Miracle-dz/UniFAR-FTUs huggingface dataset:
Pseudo‐symmetry of C19‐steroids, alternative binding orientations and multispecificity in human estrogenic 17β‐hydroxysteroid dehydrogenase

Steroids are implicated in many physiological processes, such as reproduction, aging, metabolism, and cancer. To understand the molecular basis for steroid recognition and discrimination, we studied the human estrogenic 17β‐hydroxysteroid dehydrogenase (17β‐HSD1) responsible for the last step in the bioactivation of all estrogens. Here we report the first observation of the conversion of dihydrotestosterone (DHT) into 3β,17β‐androstanediol (3β‐diol) by 17β‐HSD1, an estrogenic enzyme studied for more than half a century. Kinetic observations demonstrate that both the 3β‐reduction of DHT into 3β‐diol (kcat = 0.040 s−1; Km = 32 ± 9 μM) and the 17β‐oxidation of DHT into androstandione (A‐dione) (kcat = 0.19 s−1; Km = 26 ±6 μM) are catalyzed by 17β‐HSD1 via alternative binding orientation of the steroid. The reduction of DHT was also observed in intact cells by using HEK‐293 cells stably transformed with 17β‐HSD1. The high‐resolution structure of a 17β‐HSD1‐C19‐steroid (testosterone) complex solved at 1.54 Å demonstrates that the steroid is reversibly oriented in the active site, which strongly supports the existence of alternative binding mode. Such a phenomenon can be explained by the pseudo‐symmetric structure of C19‐steroids. Our results confirm the role of the Leu149 residue in C18/C19‐steroid discrimination and suggest a possible mechanism of 17β‐HSD1 in the modulation of DHT levels in tissues, such as the breast, where both the enzyme and DHT are present.
AN ADAPTIVE WALK BY HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 THROUGH A FLUCTUATING FITNESS LANDSCAPE

The mutational landscape model of adaptive sequence evolution has been used to explain an unexpected strong positive linear relationship between marginal fitness and mean site‐specific amino acid frequency in the functionally important HIV‐1 gp120 V3 protein region. The model predicts a positive linear relationship between the probability that a particular beneficial allele, among several, is the next to spread to fixation during an adaptive walk, its transition probability, and the allele's selection coefficient. Here, stochastic simulation is used to confirm the intuition that the linear relationship between transition probabilities and selection coefficients, predicted by the model, should, under fluctuating selection, produce a linear relationship between allele frequency, averaged across populations, and fitness. In addition, these relationships hold for the effective population size and mutation rate of HIV‐1 and for the moderately strong selection observed for V3. A survey of the strength of mutation for diverse organisms suggests that these relationships may be widely applicable.
Diversity, relative abundance and metabolic potential of bacterial endosymbionts in three Bathymodiolus mussel species from cold seeps in the Gulf of Mexico.

Cold seeps in the Gulf of Mexico are often dominated by mussels of the genus Bathymodiolus that harbour symbiotic bacteria in their gills. In this study, we analysed symbiont diversity, abundance and metabolic potential in three mussel species from the northern Gulf of Mexico: Bathymodiolus heckerae from the West Florida Escarpment, Bathymodiolus brooksi from Atwater Valley and Alaminos Canyon, and 'Bathymodiolus' childressi, which co-occurs with B. brooksi in Alaminos Canyon. Comparative 16S rRNA sequence analysis confirmed a single methanotroph-related symbiont in 'B. ' childressi and a dual symbiosis with a methanotroph- and thiotroph-related symbiont in B. brooksi. A previously unknown diversity of four co-occurring symbionts was discovered in B. heckerae: a methanotroph, two phylogenetically distinct thiotrophs and a methylotroph-related phylotype not previously described from any marine invertebrate symbiosis. A gene characteristic of methane-oxidzing bacteria, pmoA, was identified in all three mussel species confirming the methanotrophic potential of their symbionts. Stable isotope analyses of lipids and whole tissue also confirmed the importance of methanotrophy in the carbon nutrition of all of the mussels. Analyses of absolute and relative symbiont abundance in B. heckerae and B. brooksi using fluorescence in situ hybridization (FISH) and rRNA slot blot hybridization indicated a clear dominance of methanotrophic over thiotrophic symbionts in their gill tissues. A site-dependent variability in total symbiont abundance was observed in B. brooksi, with specimens from Alaminos Canyon harbouring much lower densities than those from Atwater Valley. This shows that symbiont abundance is not species-specific but can vary considerably between populations.
Effects of simulated weightlessness on bone mineral metabolism.

Space flight and bedrest result in a negative calcium balance and osteopenia. The mechanisms underlying these events are not well understood. In particular, it is not clear whether systemic or local factors are preeminent in mediating the effects of gravity on bone mineral content. Using a rat model that unweights only the hindlimbs, we determined whether the osteopenia induced in these rats was generalized or restricted to the unweighted limbs, and whether changes in intestinal calcium transport contributed to the alterations in bone calcium content. In this model, the hindquarters were elevated using the tail at an approximately 40 degrees angle for up to 15 days. The tibia and lumbar vertebra from experimental rats contained substantially less calcium than the same bones from pair-fed controls; at 15 days, the tibia was 86.2 +/- 2.5% of the control value (mean +/- SE), and the vertebra was 75.5 +/- 3.5% of control value (mean +/- SE). However, these differences were found only for the unweighted bones; the mandible and humerus showed no differences between experimental and pair-fed control rats. When calcium uptake by bone was evaluated after 45Ca administration, we observed an initial decrease in uptake at 5 days only in the tibia [percentage of control value, 60.5 +/- 5.5, (mean +/- SE)] and vertebra (percentage of control value, 74.3 +/- 3.7) when experimental animals were compared to pair-fed controls; there was no decrease in the humerus and mandible. However, after 10 days of unweighting , calcium uptake in the tibia and vertebra of experimental animals returned to control levels and by 15 days exceeded control levels (the tibia was 125.8 +/- 5.8% of the control value and the vertebra was 136.2 +/- 9.6% of the control value) despite the progressive decrease in total bone calcium compared to that in pair-fed controls. At no time could we demonstrate a difference in duodenal calcium transport between experimental and control animals. These data suggest that in this model, which simulates certain aspects of weightlessness, changes in local factors within the unweighted bones may have a greater impact on bone mass and turnover than changes in systemic factors that regulate overall bone mineral homeostasis.
Polyglot machine translation

Machine Translation (MT) requires a large amount of linguistic resources, which leads current MT systems to leaving unknown words untranslated. This can be annoying for end users, as they might not understand at all such untranslated words. However, most language families share a common vocabulary, therefore this knowledge can be leveraged to produce more understandable translations, typically for “assimilation” or gisting use. Based on this observation, we propose a method that constructs polyglot translations tailored to a particular user language. Simply put, an unknown word is translated into a set of languages that relate to the user’s language, and the translated word that is closest to the user’s language is used as a replacement of the unknown word. Experimental results on language coverage over three language families indicate that our method may improve the usefulness of MT systems. As conﬁrmed by a subsequent human evaluation, polyglot translations look indeed familiar to the users, and are perceived to be easier to read and understand than translations in their related natural languages.
A Novel Approach for Intracellular 3D Immuno‐Labeling for Electron Tomography

Electron tomography (ET) is an indispensable high‐resolution tool for three dimensional (3D) imaging in cell biology. When applied to immuno‐labeled cells, ET can provide essential insights in both the cellular architecture and the dynamics. Current protocols for 3D immuno‐labeling of intracellular antigens include permeabilization steps that cause random, extensive cell membrane disruption. This permeabilization results in a poor cell ultrastructure, limiting the usefulness of the specimens for high‐resolution studies. Here we describe a novel method, based on a well‐controlled permeabilization by targeted laser cell perforation, that allows for the 3D immuno‐localization of cytoplasmic antigens in cultured cells. The approach is unique since it is applicable to both chemically and cryo‐fixed cells and leads to a superior ultrastructural preservation for electron microscopy and tomography.
Deletion at the SLC1A1 glutamate transporter gene co‐segregates with schizophrenia and bipolar schizoaffective disorder in a 5‐generation family

Growing evidence for genetic overlap between schizophrenia (SCZ) and bipolar disorder (BPD) suggests that causal variants of large effect on disease risk may cross traditional diagnostic boundaries. Extended multigenerational families with both SCZ and BPD cases can be a valuable resource for discovery of shared biological pathways because they can reveal the natural evolution of the underlying genetic disruptions and their phenotypic expression. We investigated a deletion at the SLC1A1 glutamate transporter gene originally identified as a copy number variant exclusively carried by members of a 5‐generation Palauan family. Using an expanded sample of 21 family members, quantitative PCR confirmed the deletion in all seven individuals with psychosis, three “obligate‐carrier” parents and one unaffected sibling, while four marry‐in parents were non‐carriers. Linkage analysis under an autosomal dominant model generated a LOD‐score of 3.64, confirming co‐segregation of the deletion with psychosis. For more precise localization, we determined the approximate deletion end points using alignment of next‐generation sequencing data for one affected deletion‐carrier and then designed PCR amplicons to span the entire deletion locus. These probes established that the deletion spans 84,298 bp, thus eliminating the entire promoter, the transcription start site, and the first 59 amino acids of the protein, including the first transmembrane Na2+/dicarboxylate symporter domain, one of the domains that perform the glutamate transport action. Discovery of this functionally relevant SLC1A1 mutation and its co‐segregation with psychosis in an extended multigenerational pedigree provides further support for the important role played by glutamatergic transmission in the pathophysiology of psychotic disorders. © 2013 Wiley Periodicals, Inc.
An actor-based runtime monitoring system for web and desktop applications

In this paper, we introduce a runtime monitoring method for Actor-based programs and present a Scala module that realizes the proposed method. The primary characteristic of our method is that it supports asynchronous message-passing based on the Actor model. Besides, the module does not require specialized languages for describing application properties to be monitored. Once a developer incorporates the module in his/her application, it continuously checks whether the application satisfies certain properties described as Scala code and invokes mitigation code when it finds the violation of the properties. This paper also provides two non-trivial use cases to illustrate how the module can be seamlessly integrated into actual modern Scala applications. We also demonstrate the efficiency of the module using a set of benchmarks that resulted in only 8% of the experiments causing more than 5% runtime overhead.
Validating and updating a prediction rule for neurological sequelae after childhood bacterial meningitis

Recently, a prediction rule for developing neurological sequelae after childhood bacterial meningitis was developed on a small derivation set. Before implementing in practice a prediction rule must first be tested in new patients (external validation). Our aim was to study the external validity of this rule and, if necessary, to update the rule. The prediction rule was tested on newly available data (validation set) by assessing the rule's calibration and discrimination. We updated the prediction rule by adding extra predictors and re-estimating the regression coefficients of the original predictors in the combined datasets. The rule showed poor agreement between predicted risks and observed frequencies. The ROC area was 0.65 (95% CI 0.57–0.72), which was statistically significantly lower than in the derivation set (0.87 (0.78–0.96)), p-value <0.01. The updated prediction rule showed adequate performance in the combined data sets; the ROC area was 0.77 (95% CI 0.72–0.82). Further study of the generalizability of this updated rule may stimulate application in clinical practice.
Virtues of SIN

The labor market integration of immigrants is a top political priority throughout the Organization for Economic Cooperation and Development (OECD) countries. Social and fiscal gains, as well as sustained future labor supply make governments search for effective policies to increase employment among the mostly disadvantaged. The author studies SIN, a Swedish pilot workplace introduction program targeting these groups, using very detailed individual data and allowing for effects through several channels. The results show increased transitions from unemployment to work experience schemes and improved future employment probabilities for those who entered these schemes. A rough calculation suggests that each job year created cost about Euro 30,000.
The store front, Fountain House, and the rehabilitation alliance.

This unique approach to improving the psychiatric and medical well-being of men and women with serious mental illness is a revolutionary one, just as the original Fountain House was in its inception. It represents both a challenge and a potential solution to the problems articulated in this paper; unfortunately a challenge that has yet to be accepted in either the medical or psychiatric field by most practitioners, despite the success attained over the past 11 years through the storefront partnership with Fountain House. A series of goals and objectives has been identified which, if followed, could lead to substantial economic growth, increased social awareness, and improved mental and physical health for a heretofore significant and significantly neglected population. Much work needs to be done to educate the psychiatric and primary care segments of the health field. What has been described in this presentation is a pilot demonstration of how these goals and objectives might be achieved. Positive results could be recorded almost immediately through diagnosis, intervention, and remission data, but transference and replication of such methods and results to other settings depends on the good will and vision of healthcare providers.
LOSARTAN PREVENTS SEPSIS-INDUCED ACUTE LUNG INJURY AND DECREASES ACTIVATION OF NUCLEAR FACTOR&kgr;B AND MITOGEN-ACTIVATED PROTEIN KINASES

Lack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Losartan is a potent pharmaceutical drug for ALI/ARDS. However, the protective effects and mechanisms of losartan remain incompletely known. This study evaluates the effects of losartan on ALI/ARDS and further investigates the possible mechanisms of these protective effects. Mice received i.p. injections of the AT1 inhibitor losartan (15 mg/kg), or control vehicle, half hour after cecal ligation and puncture (CLP). Plasma TNF-&agr;, IL-1&bgr;, and IL-6 cytokines were assayed 6 h after CLP. Blood gas, wet/dry lung weight ratio, lung tissue histology for occurrence of ALI/ARDS, and survival were examined. Lastly, nuclear factor &kgr;B (NF-&kgr;B) activations, I&kgr;B-&agr; degradations, phosphorylations of p38 MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase expressions were evaluated in lung tissue. Losartan treatment significantly attenuated TNF-&agr;, IL-6, and IL-1&bgr; 6 h after CLP. Furthermore, losartan prevented blood gas and histopathologic appearance of ALI/ARDS after sepsis and significantly improved survival. Finally, losartan given after sepsis led to inhibition of lung tissue NF-&kgr;B activation (P < 0.01 vs. CLP group), attenuated degradation of I&kgr;B-&agr;, and inhibited phosphorylation of p38MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, pathways critical for cytokine release. These data reveal that losartan exerts a protective effect on ALI/ARDS, and this protective effect may be dependent, at least in part, on NF-&kgr;B and MAPK mechanisms.
Development of a Monte Carlo sampling shell for the pesticide root zone model and its application by the Federal Insecticide, Fungicide, and Rodenticide Act Environmental modeling validation Task Force

A user interface to the U.S. Environmental Protection Agency pesticide root zone model (PRZM) was constructed to allow Monte Carlo sampling of input parameter distributions. The interface was constructed employing the Visual Basic for Applications development environment, along with the functionality of the Crystal Ball Professional forecasting and risk analysis package. The tool has been utilized by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force to perform detailed statistical analyses of model input parameter uncertainty and the propagation of this uncertainty on the model outputs as well as comparisons of modeled and field‐measured data.
An Improved Decoding Algorithm for Generalized RDP Codes

The generalized RDP codes are identified as the most practical and efficient triple-erasure correcting MDS (maximum-distance separable) codes, since they can encode optimally and support arbitrary code length. However, none of the existing decoding algorithms for these codes is adequate in that their decoding complexity leaves a relatively large room for improvement. In this letter, we present an improved decoding algorithm for the generalized RDP codes. Compared with the existing decoding algorithms, the proposed algorithm has a much lower decoding complexity, which is very close to the theoretical lower bound.
FARKLI GELİŞME DÖNEMLERİNDE UYGULANAN TUZLU VE NORMAL SULARIN PATLICAN (Solanum melongena L.) BİTKİSİNİN BAZI ÖZELLİKLERİNE VE TOPRAK TUZLULUĞUNA ETKİSİ

Bu calisma patlican bitkisinde, gelisme periyodu 3 doneme ayrilarak bu donemlerin farkli kombinasyonlarinda uygulanan normal ve tuzlu suyun, bitki gelisimine ve toprak tuzluluguna etkisini belirlemek amaciyla yurutulmustur. Calismada tuzlu su olarak 5 dS/m ve normal su olarak da 0.25 dS/m elektriksel iletkenlige sahip sular kullanilmistir. Ozellikle ilk donemlerde olmak uzere farkli donemlerde uygulanan tuzlu suyun; bitki su tuketimini, bitki boyunu, bitki agirligini onemli duzeyde azalttigi buna karsilik yapraklarin mineral madde icerigini ve toprak tuzlulugunu onemli duzeyde artirdigi belirlenmistir. Ayrica yuksek tuzlu su uygulamalarinda mutlaka yikama yapilmasinin gerektigi ortaya cikmistir.
A novel organizing scheme of single topic user group based on trust chain model in social network

Social network sites (SNS) presently face the task of grouping users into small subsets within themselves. In this study, an organizing scheme for single‐topic user groups is proposed for facilitating user sharing and communicating under common interests. The main rationales of the proposed scheme are (1) only an influential single topic is selected through its impact evaluation to attract users; (2) only the users having high degree of interest, explicit or implicit, on the topic should be grouped; and (3) trustworthy relationships among users are taken into consideration to enlarge the scale of user group. The proposed organizing scheme comprises 3 features: topic impact evaluation, interest degree measurement, and trust chain‐based organizing. The main structure of our proposed scheme is (1) an overview of the proposed scheme and its formal related definitions; (2) a topic impact evaluation method, ie, an importance evaluation and a popularity calculation; (3) a user interest degree measurement method, ie, explicit and implicit interest evaluation with dynamic factors included; (4) a trust chain calculation method based on the topology features of the trust chain; (5) an organizing algorithm for single topic user group, and finally, some experimental results and discussions to illustrate the effectiveness and feasibility of our scheme.
Total variational denoising using improved Adaptive Fidelity term

Denoising is an important part of digital image processing. Adaptive Fidelity term Total Variation (AFTV) method can effectively remove the noise and can preserve the edge and detail information of the image. However, noise variance should be given in the method, and the mothed is sensitive to noise, which will lead to unsatisfactory denoising results in edges of image. Therefore, an improved Adaptive Fidelity Total Variation algorithm is proposed. The method first uses the local variance of the noise image to initially estimate the confidence parameters, then the optimized parameters are obtained with anisotropic convolution. The experiments with several images demonstrate that the proposed method is superior to AFTV method at different noise levels.
Semantic data factory: A framework for using domain knowledge in software application development

This paper addresses the semantic gap between the domain knowledge and software application engineering by proposing a framework for mapping and integrating multiple heterogeneous data sources with application business logic by means of data semantic enrichment, aggregation, filtering and processing. Based on the main drawbacks identified in the current knowledge enhanced software application architectures, a generic framework for automating their development process is proposed. The framework reduces the implementation stage of complex applications to a simple task of editing a configuration file which can be performed even by the domain expert himself. Two use cases of the proposed framework are presented for developing semantically-enhanced applications. The first use case is described within the FP7 GEYSER research project in the context of energy-efficiency, while the second use-case is presented in the e-health context for generating applications over the Fitbit platform.
Development of echo control strategy for AK prosthesis: An embedded system approach

In spite of wide availability, the current prosthesis does not meet most of the functional requirements along with the other parameters like metabolic energy, training period and cost. This paper presents the development of a low cost Above Knee (AK) prosthesis which regulates the knee damping automatically by calculating the speed of walking from the data of the normal limb. The prosthesis uses an additional hardware of wireless transmission system, which does not add to the cost significantly, but promises a speed adaptive control of AK prosthesis and thus requires significantly less training time for the amputee.