Miracle-dz/UniFAR-FTUs huggingface dataset:
Isolation and Characterization of Antimicrobial Compounds in Plant Extracts against Multidrug-Resistant Acinetobacter baumannii

The number of fully active antibiotic options that treat nosocomial infections due to multidrug-resistant Acinetobacter baumannii (A. baumannii) is extremely limited. Magnolia officinalis, Mahonia bealei, Rabdosia rubescens, Rosa rugosa, Rubus chingii, Scutellaria baicalensis, and Terminalia chebula plant extracts were previously shown to have growth inhibitory activity against a multidrug-resistant clinical strain of A. baumannii. In this study, the compounds responsible for their antimicrobial activity were identified by fractionating each plant extract using high performance liquid chromatography, and determining the antimicrobial activity of each fraction against A. baumannii. The chemical structures of the fractions inhibiting >40% of the bacterial growth were elucidated by liquid chromatography/mass spectrometry analysis and nuclear magnetic resonance spectroscopy. The six most active compounds were identified as: ellagic acid in Rosa rugosa; norwogonin in Scutellaria baicalensis; and chebulagic acid, chebulinic acid, corilagin, and terchebulin in Terminalia chebula. The most potent compound was identified as norwogonin with a minimum inhibitory concentration of 128 µg/mL, and minimum bactericidal concentration of 256 µg/mL against clinically relevant strains of A. baumannii. Combination studies of norwogonin with ten anti-Gram negative bacterial agents demonstrated that norwogonin did not enhance the antimicrobial activity of the synthetic antibiotics chosen for this study. In conclusion, of all identified antimicrobial compounds, norwogonin was the most potent against multidrug-resistant A. baumannii strains. Further studies are warranted to ascertain the prophylactic and therapeutic potential of norwogonin for infections due to multidrug-resistant A. baumannii.
Practice of Epidemiology Comparison of Statistical Approaches for DealingWith Immortal TimeBias in Drug Effectiveness Studies

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-upmay result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a timedependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to bemore useful than thePTDMapproach (Cox: bias =−0.002,mean squared error = 0.025; PTDM: bias = −1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995–2008).
Mode I interlaminar fracture toughness of Nylon 66 nanofibrilmat interleaved carbon/epoxy laminates

Carbon/epoxy laminates interleaved with laboratory scale electrospun Nylon 66 nanofibrilmat and spunbonded nonwoven mats were investigated. The effect of the nanoscale fibers on the fracture toughness of the composite under pure Mode I loading was evaluated. It was shown that the nanofibrilmat is responsible for a major interlaminar fracture toughness improvement, as high as 255–322%, compared to a noninterleaved carbon/epoxy reference laminate. We further studied the improvement mechanism of the electrospun nanofibrilmat compared to a commercial spunbonded nonwoven Nylon 66 mat. A combination of two interlayer fracture mechanisms responsible for the toughness improvement is suggested: the first is related to the high energy dissipated by bridged thermoplastic nanofibers and the second is attributed to the generation of a plastic zone near the crack tip. The interlaminar fracture mechanisms of both electrospun nanofibrilmat and the nonwoven mat interleaving was analyzed and discussed. POLYM. COMPOS. , 2011. © 2011 Society of Plastics Engineers
Celiac Disease and Concomitant Conditions: A Case-based Review

Celiac disease is a chronic autoimmune disease with genetic predisposition, triggered by the ingestion of gluten. It has a wide range of clinical manifestations ranging from asymptomatic forms to classic presentation of malabsorption with diarrhea and abdominal cramps. Celiac disease can also present with several other concomitant disorders (at the time of diagnosis or during the course of celiac disease) such as: type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis, thyroid disorders, nutritional deficiencies, and gram-negative sepsis. We present a 57-year-old female with past medical history of rheumatoid arthritis, who presented to the emergency department with a complaint of chronic diarrhea, complicated by gram-negative sepsis. The family history of the patient was significant for celiac disease, type 1 diabetes, and rheumatoid arthritis. The patient was closely monitored and treated appropriately. In this case-based review, we explore different associated conditions of celiac disease in the literature, as well as the patient's risk of developing malignancy.
Pathways to high and low performance: factors differentiating primary care facilities under performance-based financing in Nigeria

Abstract The determinants of primary health facility performance in developing countries have not been well studied. One of the most under-researched areas is health facility management. This study investigated health facilities under the pilot performance-based financing (PBF) scheme in Nigeria, and aimed to understand which factors differentiated primary health care centres (PHCCs) which had performed well, vs those which had not, with a focus on health facility management practices. We used a multiple case study where we compared two high-performing PHCCs and two low-performing PHCCs for each of the two PBF target states. Two teams of two trained local researchers spent 1 week at each PHCC and collected semi-structured interview, observation and documentary data. Data from interviews were transcribed, translated and coded using a framework approach. The data for each PHCC were synthesized to understand dynamic interactions of different elements in each case. We then compared the characteristics of high and low performers. The areas in which critical differences between high and low-performers emerged were: community engagement and support; and performance and staff management. We also found that (i) contextual and health system factors particularly staffing, access and competition with other providers; (ii) health centre management including community engagement, performance management and staff management; and (iii) community leader support interacted and drove performance improvement among the PHCCs. Among them, we found that good health centre management can overcome some contextual and health system barriers and enhance community leader support. This study findings suggest a strong need to select capable and motivated health centre managers, provide long-term coaching in managerial skills, and motivate them to improve their practices. The study also highlights the need to position engagement with community leaders as a key management practice and a central element of interventions to improve PHCC performance.
Viscoelastic FE Modeling of Asphalt Pavements and Its Application to U.S. 30 Perpetual Pavement

LIAO, YUN, Ph.D., November 2007. Integrated Engineering VISCOELASTIC FE MODELING OF ASPHALT PAVEMENTS AND ITS APPLICATION TO U.S. 30 PERPETUAL PAVEMENT (146 pp.) Director of Dissertation: Shad M. Sargand The primary objective of this research consisted of incorporating laboratorydetermined viscoelastic material properties into a three-dimensional finite element model to accurately simulate the behavior of a perpetual pavement structure subjected to vehicular loading at different pavement temperatures and vehicular speeds. With this finite element model, statistical models that were based on Falling Weight Deflectometer testing were developed to predict the structural response of a perpetual pavement. In this research, the dynamic modulus test was chosen to determine viscoelastic properties of hot-mix-asphalt materials in the laboratory. A 5-term Prony series was used to describe the viscoelastic behavior of hot-mix-asphalt materials. Resilient modulus tests were performed to measure resilient moduli of hot-mix-asphalt mixtures and subgrade soils. All these laboratory-determined material properties were inputted into the developed viscoelastic finite element model to predict pavement response. The developed viscoelastic finite element model was validated by and calibrated to field-measured pavement responses collected at the U.S. 30 perpetual pavement constructed in Wayne County, Ohio. The results demonstrated that the developed viscoelastic finite element model can predict pavement responses accurately. Parametric studies revealed that the developed viscoelastic finite element model performed better in pavement thickness design compared with perpetual-pavementdesign-oriented software PerRoad which underestimated pavement responses. Layer modulus variation did not affect pavement response significantly. The ratio maximumtensile-strain/load was independent of the axle load. The ratio maximum-tensilestrain/speed increased with decreasing in vehicular speeds. A nomograph was developed to correlate the maximum tensile strain to the pavement temperature depending on the thickness of the ODOT302 layer and the aggregate base. Finally, the developed finite element model was tailored to work for Falling Weight Deflectometer tests. Statistical models were developed to estimate pavement response using the Falling Weight Deflectometer upon the completion of a perpetual pavement. These models are important in practice to assess pavement quality using the Falling Weight Deflectometer. Outcomes of this research are significantly important to improve the accuracy of current design and analysis methods which are widely used in predicting pavement responses and to provide practical guidelines for perpetual pavement design and analysis. Approved: ________________________________________________ Shad M. Sargand Russ Professor of Civil Engineering
Planting exotic relatives has increased the threat posed by Dothistroma septosporum to the Caledonian pine populations of Scotland

To manage emerging forest diseases and prevent their occurrence in the future, it is essential to determine the origin(s) of the pathogens involved and identify the management practices that have ultimately caused disease problems. One such practice is the widespread planting of exotic tree species within the range of related native taxa. This can lead to emerging forest disease both by facilitating introduction of exotic pathogens and by providing susceptible hosts on which epidemics of native pathogens can develop. We used microsatellite markers to determine the origins of the pathogen Dothistroma septosporum responsible for the current outbreak of Dothistroma needle blight (DNB) on native Caledonian Scots pine (Pinus sylvestris) populations in Scotland and evaluated the role played by widespread planting of two exotic pine species in the development of the disease outbreak. We distinguished three races of D. septosporum in Scotland, one of low genetic diversity associated with introduced lodgepole pine (Pinus contorta), one of high diversity probably derived from the DNB epidemic on introduced Corsican pine (Pinus nigra subsp. laricio) in England and a third of intermediate diversity apparently endemic on Caledonian Scots pine. These races differed for both growth rate and exudate production in culture. Planting of exotic pine stands in the UK appears to have facilitated the introduction of two exotic races of D. septosporum into Scotland which now pose a threat to native Caledonian pines both directly and through potential hybridization and introgression with the endemic race. Our results indicate that both removal of exotic species from the vicinity of Caledonian pine populations and restriction of movement of planting material are required to minimize the impact of the current DNB outbreak. They also demonstrate that planting exotic species that are related to native species reduces rather than enhances the resilience of forests to pathogens.
Early hypertension is associated with better clinical outcomes in gastric cancer patients treated with ramucirumab plus paclitaxel

Anti-vascular endothelial growth factor (VEGF) therapeutics such as bevacizumab, which are widely used in cancer treatment, commonly leads to hypertension. Moreover, bevacizumab-induced hypertension is associated with improved clinical outcomes in several cancers. We retrospectively analyzed 89 patients with histologically confirmed advanced gastric cancer who received the human monoclonal anti-VEGF receptor-2 antibody ramucirumab plus paclitaxel at our hospital between June 2015 and October 2016 to evaluate the impact of treatment-associated hypertension occurring within the first two treatment cycles (“early hypertension”) on outcome. The objective response rate was 40%, median progression-free survival was 5.4 months, and overall survival was 10.4 months, which is similar to previous reports. Early hypertension in patients who received more than two cycles of ramucirumab + paclitaxel was associated with longer progression-free and overall survival. Objective response rates were also higher in patients with early hypertension. These data indicate that early hypertension may be predictive of better outcomes in gastric cancer patients who receive ramucirumab + paclitaxel treatment.
Multi-target Voice Conversion without Parallel Data by Adversarially Learning Disentangled Audio Representations

Recently, cycle-consistent adversarial network (Cycle-GAN) has been successfully applied to voice conversion to a different speaker without parallel data, although in those approaches an individual model is needed for each target speaker. In this paper, we propose an adversarial learning framework for voice conversion, with which a single model can be trained to convert the voice to many different speakers, all without parallel data, by separating the speaker characteristics from the linguistic content in speech signals. An autoencoder is first trained to extract speaker-independent latent representations and speaker embedding separately using another auxiliary speaker classifier to regularize the latent representation. The decoder then takes the speaker-independent latent representation and the target speaker embedding as the input to generate the voice of the target speaker with the linguistic content of the source utterance. The quality of decoder output is further improved by patching with the residual signal produced by another pair of generator and discriminator. A target speaker set size of 20 was tested in the preliminary experiments, and very good voice quality was obtained. Conventional voice conversion metrics are reported. We also show that the speaker information has been properly reduced from the latent representations.
Brain Activity during Methamphetamine Anticipation in a Non-Invasive Self-Administration Paradigm in Mice

Visual Abstract The ability to sense time and anticipate events is critical for survival. Learned responses that allow anticipation of the availability of food or water have been intensively studied. While anticipatory behaviors also occur prior to availability of regularly available rewards, there has been relatively little work on anticipation of drugs of abuse, specifically methamphetamine (MA). In the present study, we used a protocol that avoided possible CNS effects of stresses of handling or surgery by testing anticipation of MA availability in animals living in their home cages, with daily voluntary access to the drug at a fixed time of day. Anticipation was operationalized as the amount of wheel running prior to MA availability. Mice were divided into four groups given access to either nebulized MA or water, in early or late day. Animals with access to MA, but not water controls, showed anticipatory activity, with more anticipation in early compared to late day and significant interaction effects. Next, we explored the neural basis of the MA anticipation, using c-FOS expression, in animals euthanized at the usual time of nebulization access. In the dorsomedial hypothalamus (DMH) and orbitofrontal cortex (OFC), the pattern of c-FOS expression paralleled that of anticipatory behavior, with significant main and interaction effects of treatment and time of day. The results for the lateral septum (LS) were significant for main effects and marginally significant for interaction effects. These studies suggest that anticipation of MA is associated with activation of brain regions important in circadian timing, emotional regulation, and decision making.
Rett syndrome from bench to bedside: recent advances

Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene ( MECP2). Mecp2 is known to play a role in chromatin organization and transcriptional regulation. In this review, we report the latest advances on the molecular function of Mecp2 and the new animal and cellular models developed to better study Rett syndrome. Finally, we present the latest innovative therapeutic approaches, ranging from classical pharmacology to correct symptoms to more innovative approaches intended to cure the pathology.
Dielectric breakdown characteristics of DGEBA/MDA/SN-Al/sub 2/O/sub 3/ composite system

The dielectric breakdown characteristics of Al/sub 2/O/sub 3/ filled DGEBA (diglycidyl ether of bisphenol A)/MDA (4,4'-methylene dianilene/SN (succinonitrile) system were investigated. To simulate the stress concentration the sharp-pointed needle and plane electrode geometry was used. It was shown that as the filler contents increased the dielectric breakdown strength increased and then decreased at higher filler content than 5 phr because of the increment of weak point, especially at the interface of filler and epoxy resin initiated from the weakest point of the needle electrode tip. To increase the resistance to the higher electrical stress the curing condition should be modified and a new coupling agent should be introduced.
Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis

Herein, we report the first identification of biallelic‐inherited mutations in ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated patients. ALPI encodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll‐like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter‐subunit interactions, and heterologous expression in HEK293T cells demonstrated that all ALPI mutations were loss of function. ALPI mutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide‐dependent signalling. Furthermore, ALPI expression was reduced in patients’ biopsies, and ALPI activity was undetectable in ALPI‐deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host–microbiota interactions and restraining host inflammatory responses. These results indicate that ALPI mutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI‐based treatments in intestinal inflammatory disorders.
The Metric Space of Networks

We study the question of reconstructing a weighted, directed network up to isomorphism from its motifs. In order to tackle this question we first relax the usual (strong) notion of graph isomorphism to obtain a relaxation that we call weak isomorphism. Then we identify a definition of distance on the space of all networks that is compatible with weak isomorphism. This global approach comes equipped with notions such as completeness, compactness, curves, and geodesics, which we explore throughout this paper. Furthermore, it admits global-to-local inference in the following sense: we prove that two networks are weakly isomorphic if and only if all their motif sets are identical, thus answering the network reconstruction question. Further exploiting the additional structure imposed by our network distance, we prove that two networks are weakly isomorphic if and only if certain essential associated structures---the skeleta of the respective networks---are strongly isomorphic.
Mining DNA methylation alterations towards a classification of placental pathologies

Abstract Placental health is a key component to a successful pregnancy. Placental insufficiency (PI), inadequate nutrient delivery to the fetus, is associated with preeclampsia (PE), a maternal hypertensive disorder, and intrauterine growth restriction (IUGR), pathologically poor fetal growth. PI is more common in early-onset PE (EOPE) than late-onset PE (LOPE). However, the relationship between these disorders remains unclear. While DNA methylation (DNAm) alterations have been identified in PE and IUGR, these entities can overlap and few studies have analysed them separately. This study aims to utilize DNAm profiling to better understand the underlying placental variation associated with PE and IUGR. Placental samples from a discovery (43 controls, 22 EOPE, 18 LOPE, 11 IUGR) and validation cohort (15 controls, 22 EOPE, 11 LOPE) were evaluated using the Illumina HumanMethylation450 array. To account for gestational age (GA) effects, EOPE samples were compared with pre-term births of varying etiologies (GA <37 weeks). LOPE and IUGR were compared with term controls (GA >37 weeks). While 1703 sites were differentially methylated (DM) (FDR < 0.05, Δβ > 0.1) in EOPE, few changes were associated with LOPE (N = 5), or IUGR (N = 0). Of the 1703 EOPE sites, 599 validated in the second cohort. Using these 599 sites, both cohorts clustered into three distinct groups. Interestingly, LOPE samples diagnosed between 34 and 36 weeks with co-occurring IUGR clustered with the EOPE. DNAm profiling may provide an independent tool to refine clinical/pathological diagnoses into subgroups with more uniform pathology. Despite large changes observed in EOPE, there were challenges in reproducing genome-wide DNAm hits that are discussed.