Miracle-dz/UniFAR-FTUs huggingface dataset:
An In Vitro Deletion in ribE Encoding Lumazine Synthase Contributes to Nitrofurantoin Resistance in Escherichia coli

ABSTRACT Nitrofurantoin has been used for decades for the treatment of urinary tract infections (UTIs), but clinically significant resistance in Escherichia coli is uncommon. Nitrofurantoin concentrations in the gastrointestinal tract tend to be low, which might facilitate selection of nitrofurantoin-resistant (NIT-R) strains in the gut flora. We subjected two nitrofurantoin-susceptible intestinal E. coli strains (ST540-p and ST2747-p) to increasing nitrofurantoin concentrations under aerobic and anaerobic conditions. Whole-genome sequencing was performed for both susceptible isolates and selected mutants that exhibited the highest nitrofurantoin resistance levels aerobically (ST540-a and ST2747-a) and anaerobically (ST540-an and ST2747-an). ST540-a/ST540-an and ST2747-a (aerobic MICs of >64 μg/ml) harbored mutations in the known nitrofurantoin resistance determinants nfsA and/or nfsB, which encode oxygen-insensitive nitroreductases. ST2747-an showed reduced nitrofurantoin susceptibility (aerobic MIC of 32 μg/ml) and exhibited remarkable growth deficits but did not harbor nfsA/nfsB mutations. We identified a 12-nucleotide deletion in ribE, encoding lumazine synthase, an essential enzyme involved in the biosynthesis of flavin mononucleotide (FMN), which is an important cofactor for NfsA and NfsB. Complementing ST2747-an with a functional wild-type lumazine synthase restored nitrofurantoin susceptibility. Six NIT-R E. coli isolates (NRCI-1 to NRCI-6) from stools of UTI patients treated with nitrofurantoin, cefuroxime, or a fluoroquinolone harbored mutations in nfsA and/or nfsB but not ribE. Sequencing of the ribE gene in six intestinal and three urinary E. coli strains showing reduced nitrofurantoin susceptibility (MICs of 16 to 48 μg/ml) also did not identify any relevant mutations. NRCI-1, NRCI-2, and NRCI-5 exhibited up to 4-fold higher anaerobic MICs, compared to the mutants generated in vitro, presumably because of additional mutations in oxygen-sensitive nitroreductases.
The XMM-Newton survey of the ELAIS-S1 field - II. Optical identifications and multiwavelength catalogue of X-ray sources

We present the optical identifications and a multi-band catalogue of a sample of 478 X-ray sources detected in the XMM-Newton and Chandra surveys of the central 0.6 deg 2 of the ELAIS-S1 field. The most likely optical/infrared counterpart of each X-ray source was identified using the chance coincidence probability in the R and IRAC 3.6 μm bands. This method was complemented by the precise positions obtained through Chandra observations. We were able to associate a counterpart to each X-ray source in the catalogue. Approximately 94% of them are detected in the R band, while the remaining are blank fields in the optical down to R ∼ 24.5, but have a near-infrared counterpart detected by IRAC within 6 �� from the XMM-Newton centroid. The multi-band catalogue, produced using the positions of the identified optical counterparts, contains photometry in ten photometric bands, from B to the MIPS 24 μm band. The spectroscopic follow-up allowed us to determine the redshift and classification for 237 sources (∼50% of the sample) brighter than R = 24. The spectroscopic redshifts were complemented by reliable photometric redshifts for 68 sources. We classified 47% of the sources with spectroscopic redshift as broad-line active galactic nuclei (BL AGNs) with z = 0.1−3.5, while sources without broadlines (NOT BL AGNs) are about 46% of the spectroscopic sample and are found up to z = 2.6. The remaining fraction is represented by extended X-ray sources and stars. We spectroscopically identified 11 type 2 QSOs among the sources with F(2−10 keV)/F(R) > 8, with redshift between 0.9 and 2.6, high 2−10 keV luminosity (log L2−10 keV ≥ 43.8 erg s −1 ) and hard X-ray colors suggesting large absorbing columns at the rest frame (log NH up to 23.6 cm −2 ). BL AGNs show on average blue optical-to-near-infrared colors, softer X-ray colors and X-ray-to-optical colors typical of optically selected AGNs. Conversely, narrow-line sources show redder optical colors, harder X-ray flux ratio and span a wider range of X-ray-to-optical colors. On average the Spectral Energy Distributions (SEDs) of high-luminosity BL AGNs resemble the power-law typical of unobscured AGNs. The SEDs of NOT BL AGNs are dominated by the galaxy emission in the optical/near-infrared, and show a rise in the mid-infrared which suggests the presence of an obscured active nucleus. We study the infrared-to-optical colors and near-infrared SEDs to infer the properties of the AGN host galaxies.
Bacterial self–organization: co–enhancement of complexification and adaptability in a dynamic environment

During colonial development, bacteria generate a wealth of patterns, some of which are reminiscent of those occurring in abiotic systems. They can exhibit rich behaviour, reflecting informative communication capabilities that include exchange of genetic materials and the fact that the colony's building blocks are biotic. Each has internal degrees of freedom, informatic capabilities and freedom to respond by altering itself and others via emission of signals in a self–regulated manner. To unravel the special secrets of bacterial self–organization, we conducted an integrative (experimental and theoretical) study of abiotic and biotic systems. Guided by the notion of general biotic motives and principles, I propose that the informative communication between individuals makes possible the enhancement of the individuals' regulated freedom, while increasing their cooperation. This process is accomplished via cooperative complexification of the colony through self–organization of hierarchical spatio–temporal patterning. The colonial higher complexity provides the degree of plasticity and flexibility required for better colonial adaptability and endurability in a dynamic environment. The biotic system can modify the environment and obtain environmental information for further self–improvement. I reflect on the potential applications of the new understanding on ‘engineered self–organization of systems too complex to design’ and other issues.
The hyperphagic effect of ghrelin is inhibited in mice by a diet high in fat.

BACKGROUND & AIMS Ghrelin is the only peripheral hormone known to increase food intake. It is released from the stomach and is thought to function as a signal of energy deficit and a meal initiator. We generated transgenic mice in which levels of bioactive ghrelin are increased in the stomach and circulation. These mice, as expected, are hyperphagic and glucose intolerant. We investigated whether exposure to a high-fat diet (HFD) would exacerbate this phenotype. METHODS We investigated the effect of HFD on energy and glucose homeostasis in ghrelin transgenic mice. We determined dietary preference; expression of hypothalamic neuropeptides that control food intake; and, using fast-performance liquid chromatography, the circulating forms of ghrelin. We measured food intake during continuous administration of ghrelin in wild-type mice fed either regular chow or an HFD. RESULTS Ghrelin transgenic mice were resistant to diet-induced obesity because of their reduced food intake. This was not caused by alterations to food preference, hypothalamic signaling of neuropeptides that control food intake, or the form of circulating acylated ghrelin. Long-term administration of ghrelin to wild-type mice failed to increase ingestion of an HFD but, as expected, increased intake of regular chow. CONCLUSIONS This is the first report that diets high in fat inhibit the hyperphagic effect of ghrelin; these findings indicate that features of the diet are important determinants of ghrelin's function. This information is important for the development of anti-obesity drugs that target ghrelin signaling.
Role of CXCR 2 / CXCR 2 ligands in vascular remodeling during bronchiolitis obliterans syndrome

Angiogenesis and vascular remodeling support fibroproliferative processes; however, no study has addressed the importance of angiogenesis during fibro-obliteration of the allograft airway during bronchiolitis obliterans syndrome (BOS) that occurs after lung transplantation. The ELR+ CXC chemokines both mediate neutrophil recruitment and promote angiogenesis. Their shared endothelial cell receptor is the G-coupled protein receptor CXC chemokine receptor 2 (CXCR2). We found that elevated levels of multiple ELR+ CXC chemokines correlated with the presence of BOS. Proof-of-concept studies using a murine model of BOS not only demonstrated an early neutrophil infiltration but also marked vascular remodeling in the tracheal allografts. In addition, tracheal allograft ELR+ CXC chemokines were persistently expressed even in the absence of significant neutrophil infiltration and were temporally associated with vascular remodeling during fibro-obliteration of the tracheal allograft. Furthermore, in neutralizing studies, treatment with anti-CXCR2 Abs inhibited early neutrophil infiltration and later vascular remodeling, which resulted in the attenuation of murine BOS. A more profound attenuation of fibro-obliteration was seen when CXCR2–/– mice received cyclosporin A. This supports the notion that the CXCR2/CXCR2 ligand biological axis has a bimodal function during the course of BOS: early, it is important for neutrophil recruitment and later, during fibro-obliteration, it is important for vascular remodeling independent of neutrophil recruitment. Article Transplantation
Experimental and Numerical Investigation on the Layering Configuration Effect to the Laminated Aluminium/Steel Panel Subjected to High Speed Impact Test

This paper presents the effect of laminated aluminium-steel panel with different configurations in a high-speed impact test. Layering aluminium plate with high strength steel has become an interest in reducing the overall density of armour vehicle body while improving the ballistic resistance. Different layering configurations differ in laminated panel performance. Two layering configurations of double-layered panel achieving 25% of existing panel weight reduction were tested using experiment and computational method to investigate their behaviours when impacted with 7.62-mm full metal jacket at velocity range of 800–850 m/s. The ballistic performance of each configuration plate in terms of ballistic limit velocity, penetration process and permanent deformation was quantified and considered. Laminated panel with aluminium as the front layer reduced the ballistic performance of existing panel to 50% and the other panel maintained its performance. Thus, the laminated panel with aluminium as the back layer can be used in designing a protective structure for armoured vehicle while maintaining the performance of the existing vehicle in achieving weight reduction.
Emerging applications of ultrasonication and cavitation in dairy industry: a review

Abstract In recent years, there has been emerging trends and gaining popularity of researching, exploring and applying the physical and chemical effects of ultrasonication and cavitation in dairy industry. An overview of ultrasonication and other cavitation techniques is provided here. Effect of hydrodynamic cavitation (HC) and high energy low-frequency ultrasonication on milk components such as fat, protein, and other milk constituents have been highlighted here. Detailed summary of various research studies and applications of the HC and ultrasonication in dairy processing area such as homogenization, viscosity reduction, cheese, cream and yogurt making, food safety, microbial inactivation, waste management, and cleaning are provided here. Furthermore, various research and application of low-intensity high-frequency ultrasound for dairy products analysis have been outlined here. While some applications of ultrasound and cavitation are well established in other industry, the ultrasonic and HC processing of dairy ingredients and products are gaining much attention recently and it has a great potential to become a mainstream process in dairy industry in the near future.
The Generation and Application of Patient-Derived Xenograft Model for Cancer Research

Establishing an appropriate preclinical model is crucial for translational cancer research. The most common way that has been adopted by far is grafting cancer cell lines, derived from patients. Although this xenograft model is easy to generate, but has several limitations because this cancer model could not represent the unique features of each cancer patient sufficiently. Moreover, accumulating evidences demonstrate cancer is a highly heterogeneous disease so that a tumor is comprised of cancer cells with diverse characteristics. In attempt to avoid these discrepancies between xenograft model and patients’ tumor, a patient-derived xenograft (PDX) model has been actively generated and applied. The PDX model can be developed by the implantation of cancerous tissue from a patient’s tumor into an immune-deficient mouse directly, thereby it preserves both cell-cell interactions and tumor microenvironment. In addition, the PDX model has shown advantages as a preclinical model in drug screening, biomarker development and co-clinical trial. In this review, we will summarize the methodology and applications of PDX in detail, and cover critical issues for the development of this model for preclinical research.
Building-Related Symptoms, Energy, and Thermal Control in the Workplace: Personal and Open Plan Offices

This study compared building-related symptoms in personal and open plan offices, where high and low levels of control over the thermal environment were provided, respectively. The individualized approach in Norway provided every user with a personal office, where they had control over an openable window, door, blinds, and thermostat. In contrast, the open plan case studies in the United Kingdom provided control over openable windows and blinds only for limited occupants seated around the perimeter of the building, with users seated away from the windows having no means of environmental control. Air conditioning was deployed in the Norwegian case study buildings, while displacement ventilation and natural ventilation were utilized in the British examples. Field studies of thermal comfort were applied with questionnaires, environmental measurements, and interviews. Users’ health was better in the Norwegian model (28%), while the British model was much more energy efficient (up to 10 times). The follow-up interviews confirmed the effect of lack of thermal control on users’ health. A balanced appraisal was made of energy performance and users’ health between the two buildings.
T cell recognition of HLA‐A2 restricted tumor antigens is impaired by the oncogene HER2

The HER2 oncogene is frequently over‐expressed in human cancers and a promising target for immune therapy. Previous studies have shown that over‐expression of mouse or rat HER2 leads to markedly reduced levels of major histocompatibility complex (MHC) class I and molecules of the antigen processing and presentation machinery (APM), thus resulting in a phenotype promoting tumor escape from the immune system. Our study focuses on analyzing the effect of HER2 on MHC class I antigen presentation and sensitivity to tumor‐antigen specific cytotoxic T lymphocytes (CTLs) in HLA‐A2.1+ melanoma cell lines. We demonstrate significant inverse correlations both between the expression of HER2 and total MHC class I surface expression as well as between HER2 and HLA‐A2. A significant reduction of HLA‐A2 levels was found when melanoma and carcinoma cell lines were transfected with a human HER2 gene. A signaling‐competent HER2 molecule was crucial for the observed HLA‐A2 down‐regulation, as transfectants expressing high levels of HER2 mutated in the tyrosine signaling domain did not show altered HLA‐A2 expression. Importantly, the human melanoma cell line EST049 demonstrated reduced HER2 and melanoma antigen‐specific recognition by CTLs upon HER2 transfection. In addition, high expression of HER2 prevented both IFN‐γ mediated HLA‐A2 up‐regulation and improved recognition by HLA‐A2‐restricted CTLs in treated cells. Moreover, key APM molecules were down‐regulated by HER2. These findings implicate that HER2 over‐expressing tumors may be more prone to escape from HLA‐A2 restricted CTLs suggesting that immunotherapy approaches inducing an integrated humoral, cellular and innate immune response would be most effective.
Character-Level Question Answering with Attention

We show that a character-level encoder-decoder framework can be successfully applied to question answering with a structured knowledge base. We use our model for single-relation question answering and demonstrate the effectiveness of our approach on the SimpleQuestions dataset (Bordes et al., 2015), where we improve state-of-the-art accuracy from 63.9% to 70.9%, without use of ensembles. Importantly, our character-level model has 16x fewer parameters than an equivalent word-level model, can be learned with significantly less data compared to previous work, which relies on data augmentation, and is robust to new entities in testing.
Attenuated responses to emotional expressions in women with generalized anxiety disorder

Background Generalized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD. Method A total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner. Results The only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response. Conclusions In contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes.
Measuring Neural Net Robustness with Constraints

Despite having high accuracy, neural nets have been shown to be susceptible to adversarial examples, where a small perturbation to an input can cause it to become mislabeled. We propose metrics for measuring the robustness of a neural net and devise a novel algorithm for approximating these metrics based on an encoding of robustness as a linear program. We show how our metrics can be used to evaluate the robustness of deep neural nets with experiments on the MNIST and CIFAR-10 datasets. Our algorithm generates more informative estimates of robustness metrics compared to estimates based on existing algorithms. Furthermore, we show how existing approaches to improving robustness "overfit" to adversarial examples generated using a specific algorithm. Finally, we show that our techniques can be used to additionally improve neural net robustness both according to the metrics that we propose, but also according to previously proposed metrics.
Ectopic TLX1 Expression Accelerates Malignancies in Mice Deficient in DNA-PK

The noncluster homeobox gene HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell acute lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHμ-TLX1Tg mice which develop mature B cell lymphoma after a long latency period, suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHμ-TLX1Tg mice with mice deficient in the DNA repair enzyme DNA-PK (PrkdcScid/Scid mice). IgHµ-TLX1TgPrkdcScid/Scid mice developed T-ALL and acute myeloid leukemia (AML) with reduced latency relative to control PrkdcScid/Scid mice. Further analysis of thymi from premalignant mice revealed greater thymic cellularity concomitant with increased thymocyte proliferation and decreased apoptotic index. Moreover, premalignant and malignant thymocytes exhibited impaired spindle checkpoint function, in association with aneuploid karyotypes. Gene expression profiling of premalignant IgHµ-TLX1TgPrkdcScid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic and mitotic spindle checkpoint genes in double negative 2 (DN2) and DN3 stage thymocytes. Collectively, these findings reveal a novel synergy between TLX1 and impaired DNA repair pathway in leukemogenesis.
Genital Tract, Cord Blood, and Amniotic Fluid Exposures of Seven Antiretroviral Drugs during and after Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women

ABSTRACT The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy, delivery, and postpartum. This prospective, open-label, longitudinal study collected paired blood plasma (BP) and genital tract (GT) aspirates antepartum, at delivery, and up to 12 weeks postpartum. Antiretroviral cord BP and amniotic fluid concentrations were also measured. Drug concentrations were analyzed by validated high-performance liquid chromatography/UV and liquid chromatography/tandem mass spectrometry methods, with secondary compartment concentrations presented as the percentage of BP. Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir (n = 7), nelfinavir (n = 6), or nevirapine (n = 1) were enrolled; four also received tenofovir. GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine. Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester (geometric mean ratio [GMR], 179.3) or third trimester (GMR, 41.9). Compared to nonpregnant historical controls, antepartum GT penetration was significantly lower (P < 0.05) for zidovudine (GMR, 0.25) and lopinavir (GMR, 0.03); postpartum lopinavir GT penetration continued to be significantly lower (GMR, 0.27). Cord BP exposures were highest for lamivudine and tenofovir (≥100%), with cord BP levels of the remaining drugs ranging from 49 to 86% of that of the respective BP level. Amniotic exposures for lamivudine, zidovudine, tenofovir, and nelfinavir were ≥100%, nevirapine exposure was 53%, and lopinavir and ritonavir exposures were ≤6% that of BP. We conclude that GT, cord BP, and amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites. Measurement of antiretroviral exposure in maternal genital secretions, cord BP, and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure.