4,309 research outputs found
Polar residues in the protein core of Escherichia coli thioredoxin are important for fold specificity
Most globular proteins contain a core of hydrophobic residues that are inaccessible to solvent in the folded state. In general, polar residues in the core are thermodynamically unfavorable except when they are able to form intramolecular hydrogen bonds. Compared to hydrophobic interactions, polar interactions are more directional in character and may aid in fold specificity. In a survey of 263 globular protein structures, we found a strong positive correlation between the number of polar residues at core positions and protein size. To probe the importance of buried polar residues, we experimentally tested the effects of hydrophobic mutations at the five polar core residues in Escherichia coli thioredoxin. Proteins with single hydrophobic mutations (D26I, C32A, C35A, T66L, and T77V) all have cooperative unfolding transitions like the wild type (wt), as determined by chemical denaturation. Relative to wt, D26I is more stable while the other point mutants are less stable. The combined 5-fold mutant protein (IAALV) is less stable than wt and has an unfolding transition that is substantially less cooperative than that of wt. NMR spectra as well as amide deuterium exchange indicate that IAALV is likely sampling a number of low-energy structures in the folded state, suggesting that polar residues in the core are important for specifying a well-folded native structure
Meaning and method : a comparative study of Edmund Husserl and Ezra Pound
In his essay entitled Phenomenology of Heading Georges Poulet explains how a reading is possible
The universe of fiction is infinitely more elastic than the world of objective reality. It lends itself to any use; it yields with little resistance to the importunities of the mind. Moreover - and of all the benefits I find this the most appealing - this interior universe constituted by language does not seem radically opposed to the me who thinks it.... In short, since everything has become part of my mind, thanks to the intervention of language, the opposition between the subject and its objects has been considerably attenuated. And thus the greatest advantage of literature is that I am freed from my usual sense of incompatibility between my consciousness and its objects.
The dissolution of this subject-object dualism is not the only factor involved. Poulet shows that reading is a way of giving way not only to a host of alien words, images, ideas, but also to the very alien principle which utters them and shelters them
Bluetongue virus infection creates light averse Culicoides vectors and serious errors in transmission risk estimates.
BackgroundPathogen manipulation of host behavior can greatly impact vector-borne disease transmission, but almost no attention has been paid to how it affects disease surveillance. Bluetongue virus (BTV), transmitted by Culicoides biting midges, is a serious disease of ruminant livestock that can cause high morbidity and mortality and significant economic losses. Worldwide, the majority of surveillance for Culicoides to assess BTV transmission risk is done using UV-light traps. Here we show that field infection rates of BTV are significantly lower in midge vectors collected using traps baited with UV light versus a host cue (CO2).MethodsWe collected Culicoides sonorensis midges in suction traps baited with CO2, UV-light, or CO2 + UV on three dairies in southern California to assess differences in the resulting estimated infection rates from these collections. Pools of midges were tested for BTV by qRT-PCR, and maximum likelihood estimates of infection rate were calculated by trap. Infection rate estimates were also calculated by trapping site within a dairy. Colonized C. sonorensis were orally infected with BTV, and infection of the structures of the compound eye was examined using structured illumination microscopy.ResultsUV traps failed entirely to detect virus both early and late in the transmission season, and underestimated virus prevalence by as much as 8.5-fold. CO2 + UV traps also had significantly lower infection rates than CO2-only traps, suggesting that light may repel infected vectors. We found very high virus levels in the eyes of infected midges, possibly causing altered vision or light perception. Collecting location also greatly impacts our perception of virus activity.ConclusionsBecause the majority of global vector surveillance for bluetongue uses only light-trapping, transmission risk estimates based on these collections are likely severely understated. Where national surveillance programs exist, alternatives to light-trapping should be considered. More broadly, disseminated infections of many arboviruses include infections in vectors' eyes and nervous tissues, and this may be causing unanticipated behavioral effects. Field demonstrations of pathogen-induced changes in vector behavior are quite rare, but should be studied in more systems to accurately predict vector-borne disease transmission
Pengaruh Keragaman Produk Dan Kualitas Pelayananterhadap Keputusan Pembelian Ulangmelalui Kepuasan Konsumen Sebagai Variabel Intervening (Studi Pada Konsumen Gelael Mall Ciputra Semarang)
Growth retail business a rapid progress in a few years make competition is tight. Consumer behavior in a shop at a outlet influenced by several factors of them are the diversity products and the quality of services. Supermaket Gelael Mall Ciputra Semarang is one of the supermarkets known in Semarang city. Problems in this research s a reduction turnover income Supermarkets Gelael Ciputra Semarang in 2015, impact on the number of monthly transactions in the growth supermarkets other Semarang city.This study aims to to find out whether is the products diversity and quality service of the decision the purchase repeated through customer satisfaction on the consumer Supermarkets Gelael Ciputra Semarang. Data collection techniques used the interview and questionnaires , while the sample techniques used non probability of sampling with 100 the total sample. Data in analysis with system validity test, reliability test , the coefficients determination test, simple linear regression, multiple linear regression, t test and f test , sobel test and path analysis. Analysis of data done quantitatively on the SPSS program version 19.0.The result showed that diversity of products and quality of services have a positive influence and significant of the decision re purchase through customer satisfaction. This can be seen from the results of the simple analysis linear regression, multiple linear regression, t test , f test, the coefficients determination test , sobel test and path analysis. Customer satisfaction as variable intervening mediate between the diversity of the decision to buy them are full mediation As well as customer satisfaction as variable intervening mediate between product diversity of the decision repeated purchases that is both partial mediation. Of the result of this research,Companies should improve the diversity of products and services to consumer to the customer satisfaction and will may make it a cause loyal to buy replenished so it the sale of company can increase
Iterative approach to computational enzyme design
A general approach for the computational design of enzymes to catalyze arbitrary reactions is a goal at the forefront of the field of protein design. Recently, computationally designed enzymes have been produced for three chemical reactions through the synthesis and screening of a large number of variants. Here, we present an iterative approach that has led to the development of the most catalytically efficient computationally designed enzyme for the Kemp elimination to date. Previously established computational techniques were used to generate an initial design, HG-1, which was catalytically inactive. Analysis of HG-1 with molecular dynamics simulations (MD) and X-ray crystallography indicated that the inactivity might be due to bound waters and high flexibility of residues within the active site. This analysis guided changes to our design procedure, moved the design deeper into the interior of the protein, and resulted in an active Kemp eliminase, HG-2. The cocrystal structure of this enzyme with a transition state analog (TSA) revealed that the TSA was bound in the active site, interacted with the intended catalytic base in a catalytically relevant manner, but was flipped relative to the design model. MD analysis of HG-2 led to an additional point mutation, HG-3, that produced a further threefold improvement in activity. This iterative approach to computational enzyme design, including detailed MD and structural analysis of both active and inactive designs, promises a more complete understanding of the underlying principles of enzymatic catalysis and furthers progress toward reliably producing active enzymes
Seasonal variation and impact of waste-water lagoons as larval habitat on the population dynamics of Culicoides sonorensis (Diptera:Ceratpogonidae) at two dairy farms in northern California.
The Sacramento (northern Central) Valley of California (CA) has a hot Mediterranean climate and a diverse ecological landscape that is impacted extensively by human activities, which include the intensive farming of crops and livestock. Waste-water ponds, marshes, and irrigated fields associated with these agricultural activities provide abundant larval habitats for C. sonorensis midges, in addition to those sites that exist in the natural environment. Within this region, C. sonorensis is an important vector of bluetongue (BTV) and related viruses that adversely affect the international trade and movement of livestock, the economics of livestock production, and animal welfare. To characterize the seasonal dynamics of immature and adult C. sonorensis populations, abundance was monitored intensively on two dairy farms in the Sacramento Valley from August 2012- to July 2013. Adults were sampled every two weeks for 52 weeks by trapping (CDC style traps without light and baited with dry-ice) along N-S and E-W transects on each farm. One farm had large operational waste-water lagoons, whereas the lagoon on the other farm was drained and remained dry during the study. Spring emergence and seasonal abundance of adult C. sonorensis on both farms coincided with rising vernal temperature. Paradoxically, the abundance of midges on the farm without a functioning waste-water lagoon was increased as compared to abundance on the farm with a waste-water lagoon system, indicating that this infrastructure may not serve as the sole, or even the primary larval habitat. Adult midges disappeared from both farms from late November until May; however, low numbers of parous female midges were detected in traps set during daylight in the inter-seasonal winter period. This latter finding is especially critical as it provides a potential mechanism for the "overwintering" of BTV in temperate regions such as northern CA. Precise documentation of temporal changes in the annual abundance and dispersal of Culicoides midges is essential for the creation of models to predict BTV infection of livestock and to develop sound abatement strategies
Model ab initio study of charge carrier solvation and large polaron formation on conjugated carbon chains
Using long C_{N}H_{2} conjugated carbon chains with the polyynic structure as
prototypical examples of one-dimensional (1D) semiconductors, we discuss
self-localization of excess charge carriers into 1D large polarons in the
presence of the interaction with a surrounding polar solvent. The solvation
mechanism of self-trapping is different from the polaron formation due to
coupling with bond-length modulations of the underlying atomic lattice
well-known in conjugated polymers. Model ab initio computations employing the
hybrid B3LYP density functional in conjunction with the polarizable continuum
model are carried out demonstrating the formation of both electron- and
hole-polarons. Polarons can emerge entirely due to solvation but even larger
degrees of charge localization occur when accompanied by atomic displacements
Behavior patterns in hormonal treatments using fuzzy logic models
Assisted reproductive technologies are a combination of medical strategies designed to treat infertility patients. Ideal stimulation treatment has to be individualized, but one of the main challenges which clinicians face in the everyday clinic is how to select the best medical protocol for a patient. This work aims to look for behavior patterns in this kind of treatments, using fuzzy logic models with the objective of helping gynecologists and embryologists to make decisions that could improve the process of in vitro fertilization. For this purpose, a real-world dataset composed of one hundred and twenty-three (123) patients and five hundred and fifty-nine (559) treatments applied in relation to such patients provided by an assisted reproduction clinic, has been used to obtain the fuzzy models. As conclusion, this work corroborates some known clinic experiences, provides some new ones and proposes a set of questions to be solved in future experiments.Ministerio de Economía y Competitividad TIN2013-46928-C3-3-RMinisterio de Economía y Competitividad TIN2016-76956- C3-2-RMinisterio de Economía y Competitividad TIN2015-71938-RED
The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth.
INTRODUCTION: Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. METHODS: We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. RESULTS: The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P < 0.001). The lowest decile of placental weight was associated with 0.73 SD higher umbilical artery Doppler PI at 36 weeks (95% CI: 0.54 to 0.93, P < 0.001). The lowest decile of both placental weight and placental area were associated with reduced growth velocity of the fetal abdominal circumference between 20 and 36 weeks (both P < 0.001). CONCLUSION: Placental area and weight are associated with uterine and umbilical blood flow, respectively, and both are associated with fetal growth rate.This study was funded by the NIHR Cambridge Comprehensive Biomedical Research Centre (grant number A019057) and Stillbirth and Neonatal Death Society (SANDS). GE donated two ultrasound machines for use in the project.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.placenta.2015.12.00
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