Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of a Vancomycin-Intermediate Staphylococcus aureus Strain In Vivo: Multiple Changes in the Antibiotic Resistance Phenotypes of a Single Lineage of Methicillin-Resistant S. aureus under the Impact of Antibiotics Administered for Chemotherapy

ABSTRACT A number of methicillin-resistant Staphylococcus aureus (MRSA) isolates were recovered over a period of several weeks from blood samples and from the heart valve of a patient who underwent extensive vancomycin chemotherapy for persistent S. aureus bacteremia. Consecutive isolates showed gradually decreasing growth rates during in vitro cultivation and increasing vancomycin MICs, from an MIC of 1 μg/ml for the initial isolate to an MIC of 8 μg/ml for the final MRSA isolates, which also became tolerant to vancomycin. Major changes were observed in the oxacillin resistance phenotype of several of the isolates—apparently related to in vivo exposure to imipenem, which was also used during a period of chemotherapy. Both the gradually increasing vancomycin MICs and the changes in oxacillin resistance could be reproduced by appropriate exposure of the initial MRSA isolate to antibiotics in vitro. All isolates had the same pulsed-field gel electrophoresis pattern, spaA type, and multilocus sequence type (MLST), which was identified as a single-locus variant of ST5, the MLST characteristic of previously characterized MRSA isolates with reduced susceptibility to vancomycin in the United States and Japan.
Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil interface plays crucial role in metal homeostasis

Significance Plants take up iron from the soil by using a broad spectrum transporter named IRON-REGULATED TRANSPORTER 1 (IRT1). IRT1 mediates influx of potentially toxic elements such as manganese, zinc, cobalt, and cadmium. We uncovered that the localization at the cell surface of IRT1 is directly controlled by its secondary toxic substrates. When these metals are found at low levels in soils, IRT1 is located at the plasma membrane in a polar fashion facing the soil. We identified a lipid-binding protein recruited to endosomes that controls IRT1's dynamics and polarity, and plays an important role in the radial transport of metals. Altogether, our work points to an unexpected mode of radial transport of iron toward vascular tissues involving efflux transporters. In plants, the controlled absorption of soil nutrients by root epidermal cells is critical for growth and development. IRON-REGULATED TRANSPORTER 1 (IRT1) is the main root transporter taking up iron from the soil and is also the main entry route in plants for potentially toxic metals such as manganese, zinc, cobalt, and cadmium. Previous work demonstrated that the IRT1 protein localizes to early endosomes/trans-Golgi network (EE/TGN) and is constitutively endocytosed through a monoubiquitin- and clathrin-dependent mechanism. Here, we show that the availability of secondary non-iron metal substrates of IRT1 (Zn, Mn, and Co) controls the localization of IRT1 between the outer polar domain of the plasma membrane and EE/TGN in root epidermal cells. We also identify FYVE1, a phosphatidylinositol-3-phosphate-binding protein recruited to late endosomes, as an important regulator of IRT1-dependent metal transport and metal homeostasis in plants. FYVE1 controls IRT1 recycling to the plasma membrane and impacts the polar delivery of this transporter to the outer plasma membrane domain. This work establishes a functional link between the dynamics and the lateral polarity of IRT1 and the transport of its substrates, and identifies a molecular mechanism driving polar localization of a cell surface protein in plants.
Neoplastic transformation and angiogenesis in the thymus of transgenic mice expressing SV40 T and t antigen under an l‐pyruvate kinase promoter (SV12 mice)

Using several techniques, we have assessed morphological characteristics of a malignant thymic tumour in SV12 transgenic (Tg) mice expressing SV40 T and t antigens under control of an L‐PK promoter. We describe the development of a carcinoma originating from thymic hyperplasia and followed by the formation of a benign tumour composed chiefly of medullary epithelial cells expressing the transgene and of lymphocytes, a pathology very rarely reported in mice. Our study of the SV12 Tg mice represents the first description of a model of a pure malignant thymic tumour associated with extensive angiogenesis maintained in numerous descendants. The formation of a large tumoral neovascular network, observed here, has never been described in human and/or experimental thymic tumours. Tumoral transformation and angiogenesis are demonstrated by immunolabelling with antibodies against various cytokeratins (CKs) of different molecular weights, vascular endothelial cell markers and VEGF/receptor‐2 (Flk‐1) present on the neovascular endothelial cells. Different points raised by the originality of this model are discussed. These include the medullary nature of the cells expressing the SV40 transgene and their relationship with the tumoral development. The subset of different molecular weight CK components and their modifications are also considered, as well as the presence of type IV epithelial cells, progenitors of medullary epithelial cells. Finally, the cell signals involved in angiogenesis and the possible action of an angiogenic factor, probably secreted by the tumoral cells themselves, are discussed.
Variability and accuracy in mammographic interpretation using the American College of Radiology Breast Imaging Reporting and Data System.

BACKGROUND Several studies, which were limited by their small sample size and selection of difficult cases for review, have reported substantial variability among radiologists in interpretation of mammographic examinations. We have determined, in the largest study to date, intraobserver and interobserver agreement in interpreting screening mammography and accuracy of mammography by use of the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). METHODS The mammographic examinations were randomly selected on the basis of original mammographic interpretation and cancer outcome from 71,713 screening examinations performed by the Mobile Mammography Screening Program of the University of California, San Francisco, during the period from April 1985 through February 1995. The final sample included 786 abnormal examinations with no cancer detected, 267 abnormal examinations with cancer detected, and 1563 normal examinations. Films were read separately by two radiologists according to BI-RADS. Cancer status was determined by contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results Program. RESULTS There was moderate agreement between radiologists in reporting the presence of a finding when cancer was present (kappa = 0.54) and substantial agreement when cancer was not present (kappa = 0.62). Agreement was moderate in assigning one of the five assessment categories but was statistically significantly lower when cancer was present relative to when cancer was not present (kappa = 0.46 versus 0.56; two-sided P = .02). Agreement for reporting the presence of a finding and mammographic assessment was two-fold more likely for examinations with less dense breasts. Agreement was higher on repeat readings by the same radiologists than between radiologists. The sensitivity of mammography was lower with BI-RADS than with the original system for mammographic interpretation, but the positive predictive value of mammography was higher. CONCLUSION Considerable variability in interpretation of mammographic examinations exists; this variability and the accuracy of mammography are neither improved nor diminished with use of BI-RADS.
The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats

A number of inflammatory disease states occur with greatly increased frequency in individuals inheriting the human major histocompatibility complex class I allele HLA-B27. In a minority of cases, namely those with B27-associated reactive arthritis, there is good evidence that the disease state is triggered by infection with an enteric or genitourinary bacterial pathogen. For the majority of B27-associated disease, no definite pathogenetic role for bacteria has been established. However, in these latter cases intestinal inflammation can often be demonstrated, and it sometimes occupies a major part of the clinical picture. Rats transgenic for B27 are known to develop a disorder resembling B27-associated human disease, with prominent intestinal, joint, skin, and male genital inflammatory lesions. We report here that B27 transgenic rats raised in a germfree environment do not develop inflammatory intestinal or peripheral joint disease, whereas the skin and genital inflammatory lesions are unaffected by the germfree state. These findings support the concept that gut and joint inflammation are pathogenetically closely related, and they provide direct evidence that the commensal gut flora play an important role in the pathogenesis of B27-associated gut and joint inflammation.
Generation of F 0 Contours for Mandar in Speech in Combination with Rule-based and Corpus-based Methods

A method was developed for synthesizing sentence fundamental frequency (F0) contours of Mandarin speech. It is based on representing an F0 contour in logarithmic frequency scale as a superposition of tone components on phrase components as in the case of generation process model (F0 model). The tone components are realized by concatenating their fragments at tone nuclei predicted by a corpus-based method, while the phrase components are generated by rules under the F0 model framework. To keep the time-alignment between the phrase and tone components, the phrase components are first generated and their information is added to the inputs for the prediction of tone nucleus F0 patterns. Result of listening tests on synthetic speech with the synthesized F0 contours verified the validity of the developed method. Furthermore, it was shown through an experiment of word emphasis that a flexible F0 control was possible by the proposed method.
Evolving response to smart irrigation controllers in high water‐use central Florida homes

Efforts to improve urban irrigation efficiency through the promotion of smart controllers represent a critical water resource management strategy in Florida. However, targeted initiatives require knowledge of household characteristics and preferences among high irrigators to ensure acceptance and continued use of the devices. This article compares survey data collected in 2014 and 2017 from high‐water‐use homes in Orange County, Florida, with soil moisture sensor and evapotranspiration controllers installed, to evaluate long‐term response to the technologies. Results indicate the perceived water‐saving effectiveness of the controllers and whether challenges were experienced operating them significantly predicted satisfaction with the controllers and the likelihood of continuing to use them, respectively, during both periods. The likelihood of continued use after 2017 was almost 12 times higher if a respondent was satisfied with the controller and 82% lower if any challenge was experienced with it. Increased familiarity and comfort with the controllers would enhance long‐term adoption.
Quantitative assessment of insertion sequence impact on bacterial genome architecture

Insertion sequence (IS) elements are important mediators of genome plasticity and can lead to phenotypic changes with evolutionary significance. In multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae, IS elements have contributed significantly to the mobilization of genes that encode resistance to antimicrobial drugs. A systematic analysis of IS elements is needed for a more comprehensive understanding of their evolutionary impact. We developed a computational approach (ISseeker) to annotate IS elements in draft genome assemblies and applied the method to analysis of IS elements in all publicly available A. baumannii(>1000) and K. pneumoniae(>800) genome sequences, in a phylogenetic context. Most IS elements in A. baumanniigenomes are species-specific ISAba elements, whereas K. pneumoniaegenomes contain significant numbers of both ISKpn elements and elements that are found throughout the Enterobacteriaceae. A. baumanniigenomes have a higher density of IS elements than K. pneumoniae, averaging ~33 vs ~27 copies per genome. In K. pneumoniae, several insertion sites are shared by most genomes in the ST258 clade, whereas in A. baumannii, different IS elements are abundant in different phylogenetic groups, even among closely related Global Clone 2 strains. IS elements differ in the distribution of insertion locations relative to genes, with some more likely to disrupt genes and others predominantly in intergenic regions. Several genes and intergenic regions had multiple independent insertion events, suggesting that those events may confer a selective advantage. Genome- and taxon-wide characterization of insertion locations revealed that IS elements have been active contributors to genome diversity in both species.
HeLa cell adherence and cytotoxin production by enteropathogenic Escherichia coli isolated from infants with diarrhea in Thailand

Enteropathogenic Escherichia coli (EPEC) strains isolated from hospitalized infants with diarrhea in Thailand were examined for HeLa cell adherence and cytotoxin production. Of 101 strains examined, 56 adhered to HeLa cells in a localized pattern (LA), 27 adhered in a diffuse pattern (DA), and 18 did not adhere. All 56 LA EPEC strains were O:K serotype O119:K69. A total of 20 (83%) of 24 EPEC O86:K61 strains and 7 (38%) of 19 EPEC strains belonging to six other O:K serotypes exhibited DA. All LA EPEC strains hybridized with a DNA probe for genes encoding EPEC adherence factor, whereas none of the 27 DA or 18 nonadherent EPEC strains hybridized with EPEC adherence factor probe. Sonic extracts of 57 (58%) of 98 EPEC strains tested at a dilution of 1:100 caused greater than 25% mortality of HeLa cell monolayers. A total of 50 (88%) of 57 cytotoxic sonic extracts were inhibited to various degrees by a 1:500 dilution of polyclonal rabbit antisera to purified Shiga toxin. The mean percent inhibition of cytotoxic sonic extracts by anti-Shiga toxin was 67% (range, 29 to 89%). Fifty percent (38 of 56) of LA EPEC strains, fifty-two percent (14 of 27) of DA EPEC strains, and fifty-three percent (8 of 15) of nonadherent EPEC strains produced Shiga-like toxins. Both adherence and low levels of cell-associated cytotoxins were identified in EPEC strains from Thailand, but there did not appear to be an association between these two factors.
Endogenous lipid mediators in the resolution of airway inflammation

Acute inflammation in the lung is fundamentally important to host defence, but chronic or excessive inflammation leads to several common respiratory diseases, including asthma and acute respiratory distress syndrome. The resolution of inflammation is an active process. In health, events at the onset of acute inflammation establish biosynthetic circuits for specific chemical mediators that later serve as agonists to orchestrate a return to tissue homeostasis. In addition to an overabundance of pro-inflammatory stimuli, pathological inflammation can also result from defects in resolution signalling. The understanding of anti-inflammatory, pro-resolution molecules and their counter-regulatory signalling pathways is providing new insights into the molecular pathophysiology of lung disease and opportunities for the design of therapeutic strategies. In the present review, the growing family of lipid mediators of resolution is examined, including lipoxins, resolvins, protectins, cyclopentenones and presqualene diphosphate. Roles are uncovered for these compounds, or their structural analogues, in regulating airway inflammation.
Secure 5G Wireless Communications: A Joint Relay Selection and Wireless Power Transfer Approach

In this paper, we investigate the secrecy performance of an energy harvesting relay system, where a legitimate source communicates with a legitimate destination via the assistance of multiple trusted relays. In the considered system, the source and relays deploy the time-switching-based radio frequency energy harvesting technique to harvest energy from a multi-antenna beacon. Different antenna selection and relay selection schemes are applied to enhance the security of the system. Specifically, two relay selection schemes based on the partial and full knowledge of channel state information, i.e., optimal relay selection and partial relay selection, and two antenna selection schemes for harvesting energy at source and relays, i.e., maximizing energy harvesting channel for the source and maximizing energy harvesting channel for the selected relay, are proposed. The exact and asymptotic expressions of secrecy outage probability in these schemes are derived. We demonstrate that applying relay selection approaches in the considered energy harvesting system can enhance the security performance. In particular, optimal relay selection scheme outperforms partial relay selection scheme and achieves full secrecy diversity order, regardless of energy harvesting scenarios.
Tracking Gaze and Visual Focus of Attention of People Involved in Social Interaction

The visual focus of attention (VFOA) has been recognized as a prominent conversational cue. We are interested in estimating and tracking the VFOAs associated with multi-party social interactions. We note that in this type of situations the participants either look at each other or at an object of interest; therefore their eyes are not always visible. Consequently both gaze and VFOA estimation cannot be based on eye detection and tracking. We propose a method that exploits the correlation between eye gaze and head movements. Both VFOA and gaze are modeled as latent variables in a Bayesian switching state-space model (also referred switching Kalman filter). The proposed formulation leads to a tractable learning method and to an efficient online inference procedure that simultaneously tracks gaze and visual focus. The method is tested and benchmarked using two publicly available datasets, Vernissage and LAEO, that contain typical multi-party human-robot and human-human interactions.
Direct Ex Vivo Analysis of Antigen-Specific IFN-γ-Secreting CD4 T Cells in Mycobacterium tuberculosis-Infected Individuals: Associations with Clinical Disease State and Effect of Treatment1

The wide spectrum of clinical outcomes following infection with Mycobacterium tuberculosis is largely determined by the host immune response; therefore, we studied several clinically defined groups of individuals (n = 120) that differ in their ability to contain the bacillus. To quantitate M. tuberculosis-specific T cells directly ex vivo, we enumerated IFN-γ-secreting CD4 T cells specific for ESAT-6, a secreted Ag that is highly specific for M. tuberculosis, and a target of protective immune responses in animal models. We found that frequencies of circulating ESAT-6 peptide-specific IFN-γ-secreting CD4 T cells were higher in latently infected healthy contacts and subjects with minimal disease and low bacterial burdens than in patients with culture-positive active pulmonary tuberculosis (p = 0.009 and p = 0.002, respectively). Importantly, the frequency of these Ag-specific CD4 T cells fell progressively in all groups with treatment (p = 0.005), suggesting that the lower responses in patients with more extensive disease were not due to tuberculosis-induced immune suppression. This population of M. tuberculosis Ag-specific Th1-type CD4 T cells appears to correlate with clinical phenotype and declines during successful therapy; these features are consistent with a role for these T cells in the containment of M. tuberculosis in vivo. Such findings may assist in the design and evaluation of novel tuberculosis vaccine candidates.
Whole Brain Imaging with Serial Two-Photon Tomography

Imaging entire mouse brains at submicron resolution has historically been a challenging undertaking and largely confined to the province of dedicated atlasing initiatives. This has limited systematic investigations into important areas of neuroscience, such as neural circuits, brain mapping and neurodegeneration. In this article, we describe in detail Serial Two-Photon (STP) tomography, a robust, reliable method for imaging entire brains with histological detail. We provide examples of how the basic methodology can be extended to other imaging modalities, such as Optical Coherence Tomography (OCT), in order to provide unique contrast mechanisms. Furthermore, we provide a survey of the research that STP tomography has enabled in the field of neuroscience, provide examples of how this technology enables quantitative whole brain studies, and discuss the current limitations of STP tomography-based approaches.
The computer as von Neumann planned it

John von Neumann made a key contribution to the understanding and development of computer architecture and design in his unpublished report titled 'First Draft of a Report on the EDVAC'. The architecture given in the von Neumann report is presented in a form that is accessible to a wider audience. This definition is compared with the definition of the constructed EDVAC system. In doing this, the authors hope to clarify important but previously unrecognized features of the von Neumann design and to clarify a number of the confusions that have arisen over the years. <<ETX>>
SF3b1 mutations associated with myelodysplastic syndromes alter the fidelity of branchsite selection in yeast

Abstract RNA and protein components of the spliceosome work together to identify the 5΄ splice site, the 3΄ splice site, and the branchsite (BS) of nascent pre-mRNA. SF3b1 plays a key role in recruiting the U2 snRNP to the BS. Mutations in human SF3b1 have been linked to many diseases such as myelodysplasia (MDS) and cancer. We have used SF3b1 mutations associated with MDS to interrogate the role of the yeast ortholog, Hsh155, in BS selection and splicing. These alleles change how the spliceosome recognizes the BS and alter splicing when nonconsensus nucleotides are present at the −2, −1 and +1 positions relative to the branchpoint adenosine. This indicates that changes in BS usage observed in humans with SF3b1 mutations may result from perturbation of a conserved mechanism of BS recognition. Notably, different HSH155 alleles elicit disparate effects on splicing: some increase the fidelity of BS selection while others decrease fidelity. Our data support a model wherein conformational changes in SF3b1 promote U2 association with the BS independently of the action of the DEAD-box ATPase Prp5. We propose that SF3b1 functions to stabilize weak U2/BS duplexes to drive spliceosome assembly and splicing.
Investigation for methods of anesthesia and euthanasia for rat fetuses in developmental toxicity studies

Japan Association for Laboratory Animal Medicine (JALAM) recommends humane handling of rat fetuses. However, it is a challenge to accept proposed euthanizing methods such as cervical dislocation, decapitation and/or intracardiac injection of potassium chloride, because these methods would damage fetal specimens for skeletal and visceral examinations in developmental toxicity studies. The present study aimed at seeking better methodologies for fetal euthanasia and anesthesia. We were unable to accomplish fetal euthanasia directly, but instead, we could euthanize fetuses under pain‐controlled anesthesia. It is recommended that hypothermia by immersion in cold physiological saline is an appropriate method for anesthesia. Moreover, we recommend that the anesthetized fetuses should be euthanized immediately by removal of the vital organs or immersion in appropriate fixatives.