Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance to AFN-1252 Arises from Missense Mutations in Staphylococcus aureus Enoyl-acyl Carrier Protein Reductase (FabI)*

Background: AFN-1252 is a FabI inhibitor developed to treat Staphylococcus aureus. Results: AFN-1252 resistance arises from a single missense mutation that produces a FabI(M99T) protein. Conclusion: The interaction between Met-99 and AFN-1252 accounts for the staphylococcal selectivity of the drug. Significance: The AFN-1252-resistant strains remain susceptible to drug concentrations typically achieved in antibiotic therapy. AFN-1252 is a potent antibiotic against Staphylococcus aureus that targets the enoyl-acyl carrier protein reductase (FabI). A thorough screen for AFN-1252-resistant strains was undertaken to identify the spectrum of mechanisms for acquired resistance. A missense mutation in fabI predicted to encode FabI(M99T) was isolated 49 times, and a single isolate was predicted to encode FabI(Y147H). AFN-1252 only bound to the NADPH form of FabI, and the close interactions between the drug and Met-99 and Tyr-147 explained how the mutations would result in resistant enzymes. The clone expressing FabI(Y147H) had a pronounced growth defect that was rescued by exogenous fatty acid supplementation, and the purified protein had less than 5% of the enzymatic activity of FabI. FabI(Y147F) was also catalytically defective but retained its sensitivity to AFN-1252, illustrating the importance of the conserved Tyr-147 hydroxyl group in FabI function. The strains expressing FabI(M99T) exhibited normal growth, and the biochemical properties of the purified protein were indistinguishable from those of FabI. The AFN-1252 Kiapp increased from 4 nm in FabI to 69 nm in FabI(M99T), accounting for the increased resistance of the corresponding mutant strain. The low activity of FabI(Y147H) precluded an accurate Ki measurement. The strain expressing FabI(Y147H) was also resistant to triclosan; however, the strain expressing FabI(M99T) was more susceptible. Strains with higher levels of AFN-1252 resistance were not obtained. The AFN-1252-resistant strains remained sensitive to submicromolar concentrations of AFN-1252, which blocked growth through inhibition of fatty acid biosynthesis at the FabI step.
Induction of Th1/Th17 immune response by Mycobacterium tuberculosis: role of dectin‐1, mannose receptor, and DC‐SIGN

Mtb influences DC activity and T cell‐mediated immune responses. We show that the treatment of immature monocyte‐derived DC with Mtb elicited the formation of mature DC, producing TNF‐α, IL‐1β, IL‐6, and IL‐23 and instructing CD4+ cells to secrete IFN‐γ and IL‐17. Mtb‐induced cytokine release by DC depended on dectin‐1 receptor engagement, whereas MR or DC‐SIGN stimulation inhibited this process. A selective dectin‐1 binding by the receptor agonist glucan was sufficient to enable DC to generate Th1/Th17 lymphocytes, showing features comparable with those induced by Mtb‐treated DC. Interestingly, DC‐SIGN or MR engagement inhibited Th17 and increased Th1 generation by glucan‐ or Mtb‐treated DC. Our results indicate that Mtb modulates the lymphocyte response by affecting DC maturation and cytokine release. Dectin‐1 engagement by Mtb enables DC to promote a Th1/Th17 response, whereas DC‐SIGN and MR costimulation limits dectin‐1‐dependent Th17 generation and favors a Th1 response, probably by interfering with release of cytokines.
Ultra-broadband V-band fractal T-square antenna

A corner CPW-fed T-square fractal antenna is proposed. This fractal layout provides a wider bandwidth compared to typical square patches. The proposed antenna is designed to operate within the V-band millimeter-wave frequency range and found to cover a 10 dB return loss bandwidth of 19.2 GHz which presents 54.9% of the entire V-band. The ground plane of the antenna is limited to the feeding line, and a monopole-like radiation pattern is achieved. The gain values gradually increase throughout the ultra-broadband operational bandwidth and reaches a maximum value of 5.7 dBi. The efficiency of the antenna is considered high with a maximum value of 87.6%. The layout of the antenna can be scaled in order to fit other frequency bands; such as the ultra-wideband frequency band.
Prospective studies on mental status and quality of life in patients with head and neck cancer treated by radiation

Factors affecting the quality of life (QOL) in patients undergoing radiation therapy for head and neck cancer were determined in a prospective study. Full psychiatric interviews and self‐report questionnaires concerning patients' QOL, pain, anxiety, mood, coping style and personality were administered to 35 patients with Stage I or II head and neck cancer before radiation therapy (week 0), and approximately one month (week 4) and two months (week 8) after starting of radiation. Anxiety, depression and pain were more severe at week 4 than at baseline. Anxiety was less at week 8, but depressive symptoms remained remarkable. Stepwise regression analyses revealed that changes in depressed mood and pain partially accounted for changes in disease‐specific QOL. General health QOL related to a premorbid personality of openness and an emotional aspect of a coping style. Therapeutic interventions including psychiatric management of depression and physical management of pain appear to be crucial for preserving QOL during radiation treatment of patients with head and neck cancer. Copyright © 2005 John Wiley & Sons, Ltd.
Olfactory Receptor Trafficking Involves Conserved Regulatory Steps*

Olfactory receptors are difficult to functionally express in heterologous cells. They are typically retained in the endoplasmic reticulum of cells commonly used for functional expression studies and are only released to the plasma membrane in mature cells of the olfactory receptor neuron lineage. A recently developed olfactory cell line, odora, traffics olfactory receptors to the plasma membrane when differentiated. We found that undifferentiatedodora cells do not traffic olfactory receptors to their surface, even though they release the receptors to the Golgi apparatus and endosomes. This behavior differs from other cell lines tested thus far. Differentiated odora cells also properly traffic vomeronasal receptors of the VN1 type, which lack sequence similarity to olfactory receptors. ODR-4, a protein that is necessary for plasma membrane trafficking of a chemosensory receptor in nematodes, facilitates trafficking of rat olfactory receptor U131 inodora and Chinese hamster ovary cells. Olfactory receptor trafficking from the endoplasmic reticulum to the plasma membrane involves at least two steps whose regulation depends on the maturation state of cells in the olfactory receptor neuron lineage. These results also indicate that some components of the regulatory mechanism are conserved.
Development of cultural psychiatry in China

The development of cultural psychiatry is reviewed at different stages historically in contemporary China during the past two and a half decades. Comments are made about the social, political, and professional reasons why the development of cultural psychiatry has been delayed, and what needs to be done to improve the situation in the near future, particularly to expand the concern from the minority issues to more broad aspects including how people need to adjust to the socio-cultural change, modernization, urbanization and internal migration.
Relation between magnetospheric state parameters and the occurrence of plasma depletion events in the nighttime midlatitude F region

[1] Studies using all-sky imagers have revealed the presence of various ionospheric irregularities in the nighttime midlatitude F region. The most prevalent and well known of these are the medium-scale traveling ionospheric disturbances (MSTIDs) that usually occur when the geomagnetic activity is low and midlatitude spread F plumes that are often observed when the geomagnetic activity is high. The inverse and direct relations between geomagnetic activity and the occurrence rate of MSTIDs and midlatitude plumes, respectively, have been observed by several studies using different instruments; however, most of them focus on MSTIDs only and use only Kp to characterize geomagnetic activity. In order to understand the underlying causes of these two relations and to distinguish between MSTIDs and plumes, it is illuminating to better characterize the occurrence of MSTIDs and plumes using multiple magnetospheric state parameters. Here we statistically compare multiple geomagnetic driver and response parameters (such as Kp, AE, Dst, and solar wind parameters) with the occurrence rates of nighttime MSTIDs and plumes observed using an all-sky imager at Arecibo Observatory (AO) between 2003 and 2008. We also present seasonal and annual variations of MSTIDs and plumes at AO. The results not only allow us to better distinguish MSTIDs and plumes, but also to shed further light on the generation mechanism and electrodynamics of these two different phenomena occurring at nighttime in the midlatitude F region.
Comparison of elective stenting of severe vs moderate intracranial atherosclerotic stenosis

Objective: To test whether symptomatic severe intracranial atherosclerotic stenosis was associated with a higher subsequent stroke risk than moderate stenosis after elective angioplasty with a balloon-expandable stent and to explore which factors were associated with the subsequent stroke. Methods: Between September 2001 and June 2005, there were 220 symptomatic intracranial atherosclerotic stenoses in 213 patients undergoing elective stenting at our institute. Of these stenoses, 126 in 121 patients were ≥70% severe stenoses, and 94 in 92 patients were 50% to 69% moderate stenoses. Primary endpoints included lesion-related ischemic stroke, and symptomatic brain or subarachnoid hemorrhage. Results: Ten primary endpoint events occurred in the severe stenosis group (six within 30 days and four in mean follow-up of 26.0 months after 30 days), and seven occurred in the moderate stenosis group (four within 30 days and three in mean follow-up of 27.6 months after 30 days). There was no significant difference in cumulative probability of primary endpoints between the severe (7.2% at 1 year and 8.2% at 2 years) and moderate (5.3% at 1 year and 8.3% at 2 years) stenosis groups. No single factor was found to be associated with primary endpoints in the moderate stenosis group. Multivariable analysis revealed that stent failure was the only predictor of primary endpoints in the severe stenosis group (hazard ratio 5.31, 95% CI 1.35 to 20.91). Conclusion: Symptomatic severe intracranial atherosclerotic stenosis did not present a higher subsequent stroke risk than moderate stenosis after elective angioplasty with a balloon-expandable stent. Patients with severe stenosis may benefit from successful stent placement, and randomized trials are necessary to demonstrate this possible benefit.
p120ctn Binds to the Membrane-proximal Region of the E-cadherin Cytoplasmic Domain and Is Involved in Modulation of Adhesion Activity*

Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Previously, we showed that the conserved membrane-proximal region of the E-cadherin cytoplasmic domain negatively regulates adhesion activity. In this report, we provide several lines of evidence that p120ctn is involved in this negative regulation. p120ctn binds to the membrane-proximal region of the nonfunctional carboxyl-terminally deleted E-cadherin protein. An additional internal deletion in this region prevented the association with p120ctn and activated the protein, as seen in an aggregation assay. Furthermore, the nonfunctional E-cadherin can be activated through coexpression of p120ctn proteins with amino-terminal deletions, which eliminate several potential serine/threonine phosphorylation sites but do not affect the ability to bind to cadherins. Finally, we show that staurosporine, a kinase inhibitor, induces an increased electrophoretic mobility of p120ctn bound to E-cadherin polypeptides, activates the nonfunctional E-cadherin protein, and converts the wild-type E-cadherin and an E-cadherin-α-catenin chimeric protein from a cytochalasin D-sensitive to a cytochalasin D-insensitive state. Together, these results indicate that p120ctn is a modulator of E-cadherin-mediated cell adhesion.
Detection of Enteric Viruses in Shellfish from the Norwegian Coast

ABSTRACT Common blue mussels (Mytilus edulis), horse mussels (Modiolus modiolus), and flat oysters (Ostrea edulis) obtained from various harvesting and commercial production sites along the Norwegian coast were screened for the presence of norovirus by a real-time reverse transcription (RT)-nested PCR assay and for possible indicators of fecal contamination, i.e., for F-specific RNA bacteriophages (F-RNA phages) by plaque assay and for human adenoviruses and human circoviruses by nested PCR assay. The aims were to obtain relevant information for assessing the risk of transmission of enteric viruses by shellfish and to investigate the potential of various indicator viruses in routine screening. Noroviruses were detected in 6.8% of the samples, and the indicators were detected in 23.8% (F-RNA phages), 18.6% (adenoviruses), and 8.0% (circoviruses) of the samples. A seasonal variation was observed, with the exception of circoviruses, with more positive samples in the winter. A positive correlation was found between F-RNA phages and noroviruses. However, F-RNA phages were present in only 43% of the norovirus-positive samples. The results show that mussels from the Norwegian coast can constitute a risk of infection with enteric viruses and that routine testing of samples may be justified. Advantages and disadvantages of various options for screening are discussed.
Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels.

1. We used the tested fiber method to record from single myelinated afferents axons ending in a chronic nerve injury site (neuroma) in the rat sciatic nerve or L4,5 dorsal root. Axons were chosen for study that fired spontaneously with a stable tonic or interrupted (bursty) autorhythmic firing pattern. 2. Agents that block voltage-sensitive Na+ channels [tetrodotoxin (TTX), lidocaine], voltage-sensitive Ca2+ channels (Cd2+, Co2+, Ni2+, verapamil, D600, nifedipine, and fluarizine), volt-age-sensitive K+ channels [tetraethylammonium (TEA), 4-aminopyridine (4-AP)], and Ca(2+)-activated K+ channels (gK+Ca2+;quinidine, apamine) were applied topically to the neuroma. Effects on baseline rhythmogenesis and on the duty cycle of bursting were documented. Spike pattern analysis was used to determine whether changes in firing frequency were associated with changes in impulse initiation (electrogenesis), or resulted from (partial) block of impulse propagation downstream from the site of electrogenesis. Effects of veratridine were also noted. 3. Na+ channel blockers consistently quenched neuroma firing, and they did so by suppressing the process of impulse initiation. Only rarely was propagation block the dominant process. In bursty fibers the duration of on-periods shortened as the duration of off-periods lengthened, without a significant change in the baseline interspike interval (ISI). Veratridine accelerated firing, also via the impulse generating process. 4. Ca2+ channel blockers had essentially no effect on baseline firing rate (i.e., ISI). 5. Ca2+ channel blockers, as well as blockers of gK+Ca2+, had substantial, but inconsistent effects on burst pattern. It is not clear whether this reflects variability in the experimental conditions, or heterogeneity among the fibers sampled. 6. Blockade of K+ channels failed to evoke rhythmogenesis in acutely cut axons as it does in chronically injured axons, even in the presence of veratridine. This is consistent with other evidence that ectopic neuroma firing depends on postinjury remodeling of membrane electrical properties. 7. The data indicate that, in chronically injured axons, the inward currents that underly electrogenicity, enable ectopic discharge, and, together with outward K+ currents, set the fundamental firing rhythm (ISI), operate primarily with the use of voltage-sensitive Na+ rather than Ca2+ channels. 8. The on-off duty cycle in bursty fibers was affected by Na+ channel ligands and also, although less so, and less consistently by, Ca2+ channel ligands. This indicates that both may play a role in the slow modulations of membrane potential that presumably underly interrupted autorhythmicity.
Magnetic signal processing & analysis for airfield traffic surveillance

This paper presents an innovative system for airport surface surveillance based on a novel magnetic sensing technology. Ferromagnetic objects such as vehicle motors, aircraft engines, and landing gears are detected through their deformation of the Earth's magnetic field. Tests have shown that although the local changes of the Earth's magnetic field are extremely small, the proposed sensing technology is able to detect them reliably. The primary objective of the proposed approach is to provide a complementary surveillance system for existing and future Advanced Surface Movement Guidance and Control Systems (A-SMGCS) at large airports or a cost-effective surveillance solution for monitoring critical areas at medium and small airports. Unaffected by weather conditions, interference and shadowing effects, the system provides reliable position, velocity, and direction information without requiring any equipment in aircraft or ground vehicles. The outcome of a comprehensive market analysis is discussed and test results under real life conditions at two airports are evaluated analytically.
IIIIPIP ^ PIIBipilBPPHilBBBililP for Improved Generalization in Artificial Neural Networks DISSERTATION

When training an artificial neural network (ANN) for classification using backpropagation of error, the weights are usually updated by minimizing the sum-squared error on the training set. As training ensues, overtraining may be observed as the network begins to memorize the training data. This occurs because, as the magnitude of the weight vector, ||w||, grows, the decision boundaries become overly complex in much the same way as a too-high order polynomial approximation can overfit a data set in a regression problem. Since ||w|| grows during standard backpropagation, it is important to initialize the weights with consideration to the importance of the weight vector magnitude, ||w||. With this in mind, the expected value of the magnitude of the initial weight vector is here derived for the separate cases of each weight drawn from a normal or uniform distribution. The usefulness of this derivation is universal since the magnitude of the weight vector plays such an important role in the formation of the classification boundaries. When the network overtrains on the training data, it will not exhibit consistently low error on subsequent test data. One way to overcome this overtraining problem is to stop the training early, which limits the magnitude of the weight vector below what it would be if the training were allowed to continue until a near-global training error minimum were found. The question then is when to stop the training. Here, the relationship between training data set size and the magnitude of the weight vector providing good generalization results is empirically established using crossvalidational analysis on small subsets of the training data. These results are then used to estimate at what weight vector magnitude the training should be stopped when using the full data set. The general classification ability of an ANN trained in this manner is shown to increase the percentage of correctly classified test data points by an average of 1.5% over that of one trained using true cross-validational early stopping on a smaller data set. The technique of hyperspherical backpropagation, which entails training at a set weight vector magnitude, is also introduced and shown to be useful in lowering the validation error during training. Table of
Bone Morphogenetic Proteins in Spinal Surgery: What Is the Fusion Rate and Do They Cause Cancer?

Study Design. A retrospective cohort study. Objective. The aim of this study was to determine the fusion rate using recombinant human bone morphogenetic protein (rhBMP) in spinal surgery and to estimate the risk of cancer subsequent to their use. Summary of Background Data. rhBMP may obviate the need for iliac crest bone graft harvest and provides similar or higher fusion rates than autologous bone graft. Recently, there are concerns that rhBMPs may either cause cancer or accelerate progression. Methods. Patients were treated by 2 spine surgeons between 2002 and 2012. Inclusion criteria were patients who resided in the state of Victoria, Australia, undergoing lumbar fusion (anterior, lateral, posterior, and posterolateral) with rhBMP [either rhBMP‐2 (Infuse) or rhBMP‐7 (OP‐1)]. Exclusion criteria were patients who reported having an invasive cancer diagnosis before the spinal fusion procedure. The occurrence of incident cancers was obtained from record linkage to the Victorian Cancer Registry. Results. A total of 527 patients were included in the cohort, with a mean follow‐up of 4.4 years (1.8–11.5). Patients received Infuse in 77% of cases and OP‐1 in 23%. The mean Infuse does was 10.2 mg (2.5–48.0) and 3.3 mg (1.7–6.6) for OP‐1. There was no significant difference in fusion rates between Infuse (90.1%) and OP‐1 (91.9%) (P = 0.42). The overall success of interbody fusion with rhBMP was 93.5% at 12 months. Twenty‐seven patients were diagnosed with an invasive cancer since treatment (20 Infuse and 7 OP‐1 patients). Comparing the observed numbers in our study cohort with those expected on the basis of the Victorian population's age and sex‐specific rates, we observed that the study cohort was not at a significantly increased risk of cancer. The standardized incidence ratio for cancer overall (of any type) was 0.84 [95% confidence interval (95% CI) 0.56–1.21]. Conclusion. Off‐label use of rhBMP provided high fusion rates with no evidence of a significantly increased risk of cancer. Level of Evidence: 4