Asymmetric stochastic switching driven by intrinsic molecular noise

Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

The Prediction of Creep and Shrinkage Properties of Concrete, HR-136, 1970

This report is concerned with the prediction of the long-time creep and shrinkage behavior of concrete. It is divided into three main areas. l. The development of general prediction methods that can be used by a design engineer when specific experimental data are not available. 2. The development of prediction methods based on experimental data. These methods take advantage of equations developed in item l, and can be used to accurately predict creep and shrinkage after only 28 days of data collection. 3. Experimental verification of items l and 2, and the development of specific prediction equations for four sand-lightweight aggregate concretes tested in the experimental program. The general prediction equations and methods are developed in Chapter II. Standard Equations to estimate the creep of normal weight concrete (Eq. 9), sand-lightweight concrete (Eq. 12), and lightweight concrete (Eq. 15) are recommended. These equations are developed for standard conditions (see Sec. 2. 1) and correction factors required to convert creep coefficients obtained from equations 9, 12, and 15 to valid predictions for other conditions are given in Equations 17 through 23. The correction factors are shown graphically in Figs. 6 through 13. Similar equations and methods are developed for the prediction of the shrinkage of moist cured normal weight concrete (Eq. 30}, moist cured sand-lightweight concrete (Eq. 33}, and moist cured lightweight concrete (Eq. 36). For steam cured concrete the equations are Eq. 42 for normal weight concrete, and Eq. 45 for lightweight concrete. Correction factors are given in Equations 47 through 52 and Figs., 18 through 24. Chapter III summarizes and illustrates, by examples, the prediction methods developed in Chapter II. Chapters IV and V describe an experimental program in which specific prediction equations are developed for concretes made with Haydite manufactured by Hydraulic Press Brick Co. (Eqs. 53 and 54}, Haydite manufactured by Buildex Inc. (Eqs. 55 and 56), Haydite manufactured by The Cater-Waters Corp. (Eqs. 57 and 58}, and Idealite manufactured by Idealite Co. (Eqs. 59 and 60). General prediction equations are also developed from the data obtained in the experimental program (Eqs. 61 and 62) and are compared to similar equations developed in Chapter II. Creep and Shrinkage prediction methods based on 28 day experimental data are developed in Chapter VI. The methods are verified by comparing predicted and measured values of the long-time creep and shrinkage of specimens tested at the University of Iowa (see Chapters IV and V) and elsewhere. The accuracy obtained is shown to be superior to other similar methods available to the design engineer.

Loss of Prestress, Camber, and Deflection of Non-Composite and Composite Structures Using Different Weight Concretes, HR-137, 1970

General equations are presented for predicting loss of prestress and camber of both composite and non- composite prestressed concrete structures. Continuous time functins of all parameters needed to solve the equations are given, and sample results included. Computed prestress loss and camber are compared with experimental data for normal weight and lightweight concrete. Methods are also presented for predicting the effect of non-prestressed tension steel in reducing time-dependent loss of prestress and camber, and for the determination of short-time deflections of uncracked and cracked prestressed members. Comparisons with experimental results are indicated for these partially prestressed methods.

On the diurnal soil water content dynamics during evaporation using dielectric methods

The water content dynamics in the upper soil surface during evaporation is a key element in land-atmosphere exchanges. Previous experimental studies have suggested that the soil water content increases at the depth of 5 to 15 cm below the soil surface during evapo- ration, while the layer in the immediate vicinity of the soil surface is drying. In this study, the dynamics of water content profiles exposed to solar radiative forcing was monitored at a high temporal resolution using dielectric methods both in the presence and absence of evaporation. A 4-d comparison of reported moisture content in coarse sand in covered and uncovered buckets using a commercial dielectric-based probe (70 MHz ECH2O-5TE, Decagon Devices, Pullman, WA) and the standard 1-GHz time domain reflectometry method. Both sensors reported a positive correlation between temperature and water content in the 5- to 10-cm depth, most pronounced in the morning during heating and in the afternoon during cooling. Such positive correlation might have a physical origin induced by evaporation at the surface and redistribution due to liquid water fluxes resulting from the temperature- gradient dynamics within the sand profile at those depths. Our experimental data suggest that the combined effect of surface evaporation and temperature-gradient dynamics should be considered to analyze experimental soil water profiles. Additional effects related to the frequency of operation and to protocols for temperature compensation of the dielectric sensors may also affect the probes' response during large temperature changes.

Schizophrenia: glutathione deficit as a new vulnerability factor for disconnectivity syndrome

(from the journal abstract) Schizophrenia, a major psychiatric disease, affects individuals in the centre of their personality. Its aetiology is not clearly established. In this review, we will present evidence that patients suffering of schizophrenia present a brain deficit in glutathione, a major endogenous redox regulator and antioxidant. We will also show that, in experimental models, a decrease in glutathione, particularly during development, induces morphological, electrophysiological and behavioural anomalies consistent with those observed in the disease. In the cerebrospinal fluid of drug-naive schizophrenics, glutathione level was decreased by 27% and its direct metabolite of glutathione by 16%. Glutathione level in prefrontal cortex of patients, measured by magnetic resonance spectroscopy, was 52% lower than in controls. Patients' fibroblasts reveal a decrease in mRNA levels of the two glutathione synthesising enzymes, glutamatecysteine ligase modulatory subunit (GCLM) and glutathione synthetase. GCLM expression level in fibroblasts correlates negatively with symptoms severity. Glutathione is an important endogenous redox regulator and neuroactive substance. It is protecting cells from damage by reactive oxygen species generated, among others, by dopamine metabolism. A glutathione deficit-induced oxidative stress would lead to lipid peroxidation and micro-lesions at the level of dendritic spines, a synaptic damage responsible for abnormal nervous connections or structural disconnectivity. On the other hand, a glutathione deficit could also lead to a functional disconnectivity by depressing NMDA neurotransmission, in analogy to phencyclidine effects. Present experimental data are consistent with the proposed hypothesis: decreasing pharmacologically glutathione level in experimental models, with or without blocking dopamine (DA) uptake (GBR12909), induces morphological, electrophysiological and behavioural changes similar to those observed in patients. In summary, a deficit of glutathione and/or glutathione-related enzymes during early development would lead to both a functional and a structural disconnectivity, which could be at the basis of some perceptive, cognitive and behavioural troubles of the disease. It could constitute a major vulnerability factor for schizophrenia. Attempts to restore physiological glutathione functions could open new therapeutic avenues. This translational research, made possible by a close interaction between clinicians and neuroscientists, should also pave the way to the identification of biological markers for schizophrenia. In turn, they should allow early diagnostic and hopefully preventive intervention to this devastating disease. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

A Continuous Span Aluminum Girder Concrete Deck Bridge - Part 2 of 2: Fatigue Tests of Aluminum Girders, Final Report, 1997

In 1957, the Iowa State Highway Commission, with financial assistance from the aluminum industry, constructed a 220-ft (67-m) long, four-span continuous, aluminum girder bridge to carry traffic on Clive Road (86th Street) over Interstate 80 near Des Moines, Iowa. The bridge had four, welded I-shape girders that were fabricated in pairs with welded diaphragms between an exterior and an interior girder. The interior diaphragms between the girder pairs were bolted to girder brackets. A composite, reinforced concrete deck served as the roadway surface. The bridge, which had performed successfully for about 35 years of service, was removed in the fall of 1993 to make way for an interchange at the same location. Prior to the bridge demolition, load tests were conducted to monitor girder and diaphragm bending strains and deflections in the northern end span. Fatigue testing of the aluminum girders that were removed from the end spans were conducted by applying constant-amplitude, cyclic loads. These tests established the fatigue strength of an existing, welded, flange-splice detail and added, welded, flange-cover plates and horizontal web plate attachment details. This part, Part 2, of the final report focuses on the fatigue tests of the aluminum girder sections that were removed from the bridge and on the analysis of the experimental data to establish the fatigue strength of full-size specimens. Seventeen fatigue fractures that were classified as Category E weld details developed in the seven girder test specimens. Linear regression analyses of the fatigue test results established both nominal and experimental stress-range versus load cycle relationships (SN curves) for the fatigue strength of fillet-welded connections. The nominal strength SN curve obtained by this research essentially matched the SN curve for Category E aluminum weldments given in the AASHTO LRFD specifications. All of the Category E fatigue fractures that developed in the girder test specimens satisfied the allowable SN relationship specified by the fatigue provisions of the Aluminum Association. The lower-bound strength line that was set at two standard deviations below the least squares regression line through the fatigue fracture data points related well with the Aluminum Association SN curve. The results from the experimental tests of this research have provided additional information regarding behavioral characteristics of full-size, aluminum members and have confirmed that aluminum has the strength properties needed for highway bridge girders.

CO2-response function of radiation use efficiency in rice for climate change scenarios

The objective of this work was to evaluate a generalized response function to the atmospheric CO2 concentration [f(CO2)] by the radiation use efficiency (RUE) in rice. Experimental data on RUE at different CO2 concentrations were collected from rice trials performed in several locations around the world. RUE data were then normalized, so that all RUE at current CO2 concentration were equal to 1. The response function was obtained by fitting normalized RUE versus CO2 concentration to a Morgan-Mercer-Flodin (MMF) function, and by using Marquardt's method to estimate the model coefficients. Goodness of fit was measured by the standard deviation of the estimated coefficients, the coefficient of determination (R²), and the root mean square error (RMSE). The f(CO2) describes a nonlinear sigmoidal response of RUE in rice, in function of the atmospheric CO2 concentration, which has an ecophysiological background, and, therefore, renders a robust function that can be easily coupled to rice simulation models, besides covering the range of CO2 emissions for the next generation of climate scenarios for the 21st century.

Controls on 13C and 14C variability in soil CO2

14C dating of groundwater depends on the isotopic composition of both the solid carbonate and the soil CO2 and requires the use of 14C age correction models. To better assess the variability of the 14C activity of soil CO2 (A14Csoil-CO2) and the δ13C of soil CO2 (δ13Csoil-CO2), which are two parameters used in 14C age correction models, we studied the different processes involving carbon isotopes in the soil. The approach used experimental data from two sites in France (Fontainebleau sands and Astian sands) and a steady-state transport model. In most cases, the 14C activity (A14C) of atmospheric CO2 is directly used in the 14C age correction models as the A14Csoil-CO2. However, we demonstrate that since 1950, the evolution of the A14Csoil-CO2 reflects the competition between the fluxes of root-derived CO2 and organic matter-derived CO2. Therefore, the A14Csoil-CO2 must be used to date groundwater that is younger than 60 years old. Moreover, the δ13C of soil CO2 (δ13Csoil-CO2) showed large seasonal variations that must be taken into account in selecting the δ13Csoil-CO2 for 14C age correction models.

Probabilistic algorithms for blind adaptive multiuser detection

In this paper, two probabilistic adaptive algorithmsfor jointly detecting active users in a DS-CDMA system arereported. The first one, which is based on the theory of hiddenMarkov models (HMM’s) and the Baum–Wech (BW) algorithm,is proposed within the CDMA scenario and compared withthe second one, which is a previously developed Viterbi-basedalgorithm. Both techniques are completely blind in the sense thatno knowledge of the signatures, channel state information, ortraining sequences is required for any user. Once convergencehas been achieved, an estimate of the signature of each userconvolved with its physical channel response (CR) and estimateddata sequences are provided. This CR estimate can be used toswitch to any decision-directed (DD) adaptation scheme. Performanceof the algorithms is verified via simulations as well as onexperimental data obtained in an underwater acoustics (UWA)environment. In both cases, performance is found to be highlysatisfactory, showing the near–far resistance of the analyzed algorithms.

Cellules gliales et douleur chronique: du laboratoire a l'espoir clinique [Glial cells and chronic pain: from the laboratory to clinical hope].

Despite their high prevalence, associated disability and seemingly rich pharmacopeia, the various forms of chronic pain remain frequently intractable. The past decade witnessed the rise of a concept stating that non-neuronal cells of the central nervous system, astrocytes and microglia, are crucial elements in pathological pain. This review gathers and summarizes the experimental data underpinning this theory in animal models and addresses their pertinence in humans. The potential opportunities and constraints of glial inhibition are exposed and compared to more moderate strategies of selective modulation. This therapeutic hope is particularly highlighted in our discussion of the first completed clinical trials employing glial inhibitors in the treatment of chronic pain.

Kinetics of selective oxidation of lactose to lactobionic acid over Pd-active carbon catalyst

Laktoosi eli maitosokeri on tärkein ainesosa useimpien nisäkkäiden tuottamassa maidossa. Sitä erotetaan herasta, juustosta ja maidosta. Laktoosia käytetään elintarvike- ja lääketeollisuuden raaka-aineena monissaeri tuotteissa. Lääketeollisuudessa laktoosia käytetään esimerkiksi tablettien täyteaineena. Hapettamalla laktoosia voidaan valmistaa laktobionihappoa, 2-keto-laktobionihappoa ja laktuloosia. Laktobionihappoa käytetään biohajoavien pintojen ja kosmetiikkatuotteiden valmistuksessa, sekä sisäelinten säilöntäliuoksissa, joissa laktobionihappo estää happiradikaalien aiheuttamien kudosvaurioiden syntymistä. Tässä työssä laktoosia hapetettiin laktobionihapoksi sekoittimella varustetussa laboratoriomittakaavaisessa panosreaktorissa käyttäenkatalyyttinä palladiumia aktiivihiilellä. Muutamissa kokeissa katalyytin promoottorina käytettiin vismuttia, joka hidastaa katalyytin deaktivoitumista. Työn tarkoituksena oli saada lisää tietoa laktoosin hapettamisen kinetiikasta. Laktoosin hapettumisessa laktobionihapoksi havaittiin selektiivisyyteen vaikuttavan muunmuassa reaktiolämpötila, paine, pH ja käytetyn katalyytin määrä. Katalyyttiä kierrättämällä eri kokeiden välillä saatiin paremmat konversiot, selektiivisyydet ja saannot. Parhaat koetulokset saatiin hapetettaessa synteettisellä ilmalla 60 oC lämpötilassa ja 1 bar paineessa. Tehdyissä kokeissa pH:n säätö tehtiin manuaalisesti, joten pH ei pysynyt koko ajan haluttuna. Laktoosin konversio oli parhaimmillaan 95 %. Laktobionihapon suhteellinen selektiivisyys oli 100% ja suhteellinen saanto 100 %. Kinetiikan matemaattinen mallinnus tehtiin Modest-ohjelmalla käyttäen kokeista saatuja mittaustuloksia.Ohjelman avulla estimoitiin parametreja ja saatiin matemaattinen malli reaktorille. Tässä työssä tehtiin kineettinen mallinnus myös ravistelureaktorissa tehdyille laktoosin hapetuskokeille, missä pH pysyi koko ajan haluttuna 'in-situ' titrauksen avulla. Työn yhteydessä selvitettiin myös mahdollisuutta käyttää monoliittikatalyyttejä laktoosin hapetusreaktiossa.

Investigation ofsolid - state cooler based on electrocaloric effect

Electrocaloric cooling based on ability of material to change temperature by applying an electric field under adiabatic conditions is relatively new and challenging direction of ferroelectrics research. In this work we report about analytical, simulation and experimental data for BaSrTiO3 thin film and bulk ceramic samples. Detailed discussion of a theoretical base of the electrocaloric effect is included. Demonstrated experimental and computational results exemplify rational approach to a problem of solid-state cooler construction.

Acute pulmonary toxicity following occupational exposure to a floor stain protector in the building industry in Switzerland.

BACKGROUND: Waterproofing agents are widely applied to leather and textile garments; they are also used as floor stain protectors by professionals. Acute respiratory injury is described in three cases of young healthy adults following occupational inhalation of a new waterproofing formulation containing an acrylate fluoropolymer. Within 1 or 2 h after exposure they developed a rapidly progressive dyspnoea; two of them had hypoxaemia and flu-like reactions. All patients improved with supportive treatment in a few days. The mechanism of toxicity is still under investigation, but experimental data suggest the role of this new acrylate fluoropolymer. CONCLUSION: Tilers should be warned against spraying floor stain repellents; there is also a need to make consumers aware that the spraying of waterproofing agents in a closed environment and concomitant smoking should be avoided.

An Assessment ofFatigue Strength of Load Carrying Welded Joints with Lack of Penetration

On yleisesti tiedossa, että väsyttävän kuormituksen alaisena olevat hitsatut rakenteet rikkoutuvat juuri hitsausliitoksista. Täyden tunkeuman hitsausliitoksia sisältävien rakenteiden asiantunteva suunnittelu janykyaikaiset valmistusmenetelmät ovat lähes eliminoineet väsymisvauriot hitsatuissa rakenteissa. Väsymislujuuden parantaminen tiukalla täyden tunkeuman vaatimuksella on kuitenkin epätaloudellinen ratkaisu. Täyden tunkeuman hitsausliitoksille asetettavien laatuvaatimuksien on määriteltävä selkeät tarkastusohjeet ja hylkäämisperusteet. Tämän diplomityön tarkoituksena oli tutkia geometristen muuttujien vaikutusta kuormaa kantavien hitsausliitosten väsymislujuuteen. Huomio kiinnitettiin pääasiassa suunnittelumuuttujiin, joilla on vaikutusta väsymisvaurioiden syntymiseen hitsauksen juuren puolella. Nykyiset määräykset ja standardit, jotka perustuvat kokeellisiin tuloksiin; antavat melko yleisiä ohjeita hitsausliitosten väsymismitoituksesta. Tämän vuoksi muodostettiin kokonaan uudet parametriset yhtälöt sallitun nimellisen jännityksen kynnysarvon vaihteluvälin, ¿¿th, laskemiseksi, jotta vältettäisiin hitsausliitosten juuren puoleiset väsymisvauriot. Lisäksi, jokaiselle liitostyypille laskettiin hitsin juuren puolen väsymisluokat (FAT), joita verrattiin olemassa olevilla mitoitusohjeilla saavutettuihin tuloksiin. Täydentäviksi referensseiksi suoritettiin useita kolmiulotteisia (3D) analyysejä. Julkaistuja kokeellisiin tuloksiin perustuvia tietoja käytettiin apuna hitsausliitosten väsymiskäyttäytymisen ymmärtämiseksi ja materiaalivakioiden määrittämiseksi. Kuormaa kantavien vajaatunkeumaisten hitsausliitosten väsymislujuus määritettiin käyttämällä elementtimenetelmää. Suurimman pääjännityksen kriteeriä hyödynnettiin murtumiskäyttäytymisen ennakoimiseksi. Valitulle hitsatulle materiaalille ja koeolosuhteille murtumiskäyttäytymistä mallinnettiin särön kasvunopeudella da/dN ja jännitysintensiteettikertoimen vaihteluvälillä, 'K. Paris:n yhtälön numeerinen integrointi suoritettiin FRANC2D/L tietokoneohjelmalla. Saatujen tulosten perusteella voidaan laskea FAT tutkittavassa tapauksessa. ¿¿th laskettiin alkusärön jännitysintensiteettikertoimen vaihteluvälin ja kynnysjännitysintensiteettikertoimen, 'Kth, perusteella. ¿Kth arvoa pienemmällä vaihteluvälillä särö ei kasva. Analyyseissäoletuksena oli hitsattu jälkikäsittelemätön liitos, jossa oli valmis alkusärö hitsin juuressa. Analyysien tulokset ovat hyödyllisiä suunnittelijoille, jotka tekevät päätöksiä koskien geometrisiä parametreja, joilla on vaikutusta hitsausliitosten väsymislujuuteen.

Unifying Time to Contact Estimation and Collision Avoidance across Species

The -function and the -function are phenomenological models that are widely used in the context of timing interceptive actions and collision avoidance, respectively. Both models were previously considered to be unrelated to each other: is a decreasing function that provides an estimation of time-to-contact (ttc) in the early phase of an object approach; in contrast, has a maximum before ttc. Furthermore, it is not clear how both functions could be implemented at the neuronal level in a biophysically plausible fashion. Here we propose a new framework the corrected modified Tau function capable of predicting both -type ("") and -type ("") responses. The outstanding property of our new framework is its resilience to noise. We show that can be derived from a firing rate equation, and, as , serves to describe the response curves of collision sensitive neurons. Furthermore, we show that predicts the psychophysical performance of subjects determining ttc. Our new framework is thus validated successfully against published and novel experimental data. Within the framework, links between -type and -type neurons are established. Therefore, it could possibly serve as a model for explaining the co-occurrence of such neurons in the brain.