Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of vascular endothelial barrier function.

The increase in endothelial permeability in response to inflammatory mediators such as alpha-thrombin and histamine is accompanied by cell rounding and interendothelial gap formation, implicating that the predominant transport pathway is a diffusive one [i.e., via cellular junctions (paracellular transport)]. However, the possible contribution by vesicle-mediated transport (i.e., via albumin binding protein gp60) to the overall permeability increase needs investigation. Regulation of paracellular transport in endothelial cells is associated with modulation of actin-based systems which anchor the cell to its neighbor or extracellular matrix, thus maintaining endothelial integrity. At the cell-cell junctions, actin is linked indirectly to the plasma membrane by linking proteins (e.g., vinculin, catenins, alpha-actinin) to cadherins, which function in homophilic intercellular adhesion. Cadherins may also play a role in regulating the formation of tight junctions, which also may be associated with actin. At endothelial focal contacts, the transmembrane receptors (integrins) for matrix proteins are linked to actin via linking proteins (i.e., vinculin, talin, alpha-actinin). In response to inflammatory mediators, second messengers signal two regulatory pathways which modulate the actin-based systems, which may lead to impairment of the endothelial barrier integrity. One pathway is based on protein kinase C (PKC) isozyme-specific phosphorylation of linking proteins at the cell-cell and cell-matrix junctions. The increased phosphorylation is associated with actin reorganization, cell rounding, and increased paracellular transport. The other is the activation of myosin light-chain kinase, (MLCK), which causes an actin-myosin-based contraction that may lead to a centripetal retraction of endothelial cells. Current research is in the identification of protein substrates of PKC isozymes, the specific role of their phosphorylation in barrier function, and determining the precise role of MLCK in modulation of endothelial barrier function.
Urine proteomics for profiling of human disease using high accuracy mass spectrometry

Knowledge of the biologically relevant components of human tissues has enabled the invention of numerous clinically useful diagnostic tests, as well as non‐invasive ways of monitoring disease and its response to treatment. Recent use of advanced MS‐based proteomics revealed that the composition of human urine is more complex than anticipated. Here, we extend the current characterization of the human urinary proteome by extensively fractionating urine using ultracentrifugation, gel electrophoresis, ion exchange and reverse‐phase chromatography, effectively reducing mixture complexity while minimizing loss of material. By using high‐accuracy mass measurements of the linear ion trap‐Orbitrap mass spectrometer and LC‐MS/MS of peptides generated from such extensively fractionated specimens, we identified 2362 proteins in routinely collected individual urine specimens, including more than 1000 proteins not described in previous studies. Many of these are biomedically significant molecules, including glomerularly filtered cytokines and shed cell surface molecules, as well as renally and urogenitally produced transporters and structural proteins. Annotation of the identified proteome reveals distinct patterns of enrichment, consistent with previously described specific physiologic mechanisms, including 336 proteins that appear to be expressed by a variety of distal organs and glomerularly filtered from serum. Comparison of the proteomes identified from 12 individual specimens revealed a subset of generally invariant proteins, as well as individually variable ones, suggesting that our approach may be used to study individual differences in age, physiologic state and clinical condition. Consistent with this, annotation of the identified proteome by using machine learning and text mining exposed possible associations with 27 common and more than 500 rare human diseases, establishing a widely useful resource for the study of human pathophysiology and biomarker discovery.
CoSense: Interference resilient ZigBee detection in heterogeneous wireless networks

The concurrent deployment of heterogeneous wireless networks such as Wi-Fi, Bluetooth, and ZigBee has led to the severe interference problems in the 2.4GHz ISM band. In particular, ZigBee networks are susceptible to the interferences from other wireless technologies; For example, strong Wi-Fi signals trigger false alarms to ZigBee device that is performing low power idle listening and cause appreciable energy waste. In this paper, we propose a novel ZigBee signal detection scheme, called CoSense that accurately identifies ZigBee signals in the presence of the cross-technology interferences. CoSense, which is a highly reliable signal correlation technique, enjoys the following three advantages: First, CoSense reduces false wake-ups, which typically consume energy unnecessarily. Secondly, CoSense is robust against heterogeneous interference scenarios because its signal correlation feature has been shown to work well in bad channel conditions. Third, CoSense is backward-compatible and does not require to change the traditional ZigBee networks. We have implemented CoSense on the USRP/GNURadio platform in order to prove its feasibility. The results show that, under typical setting, CoSense indeed reduces the false alarm rate and its overhead is tolerable. We can conclude that CoSense saves energy by up to 63% in heterogeneous network environments where weak ZigBee signals are overwhelmed by strong signals such as Wi-Fi.
Aggregation of cellular prion protein is initiated by proximity‐induced dimerization

Prion diseases or transmissible spongiform encephalopathies (TSEs) are infectious and fatal neurodegenerative disorders in humans and animals. Pathological features of TSEs include the conversion of cellular prion protein (PrPC) into an altered disease‐associated conformation generally designated PrPSc, abnormal deposition of PrPSc aggregates, and spongiform degeneration of the brain. The molecular steps leading to PrPC aggregation are unknown. Here, we have utilized an inducible oligomerization strategy to test if, in the absence of any infectious prion particles, the encounter between PrPC molecules may trigger its aggregation in neuronal cells. A chimeric PrPC composed of one (Fv1) or two (Fv2) modified FK506‐binding protein (Fv) fused with PrPC were created, and transfected in N2a cells. Similar to PrPC, Fv1‐PrP and Fv2‐PrP were glycosylated, displayed normal localization, and anti‐apoptotic function. When cells were treated with the dimeric Fv ligand AP20187, to induce dimerization (Fv1) or oligomerization (Fv2) of PrPC, both dimerization and oligomerization of PrPC resulted in the de novo production, release and deposition of extracellular PrP aggregates. Aggregates were insoluble in non‐ionic detergents and partially resistant to proteinase K. These findings demonstrate that homologous interactions between PrPC molecules may constitute a minimal and sufficient molecular event leading to PrPC aggregation and extracellular deposition.
Treatment of Clostridium difficile infection in a French university hospital

Abstract The management of Clostridium difficile infection (CDI) has become very daunting over the past decade because of increased incidence and severity both in hospital and the community. Guidelines recommend metronidazole, vancomycin, or fidaxomicin, depending on clinical presentation. Objective. Our objective was to describe CDI management and assess empirical CDI therapy complying with practice guidelines. Methods. We performed a 2-year prospective cohort study in a university teaching hospital in Lyon, France. Criteria assessing the conformity of CDI patient management were: time elapsed between testing and start of treatment specific to CDI, antibiotics to fight CDI and treatment duration according to infection severity, concomitant therapy, and use of antidiarrheal drugs. Results. Among 118 patients with confirmed CDI, 98 (83%) were specifically treated for CDI. Severe CDI was observed in 63 patients (53.9%). Treatment included metronidazole alone in 72 patients (73.5%), vancomycin alone in 1 patient (1%), and both in 25 patients (25.5%). The percentage of CDI treatment compliance with published guidelines in our hospital at the study period varied between 22% and 93%. A total of 16 patients (13.6%) died within 30 days after diagnosis. Death was related to CDI in nine patients (56.3% of deceased cases). Conclusion. This study identified significant gaps in our knowledge of CDI treatment. Increasing disease severity highlights the need to investigate antibiotic treatment in severely ill CDI patients, as data on this group are currently lacking.
Identification of an Amygdala–Thalamic Circuit That Acts as a Central Gain Mechanism in Taste Perceptions

Peripheral sources of individual variation in taste intensity perception have been well described. The existence of a central source has been proposed but remains unexplored. Here we used functional magnetic resonance imaging in healthy human participants (20 women, 8 men) to evaluate the hypothesis that the amygdala exerts an inhibitory influence that affects the “gain” of the gustatory system during tasting. Consistent with the existence of a central gain mechanism (CGM), we found that central amygdala response was correlated with mean intensity ratings across multiple tastants. In addition, psychophysiological and dynamic causal modeling analyses revealed that the connection strength between inhibitory outputs from amygdala to medial dorsal and ventral posterior medial thalamus predicted individual differences in responsiveness to taste stimulation. These results imply that inhibitory inputs from the amygdala to the thalamus act as a CGM that influences taste intensity perception. SIGNIFICANCE STATEMENT Whether central circuits contribute to individual variation in taste intensity perception is unknown. Here we used functional magnetic resonance imaging in healthy human participants to identify an amygdala–thalamic circuit where network dynamics and connectivity strengths during tasting predict individual variation in taste intensity ratings. This finding implies that individual differences in taste intensity perception do not arise solely from variation in peripheral gustatory factors.
Assessment of individual fatty acid intake

Dietary assessment of individual fatty acid intake is difficult due to a number of limitations. Information regarding the type, quantity and brand-name of fat used in cooking and at the table is required. In addition, margarine manufacturers may change the component oils used for reasons of cost, which changes the fatty acid composition of their products from season-to-season. Independent markers of fatty acid intake are required, therefore, to compensate for these limitations. Adipose tissue concentrations have been used as a measure of habitual intake of fatty acid groups and individual fatty acids in numerous studies. Saturated (SFA) and monounsaturated fatty acids (MUFA) are generally poorly correlated with adipose tissue concentrations, which can be explained partly by endogenous synthesis. In general, adipose tissue concentrations of exogenously-produced fatty acids (n-3 and n-6 polyunsaturated fatty acids (PUFA)) are well correlated with estimates of habitual intake. Correlations between dietary trans unsaturated fatty acids (TUFA) and adipose tissue concentrations vary between countries, which may be due to differences in dietary sources. Correlations may be affected by differences in bioavailability or selective retention of fatty acids in certain tissue lipids.
YMDD motif variants in inactive hepatitis B carriers detected by Inno‐Lipa HBV DR assay

Introduction: Mutations of hepatitis B virus (HBV) polymerase, especially occurring at the highly conserved YMDD region, are related to resistance to lamivudine. Although these mutations are frequently secondary to lamivudine use, they can also occur naturally. The aim of the present study was to determine the prevalence of YMDD variants that exist naturally in patients who are inactive HBV carriers.
Otopathology of Vasculitis in Granulomatosis With Polyangitis

Objective: To describe the temporal bone histopathology of vasculitis in granulomatosis with polyangitis. Background: Granulomatosis with polyangitis is an autoimmune disease that presents as granulomatosis and vasculitis. Otologic findings, including otitis media, hearing loss, vertigo, and facial paralysis are common in this condition. Material and Methods: The temporal bones of four subjects with manifestations of vasculitis attributed to granulomatosis with polyangitis were studied under light microscopy. Results: The four subjects had manifestations of vasculitis including hemorrhage within the cochlea and vestibule, and inflammation and occlusion of vessels in the lateral cochlear wall and the vasa nervorum of the facial nerve. Conclusions: We infer that sensorineural hearing loss, vestibulopathy, and facial nerve paresis in granulomatosis with polyangitis can be the results of vasculitis.
Solution structure of the pseudoknot of SRV-1 RNA, involved in ribosomal frameshifting1

Abstract RNA pseudoknots play important roles in many biological processes. In the simian retrovirus type-1 (SRV-1) a pseudoknot together with a heptanucleotide slippery sequence are responsible for programmed ribosomal frameshifting, a translational recoding mechanism used to control expression of the Gag-Pol polyprotein from overlapping gag and pol open reading frames. Here we present the three-dimensional structure of the SRV-1 pseudoknot determined by NMR. The structure has a classical H-type fold and forms a triple helix by interactions between loop 2 and the minor groove of stem 1 involving base-base and base-sugar interactions and a ribose zipper motif, not identified in pseudoknots so far. Further stabilization is provided by a stack of five adenine bases and a uracil in loop 2, enforcing a cytidine to bulge. The two stems of the pseudoknot stack upon each other, demonstrating that a pseudoknot without an intercalated base at the junction can induce efficient frameshifting. Results of mutagenesis data are explained in context with the present three-dimensional structure. The two base-pairs at the junction of stem 1 and 2 have a helical twist of approximately 49°, allowing proper alignment and close approach of the three different strands at the junction. In addition to the overwound junction the structure is somewhat kinked between stem 1 and 2, assisting the single adenosine in spanning the major groove of stem 2. Geometrical models are presented that reveal the importance of the magnitude of the helical twist at the junction in determining the overall architecture of classical pseudoknots, in particular related to the opening of the minor groove of stem 1 and the orientation of stem 2, which determines the number of loop 1 nucleotides that span its major groove.
High Prevalence of Antiretroviral Drug Resistance among HIV-1-Untreated Patients in Guinea-Conakry and in Niger

Background The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger. Methods The study was performed in two countries of Western Africa – Guinea-Conakry and Niger – using the same survey method in both sites. All newly HIV-1 diagnosed patients, naive of antiretroviral drugs, were consecutively included during September 2009 in each of the two sites. Protease and reverse transcriptase sequencing was performed using the ANRS procedures. Drug resistance mutations were identified according to the 2009 update surveillance drug resistance mutations. Results In Conakry, 99 patients were included, most of whom (89%) were infected with CRF02_AG recombinant virus. Resistance analysis among the 93 samples showed that ≥1 drug resistance mutation was observed in 8 samples, leading to a prevalence of primary resistance of 8.6% (95% CI 2.91–14.29%). In Niamey, 96 patients were included; a high diversity in HIV-1 subtypes was observed with 47 (51%) patients infected with CRF02_AG. Resistance analysis performed among the 92 samples with successful genotypic resistance test showed that ≥1 drug resistance mutation was observed in 6 samples, leading to a prevalence of primary resistance of 6.5% (95% CI 1.50–11.50%). Conclusions We reported the first antiretroviral drug resistance survey studies in antiretroviral-naive patients living in Guinea-Conakry and in Niger. The prevalence of resistance was between 6% and 9% in both sites, which is higher than most of the other countries from Western Africa region.
Mobile connection: An examination of antecedents to engage consumer in social network app

With the popularity of mobile handset devices, such as smart phones or tablet computers, it is very convenient for consumers to access wireless service on the go and for service providers to offer very instant and location-based services (LBS) via mobile applications. Marketers prefer to adopt social network applications (SNAs) as a new customized marketing tool to connect with their consumers nowadays. As a result, consumers face a variety of choices in SNAs. How to engage consumers in one SNA should be important for the service providers and sponsoring brands of SNAs. This study intended to explore the motivation of consumer engagement in mobile SNAs by adopting the conceptual framework of content, process and social gratification in Uses and Gratification Theory. A questionnaire survey was designed to sampling the response of app users who reported to use any social network app on mobile devices. 543 valid questionnaires were reserved for further SEM analyses. Research findings provided the evidence that entertainment was the key content gratification that motivated more consumer engagement in SNAs. Process gratification of LBS and instant service were found to be critical to consumer engagement in SNAs. Lastly, socialization gratification of self-expression and social influence also enhanced consumer engagement in SNAs.
A New Power System Digital Harmonic Analyzer

In this paper, new digital instruments measuring power-quality indicators and harmonic analyzers are developed. A new technique for simultaneous local system frequency and amplitudes of the fundamental and higher harmonics estimation from either a voltage or current signal is presented. The structure consists of three decoupled modules: the first one for an adaptive filter of input signal, the second one for frequency estimation, and the third one for harmonic amplitude estimation. A very suitable algorithm for frequency and harmonic amplitude estimation is obtained. This technique provides accurate frequency estimates with error in the range of 0.002 Hz and amplitude estimates with error in the range of 0.03% for SNR = 60 dB in about 25 ms. The theoretical basis and practical implementation of the technique are described. To demonstrate the performance of the developed algorithm, computer simulated data records are processed. Data of the distribution power system voltage signals are also collected in the laboratory environment and are processed in a newly developed digital PC-based harmonic analyzer. It has been found that the proposed method really meets the need of offline applications. Even more, by using the parallel computation algorithms, this method should meet the need of online applications and should be more practical
Clinical outcome and health-related quality-of-life following microsurgical reconstruction in patients with oral and oropharyngeal cancer

Abstract Conclusion: Radial forearm free flap (RFFF) and fibula free flap (FFF) provide high safety and reliability with low incidence of free flap failure and an acceptable level of complications and health-related quality-of-life (HRQoL). Objectives: To determine the clinical outcomes and long-term HRQoL in patients with oral or oropharyngeal cancer following free flap reconstruction. Methods: A retrospective review of medical records and self-administered HRQoL questionnaires, EORTC QLQ-C30, and -H&N35. All patients who underwent surgery for oral or oropharyngeal cancer followed by primary reconstruction by RFFF or FFF at Rigshospitalet between September 2001 and November 2011 were included. Results: The study comprised 19 patients still alive out of 61 patients. The free flap success rate was 94.7%. Early post-operative complications occurred in 11 patients (57.9%); however, only three cases (15.8%) required re-surgery. Nine patients (47.4%) developed late complications, including mandibular osteoradionecrosis in six cases (31.6%). Most patients obtained acceptable values of global quality-of-life and relatively high scores on the functional scales.
Advanced sequencing technologies and their wider impact in microbiology

SUMMARY In the past 10 years, microbiology has undergone a revolution that has been driven by access to cheap high-throughput DNA sequencing. It was not long ago that the cloning and sequencing of a target gene could take months or years, whereas now this entire process has been replaced by a 10 min Internet search of a public genome database. There has been no single innovation that has initiated this rapid technological change; in fact, the core chemistry of DNA sequencing is the same as it was 30 years ago. Instead, progress has been driven by large sequencing centers that have incrementally industrialized the Sanger sequencing method. A side effect of this industrialization is that large-scale sequencing has moved out of small research labs, and the vast majority of sequence data is now generated by large genome centers. Recently, there have been advances in technology that will enable high-throughput genome sequencing to be established in research labs using bench-top instrumentation. These new technologies are already being used to explore the vast microbial diversity in the natural environment and the untapped genetic variation that can occur in bacterial species. It is expected that these powerful new methods will open up new questions to genomic investigation and will also allow high-throughput sequencing to be more than just a discovery exercise but also a routine assay for hypothesis testing. While this review will concentrate on microorganisms, many of the important arguments about the need to measure and understand variation at the species, population and ecosystem level will hold true for many other biological systems.
Replication and Validation of the Drinking Motive Questionnaire Revised (DMQ-R, Cooper, 1994) among Adolescents in Switzerland

This paper has two aims: (1) to replicate the four-dimensional structure of the Drinking Motive Questionnaire Revised (DMQ-R) in a national representative sample from Switzerland, and (2) to validate the relevance of distinguishing drinking motives by inspecting the relations with expected consequences, alcohol use, and alcohol-related and other problems. Confirmatory factor analysis and linear structural equation models were estimated based on answers of 5,617 8th to 10th graders (mean 15.1 years; SD = 0.95). The results confirm the four-dimensional factor structure in general and among subpopulations defined by gender, age, and linguistic region. It could also be confirmed that enhancement motives followed by coping motives were strongly related to alcohol use and heavy drinking, whereas conformity motives were negatively related. Coping motives were related to problems independent of whether they were assessed as alcohol-related or not, while enhancement motives were associated solely with alcohol-related problems. In sum, the results demonstrate the robustness of the DMQ-R and its usefulness for assessing drinking motives among European adolescents from different cultural backgrounds.