Miracle-dz/UniFAR-FTUs huggingface dataset:
Substrate-induced changes in the structural properties of LacY

Significance Lactose permease of Escherichia coli (LacY), a model for the major facilitator superfamily, catalyzes galactopyranoside/H+ symport across the membrane by a mechanism in which large conformational changes expose the sugar-binding site in the middle of the molecule alternatively to either side of the membrane (an alternating access mechanism). Despite substantial progress with respect to static X-ray crystal structures of LacY, the dynamics of the transport mechanism are not fully understood. Here we use dynamic single-molecule force spectroscopy to quantify the structural properties that change upon substrate binding. The results reveal very significant changes in conformational, kinetic, energetic, and mechanical properties primarily in the N-terminal 6-helix bundle, while the C-terminal 6-helix bundle remains largely unaffected. The lactose permease (LacY) of Escherichia coli, a paradigm for the major facilitator superfamily, catalyzes the coupled stoichiometric translocation of a galactopyranoside and an H+ across the cytoplasmic membrane. To catalyze transport, LacY undergoes large conformational changes that allow alternating access of sugar- and H+-binding sites to either side of the membrane. Despite strong evidence for an alternating access mechanism, it remains unclear how H+- and sugar-binding trigger the cascade of interactions leading to alternating conformational states. Here we used dynamic single-molecule force spectroscopy to investigate how substrate binding induces this phenomenon. Galactoside binding strongly modifies kinetic, energetic, and mechanical properties of the N-terminal 6-helix bundle of LacY, whereas the C-terminal 6-helix bundle remains largely unaffected. Within the N-terminal 6-helix bundle, the properties of helix V, which contains residues critical for sugar binding, change most radically. Particularly, secondary structures forming the N-terminal domain exhibit mechanically brittle properties in the unbound state, but highly flexible conformations in the substrate-bound state with significantly increased lifetimes and energetic stability. Thus, sugar binding tunes the properties of the N-terminal domain to initiate galactoside/H+ symport. In contrast to wild-type LacY, the properties of the conformationally restricted mutant Cys154➝Gly do not change upon sugar binding. It is also observed that the single mutation of Cys154➝Gly alters intramolecular interactions so that individual transmembrane helices manifest different properties. The results support a working model of LacY in which substrate binding induces alternating conformational states and provides insight into their specific kinetic, energetic, and mechanical properties.
An Analysis of the Mechanical Disadvantage of Myocardial Infarction in the Canine Left Ventricle

An isotropic, initially spherical, membrane model of the infarcted ventricle satisfactorily predicts ventricular function in the infarcted heart when compared to clinical information and available ventricular models of higher complexity. Computations based on finite element solutions of this membrane model yield end-diastolic and end-systolic pressure-volume curves, from which ventricular function curves are calculated, for infarcts of varying size and material properties. These computations indicate a progressive degradation of cardiac performance with increasing infarct size such that normal cardiac outputs can be maintained with Frank-Starling compensation and increased heart rate for acute infarcts no larger than 41% of the ventricular surface. The relationship between infarct stiffness and cardiac function is found to be complex and dependent on both infarct size and end-diastolic pressure, although moderately stiff subacute infarcts are associated with better function than extensible acute infarcts. Also, calculations of extensions and stresses suggest considerable disruption of the border zone contraction pattern, as well as elevated border zone systolic stresses. Circ Res 47: 728-741, 1980
Broad-Spectrum Drugs Against Viral Agents

Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance.
Trajectory clustering with mixtures of regression models

In this paper we address the problem of clustering trajectories, namely sets of short se quences of data measured as a function of a dependent variable such as time. Examples include storm path trajectories, longitudinal data such as drug therapy response, func tional expression data in computational biology, and movements of objects or individuals in video sequences. Our clustering algorithm is based on a principled method for probabilistic modelling of a set of trajectories as individual sequences of points generated from a finite mixture model consisting of regression model components. Unsupervised learning is carried out using maximum likelihood principles. Specifically, the EM algorithm is used to cope with the hidden data problem (i.e., the cluster memberships). We also develop general izations of the method to handle non-parametric (kernel) regression components as well as multi-dimensional outputs. Simulation results comparing our method with other clustering methods such as K-means and Gaussian mixtures are presented as well as experimental results on real data sets.
Spatiotemporal Independent Component Analysis for the Detection of Functional Responses in Cat Retinal Images

In the early stages of some retinal diseases, such as glaucoma, loss of retinal activity may be difficult to detect with current clinical instruments. Because current instruments require unattainable levels of patient cooperation, high sensitivity and specificity are difficult to attain. We have devised a new retinal imaging system that detects intrinsic optical signals which reflect functional changes in the retina and that do not require patient cooperation. Measured changes in reflectance in response to the visual stimulus are on the order of 0.1%-1% of the total reflected intensity level, which makes the functional signal difficult to detect by standard methods. The desired functional signal is masked by other physiological signals and by imaging system noise. In this paper, we quantify the limits of independent component analysis (ICA) for detecting the low intensity functional signal and apply ICA to 60 video sequences from experiments using an anesthetized cat whose retina is presented with different patterned stimuli. The results of the analysis show that using ICA, in principle, signal levels of 0.1% can be detected. The study found that in 86% of the animal experiments the patterned stimuli effects on the retina can be detected and extracted.
Mutational Analysis of Encephalitozoon cuniculi mRNA Cap (Guanine-N7) Methyltransferase, Structure of the Enzyme Bound to Sinefungin, and Evidence That Cap Methyltransferase Is the Target of Sinefungin's Antifungal Activity*

Cap (guanine-N7) methylation is an essential step in eukaryal mRNA synthesis and a potential target for antiviral, antifungal, and antiprotozoal drug discovery. Previous mutational and structural analyses of Encephalitozoon cuniculi Ecm1, a prototypal cellular cap methyltransferase, identified amino acids required for cap methylation in vivo, but also underscored the nonessentiality of many side chains that contact the cap and AdoMet substrates. Here we tested new mutations in residues that comprise the guanine-binding pocket, alone and in combination. The outcomes indicate that the shape of the guanine binding pocket is more crucial than particular base edge interactions, and they highlight the contributions of the aliphatic carbons of Phe-141 and Tyr-145 that engage in multiple van der Waals contacts with guanosine and S-adenosylmethionine (AdoMet), respectively. We purified 45 Ecm1 mutant proteins and assayed them for methylation of GpppA in vitro. Of the 21 mutations that resulted in unconditional lethality in vivo,14 reduced activity in vitro to < 2% of the wild-type level and 5 reduced methyltransferase activity to between 4 and 9% of wild-type Ecm1. The natural product antibiotic sinefungin is an AdoMet analog that inhibits Ecm1 with modest potency. The crystal structure of an Ecm1-sinefungin binary complex reveals sinefungin-specific polar contacts with main-chain and side-chain atoms that can explain the 3-fold higher affinity of Ecm1 for sinefungin versus AdoMet or S-adenosylhomocysteine (AdoHcy). In contrast, sinefungin is an extremely potent inhibitor of the yeast cap methyltransferase Abd1, to which sinefungin binds 900-fold more avidly than AdoHcy or AdoMet. We find that the sensitivity of Saccharomyces cerevisiae to growth inhibition by sinefungin is diminished when Abd1 is overexpressed. These results highlight cap methylation as a principal target of the antifungal activity of sinefungin.
Vision Based Gesture Recognition for Alphabetical Hand Gestures Using the SVM Classifier

In this paper we discuss how a Gesture Recognition system for Alphabetical Hand Gestures is built. The main motive was to develop a system that can simplify the way humans interact with computers. The system is designed using the Support Vector Machine (SVM) Classifier which is widely used for classification and regression testing. SVM training algorithm builds a model that predicts whether a new example falls into one category or other. And the SVM classifier learns from the data points in examples when they are classified belonging to their respective categories.
Advancing a Model of Avatar Evaluation and Selection

Viewers (N = 261) evaluated and chose avatars to represent them online. The viewers rated 92 potential avatars that were manipulated along three dimensions ± sex, humanness, and integrity. Perceived gender of the image, its anthropomorphic intensity, and realism mediated the effects of the manipulated variables on judgments of homophily as a representation of self, credibility, and the likelihood that it would be used as an avatar during future interactions. Results indicated that anthropomorphic intensity enhanced image homophily, in part by increasing perceived realism. Image gender was found to produce a combination of positive and negative effects on competence ratings and avatar choice. The theoretical and practical implications of the findings are discussed.
An Investigation of the Role of Distinctiveness on the Production Effect

The current study examined the role of distinctive processing on the production effect (i.e., enhanced memory for words read aloud versus silently). Participants read a mixed list of thirtysix words presented one at a time for three-seconds each. Half of the items were read aloud and half were read silently; these word lists were comprised of items belonging to either natural categories or ad hoc categories. Immediately following study, participants completed a free recall test then a recognition test two days later. Results from recall and recognition tests support a distinctiveness account of the production effect. The current results support MacLeod et. al’s (2010) suggestion that distinctiveness underlies the production effect. Specifically, reading words aloud increases item-specific processing, a crucial component of distinctive processing.
When Structure Affects Function – The Need for Partial Volume Effect Correction in Functional and Resting State Magnetic Resonance Imaging Studies

Both functional and also more recently resting state magnetic resonance imaging have become established tools to investigate functional brain networks. Most studies use these tools to compare different populations without controlling for potential differences in underlying brain structure which might affect the functional measurements of interest. Here, we adapt a simulation approach combined with evaluation of real resting state magnetic resonance imaging data to investigate the potential impact of partial volume effects on established functional and resting state magnetic resonance imaging analyses. We demonstrate that differences in the underlying structure lead to a significant increase in detected functional differences in both types of analyses. Largest increases in functional differences are observed for highest signal-to-noise ratios and when signal with the lowest amount of partial volume effects is compared to any other partial volume effect constellation. In real data, structural information explains about 25% of within-subject variance observed in degree centrality – an established resting state connectivity measurement. Controlling this measurement for structural information can substantially alter correlational maps obtained in group analyses. Our results question current approaches of evaluating these measurements in diseased population with known structural changes without controlling for potential differences in these measurements.
Daily life of persons with dementia and their spouses supported by a passive positioning alarm

Olsson, A. (2013): Daily life of persons with dementia and their spouses supported by a passive positioning alarm. Örebro Studies in Care Sciences 44, 81 pp. The overall aim was to describe how persons with dementia (PwDs) reflect on being outdoors and to investigate the support provided by a passive positioning alarm (PPA) in making daily life safer for PwDs and their spouses. Repeated conversations were held with 11 PwDs living in their own homes regarding their reflections on being outdoors (Study I). Interview study with 14 spouses to a person with dementia (PwD) with their reflections on different kinds of information and communication technology (ICT) devices that were used or can be used in the daily care of PwDs (Study II). An ethnographic approach with participant observations and conversations with five couples, a PwD and his/her spouse, describing and exploring their use and experiences of using a PPA, over time, in daily life (Study III). An experimental single-case ABAB-design with three cases, a PwD and his spouse, investigating the effects of using tracking technology on independent outdoor activities and psychological well-being (Study IV). In summary, the results of the thesis show that being outdoors was described by the PwDs as a confirmation of their identity, the `Self ́. The use of ICT in daily care of PwDs was described by the spouses as shifting between their own needs for safety and security and the perceived need for safety and security from the perspective of the PwD. The use of a PPA in daily life among PwDs living in their own homes can give a sense of freedom, support and strengthen the feeling of independence for both PwDs and their spouses as well as give a feeling of safety and security for them both. Use of the PPA may also increase PwDs’ independent outdoor activities and decrease spouses’ worries.
Evolution of sexual dichromatism : contribution of carotenoid-versus melanin-based coloration

In birds, carotenoid-based plumage coloration is more dependent on physical condition and foraging abilities and less constrained developmentally than is melanin-based coloration. Thus, female mate choice for honest signals should result in more intense sexual selection on carotenoidthan on melanin-based plumage coloration. Using variation in sexual dimorphism as an indirect measure of the intensity of sexual selection, we tested the prediction that variation in sexual dimorphism is driven more by change in carotenoid-based coloration between males and females than by change in melanin-based coloration. Examination of historical changes in carotenoidversus melanin-based pigmentation in 126 extant species of Cardueline finches supported this prediction. We found that carotenoid-derived coloration changed more frequently among congeners than melanin-based coloration. In both sexes, increase in carotenoid-based coloration score, but not in melanin-based coloration score, was strongly associated with increase in sexual dichromatism. In addition, sexual dimorphism in carotenoid-based coloration contributed more to overall dichromatism than dimorphism in melanin-based plumage. Our results supported the hypothesis that melanin-based and carotenoid-based coloration have fundamentally different signal content and suggest that combining melanin-based and carotenoid-based coloration in comparative analyses is not appropriate.
Are Routine Dilatations Necessary Post Pull-Through Surgery for Hirschsprung Disease?

Abstract Introduction We aim to compare the anastomotic stricture and enterocolitis rates between groups who either had or did not have anal dilatations (AD or NAD) prescribed routinely post pull-through surgery for Hirschsprung disease (HD); by this means, we will evaluate the benefit of routine dilatations. Methods A retrospective review of the records of all children operated on for HD between 1997 and 2010 was performed. Associated Down syndrome and total colonic aganglionosis were excluded. Two cohorts were identified; those who had anal dilatation prescribed routinely (AD) and those who did not (NAD). In the latter group, if an anastomotic stricture was subsequently diagnosed, anal dilatations were initiated. The anastomotic stricture and enterocolitis rates between groups were compared. Significance was set at p < 0.05. Results There were 73 children that met the inclusion criteria (30 AD and 43 NAD). The NAD group had the longer mean follow-up period of 91 versus 59 months (p = 0.026); however, follow-up duration was unrelated to the anastomotic stricture rates (p = 0.575) and enterocolitis rates (p = 0.150). The anastomotic stricture rates were 13% (n = 4) versus 14% (n = 6) (p = 1.000) for the AD and NAD groups, respectively (relative risk [95% confidence interval] RR [95% CI], 0.95 [0.29 to 3.09]; p = 0.94). The mean duration between surgery and stricture occurrence was 348 versus 74 days for the AD and NAD groups, respectively. The enterocolitis rates were 23% (n = 7) versus 28% (n = 12) (p = 0.788) for the AD and NAD groups, respectively (RR [95% CI], 0.84 [0.37 to 1.87]; p = 0.66). Conclusion We have not shown a reduced risk of developing anastomotic strictures or enterocolitis if anal dilatations are prescribed routinely. However, when routine dilatations were prescribed, predominantly late onset strictures of perhaps a different etiology occurred.
Artificial insect wings of diverse morphology for flapping-wing MAVs

The development of flapping-wing micro air vehicles (MAVs) demands a systematic exploration of the available design space to identify ways in which the unsteady mechanisms governing flapping-wing flight can best be utilized for producing optimal thrust or maneuverability. Mimicking the wing kinematics of biological flight requires examining the potential effects of wing morphology on flight performance, as wings may be specially adapted for flapping flight. For example, insect wings passively deform during flight, leading to instantaneous and potentially unpredictable changes in aerodynamic behavior. Previous studies have postulated various explanations for insect wing complexity, but there lacks a systematic approach for experimentally examining the functional significance of components of wing morphology, and for determining whether or not natural design principles can or should be used for MAVs. In this work, a novel fabrication process to create centimeter-scale wings of great complexity is introduced; via this process, a wing can be fabricated with a large range of desired mechanical and geometric characteristics. We demonstrate the versatility of the process through the creation of planar, insect-like wings with biomimetic venation patterns that approximate the mechanical properties of their natural counterparts under static loads. This process will provide a platform for studies investigating the effects of wing morphology on flight dynamics, which may lead to the design of highly maneuverable and efficient MAVs and insight into the functional morphology of natural wings. Key index words: Insect aerodynamics, micro air vehicles, flapping-wing aerodynamics, biomimetics, wing flexibility
The Effect Temperature on the Growth Characteristics of Ethanol Producing Yeast Strains

For commercial corn mash to ethanol production it is known that increasing temperature can maximize ethanol yield, although care must be taken to avoid causing heat shock resulting in the death of the yeast culture. Despite the potentially negative effects of high temperature, short sub-lethal stress has been reported to procure a benefit to yeast cells. However, the effect of such yeast pre-treatment on bioethanol fermentations has not previously been investigated. In order to understand more about the effects of the temperature on yeast prior corn mash fermentation, the growth characteristic of four industrial ethanologenic yeast strains to heat stress was determined. The spot plate method and analysis of yeast growth in liquid medium were used in this study. Our obtained results offer an optimal condition for the use of yeast cells in pre- conditioning before the fermentation of corn mash or other materials to bioethanol.
Truncation and Activation of Calcineurin A by Calpain I in Alzheimer Disease Brain*

A disturbance of calcium homeostasis is believed to play an important role in the neurodegeneration of the brains of Alzheimer disease (AD) patients, but the molecular pathways by which it contributes to the disease are not well understood. Here we studied the activation of two major Ca2+-regulated brain proteins, calpain and calcineurin, in AD brain. We found that calpain I is activated, which in turn cleaves and activates calcineurin in AD brain. Mass spectrometric analysis indicated that the cleavage of calcineurin by calpain I is at lysine 501, a position C-terminal to the autoinhibitory domain, which produces a 57-kDa truncated form. The 57-kDa calcineurin maintains its Ca2+/calmodulin dependence of the phosphatase activity, but the phosphatase activity is remarkably activated upon truncation. The cleavage and activation of calcineurin correlate to the number of neurofibrillary tangles in human brains. These findings suggest that the overactivation of calpain I and calcineurin may mediate the role of calcium homeostatic disturbance in the neurodegeneration of AD.
Constraint based Interesting Location and Mobile Web Service Sequence Mining in M-Commerce Environment

Recently, mobile web services have become a more emerging topic due to popularity of smart phones and laptops. Mobile web services are becoming popular because the growth of internet speeds. Mobile web service is not only useful for particular user, but also for business purposes. It is useful for growth of a particular business. For a particular business, it is important to have the knowledge of user's interest. In M-commerce environment user's interesting web service sequence mining is also an emerging topic now a day. If a business person knows the web service accessing sequence of any user, he can plan new information for that particular user. Today, user's web service accessing sequence mining is based on type of service, visiting locations, timing and some specific constraints. The constraint may define the importance or utility of a particular web service. Here, we consider utility based constraint for particular user in M-commerce environment. We proposed an efficient approach, namely Mobile Web Service Sequence Mining to mine utility based user's interesting web service accessing sequence. Experimental results show that the proposed approach is better than previous constraint based approaches.