-digital conversion and periodic control over equilibrium systems, are obtained by linking multiple network modules in microfluidic flow reactors. The methodology developed here provides a general framework to construct dissipative, tunable and robust (bio)chemical reaction networks.

Testing the rationality assumption using a design difference in the TV game show 'Jeopardy'

OpenAIRE

Sjögren Lindquist, Gabriella; Säve-Söderbergh, Jenny

2006-01-01

Abstract This paper empirically investigates the rationality assumption commonly applied in economic modeling by exploiting a design difference in the game-show Jeopardy between the US and Sweden. In particular we address the assumption of individuals’ capabilities to process complex mathematical problems to find optimal strategies. The vital difference is that US contestants are given explicit information before they act, while Swedish contestants individually need to calculate the same info...

Virus-Like Particle Engineering: From Rational Design to Versatile Applications.

Science.gov (United States)

Ding, Xuanwei; Liu, Dong; Booth, George; Gao, Wei; Lu, Yuan

2018-05-01

As mimicking natural virus structures, virus-like particles (VLPs) have evolved to become a widely accepted technology used for humans which are safe, highly efficacious, and profitable. Several remarkable advantages have been achieved to revolutionize the molecule delivery for diverse applications in nanotechnology, biotechnology, and medicine. Here, the rational structure design, manufacturing process, functionalization strategy, and emerging applications of VLPs is reviewed. The situation and challenges in the VLP engineering, the key development orientation, and future applications have been discussed. To develop a good VLP design concept, the virus/VLP-host interactions need to be examined and the screening methods of the VLP stabilization factors need to be established. The functionalization toolbox can be expanded to fabricate smart, robust, and multifunctional VLPs. Novel robust VLP manufacturing platforms are required to deliver vaccines in resource-poor regions with a significant reduction in the production time and cost. The future applications of VLPs are always driven by the development of emerging technologies and new requirements of modern life. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rationality of limited rationality : some aggregate implications

OpenAIRE

Uri M. Possen; Mikko Puhakka

1994-01-01

In this paper we let economic agents choose whether to become fully rational or stay boundedly rational. Boundedly rational agents are less sophisticated in their information processing abilities. It is costly to acquire information needed to become fully rational, and thus not all agents are willing to incur those costs. We then explore the aggregate effects of endogenizing the decision whether the agent should or should not become fully rational in handling information. Since fully and boun...

Rationalization with ruled surfaces in architecture

DEFF Research Database (Denmark)

Steenstrup, Kasper Hornbak

This thesis addresses the problems of rationalizing and segmenting large scale 3D models, and how to handle difficult production constraints in this area. The design choices when constructing large scale architecture are influenced by the budget. Therefore I strive to minimize the amount of time...... and material needed for production. This makes advanced free form architecture viable for low cost projects, allowing the architects to realize their designs. By pre-cutting building blocks using hot wire robots, the amount of milling necessary can be reduced drastically. I do this by rationalizing...

GREEN: A program package for docking studies in rational drug design

Science.gov (United States)

Tomioka, Nobuo; Itai, Akiko

1994-08-01

A program package, GREEN, has been developed that enables docking studies between ligand molecules and a protein molecule. Based on the structure of the protein molecule, the physical and chemical environment of the ligand-binding site is expressed as three-dimensional grid-point data. The grid-point data are used for the real-time evaluation of the protein-ligand interaction energy, as well as for the graphical representation of the binding-site environment. The interactive docking operation is facilitated by various built-in functions, such as energy minimization, energy contribution analysis and logging of the manipulation trajectory. Interactive modeling functions are incorporated for designing new ligand molecules while considering the binding-site environment and the protein-ligand interaction. As an example of the application of GREEN, a docking study is presented on the complex between trypsin and a synthetic trypsin inhibitor. The program package will be useful for rational drug design, based on the 3D structure of the target protein.

Rational Design Approach for Enhancing Higher-Mode Response of a Microcantilever in Vibro-Impacting Mode

Directory of Open Access Journals (Sweden)

Ieva Migliniene

2017-12-01

Full Text Available This paper proposes an approach for designing an efficient vibration energy harvester based on a vibro-impacting piezoelectric microcantilever with a geometric shape that has been rationally modified in accordance with results of dynamic optimization. The design goal is to increase the amplitudes of higher-order vibration modes induced during the vibro-impact response of the piezoelectric transducer, thereby providing a means to improve the energy conversion efficiency and power output. A rational configuration of the energy harvester is proposed and it is demonstrated that the new design retains essential modal characteristics of the optimal microcantilever structures, further providing the added benefit of less costly fabrication. The effects of structural dynamics associated with advantageous exploitation of higher vibration modes are analyzed experimentally by means of laser vibrometry as well as numerically via transient simulations of microcantilever response to random excitation. Electrical characterization results indicate that the proposed harvester outperforms its conventional counterpart (based on the microcantilever of the constant cross-section in terms of generated electrical output. Reported results may serve for the development of impact-type micropower generators with harvesting performance that is enhanced by virtue of self-excitation of large intensity higher-order mode responses when the piezoelectric transducer is subjected to relatively low-frequency excitation with strongly variable vibration magnitudes.

Rationalization and Design of the Complementarity Determining Region Sequences in an Antibody-Antigen Recognition Interface

Science.gov (United States)

Chen, Ing-Chien; Lee, Yu-Ching; Chen, Jun-Bo; Tsai, Keng-Chang; Chen, Ching-Tai; Chang, Jeng-Yih; Yang, Ei-Wen; Hsu, Po-Chiang; Jian, Jhih-Wei; Hsu, Hung-Ju; Chang, Hung-Ju; Hsu, Wen-Lian; Huang, Kai-Fa; Ma, Alex Che; Yang, An-Suei

2012-01-01

Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes. PMID:22457753

Rational design of new materials using recombinant structural proteins: Current state and future challenges.

Science.gov (United States)

Sutherland, Tara D; Huson, Mickey G; Rapson, Trevor D

2018-01-01

Sequence-definable polymers are seen as a prerequisite for design of future materials, with many polymer scientists regarding such polymers as the holy grail of polymer science. Recombinant proteins are sequence-defined polymers. Proteins are dictated by DNA templates and therefore the sequence of amino acids in a protein is defined, and molecular biology provides tools that allow redesign of the DNA as required. Despite this advantage, proteins are underrepresented in materials science. In this publication we investigate the advantages and limitations of using proteins as templates for rational design of new materials. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

Science.gov (United States)

Hudson, Lauren E.; Anderson, Sarah E.; Corbett, Anita H.

2016-01-01

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases. PMID:27856521

Rational Design of Coordination Polymers with Flexible Oxyethylene Side Chains

International Nuclear Information System (INIS)

Choi, Eun Young; Gao, Chunji; Lee, Suck Hyun; Kwon, O Pil

2012-01-01

We rationally designed and synthesized metallopolymers with organic 1,4-benzenedicarboxylic acid (BDC) linkers with different lengths of oxyethylene side chains in order to examine the influence of side chains on the coordination characteristics. While in a previous report the BDC linkers with alkyl side chains were found to form three-dimensional (3D) isoreticular metal-organic framework (IRMOF) structures or one-dimensional (1D) coordination polymeric structures with short -O(CH 2 ) 6 CH 3 or long -O(CH 2 ) 9 CH 3 side chains, respectively, new BDC linkers with oxyethylene side chains of the same lengths, -(OCH 2 CH 2 ) 2 CH 3 and -(OCH 2 CH 2 ) 3 CH 3 , form only 3D IRMOF structures. This result is attributed to the higher flexibility and smaller volume of oxyethylene side chains compared to alkyl side chains

Improving specific activity and thermostability of Escherichia coli phytase by structure-based rational design.

Science.gov (United States)

Wu, Tzu-Hui; Chen, Chun-Chi; Cheng, Ya-Shan; Ko, Tzu-Ping; Lin, Cheng-Yen; Lai, Hui-Lin; Huang, Ting-Yung; Liu, Je-Ruei; Guo, Rey-Ting

2014-04-10

Escherichia coli phytase (EcAppA) which hydrolyzes phytate has been widely applied in the feed industry, but the need to improve the enzyme activity and thermostability remains. Here, we conduct rational design with two strategies to enhance the EcAppA performance. First, residues near the substrate binding pocket of EcAppA were modified according to the consensus sequence of two highly active Citrobacter phytases. One out of the eleven mutants, V89T, exhibited 17.5% increase in catalytic activity, which might be a result of stabilized protein folding. Second, the EcAppA glycosylation pattern was modified in accordance with the Citrobacter phytases. An N-glycosylation motif near the substrate binding site was disrupted to remove spatial hindrance for phytate entry and product departure. The de-glycosylated mutants showed 9.6% increase in specific activity. On the other hand, the EcAppA mutants that adopt N-glycosylation motifs from CbAppA showed improved thermostability that three mutants carrying single N-glycosylation motif exhibited 5.6-9.5% residual activity after treatment at 80°C (1.8% for wild type). Furthermore, the mutant carrying all three glycosylation motifs exhibited 27% residual activity. In conclusion, a successful rational design was performed to obtain several useful EcAppA mutants with better properties for further applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous inhibition of aberrant cancer kinome using rationally designed polymer-protein core-shell nanomedicine.

Science.gov (United States)

Chandran, Parwathy; Gupta, Neha; Retnakumari, Archana Payickattu; Malarvizhi, Giridharan Loghanathan; Keechilat, Pavithran; Nair, Shantikumar; Koyakutty, Manzoor

2013-11-01

Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34(+)/CD38(-)) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core (~250 nm) loaded with mTOR inhibitor, everolimus, and albumin shell (~25 nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure (~290 nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use. Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical engineering in the electronics industry: progress towards the rational design of organic semiconductor heterojunctions

KAUST Repository

Clancy, Paulette

2012-05-01

We review the current status of heterojunction design for combinations of organic semiconductor materials, given its central role in affecting the device performance for electronic devices and solar cell applications. We provide an emphasis on recent progress towards the rational design of heterojunctions that may lead to higher performance of charge separation and mobility. We also play particular attention to the role played by computational approaches and its potential to help define the best choice of materials for solar cell development in the future. We report the current status of the field with respect to such goals. © 2012 Elsevier Ltd.

Chemical engineering in the electronics industry: progress towards the rational design of organic semiconductor heterojunctions

KAUST Repository

Clancy, Paulette

2012-01-01

We review the current status of heterojunction design for combinations of organic semiconductor materials, given its central role in affecting the device performance for electronic devices and solar cell applications. We provide an emphasis on recent progress towards the rational design of heterojunctions that may lead to higher performance of charge separation and mobility. We also play particular attention to the role played by computational approaches and its potential to help define the best choice of materials for solar cell development in the future. We report the current status of the field with respect to such goals. © 2012 Elsevier Ltd.

Theory and simulation of DNA-coated colloids: a guide for rational design.

Science.gov (United States)

Angioletti-Uberti, Stefano; Mognetti, Bortolo M; Frenkel, Daan

2016-03-07

By exploiting the exquisite selectivity of DNA hybridization, DNA-coated colloids (DNACCs) can be made to self-assemble in a wide variety of structures. The beauty of this system stems largely from its exceptional versatility and from the fact that a proper choice of the grafted DNA sequences yields fine control over the colloidal interactions. Theory and simulations have an important role to play in the optimal design of self assembling DNACCs. At present, the powerful model-based design tools are not widely used, because the theoretical literature is fragmented and the connection between different theories is often not evident. In this Perspective, we aim to discuss the similarities and differences between the different models that have been described in the literature, their underlying assumptions, their strengths and their weaknesses. Using the tools described in the present Review, it should be possible to move towards a more rational design of novel self-assembling structures of DNACCs and, more generally, of systems where ligand-receptor are used to control interactions.

Rational In Silico Design of an Organic Semiconductor with Improved Electron Mobility.

Science.gov (United States)

Friederich, Pascal; Gómez, Verónica; Sprau, Christian; Meded, Velimir; Strunk, Timo; Jenne, Michael; Magri, Andrea; Symalla, Franz; Colsmann, Alexander; Ruben, Mario; Wenzel, Wolfgang

2017-11-01

Organic semiconductors find a wide range of applications, such as in organic light emitting diodes, organic solar cells, and organic field effect transistors. One of their most striking disadvantages in comparison to crystalline inorganic semiconductors is their low charge-carrier mobility, which manifests itself in major device constraints such as limited photoactive layer thicknesses. Trial-and-error attempts to increase charge-carrier mobility are impeded by the complex interplay of the molecular and electronic structure of the material with its morphology. Here, the viability of a multiscale simulation approach to rationally design materials with improved electron mobility is demonstrated. Starting from one of the most widely used electron conducting materials (Alq 3 ), novel organic semiconductors with tailored electronic properties are designed for which an improvement of the electron mobility by three orders of magnitude is predicted and experimentally confirmed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of a Discrete Tracking Controller for a Magnetic Levitation System: A Nonlinear Rational Model Approach

Directory of Open Access Journals (Sweden)

Fernando Gómez-Salas

2015-01-01

Full Text Available This work proposes a discrete-time nonlinear rational approximate model for the unstable magnetic levitation system. Based on this model and as an application of the input-output linearization technique, a discrete-time tracking control design will be derived using the corresponding classical state space representation of the model. A simulation example illustrates the efficiency of the proposed methodology.

Rational design of a bi-layered reduced graphene oxide film on polystyrene foam for solar-driven interfacial water evaporation

KAUST Repository

Shi, Le; Wang, Yuchao; Zhang, Lianbin; Wang, Peng

2016-01-01

Solar-driven water evaporation has been emerging as a highly efficient way for utilizing solar energy for clean water production and wastewater treatment. Here we rationally designed and fabricated a bi-layered photothermal membrane with a porous

Rational Design, Synthesis and Pharmacological Evaluation of the (2R)- and (2S)-Stereoisomers of 3-(2-Carboxypyrrolidinyl)-2-methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors

DEFF Research Database (Denmark)

Rasmussen, Julie; Storgaard, Morten; Pickering, Darryl S

2011-01-01

In this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)-glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high-affinity Glu analogue SYM...

Rational design of stealthy hyperuniform two-phase media with tunable order

Science.gov (United States)

DiStasio, Robert A.; Zhang, Ge; Stillinger, Frank H.; Torquato, Salvatore

2018-02-01

Disordered stealthy hyperuniform materials are exotic amorphous states of matter that have attracted recent attention because of their novel structural characteristics (hidden order at large length scales) and physical properties, including desirable photonic and transport properties. It is therefore useful to devise algorithms that enable one to design a wide class of such amorphous configurations at will. In this paper, we present several algorithms enabling the systematic identification and generation of discrete (digitized) stealthy hyperuniform patterns with a tunable degree of order, paving the way towards the rational design of disordered materials endowed with novel thermodynamic and physical properties. To quantify the degree of order or disorder of the stealthy systems, we utilize the discrete version of the τ order metric, which accounts for the underlying spatial correlations that exist across all relevant length scales in a given digitized two-phase (or, equivalently, a two-spin state) system of interest. Our results impinge on a myriad of fields, ranging from physics, materials science and engineering, visual perception, and information theory to modern data science.

Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

Science.gov (United States)

Carter, Daniel C. (Inventor)

1994-01-01

This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

Rationalization: A Bibliography.

Science.gov (United States)

Pedrini, D. T.; Pedrini, Bonnie C.

Rationalization was studied by Sigmund Freud and was specifically labeled by Ernest Jones. Rationalization ought to be differentiated from rational, rationality, logical analysis, etc. On the one hand, rationalization is considered a defense mechanism, on the other hand, rationality is not. Haan has done much work with self-report inventories and…

Public policy, rationality and reason

Directory of Open Access Journals (Sweden)

Rodolfo Canto Sáenz

2015-07-01

Full Text Available This work suggests the incorporation of practical reason in the design, implementation and evaluation of public policies, alongside instrumental rationality. It takes two proposals that today point in this direction: Rawls distinction between reasonable (practical reason and rational (instrumental reason and what this author calls the CI Procedure (categorical imperative procedure and Habermas model of deliberative democracy. The main conclusion is that the analysis of public policies can not be limited to rather narrow limits of science, but requires the contribution of political and moral philosophy.

Rational Design and Synthesis of Efficient Sunscreens To Boost the Solar Protection Factor.

Science.gov (United States)

Losantos, Raúl; Funes-Ardoiz, Ignacio; Aguilera, José; Herrera-Ceballos, Enrique; García-Iriepa, Cristina; Campos, Pedro J; Sampedro, Diego

2017-03-01

Skin cancer incidence has been increasing in the last decades, but most of the commercial formulations used as sunscreens are designed to protect only against solar erythema. Many of the active components present in sunscreens show critical weaknesses, such as low stability and toxicity. Thus, the development of more efficient components is an urgent health necessity and an attractive industrial target. We have rationally designed core moieties with increased photoprotective capacities and a new energy dissipation mechanism. Using these scaffolds, we have synthesized a series of compounds with tunable properties suitable for their use in sunscreens, and enhanced properties in terms of stability, light energy dissipation, and toxicity. Moreover, some representative compounds were included in final sunscreen formulations and a relevant solar protection factor boost was measured. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational Decision Making as Performative Praxis: Explaining Rationality's Éternel Retour

OpenAIRE

Cabantous, L.; Gond, J-P.

2011-01-01

Organizational theorists built their knowledge of decision making through a progressive critique of rational choice theory. Their positioning towards rationality, however, is at odds with the observation of rationality persistence in organizational life. This paper addresses this paradox. It proposes a new perspective on rationality that allows the theorizing of the production of rational decisions by organizations. To account for rationality's éternel retour, we approach rational decision ma...

Rational Design of a Green-Light-Mediated Unimolecular Platform for Fast Switchable Acidic Sensing.

Science.gov (United States)

Zhou, Yunyun; Zou, Qi; Qiu, Jing; Wang, Linjun; Zhu, Liangliang

2018-02-01

A controllable sensing ability strongly connects to complex and precise events in diagnosis and treatment. However, imposing visible light into the molecular-scale mediation of sensing processes is restricted by the lack of structural relevance. To address this critical challenge, we present the rational design, synthesis, and in vitro studies of a novel cyanostyryl-modified azulene system for green-light-mediated fast switchable acidic sensing. The advantageous features of the design include a highly efficient green-light-driven Z/E-isomerization (a quantum yield up to 61.3%) for fast erasing chromatic and luminescent expressions and a superior compatibility with control of ratiometric protonation. Significantly, these merits of the design enable the development of a microfluidic system to perform a green-light-mediated reusable sensing function toward a gastric acid analyte in a miniaturized platform. The results may provide new insights for building future integrated green materials.

Molecular and macro-scale analysis of enzyme-crosslinked silk hydrogels for rational biomaterial design.

Science.gov (United States)

McGill, Meghan; Coburn, Jeannine M; Partlow, Benjamin P; Mu, Xuan; Kaplan, David L

2017-11-01

Silk fibroin-based hydrogels have exciting applications in tissue engineering and therapeutic molecule delivery; however, their utility is dependent on their diffusive properties. The present study describes a molecular and macro-scale investigation of enzymatically-crosslinked silk fibroin hydrogels, and demonstrates that these systems have tunable crosslink density and diffusivity. We developed a liquid chromatography tandem mass spectroscopy (LC-MS/MS) method to assess the quantity and order of covalent tyrosine crosslinks in the hydrogels. This analysis revealed between 28 and 56% conversion of tyrosine to dityrosine, which was dependent on the silk concentration and reactant concentration. The crosslink density was then correlated with storage modulus, revealing that both crosslinking and protein concentration influenced the mechanical properties of the hydrogels. The diffusive properties of the bulk material were studied by fluorescence recovery after photobleaching (FRAP), which revealed a non-linear relationship between silk concentration and diffusivity. As a result of this work, a model for synthesizing hydrogels with known crosslink densities and diffusive properties has been established, enabling the rational design of silk hydrogels for biomedical applications. Hydrogels from naturally-derived silk polymers offer versitile opportunities in the biomedical field, however, their design has largely been an empirical process. We present a fundamental study of the crosslink density, storage modulus, and diffusion behavior of enzymatically-crosslinked silk hydrogels to better inform scaffold design. These studies revealed unexpected non-linear trends in the crosslink density and diffusivity of silk hydrogels with respect to protein concentration and crosslink reagent concentration. This work demonstrates the tunable diffusivity and crosslinking in silk fibroin hydrogels, and enables the rational design of biomaterials. Further, the characterization methods

Rational design of carbon and TiO2 assembly materials: covered or strewn, which is better for photocatalysis?

Science.gov (United States)

Cui, Guan-wei; Wang, Wei-liang; Ma, Ming-yue; Zhang, Ming; Xia, Xin-yuan; Han, Feng-yun; Shi, Xi-feng; Zhao, Ying-qiang; Dong, Yu-bin; Tang, Bo

2013-07-21

The rational design of carbonaceous hybrid nanostructures is very important for obtaining high photoactivity. TiO2 particles strewn with an optimal quantity of carbon nanodots have a much higher photoactivity than that of TiO2 covered with a carbon layer, showing the importance of carbon morphology in the photocatalysis of carbonaceous hybrid nanostructures.

Laccase engineering: from rational design to directed evolution.

Science.gov (United States)

Mate, Diana M; Alcalde, Miguel

2015-01-01

Laccases are multicopper oxidoreductases considered by many in the biotechonology field as the ultimate "green catalysts". This is mainly due to their broad substrate specificity and relative autonomy (they use molecular oxygen from air as an electron acceptor and they only produce water as by-product), making them suitable for a wide array of applications: biofuel production, bioremediation, organic synthesis, pulp biobleaching, textiles, the beverage and food industries, biosensor and biofuel cell development. Since the beginning of the 21st century, specific features of bacterial and fungal laccases have been exhaustively adapted in order to reach the industrial demands for high catalytic activity and stability in conjunction with reduced production cost. Among the goals established for laccase engineering, heterologous functional expression, improved activity and thermostability, tolerance to non-natural media (organic solvents, ionic liquids, physiological fluids) and resistance to different types of inhibitors are all challenges that have been met, while obtaining a more comprehensive understanding of laccase structure-function relationships. In this review we examine the most significant advances in this exciting research area in which rational, semi-rational and directed evolution approaches have been employed to ultimately convert laccases into high value-added biocatalysts. Copyright © 2014 Elsevier Inc. All rights reserved.

Rationality in Society

NARCIS (Netherlands)

Flache, Andreas; Dijkstra, Jacob; Wright, James D.

2015-01-01

Contemporary theories of rational behavior in human society augment the orthodox model of rationality both by adding various forms of bounded rationality and relaxing the assumptions of self-interest and materialistic preferences. This entry discusses how these extensions of the theory of rational

A Rational Approach to Rational Suicide.

Science.gov (United States)

Richman, Joseph

1992-01-01

Describes suicide as reaction to internal and external sources of stress and the impact of life events. Notes that, in the elderly, these situations are prevalent in many who are not suicidal. Contends that much more is written about rational suicide than its alternative (rational nonsuicide). Reviews reasons for this and suggests rational…

Rational design of competitive electrocatalysts for the oxygen reduction reaction in hydrogen fuel cells

Science.gov (United States)

Stolbov, Sergey; Alcántara Ortigoza, Marisol

2012-02-01

The large-scale application of one of the most promising clean and renewable sources of energy, hydrogen fuel cells, still awaits efficient and cost-effective electrocatalysts for the oxygen reduction reaction (ORR) occurring on the cathode. We demonstrate that truly rational design renders electrocatalysts possessing both qualities. By unifying the knowledge on surface morphology, composition, electronic structure and reactivity, we solve that sandwich-like structures are an excellent choice for optimization. Their constituting species couple synergistically yielding reaction-environment stability, cost-effectiveness and tunable reactivity. This cooperative-action concept enabled us to predict two advantageous ORR electrocatalysts. Density functional theory calculations of the reaction free-energy diagrams confirm that these materials are more active toward ORR than the so far best Pt-based catalysts. Our designing concept advances also a general approach for engineering materials in heterogeneous catalysis.

Geometric Rationalization for Freeform Architecture

KAUST Repository

Jiang, Caigui

2016-06-20

The emergence of freeform architecture provides interesting geometric challenges with regards to the design and manufacturing of large-scale structures. To design these architectural structures, we have to consider two types of constraints. First, aesthetic constraints are important because the buildings have to be visually impressive. Sec- ond, functional constraints are important for the performance of a building and its e cient construction. This thesis contributes to the area of architectural geometry. Specifically, we are interested in the geometric rationalization of freeform architec- ture with the goal of combining aesthetic and functional constraints and construction requirements. Aesthetic requirements typically come from designers and architects. To obtain visually pleasing structures, they favor smoothness of the building shape, but also smoothness of the visible patterns on the surface. Functional requirements typically come from the engineers involved in the construction process. For exam- ple, covering freeform structures using planar panels is much cheaper than using non-planar ones. Further, constructed buildings have to be stable and should not collapse. In this thesis, we explore the geometric rationalization of freeform archi- tecture using four specific example problems inspired by real life applications. We achieve our results by developing optimization algorithms and a theoretical study of the underlying geometrical structure of the problems. The four example problems are the following: (1) The design of shading and lighting systems which are torsion-free structures with planar beams based on quad meshes. They satisfy the functionality requirements of preventing light from going inside a building as shad- ing systems or reflecting light into a building as lighting systems. (2) The Design of freeform honeycomb structures that are constructed based on hex-dominant meshes with a planar beam mounted along each edge. The beams intersect without

Guidelines for Rational Cancer Therapeutics

Directory of Open Access Journals (Sweden)

Byunghee Yoo

2017-12-01

Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

Rational design of DNA sequences for nanotechnology, microarrays and molecular computers using Eulerian graphs.

Science.gov (United States)

Pancoska, Petr; Moravek, Zdenek; Moll, Ute M

2004-01-01

Nucleic acids are molecules of choice for both established and emerging nanoscale technologies. These technologies benefit from large functional densities of 'DNA processing elements' that can be readily manufactured. To achieve the desired functionality, polynucleotide sequences are currently designed by a process that involves tedious and laborious filtering of potential candidates against a series of requirements and parameters. Here, we present a complete novel methodology for the rapid rational design of large sets of DNA sequences. This method allows for the direct implementation of very complex and detailed requirements for the generated sequences, thus avoiding 'brute force' filtering. At the same time, these sequences have narrow distributions of melting temperatures. The molecular part of the design process can be done without computer assistance, using an efficient 'human engineering' approach by drawing a single blueprint graph that represents all generated sequences. Moreover, the method eliminates the necessity for extensive thermodynamic calculations. Melting temperature can be calculated only once (or not at all). In addition, the isostability of the sequences is independent of the selection of a particular set of thermodynamic parameters. Applications are presented for DNA sequence designs for microarrays, universal microarray zip sequences and electron transfer experiments.

Harvesting bioenergy with rationally designed complex functional materials

Science.gov (United States)

Kuang, Liangju

A key challenge in renewable energy is to capture, convert and store solar power with earth-abundant materials and environmentally benign technologies. The goal of this thesis is to develop rationally designed complex functional materials for bio-renewable energy applications. On one hand, photoconversion membrane proteins (MPs) are nature's nanoengineering feats for renewable energy management. Harnessing their functions in synthetic systems could help understand, predict, and ultimately control matter and energy at the nanoscale. This is particularly enticing in the post-genome era as recombinant or cell-free expression of many MPs with high yields becomes possible. However, the labile nature of lipid bilayers renders them unsuitable for use in a broad range of engineered systems. A knowledge gap exists about how to design robust synthetic nanomembranes as lipid-bilayer-mimics to support MP functions and how to direct hierarchical MP reconstitution into those membranes to form 2-D or 3-D ordered proteomembrane arrays. Our studies on proteorhodopsin (PR) and bacterial reaction center (BRC), the two light-harvesting MPs, reveal that a charge-interaction-directed reconstitution (CIDR) mechanism induces spontaneous reconstitution of detergent-solubilized MPs into various amphiphilic block copolymer membranes, many of which have far superior stability than lipid bilayers. Our preliminary data also suggest MPs are not enslaved by the biological membranes they derive from; rather, the chemically nonspecific material properties of MP-supporting membranes may act as allosteric regulators. Versatile chemical designs are possible to modulate the conformational energetics of MPs, hence their transport performance in synthetic systems. On the other hand, microalgae are widely regarded as a sustainable feedstock for biofuel production. Microalgae-derived biofuels have not been commercialized yet because current technologies for microalgae dewatering add a huge cost to the

A rational and economical seismic design of beam columns in steel frames

International Nuclear Information System (INIS)

Gupta, A.K.; Fang, S.-J.; Chu, S.-L.

1977-01-01

In the present study, a new rational procedure is used in which simultaneous variation in various response quantities is predicted. For designing the beam column section according to the AISC Manual of Steel Construction, one has to know the values of the axial force, the moment about x and y axes at the two ends, and the maximum moments about x, y axes near the center of the beam column, which altogether constitutes seven response quantities of interest for each beam column element. Normally, seven equivalent modes will be required to represent the response. However, by designing the two end sections and the intermediate section independently one can consider three equivalent modes for each section, thus simplifying the problem a great deal. An existing computer program is used for the implementation of the proposed method. Results for typical example problems have been presented. It is shown that savings up to 42% in the steel cross-sectional area can be obtained depending upon combination of various forces and moments. The propposed method is 'exact' within the existing assumptions of the SRSS (square root of the sum of the squares) or the double sum method

Rational design of botulinum neurotoxin A1 mutants with improved oxidative stability.

Science.gov (United States)

López de la Paz, Manuela; Scheps, Daniel; Jurk, Marcel; Hofmann, Fred; Frevert, Jürgen

2018-06-01

Botulinum neurotoxins (BoNTs) are the most potent toxic proteins to mankind known but applied in low doses trigger a localized muscle paralysis that is beneficial for the therapy of several neurological disorders and aesthetic treatment. The paralytic effect is generated by the enzymatic activity of the light chain (LC) that cleaves specifically one of the SNARE proteins responsible for neurotransmitter exocytosis. The activity of the LC in a BoNT-containing therapeutic can be compromised by denaturing agents present during manufacturing and/or in the cell. Stabilization of the LC by reducing vulnerability towards denaturants would thus be advantageous for the development of BoNT-based therapeutics. In this work, we focused on increasing the stability of LC of BoNT/A1 (LC/A1) towards oxidative stress. We tackled this task by rational design of mutations at cysteine and methionine LC/A1 sites. Designed mutants showed improved oxidative stability in vitro and equipotency to wildtype toxin in vivo. Our results suggest that suitable modification of the catalytic domain can lead to more stable BoNTs without impairing their therapeutic efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease

Science.gov (United States)

Gorzelic, P.; Schiff, S. J.; Sinha, A.

2013-04-01

Objective. To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). Approach. A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. Main Results. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Significance. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

Rational design of peptide affinity ligands for the purification of therapeutic enzymes.

Science.gov (United States)

Trasatti, John P; Woo, James; Ladiwala, Asif; Cramer, Steven; Karande, Pankaj

2018-04-25

Non-mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof-of-concept for developing affinity peptide-based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Bioinformatics and multiepitope DNA immunization to design rational snake antivenom.

Directory of Open Access Journals (Sweden)

Simon C Wagstaff

2006-06-01

Full Text Available Snake venom is a potentially lethal and complex mixture of hundreds of functionally diverse proteins that are difficult to purify and hence difficult to characterize. These difficulties have inhibited the development of toxin-targeted therapy, and conventional antivenom is still generated from the sera of horses or sheep immunized with whole venom. Although life-saving, antivenoms contain an immunoglobulin pool of unknown antigen specificity and known redundancy, which necessitates the delivery of large volumes of heterologous immunoglobulin to the envenomed victim, thus increasing the risk of anaphylactoid and serum sickness adverse effects. Here we exploit recent molecular sequence analysis and DNA immunization tools to design more rational toxin-targeted antivenom.We developed a novel bioinformatic strategy that identified sequences encoding immunogenic and structurally significant epitopes from an expressed sequence tag database of a venom gland cDNA library of Echis ocellatus, the most medically important viper in Africa. Focusing upon snake venom metalloproteinases (SVMPs that are responsible for the severe and frequently lethal hemorrhage in envenomed victims, we identified seven epitopes that we predicted would be represented in all isomers of this multimeric toxin and that we engineered into a single synthetic multiepitope DNA immunogen (epitope string. We compared the specificity and toxin-neutralizing efficacy of antiserum raised against the string to antisera raised against a single SVMP toxin (or domains or antiserum raised by conventional (whole venom immunization protocols. The SVMP string antiserum, as predicted in silico, contained antibody specificities to numerous SVMPs in E. ocellatus venom and venoms of several other African vipers. More significantly, the antiserum cross-specifically neutralized hemorrhage induced by E. ocellatus and Cerastes cerastes cerastes venoms.These data provide valuable sequence and structure

The influence of live tularemia vaccine on counter-suppression of lymphocytes and end-results of combined treatment of endometrial carcinoma

International Nuclear Information System (INIS)

Adamyan, R.T.; Markosyan, K.M.

2001-01-01

Randomized investigation in two patients groups suffered with endometrial carcinoma (EC) of 1-2 and 3-4 stages (FIGO, 1977) is performed. Effect of blood lymphocytes contrasuppression before and after combined treatment (operation + radiotherapy) is studied as well as delayed therapy results. A part of patients was immunized with tularemia live vaccine (TLV) before treatment. It is shown that the delayed combined treatment results in EC patients correlate with contrasuppression effect revealed in them before therapy. It is concluded that the index of contrasuppression effect revealability and delayed results of combined therapy in EC patients immunized with TLV before therapy have an expressed tendency to improving as compared to nonimmunized patients of the same stages [ru

Pragmatics & rationality.

OpenAIRE

Allott, N. E.

2007-01-01

This thesis is about the reconciliation of realistic views of rationality with inferential-intentional theories of communication. Grice (1957 1975) argued that working out what a speaker meant by an utterance is a matter of inferring the speaker's intentions on the presumption that she is acting rationally. This is abductive inference: inference to the best explanation for the utterance. Thus an utterance both rationalises and causes the interpretation the hearer constructs. Human rationality...

Baseline rationing

DEFF Research Database (Denmark)

Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

The standard problem of adjudicating conflicting claims describes a situation in which a given amount of a divisible good has to be allocated among agents who hold claims against it exceeding the available amount. This paper considers more general rationing problems in which, in addition to claims...... to international protocols for the reduction of greenhouse emissions, or water distribution in drought periods. We define a family of allocation methods for such general rationing problems - called baseline rationing rules - and provide an axiomatic characterization for it. Any baseline rationing rule within...... the family is associated with a standard rule and we show that if the latter obeys some properties reflecting principles of impartiality, priority and solidarity, the former obeys them too....

Rationing with baselines

DEFF Research Database (Denmark)

Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

2013-01-01

We introduce a new operator for general rationing problems in which, besides conflicting claims, individual baselines play an important role in the rationing process. The operator builds onto ideas of composition, which are not only frequent in rationing, but also in related problems...... such as bargaining, choice, and queuing. We characterize the operator and show how it preserves some standard axioms in the literature on rationing. We also relate it to recent contributions in such literature....

Protein engineering of Bacillus acidopullulyticus pullulanase for enhanced thermostability using in silico data driven rational design methods.

Science.gov (United States)

Chen, Ana; Li, Yamei; Nie, Jianqi; McNeil, Brian; Jeffrey, Laura; Yang, Yankun; Bai, Zhonghu

2015-10-01

Thermostability has been considered as a requirement in the starch processing industry to maintain high catalytic activity of pullulanase under high temperatures. Four data driven rational design methods (B-FITTER, proline theory, PoPMuSiC-2.1, and sequence consensus approach) were adopted to identify the key residue potential links with thermostability, and 39 residues of Bacillus acidopullulyticus pullulanase were chosen as mutagenesis targets. Single mutagenesis followed by combined mutagenesis resulted in the best mutant E518I-S662R-Q706P, which exhibited an 11-fold half-life improvement at 60 °C and a 9.5 °C increase in Tm. The optimum temperature of the mutant increased from 60 to 65 °C. Fluorescence spectroscopy results demonstrated that the tertiary structure of the mutant enzyme was more compact than that of the wild-type (WT) enzyme. Structural change analysis revealed that the increase in thermostability was most probably caused by a combination of lower stability free-energy and higher hydrophobicity of E518I, more hydrogen bonds of S662R, and higher rigidity of Q706P compared with the WT. The findings demonstrated the effectiveness of combined data-driven rational design approaches in engineering an industrial enzyme to improve thermostability. Copyright © 2015 Elsevier Inc. All rights reserved.

Rational design of metal-organic electronic devices: A computational perspective

Science.gov (United States)

Chilukuri, Bhaskar

engineers to choose the appropriate metal electrodes considering the chemical interactions at the interface. Additionally, the calculations performed on the interfaces provided valuable insight into binding energies, charge redistribution, change in the energy levels, dipole formation, etc., which are important parameters to consider while fabricating an electronic device. The research described in this dissertation highlights the application of unique computational modeling methods at different levels of theory to guide the experimental chemists and device engineers toward a rational design of transition metal based electronic devices with low cost and high performance.

Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances.

Science.gov (United States)

Vicente, Tiago; Mota, José P B; Peixoto, Cristina; Alves, Paula M; Carrondo, Manuel J T

2011-01-01

The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. Copyright © 2011 Elsevier Inc. All rights reserved.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

Science.gov (United States)

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

Rational design of hypoallergens applied to the major cat allergen Fel d 1.

Science.gov (United States)

Saarne, T; Kaiser, L; Grönlund, H; Rasool, O; Gafvelin, G; van Hage-Hamsten, M

2005-05-01

Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.

Personal Autonomy and Rational Suicide.

Science.gov (United States)

Webber, May A.; Shulman, Ernest

That certain suicides (which can be designated as rational) ought not to be interfered with is closely tied to the notion of the "right to autonomy." Specifically it is because the individual in question has this right that interference is prohibited. A proper understanding of the right to autonomy, while essential to understanding why…

Inaugurating Rationalization: Three Field Studies Find Increased Rationalization When Anticipated Realities Become Current.

Science.gov (United States)

Laurin, Kristin

2018-04-01

People will often rationalize the status quo, reconstruing it in an exaggeratedly positive light. They will even rationalize the status quo they anticipate, emphasizing the upsides and minimizing the downsides of sociopolitical realities they expect to take effect. Drawing on recent findings on the psychological triggers of rationalization, I present results from three field studies, one of which was preregistered, testing the hypothesis that an anticipated reality becoming current triggers an observable boost in people's rationalizations. San Franciscans rationalized a ban on plastic water bottles, Ontarians rationalized a targeted smoking ban, and Americans rationalized the presidency of Donald Trump, more in the days immediately after these realities became current compared with the days immediately before. Additional findings show evidence for a mechanism underlying these behaviors and rule out alternative accounts. These findings carry implications for scholarship on rationalization, for understanding protest behavior, and for policymakers.

Realization theory for rational systems: Minimal rational realizations

NARCIS (Netherlands)

J. Nemcová (Jana); J.H. van Schuppen (Jan)

2010-01-01

htmlabstractThe study of realizations of response maps is a topic of control and system theory. Realization theory is used in system identification and control synthesis. A minimal rational realization of a given response map p is a rational realization of p such that the dimension of its state

The Boundedly Rational User Equilibrium : A parametric analysis with application to the Network Design Problem

NARCIS (Netherlands)

Eikenbroek, Oskar Adriaan Louis; Still, Georg J.; van Berkum, E.C.; Kern, Walter

In this paper, we study a static traffic assignment that accounts for the boundedly rational route choice behavior of travelers. This assignment induces uncertainties to the ex-ante evaluation of a policy measure: the boundedly rational assignment is non-unique and the indifference band is an

Elaborating and Making Rational Decisions in Designing Process Operations of a Group of Holes

Directory of Open Access Journals (Sweden)

A. I. Solov'ev

2015-01-01

Full Text Available To manufacture engineering products are used expensive multi-purpose CNC machines with five operated coordinates, allowing a single setup of the work-piece to process a group of holes in the housing part from all sides.Because of the haphazard arrangement of a large number of holes available in the space it is difficult to ensure the effective use of these machines.Onsite operational research, conducted on six CNC GS-500 models, involved actual observations and time measurements during 15 working shifts, processing of observation results, and calculations of equipment performance parameters such as machine utilization rate, arrangement and changeover time loss, and real output. Time loss (downtime because of arrangement amounted 44.52%, while that of due to changeover was 20.1% of the total downtime value. These downtimes hide irrational design solutions concerning the engineering process and a large number of changeovers for a new operation to process a group of the specified work-pieces.It is found that to reduce the changeover downtimes it is necessary to increase, first of all, the average number of single tool travels per one setup in generalized characteristics of a group of the work-pieces. That means to increase a changeover concentration of processing within a single operation, as well as to choose rational values for machining a batch of the work-pieces. Under study conditions, it is, at least. 20-50 pieces.To implement a development of the principle of increasing concentration of the processing changeovers it is advised to apply the developed mathematical models, algorithms, and programs that can be used, as modules or their parts, in computer-aided design (CAD systems. This allows a 3-5 times reduction in time to find the rational option of the work-piece position on the machine work surface when developing a process technology, a review and an analysis of more than the usual number of such possible options. It also improves the

The Effect of Soy Sauce Waste in Ration on Performance of Mojosari Duck

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G. A. A. Larasati

2017-06-01

Full Text Available The purpose of study was to determined the effect of soy sauce waste in ration in the ration on the performance of Mojosari duck. The materials used were 240 of Mojosari which are 20 weeks olds with average body weight 1,385.0 ± 130.85 grams (CV = 9.44%. Feed ingredients used were, rice bran, soybean meal, yellow corn, fish meal, pollard and premix. The design that used was Completely Randomized Design (CRD with 4 treatments and 6 replications.The treatment applied soy sauce waste at level 5, 7,5 and 10%. The parameters observed were consumption, egg production, feed conversion. The data were analyzed by analysis of variance with F test. The results showed that soy sauce waste did not effected on performance (consumption of ration, egg production, ration conversion of Mojosari duck. The conclusion of this research is soy sauce waste be used as feed stuff of Mojosari duck ration until level 10%.

Many faces of rationality: Implications of the great rationality debate for clinical decision‐making

Science.gov (United States)

Elqayam, Shira

2017-01-01

Abstract Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people “should” or “ought to” make their decisions) and descriptive theories of decision‐making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence‐based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision‐making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret‐based rationality, pragmatic/substantive rationality, and meta‐rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is “rational” behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context‐poor situations, such as policy decision‐making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision�

Rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid

DEFF Research Database (Denmark)

Bunch, Lennart; Liljefors, Tommy; Greenwood, Jeremy R

2003-01-01

conformationally restricted (S)-glutamic acid (Glu) analogue intended as a mimic of the folded Glu conformation. The synthesis of 1 was completed in its racemic form in eight steps from commercially available starting materials. As a key step, the first facially selective hydroboration of a 5-methylidene[2......The design and synthesis of conformationally restricted analogues of alpha-amino acids is an often used strategy in medicinal chemistry research. Here we present the rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid (1), a novel...... studies on native 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) (IC(50) > 300 microM, [(3)H]AMPA) or kainic acid (IC(50) > 160 microM, [(3)H]kainic acid) receptors nor in binding studies on the cloned iGluR5,6 subtypes (IC(50) > 300 microM, [(3)H]kainic acid)....

Rational design of single-molecule magnets: a supramolecular approach.

Science.gov (United States)

Glaser, Thorsten

2011-01-07

Since the discovery that Mn(12)OAc acts as a single-molecule magnet (SMM), an increasing number of transition metal complexes have been demonstrated to behave as SMMs. The signature of a SMM is a slow relaxation of the magnetization at low temperatures accompanied by a magnetic hysteresis. The origin of SMM behaviour is the existence of an appreciable thermal barrier U for spin-reversal called magnetic anisotropy barrier which is related to the combination of a large total spin ground state (S(t)) and an easy-axis magnetic anisotropy. The extensive research on Mn(12)OAc and other SMMs has established more prerequisites for a rational development of new SMMs besides the high-spin ground state and the magnetic anisotropy: the symmetry should be at least C(3) to minimize the quantum tunneling of the magnetization through the anisotropy barrier but lower than cubic to avoid the cancellation of the local anisotropies upon projection onto the spin ground state. Based on these prerequisites, we have designed the ligand triplesalen which combines the phloroglucinol bridging unit for high spin ground states by the spin-polarization mechanism with a salen-like ligand environment for single-site magnetic anisotropies by a strong tetragonal ligand field. The C(3) symmetric, trinuclear complexes of the triplesalen ligand (talen(t-Bu(2)))(6-) exhibit a strong ligand folding resulting in an overall bowl-shaped molecular structure. This ligand folding preorganizes the axial coordination sites of the metal salen subunits for the complementary binding of three facial nitrogen atoms of a hexacyanometallate unit. This leads to a high driving force for the formation of heptanuclear complexes [M(t)(6)M(c)](n+) by the assembly of three molecular building blocks. Attractive van der Waals interactions of the tert-butyl phenyl units of two triplesalen trinuclear building blocks increase the driving force. In this respect, we have been able to synthesize the isostructural series [Mn(III)(6

Many faces of rationality: Implications of the great rationality debate for clinical decision-making.

Science.gov (United States)

Djulbegovic, Benjamin; Elqayam, Shira

2017-10-01

Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models. Rationality is typically classified under umbrella of normative (addressing the question how people "should" or "ought to" make their decisions) and descriptive theories of decision-making (which portray how people actually make their decisions). Normative theories of rational thought of relevance to medicine include epistemic theories that direct practice of evidence-based medicine and expected utility theory, which provides the basis for widely used clinical decision analyses. Descriptive theories of rationality of direct relevance to medical decision-making include bounded rationality, argumentative theory of reasoning, adaptive rationality, dual processing model of rationality, regret-based rationality, pragmatic/substantive rationality, and meta-rationality. For the first time, we provide a review of wide range of theories and models of rationality. We showed that what is "rational" behaviour under one rationality theory may be irrational under the other theory. We also showed that context is of paramount importance to rationality and that no one model of rationality can possibly fit all contexts. We suggest that in context-poor situations, such as policy decision-making, normative theories based on expected utility informed by best research evidence may provide the optimal approach to medical decision-making, whereas in the context

Rationality and drug use: an experimental approach.

Science.gov (United States)

Blondel, Serge; Lohéac, Youenn; Rinaudo, Stéphane

2007-05-01

In rational addiction theory, higher discount rates encourage drug use. We test this hypothesis in the general framework of rationality and behaviour under risk. We do so using an experimental design with real monetary incentives. The decisions of 34 drug addicts are compared with those of a control group. The decisions of drug users (DU) are not any less consistent with standard theories of behaviour over time and under risk. Further, there is no difference in the estimated discount rate between drug users and the control group, but the former do appear to be more risk-seeking.

Adolescent rationality.

Science.gov (United States)

Moshman, David

2013-01-01

Adolescents are commonly seen as irrational, a position supported to varying degrees by many developmentalists, who often appeal to recent research on adolescent brains. Careful review of relevant evidence, however, shows that (1) adults are less rational than is generally assumed, (2) adolescents (and adults) are categorically different from children with respect to the attainment of advanced levels of rationality and psychological functioning, and (3) adolescents and adults do not differ categorically from each other with respect to any rational competencies, irrational tendencies, brain structures, or neurological functioning. Development often continues in adolescence and beyond but categorical claims about adolescents as distinct from adults cannot be justified. A review of U.S. Supreme Court decisions concerning intellectual freedom, reproductive freedom, and criminal responsibility shows ongoing ambivalence and confusion about the rationality of adolescents. Developmental theory and research suggest that adolescents should be conceptualized as young adults, not immature brains, with important implications for their roles, rights, and responsibilities.

Love and rationality: on some possible rational effects of love

Directory of Open Access Journals (Sweden)

Gustavo Ortiz-Millán

Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.

Rational design of highly potent HIV-1 fusion inhibitory proteins: Implication for developing antiviral therapeutics

International Nuclear Information System (INIS)

Ni Ling; Gao, George F.; Tien Po

2005-01-01

Recombinant protein containing one heptad-repeat 1 (HR1) segment and one HR2 segment of the HIV-1 gp41 (HR1-HR2) has been shown to fold into thermally stable six-helix bundle, representing the fusogenic core of gp41. In this study, we have used the fusogenic core as a scaffold to design HIV-1 fusion inhibitory proteins by linking another HR1 to the C terminus of HR1-HR2 (HR121) or additional HR2 to the N terminus of HR1-HR2 (HR212). Both recombinant proteins could be abundantly and solubly expressed and easily purified, exhibiting high stability and potent inhibitory activity on HIV-1 fusion with IC 50 values of 16.2 ± 2.8 and 2.8 ± 0.63 nM, respectively. These suggest that these rationally designed proteins can be further developed as novel anti-HIV-1 therapeutics

CONTRIBUTIONS TO RATIONAL APPROXIMATION,

Science.gov (United States)

Some of the key results of linear Chebyshev approximation theory are extended to generalized rational functions. Prominent among these is Haar’s...linear theorem which yields necessary and sufficient conditions for uniqueness. Some new results in the classic field of rational function Chebyshev...Furthermore a Weierstrass type theorem is proven for rational Chebyshev approximation. A characterization theorem for rational trigonometric Chebyshev approximation in terms of sign alternation is developed. (Author)

Rational points, rational curves, and entire holomorphic curves on projective varieties

CERN Document Server

Gasbarri, Carlo; Roth, Mike; Tschinkel, Yuri

2015-01-01

This volume contains papers from the Short Thematic Program on Rational Points, Rational Curves, and Entire Holomorphic Curves and Algebraic Varieties, held from June 3-28, 2013, at the Centre de Recherches Mathématiques, Université de Montréal, Québec, Canada. The program was dedicated to the study of subtle interconnections between geometric and arithmetic properties of higher-dimensional algebraic varieties. The main areas of the program were, among others, proving density of rational points in Zariski or analytic topology on special varieties, understanding global geometric properties of rationally connected varieties, as well as connections between geometry and algebraic dynamics exploring new geometric techniques in Diophantine approximation.

Application of 3D-QSAR in the rational design of receptor ligands and enzyme inhibitors.

Science.gov (United States)

Mor, Marco; Rivara, Silvia; Lodola, Alessio; Lorenzi, Simone; Bordi, Fabrizio; Plazzi, Pier Vincenzo; Spadoni, Gilberto; Bedini, Annalida; Duranti, Andrea; Tontini, Andrea; Tarzia, Giorgio

2005-11-01

Quantitative structure-activity relationships (QSARs) are frequently employed in medicinal chemistry projects, both to rationalize structure-activity relationships (SAR) for known series of compounds and to help in the design of innovative structures endowed with desired pharmacological actions. As a difference from the so-called structure-based drug design tools, they do not require the knowledge of the biological target structure, but are based on the comparison of drug structural features, thus being defined ligand-based drug design tools. In the 3D-QSAR approach, structural descriptors are calculated from molecular models of the ligands, as interaction fields within a three-dimensional (3D) lattice of points surrounding the ligand structure. These descriptors are collected in a large X matrix, which is submitted to multivariate analysis to look for correlations with biological activity. Like for other QSARs, the reliability and usefulness of the correlation models depends on the validity of the assumptions and on the quality of the data. A careful selection of compounds and pharmacological data can improve the application of 3D-QSAR analysis in drug design. Some examples of the application of CoMFA and CoMSIA approaches to the SAR study and design of receptor or enzyme ligands is described, pointing the attention to the fields of melatonin receptor ligands and FAAH inhibitors.

Irrational Rationality of Terrorism

Directory of Open Access Journals (Sweden)

Robert Nalbandov

2013-12-01

Full Text Available The present article deals with the ontological problem of applying the rational choice frameworks to the study of terrorism. It testing the application of the rational choice to the “old” (before the end of the Cold War and the “new” (after the end of the Cold War terrorisms. It starts with analyzing the fundamentals of rationality and applies it at two levels: the individual (actors and group (collective via two outlooks: tactical (short-term and strategic (long-term. The main argument of the article is that while the “old” terrorism can be explained by the rational choice theory its “new” version represents a substantial departure from rationality.

Appendix to rationally designing of machine tools for example of universal lathe

Directory of Open Access Journals (Sweden)

Pejović Branko B.

2015-01-01

Full Text Available In this paper, for the universal machine tool for turning and function of the thrust of the cutting speed for blasting area efficiency and stability of the tool and sectional filings. These dependencies were used to determine the main characteristics of the optimal and maximum operating power equipment. Based on this, an analysis of the increase in operating power equipment typical cases in order to adapt to the new needs of exploitation properties and improve productivity. Using the previous analysis, it was determined the best solution in terms of the rational design of machines, by ensuring the simultaneous use of the main features on the basis of increase in speed with the use of tools and higher stability. In order to better display problems, an analysis of the appropriate diagrams P-V and V-D. On a typical example of the manufacturing practice at the end of the work, we demonstrate improvement of exploitation characteristics of a universal machine through appropriate calculations in terms of new needs adjustment feature, where it is expected that the reconstruction of the smallest machines.

Lying for Strategic Advantage: Rational and Boundedly Rational Misrepresentation of Intentions

OpenAIRE

Crawford, Vincent P.

2001-01-01

Starting from Hendricks and McAfee's (2000) example of the Allies' decision to feint at Calais and attack at Normandy on D-Day, this paper models misrepresentation of intentions to competitors or enemies. Allowing for the possibility of bounded strategic rationality and rational players' responses to it yields a sensible account of lying via costless, noiseless messages. In many cases the model has generically unique pure-strategy sequential equilibria, in which rational players exploit bound...

Determinants of Actor Rationality

DEFF Research Database (Denmark)

Ellegaard, Chris

Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer-supplier...... relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

Two Concepts of Rationality

Directory of Open Access Journals (Sweden)

Danny Frederick

2010-02-01

Full Text Available The dominant tradition in Western philosophy sees rationality as dictating. Thus rationality may require that we believe the best explanation and simple conceptual truths and that we infer in accordance with evident rules of inference. I argue that, given what we know about the growth of knowledge, this authoritarian concept of rationality leads to absurdities and should be abandoned. I then outline a libertarian concept of rationality, derived from Popper, which eschews the dictates and which sees a rational agent as one who questions, criticises, conjectures and experiments. I argue that, while the libertarian approach escapes the absurdities of the authoritarian, it requires two significant developments and an important clarification to be made fully consistent with itself.

Rationality and institutions : an inquiry into the normative implications of rational choice theory

OpenAIRE

Engelen, Bart

2007-01-01

I aim to analyze in this dissertation what a desirable basic institutional structure looks like from the perspective of rationality. While the main topic is thus normative in nature, I start by clarifying in the first part what the notion of rationality exactly entails. I do so by focusing explicitly on the economic conception of rationality, according to which a rational individual is motivated to serve his self-interest on the basis of cost-benefit calculations. Such a Homo Economicus is ch...

Rational Behavior Training: A Seven Lesson Sequence for Teaching Rational Behavior Skills to Students with Social and Emotional Disabilities.

Science.gov (United States)

Patton, Patricia Lucey

This seven lesson curriculum sequence is designed to help teachers teach principles of Rational Behavior Training (RBT) which targets thinking behaviors, feeling behaviors, and behavioral responses to the environment. The program is appropriate for students with social and emotional disabilities and also develops reading, writing, spelling,…

Rationing medical education.

African Journals Online (AJOL)

This paper discussed the pros and cons of the application of rationing to medical education and the different ... Different types of rationing exist in healthcare professional education. ... state-of-the-art resources, technology and tutors con-.

Rationality problem for algebraic tori

CERN Document Server

Hoshi, Akinari

2017-01-01

The authors give the complete stably rational classification of algebraic tori of dimensions 4 and 5 over a field k. In particular, the stably rational classification of norm one tori whose Chevalley modules are of rank 4 and 5 is given. The authors show that there exist exactly 487 (resp. 7, resp. 216) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 4, and there exist exactly 3051 (resp. 25, resp. 3003) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 5. The authors make a procedure to compute a flabby resolution of a G-lattice effectively by using the computer algebra system GAP. Some algorithms may determine whether the flabby class of a G-lattice is invertible (resp. zero) or not. Using the algorithms, the suthors determine all the flabby and coflabby G-lattices of rank up to 6 and verify that they are stably permutation. The authors also show that the Krull-Schmidt theorem for G-...

Rational Approximations to Rational Models: Alternative Algorithms for Category Learning

Science.gov (United States)

Sanborn, Adam N.; Griffiths, Thomas L.; Navarro, Daniel J.

2010-01-01

Rational models of cognition typically consider the abstract computational problems posed by the environment, assuming that people are capable of optimally solving those problems. This differs from more traditional formal models of cognition, which focus on the psychological processes responsible for behavior. A basic challenge for rational models…

Adsorption of rationally designed "surf-tides" to a liquid-crystal interface.

Science.gov (United States)

Badami, Joseph V; Bernstein, Chaim; Maldarelli, Charles; Tu, Raymond S

2015-09-07

The interfacial adsorption of proteins in surfactant laden systems occurs both in nature and industrial processing, yet much of the fundamental behavior behind these systems is still not well understood. We report the development of a system that monitors optical transitions of a liquid-crystalline/aqueous interface to examine the dynamics of adsorption of two rationally designed model peptide molecules. The two molecules synthesized in this study were both designed to become surface-active upon folding and contain the same net charge of +3, but one of the peptides, K-2.5, has its three charges separated by 2.5 amino acids as compared to K-6.0, which has its three charges separated by 6 amino acids. Our study examines the roles that surfactant adsorption, peptide charge distribution and secondary structure have on the relative adsorption dynamics of these two models peptides onto a fluid/fluid interface. Using the optical detection of molecular adsorption and image analysis of these events, we obtain quantitative information about the dynamics as a function of the charge spacing and initial peptide concentration. We show that both peptides initially follow a diffusion-limited adsorption model onto the interface. Additionally, our results suggest that the K-6.0 peptides demonstrate enhanced adsorption kinetics, where the enhanced rates are a consequence of the well-folded adsorbed state and spatial distribution on the surface. These findings provide further insights into the role that charge spacing has on secondary structure and subsequently the dynamics of adsorption, while developing a versatile system capable of extracting quantitative information from a simple inexpensive optical system.

METHODOLOGICAL ASPECTS OF RATIONAL DESIGN FORMATION OF INFRASTRUCTURE OF AGRARIAN SECTOR OF UKRAINE

Directory of Open Access Journals (Sweden)

Ivan Korchynskyy

2016-11-01

Full Text Available Methodological aspects of formation of rational design of infrastructure of agrarian sector of Ukraine on the basis of the institutional approach and laws of architectonics are examined. It is shown that the agrarian sector of Ukraine is a complex socio-economic system, the formation and development of which is in the process of market transformation what is caused by institutional influences. In general the process of relations institutionalization imply their formalization and standardization, in other case the subject of public life could not predict the actions of other entities associated with him and ensure their cooperation. One of the specific characteristic of human society is formed institutional system that regulates behaviour. In the article the factors of influence on the conduct of being in charge subjects are considered in the conditions of development of market economy. The special attention is spared the institutional factors of the economy growing. Methodology. The meaning of “agricultural field” and “infrastructure” and their mutual consistency is classified. As the scientific method, the institutional approach of principles of architectonics has been used, which allowed to justify the creation of a rational approach to the design of infrastructure in agrarian sector as a whole on the basis, relation and interdependence of its elements, based on the fundamental laws of architectonics (law of equilibrium, law of the golden mean structuring. The article demonstrates a necessary of the choice of a theory of institutionalism as the main methodological basis for the study of the process of innovation development of economic system of Ukraine. It is determined that the inefficient activities of institutions in Ukraine are the main cause of the low level of innovation, which has a negative impact on the development of the economy as a whole. Results. Research points on new aspects of infrastructure as a part of the entire

Rational design of protamine nanocapsules as antigen delivery carriers.

Science.gov (United States)

González-Aramundiz, José Vicente; Presas, Elena; Dalmau-Mena, Inmaculada; Martínez-Pulgarín, Susana; Alonso, Covadonga; Escribano, José M; Alonso, María J; Csaba, Noemi Stefánia

2017-01-10

Current challenges in global immunization indicate the demand for new delivery strategies, which could be applied to the development of new vaccines against emerging diseases, as well as to improve safety and efficacy of currently existing vaccine formulations. Here, we report a novel antigen nanocarrier consisting of an oily core and a protamine shell, further stabilized with pegylated surfactants. These nanocarriers, named protamine nanocapsules, were rationally designed to promote the intracellular delivery of antigens to immunocompetent cells and to trigger an efficient and long-lasting immune response. Protamine nanocapsules have nanometric size, positive zeta potential and high association capacity for H1N1 influenza hemagglutinin, a protein that was used here as a model antigen. The new formulation shows an attractive stability profile both, as an aqueous suspension or a freeze-dried powder formulation. In vitro studies showed that protamine nanocapsules were efficiently internalized by macrophages without eliciting significant toxicity. In vivo studies indicate that antigen-loaded nanocapsules trigger immune responses comparable to those achieved with alum, even when using significantly lower antigen doses, thus indicating their adjuvant properties. These promising in vivo data, alongside with their versatility for the loading of different antigens and oily immunomodulators and their excellent stability profile, make these nanocapsules a promising platform for the delivery of antigens. Protamine sulphate (PubChem SID: 7849283), Sodium Cholate (PubChem CID: 23668194), Miglyol (PubChem CID: 53471835), α tocopherol (PubChem CID: 14985), Tween® 20(PubChem CID: 443314), Tween® 80(PubChem CID: 5281955), TPGS (PubChem CID: 71406). Copyright © 2016 Elsevier B.V. All rights reserved.

Rationally Designed TLR4 Ligands for Vaccine Adjuvant Discovery

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Kelsey A. Gregg

2017-05-01

Full Text Available Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS, altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC as a method to generate rationally designed, functionally diverse lipid A. BECC removes endogenous or introduces exogenous lipid A-modifying enzymes to bacteria, effectively reprogramming the lipid A biosynthetic pathway. In this study, BECC is applied within an avirulent strain of Yersinia pestis to develop structurally distinct LOS molecules that elicit differential Toll-like receptor 4 (TLR4 activation. Using reporter cell lines that measure NF-κB activation, BECC-derived molecules were screened for the ability to induce a lower proinflammatory response than Escherichia coli LOS. Their structures exhibit varied, dose-dependent, TLR4-driven NF-κB activation with both human and mouse TLR4 complexes. Additional cytokine secretion screening identified molecules that induce levels of tumor necrosis factor alpha (TNF-α and interleukin-8 (IL-8 comparable to the levels induced by phosphorylated hexa-acyl disaccharide (PHAD. The lead candidates demonstrated potent immunostimulation in mouse splenocytes, human primary blood mononuclear cells (PBMCs, and human monocyte-derived dendritic cells (DCs. This newly described system allows directed programming of lipid A synthesis and has the potential to generate a diverse array of TLR4 agonist candidates.

Optimal public rationing and price response.

Science.gov (United States)

Grassi, Simona; Ma, Ching-To Albert

2011-12-01

We study optimal public health care rationing and private sector price responses. Consumers differ in their wealth and illness severity (defined as treatment cost). Due to a limited budget, some consumers must be rationed. Rationed consumers may purchase from a monopolistic private market. We consider two information regimes. In the first, the public supplier rations consumers according to their wealth information (means testing). In equilibrium, the public supplier must ration both rich and poor consumers. Rationing some poor consumers implements price reduction in the private market. In the second information regime, the public supplier rations consumers according to consumers' wealth and cost information. In equilibrium, consumers are allocated the good if and only if their costs are below a threshold (cost effectiveness). Rationing based on cost results in higher equilibrium consumer surplus than rationing based on wealth. Copyright © 2011 Elsevier B.V. All rights reserved.

Exploring rationality in schizophrenia

DEFF Research Database (Denmark)

Revsbech, Rasmus; Mortensen, Erik Lykke; Owen, Gareth

2015-01-01

Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Meth...... differences became non-significant. Conclusions When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality.......Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Method...... Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence...

Respect for rational autonomy.

Science.gov (United States)

Walker, Rebecca L

2009-12-01

The standard notion of autonomy in medical ethics does not require that autonomous choices not be irrational. The paper gives three examples of seemingly irrational patient choices and discusses how a rational autonomy analysis differs from the standard view. It then considers whether a switch to the rational autonomy view would lead to overriding more patient decisions but concludes that this should not be the case. Rather, a determination of whether individual patient decisions are autonomous is much less relevant than usually considered in determining whether health care providers must abide by these decisions. Furthermore, respect for rational autonomy entails strong positive requirements of respect for the autonomy of the person as a rational decision maker. The rationality view of autonomy is conceptually stronger than the standard view, allows for a more nuanced understanding of the practical moral calculus involved in respecting patient autonomy, and promotes positive respect for patient autonomy.

Embodying rationality

OpenAIRE

Mastrogiorgio, Antonio; Petracca, Enrico

2016-01-01

The current notions of bounded rationality in economics share distinctive features with Simon’s original notion, which still influences the theoretical and experimental research in the fields of choice, judgment, decision making, problem solving, and social cognition. All these notions of bounded rationality are in fact equally rooted in the information-processing approach to human cognition, expressing the view that reasoning is disembodied and that it can be reduced to the processing of abs...

Suicide: rationality and responsibility for life.

Science.gov (United States)

Ho, Angela Onkay

2014-03-01

Death by suicide is widely held as an undesirable outcome. Most Western countries place emphasis on patient autonomy, a concept of controversy in relation to suicide. This paper explores the tensions between patients' rights and many societies' overarching desire to prevent suicide, while clarifying the relations between mental disorders, mental capacity, and rational suicide. A literature search was conducted using search terms of suicide and ethics in the PubMed and LexisNexis Academic databases. Article titles and abstracts were reviewed and deemed relevant if the paper addressed topics of rational suicide, patient autonomy or rights, or responsibility for life. Further articles were found from reference lists and by suggestion from preliminary reviewers of this paper. Suicidal behaviour in a person cannot be reliably predicted, yet various associations and organizations have developed standards of care for managing patients exhibiting suicidal behaviour. The responsibility for preventing suicide tends to be placed on the treating clinician. In cases where a person is capable of making treatment decisions--uninfluenced by any mental disorder--there is growing interest in the concept of rational suicide. There is much debate about whether suicide can ever be rational. Designating suicide as an undesirable event that should never occur raises the debate of who is responsible for one's life and runs the risk of erroneously attributing blame for suicide. While upholding patient rights of autonomy in psychiatric care is laudable, cases of suicidality warrant a delicate consideration of clinical judgment, duty of care, and legal obligations.

Capital Requirements and Credit Rationing

OpenAIRE

Itai Agur

2010-01-01

This paper analyzes the trade-off between financial stability and credit rationing that arises when increasing capital requirements. It extends the Stiglitz-Weiss model of credit rationing to allow for bank default. Bank capital structure then matters for lending incentives. With default and rationing endogenous, optimal capital requirements can be analyzed. Introducing bank financiers, the paper also shows that uninsured funding raises the sensitivity of rationing to capital requirements. In...

Rationally designed, heterologous S. cerevisiae transcripts expose novel expression determinants

Science.gov (United States)

Ben-Yehezkel, Tuval; Atar, Shimshi; Zur, Hadas; Diament, Alon; Goz, Eli; Marx, Tzipy; Cohen, Rafael; Dana, Alexandra; Feldman, Anna; Shapiro, Ehud; Tuller, Tamir

2015-01-01

Deducing generic causal relations between RNA transcript features and protein expression profiles from endogenous gene expression data remains a major unsolved problem in biology. The analysis of gene expression from heterologous genes contributes significantly to solving this problem, but has been heavily biased toward the study of the effect of 5′ transcript regions and to prokaryotes. Here, we employ a synthetic biology driven approach that systematically differentiates the effect of different regions of the transcript on gene expression up to 240 nucleotides into the ORF. This enabled us to discover new causal effects between features in previously unexplored regions of transcripts, and gene expression in natural regimes. We rationally designed, constructed, and analyzed 383 gene variants of the viral HRSVgp04 gene ORF, with multiple synonymous mutations at key positions along the transcript in the eukaryote S. cerevisiae. Our results show that a few silent mutations at the 5′UTR can have a dramatic effect of up to 15 fold change on protein levels, and that even synonymous mutations in positions more than 120 nucleotides downstream from the ORF 5′end can modulate protein levels up to 160%–300%. We demonstrate that the correlation between protein levels and folding energy increases with the significance of the level of selection of the latter in endogenous genes, reinforcing the notion that selection for folding strength in different parts of the ORF is related to translation regulation. Our measured protein abundance correlates notably(correlation up to r = 0.62 (p=0.0013)) with mean relative codon decoding times, based on ribosomal densities (Ribo-Seq) in endogenous genes, supporting the conjecture that translation elongation and adaptation to the tRNA pool can modify protein levels in a causal/direct manner. This report provides an improved understanding of transcript evolution, design principles of gene expression regulation, and suggests simple

[Rationalization and rationing at the bedside. A normative and empirical status quo analysis].

Science.gov (United States)

Strech, D

2014-02-01

The topic of bedside rationing is increasingly discussed in Germany. Further need for clarification exists for the question how bedside rationing (e.g., in the area of overcare) can be justified despite coexistent inefficiencies. This paper outlines and analyses the relationship of waste avoidance and rationing from an ethical perspective. Empirical findings regarding the status quo of bedside rationing and rationalization are presented. These normative and empirical explorations will then be further specified regarding opportunities for future physician-driven activities to tackle overuse. The self-government partners in Germany should communicate more explicitly within their communities and to the public how and with which benchmarks they aim to reduce inefficient health care (overuse) in an appropriate manner. Physician-driven activities such as the "Choosing Wisely®" initiative in the USA could provide a first step to raise the awareness for overuse among physicians as well as in the public.

Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

Science.gov (United States)

Yu, Meiling; Yao, Qing; Zhang, Yan; Chen, Huilin; He, Haibing; Zhang, Yu; Yin, Tian; Tang, Xing; Xu, Hui

2018-02-27

the microspheres prepared by various methods were mainly controlled by either the porosity inside the microspheres or the degradation of materials, which could, therefore, lead to different release behaviours. This results indicated great potential of the PLGA microsphere formulation as an injectable depot for controllable in vivo release profile via rational core phase design. Core/shell microspheres fabricated by modified double emulsification-solvent evaporation methods, with various inner phases, to obtain high loading drugs system, as well as appropriate release behaviours. Accordingly, control in vivo release profile via rational core phase design.

Rational BRDF.

Science.gov (United States)

Pacanowski, Romain; Salazar Celis, Oliver; Schlick, Christophe; Granier, Xavier; Poulin, Pierre; Cuyt, Annie

2012-11-01

Over the last two decades, much effort has been devoted to accurately measuring Bidirectional Reflectance Distribution Functions (BRDFs) of real-world materials and to use efficiently the resulting data for rendering. Because of their large size, it is difficult to use directly measured BRDFs for real-time applications, and fitting the most sophisticated analytical BRDF models is still a complex task. In this paper, we introduce Rational BRDF, a general-purpose and efficient representation for arbitrary BRDFs, based on Rational Functions (RFs). Using an adapted parametrization, we demonstrate how Rational BRDFs offer 1) a more compact and efficient representation using low-degree RFs, 2) an accurate fitting of measured materials with guaranteed control of the residual error, and 3) efficient importance sampling by applying the same fitting process to determine the inverse of the Cumulative Distribution Function (CDF) generated from the BRDF for use in Monte-Carlo rendering.

Clinical Characteristics of Ulceroglandular Tularemia in Two Bulgarian Regions, 2014-2015: a Report of Five Cases

Directory of Open Access Journals (Sweden)

Pekova Liliya M.

2017-12-01

Full Text Available We present here the first five human cases with tularemia from two regions in South Bulgaria in which there had been no previous report of the infection. The cases occurred over a period of 8 months (December 2014 - August 2015. They were treated at the Department of Infectious Diseases in Stara Zagora University Hospital, Bulgaria. We present the clinical, epidemiological and laboratory data for four men and one woman (age range 52 to 73 years. Three men were hunters, four patients took part in handling, preparing/skinning and cooking the game animals. One man marked agricultural work and contact with straw stems. After a mean incubation period of 4.8±1.4 days ulcers appeared, followed by local painful lymphadenitis. All patients presented with liver enlargement and elevation in acute phase reactants. The etiological diagnosis was made by tube agglutination test in all cases, PCR positive result was found in one. The administered antibacterial treatment was a combination of aminoglycosides and 4-quinolones with the outcome being favorable for all patients. The current report suggests presence of Francisella tularensis in South Bulgaria.

Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

Energy Technology Data Exchange (ETDEWEB)

Guliants, Vadim [Univ. of Cincinnati, OH (United States)

2015-02-16

This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

Is It Rational to Assume that Infants Imitate Rationally? A Theoretical Analysis and Critique

Science.gov (United States)

Paulus, Markus

2012-01-01

It has been suggested that preverbal infants evaluate the efficiency of others' actions (by applying a "principle of rational action") and that they imitate others' actions rationally. The present contribution presents a conceptual analysis of the claim that preverbal infants imitate rationally. It shows that this ability rests on at least three…

Adapting Rational Unified Process (RUP) approach in designing a secure e-Tendering model

Science.gov (United States)

Mohd, Haslina; Robie, Muhammad Afdhal Muhammad; Baharom, Fauziah; Darus, Norida Muhd; Saip, Mohamed Ali; Yasin, Azman

2016-08-01

e-Tendering is an electronic processing of the tender document via internet and allow tenderer to publish, communicate, access, receive and submit all tender related information and documentation via internet. This study aims to design the e-Tendering system using Rational Unified Process approach. RUP provides a disciplined approach on how to assign tasks and responsibilities within the software development process. RUP has four phases that can assist researchers to adjust the requirements of various projects with different scope, problem and the size of projects. RUP is characterized as a use case driven, architecture centered, iterative and incremental process model. However the scope of this study only focusing on Inception and Elaboration phases as step to develop the model and perform only three of nine workflows (business modeling, requirements, analysis and design). RUP has a strong focus on documents and the activities in the inception and elaboration phases mainly concern the creation of diagrams and writing of textual descriptions. The UML notation and the software program, Star UML are used to support the design of e-Tendering. The e-Tendering design based on the RUP approach can contribute to e-Tendering developers and researchers in e-Tendering domain. In addition, this study also shows that the RUP is one of the best system development methodology that can be used as one of the research methodology in Software Engineering domain related to secured design of any observed application. This methodology has been tested in various studies in certain domains, such as in Simulation-based Decision Support, Security Requirement Engineering, Business Modeling and Secure System Requirement, and so forth. As a conclusion, these studies showed that the RUP one of a good research methodology that can be adapted in any Software Engineering (SE) research domain that required a few artifacts to be generated such as use case modeling, misuse case modeling, activity

Tularemia live vaccine effect of contrasuppression of blood lymphocytes in patients with cancer of corpus uteri during combined treatment and later

International Nuclear Information System (INIS)

Movsesyan, M.A.; Adamyan, R.T.; Markosyan, K.M.

1999-01-01

A significant decrease in the percentage of women showing contrasuppression of blood lymphocytes, as compared with control, was identified (p ≤ 0.1); it was particularly low at terminal stage (III - IV). Surgery and subsequent radiotherapy were followed by further inhibition, particularly in terminally-ill patients. Two or three years after treatment the numbers of patients in all stage groups, showing contrasuppression increased reaching the initial, i.e. lower than normal levels. However, contrasuppression induces rose to normal in patients immunized with tularemia live vaccine (p ≥ 0.05). This effect was observed in patients of all stage groups, immunized prior to treatment, on days 15 - 20 after immunization. Normal levels of contrasuppression were maintained during treatment and 2 - 3 years on. Both contrasuppression level and stage of tumor may serve as a criterion of gravity of disease and prognosis [ru

Bounded Rationality and Budgeting

OpenAIRE

Ibrahim, Mukdad

2016-01-01

This article discusses the theory of bounded rationality which had been introduced by Herbert Simon in the 1950s. Simon introduced the notion of bounded rationality stating that while decision-makers strive for rationality, they are limited by the effect of the environment, their information process capacity and by the constraints on their information storage and retrieval capabilities. Moreover, this article tries to specifically blend this notion into budgeting, using the foundations of inc...

Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers

Science.gov (United States)

Araya-Durán, Ingrid; Varas-Concha, Ignacio; Almonacid, Daniel Eduardo; González-Nilo, Fernando Danilo

2015-01-01

Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. PMID:26382062

An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia.

Directory of Open Access Journals (Sweden)

Sivakumar Periasamy

2016-03-01

Full Text Available Inhalation of Francisella tularensis (Ft causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection.

An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia

Science.gov (United States)

Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.

2016-01-01

Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

Rational valuations

Directory of Open Access Journals (Sweden)

Georg Spielthenner

2007-01-01

Full Text Available Valuations are ubiquitous. We may be for or against genetically modified food; we find some politicians irresponsible; we prefer Beethoven to rock ‘n’ roll or vice versa; some enjoy bird-watching while others find it boring; and we may think that we have to tighten up on green-house gas emissions. Valuing is pervasive and often we are not even aware that we are valuing. However, many of ourvaluations are ill grounded and rationally defective. They are frequently based on misinformation, sloppy thinking, prejudice, and are biased in many ways as psychological research shows. For this reason there is widespread agreement among phi-losophers that we need an account of substantive valuational rationality, both for the theory of practical reasoning and for ethics as well. My main objectin this paper is to outline such an account and to present a principle that allows a non-technical rational criticism of valuations

Rational emotions.

Science.gov (United States)

Meshulam, Meir; Winter, Eyal; Ben-Shakhar, Gershon; Aharon, Itzhak

2012-01-01

We present here the concept of rational emotions: Emotions may be directly controlled and utilized in a conscious, analytic fashion, enabling an individual to size up a situation, to determine that a certain "mental state" is strategically advantageous and adjust accordingly. Building on the growing body of literature recognizing the vital role of emotions in determining decisions, we explore the complementary role of rational choice in choosing emotional states. Participants played the role of "recipient" in the dictator game, in which an anonymous "dictator" decides how to split an amount of money between himself and the recipient. A subset of recipients was given a monetary incentive to be angry at low-split offers. That subset demonstrated increased physiological arousal at low offers relative to high offers as well as more anger than other participants. These results provide a fresh outlook on human decision-making and contribute to the continuing effort to build more complete models of rational behavior.

Models for Rational Number Bases

Science.gov (United States)

Pedersen, Jean J.; Armbruster, Frank O.

1975-01-01

This article extends number bases to negative integers, then to positive rationals and finally to negative rationals. Methods and rules for operations in positive and negative rational bases greater than one or less than negative one are summarized in tables. Sample problems are explained and illustrated. (KM)

Rational Design of Disulfide Bonds Increases Thermostability of a Mesophilic 1,3-1,4-β-Glucanase from Bacillus terquilensis.

Directory of Open Access Journals (Sweden)

Chengtuo Niu

Full Text Available 1,3-1,4-β-glucanase is an important biocatalyst in brewing industry and animal feed industry, while its low thermostability often reduces its application performance. In this study, the thermostability of a mesophilic β-glucanase from Bacillus terquilensis was enhanced by rational design and engineering of disulfide bonds in the protein structure. Protein spatial configuration was analyzed to pre-exclude the residues pairs which negatively conflicted with the protein structure and ensure the contact of catalytic center. The changes in protein overall and local flexibility among the wild-type enzyme and the designated mutants were predicted to select the potential disulfide bonds for enhancement of thermostability. Two residue pairs (N31C-T187C and P102C-N125C were chosen as engineering targets and both of them were proved to significantly enhance the protein thermostability. After combinational mutagenesis, the double mutant N31C-T187C/P102C-N125C showed a 48.3% increase in half-life value at 60°C and a 4.1°C rise in melting temperature (Tm compared to wild-type enzyme. The catalytic property of N31C-T187C/P102C-N125C mutant was similar to that of wild-type enzyme. Interestingly, the optimal pH of double mutant was shifted from pH6.5 to pH6.0, which could also increase its industrial application. By comparison with mutants with single-Cys substitutions, the introduction of disulfide bonds and the induced new hydrogen bonds were proved to result in both local and overall rigidification and should be responsible for the improved thermostability. Therefore, the introduction of disulfide bonds for thermostability improvement could be rationally and highly-effectively designed by combination with spatial configuration analysis and molecular dynamics simulation.

Rational design of modular circuits for gene transcription: A test of the bottom-up approach

Directory of Open Access Journals (Sweden)

Giordano Emanuele

2010-11-01

Full Text Available Abstract Background Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design. Results We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure. Conclusions This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.

Are security analysts rational? a literature review

OpenAIRE

Peixinho, Rúben; Coelho, Luís; Taffler, Richard J.

2005-01-01

Rational choice theory and bounded rationality constitute the basis for the discussion in several areas regarding human rationality. In finance, this discussion has been made between traditional finance and behavioural finance approach, which have different perspectives concerning market agents’ rationality. This paper reviews several studies addressing rationality among security analysts. The analysis shows that analysts’systematic optimism seems to be inconsistent with rationality....

Future product design

DEFF Research Database (Denmark)

Andreasen, Mogens Myrup

1997-01-01

This paper (in form of overheads) formulate new challenges and possibilities for engineering design, utilizing rationalization effect from modularisation, re-use and transparaency.......This paper (in form of overheads) formulate new challenges and possibilities for engineering design, utilizing rationalization effect from modularisation, re-use and transparaency....

Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

Science.gov (United States)

Jeschek, Markus; Gerngross, Daniel; Panke, Sven

2016-03-31

Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways.

Empirical evidence for resource-rational anchoring and adjustment.

Science.gov (United States)

Lieder, Falk; Griffiths, Thomas L; M Huys, Quentin J; Goodman, Noah D

2018-04-01

People's estimates of numerical quantities are systematically biased towards their initial guess. This anchoring bias is usually interpreted as sign of human irrationality, but it has recently been suggested that the anchoring bias instead results from people's rational use of their finite time and limited cognitive resources. If this were true, then adjustment should decrease with the relative cost of time. To test this hypothesis, we designed a new numerical estimation paradigm that controls people's knowledge and varies the cost of time and error independently while allowing people to invest as much or as little time and effort into refining their estimate as they wish. Two experiments confirmed the prediction that adjustment decreases with time cost but increases with error cost regardless of whether the anchor was self-generated or provided. These results support the hypothesis that people rationally adapt their number of adjustments to achieve a near-optimal speed-accuracy tradeoff. This suggests that the anchoring bias might be a signature of the rational use of finite time and limited cognitive resources rather than a sign of human irrationality.

Limited rationality and strategic interaction

DEFF Research Database (Denmark)

Fehr, Ernst; Tyran, Jean-Robert

2008-01-01

Much evidence suggests that people are heterogeneous with regard to their abilities to make rational, forward-looking decisions. This raises the question as to when the rational types are decisive for aggregate outcomes and when the boundedly rational types shape aggregate results. We examine...... this question in the context of a long-standing and important economic problem: the adjustment of nominal prices after an anticipated monetary shock. Our experiments suggest that two types of bounded rationality-money illusion and anchoring-are important behavioral forces behind nominal inertia. However......, depending on the strategic environment, bounded rationality has vastly different effects on aggregate price adjustment. If agents' actions are strategic substitutes, adjustment to the new equilibrium is extremely quick, whereas under strategic complementarity, adjustment is both very slow and associated...

Interpolation of rational matrix functions

CERN Document Server

Ball, Joseph A; Rodman, Leiba

1990-01-01

This book aims to present the theory of interpolation for rational matrix functions as a recently matured independent mathematical subject with its own problems, methods and applications. The authors decided to start working on this book during the regional CBMS conference in Lincoln, Nebraska organized by F. Gilfeather and D. Larson. The principal lecturer, J. William Helton, presented ten lectures on operator and systems theory and the interplay between them. The conference was very stimulating and helped us to decide that the time was ripe for a book on interpolation for matrix valued functions (both rational and non-rational). When the work started and the first partial draft of the book was ready it became clear that the topic is vast and that the rational case by itself with its applications is already enough material for an interesting book. In the process of writing the book, methods for the rational case were developed and refined. As a result we are now able to present the rational case as an indepe...

Rational design of anatase TiO2 architecture with hierarchical nanotubes and hollow microspheres for high-performance dye-sensitized solar cells

Science.gov (United States)

Gu, Jiuwang; Khan, Javid; Chai, Zhisheng; Yuan, Yufei; Yu, Xiang; Liu, Pengyi; Wu, Mingmei; Mai, Wenjie

2016-01-01

Large surface area, sufficient light-harvesting and superior electron transport property are the major factors for an ideal photoanode of dye-sensitized solar cells (DSSCs), which requires rational design of the nanoarchitectures and smart integration of state-of-the-art technologies. In this work, a 3D anatase TiO2 architecture consisting of vertically aligned 1D hierarchical TiO2 nanotubes (NTs) with ultra-dense branches (HTNTs, bottom layer) and 0D hollow TiO2 microspheres with rough surface (HTS, top layer) is first successfully constructed on transparent conductive fluorine-doped tin oxide glass through a series of facile processes. When used as photoanodes, the DSSCs achieve a very large short-current density of 19.46 mA cm-2 and a high overall power conversion efficiency of 8.38%. The remarkable photovoltaic performance is predominantly ascribed to the enhanced charge transport capacity of the NTs (function as the electron highway), the large surface area of the branches (act as the electron branch lines), the pronounced light harvesting efficiency of the HTS (serve as the light scattering centers), and the engineered intimate interfaces between all of them (minimize the recombination effect). Our work demonstrates a possibility of fabricating superior photoanodes for high-performance DSSCs by rational design of nanoarchitectures and smart integration of multi-functional components.

Decision-Making: Are Plants More Rational than Animals?

Science.gov (United States)

Schmid, Bernhard

2016-07-25

A new study presents a novel experimental design and allows a test of risk sensitivity in plants. Faced with a choice between constant and variable resource supply, they make a rational decision for the option that maximizes fitness, a fact rarely observed in animals. Copyright © 2016 Elsevier Ltd. All rights reserved.

History of Economic Rationalities

DEFF Research Database (Denmark)

This book concentrates upon how economic rationalities have been embedded into particular historical practices, cultures, and moral systems. Through multiple case-studies, situated in different historical contexts of the modern West, the book shows that the development of economic rationalities...... takes place in the meeting with other regimes of thought, values, and moral discourses. The book offers new and refreshing insights, ranging from the development of early economic thinking to economic aspects and concepts in the works of classical thinkers such as Thomas Hobbes, John Locke and Karl Marx......, to the role of economic reasoning in contemporary policies of art and health care. With economic rationalities as the read thread, the reader is offered a unique chance of historical self-awareness and recollection of how economic rationality became the powerful ideological and moral force that it is today....

Effects of forage ensiling and ration fermentation on total mixed ration pH, ruminal fermentation and performance of growing Holstein-Zebu cross steers.

Science.gov (United States)

Meenongyai, Watcharawit; Pattarajinda, Virote; Stelzleni, Alexander M; Sethakul, Jutarat; Duangjinda, Monchai

2017-09-01

Our objective was to determine the effect of forage ensiling and ration fermentation on total mixed ration pH, ruminal fermentation and animal performance. Thirty Holstein-Zebu cross steers were allotted to feeding treatments for 188 days in a randomized complete block design including: fresh grass-total mixed ration (GTMR; pH 4.7), grass silage-TMR (STMR; pH 4.0) and fermented-TMR (FTMR; pH 3.5). Average daily gain for STMR was greatest during the first 3 months period; however, that for FTMR tended to be greater than GTMR during the second 3 months period (P ruminal NH 3 -N content than STMR. Total volatile fatty acids post-feeding was greatest for GTMR (P Ruminal proportions of acetic and butyric acids were greater for FTMR than GTMR (P ruminal pH. STMR and FTMRs can be used to maintain performance of growing crossbred Holstein steers. © 2017 Japanese Society of Animal Science.

Psychology and the Rationality of Emotion.

Science.gov (United States)

Clore, Gerald L

2011-04-01

Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome.

Psychology and the Rationality of Emotion*

OpenAIRE

Clore, Gerald L.

2011-01-01

Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome.

Design thinking between rationalism and romanticism

DEFF Research Database (Denmark)

Engholm, Ida; Goldschmidt Salamon, Karen-Lisa

2017-01-01

This article presents a longue durée history of modern design thought, with particular focus on recurrent ideological frictions. Drawing on design history, design anthropology and cultural studies, the authors present an overview of more than 200 years of developments in European and North Americ...

Moral Credentialing and the Rationalization of Misconduct

Science.gov (United States)

Brown, Ryan P.; Tamborski, Michael; Wang, Xiaoqian; Barnes, Collin D.; Mumford, Michael D.; Connelly, Shane; Devenport, Lynn D.

2010-01-01

Recent studies lead to the paradoxical conclusion that the act of affirming one’s egalitarian or pro-social values and virtues might subsequently facilitate prejudiced or self-serving behavior, an effect previously referred to as “moral credentialing.” The present study extends this paradox to the domain of academic misconduct and investigates the hypothesis that such an effect might be limited by the extent to which misbehavior is rationalizable. Using a paradigm designed to investigate deliberative and rationalized forms of cheating (von Hippel, Lakin, & Shakarchi, 2005), we found that when participants had credentialed themselves (versus a non-close acquaintance) via a set of hypothetical moral dilemmas, they were more likely to cheat on a subsequent math task, but only if cheating was highly rationalizable. When cheating was difficult to rationalize, moral credentialing had almost no impact on cheating. PMID:21503267

Testing bounded rationality against full rationality in job changing behavior

OpenAIRE

Contini, Bruno; Morini, Matteo

2007-01-01

In this paper we question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers' performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new ...

Testing Bounded Rationality Against Full Rationality in Job Changing Behavior

OpenAIRE

Bruno Contini

2008-01-01

In this paper I question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers’ performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new o...

Rational design of multifunctional devices based on molybdenum disulfide and graphene hybrid nanostructures

Energy Technology Data Exchange (ETDEWEB)

Lim, Yi Rang; Lee, Young Bum; Kim, Seong Ku; Kim, Seong Jun [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Kim, Yooseok; Jeon, Cheolho [Nano-Surface Research Group, Korea Basic Science Institute, Daejeon, 302-333 (Korea, Republic of); Song, Wooseok, E-mail: wssong@krict.re.kr [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Myung, Sung; Lee, Sun Sook; An, Ki-Seok [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Lim, Jongsun, E-mail: jslim@krict.re.kr [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of)

2017-01-15

Highlights: • We fabricated MoS{sub 2}-graphene hybrid thin films for multifunctional applications. • Large-area, uniform multilayer MoS{sub 2} was synthesized on TCVD-grown graphene. • The mobility and photocurrent of the hybrid devices were improved significantly. - Abstract: We rationally designed a new type of hybrid materials, molybdenum disulfide (MoS{sub 2}) synthesized by Mo pre-deposition followed by subsequent sulfurization process directly on thermal chemical vapor deposition (TCVD)-grown graphene, for applications in a multifunctional device. The synthesis of stoichiometric and uniform multilayer MoS{sub 2} and high-crystalline monolayer graphene was evaluated by X-ray photoelectron spectroscopy and Raman spectroscopy. To examine the electrical transport and photoelectrical properties of MoS{sub 2}-graphene hybrid films, field effect transistors (FETs) and visible-light photodetectors based on MoS{sub 2}-graphene were both fabricated. As a result, the extracted mobility for MoS{sub 2}-graphene hybrid FETs was two times higher than that of MoS{sub 2} FETs. In addition, the MoS{sub 2}-graphene photodetectors revealed a significant photocurrent with abrupt switching behavior under periodic illumination.

Psychology and the Rationality of Emotion*

Science.gov (United States)

Clore, Gerald L.

2014-01-01

Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome. PMID:25125770

The political economy of rationing health care in England and the US: the 'accidental logics' of political settlements.

Science.gov (United States)

Bevan, Gwyn; Brown, Lawrence D

2014-07-01

This article considers how the 'accidental logics' of political settlements for the English National Health Service (NHS) and the Medicare and Medicaid programmes in the United States have resulted in different institutional arrangements and different implicit social contracts for rationing, which we define to be the denial of health care that is beneficial but is deemed to be too costly. This article argues that rationing is designed into the English NHS and designed out of US Medicare; and compares rationing for the elderly in the United States and in England for acute care, care at the end of life, and chronic care.

DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

Science.gov (United States)

A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe.

Science.gov (United States)

Verwilst, Peter; Kim, Hye-Ri; Seo, Jinho; Sohn, Nak-Won; Cha, Seung-Yun; Kim, Yeongmin; Maeng, Sungho; Shin, Jung-Won; Kwak, Jong Hwan; Kang, Chulhun; Kim, Jong Seung

2017-09-27

The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 ( 306 VQIVYK 311 ) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aβ-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aβ plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.

Final Report: Rational Design of Wide Band Gap Buffer Layers for High-Efficiency Thin-Film Photovoltaics

Energy Technology Data Exchange (ETDEWEB)

Lordi, Vincenzo [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-09-30

The main objective of this project is to enable rational design of wide band gap buffer layer materials for CIGS thin-film PV by building understanding of the correlation of atomic-scale defects in the buffer layer and at the buffer/absorber interface with device electrical properties. Optimized wide band gap buffers are needed to reduce efficiency loss from parasitic absorption in the buffer. The approach uses first-principles materials simulations coupled with nanoscale analytical electron microscopy as well as device electrical characterization. Materials and devices are produced by an industrial partner in a manufacturing line to maximize relevance, with the goal of enabling R&D of new buffer layer compositions or deposition processes to push device efficiencies above 21%. Cadmium sulfide (CdS) is the reference material for analysis, as the prototypical high-performing buffer material.

Rational design of single-ion magnets and spin qubits based on mononuclear lanthanoid complexes.

Science.gov (United States)

Baldoví, José J; Cardona-Serra, Salvador; Clemente-Juan, Juan M; Coronado, Eugenio; Gaita-Ariño, Alejandro; Palii, Andrew

2012-11-19

Here we develop a general approach to calculating the energy spectrum and the wave functions of the low-lying magnetic levels of a lanthanoid ion submitted to the crystal field created by the surrounding ligands. This model allows us to propose general criteria for the rational design of new mononuclear lanthanoid complexes behaving as single-molecule magnets (SMMs) or acting as robust spin qubits. Three typical environments exhibited by these metal complexes are considered, namely, (a) square antiprism, (b) triangular dodecahedron, and (c) trigonal prism. The developed model is used to explain the properties of some representative examples showing these geometries. Key questions in this area, such as the chemical tailoring of the superparamagnetic energy barrier, tunneling gap, or spin relaxation time, are discussed. Finally, in order to take into account delocalization and/or covalent effects of the ligands, this point-charge model is complemented with ab initio calculations, which provide accurate information on the charge distribution around the metal, allowing for an explanation of the SMM behavior displayed by some sandwich-type organometallic compounds.

Production and Energy Partition of Lactating Dairy Goats Fed Rations Containing Date Fruit Waste

Directory of Open Access Journals (Sweden)

E. Yuniarti

2016-04-01

Full Text Available Dates fruit waste (DFW is a by-product of dates juice industry that contains high energy. So, it is suitable for an energy source in dairy goat ration. This study was conducted to observe the effect of DFW utilization in the ration on energy partition and productivity of lactating dairy goats. The experimental design was randomized block design using 9 primiparous lactating dairy goats. There were three types of ration as treatments used in this study, i.e. R0= 35% forage + 65% concentrate, R1= 35% forage + 55% concentrate + 10% DFW, and R2= 35% forage + 45% concentrate + 20% DFW. Data were analyzed using ANOVA and polynomial orthogonal test. The evaluated variables were dry matter intake (DMI, energy partition including energy intake, digestible and metabolizable energy, fecal and urine energy, energy in methane gas, and energy in milk, milk production and quality. The results showed that the linear decreased of DMI, energy intake, digestible energy, metabolizable energy, and urine energy with the increased of DFW level in the rations. The use of 10% DFW (R1 showed the lowest energy loss through feces and methane gas of all treatments about 1089.57 kcal/head/d and 2.36 kcal/head/d, respectively. The use of DFW did not affect energy retention in milk. The utilization of DFW in ration did not significantly prevent the decline of milk production and milk quality. It can be concluded that DFW can be used as an alternative feed for the lactating dairy goat up to 10% in the ration.

Rational design and validation of an anti-protein kinase C active-state specific antibody based on conformational changes.

Science.gov (United States)

Pena, Darlene Aparecida; Andrade, Victor Piana de; Silva, Gabriela Ávila Fernandes; Neves, José Ivanildo; Oliveira, Paulo Sergio Lopes de; Alves, Maria Julia Manso; Devi, Lakshmi A; Schechtman, Deborah

2016-02-25

Protein kinase C (PKC) plays a regulatory role in key pathways in cancer. However, since phosphorylation is a step for classical PKC (cPKC) maturation and does not correlate with activation, there is a lack of tools to detect active PKC in tissue samples. Here, a structure-based rational approach was used to select a peptide to generate an antibody that distinguishes active from inactive cPKC. A peptide conserved in all cPKCs, C2Cat, was chosen since modeling studies based on a crystal structure of PKCβ showed that it is localized at the interface between the C2 and catalytic domains of cPKCs in an inactive kinase. Anti-C2Cat recognizes active cPKCs at least two-fold better than inactive kinase in ELISA and immunoprecipitation assays, and detects the temporal dynamics of cPKC activation upon receptor or phorbol stimulation. Furthermore, the antibody is able to detect active PKC in human tissue. Higher levels of active cPKC were observed in the more aggressive triple negative breast cancer tumors as compared to the less aggressive estrogen receptor positive tumors. Thus, this antibody represents a reliable, hitherto unavailable and a valuable tool to study PKC activation in cells and tissues. Similar structure-based rational design strategies can be broadly applied to obtain active-state specific antibodies for other signal transduction molecules.

Max Weber's Types of Rationality: Cornerstones for the Analysis of Rationalization Processes in History.

Science.gov (United States)

Kalberg, Stephen

1980-01-01

Explores rationality in Max Weber's works and identifies four types of rationality which play major roles in his writing--practical, theoretical, substantive, and formal. Implications for society and education are discussed. (DB)

The concept of rational suicide.

Science.gov (United States)

Mayo, D J

1986-05-01

Suicide has been condemned in our culture in one way or another since Augustine offered theological arguments against it in the sixth century. More recently, theological condemnation has given way to the view that suicidal behavior must always be symptomatic of emotional disturbance and mental illness. However, suicide has not always been viewed so negatively. In other times and cultures, it has been held that circumstances might befall a person in which suicide would be a perfectly rational course of action, in the same sense that any other course of action could be rational: that it could be sensible, i.e., defensible by good reasons, or that it could be in keeping with the agent's fundamental interests. Indiscriminate use of modern life-sustaining technologies has renewed interest in the possibility of rational suicide. Today proponents of rational suicide tend to equate the rationality of suicide with the competence of the decision to commit suicide.

Experiential versus rational training: a comparison of student attitudes toward homosexuality.

Science.gov (United States)

Guth, Lorraine J; Lopez, David F; Rojas, Julio; Clements, Kimberly D; Tyler, J Michael

2004-01-01

Based on Epstein's (1994a) cognitive-experiential self-theory, two new training interventions were designed to teach students about gay, lesbian and bisexual issues. The efficacy of these theoretically based interventions was assessed in a short-term (7-week, three occasion) longitudinal study. Fifty undergraduate psychology students were randomly assigned to one of three treatment groups: Rational Training, Experiential Training, or Control Group. A residualized change score procedure was used to analyze change in levels of sexual prejudice and affect across the three types of measurement (pre-test, post-test, and follow-up). A 3 (Rational Training, Experiential Training, Control Group) x 2 (Low Sexual Prejudice, High Sexual Prejudice) MANOVA revealed that after the training, participants in the Experiential Group (affective training) had more accepting attitudes toward homosexuality compared to the Control Group. In addition, participants in the Experiential Group experienced more positive affect compared to the Rational and Control Groups and experienced more negative affect compared to the Rational Group. Findings are discussed and suggestions for future research are provided.

Rational Ligand Design for U(VI) and Pu(IV)

International Nuclear Information System (INIS)

Szigethy, Geza

2009-01-01

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO 2 2+ ). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative saturation, these

Rational Ligand Design for U(VI) and Pu(IV)

Energy Technology Data Exchange (ETDEWEB)

Szigethy, Geza [Univ. of California, Berkeley, CA (United States)

2009-08-12

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO₂ ²⁺). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative

RATGRAPH: Computer Graphing of Rational Functions.

Science.gov (United States)

Minch, Bradley A.

1987-01-01

Presents an easy-to-use Applesoft BASIC program that graphs rational functions and any asymptotes that the functions might have. Discusses the nature of rational functions, graphing them manually, employing a computer to graph rational functions, and describes how the program works. (TW)

F-theory and all things rational: surveying U(1) symmetries with rational sections

International Nuclear Information System (INIS)

Lawrie, Craig; Schäfer-Nameki, Sakura; Wong, Jin-Mann

2015-01-01

We study elliptic fibrations for F-theory compactifications realizing 4d and 6d supersymmetric gauge theories with abelian gauge factors. In the fibration these U(1) symmetries are realized in terms of additional rational section. We obtain a universal characterization of all the possible U(1) charges of matter fields by determining the corresponding codimension two fibers with rational sections. In view of modelling supersymmetric Grand Unified Theories, one of the main examples that we analyze are U(1) symmetries for SU(5) gauge theories with 5̄ and 10 matter. We use a combination of constraints on the normal bundle of rational curves in Calabi-Yau three- and four-folds, as well as the splitting of rational curves in the fibers in codimension two, to determine the possible configurations of smooth rational sections. This analysis straightforwardly generalizes to multiple U(1)s. We study the flops of such fibers, as well as some of the Yukawa couplings in codimension three. Furthermore, we carry out a universal study of the U(1)-charged GUT singlets, including their KK-charges, and determine all realizations of singlet fibers. By giving vacuum expectation values to these singlets, we propose a systematic way to analyze the Higgsing of U(1)s to discrete gauge symmetries in F-theory.

"Leaky" Rationality: How Research on Behavioral Decision Making Challenges Normative Standards of Rationality.

Science.gov (United States)

Keys, Daniel J; Schwartz, Barry

2007-06-01

For more than 30 years, decision-making research has documented that people often violate various principles of rationality, some of which are so fundamental that theorists of rationality rarely bother to state them. We take these characteristics of decision making as a given but argue that it is problematic to conclude that they typically represent departures from rationality. The very psychological processes that lead to "irrational" decisions (e.g., framing, mental accounting) continue to exert their influence when one experiences the results of the decisions. That is, psychological processes that affect decisions may be said also to "leak" into one's experience. The implication is that formal principles of rationality do not provide a good enough normative standard against which to assess decision making. Instead, what is needed is a substantive theory of rationality-one that takes subjective experience seriously, considers both direct and indirect consequences of particular decisions, considers how particular decisions fit into life as a whole, and considers the effects of decisions on others. Formal principles may play a role as approximations of the substantive theory that can be used by theorists and decision makers in cases in which the formal principles can capture most of the relevant considerations and leakage into experience is negligible. © 2007 Association for Psychological Science.

Popper, Rationality and the Possibility of Social Science

Directory of Open Access Journals (Sweden)

Danny Frederick

2013-02-01

Full Text Available Social science employs teleological explanations which depend upon the rationality principle, according to which people exhibit instrumental rationality. Popper points out that people also exhibit critical rationality, the tendency to stand back from, and to question or criticise, their views. I explain how our critical rationality impugns the explanatory value of the rationality principle and thereby threatens the very possibility of social science. I discuss the relationship between instrumental and critical rationality and show how we can reconcile our critical rationality with the possibility of social science if we invoke Popper’s conception of limited rationality and his indeterminism.

Ethics of rationing of nursing care.

Science.gov (United States)

Rooddehghan, Zahra; Yekta, Zohreh Parsa; Nasrabadi, Alireza N

2016-09-21

Rationing of various needed services, for example, nursing care, is inevitable due to unlimited needs and limited resources. Rationing of nursing care is considered an ethical issue since it requires judgment about potential conflicts between personal and professional values. The present research sought to explore aspects of rationing nursing care in Iran. This study applied qualitative content analysis, a method to explore people's perceptions of everyday life phenomena and interpret the subjective content of text data. Data collection was performed through in-depth, unstructured, face-to-face interviews with open-ended questions. The study population included Iranian nurses of all nursing positions, from clinical nurses to nurse managers. Purposive sampling was employed to select 15 female and 3 male nurses (11 clinical nurses, 3 supervisors, 1 matron, 1 nurse, and 2 members of the Nursing Council) working in hospitals of three cities in Iran. The study protocol was approved by Tehran University of Medical Sciences (91D1302870). Written informed consent was also obtained from all participants. According to the participants, rationing of nursing care consisted of two categories, that is, causes of rationing and consequences of rationing. The first category comprised three subcategories, namely, patient needs and demands, routinism, and VIP patients. The three subcategories forming the second category were missed nursing care, patient dissatisfaction, and nurses' feeling of guilt. Levels at which healthcare practices are rationed and clarity of the rationing are important structural considerations in the development of an equal, appropriate, and ethical healthcare system. Moreover, the procedure of rationing is critical as it not only influences people's lives but also reflects the values that dominate in the society. Therefore, in order to minimize the negative consequences of rationing of nursing care, further studies on the ethical dimensions of this phenomenon

Casebook on rationalization of power use

International Nuclear Information System (INIS)

1986-06-01

This book introduces the cases on rationalization of power use, which is divided into four parts. The first part refers the goal of rational use of energy and the result. The second part deals with the excellent cases on rationalization of domestic power use, which list the name of the company, hotel and factory according to the field such as building, textile and food. The third part contains the outstanding cases on rationalization of foreign power use, which were listed by the specific way to reduce electricity use each section. The fourth part is comprised of two chapters, which deals with the cases of domestic technical data and foreign technical data for rational use of energy.

Rational Design of a New Trypanosoma rangeli Trans-Sialidase for Efficient Sialylation of Glycans

DEFF Research Database (Denmark)

Jers, Carsten; Michalak, Malwina; Larsen, Dorte Møller

2014-01-01

This paper reports rational engineering of Trypanosoma rangeli sialidase to develop an effective enzyme for a potentially important type of reactivity: production of sialylated prebiotic glycans. The Trypanosoma cruzi trans-sialidase and the homologous T. rangeli sialidase has previously been use...

From rational creatures to the rational Creator: ancient and patristic analogies of the “fine-tuning” argument

Directory of Open Access Journals (Sweden)

Alexey Fokin

2017-12-01

Full Text Available In this article the author deals with the proofs of the existence of God, based on the fact of the presence of rational beings in the world. These proofs can be found in Greek and Roman Classical philosophy and early Patristics, and can be viewed as an analogue of the modern “fine-tuning argument”. The author considers the origins and development of this argument in the Greek and Roman philosophy: in Socrates, Plato, Cicero, Sextus Empiricus, and especially the Stoics, who gave to the argument a logical form, based on the relationship between “the parts and the whole”: if the world as a whole produces and contains rational beings as its parts, it should also be rational or contain a rational principle that generates all its parts and governs them, just as human soul governs human body. The correction of this argument was proposed by Sextus Empiricus, who introduced the concept of "spermatic logoi", or rational principles, to explain the generation of the rational beings by the world, so that if the world contains the spermatic logoi of rational and living beings, then the world as a whole is also rational. The author also investigates the reception of the argument based on the existence of rational beings in the world in Latin Patristics: in Minucius Felix, Tertullian and especially Lactantius, in whom this argument has reached the climax of its development. At the same time it was shown, that the ancient argument has undergone a transformation from the postulation of the rationality of the world as a whole or its equation with God himself to a genuine proof of the existence of the one God who is the Creator both of the world and human beings, superior to the both as the all-powerful and transcendent Mind.

Thermodynamic dissection of the binding energetics of proline-rich peptides to the Abl-SH3 domain: implications for rational ligand design.

Science.gov (United States)

Palencia, Andrés; Cobos, Eva S; Mateo, Pedro L; Martínez, Jose C; Luque, Irene

2004-02-13

The inhibition of the interactions between SH3 domains and their targets is emerging as a promising therapeutic strategy. To date, rational design of potent ligands for these domains has been hindered by the lack of understanding of the origins of the binding energy. We present here a complete thermodynamic analysis of the binding energetics of the p41 proline-rich decapeptide (APSYSPPPPP) to the SH3 domain of the c-Abl oncogene. Isothermal titration calorimetry experiments have revealed a thermodynamic signature for this interaction (very favourable enthalpic contributions opposed by an unfavourable binding entropy) inconsistent with the highly hydrophobic nature of the p41 ligand and the Abl-SH3 binding site. Our structural and thermodynamic analyses have led us to the conclusion, having once ruled out any possible ionization events or conformational changes coupled to the association, that the establishment of a complex hydrogen-bond network mediated by water molecules buried at the binding interface is responsible for the observed thermodynamic behaviour. The origin of the binding energetics for proline-rich ligands to the Abl-SH3 domain is further investigated by a comparative calorimetric analysis of a set of p41-related ligands. The striking effects upon the enthalpic and entropic contributions provoked by conservative substitutions at solvent-exposed positions in the ligand confirm the complexity of the interaction. The implications of these results for rational ligand design are discussed.

Rationing medical education | Walsh | African Health Sciences

African Journals Online (AJOL)

Even though some stakeholders in medical education might be taken aback at the prospect of rationing, the truth is that rationing has always occurred in one form or another in medical education and in healthcare more broadly. Different types of rationing exist in healthcare professional education. For example rationing may ...

Rationality and antiemotionality as a risk factor for cancer: concept differentiation.

Science.gov (United States)

van der Ploeg, H M; Kleijn, W C; Mook, J; van Donge, M; Pieters, A M; Leer, J W

1989-01-01

Control and repression of emotions may be coping styles or personality characteristics found more often in patients with cancer than in other patients and healthy subjects. Previous research indicated a possible relationship between high scores on a 'rationality and antiemotionality' scale and cancer. In the two studies reported, the psychometric properties of this scale and the meaning of the concept as a personality variable related to the control of emotions were investigated. It was found that the internal consistency of the scale could be improved by re-designing it into a personality inventory. Factor analysis repeatedly yielded more than one factor, indicating the complexity of the concept. 'Rationality and antiemotionality' seems related to the control, suppression or repression of anger. Our findings tentatively support the view that rationality and antiemotionality may be an important distinctive personality characteristic in patients with cancer.

Effects of Rational-Emotive Therapy, Rational Role Reversal, and Rational-Emotive Imagery on the Emotional Adjustment of Community Mental Health Center Patients.

Science.gov (United States)

Lipsky, Marc J.; And Others

1980-01-01

Results showed that rational-emotive therapy (RET), with the addition of rational role reversal, produced significantly better results than did relaxation training and support or no contact. This was the first study to demonstrate the efficacy of RET with multisymptomatic applicants to a community mental health center. (Author/BEF)

Argumentation, rationality, and psychology of reasoning

Directory of Open Access Journals (Sweden)

David Godden

2015-05-01

Full Text Available This paper explicates an account of argumentative rationality by articulating the common, basic idea of its nature, and then identifying a collection of assumptions inherent in it. Argumentative rationality is then contrasted with dual-process theories of reasoning and rationality prevalent in the psychology of reasoning. It is argued that argumentative rationality properly corresponds only with system-2 reasoning in dual-process theories. This result challenges the prescriptive force of argumentative norms derives if they derive at all from their descriptive accuracy of our cognitive capacities. In response, I propose an activity-based account of reasoning which retains the assumptions of argumentative rationality while recontextualizing the relationship between reasoning as a justificatory activity and the psychological states and processes underlying that activity.

Rational design of molecularly imprinted polymer: the choice of cross-linker.

Science.gov (United States)

Muhammad, Turghun; Nur, Zohre; Piletska, Elena V; Yimit, Osmanjan; Piletsky, Sergey A

2012-06-07

The paper describes a rational approach for the selection of cross-linkers during the development of molecularly imprinted polymers (MIPs). As a model system for this research MIPs specific for the drug zidovudine (AZT) were designed and tested. Three cross-linkers trimethylolpropane trimethacrylate (TRIM), ethylene glycol dimethacrylate (EGDMA) and divinylbenzene (DVB) were studied. The analogue of zidovudine (AZT) ester (AZT-ES) was used as a dummy template. The imprinting factors for all of the polymers in the static adsorption experiments were calculated. The data on the AZT adsorption by control polymers (CP), which were prepared with different cross-linkers without a functional monomer, was also analyzed. DVB was found to be more inert towards zidovudine than EGDMA and TRIM, which was confirmed by both molecular modelling and adsorption experiments. It was demonstrated that DVB-based polymers had a higher imprinting factor (I = 1.85) compared with other tested cross-linked polymers. It was suggested that the selection of the cross-linker should be based on the strength of the interaction with the template: the cross-linker which displays lower binding of the template should be preferential because it generates MIPs with lower non-specific binding and a higher imprinting factor, and therefore specificity. Which cross-linker to use for the preparation of any particular MIP can be determined by analysis of the interactions between the cross-linker and template. This could be done either virtually using computational modelling or by template adsorption using a small library of polymers prepared using different cross-linkers.

Rational Thinking in School-Based Practice

Science.gov (United States)

Clark, Mary Kristen; Flynn, Perry

2011-01-01

Purpose: We reflect on Alan Kamhi's (2011) prologue on balancing certainty and uncertainty as it pertains to school-based practice. Method: In schools, rational thinking depends on effective team processes, much like professional learning communities. We consider the conditions that are required for rational thinking and how rational team dialogue…

Milk Production, Physiological Condition and Performance of Etawa Crossbreed Goats Feed by Ration Supplemented with Mangosteen Peel Flour

Science.gov (United States)

Dzarnisa; Rachmadi, D.; Azhar, A.; Fakhrur Riza, R.; Hidayati, A.

2018-02-01

Study on the effect of the addition of mangosteen (Garcinia mangostana L.) peel flour on physiological condition and performance of Etawa crossbreed goats was done. This was to grant the use of mangosteen peel flour that rich of antioxidants and has variety good benefits for health as feed additive for cattle. This study used a Complete Randomized Block Design consisting of 4 treatment groups and 4 replications each. Subjects were 16 female Etawa crossbreed goats randomly designed into treatments group based on lactation periods. Subjects were feed with traditional rations (control, A), traditional rations and 2.5% mangosteen peel flour (B), tradition rations and 5% mangosteen peel flour (C), and traditional rations and 7,5 % mangosteen peel flour (D). Data on performance (milk production) and physiological condition (respiratory frequency, rectal temperature, and heart rate) obtained were analyzed using analysis of variance (ANOVA). The results showed that the addition of mangosteen peel flour as food additive in the rations resulted in variations in the milk production, physiological condition (rectal temperature, heart rate and respiration frequency) and performances (daily weigh gain, food consumption, ration conversion and breast volume) of Etawa crossbreed goats, but significant effect was only observed in the respiration frequency. The addition of 2.5% mangosteen peel flour in the ration caused the best, expected effects on milk production physiological condition and performance of Etawa crossbreed goats.

Ventilation, good indoor air quality and rational use of energy

DEFF Research Database (Denmark)

Clausen, Geo; Fernandes, E. D. O.; DeGids, W.

2003-01-01

The aim of this report is to provide information and advice to policy and decission makers, researchers, architects, designers, and manufacturers on strategies for achieving a good balance between good indoor air quality (IAQ) and the rational use of Energy in buildings, available guidelines...

Updated Army Cook Staffing Model to Reflect Workloads Generated by Current Field Feeding Operations, Group Rations, and Kitchens

National Research Council Canada - National Science Library

Kirejczyk, Harry J

2006-01-01

...: the Unitized Group Ration-A (UGR-A) and the Unitized Group Ration-Heat/Serve (UGR-H/S). These fieldings were designed to increase the frequency and quality of group hot meals and reduce the cook workloads generated by field feeding operations...

Rationality in Machiavelli and in Kant

Directory of Open Access Journals (Sweden)

Vadim Chaly

2016-11-01

Full Text Available The paper contains interpretation and comparative analysis of Machiavelli’s and Kant’s conceptions on rationality as two prime examples of “realist” and “idealist” modes of agency. Kantian model of rationality is viewed as an augmentation of the Machiavellian one, not an opposition to it. To elaborate the point, Robert Aumann’s model of act-rationality and rulerationality is applied to the two philosophical models. Kantian practical reason is interpreted as an addition to Aumann’s instrumental rationality, providing rules for rules, or “rule-rule-rationality”.

Towards a Rational Kingdom in Africa: Knowledge, Critical Rationality and Development in a Twenty-First Century African Cultural Context

Directory of Open Access Journals (Sweden)

Lawrence Ogbo Ugwuanyi

2018-03-01

Full Text Available This paper seeks to locate the kind of knowledge that is relevant for African development in the twenty-first century African cultural context and to propose the paradigm for achieving such knowledge. To do this, it advances the view that the concept of twenty-first century in an African context must be located with the colonial and post-colonial challenges of the African world and applied to serve the African demand. Anchored on this position, the paper outlines and critiques the wrong assumption on which modern state project was anchored in post-colonial Africa and its development dividend to suggest that this is an outcome of a wrong knowledge design that is foundational to the state project and which the project did not address. It proposes a shift in the knowledge paradigm in Africa and suggests critical self-consciousness as a more desirable knowledge design for Africa. It applies the term ‘rational kingdom’ (defined as a community of reason marked by critical conceptual self-awareness driven by innovation and constructivism to suggest this paradigm. ‘Innovation’ is meant as the application of reason with an enlarged capacity to anticipate and address problems with fresh options and ‘constructivism’ is meant as the disposition to sustain innovation by advancing an alternative but more reliable worldview that can meet the exigencies of modernity in an African cultural context. The paper then proceeds to outline the nature of the rational kingdom and its anticipated gains and outcomes. It applies the method of inductive reasoning to advance its position. To do this it invokes selected but crucial areas of African life to locate how the developmental demands of these aspects of life suggest a critical turn in African rationality.

Effective Entrepreneurial Choice: The Role of Rationality and Non-Rationality in Three Entrepreneurs Success Stories

OpenAIRE

Chong, Anne Michele, Siang Yoon

2007-01-01

Good entrepreneurship is important for economic growth and productivity in any modern economy. The purpose of this dissertation is to research how good entrepreneurial decisions are made. In theory, optimal or rational decision making means choosing the best alternative in response to the problem. However, in reality, people do not act rationally because they often cannot make rational choices. The reason is that people do not have enough brain power, time or resources to process the compl...

Rationalization and Design of Enhanced Photoinduced Cycloreversion in Photochromic Dimethyldihydropyrenes by Theoretical Calculations.

Science.gov (United States)

Boggio-Pasqua, Martial; Garavelli, Marco

2015-06-11

This study presents a computational investigation of the initial step of the dimethyldihydropyrene (DHP) to cyclophanediene (CPD) photoinduced ring-opening reaction using time-dependent density functional theory (TD-DFT). In particular, the photochemical path corresponding to the formation of the CPD precursor (CPD*) on the zwitterionic state is scrutinized. The TD-DFT approach was first validated on the parent compound against accurate ab initio calculations. It confirms that CPD* formation is efficiently quenched in this system by an easily accessible S2/S1 conical intersection located in the vicinity of the CPD* minimum and leading to a locally excited state minimum responsible for DHP luminescence. Increased ring-opening quantum yields were observed in benzo[e]-fused-DHP (DHP-1), isobutenyl-DHP (DHP-2), and naphthoyl-DHP (DHP-3). The calculations show that CPD* formation is much more favorable in these systems, either due to an inversion of electronic states in DHP-1, suppressing the formation of the locally excited state, or due to efficient stabilization of CPD* on the S1 potential energy surface in DHP-2 and DHP-3. Both effects can be combined in a rationally designed benzo[e]-fused-naphthoyl-DHP (DHP-4) for which we anticipate an unprecedented efficiency.

Changing fields of rationality - a policy for change?

Energy Technology Data Exchange (ETDEWEB)

Strumse, Einar; Westskog, Hege; Winther, Tanja

2010-07-01

Work objective: To analyze effective strategies for changing households' energy consumption based on an interdisciplinary model for understanding change. Methodology: In this paper we develop a conceptual model for understanding individuals' energy consumption. We synthesize insights from anthropology, social psychology and economics grasping perspectives from behaviour to practice and from the Bourdieu's fields to rationality thinking in economics. We use this insight to analyze strategies for change. Abstract: In this paper we analyze effective strategies for changing households' energy consumption based on an interdisciplinary model for understanding change. The model focuses on four main categories for understanding individual consumption: a. Material constraints b. Values and identity c. Norms d. Ability These are the main influencing factors of the individual's consumption level, but in interaction with the corresponding group and the societal levels for the same factors. The model can be illustrated. One combination of factors on all levels constitutes a field of rationality. We claim that an important strategy for changing energy consumption towards sustainability is changing the field of rationality of the individual. Changing of rationality fields would from our point of view initiate reflection which is an important condition for changed behavior. One example of changing of fields is information measures that relates energy consumption to the 'citizen' field rather than the 'consumer' field. Hence, according to our conceptual framework - how policy should be framed (information measures for instance ) would be an important knowledge area for design of effective policy measures. (Author)

Discrete Choice and Rational Inattention

DEFF Research Database (Denmark)

Fosgerau, Mogens; Melo, Emerson; de Palma, André

2017-01-01

This paper establishes a general equivalence between discrete choice and rational inattention models. Matejka and McKay (2015, AER) showed that when information costs are modelled using the Shannon entropy, the result- ing choice probabilities in the rational inattention model take the multinomial...... logit form. We show that when information costs are modelled using a class of generalized entropies, then the choice probabilities in any rational inattention model are observationally equivalent to some additive random utility discrete choice model and vice versa. This equivalence arises from convex...

Rational top and its classical r-matrix

International Nuclear Information System (INIS)

Aminov, G; Arthamonov, S; Smirnov, A; Zotov, A

2014-01-01

We construct a rational integrable system (the rational top) on a co-adjoint orbit of SL N Lie group. It is described by the Lax operator with spectral parameter and classical non-dynamical skew-symmetric r-matrix. In the case of the orbit of minimal dimension the model is gauge equivalent to the rational Calogero–Moser (CM) system. To obtain the results we represent the Lax operator of the CM model in two different factorized forms—without spectral parameter (related to the spinless case) and another one with the spectral parameter. The latter gives rise to the rational top while the first one is related to generalized Cremmer–Gervais r-matrices. The gauge transformation relating the rational top and CM model provides the classical rational version of the IRF-Vertex correspondence. From the geometrical point of view it describes the modification of SL(N,C)-bundles over degenerated elliptic curve. In view of the Symplectic Hecke Correspondence the rational top is related to the rational spin CM model. Possible applications and generalizations of the suggested construction are discussed. In particular, the obtained r-matrix defines a class of KZB equations. (paper)

Fiber sources for complete calf starter rations.

Science.gov (United States)

Murdock, F R; Wallenius, R W

1980-11-01

Complete calf starter rations containing either 1) alfalfa hay, 2) cottonseed hulls, or 3) alfalfa-beet pulp as sources of fiber were fed to Holstein heifer calves at two locations on a limited milk program from 3 days to 12 wk of age. Rations were isonitrogenous and similar in content of crude fiber and acid detergent fiber. Although growth and development were normal on all rations, calves fed the cottonseed hull ration consumed more starter and gained more body weight than calves fed the other sources of fiber. The similarity of feed efficiencies, rumen pH, and molar ratios of volatile fatty acids between rations indicated no appreciable differences in rumen development or function. The growth response of calves fed the cottonseed hull ration appeared to be a result of better ration acceptability for which no reason was evident. Calves raised at Puyallup gained more body weight than calves at Pullman, and these gains were made more efficiently. These location effects may be related to seasonal differences and greater demands for production of body heat. Although the incidence of scours was less for calves fed alfalfa hay starter, the incidence and severity of bloat were higher for that ration.

Lessons from Learning to Have Rational Expectations

OpenAIRE

Lindh, Thomas

1989-01-01

This paper reviews a growing literature investigating how economic agents may learn rational expectations. Fully rational learning requires implausible initial information assumptions, therefore some form of bounded rationality has come into focus. Such learning models often converge to rational expectations equilibria within certain bounds. Convergence analysis has been much simplified by methods from adaptive control theory. Learning stability as a correspondence principle show some promise...

Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering.

Science.gov (United States)

Hadd, Andrew; Perona, John J

2014-12-19

We have taken a rational approach to redesigning the amino acid binding and aminoacyl-tRNA pairing specificities of bacterial glutaminyl-tRNA synthetase. The four-stage engineering incorporates generalizable design principles and improves the pairing efficiency of noncognate glutamate with tRNA(Gln) by over 10(5)-fold compared to the wild-type enzyme. Better optimized designs of the protein-RNA complex include substantial reengineering of the globular core region of the tRNA, demonstrating a role for specific tRNA nucleotides in specifying the identity of the genetically encoded amino acid. Principles emerging from this engineering effort open new prospects for combining rational and genetic selection approaches to design novel aminoacyl-tRNA synthetases that ligate noncanonical amino acids onto tRNAs. This will facilitate reconstruction of the cellular translation apparatus for applications in synthetic biology.

Starlings uphold principles of economic rationality for delay and probability of reward.

Science.gov (United States)

Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

2013-04-07

Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed.

Strategy selection as rational metareasoning.

Science.gov (United States)

Lieder, Falk; Griffiths, Thomas L

2017-11-01

Many contemporary accounts of human reasoning assume that the mind is equipped with multiple heuristics that could be deployed to perform a given task. This raises the question of how the mind determines when to use which heuristic. To answer this question, we developed a rational model of strategy selection, based on the theory of rational metareasoning developed in the artificial intelligence literature. According to our model people learn to efficiently choose the strategy with the best cost-benefit tradeoff by learning a predictive model of each strategy's performance. We found that our model can provide a unifying explanation for classic findings from domains ranging from decision-making to arithmetic by capturing the variability of people's strategy choices, their dependence on task and context, and their development over time. Systematic model comparisons supported our theory, and 4 new experiments confirmed its distinctive predictions. Our findings suggest that people gradually learn to make increasingly more rational use of fallible heuristics. This perspective reconciles the 2 poles of the debate about human rationality by integrating heuristics and biases with learning and rationality. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Should informed consent be based on rational beliefs?

Science.gov (United States)

Savulescu, J; Momeyer, R W

1997-10-01

Our aim is to expand the regulative ideal governing consent. We argue that consent should not only be informed but also based on rational beliefs. We argue that holding true beliefs promotes autonomy. Information is important insofar as it helps a person to hold the relevant true beliefs. But in order to hold the relevant true beliefs, competent people must also think rationally. Insofar as information is important, rational deliberation is important. Just as physicians should aim to provide relevant information regarding the medical procedures prior to patients consenting to have those procedures, they should also assist patients to think more rationally. We distinguish between rational choice/action and rational belief. While autonomous choice need not necessarily be rational, it should be based on rational belief. The implication for the doctrine of informed consent and the practice of medicine is that, if physicians are to respect patient autonomy and help patients to choose and act more rationally, not only must they provide information, but they should care more about the theoretical rationality of their patients. They should not abandon their patients to irrationality. They should help their patients to deliberate more effectively and to care more about thinking rationally. We illustrate these arguments in the context of Jehovah's Witnesses refusing life-saving blood transfusions. Insofar as Jehovah's Witnesses should be informed of the consequences of their actions, they should also deliberate rationally about these consequences.

Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona.

Science.gov (United States)

Gandhi, Shashank; Haeussler, Maximilian; Razy-Krajka, Florian; Christiaen, Lionel; Stolfi, Alberto

2017-05-01

The CRISPR/Cas9 system has emerged as an important tool for various genome engineering applications. A current obstacle to high throughput applications of CRISPR/Cas9 is the imprecise prediction of highly active single guide RNAs (sgRNAs). We previously implemented the CRISPR/Cas9 system to induce tissue-specific mutations in the tunicate Ciona. In the present study, we designed and tested 83 single guide RNA (sgRNA) vectors targeting 23 genes expressed in the cardiopharyngeal progenitors and surrounding tissues of Ciona embryo. Using high-throughput sequencing of mutagenized alleles, we identified guide sequences that correlate with sgRNA mutagenesis activity and used this information for the rational design of all possible sgRNAs targeting the Ciona transcriptome. We also describe a one-step cloning-free protocol for the assembly of sgRNA expression cassettes. These cassettes can be directly electroporated as unpurified PCR products into Ciona embryos for sgRNA expression in vivo, resulting in high frequency of CRISPR/Cas9-mediated mutagenesis in somatic cells of electroporated embryos. We found a strong correlation between the frequency of an Ebf loss-of-function phenotype and the mutagenesis efficacies of individual Ebf-targeting sgRNAs tested using this method. We anticipate that our approach can be scaled up to systematically design and deliver highly efficient sgRNAs for the tissue-specific investigation of gene functions in Ciona. Copyright © 2017 Elsevier Inc. All rights reserved.

Rational design of an EGF-IL18 fusion protein: Implication for developing tumor therapeutics

International Nuclear Information System (INIS)

Lu Jianxin; Peng Ying; Meng Zhefeng; Jin Liqin; Lu Yongsui; Guan Minxin

2005-01-01

Interleukin-18 (IL-18) is a proinflammatory cytokine. This protein has a role in regulating immune responses and exhibits significant anti-tumor activities. Epidermal growth factor (EGF) is an important growth factor that plays a central role in the regulation of cell cycle and differentiation. It was proposed that a targeted delivery of IL-18 by generation of IL-18-EGF fusion protein might decrease adverse effects and result in enhancing cytotoxic and antitumor activities. In the present study, a fusion protein, consisting of EGFR binding domain fused to human IL-18 mature peptide via a linker peptide of (Gly 4 Ser) 3, was constructed and expressed in the insect cell line Sf9 using Bac-to-Bac baculovirus expression system. We showed that the purified recombinant fusion protein induced similar levels of IFN-γ to that of native IL-18 protein in human PBMC in the presence of ConA. Furthermore, EGF receptor competitive test in human epithelial cancer A431 cell line showed that EGF-IL18 fusion protein can specifically bind with EGFR by competing with native EGF protein. These suggest that this rationally designed protein can be further developed as novel tumor therapeutics

Rational optimization of reliability and safety policies

International Nuclear Information System (INIS)

Melchers, Robert E.

2001-01-01

Optimization of structures for design has a long history, including optimization using numerical methods and optimality criteria. Much of this work has considered a subset of the complete design optimization problem--that of the technical issues alone. The more general problem must consider also non-technical issues and, importantly, the interplay between them and the parameters which influence them. Optimization involves optimal setting of design or acceptance criteria and, separately, optimal design within the criteria. In the modern context of probability based design codes this requires probabilistic acceptance criteria. The determination of such criteria involves more than the nominal code failure probability approach used for design code formulation. A more general view must be taken and a clear distinction must be made between those matters covered by technical reliability and non-technical reliability. The present paper considers this issue and outlines a framework for rational optimization of structural and other systems given the socio-economic and political systems within which optimization must be performed

Product differentiation under bounded rationality

NARCIS (Netherlands)

Vermeulen, B.; Poutré, La J.A.; Kok, de A.G.; Pyka, A.; Handa, H.; Ishibuchi, H.; Ong, Y.-S.; Tan, K.-C.

2015-01-01

We study product differentiation equilibria and dynamics on the Salop circle under bounded rationality. Due to bounded rationality, firms tend to agglomerate in pairs. Upon adding a second tier of component suppliers, downstream assemblers may escape pairwise horizontal agglomeration. Moreover, we

On the choice of a rational system of water economy of the industrial enterprice

International Nuclear Information System (INIS)

Tsikhelashvili, Z.; Khatiuri, Kh.; Verulava, G.; Zakutashvili, G.

2009-01-01

Rational systems and projects of water economy of the industrial enterprise (allowing for the development of waste-free production processes, industrial water recycling with water treatment or without it, and cooling recycling) are discussed. The analysis of rational systems is of primary importance when designing and/or reconstructing the industrial water economy. Such systems and projects must account for all local conditions determining the advantage of their employment from the sanitary and economic viewpoints. (author)

An evaluation of rational-emotive imagery as a component of rational-emotive therapy in the treatment of test anxiety.

Science.gov (United States)

Hymen, S P; Warren, R

1978-06-01

This study evaluated the efficacy of rational-emotive imagery as a component of rational-emotive therapy in reduction of college students' test anxiety. 11 volunteers met for 6 1-hr. group treatment sessions over a 3-wk. period. After 2 initial treatment sessions subjects were randomly assigned to groups given either rational-emotive therapy with rational-emotive imagery or rational-emotive therapy without imagery. Contrary to predictions, improvement between groups on self-report and performance measures was nonsignificant. Failure to obtain differences was attributed to similarities in content of treatment sessions and short treatment time. Combined groups reported significant improvement on all dependent measures. Although the study did not yield the predicted benefits of the imagery, results lend further support to the efficacy of rational-emotive therapy procedures in the reduction of test anxiety.

Rationing in health systems: A critical review.

Science.gov (United States)

Keliddar, Iman; Mosadeghrad, Ali Mohammad; Jafari-Sirizi, Mehdi

2017-01-01

Background: It is difficult to provide health care services to all those in need of such services due to limited resources and unlimited demands. Thus, priority setting and rationing have to be applied. This study aimed at critically examining the concept of rationing in health sector and identifying its purposes, influencing factors, mechanisms, and outcomes. Methods: The critical interpretive synthesis methodology was used in this study. PubMed, Cochrane, and Proquest databases were searched using the related key words to find related documents published between 1970 and 2015. In total, 161 published reports were reviewed and included in the study. Thematic content analysis was applied for data analysis. Results: Health services rationing means restricting the access of some people to useful or potentially useful health services due to budgetary limitation. The inherent features of the health market and health services, limited resources, and unlimited needs necessitate health services rationing. Rationing can be applied in 4 levels: health care policy- makers, health care managers, health care providers, and patients. Health care rationing can be accomplished through fixed budget, benefit package, payment mechanisms, queuing, copayments, and deductibles. Conclusion: This paper enriched our understanding of health services rationing and its mechanisms at various levels and contributed to the literature by broadly conceptualizing health services rationing.

Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics

Science.gov (United States)

Chen, Chun-Long; Qi, Jiahui; Tao, Jinhui; Zuckermann, Ronald N.; DeYoreo, James J.

2014-01-01

In nature, proteins play a significant role in biomineral formation. One of the ultimate goals of bioinspired materials science is to develop highly stable synthetic molecules that mimic the function of these natural proteins by controlling crystal formation. Here, we demonstrate that both the morphology and the degree of acceleration or inhibition observed during growth of calcite in the presence of peptoids can be rationally tuned by balancing the electrostatic and hydrophobic interactions, with hydrophobic interactions playing the dominant role. While either strong electrostatic or hydrophobic interactions inhibit growth and reduces expression of the {104} faces, correlations between peptoid-crystal binding energies and observed changes in calcite growth indicate moderate electrostatic interactions allow peptoids to weakly adsorb while moderate hydrophobic interactions cause disruption of surface-adsorbed water layers, leading to growth acceleration with retained expression of the {104} faces. This study provides fundamental principles for designing peptoids as crystallization promoters, and offers a straightforward screening method based on macroscopic crystal morphology. Because peptoids are sequence-specific, highly stable, and easily synthesized, peptoid-enhanced crystallization offers a broad range of potential applications. PMID:25189418

Rational Design of Zirconium-doped Titania Photocatalysts with Synergistic Brønsted Acidity and Photoactivity.

Science.gov (United States)

Ma, Runyuan; Wang, Liang; Zhang, Bingsen; Yi, Xianfeng; Zheng, Anmin; Deng, Feng; Yan, Xuhua; Pan, Shuxiang; Wei, Xiao; Wang, Kai-Xue; Su, Dang Sheng; Xiao, Feng-Shou

2016-10-06

The preparation of photocatalysts with high activities under visible-light illumination is challenging. We report the rational design and construction of a zirconium-doped anatase catalyst (S-Zr-TiO 2 ) with Brønsted acidity and photoactivity as an efficient catalyst for the degradation of phenol under visible light. Electron microscopy images demonstrate that the zirconium sites are uniformly distributed on the sub-10 nm anatase crystals. UV-visible spectrometry indicates that the S-Zr-TiO 2 is a visible-light-responsive catalyst with narrower band gap than conventional anatase. Pyridine-adsorption infrared and acetone-adsorption 13 C NMR spectra confirm the presence of Brønsted acidic sites on the S-Zr-TiO 2 sample. Interestingly, the S-Zr-TiO 2 catalyst exhibits high catalytic activity in the degradation of phenol under visible-light illumination, owing to a synergistic effect of the Brønsted acidity and photoactivity. Importantly, the S-Zr-TiO 2 shows good recyclability. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rationally Designed, Multifunctional Self-Assembled Nanoparticles for Covalently Networked, Flexible and Self-Healable Superhydrophobic Composite Films.

Science.gov (United States)

Lee, Yujin; You, Eun-Ah; Ha, Young-Geun

2018-03-21

For constructing bioinspired functional films with various superhydrophobic functions, including self-cleaning, anticorrosion, antibioadhesion, and oil-water separation, hydrophobic nanomaterials have been widely used as crucial structural components. In general, hydrophobic nanomaterials, however, cannot form strong chemical bond networks in organic-inorganic hybrid composite films because of the absence of chemically compatible binding components. Herein, we report the rationally designed, multifunctional self-assembled nanoparticles with tunable functionalities of covalent cross-linking and hydrophobicity for constructing three-dimensionally interconnected superhydrophobic composite films via a facile solution-based fabrication at room temperature. The multifunctional self-assembled nanoparticles allow the systematic control of functionalities of composite films, as well as the stable formation of covalently linked superhydrophobic composite films with excellent flexibility (bending radii of 6.5 and 3.0 mm, 1000 cycles) and self-healing ability (water contact angle > 150°, ≥10 cycles). The presented strategy can be a versatile and effective route to generating other advanced functional films with covalently interconnected composite networks.

Research on Bounded Rationality of Fuzzy Choice Functions

Directory of Open Access Journals (Sweden)

Xinlin Wu

2014-01-01

Full Text Available The rationality of a fuzzy choice function is a hot research topic in the study of fuzzy choice functions. In this paper, two common fuzzy sets are studied and analyzed in the framework of the Banerjee choice function. The complete rationality and bounded rationality of fuzzy choice functions are defined based on the two fuzzy sets. An assumption is presented to study the fuzzy choice function, and especially the fuzzy choice function with bounded rationality is studied combined with some rationality conditions. Results show that the fuzzy choice function with bounded rationality also satisfies some important rationality conditions, but not vice versa. The research gives supplements to the investigation in the framework of the Banerjee choice function.

Fundamental Investigations and Rational Design of Durable High-Performance SOFC Cathodes

Energy Technology Data Exchange (ETDEWEB)

Chen, Yu [Georgia Inst. of Technology, Atlanta, GA (United States); Ding, Dong [Georgia Inst. of Technology, Atlanta, GA (United States); Wei, Tao [Georgia Inst. of Technology, Atlanta, GA (United States); Liu, Meilin [Georgia Inst. of Technology, Atlanta, GA (United States)

2016-03-31

The main objective of this project is to unravel the degradation mechanism of LSCF cathodes under realistic operating conditions with different types of contaminants, aiming towards the rational design of cathodes with high-performance and enhanced durability by combining a porous backbone (such as LSCF) with a thin catalyst coating. The mechanistic understanding will help us to optimize the composition and morphology of the catalyst layer and microstructure of the LSCF backbone for better performance and durability. More specifically, the technical objectives include: (1) to unravel the degradation mechanism of LSCF cathodes under realistic operating conditions with different types of contaminants using in situ and ex situ measurements performed on specially-designed cathodes; (2) to examine the microstructural and compositional evolution of LSCF cathodes as well as the cathode/electrolyte interfaces under realistic operating conditions; (3) to correlate the fuel cell performance instability and degradation with the microstructural and morphological evolution and surface chemistry change of the cathode under realistic operating conditions; (4) to explore new catalyst materials and electrode structures to enhance the stability of the LSCF cathode under realistic operating conditions; and (5) to validate the long term stability of the modified LSCF cathode in commercially available cells under realistic operating conditions. We have systematically evaluated LSCF cathodes in symmetrical cells and anode supported cells under realistic conditions with different types of contaminants such as humidity, CO₂, and Cr. Electrochemical models for the design of test cells and understanding of mechanisms have been developed for the exploration of fundamental properties of electrode materials. It is demonstrated that the activity and stability of LSCF cathodes can be degraded by the introduction of contaminants. The microstructural and compositional evolution of LSCF

Rational risk-based decision support for drinking water well managers by optimized monitoring designs

Science.gov (United States)

Enzenhöfer, R.; Geiges, A.; Nowak, W.

2011-12-01

Advection-based well-head protection zones are commonly used to manage the contamination risk of drinking water wells. Considering the insufficient knowledge about hazards and transport properties within the catchment, current Water Safety Plans recommend that catchment managers and stakeholders know, control and monitor all possible hazards within the catchments and perform rational risk-based decisions. Our goal is to supply catchment managers with the required probabilistic risk information, and to generate tools that allow for optimal and rational allocation of resources between improved monitoring versus extended safety margins and risk mitigation measures. To support risk managers with the indispensable information, we address the epistemic uncertainty of advective-dispersive solute transport and well vulnerability (Enzenhoefer et al., 2011) within a stochastic simulation framework. Our framework can separate between uncertainty of contaminant location and actual dilution of peak concentrations by resolving heterogeneity with high-resolution Monte-Carlo simulation. To keep computational costs low, we solve the reverse temporal moment transport equation. Only in post-processing, we recover the time-dependent solute breakthrough curves and the deduced well vulnerability criteria from temporal moments by non-linear optimization. Our first step towards optimal risk management is optimal positioning of sampling locations and optimal choice of data types to reduce best the epistemic prediction uncertainty for well-head delineation, using the cross-bred Likelihood Uncertainty Estimator (CLUE, Leube et al., 2011) for optimal sampling design. Better monitoring leads to more reliable and realistic protection zones and thus helps catchment managers to better justify smaller, yet conservative safety margins. In order to allow an optimal choice in sampling strategies, we compare the trade-off in monitoring versus the delineation costs by accounting for ill

The Application of Rational-Emotive Behavior Therapy to Reduce Stress among Mother with Leukemia Children

Directory of Open Access Journals (Sweden)

Yuni Sufyanti Arief

2016-09-01

Full Text Available Introduction: A child who is diagnosed with Leukemia will undergo several procedures are long and painful action. During the process of hospitalization due to leukemia children and parents can experience a variety of events or actions handling according to various studies shown by the experience very traumatic and stressful (Supartini 2004 in Arif, SY, 2007. Some of the methods used to deal with anxiety is psikoprofilaksis, relaxation and imagination (Reeder et al., 2011. Rational-emotive behavior therapy by Albert Ellis in 1990 describes a unique man who is basically have a tendency to think rational and irrational. Methods: aim of this study is to explain the effect of Rational Emotive Behavior Therapy (REBT for stress levels of mothers with children suffering from Leukemia. The study design used was a pre-experiment Quasy-post control group design. The sample was 10 mothers of children diagnosed with leukemia are treated in a child hematology ward Soetomo hospital. Variable in this study is the level of depression and anxiety mothers with children suffering from leukemia. Result: Based on the results obtained Wilcoxon statistical test p = 0.025 in the treatment group and p = 0.32 in the control group. Mann Whitney test results obtained p = 0.012. Conclution: Rational-emotive behavior therapy can reduce levels of depression and anxiety (stress mothers with children suffering from leukemia. It is expected that the application of rational -emotive behavior therapy can be done to reduce depression and anxiety in women with chronic disease cases while maintaining the effectiveness the goal of REBT. Keywords: stress, anxiety, depression, rational-emotive behavior

Development of modified rational buyer auction for procurement of ancillary services utilizing participation matrix

International Nuclear Information System (INIS)

Jamalzadeh, R.; Ardehali, M.M.; Rashidinejad, M.

2008-01-01

The rational buyer auction is based on a simultaneous auction that is the redesigned auction mechanism for ancillary services by the California independent system operator (CAISO). The incentive for the rational buyer auction is CAISO's intent to adopt a common sense rule of substituting higher-quality lower-cost services for lower-quality higher-cost services, when it results in reduced total procurement cost. For the purposes of designing a desirable auction where the minimum cost for the objective function as well as prevention of price reversal are achieved, either the payment cost in marginal pricing auction must be lowered or price reversal in rational buyer auction must be avoided. The objectives of this study are (a) to develop a newly proposed 'modified rational buyer' auction that does not allow price reversal and (b) to propose and validate a solution procedure that is based on participation matrix and discrete programming. The validation of the proposed solution procedure is accomplished through examination of two case studies available in the literature. Based on the first case study data, it is shown that the newly developed modified rational buyer auction avoids price reversal occurrence, while the total payment of ISO is increased by 5.8%, as compared with rational buyer auction. Also in comparison with marginal pricing auction, the ISO payment is lowered by 38.8%, when the newly developed modified rational buyer auction is utilized. For future work, it is recommended that the application of the modified rational buyer auction to joint dispatch of energy and ancillary services is investigated

Using Rational-Emotive Therapy to Prevent Classroom Problems.

Science.gov (United States)

Webber, Jo; Coleman, Maggie

1988-01-01

Teachers are encouraged to utilize rational-emotive therapy to prevent and deal with classroom behavior problems. Rational-emotive therapy is defined, the ABC model of rational thinking briefly explained, types of irrational thinking identified, and suggestions for becoming a rational thinker are offered. Classroom examples are given. (DB)

[Rationalization, rationing, prioritization: terminology and ethical approaches to the allocation of limited resources in hematology/oncology].

Science.gov (United States)

Winkler, Eva

2011-01-01

The field of oncology with its numerous high-priced innovations contributes considerably to the fact that medical progress is expensive. Additionally, due to the demographic changes and the increasing life expectancy, a growing number of cancer patients want to profit from this progress. Since resources are limited also in the health system, the fair distribution of the available resources urgently needs to be addressed. Dealing with scarcity is a typical problem in the domain of justice theory; therefore, this article first discusses different strategies to manage limited resources: rationalization, rationing, and prioritization. It then presents substantive as well as procedural criteria that assist in the just distribution of effective health benefits. There are various strategies to reduce the utilization of limited resources: Rationalization means that efficiency reserves are being exhausted; by means of rationing, effective health benefits are withheld due to cost considerations. Rationing can occur implicitly and thus covertly, e.g. through budgeting or the implementation of waiting periods, or explicitly, through transparent rules or policies about healthcare coverage. Ranking medical treatments according to their importance (prioritization) is often a prerequisite for rationing decisions. In terms of requirements of justice, both procedural and substantive criteria (e.g. equality, urgency, benefit) are relevant for the acceptance and quality of a decision to limit access to effective health benefits. Copyright © 2011 S. Karger AG, Basel.

Rational design of improved pharmabiotics.

LENUS (Irish Health Repository)

Sleator, Roy D

2009-01-01

Herein we review the most recent advances in probiotic research and applications with particular emphasis on the novel concept of patho-biotechnology: the application of pathogen-derived (ex vivo and in vivo) stress survival strategies for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications.

Differential Rationality and Personal Development.

Science.gov (United States)

Fincher, Cameron

This publication discusses differential rationality; it asserts that the development of institutions, professions, and individuals involves the differentiation of forms and styles of thinking and knowing that are, in various ways, idiosyncratic. Based on this understanding, differential rationality can be seen as a developmental construct that…

Rational reconstructions of modern physics

CERN Document Server

Mittelstaedt, Peter

2013-01-01

Newton’s classical physics and its underlying ontology are loaded with several metaphysical hypotheses that cannot be justified by rational reasoning nor by experimental evidence. Furthermore, it is well known that some of these hypotheses are not contained in the great theories of Modern Physics, such as the theory of Special Relativity and Quantum Mechanics. This book shows that, on the basis of Newton’s classical physics and by rational reconstruction, the theory of Special Relativity as well as Quantum Mechanics can be obtained by partly eliminating or attenuating the metaphysical hypotheses. Moreover, it is shown that these reconstructions do not require additional hypotheses or new experimental results. In the second edition the rational reconstructions are completed with respect to General Relativity and Cosmology. In addition, the statistics of quantum objects is elaborated in more detail with respect to the rational reconstruction of quantum mechanics. The new material completes the approach of t...

Rational Choice and the Framing of Decisions.

Science.gov (United States)

1986-05-29

survival in a competitive environment , and a minority of rational individuals can sometimes impose rationality on the whole market. Third, the...intuitive appeal of the axioms of rational choice makes it plausible that the theory derived from these axioms should provide an acceptable account of choice...rn-use U? RATIONAL CHOICE AMD THE FINNING OF KCISIOUS(U mi/ STANFORD UNIV CR A TYERSEY ET AL. 29 NAYN4-S4-K-S61SWICLASS IF lED FO 5/10S IL EEEEEEEE

Intergroup conflict and rational decision making.

Science.gov (United States)

Martínez-Tur, Vicente; Peñarroja, Vicente; Serrano, Miguel A; Hidalgo, Vanesa; Moliner, Carolina; Salvador, Alicia; Alacreu-Crespo, Adrián; Gracia, Esther; Molina, Agustín

2014-01-01

The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict -associated with indicators of the activation of negative feelings (negative affect state and heart rate)- has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making.

Intergroup Conflict and Rational Decision Making

Science.gov (United States)

Martínez-Tur, Vicente; Peñarroja, Vicente; Serrano, Miguel A.; Hidalgo, Vanesa; Moliner, Carolina; Salvador, Alicia; Alacreu-Crespo, Adrián; Gracia, Esther; Molina, Agustín

2014-01-01

The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict –associated with indicators of the activation of negative feelings (negative affect state and heart rate)– has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making. PMID:25461384

Intergroup conflict and rational decision making.

Directory of Open Access Journals (Sweden)

Vicente Martínez-Tur

Full Text Available The literature has been relatively silent about post-conflict processes. However, understanding the way humans deal with post-conflict situations is a challenge in our societies. With this in mind, we focus the present study on the rationality of cooperative decision making after an intergroup conflict, i.e., the extent to which groups take advantage of post-conflict situations to obtain benefits from collaborating with the other group involved in the conflict. Based on dual-process theories of thinking and affect heuristic, we propose that intergroup conflict hinders the rationality of cooperative decision making. We also hypothesize that this rationality improves when groups are involved in an in-group deliberative discussion. Results of a laboratory experiment support the idea that intergroup conflict -associated with indicators of the activation of negative feelings (negative affect state and heart rate- has a negative effect on the aforementioned rationality over time and on both group and individual decision making. Although intergroup conflict leads to sub-optimal decision making, rationality improves when groups and individuals subjected to intergroup conflict make decisions after an in-group deliberative discussion. Additionally, the increased rationality of the group decision making after the deliberative discussion is transferred to subsequent individual decision making.

Rational Design of Improved Pharmabiotics

Directory of Open Access Journals (Sweden)

Roy D. Sleator

2009-01-01

Full Text Available Herein we review the most recent advances in probiotic research and applications with particular emphasis on the novel concept of patho-biotechnology: the application of pathogen-derived (ex vivo and in vivo stress survival strategies for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications.

Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

DEFF Research Database (Denmark)

Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.

2006-01-01

The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglut......The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S...

Rational-Emotive Therapy versus Systematic Desensitization: A Comment on Moleski and Tosi.

Science.gov (United States)

Atkinson, Leslie

1983-01-01

Questioned the statistical analyses of the Moleski and Tosi investigation of rational-emotive therapy versus systematic desensitization. Suggested means for lowering the error rate through a more efficient experimental design. Recommended a reanalysis of the original data. (LLL)

Rational customs clearance technology choice

OpenAIRE

Shramenko, N.; Andriets, V.

2008-01-01

Issues concerning cargo delivery efficiencyincrease by choice of rational customs clearance technology have been considered. Three possible variants of customs clearance andmethods which allow to define the most rational version of cargo delivery in international road communication based on main efficiency criteria for definite distance have been presented.

Rationally Designed Peptides and Peptidomimetics as Inhibitors of Amyloid-β (Aβ) Aggregation: Potential Therapeutics of Alzheimer's Disease.

Science.gov (United States)

Goyal, Deepti; Shuaib, Suniba; Mann, Sukhmani; Goyal, Bhupesh

2017-02-13

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The worldwide effort to develop peptide-based inhibitors of amyloid-β (Aβ) aggregation can be considered an unplanned combinatorial experiment. An understanding of what has been done and achieved may advance our understanding of AD pathology and the discovery of effective therapeutic agents. We review here the history of such peptide-based inhibitors, including those based on the Aβ sequence and those not derived from that sequence, containing both natural and unnatural amino acid building blocks. Peptide-based aggregation inhibitors hold significant promise for future AD therapy owing to their high selectivity, effectiveness, low toxicity, good tolerance, low accumulation in tissues, high chemical and biological diversity, possibility of rational design, and highly developed methods for analyzing their mode of action, proteolytic stability (modified peptides), and blood-brain barrier (BBB) permeability.

Cognitive Rationality and Its Logic-Mathematical Language

Science.gov (United States)

Masalova, Svetlana

2012-01-01

The article deals with the cognitive (flexible) rationality, combining rational and irrational moments of the scientific search of the cognizing subject. Linguo-cognitive model of the concept as the flexible regulative rationality reveals the activity of the cognitive processes and the mentality of the epistemological-ontic subject, its leading…

Linking patient satisfaction with nursing care: the case of care rationing - a correlational study

Science.gov (United States)

2014-01-01

Background Implicit rationing of nursing care is the withholding of or failure to carry out all necessary nursing measures due to lack of resources. There is evidence supporting a link between rationing of nursing care, nurses’ perceptions of their professional environment, negative patient outcomes, and placing patient safety at risk. The aims of the study were: a) To explore whether patient satisfaction is linked to nurse-reported rationing of nursing care and to nurses’ perceptions of their practice environment while adjusting for patient and nurse characteristics. b) To identify the threshold score of rationing by comparing the level of patient satisfaction factors across rationing levels. Methods A descriptive, correlational design was employed. Participants in this study included 352 patients and 318 nurses from ten medical and surgical units of five general hospitals. Three measurement instruments were used: the BERNCA scale for rationing of care, the RPPE scale to explore nurses’ perceptions of their work environment and the Patient Satisfaction scale to assess the level of patient satisfaction with nursing care. The statistical analysis included the use of Kendall’s correlation coefficient to explore a possible relationship between the variables and multiple regression analysis to assess the effects of implicit rationing of nursing care together with organizational characteristics on patient satisfaction. Results The mean score of implicit rationing of nursing care was 0.83 (SD = 0.52, range = 0–3), the overall mean of RPPE was 2.76 (SD = 0.32, range = 1.28 – 3.69) and the two scales were significantly correlated (τ = −0.234, p patient satisfaction, even after controlling for nurse and patient characteristics. The results from the adjusted regression models showed that even at the lowest level of rationing (i.e. 0.5) patients indicated low satisfaction. Conclusions The results support the relationships between

Probabilistic approach to rationalization of plants maintenance

International Nuclear Information System (INIS)

Kasai, Masao; Notoya, Junichi; Uchimoto, Tetsuya; Miya, Kenzo

2001-01-01

Since there are a lot of equipments in large plants, their safety and reliability cannot be kept as high level as designed without maintenance activities. Then preventive maintenance is intensively executed in some large plants. However, it will be inefficient to perform the preventive maintenance blindly. To make maintenance activities effective, it is essential to identify the critical equipments influencing plant safety and/or reliability and carry out the maintenance by focusing attentions on these equipments. It needs quantitative analyses to identify the critical equipments based on the data of failure rates. However, complete data set of failure rates cannot necessarily be available for some plants such as nuclear power plants. In this study, we carry out the reliability analysis for generic LNG plant and calculate various quantitative risk importance measures for each equipment. We propose rather qualitative representations for some quantitative measures, considering the situation without complete data set and conclude that it is possible to rationalize maintenance procedure by using these rather qualitative measures, though the level of rationalization is of course limited. (author)

Book Selection, Collection Development, and Bounded Rationality.

Science.gov (United States)

Schwartz, Charles A.

1989-01-01

Reviews previously proposed schemes of classical rationality in book selection, describes new approaches to rational choice behavior, and presents a model of book selection based on bounded rationality in a garbage can decision process. The role of tacit knowledge and symbolic content in the selection process are also discussed. (102 references)…

Love and rationality: on some possible rational effects of love

Directory of Open Access Journals (Sweden)

Gustavo Ortiz-Millán

2007-01-01

Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.Neste artigo defendo a idéia de que, em vez de perturbar a racionalidade, como a concepção do senso comum o faz, o amor pode, na verdade, ajudar-nos a desenvolver modos racionais de pensar e agir. Dou bons argumentos para o amor romântico ou erótico, uma vez que esse é o tipo de amor que é mais freqüentemente associado à irracionalidade no agir e no pensar. Argumento que esse tipo de amor pode fazer-nos desenvolver formas epistêmicas e práticas de racionalidade. Com base em uma análise de suas tendências características para a ação, argumento que o amor pode ajudar-nos a desenvolver uma forma instrumental de racionalidade para se determinar o melhor meio de atingir o objeto de amor. Ele também pode limitar o número de considerações práticas que podem ajudar-nos a atingir os nossos objetivos. Finalmente, o amor pode gerar modos racionais de formação de crenças ao estruturar os parâmetros considerados na percepção e na aten

A discussion of theoretical and practical rationality

Energy Technology Data Exchange (ETDEWEB)

Wahlstroem, B. [Technical Research Centre of Finland, Espoo (Finland). VTT Automation

1999-12-01

Theoretical rationality as defined in Expected Utility Theory and amended with other considerations gives a good basis for decision making. One should however always keep in mind that practical rationality often is far more complicated. People use their everyday experience when placed before new problems and this may lead to apparently irrational choices which on a closer scrutiny may be completely rational. Theories in human decision making unfortunately becomes untestable, firstly because a theory taking all considerations into account would be to complex to be practical and secondly because the data needed to test the theory cannot be collected. The benefit of EUT is that it is simple and straightforward as compared with competing theories. In the natural sciences rationality is often seen simply as a problem of optimisation. This view is practical, but it has to include also psychological and sociological considerations. The apparent controversy between natural and behavioural sciences could at least in principle be resolved by a better understanding of the complexity of human rationality. The human mind does not work in isolation, but it is adapted to a social community and a continuously changing environment. Understanding all components of human rationality is a challenge which cannot be solved on a short term basis. An important part of human rationality is connected to the intricate balance between individual and societal utility. The human mind has over thousands of years learnt to resolve that balance, but in the modern society there are decisions which may not be solvable with an intuitive approach and a strategy of trial and error. For these decisions more solid theories of rationality will be needed. EUT can in spite of its dismerits be used as the backbone for such a theory, but it has to be extended with better explanations of both individual and social rationality. If this understanding of the practical aspects of human rationality can be reached

A discussion of theoretical and practical rationality

International Nuclear Information System (INIS)

Wahlstroem, B.

1999-01-01

Theoretical rationality as defined in Expected Utility Theory and amended with other considerations gives a good basis for decision making. One should however always keep in mind that practical rationality often is far more complicated. People use their everyday experience when placed before new problems and this may lead to apparently irrational choices which on a closer scrutiny may be completely rational. Theories in human decision making unfortunately becomes untestable, firstly because a theory taking all considerations into account would be to complex to be practical and secondly because the data needed to test the theory cannot be collected. The benefit of EUT is that it is simple and straightforward as compared with competing theories. In the natural sciences rationality is often seen simply as a problem of optimisation. This view is practical, but it has to include also psychological and sociological considerations. The apparent controversy between natural and behavioural sciences could at least in principle be resolved by a better understanding of the complexity of human rationality. The human mind does not work in isolation, but it is adapted to a social community and a continuously changing environment. Understanding all components of human rationality is a challenge which cannot be solved on a short term basis. An important part of human rationality is connected to the intricate balance between individual and societal utility. The human mind has over thousands of years learnt to resolve that balance, but in the modern society there are decisions which may not be solvable with an intuitive approach and a strategy of trial and error. For these decisions more solid theories of rationality will be needed. EUT can in spite of its dismerits be used as the backbone for such a theory, but it has to be extended with better explanations of both individual and social rationality. If this understanding of the practical aspects of human rationality can be reached

THE HICKSIAN RATIONAL CONSUMER

OpenAIRE

Manuel FERNÁNDEZ-GRELA

2005-01-01

The aim of this paper is to trace the evolution of the concept of ''rational consumer'' in Hicks's writings. After being one of the pioneers in the introduction of rationality assumptions about consumer behaviour in economic models, Hicks gradually developed a sceptical view about some of the uses to which those assumptions were put into. The focus of the paper is on continuity in Hicksian views, providing a picture of gradual changes in the long series of Hicks's works

Coping More Effectively Through Rational Self-Counseling.

Science.gov (United States)

Rogers, George W., Jr.

1981-01-01

Rational Self-Counseling, a variation of rational-emotive therapy, is a self-help therapeutic technique in which students are encouraged to be responsible for their own behavior and emotions. The primary function of self-counseling is to evaluate whether thoughts are rational. A list of questions which students might ask themselves is presented.…

Freedom and Rationality : Rousseau on Citizenship

OpenAIRE

Salvat, Christophe

2008-01-01

This paper deals with Rousseau's idea of freedom in terms of rationality and deliberation. It gives support to Berlin's interpretation of the general will as a rational and objective will but dismisses the idea that Rousseau's theory necessarily leads to authoritarianism. The general will, publicly expressed by the law, may be defined as the rational and self-regarding will agents would have if put in an independent and objective state, i.e. the state of nature. The general and the particular...

Rational Design of Si@SiO2/C Composites Using Sustainable Cellulose as a Carbon Resource for Anodes in Lithium-Ion Batteries.

Science.gov (United States)

Shen, Dazhi; Huang, Chaofan; Gan, Lihui; Liu, Jian; Gong, Zhengliang; Long, Minnan

2018-03-07

In this work, we propose a novel and facile route for the rational design of Si@SiO 2 /C anode materials by using sustainable and environment-friendly cellulose as a carbon resource. To simultaneously obtain a SiO 2 layer and a carbon scaffold, a specially designed homogeneous cellulose solution and commercial Si nanopowder are used as the starting materials, and the cellulose/Si composite is directly assembled by an in situ regenerating method. Subsequently, Si@SiO 2 /C composite is obtained after carbonization. As expected, Si@SiO 2 is homogeneously encapsulated in the cellulose-derived carbon network. The obtained Si@SiO 2 /C composite shows a high reversible capacity of 1071 mA h g -1 at a current density of 420 mA g -1 and 70% capacity retention after 200 cycles. This novel, sustainable, and effective design is a promising approach to obtain high-performance and cost-effective composite anodes for practical applications.

Rational choice in field archaelology

Directory of Open Access Journals (Sweden)

Cătălin Pavel

2011-11-01

Full Text Available In the present article I attempt to apply advances in the study of instrumental and epistemic rationality to field archaeology in order to gain insights into the ways archaeologists reason. The cognitive processes, particularly processes of decision making, that enable archaeologists to conduct the excavation in the trench have not been adequately studied so far. I take my cues from two different bodies of theory. I first inquire into the potential that rational choice theory (RCT may have in modeling archaeological behaviour, and I define subjective expected utility, which archaeologists attempt to maximize, in terms of knowledge acquisition and social gain. Following Elster’s criticism of RCT, I conclude that RCT’s standards for rational action do not correspond with those ostensibly used in field archaeology, but that instrumental rationality has a prominent role in the “archaeological experiment”. I further explore if models proposed as reaction to RCT may account for archaeological decision making. I focus on fast and frugal heuristics, and search for archaeological illustrations for some of the cognitive biases that are better documented in psychological literature. I document confirmation and congruence biases, the endowment effect, observer-expectancy bias, illusory correlation, clustering illusion, sunk cost bias, and anchoring, among others and I propose that some of these biases are used as cognitive tools by archaeologists at work and retain epistemic value. However, I find formal logic to be secondary in the development of archaeological reasoning, with default logic and defeasible logic being used instead. I emphasize scientific knowledge as an actively negotiated social product of human inquiry, and conclude that to describe rationality in field archaeology a bounded rationality model is the most promising avenue of investigation.

The rational maps Fλ(z)

Indian Academy of Sciences (India)

It is proved that the rational maps in the family {z → zm +λ/zd : λ ∈ C\\{0}} for integers m, d ≥ 2 ... The problem of the existence of Herman rings of a rational map has been studied by. Lyubich in [9] ..... Surveys 41(4) (1986) 35–95. [10] Milnor J ...

Heterogeneity and the (de)stabilizing role of rationality

International Nuclear Information System (INIS)

Cavalli, Fausto; Naimzada, Ahmad; Pireddu, Marina

2015-01-01

Highlights: • We analyze Cournot oligopolies with heterogeneous firms of generic size. • Rational and naive players are considered. • Stability with respect to oligopoly composition is studied. • In some settings, increasing the rational firms fraction introduces instability. - Abstract: In this paper we study oligopolies of generic size consisting of heterogeneous firms, which adopt best response adjustment mechanisms with either perfect foresight (rational firms) or static expectations (naive firms). Assuming an isoelastic demand function and possibly different marginal costs for the two groups of firms, we focus on the local stability of the Nash equilibrium. We show that, with respect to the oligopoly composition, described in terms of the fraction of rational firms, different scenarios are possible. We find that a high rationality degree may not always guarantee stability, in particular when rational firms have sufficiently larger marginal costs. In fact, in this situation, increasing the fraction of rational firms can even introduce instability. Besides the usual scenarios in which replacing some naive firms with rational ones leads to a stabilization of (or at least keeps unchanged) the dynamics, we provide a family of situations, characterized by costs ratio favorable to naive firms, in which equilibrium loses its stability when naive firms are replaced by rational ones. The results we present are both analytical and simulative.

Rationality and the Logic of Good Reasons.

Science.gov (United States)

Fisher, Walter R.

This paper contends that the rationality of the logic of good reasons is constituted in its use. To support this claim, the paper presents an analysis of the relationship between being reasonable and being rational. It then considers how following the logic of good reasons leads to rationality in the behavior of individuals and groups; the latter…

Rationality, mental causation and social sciences

OpenAIRE

Mladenović Ivan

2009-01-01

The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.

Physiological responses to rational-emotive self-verbalizations.

Science.gov (United States)

Master, S; Gershman, L

1983-12-01

This study tested Albert Ellis' Rational Emotive Therapy (RET) theory which predicts that cognitive beliefs, not the stimulus situation, generate human emotions. According to RET, emotions created by rational beliefs are adaptive, while irrational beliefs result in an unadaptive anxiety level. Results demonstrated that at high levels of problem relevance there was (1) a significantly greater GSR in direct response to the stimulus situation, and also to irrational statements, than to rational and control statements, and (2) no significant difference between rational and neutral control statements. The authors argue that these results are more parsimoniously explained by conditioning theory than by RET theory.

Towards a Characterization of Rational Expectations

OpenAIRE

Itai Arieli

2008-01-01

R. J. Aumann and J. H. Drèze (2008) define a rational expectation of a player i in a game G as the expected payo of some type of i in some belief system for G in which common knowledge of rationality and common priors obtain. Our goal is to characterize the set of rational expectations in terms of the game's payoff matrix. We provide such a characterization for a specific class of strategic games, called semi-elementary, which includes Myerson's "elementary" games.

Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin.

Science.gov (United States)

Judy, Eva; Pagariya, Darshna; Kishore, Nand

2018-03-20

Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

Children's selective trust decisions: rational competence and limiting performance factors.

Science.gov (United States)

Hermes, Jonas; Behne, Tanya; Bich, Anna Elisa; Thielert, Christa; Rakoczy, Hannes

2018-03-01

Recent research has amply documented that even preschoolers learn selectively from others, preferring, for example, reliable over unreliable and competent over incompetent models. It remains unclear, however, what the cognitive foundations of such selective learning are, in particular, whether it builds on rational inferences or on less sophisticated processes. The current study, therefore, was designed to test directly the possibility that children are in principle capable of selective learning based on rational inference, yet revert to simpler strategies such as global impression formation under certain circumstances. Preschoolers (N = 75) were shown pairs of models that either differed in their degree of competence within one domain (strong vs. weak or knowledgeable vs. ignorant) or were both highly competent, but in different domains (e.g., strong vs. knowledgeable model). In the test trials, children chose between the models for strength- or knowledge-related tasks. The results suggest that, in fact, children are capable of rational inference-based selective trust: when both models were highly competent, children preferred the model with the competence most predictive and relevant for a given task. However, when choosing between two models that differed in competence on one dimension, children reverted to halo-style wide generalizations and preferred the competent models for both relevant and irrelevant tasks. These findings suggest that the rational strategies for selective learning, that children master in principle, can get masked by various performance factors. © 2017 John Wiley & Sons Ltd.

Sexual harassment in healthcare: classification of harassers and rationalizations of sex-based harassment behavior.

Science.gov (United States)

Madison, J; Minichiello, V

2001-11-01

This study identified how 16 Australian registered nurses classified sex-based harassers and explained their own behavior and the behavior of the harasser. A qualitative research design, relying on in-depth interviews, was used to collect the data. The study found that harassment is linked to gender roles and that the harassed are reluctant to blame the harasser--the harassed had "sound" rationalizations for harassment. Awareness of the interactional dynamics of self-blame and these rationalizations will help nurse executives ensure a harassment-free workplace.

Rational inattention or rational overreaction?

DEFF Research Database (Denmark)

Browning, Martin; Hansen, Lars Gårn; Smed, Sinne

We investigate differences in how consumers of fish react to health information in the mass media. We specify a dynamic empirical model that allows for heterogeneity in all basic parameters of consumer behavior as well as in how consumers react to information. We estimate the model using a unique...... houshold panel tracking consumption, prices, news stories and media habits over 24 quarters. We fi nd that the consumers most likely to be ’rationally ignorant’ of health effects react more dramatically to health news than the consumers who most likely are well informed....

A density functional theory insight towards the rational design of ionic liquids for SO2 capture.

Science.gov (United States)

García, Gregorio; Atilhan, Mert; Aparicio, Santiago

2015-05-28

A systematic density functional theory (DFT) analysis has been carried out to obtain information at the molecular level on the key parameters related to efficient SO2 capture by ionic liquids (ILs). A set of 55 ILs, for which high gas solubility is expected, has been selected. SO2 solubility of ILs was firstly predicted based on the COSMO-RS (Conductor-like Screening Model for Real Solvents) method, which provides a good prediction of gas solubility data in ILs without prior experimental knowledge of the compounds' features. Then, interactions between SO2 and ILs were deeply analyzed through DFT simulations. This work provides valuable information about required factors at the molecular level to provide high SO2 solubility in ILs, which is crucial for further implementation of these materials in the future. In our opinion, systematic research on ILs for SO2 capture increases our knowledge about those factors which could be controlled at the molecular level, providing an approach for the rational design of task-specific ILs.

Rationality, mental causation and social sciences

Directory of Open Access Journals (Sweden)

Mladenović Ivan

2009-01-01

Full Text Available The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.

Pandemic ventilator rationing and appeals processes.

Science.gov (United States)

Patrone, Daniel; Resnik, David

2011-06-01

In a severe influenza pandemic, hospitals will likely experience serious and widespread shortages of patient pulmonary ventilators and of staff qualified to operate them. Deciding who will receive access to mechanical ventilation will often determine who lives and who dies. This prospect raises an important question whether pandemic preparedness plans should include some process by which individuals affected by ventilator rationing would have the opportunity to appeal adverse decisions. However, the issue of appeals processes to ventilator rationing decisions has been largely neglected in state pandemic planning efforts. If we are to devise just and effective plans for coping with a severe influenza pandemic, more attention to the issue of appeals processes for pandemic ventilator rationing decisions is needed. Arguments for and against appeals processes are considered, and some suggestions are offered to help efforts at devising more rational pandemic preparedness plans.

RATIONAL APPROXIMATIONS TO GENERALIZED HYPERGEOMETRIC FUNCTIONS.

Science.gov (United States)

Under weak restrictions on the various free parameters, general theorems for rational representations of the generalized hypergeometric functions...and certain Meijer G-functions are developed. Upon specialization, these theorems yield a sequency of rational approximations which converge to the

Many faces of rationality: Implications of the great rationality debate for clinical decision-making

OpenAIRE

Djulbegovic, B.; Elqayam, Shira

2017-01-01

open access article Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings fromThe Great Rationality Debate from t...

Rationalizing the Promotion of Non-Rational Behaviors in Organizations.

Science.gov (United States)

Smith, Peter A. C.; Sharma, Meenakshi

2002-01-01

Organizations must balance rational/technical efficiency and emotions. Action learning has been proven to be effective for developing emotional openness in the workplace. Facilitators of action learning should draw upon the disciplines of counseling, Gestalt, psychodynamics, and Eastern philosophies. (Contains 23 references.) (SK)

Generalized NLS hierarchies from rational W algebras

International Nuclear Information System (INIS)

Toppan, F.

1993-11-01

Finite rational W algebras are very natural structures appearing in coset constructions when a Kac-Moody subalgebra is factored out. The problem of relating these algebras to integrable hierarchies of equations is studied by showing how to associate to a rational W algebra its corresponding hierarchy. Two examples are worked out, the sl(2)/U(1) coset, leading to the Non-Linear Schroedinger hierarchy, and the U(1) coset of the Polyakov-Bershadsky W algebra, leading to a 3-field representation of the KP hierarchy already encountered in the literature. In such examples a rational algebra appears as algebra of constraints when reducing a KP hierarchy to a finite field representation. This fact arises the natural question whether rational algebras are always associated to such reductions and whether a classification of rational algebras can lead to a classification of the integrable hierarchies. (author). 19 refs

A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

Directory of Open Access Journals (Sweden)

Deanna M Schmitt

Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

Science.gov (United States)

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action.

A rational evaluation of structural design loads

International Nuclear Information System (INIS)

Tasaka, S.

1993-01-01

The reliability-based seismic design of structures is a design method ensuring that the structural seismic capacity is not less than the maximum seismic load or load effect for a prescribed value of the reliability index, wherein the design reference period, n, is used to specify the n-year maximum load. In the conventional Load and Resistance Factor Design (LRFD) method the design load is commonly determined on the basis of the n-year maximum the probability distribution of which may be given in some different ways. However, in contrast with the structural capacity the n-year maximum load usually involves much larger variabilities. The effort to decrease the variability would, hence, be effective for the purpose of avoiding nuclear power plant (NPP) structures having unnecessarily large capacities. A possible way to do this is to consider the joint probability distribution of the n-year 1st and 2nd maxima of the seismic load derived from the formula of extreme order statistics. Since the reliability index is conventionally associated with the n-year 1st maximum, the conditional probability distribution rather than the joint one of the n-year 1st maximum given a value of the n-year 2nd one will be considered. Three conditional extreme value distributions, which correspond to the usual extreme value distributions of Types I, II and III, and their statistical moments up to the second order are presented. Within the framework of the first-order second moment method, the conditional statistical moments are utilized to calculate the reliability index as well as the design value of the seismic load. The seismic load considered herein is represented by the peak ground acceleration (PGA) in n years. The present scheme is applied to evaluate the design PGA's at II sites in Japan where samples of the annual 1st and 2nd PGA's have been obtained by using historical seismic data. In this application the following two points are of our interest: (a) Define the reliability

Lying for the Greater Good: Bounded Rationality in a Team

Directory of Open Access Journals (Sweden)

Oktay Sürücü

2014-10-01

Full Text Available This paper is concerned with the interaction between fully and boundedly rational agents in situations where their interests are perfectly aligned. The cognitive limitations of the boundedly rational agent do not allow him to fully understand the market conditions and lead him to take non-optimal decisions in some situations. Using categorization to model bounded rationality, we show that the fully rational agent can nudge, i.e., he can manipulate the information he sends and decrease the expected loss caused by the boundedly rational agent. Assuming different types for the boundedly rational agent, who differ only in the categories used, we show that the fully rational agent may learn the type of the boundedly rational agent along their interaction. Using this additional information, the outcome can be improved and the amount of manipulated information can be decreased. Furthermore, as the length of the interaction increases the probability that the fully rational agent learns the type of the boundedly rational agent grows

A RATIONAL APPROACH TO SEPTIC TANK DESIGN

African Journals Online (AJOL)

2012-03-01

Mar 1, 2012 ... to obtain the volume of sludge accumulated in this time interval. Using a minimum ... Design charts and a Microsoft Excel based design programme were produced to ..... Jowett, E. C. and Lay, R. Comparative per- formance of ...

Normative and descriptive rationality: from nature to artifice and back

Science.gov (United States)

Besold, T. R.; Uckelman, S. L.

2018-03-01

Rationality plays a key role in both the study of human reasoning and Artificial Intelligence (AI). Certain notions of rationality have been adopted in AI as guides for the development of intelligent machines and these notions have been given a normative function. The notions of rationality in AI are often taken to be closely related to conceptions of rationality in human contexts. In this paper, we argue that the normative role of rationality differs in the human and artificial contexts. While rationality in human-focused fields of study is normative, prescribing how humans ought to reason, the normative conception in AI is built on a notion of human rationality which is descriptive, not normative, in the human context, as AI aims at building agents which reason as humans do. In order to make this point, we review prominent notions of rationality used in psychology, cognitive science, and (the history of) philosophy, as well as in AI, and discuss some factors that contributed to rationality being assigned the differing normative statuses in the differing fields of study. We argue that while 'rationality' is a normative notion in both AI and in human reasoning, the normativity of the AI conception of 'rationality' is grounded in a descriptive account of human rationality.

Momentum effect in stocks’ returns between the rational and the behavioural financial theories: Proposition of the progressive rationality

Directory of Open Access Journals (Sweden)

Faten Zoghlami

2013-01-01

Full Text Available     The puzzling momentum strategies’ payoffs defied the rational financial theory asserting the stocks returns’ unpredictability. Moreover, the momentum effect persist the main stocks returns’ anomaly escaping any risk-based explanation. The resilience of this phenomenon had favoured the development of behavioural financial field, which breaks with the investor’ full rationality hypothesis. This paper attempts to reconcile between the rational and behavioural financial theories, through the introduction of the progressive rationality concept. Especially, we argue that recognizing the temporary inappropriate investors’ reactions; can resolve the puzzling momentum anomaly. To fulfil our objective, we identify the appropriate autoregressive level that captures the significant autocorrelations involved by the investors’ over and under reactions. Then, we explore the profitability of the 6/6 momentum strategy implemented on the adjusted stocks’ returns. The adjusted momentum strategy is still profitable but no longer puzzling, since the related excess return is henceforth fully captured by a β and a size effect.Key words: Tunisian momentum effect, the rational finance theory, the behavioural finance theory, the three-factorial model and the autoregressive process.

Neurophysiology and Rationality in Political Thinking.

Science.gov (United States)

Peterson, Steven A.

Research both in cognitive psychology and psychobiology suggests that political behavior is often less rational than individuals believe it to be. Information processing, memory, and decision making are interlinked processes. Studies in cognitive psychology reveal that even though decision making requires rationality, individuals often adopt…

Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives.

Directory of Open Access Journals (Sweden)

Brian Healy

Full Text Available Nisin A is the most extensively studied lantibiotic and has been used as a preservative by the food industry since 1953. This 34 amino acid peptide contains three dehydrated amino acids and five thioether rings. These rings, resulting from one lanthionine and four methyllanthionine bridges, confer the peptide with its unique structure. Nisin A has two mechanisms of action, with the N-terminal domain of the peptide inhibiting cell wall synthesis through lipid II binding and the C-terminal domain responsible for pore-formation. The focus of this study is the three amino acid 'hinge' region (N 20, M 21 and K 22 which separates these two domains and allows for conformational flexibility. As all lantibiotics are gene encoded, novel variants can be generated through manipulation of the corresponding gene. A number of derivatives in which the hinge region was altered have previously been shown to possess enhanced antimicrobial activity. Here we take this approach further by employing simultaneous, indiscriminate site-saturation mutagenesis of all three hinge residues to create a novel bank of nisin derivative producers. Screening of this bank revealed that producers of peptides with hinge regions consisting of AAK, NAI and SLS displayed enhanced bioactivity against a variety of targets. These and other results suggested a preference for small, chiral amino acids within the hinge region, leading to the design and creation of producers of peptides with hinges consisting of AAA and SAA. These producers, and the corresponding peptides, exhibited enhanced bioactivity against Lactococcus lactis HP, Streptococcus agalactiae ATCC 13813, Mycobacterium smegmatis MC2155 and Staphylococcus aureus RF122 and thus represent the first example of nisin derivatives that possess enhanced activity as a consequence of rational design.

Positroids Induced by Rational Dyck Paths

OpenAIRE

Gotti, Felix

2017-01-01

A rational Dyck path of type $(m,d)$ is an increasing unit-step lattice path from $(0,0)$ to $(m,d) \\in \\mathbb{Z}^2$ that never goes above the diagonal line $y = (d/m)x$. On the other hand, a positroid of rank $d$ on the ground set $[d+m]$ is a special type of matroid coming from the totally nonnegative Grassmannian. In this paper we describe how to naturally assign a rank $d$ positroid on the ground set $[d+m]$, which we name rational Dyck positroid, to each rational Dyck path of type $(m,d...

Rationalization and the Role of the School Counselor.

Science.gov (United States)

Clark, Arthur J.

1995-01-01

Examines rationalization in counselors' interactions with students, parents, and teachers--provides examples of each kind of interaction. Describes the dynamics of rationalization in the schools and outlines interventions that may be used with students, parents, and teachers. Also explores counselors' use of rationalization and gives examples of…

Rationality in the Cryptographic Model

DEFF Research Database (Denmark)

Hubacek, Pavel

This thesis presents results in the field of rational cryptography. In the first part we study the use of cryptographic protocols to avoid mediation and binding commitment when implementing game theoretic equilibrium concepts. First, we concentrate on the limits of cryptographic cheap talk...... to implement correlated equilibria of two-player strategic games in a sequentially rational way. We show that there exist two-player games for which no cryptographic protocol can implement the mediator in a sequentially rational way; that is, without introducing empty threats. In the context of computational...... with appealing economic applications. Our implementation puts forward a notion of cryptographically blinded games that exploits the power of encryption to selectively restrict the information available to players about sampled action profiles, such that these desirable equilibria can be stably achieved...

The Rational Patient and Beyond: Implications for Treatment Adherence in People with Psychiatric Disabilities

Science.gov (United States)

Corrigan, Patrick W.; Rüsch, Nicolas; Ben-Zeev, Dror; Sher, Tamara

2014-01-01

Purpose/Objective Many people with psychiatric disabilities do not benefit from evidence-based practices because they often do not seek out or fully adhere to them. One way psychologists have made sense of this rehabilitation and health decision process and subsequent behaviors (of which adherence might be viewed as one) is by proposing a “rational patient;” namely, that decisions are made deliberatively by weighing perceived costs and benefits of intervention options. Social psychological research, however, suggests limitations to a rational patient theory that impact models of health decision making. Design The research literature was reviewed for studies of rational patient models and alternative theories with empirical support. Special focus was on models specifically related to decisions about rehabilitation strategies for psychiatric disability. Results Notions of the rational patient evolved out of several psychological models including the health belief model, protection motivation theory, and theory of planned behavior. A variety of practice strategies evolved to promote rational decision making. However, research also suggests limitations to rational deliberations of health. (1) Rather than carefully and consciously considered, many health decisions are implicit, potentially occurring outside awareness. (2) Decisions are not always planful; often it is the immediate exigencies of a context rather than an earlier balance of costs and benefits that has the greatest effects. (3) Cool cognitions often do not dictate the process; emotional factors have an important role in health decisions. Each of these limitations suggests additional practice strategies that facilitate a person’s health decisions. Conclusions/Implications Old models of rational decision making need to be supplanted by multi-process models that explain supra-deliberative factors in health decisions and behaviors. PMID:24446671

Recent advances in rational approaches for enzyme engineering

Directory of Open Access Journals (Sweden)

Kerstin Steiner

2012-09-01

Full Text Available Enzymes are an attractive alternative in the asymmetric syntheses of chiral building blocks. To meet the requirements of industrial biotechnology and to introduce new functionalities, the enzymes need to be optimized by protein engineering. This article specifically reviews rational approaches for enzyme engineering and de novo enzyme design involving structure-based approaches developed in recent years for improvement of the enzymes’ performance, broadened substrate range, and creation of novel functionalities to obtain products with high added value for industrial applications.

Proposed standby gasoline rationing plan: public comments

Energy Technology Data Exchange (ETDEWEB)

1978-12-01

Under the proposed plan, DOE would allocate ration rights (rights to purchase gasoline) to owners of registered vehicles. All vehicles in a given class would receive the same entitlement. Essential services would receive supplemental allotments of ration rights as pririty firms. Once every 3 months, ration checks would be mailed out to all vehicle registrants, allotting them a certain amount of ration rights. These checks would then be cashed at Coupon Issuance Points, where the bearer would receive ration coupons to be used at gasoline stations. Large users of gasoline could deposit their allotment checks in accounts at ration banks. Coupons or checks would be freely exchangeable in a white market. A certain percentage of the gasoline supply would be set aside in reserve for use in national emergencies. When the plan was published in the Federal Register, public comments were requested. DOE also solicited comments from private citizens, public interest groups, business and industry, state and local governments. A total of 1126 responses were reveived and these are analyzed in this paper. The second part of the report describes how the comments were classified, and gives a statistical breakdown of the major responses. The last section is a discussion and analysis of theissue raised by commenting agencies, firms, associations, and individuals. (MCW)

Rational design of reconfigurable prismatic architected materials

Science.gov (United States)

Overvelde, Johannes T. B.; Weaver, James C.; Hoberman, Chuck; Bertoldi, Katia

2017-01-01

Advances in fabrication technologies are enabling the production of architected materials with unprecedented properties. Most such materials are characterized by a fixed geometry, but in the design of some materials it is possible to incorporate internal mechanisms capable of reconfiguring their spatial architecture, and in this way to enable tunable functionality. Inspired by the structural diversity and foldability of the prismatic geometries that can be constructed using the snapology origami technique, here we introduce a robust design strategy based on space-filling tessellations of polyhedra to create three-dimensional reconfigurable materials comprising a periodic assembly of rigid plates and elastic hinges. Guided by numerical analysis and physical prototypes, we systematically explore the mobility of the designed structures and identify a wide range of qualitatively different deformations and internal rearrangements. Given that the underlying principles are scale-independent, our strategy can be applied to the design of the next generation of reconfigurable structures and materials, ranging from metre-scale transformable architectures to nanometre-scale tunable photonic systems.

Privacy-Enhancing Auctions Using Rational Cryptography

DEFF Research Database (Denmark)

Miltersen, Peter Bro; Nielsen, Jesper Buus; Triandopoulos, Nikolaos

2009-01-01

show how to use rational cryptography to approximately implement any given ex interim individually strictly rational equilibrium of such an auction without a trusted mediator through a cryptographic protocol that uses only point-to-point authenticated channels between the players. By “ex interim...

Principles of Economic Rationality in Mice.

Science.gov (United States)

Rivalan, Marion; Winter, York; Nachev, Vladislav

2017-12-12

Humans and non-human animals frequently violate principles of economic rationality, such as transitivity, independence of irrelevant alternatives, and regularity. The conditions that lead to these violations are not completely understood. Here we report a study on mice tested in automated home-cage setups using rewards of drinking water. Rewards differed in one of two dimensions, volume or probability. Our results suggest that mouse choice conforms to the principles of economic rationality for options that differ along a single reward dimension. A psychometric analysis of mouse choices further revealed that mice responded more strongly to differences in probability than to differences in volume, despite equivalence in return rates. This study also demonstrates the synergistic effect between the principles of economic rationality and psychophysics in making quantitative predictions about choices of healthy laboratory mice. This opens up new possibilities for the analyses of multi-dimensional choice and the use of mice with cognitive impairments that may violate economic rationality.

Decision Making: Rational, Nonrational, and Irrational.

Science.gov (United States)

Simon, Herbert A.

1993-01-01

Describes the current state of knowledge about human decision-making and problem-solving processes, explaining recent developments and their implications for management and management training. Rational goal-setting is the key to effective decision making and accomplishment. Bounded rationality is a realistic orientation, because the world is too…

Rational Development of Addiction Pharmacotherapies: Successes, Failures, and Prospects

OpenAIRE

Christopher Pierce, R.; O’Brien, Charles P.; Kenny, Paul J.; Vanderschuren, Louk J. M. J.

2012-01-01

There are currently effective, U.S. Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid addiction. In some cases these therapeutics were rationally designed and tested using a combination of various animal models of addiction. In many cases, however, effective drug therapies for addiction were derived from the testing of compounds developed for other CNS disorders (e.g., analgesics and antidepressants), which were tested clinically in the absence of prior a...

Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain - A phase 2 randomized clinical Trial.

Science.gov (United States)

Mulligan, Mark J; Stapleton, Jack T; Keitel, Wendy A; Frey, Sharon E; Chen, Wilbur H; Rouphael, Nadine; Edupuganti, Srilatha; Beck, Allison; Winokur, Patricia L; El Sahly, Hana M; Patel, Shital M; Atmar, Robert L; Graham, Irene; Anderson, Edwin; El-Kamary, Samer S; Pasetti, Marcela F; Sztein, Marcelo B; Hill, Heather; Goll, Johannes B

2017-08-24

Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was -6.9% (-16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI, 87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p<0.0001). The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695. Copyright © 2017 The Authors. Published by Elsevier

Simplifications of rational matrices by using UML

OpenAIRE

Tasić, Milan B.; Stanimirović, Ivan P.

2013-01-01

The simplification process on rational matrices consists of simplifying each entry represented by a rational function. We follow the classic approach of dividing the numerator and denominator polynomials by their common GCD polynomial, and provide the activity diagram in UML for this process. A rational matrix representation as the quotient of a polynomial matrix and a polynomial is also discussed here and illustrated via activity diagrams. Also, a class diagram giving the links between the c...

Local Choices: Rationality and the Contextuality of Decision-Making

Science.gov (United States)

Vlaev, Ivo

2018-01-01

Rational explanation is ubiquitous in psychology and social sciences, ranging from rational analysis, expectancy-value theories, ideal observer models, mental logic to probabilistic frameworks, rational choice theory, and informal “folk psychological” explanation. However, rational explanation appears to be challenged by apparently systematic irrationality observed in psychological experiments, especially in the field of judgement and decision-making (JDM). Here, it is proposed that the experimental results require not that rational explanation should be rejected, but that rational explanation is local, i.e., within a context. Thus, rational models need to be supplemented with a theory of contextual shifts. We review evidence in JDM that patterns of choices are often consistent within contexts, but unstable between contexts. We also demonstrate that for a limited, though reasonably broad, class of decision-making domains, recent theoretical models can be viewed as providing theories of contextual shifts. It is argued that one particular significant source of global inconsistency arises from a cognitive inability to represent absolute magnitudes, whether for perceptual variables, utilities, payoffs, or probabilities. This overall argument provides a fresh perspective on the scope and limits of human rationality. PMID:29301289

Local Choices: Rationality and the Contextuality of Decision-Making.

Science.gov (United States)

Vlaev, Ivo

2018-01-02

Rational explanation is ubiquitous in psychology and social sciences, ranging from rational analysis, expectancy-value theories, ideal observer models, mental logic to probabilistic frameworks, rational choice theory, and informal "folk psychological" explanation. However, rational explanation appears to be challenged by apparently systematic irrationality observed in psychological experiments, especially in the field of judgement and decision-making (JDM). Here, it is proposed that the experimental results require not that rational explanation should be rejected, but that rational explanation is local , i.e., within a context. Thus, rational models need to be supplemented with a theory of contextual shifts. We review evidence in JDM that patterns of choices are often consistent within contexts, but unstable between contexts. We also demonstrate that for a limited, though reasonably broad, class of decision-making domains, recent theoretical models can be viewed as providing theories of contextual shifts. It is argued that one particular significant source of global inconsistency arises from a cognitive inability to represent absolute magnitudes, whether for perceptual variables, utilities, payoffs, or probabilities. This overall argument provides a fresh perspective on the scope and limits of human rationality.

Techno-Optimism and Rational Superstition

DEFF Research Database (Denmark)

Wilson, Alexander

2017-01-01

our common understanding of reason and rationality? To adopt rational expectations about the world, after all, should we not attempt to avoid the emotional over-determination of our assessments? I show that applied reason is conceptually entangled with this superstitious optimism in the continued...... of retro-causation, where the future is held to somehow have a retroactive effect on the past. This suggests, I argue, that the underlying mechanism by which techno-optimism is supposed to be instrumental in bringing about the future is fundamentally superstitious. But does this superstition not go against...... successes of technology. The article thus reveals a curious sense in which reason is intrinsically superstitious. I offer an evolutionary explanation for this, showing that the biological origins of reason will by nature tend to produce rational agents which are superstitiously bound to realism...

Hydrogen initiative: An integrated approach toward rational nanocatalyst design for hydrogen production. Technical Report-Year 1

Energy Technology Data Exchange (ETDEWEB)

Vlachos, Dionisios G. [Univ. of Delaware, Newark, DE (United States); Buttrey, Douglas J. [Univ. of Delaware, Newark, DE (United States); Lauterbach, Jochen A. [Univ. of Delaware, Newark, DE (United States)

2007-03-29

The overall objective of this grant is to develop a rational framework for the discovery of low cost, robust, and active nano-catalysts that will enable efficient hydrogen production. Our approach will be the first demonstration of integrated multiscale model, nano-catalyst synthesis, and nanoscale characterization assisted high throughput experimentation (HTE). We will initially demonstrate our approach with ammonia decomposition on noble metal catalysts. Our research focuses on many elements of the Hydrogen Initiative in the Focus Area of “Design of Catalysts at the Nanoscale’. It combines high-throughput screening methods with various nanostructure synthesis protocols, advanced measurements, novel in situ and ex situ characterization techniques, and multiscale theory, modeling and simulation. This project directly addresses several of the long-term goals of the DOE/BES program. In particular, new nanoscale catalytic materials will be synthesized, characterized and modeled for the production of hydrogen from ammonia and a computational framework will be developed for efficient extraction of information from experimental data and for rational design of catalysts whose impact goes well beyond the proposed hydrogen production project. In the first year of the grant, we have carried out HTE screening using a 16 parallel microreactor coupled with an FTIR analysis system. We screened nearly twenty single metals and several bimetallic catalysts as a function of temperature, catalyst loading, inlet composition, and temperature (order of 400 experiments). We have found that Ru is the best single metal catalyst and no better catalysts were found among the library of bimetallics we have created so far. Furthermore, we have investigated promoting effects (i.e., K, Cs, and Ba) of the Ru catalyst. We have found that K is the dominant promoter of increased Ru activity. Response surface experimental design has led to substantial improvements of the Ru catalyst with promotion

Information-Theoretic Bounded Rationality and ε-Optimality

Directory of Open Access Journals (Sweden)

Daniel A. Braun

2014-08-01

Full Text Available Bounded rationality concerns the study of decision makers with limited information processing resources. Previously, the free energy difference functional has been suggested to model bounded rational decision making, as it provides a natural trade-off between an energy or utility function that is to be optimized and information processing costs that are measured by entropic search costs. The main question of this article is how the information-theoretic free energy model relates to simple ε-optimality models of bounded rational decision making, where the decision maker is satisfied with any action in an ε-neighborhood of the optimal utility. We find that the stochastic policies that optimize the free energy trade-off comply with the notion of ε-optimality. Moreover, this optimality criterion even holds when the environment is adversarial. We conclude that the study of bounded rationality based on ε-optimality criteria that abstract away from the particulars of the information processing constraints is compatible with the information-theoretic free energy model of bounded rationality.

Rationing critical care medicine: recent studies and current trends.

Science.gov (United States)

Ward, Nicholas S

2005-12-01

This paper reviews the literature on the rationing of critical care resources. Although much has been written about the concept of rationing, there have been few scientific studies as to its prevalence. A recent meta-analysis reviewed all previously published studies on rationing access to intensive care units but little is known about practices within the intensive care unit. Much literature in the past few years has focused on the growing use of critical care resources and projections for the future. Several authors suggest there may be a crisis in financial or personnel resources if some rationing does not take place. Other papers have argued that the methods of rationing critical care previously proposed, such as limiting the care of dying patients or using cost-effectiveness analysis to determine care, may not be effective or viewed as ethical by some. Finally, several recent papers review how critical care is practiced and allocated in India and Asian countries that already practice open rationing in their health care systems. There is currently no published evidence that overt rationing is taking place in critical care medicine. There is growing evidence that in the future, the need for critical care may outstrip financial resources unless some form of rationing takes place. It is also clear from the literature that choosing how to ration critical care will be a difficult task.

Decision rules and group rationality: cognitive gain or standstill?

Directory of Open Access Journals (Sweden)

Petru Lucian Curşeu

Full Text Available Recent research in group cognition points towards the existence of collective cognitive competencies that transcend individual group members' cognitive competencies. Since rationality is a key cognitive competence for group decision making, and group cognition emerges from the coordination of individual cognition during social interactions, this study tests the extent to which collaborative and consultative decision rules impact the emergence of group rationality. Using a set of decision tasks adapted from the heuristics and biases literature, we evaluate rationality as the extent to which individual choices are aligned with a normative ideal. We further operationalize group rationality as cognitive synergy (the extent to which collective rationality exceeds average or best individual rationality in the group, and we test the effect of collaborative and consultative decision rules in a sample of 176 groups. Our results show that the collaborative decision rule has superior synergic effects as compared to the consultative decision rule. The ninety one groups working in a collaborative fashion made more rational choices (above and beyond the average rationality of their members than the eighty five groups working in a consultative fashion. Moreover, the groups using a collaborative decision rule were closer to the rationality of their best member than groups using consultative decision rules. Nevertheless, on average groups did not outperformed their best member. Therefore, our results reveal how decision rules prescribing interpersonal interactions impact on the emergence of collective cognitive competencies. They also open potential venues for further research on the emergence of collective rationality in human decision-making groups.

Decision rules and group rationality: cognitive gain or standstill?

Science.gov (United States)

Curşeu, Petru Lucian; Jansen, Rob J G; Chappin, Maryse M H

2013-01-01

Recent research in group cognition points towards the existence of collective cognitive competencies that transcend individual group members' cognitive competencies. Since rationality is a key cognitive competence for group decision making, and group cognition emerges from the coordination of individual cognition during social interactions, this study tests the extent to which collaborative and consultative decision rules impact the emergence of group rationality. Using a set of decision tasks adapted from the heuristics and biases literature, we evaluate rationality as the extent to which individual choices are aligned with a normative ideal. We further operationalize group rationality as cognitive synergy (the extent to which collective rationality exceeds average or best individual rationality in the group), and we test the effect of collaborative and consultative decision rules in a sample of 176 groups. Our results show that the collaborative decision rule has superior synergic effects as compared to the consultative decision rule. The ninety one groups working in a collaborative fashion made more rational choices (above and beyond the average rationality of their members) than the eighty five groups working in a consultative fashion. Moreover, the groups using a collaborative decision rule were closer to the rationality of their best member than groups using consultative decision rules. Nevertheless, on average groups did not outperformed their best member. Therefore, our results reveal how decision rules prescribing interpersonal interactions impact on the emergence of collective cognitive competencies. They also open potential venues for further research on the emergence of collective rationality in human decision-making groups.

Development of probabilistic fast reactor fuel design method

International Nuclear Information System (INIS)

Ozawa, Takayuki

1997-01-01

Under the current method of evaluating fuel robustness in FBR fuel rod design, a variety of uncertain quantities including fuel production tolerance and power density are estimated conservatively. In the future, in order to proceed with improvements in the FBR core's performance and optimize the fuel's specifications, a rationalization of fuel design tolerance is required. Among the measures aimed at realizing this rationalization, the introduction of a probabilistic fast reactor fuel design method is currently under consideration. I have developed a probabilistic fast reactor fuel design code named BORNFREE, in order to make use of this method in FBR fuel design. At the same time, I have carried out a trial calculation of the cladding stress using this code and made a study and an evaluation of the possibility of employing tolerance rationalization in fuel rod design. In this paper, I provide an outline description of BORNFREE and report the results of the above study and evaluation. After performing cladding stress trial calculations using the probabilistic method, I was able to confirm that this method promises more rational design evaluation results than the conventional deterministic method. (author)

Anxiety reduction through group instruction in rational therapy.

Science.gov (United States)

Maxwell, J W; Wilkerson, J

1982-09-01

This study investigated the effects of group Rational Therapy in promoting rational thinking and self-enhancing emotions among 24 college students. Each subject was administered the Sixteen Personality Factor Questionnaire as a pre- and post-test measurement. Results reveal that some aspects of personality are affected by Rational Therapy group programs while others are not.

Thinking about acting logical foundations for rational decision making

CERN Document Server

Pollock, John L

2006-01-01

John Pollock aims to construct a theory of rational decision making for real agents--not ideal agents. Real agents have limited cognitive powers, but traditional theories of rationality have applied only to idealized agents that lack such constraints. Pollock argues that theories of ideal rationality are largely irrelevant to the decision making of real agents. Thinking about Acting aims to provide a theory of ""real rationality.""

Choice, internal consistency, and rationality

OpenAIRE

Aditi Bhattacharyya; Prasanta K. Pattanaik; Yongsheng Xu

2010-01-01

The classical theory of rational choice is built on several important internal consistency conditions. In recent years, the reasonableness of those internal consistency conditions has been questioned and criticized, and several responses to accommodate such criticisms have been proposed in the literature. This paper develops a general framework to accommodate the issues raised by the criticisms of classical rational choice theory, and examines the broad impact of these criticisms from both no...

Management between Rationality and Irrationality

OpenAIRE

Cene Bavec

2012-01-01

In the paper, we discuss theoretical and practical aspects of management and its rational and irrational behavior in the light of traditional management theories and contemporary social theories and theories of complexity. We exposed differences between middle and top management, where rationality is ascribed mainly to middle management, while top management often acts on seemingly irrational way. For the part of this irrationality, we cannot blame management because it originates from the na...

Francisella tularensis: No Evidence for Transovarial Transmission in the Tularemia Tick Vectors Dermacentor reticulatus and Ixodes ricinus

Science.gov (United States)

Genchi, Marco; Prati, Paola; Vicari, Nadia; Manfredini, Andrea; Sacchi, Luciano; Clementi, Emanuela; Bandi, Claudio; Epis, Sara; Fabbi, Massimo

2015-01-01

Background Tularemia is a zoonosis caused by the Francisella tularensis, a highly infectious Gram-negative coccobacillus. Due to easy dissemination, multiple routes of infection, high environmental contamination and morbidity and mortality rates, Francisella is considered a potential bioterrorism threat and classified as a category A select agent by the CDC. Tick bites are among the most prevalent modes of transmission, and ticks have been indicated as a possible reservoir, although their reservoir competence has yet to be defined. Tick-borne transmission of F. tularensis was recognized in 1923, and transstadial transmission has been demonstrated in several tick species. Studies on transovarial transmission, however, have reported conflicting results. Objective The aim of this study was to evaluate the role of ticks as reservoirs for Francisella, assessing the transovarial transmission of F. tularensis subsp. holarctica in ticks, using experimentally-infected females of Dermacentor reticulatus and Ixodes ricinus. Results Transmission electron microscopy and fluorescence in situ hybridization showed F. tularensis within oocytes. However, cultures and bioassays of eggs and larvae were negative; in addition, microscopy techniques revealed bacterial degeneration/death in the oocytes. Conclusions These results suggest that bacterial death might occur in oocytes, preventing the transovarial transmission of Francisella. We can speculate that Francisella does not have a defined reservoir, but that rather various biological niches (e.g. ticks, rodents), that allow the bacterium to persist in the environment. Our results, suggesting that ticks are not competent for the bacterium vertical transmission, are congruent with this view. PMID:26244842

Francisella tularensis: No Evidence for Transovarial Transmission in the Tularemia Tick Vectors Dermacentor reticulatus and Ixodes ricinus.

Directory of Open Access Journals (Sweden)

Marco Genchi

Full Text Available Tularemia is a zoonosis caused by the Francisella tularensis, a highly infectious Gram-negative coccobacillus. Due to easy dissemination, multiple routes of infection, high environmental contamination and morbidity and mortality rates, Francisella is considered a potential bioterrorism threat and classified as a category A select agent by the CDC. Tick bites are among the most prevalent modes of transmission, and ticks have been indicated as a possible reservoir, although their reservoir competence has yet to be defined. Tick-borne transmission of F. tularensis was recognized in 1923, and transstadial transmission has been demonstrated in several tick species. Studies on transovarial transmission, however, have reported conflicting results.The aim of this study was to evaluate the role of ticks as reservoirs for Francisella, assessing the transovarial transmission of F. tularensis subsp. holarctica in ticks, using experimentally-infected females of Dermacentor reticulatus and Ixodes ricinus.Transmission electron microscopy and fluorescence in situ hybridization showed F. tularensis within oocytes. However, cultures and bioassays of eggs and larvae were negative; in addition, microscopy techniques revealed bacterial degeneration/death in the oocytes.These results suggest that bacterial death might occur in oocytes, preventing the transovarial transmission of Francisella. We can speculate that Francisella does not have a defined reservoir, but that rather various biological niches (e.g. ticks, rodents, that allow the bacterium to persist in the environment. Our results, suggesting that ticks are not competent for the bacterium vertical transmission, are congruent with this view.

Self-Reported Rationing Behavior Among US Physicians: A National Survey.

Science.gov (United States)

Sheeler, Robert D; Mundell, Tim; Hurst, Samia A; Goold, Susan Dorr; Thorsteinsdottir, Bjorg; Tilburt, Jon C; Danis, Marion

2016-12-01

Rationing is a controversial topic among US physicians. Understanding their attitudes and behaviors around rationing may be essential to a more open and sensible professional discourse on this important but controversial topic. To describe rationing behavior and associated factors among US physicians. Survey mailed to US physicians in 2012 to evaluate self-reported rationing behavior and variables related to this behavior. US physicians across a full spectrum of practice settings. A total of 2541 respondents, representing 65.6 % of the original mailing list of 3872 US addresses. The study was a cross-sectional analysis of physician attitudes and self-reported behaviors, with neutral language representations of the behaviors as well as an embedded experiment to test the influence of the word "ration" on perceived responsibility. Overall percentage of respondents reporting rationing behavior in various contexts and assessment of attitudes toward rationing. In total, 1348 respondents (53.1 %) reported having personally refrained within the past 6 months from using specific clinical services that would have provided the best patient care, because of health system cost. Prescription drugs (n = 1073 [48.3 %]) and magnetic resonance imaging (n = 922 [44.5 %]) were most frequently rationed. Surgical and procedural specialists were less likely to report rationing behavior (adjusted odds ratio [OR] [95 % CI], 0.8 [0.9-0.9] and 0.5 [0.4-0.6], respectively) compared to primary care. Compared with small or solo practices, those in medical school settings reported less rationing (adjusted OR [95 % CI], 0.4 [0.2-0.7]). Physicians who self-identified as very or somewhat liberal were significantly less likely to report rationing (adjusted OR [95 % CI], 0.7 [0.6-0.9]) than those self-reporting being very or somewhat conservative. A more positive opinion about rationing tended to align with greater odds of rationing. More than one-half of respondents engaged in

Rational-driver approximation in car-following theory

Science.gov (United States)

Lubashevsky, Ihor; Wagner, Peter; Mahnke, Reinhard

2003-11-01

The problem of a car following a lead car driven with constant velocity is considered. To derive the governing equations for the following car dynamics a cost functional is constructed. This functional ranks the outcomes of different driving strategies, which applies to fairly general properties of the driver behavior. Assuming rational-driver behavior, the existence of the Nash equilibrium is proved. Rational driving is defined by supposing that a driver corrects continuously the car motion to follow the optimal path minimizing the cost functional. The corresponding car-following dynamics is described quite generally by a boundary value problem based on the obtained extremal equations. Linearization of these equations around the stationary state results in a generalization of the widely used optimal velocity model. Under certain conditions (the “dense traffic” limit) the rational car dynamics comprises two stages, fast and slow. During the fast stage a driver eliminates the velocity difference between the cars, the subsequent slow stage optimizes the headway. In the dense traffic limit an effective Hamiltonian description is constructed. This allows a more detailed nonlinear analysis. Finally, the differences between rational and bounded rational driver behavior are discussed. The latter, in particular, justifies some basic assumptions used recently by the authors to construct a car-following model lying beyond the frameworks of rationality.

Rationality and ritual

International Nuclear Information System (INIS)

Wynne, B.

1982-01-01

The book concerns the Windscale Public Inquiry, held to investigate the application by British Nuclear Fuels to build a 1200 tonne per year thermal oxide reprocessing plant (THORP) for spent nuclear fuels from Britain and overseas. The subject is discussed under the headings: introduction (international dimensions; the Windscale Inquiry; conflict resolution and social drama; public debate and the sociology of knowledge); the decision-making legacy; oxide reprocessing - the background; the public inquiry tradition - a comparative perspective; the emergence of THORP from a private to a public issue (local and national planning politics); the process and impact of the Inquiry (opposition groups); judicial rationality, expert conflict, and political authority); the rationality and politics of analysis (proliferation; radiation risks; relative risks; the Ravenglass issue; discharge targets; general radiation protection arrangements); conclusion. (U.K.)

Rational accountability and rational autonomy in academic practice: An extended case study of the communicative ethic of interdisciplinary science

Science.gov (United States)

Robertson, Susan Margaret

The dissertation investigates the interaction of rational accountability and rational autonomy in interdisciplinary science within the lifeworld of the university. It focuses on the cultural, social and motivational forces that university researchers draw on, and develop, to constitute and regulate interdisciplinary science. Findings are analyzed within an applied critical social theory framework that attends to the interaction of instrumental and communicative rational action within the public spaces that constitute the lifeworld of the university as a public sphere in society. The research raises questions of how academics practice interdisciplinary science and how these practices relate to the reproduction of the regulative ideal of the university as a community that practices public reason. The conceptual framework informing the research is Habermas' (1984) theory of communicative action. Using Burawoy's (1991) extended case study method as an operational strategy, two modes of constituting and regulating interdisciplinary science were found. Instrumental rational modes dominated in social contexts of interdisciplinary science where consensus on the normative goals and purposes of rational academic action were pre-existing and pre-supposed by participants. Communicative rational modes dominated in social contexts of interdisciplinary science where the normative goals and purposes of rational academic action entered a contested domain. Endorsements for interdisciplinary science policies are coinciding with demands for increased accountability and relevance of Canada's university system. At the same time that the university system must respond to external demands, it must reproduce itself as a public institution open to the discursive redemption of factual and normative validity claims. The study found that academics participate in, but also contest the instrumental regulation of academic inquiry and conduct by using their constitutional autonomy and freedom to

Effects of predation stress and food ration on perch gut microbiota.

Science.gov (United States)

Zha, Yinghua; Eiler, Alexander; Johansson, Frank; Svanbäck, Richard

2018-02-06

Gut microbiota provide functions of importance to influence hosts' food digestion, metabolism, and protection against pathogens. Factors that affect the composition and functions of gut microbial communities are well studied in humans and other animals; however, we have limited knowledge of how natural food web factors such as stress from predators and food resource rations could affect hosts' gut microbiota and how it interacts with host sex. In this study, we designed a two-factorial experiment exposing perch (Perca fluviatilis) to a predator (pike, Esox lucius), and different food ratios, to examine the compositional and functional changes of perch gut microbiota based on 16S rRNA amplicon sequencing. We also investigated if those changes are host sex dependent. We showed that overall gut microbiota composition among individual perch significantly responded to food ration and predator presence. We found that species richness decreased with predator presence, and we identified 23 taxa from a diverse set of phyla that were over-represented when a predator was present. For example, Fusobacteria increased both at the lowest food ration and at predation stress conditions, suggesting that Fusobacteria are favored by stressful situations for the host. In concordance, both food ration and predation stress seemed to influence the metabolic repertoire of the gut microbiota, such as biosynthesis of other secondary metabolites, metabolism of cofactors, and vitamins. In addition, the identified interaction between food ration and sex emphasizes sex-specific responses to diet quantity in gut microbiota. Collectively, our findings emphasize an alternative state in gut microbiota with responses to changes in natural food webs depending on host sex. The obtained knowledge from this study provided us with an important perspective on gut microbiota in a food web context.

Differential effects of gamification, nudging and rational information on travel behavior

DEFF Research Database (Denmark)

Lieberoth, Andreas; Jensen, Niels Holm; Skovgaard, Thomas

visible when “players” started displaying them on their profiles. Just-in–time feedback was sent on text and email, and information on e.g. badges accumulated on the website. A prize of further free travel was offered. The rational health information approach framed the benefits of commuting in terms...... local commuters were recruited into the experiment using a traditional campaign of media appearances and outdoor advertising. Participants were divided into groups based on their place of residence. A fourth smaller control condition was also formed. Each participant received a letter of information...... particular to the influence condition, and a free travel card good for the month. Researchers from two major universities each designed an influence strategy in accordance with literature and practices in their fields, separable into gamification, nudging and rational health information. Swipes...

RATIONAL-IRRATIONAL ELECTORAL PREFERENCES, ALTRUISM AND EXPRESSIVE BEHAVIOR

Directory of Open Access Journals (Sweden)

Mihai Ungureanu

2015-01-01

Full Text Available Caplan (2000, 2001, 2006 proposed the rational-irrationality model arguing that irrationality is a good as any other, whose consumption is maximized in relation to its costs and benefits. Applying this model to the problem of electoral behavior Caplan implies that voters ‘afford’ many irrational beliefs, because the lack of individual decisiveness renders vote as a consequenceless act. This paper contributes to the development of knowledge by analyzing the compatibility of rational irrationality with active electoral behavior. Two important arguments are being proposed: First, Wittman’s (2008 intuition that rational irrationality is incompatible with voting could be supported only about a particular type of altruism, which Caplan actually seems to reject. Second, rational irrationality seems to be compatible with expressive motivations, reinforcing the conclusion that rational-irrational individuals are active voters in mass elections.

The Problem of Rational Moral Enlistment

Science.gov (United States)

Tillson, John

2017-01-01

How can one bring children to recognize the requirements of morality without resorting only to non-rational means of persuasion (i.e. what rational ground can be offered to children for their moral enlistment)? Michael Hand has recently defended a foundationalist approach to answering this question and John White has responded by (a) criticizing…

Regret and rationalization among smokers in Thailand and Malaysia: findings from the International Tobacco Control Southeast Asia Survey.

Science.gov (United States)

Lee, Wonkyong B; Fong, Geoffrey T; Zanna, Mark P; Omar, Maizurah; Sirirassamee, Buppha; Borland, Ron

2009-07-01

To test whether differences of history and strength in tobacco control policies will influence social norms, which, in turn, will influence quit intentions, by influencing smokers' regret and rationalization. The data were from the International Tobacco Control (ITC) Policy Evaluation Southeast Asia Survey, a cohort survey of representative samples of adult smokers in Thailand (N = 2,000) and Malaysia (N = 2,006). The survey used a stratified multistage sampling design. Measures included regret, rationalization, social norms, and quit intention. Thai smokers were more likely to have quit intentions than Malaysian smokers. This difference in quit intentions was, in part, explained by the country differences in social norms, regret, and rationalization. Reflecting Thailand's history of stronger tobacco control policies, Thai smokers, compared with Malaysian smokers, perceived more negative social norms toward smoking, were more likely to regret, and less likely to rationalize smoking. Mediational analyses revealed that these differences in social norms, accounted, in part, for the country-quit intention relation and that regret and rationalization accounted, in part, for the social norm-quit intention relation. The results suggest that social norms toward smoking, which are shaped by tobacco control policies, and smokers' regret and rationalization influence quit intentions.

Pendekatan Naratif dalam Konseling Rational Emotive Behavior Therapy (Rebt) untuk Mengelola Emosi

OpenAIRE

Purbaning Tyas, Prias Hayu

2015-01-01

The research aims to obtain an overview of the effectiveness of the narrative approach in counseling Rational Emotive Behavior Therapy (REBT) to manage emotions. The approach used in this study is a quantitative approach using a quasi-experimental methods. The study design used is one group pretest-posttest design using purposive sampling technique. The samples were 6 students who score low emotion management. The instrument used in the form of guidelines for the interview to express emotion ...

Confucian Rationalism

Science.gov (United States)

Lam, Chi-Ming

2014-01-01

Nowadays, there is still a widely held view that the Chinese and Western modes of thought are quite distinct from each other. In particular, the Chinese mode of thought derived from Confucianism is considered as comparatively less rational than the Western one. In this article, I first argue that although the analogical mode of argumentation,…

Cognitive distance, absorptive capacity and group rationality: a simulation study.

Directory of Open Access Journals (Sweden)

Petru Lucian Curşeu

Full Text Available We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members and cognitive distance (as the distance between the most rational group member and the rest of the group on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality. Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.

Cognitive distance, absorptive capacity and group rationality: a simulation study.

Science.gov (United States)

Curşeu, Petru Lucian; Krehel, Oleh; Evers, Joep H M; Muntean, Adrian

2014-01-01

We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members) and cognitive distance (as the distance between the most rational group member and the rest of the group) on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality). Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.

Rational Design of Mixed-Metal Oxides for Chemical Looping Combustion of Coal via Coupled Computational-Experimental Studies

Energy Technology Data Exchange (ETDEWEB)

Mishra, Amit [North Carolina State Univ., Raleigh, NC (United States); Li, Fanxing [North Carolina State Univ., Raleigh, NC (United States); Santiso, Erik [North Carolina State Univ., Raleigh, NC (United States)

2017-09-18

Energy and global climate change are two grand challenges to the modern society. An urgent need exists for development of clean and efficient energy conversion processes. The chemical looping strategy, which utilizes regenerable oxygen carriers (OCs) to indirectly convert carbonaceous fuels via redox reactions, is considered to be one of the more promising approaches for CO2 capture by the U.S. Department of Energy (USDOE). To date, most long-term chemical looping operations were conducted using gaseous fuels, even though direct conversion of coal is more desirable from both economics and CO2 capture viewpoints. The main challenges for direct coal conversion reside in the stringent requirements on oxygen carrier performances. In addition, coal char and volatile compounds are more challenging to convert than gaseous fuels. A promising approach for direct conversion of coal is the so called chemical looping with oxygen uncoupling (CLOU) technique. In the CLOU process, a metal oxide that decomposes at the looping temperature, and releases oxygen to the gas phase is used as the OC. The overarching objective of this project was to discover the fundamental principles for rational design and optimization of oxygen carriers (OC) in coal chemical looping combustion (CLC) processes. It directly addresses Topic Area B of the funding opportunity announcement (FOA) in terms of “predictive description of the phase behavior and mechanical properties” of “mixed metal oxide” based OCs and rational development of new OC materials with superior functionality. This was achieved through studies exploring i) iron-containing mixed-oxide composites as oxygen carriers for CLOU, ii) Ca1-xAxMnO3-δ (A = Sr and Ba) as oxygen carriers for CLOU, iii) CaMn1-xBxO3-δ (B=Al, V, Fe, Co, and Ni) as oxygen carrier for CLOU and iv) vacancy creation energy in Mn-containing perovskites as an indicator chemical looping with oxygen uncoupling.

Emotions as a Vehicle for Rationality: Rational Decision Making Models Based on Emotion-Related Valuing and Hebbian Learning

NARCIS (Netherlands)

Treur, J.; Umair, M.

2015-01-01

In this paper an adaptive decision model based on predictive loops through feeling states is analysed from the perspective of rationality. Hebbian learning is considered for different types of connections in the decision model. To assess the extent of rationality, a measure is introduced reflecting

Extension of P-adic Exact Scientific Computational Library (ESCL) to Compute the Exponential of Rational Matrix

National Research Council Canada - National Science Library

Lu, Chao

2008-01-01

...) using p-adic arithmetic. New algorithms have been designed and implemented for matrix operations with rational numbers by representing numerator and denominator with arbitrary length integers, all integers and fractional...

Re-visions of rationality?

Science.gov (United States)

Newell, Ben R

2005-01-01

The appeal of simple algorithms that take account of both the constraints of human cognitive capacity and the structure of environments has been an enduring theme in cognitive science. A novel version of such a boundedly rational perspective views the mind as containing an 'adaptive toolbox' of specialized cognitive heuristics suited to different problems. Although intuitively appealing, when this version was proposed, empirical evidence for the use of such heuristics was scant. I argue that in the light of empirical studies carried out since then, it is time this 'vision of rationality' was revised. An alternative view based on integrative models rather than collections of heuristics is proposed.

Children's understanding of the costs and rewards underlying rational action.

Science.gov (United States)

Jara-Ettinger, Julian; Gweon, Hyowon; Tenenbaum, Joshua B; Schulz, Laura E

2015-07-01

Humans explain and predict other agents' behavior using mental state concepts, such as beliefs and desires. Computational and developmental evidence suggest that such inferences are enabled by a principle of rational action: the expectation that agents act efficiently, within situational constraints, to achieve their goals. Here we propose that the expectation of rational action is instantiated by a naïve utility calculus sensitive to both agent-constant and agent-specific aspects of costs and rewards associated with actions. In four experiments, we show that, given an agent's choices, children (range: 5-6 year olds; N=96) can infer unobservable aspects of costs (differences in agents' competence) from information about subjective differences in rewards (differences in agents' preferences) and vice versa. Moreover, children can design informative experiments on both objects and agents to infer unobservable constraints on agents' actions. Copyright © 2015 Elsevier B.V. All rights reserved.

Rationing medical education.

African Journals Online (AJOL)

This paper discussed the pros and cons of the application of rationing to medical education and the different ... Even though some stakeholders in medical education might be taken aback at .... Walsh K. Online educational tools to improve the.

Rationality, perception, and the all-seeing eye.

Science.gov (United States)

Felin, Teppo; Koenderink, Jan; Krueger, Joachim I

2017-08-01

Seeing-perception and vision-is implicitly the fundamental building block of the literature on rationality and cognition. Herbert Simon and Daniel Kahneman's arguments against the omniscience of economic agents-and the concept of bounded rationality-depend critically on a particular view of the nature of perception and vision. We propose that this framework of rationality merely replaces economic omniscience with perceptual omniscience. We show how the cognitive and social sciences feature a pervasive but problematic meta-assumption that is characterized by an "all-seeing eye." We raise concerns about this assumption and discuss different ways in which the all-seeing eye manifests itself in existing research on (bounded) rationality. We first consider the centrality of vision and perception in Simon's pioneering work. We then point to Kahneman's work-particularly his article "Maps of Bounded Rationality"-to illustrate the pervasiveness of an all-seeing view of perception, as manifested in the extensive use of visual examples and illusions. Similar assumptions about perception can be found across a large literature in the cognitive sciences. The central problem is the present emphasis on inverse optics-the objective nature of objects and environments, e.g., size, contrast, and color. This framework ignores the nature of the organism and perceiver. We argue instead that reality is constructed and expressed, and we discuss the species-specificity of perception, as well as perception as a user interface. We draw on vision science as well as the arts to develop an alternative understanding of rationality in the cognitive and social sciences. We conclude with a discussion of the implications of our arguments for the rationality and decision-making literature in cognitive psychology and behavioral economics, along with suggesting some ways forward.

Towards a classification of rational Hopf algebras

International Nuclear Information System (INIS)

Fuchs, J.; Ganchev, A.; Vecsernyes, P.

1994-02-01

Rational Hopf algebras, i.e. certain quasitriangular weak quasi-Hopf *-algebras, are expected to describe the quantum symmetry of rational field theories. In this paper methods are developed which allow for a classification of all rational Hopf algebras that are compatible with some prescribed set of fusion rules. The algebras are parametrized by the solutions of the square, pentagon and hexagon identities. As examples, we classify all solutions for fusion rules with not more than three sectors, as well as for the level three affine A 1 (1) fusion rules. We also establish several general properties of rational Hopf algebras and present a graphical description of the coassociator in terms of labelled tetrahedra. The latter construction allows to make contact with conformal field theory fusing matrices and with invariants of three-manifolds and topological lattice field theory. (orig.)

Bounded rational choice behaviour: applications in transport

DEFF Research Database (Denmark)

Jensen, Anders Fjendbo

2016-01-01

Even though the theory of rational behaviour has been challenged for almost 100 years, the dominant approach within the field of transport has been based upon the assumptions of neoclassical economics that we live in a world of rational decision makers who always have perfect knowledge and aim...... rational choice behaviour focuses on how the latter approach can be seriously taken into account within transport applications. As the editors discuss in the introduction, a true optimal choice can only be made if an individual has full and perfect information of all relevant attributes in his/her choice...... set. An individual is said to demonstrate bounded rational behaviour if he/she does not systematically consider all attributes deemed relevant for the decision problem at hand, does not consider all choice options and/or does not choose the best choice alternative. Such simplified representation...

Economic Rationality in the Ultimatum Game

Directory of Open Access Journals (Sweden)

Jan Fiala

2017-03-01

Full Text Available Rigorous application of experimental methodology to the interdisciplinary research of economic decision making is the main purpose of our work. In this paper, we introduce the main decisionmaking theories and outline economic rationality. We explain why we find it useful to discriminate between the “irrational” and “non-rational” components of decision making. We offer an oriented interdisciplinary point of view on economic rationality. In the applied section, we describe the main features of the Ultimatum game and summarize the up-to-date theories explaining the non-rational course of the game. We discuss in detail the reported relations between the nominal value of the stakes and the distribution of the offers and responses. We introduce the blinded, randomized Ultimatum game experiment that we conducted in our laboratory. We stress the importance of anonymity of the study subjects and the difference in salience of a factual reward against a  hypothetical reward. We present the results of our study, showing that a  duly chosen non-monetary reward, directly inconvertible into money, leads to a different offer distribution in the Ultimatum game without the necessity to invest excessive sums of money in the rewards. We compare our results to research published by other authors. According to our theory, the rational, non-rational and irrational components contribute to the decision making in Ultimatum differently depending on the different reward stakes.

Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design

Energy Technology Data Exchange (ETDEWEB)

Bogdanoff, Walter A.; Perez, Edmundo I.; López, Tomás; Arias, Carlos F.; DuBois, Rebecca M. (UNAM-Mexico); (UCSC)

2017-10-25

a single amino acid mutation induces a structural change in a loop that is responsible for antibody binding. Our findings reveal how viruses can escape antibody neutralization and provide insight for the rational design of vaccines to elicit diverse antibodies that provide broader protection from infection.

The anchoring bias reflects rational use of cognitive resources

OpenAIRE

Goodman, Noah; Huys, Quentin; Griffiths, Tom; Lieder, Falk

2017-01-01

© 2017, Psychonomic Society, Inc. Cognitive biases, such as the anchoring bias, pose a serious challenge to rational accounts of human cognition. We investigate whether rational theories can meet this challenge by taking into account the mind’s bounded cognitive resources. We asked what reasoning under uncertainty would look like if people made rational use of their finite time and limited cognitive resources. To answer this question, we applied a mathematical theory of bounded rationality to...

Minor milk constituents are affected by protein concentration and forage digestibility in the feed ration

DEFF Research Database (Denmark)

Larsen, Torben; Alstrup, Lene; Weisbjerg, Martin Riis

2016-01-01

The present study was conducted in order to investigate if selected minor milk components would be indicative for the nutritional situation of the cow. Forty-eight dairy cows were offered a high digestible ration vs. a lower digestible ration combined with 2 protein levels in a 4 × 4 Latin square...... design. Milk glucose, glucose-6-phosphate, cholesterol, triacylglycerides (TAG), uric acid and β-hydroxybutyrate (BHBA) were measured and correlated mutually and towards other milking parameters (yield, h since last milking, days in milk (DIM), urea, etc). The variation range of the suggested variables...... were broad, a fact that may support their utilisation as predictive parameters. The content of milk metabolites was significantly affected by the change in rations as milk glucose, glucose-6-phosphate, uric acid, and the ratio cholesterol: triacylglycerides increased with higher energy intake while...

Rational design and evolutional fine tuning of Saccharomyces cerevisiae for biomass breakdown.

Science.gov (United States)

Hasunuma, Tomohisa; Ishii, Jun; Kondo, Akihiko

2015-12-01

Conferring biomass hydrolysis activity on yeast through genetic engineering has paved the way for the development of groundbreaking processes for producing liquid fuels and commodity chemicals from lignocellulosic biomass. However, the overproduction and misfolding of heterologous and endogenous proteins can trigger cellular stress, increasing the metabolic burden and retarding growth. Improving the efficiency of lignocellulosic breakdown requires engineering of yeast secretory pathway based on system-wide metabolic analysis as well as DNA constructs for enhanced cellulase gene expression with advanced molecular biology tools. Also, yeast is subjected to severe stress due to toxic compounds generated during lignocellulose pretreatment in consolidated saccharification and fermentation processes. The prospect for development of robust yeast strains makes combining evolutionary and rational engineering strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Strategy of Rational Use of Energy

International Nuclear Information System (INIS)

1994-09-01

In the decade of the eighty, especially in order to this decade and so far, the Rational Use of Energy have not constituted a high-priority option and of present time for Colombia. The last politicians were guided, to favor the energy consumption with low prices of the coal, of the electricity, of those derived of the petroleum, growing subsidy to the gasoline and transfer of the productive sector toward the social one. In the recovery of the electric sector, it is contributed alternatives to improve the quality of the service of the electric industries where measured technical and investments in the industrial, commercial sectors and public would allow to reduce short term the consumptions for 5 to 10%, without reducing the production levels or of service. In the construction sector , the efficient designs of buildings could avoid a growth too much express of the energy consumption. The rational use of energy and the handling of the electric demand, should be one of the tools bigger than the State and of the electric industry, as the technical measures of reduction of losses, to respond to the financial crisis of the energy public sector, while the private sector acquires capacity of enough investment. The Colombians companies, experience the necessity to improve their energy efficiency, like one of the important areas of reduction of their costs and of increase of their competitiveness, in front of other countries, especially Latin-American. As consequence of the economic opening, the companies should modernize their processes and administration methods, what means a reduction in the energy consumptions. The reduction of the polluting, specially atmospheric emissions (industries, vehicles), as well as to elimination of having undone dangerous and industrial residuals, it is a priority in Colombia all improvement of the energy efficiency, particularly in the industries, it is accompanied of a proportional reduction of polluting emissions. Then a politics of

Rational Design of Thermally Stable Novel Biocatalytic Nanomaterials: Enzyme Stability in Restricted Spatial Dimensions

Science.gov (United States)

Mudhivarthi, Vamsi K.

Enzyme stability is of intense interest in bio-materials science as biocatalysts, and as sensing platforms. This is essentially because the unique properties of DNA, RNA, PAA can be coupled with the interesting and novel properties of proteins to produce systems with unprecedented control over their properties. In this article, the very first examples of enzyme/NA/inorganic hybrid nanomaterials and enzyme-Polyacrylic acid conjugates will be presented. The basic principles of design, synthesis and control of properties of these hybrid materials will be presented first, and this will be followed by a discussion of selected examples from our recent research findings. Data show that key properties of biological catalysts are improved by the inorganic framework especially when the catalyst is co-embedded with DNA. Several examples of such studies with various enzymes and proteins, including horseradish peroxidase (HRP), glucose oxidase (GO), cytochrome c (Cyt c), met-hemoglobin (Hb) and met-myoglobin (Mb) will be discussed. Additionally, key insights obtained by the standard methods of materials science including XRD, SEM and TEM as well as biochemical, calorimetric and spectroscopic methods will be discussed. Furthermore, improved structure and enhanced activities of the biocatalysts in specific cases will be demonstrated along with the potential stabilization mechanisms. Our hypothesis is that nucleic acids provide an excellent control over the enzyme-solid interactions as well as rational assembly of nanomaterials. These novel nanobiohybrid materials may aid in engineering more effective synthetic materials for gene-delivery, RNA-delivery and drug delivery applications.

Rational points on elliptic curves

CERN Document Server

Silverman, Joseph H

2015-01-01

The theory of elliptic curves involves a pleasing blend of algebra, geometry, analysis, and number theory. This book stresses this interplay as it develops the basic theory, thereby providing an opportunity for advanced undergraduates to appreciate the unity of modern mathematics. At the same time, every effort has been made to use only methods and results commonly included in the undergraduate curriculum. This accessibility, the informal writing style, and a wealth of exercises make Rational Points on Elliptic Curves an ideal introduction for students at all levels who are interested in learning about Diophantine equations and arithmetic geometry. Most concretely, an elliptic curve is the set of zeroes of a cubic polynomial in two variables. If the polynomial has rational coefficients, then one can ask for a description of those zeroes whose coordinates are either integers or rational numbers. It is this number theoretic question that is the main subject of this book. Topics covered include the geometry and ...

The Formation of Rational and Irrational Behaviors in Risky Investment Decision Making: Laboratory Experiment of Coping Theory Implication in Investors’ Adaptation Model

Directory of Open Access Journals (Sweden)

Wendy Wendy

2014-08-01

Full Text Available This study analyzes the stock investor's rational and irrational behavior formation through Investor's Adaptation model. Hypotheses testings were conducted by manipulating four market conditions using between-subject experimental design. The results supported the hypotheses proposed in this study. When given treatment one (opportunity-high control, investors tended to adapt the profit maximizing strategy (rational. Meanwhile, when given treatment two (opportunity-low control, three (threat-high control and four (threat-low control, they tended to adapt the profit satisfying strategy (rational-emotional, bad news handling strategy (emotional-rational, and self-preserving strategy (irrational respectively. The application of rational strategies are intended to obtain personal benefits and profit, while adapting irrational strategy is intended to recover emotional stability and reduce some other tensions. Another finding showed that for the investors, the relatively irrational decision formation was "harder" than that of rational.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

Science.gov (United States)

Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

2017-06-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

Directory of Open Access Journals (Sweden)

Morgan A Wambaugh

2017-06-01

Full Text Available Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M. O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT. We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional

Rationality, perception, and the all-seeing eye

NARCIS (Netherlands)

Felin, Teppo; Koenderink, Jan|info:eu-repo/dai/nl/070864543; Krueger, Joachim I