Miracle-dz/UniFAR-FTUs huggingface dataset:
DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis.

OBJECTIVES The influenza virus (IFV) infection models commonly used to evaluate antiviral agents (e.g. MDCK cell line and mice) are limited by physiological differences from the human respiratory tract in vivo. Here we report the pharmacodynamics of DAS181, a sialidase fusion protein that inhibits influenza infection, in the model systems of well-defined human airway epithelium (HAE) culture and ex vivo culture of fresh human bronchial tissue, both of which are close mimics of the human respiratory tract in vivo. METHODS HAE culture and ex vivo human bronchi were used to evaluate the sialic acid removal and regeneration efficiency and IFV inhibition after various DAS181 treatment levels and regimens. RESULTS DAS181 effectively desialylates HAE cultures and ex vivo bronchi tissues and therefore potently inhibits replication of different IFV strains. The treatment effect of DAS181 occurs immediately upon application to the epithelial surface and is unaffected by the respiratory mucus. In both HAE and human bronchial tissue, the inhibitory effect of DAS181 treatment lasts for at least 2 days. Approximately 80% epithelial surface desialylation and significant anti-IFV efficacy can be achieved at topical concentrations of DAS181 in the range of 5-10 microg/cm(2) when applied once daily. An additional treatment or a higher loading dose of DAS181 on the first day provides significant additional treatment benefit. Comparing the effect of DAS181 versus its two analogues, DAS180 and DAS185, has confirmed that sialidase function is critical for DAS181, and the cell-binding domain (amphiregulin tag) prolongs DAS181 retention and potentiates its function. CONCLUSIONS These results provide valuable insights into DAS181 treatment dose and potential regimens in the clinical setting.
Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. METHODS. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. RESULTS. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti–type VII collagen autoantibodies in patients’ blood or skin. CONCLUSION. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. TRIAL REGISTRATION. ClinicalTrials.gov NCT02698735. FUNDING. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and VA Merit Award.
Improved Detection of Apoptotic Cells in Archival Paraffin Sections: Immunohistochemistry Using Antibodies to Cleaved Caspase 3

Apoptosis has gained central importance in the study of many biological processes, including neoplasia, neurodegenerative diseases, and development. One of the limitations of many studies is the difficulty of specifically identifying individual apoptotic cells. Of the many specific methods developed to detect apoptotic cells, most are not applicable to histological sections of archival paraffin-embedded tissues. Recently, advances in the understanding of the molecular events in apoptosis have led to the realization that caspase activation is by far the most specific indicator of this cell suicide mechanism. Several publications have reported the development of antibodies directed at neoepitopes that are generated in various substrates through the action of caspases. One of these is that present on activated caspase 3, a ubiquitously distributed caspase that is a main effector caspase of the apoptotic cascade within cells. This study demonstrates the utility of using a recently commercially available antibody to cleaved caspase 3 in archival paraffin sections, suggesting that this may be a highly specific and sensitive method generally applicable to many studies of archival material.
Linear equations, arithmetic progressions and hypergraph property testing

For a fixed <i>k</i>-uniform hypergraph <i>D</i> (<i>k</i>-graph for short, <i>k</i> ≥ 3), we say that a <i>k</i>-graph <i>H</i> satisfies property <i>P<inf>D</inf></i> (resp. <i>P</i>*<i><inf>D</inf></i>) if it contains no copy (resp. induced copy) of <i>D. </i> Our goal in this paper is to classify the <i>k</i>-graphs <i>D</i> for which there are property-testers for testing <i>P<inf>D</inf></i> and <i>P</i>*<i><inf>D</inf></i> whose query complexity is polynomial in 1/ε. For such <i>k</i>-graphs, we say that <i>P<inf>D</inf></i> (or <i>P</i>*<i><inf>D</inf></i>) is <i>easily testable. </i>For <i>P*<inf>D</inf></i>, we prove that aside from a single 3-graph, <i>P*<inf>D</inf></i> is easily testable <b>if and only if</b> <i>D</i> is a single <i>k</i>-edge. For large <i>k</i>, we obtain stronger lower bounds than those obtained for the general case on the query complexity of testing <i>P*<inf>D</inf></i> for any <i>D</i> other than the single <i>k</i>-edge. These bounds are proved by applying a more sophisticated technique than the basic one that works for all <i>k. </i> These results extend and improve previous results about graphs [5] and <i>k</i>-graphs [18]. For <i>P<inf>D,</inf></i> we show that for any <i>k</i>-partite <i>k-</i>graph <i>D</i>, <i>P<inf>D,</inf></i> is easily testable, by giving an efficient one-sided error-property tester, which improves the one obtained by [18]. We further prove a nearly matching lower bound on the query complexity of such a property-tester. Finally, we give a sufficient condition for inferring that <i>P<inf>D</inf></i> is not easily testable. Though our results do not supply a complete characterization of the <i>k</i>-graphs for which <i>P<inf>D</inf></i> is easily testable, they are a natural extension of the previous results about graphs [1]. Our proofs combine results and arguments from additive number theory, linear algebra and extremal hypergraph theory. We also develop new techniques, which are of independent interest. The first is a construction of a dense set of integers, which does not contain a subset that satisfies a certain set of linear equations. The second is an algebraic construction of certain extremal hypergraphs. We demonstrate the applicability of this last construction by resolving several cases of an open problem raised by Brown, Erdös and Sós in 1973. These two techniques have already been applied in two recent subsequent papers [6], [27].
SoftCache: A Technique for Power and Area Reduction in Embedded Systems

Explicitly software managed cache systems are postulated as a solution for power considerations in computing devices. The savings expected in a SoftCache lies in the removal of tag storage, associativity logic, comparators, and other hardware dedicated to memory hierarchies. The penalty lies in high cache-miss cost and additional instructions required to effect a cache model. In this paper, we characterize SoftCaches by placing them in the overall computing landscape, analyzing the energy and space tradeoffs. We present results that indicate a SoftCache saves power and space over hardware caches. Based on the TSMC 0.25 m process from MOSIS, we use schematic and layout representations of hardware and SoftCache models for comparison. Accounting for additional instructions executed and simplification of logic, we examine high SoftCache miss cost in relation to the overall system. For a 256KB “mode” change every 1.45 hours, the SoftCache exhibits 1% application slowdown for energy savings of 30% or more in a low-power device such as the SA-110 microprocessor used in PocketPC platforms.
The Relationship between Wage Growth and Wage Levels

We estimate the covariance between the permanent component of wages and a random coefficient on experience in models both with potential experience and with actual experience. Actual experience is allowed to be arbitrarily correlated with both the permanent component of wages and the random component on experience. We find no evidence that workers of higher ability experience faster wage growth. Our point estimates suggest that a worker with a one standard deviation higher level of permanent ability would have a return to annual potential experience that is 0.61 of a percentage point lower. The analogous point estimate for actual experience is 0.87 of a point lower. Contrary to the popular perception, wage growth among low-skill workers appears to be at least as high as that for a medium-skilled worker. Copyright © 2009 John Wiley & Sons, Ltd.
Visual tracking for Augmented Reality

Localization of mobile devices is an essential task in Augmented Reality and has therefore been an active research topic for many years. Typically, indoor tracking approaches, such as methods based on infrared or ultra-wide-band, require preparations of the environment and special hardware sensors. Conversely, image feature tracking approaches can provide orientation estimates without special tracking hardware installations. With the advent of mobile devices equipped with sensors such as digital cameras, image based localization gains importance in Augmented Reality. Typically, fiducial marker tracking was considered as a standard image based localization method. We propose the use of natural image feature based tracking methods, which are a generalization of the same principals but do not require the presence of fiducial tracking targets.
Matrix Robustness, with an Application to Power System Observability

We initiate the study of the computational complexity of Matrix Robustness: Check whether deleting any k rows from a full-rank matrix does not change the matrix rank. This problem is motivated by applications in observability analysis of electrical power networks. We indicate the coNP-completeness of Matrix Robust- ness, provide linear programming based solutions (both exact and heuristic) and a problem-specific algorithm, and present encouraging experimental results.
Consensus shapes: an alternative to the Sankoff algorithm for RNA consensus structure prediction

MOTIVATION The well-known Sankoff algorithm for simultaneous RNA sequence alignment and folding is currently considered an ideal, but computationally over-expensive method. Available tools implement this algorithm under various pragmatic restrictions. They are still expensive to use, and it is difficult to judge if the moderate quality of results is because of the underlying model or to its imperfect implementation. RESULTS We propose to redefine the consensus structure prediction problem in a way that does not imply a multiple sequence alignment step. For a family of RNA sequences, our method explicitly and independently enumerates the near-optimal abstract shape space, and predicts as the consensus an abstract shape common to all sequences. For each sequence, it delivers the thermodynamically best structure which has this common shape. Since the shape space is much smaller than the structure space, and identification of common shapes can be done in linear time (in the number of shapes considered), the method is essentially linear in the number of sequences. Our evaluation shows that the new method compares favorably with available alternatives. AVAILABILITY The new method has been implemented in the program RNAcast and is available on the Bielefeld Bioinformatics Server. CONTACT jreeder@TechFak.Uni-Bielefeld.DE, robert@TechFak.Uni-Bielefeld.DE SUPPLEMENTARY INFORMATION: Available at http://bibiserv.techfak. uni-bielefeld.de/rnacast/supplementary.html
QCRI at IWSLT 2013: experiments in Arabic-English and English-Arabic spoken language translation

We describe the Arabic-English and English-Arabic statistical machine translation systems developed by the Qatar Computing Research Institute for the IWSLT’2013 evaluation campaign on spoken language translation. We used one phrase-based and two hierarchical decoders, exploring various settings thereof. We further experimented with three domain adaptation methods, and with various Arabic word segmentation schemes. Combining the output of several systems yielded a gain of up to 3.4 BLEU points over the baseline. Here we also describe a specialized normalization scheme for evaluating Arabic output, which was adopted for the IWSLT’2013 evaluation campaign.
An optimal control approach to robust control of nonlinear spacecraft rendezvous system with θ-D technique

In this paper, a new optimal robust control design approach is proposed for the task of spacecraft rendezvous such that both the stabilization and optimal performance are achieved. An approximate closed-form solution to the nonlinear optimal control problem is obtained by employing the θ-D technique, which is derived based on an approximate solution to the Hamilton-Jacobi-Bellman equation obtained via a perturbation technique. This approach provides a simple design procedure, and the feedback control law obtained is easy for on-board implementation. The effectiveness of the proposed approach is demonstrated through simulation studies.
Practice Makes the Difference: The Effect of Rate-Building and Rate-Controlled Practice on Retention

Six home-schooled students and one adult participant each initially practiced to accuracy two decks of five previously unknown multiplication facts. The decks were yoked for practice and reinforcement. Once accurate performance was achieved, overpractice was undertaken using custom computer software that allowed either fast (free-operant) or rate-controlled responding. Rate-building practice, to an established fluency performance standard, was used with one deck while practice with the other deck was rate-controlled. The number of times a fact was practiced was the same for both methods. Response rate and accuracy was assessed after training to accuracy, at the end of overpractice and after 4and 8-weeks of no practice. The assessment at the end of rate-building confirmed that rate-building resulted in fast and accurate responding. It also confirmed that, for the rate-controlled facts, response rates did not meet the fluency performance standard. However, the 4and 8-week retention assessments showed no consistent differences in accuracy or response rate between the rate-controlled and rate-built decks. After 8 weeks without practice, performance on the rate-built deck was not significantly different to that prior to rate-building. These results suggest that practice to fluency does not lead to superior retention when compared to the same amount of rate-controlled practice. The results also indicate that when a skill is practiced to fluency, a period without practice leads to deterioration, to pre-rate-building levels, of accuracy and response rate. This study highlights the need for research examining the role of maintenance in the effectiveness of fluency based learning like Precision Teaching.
An Estrogen Model: The Relationship between Body Mass Index, Menopausal Status, Estrogen Replacement Therapy, and Breast Cancer Risk

We present a mathematical model that lends support to the hypothesis that estrogen levels mediate the complex relationship between body mass index (BMI), menopausal status, estrogen-only hormone replacement therapy (HRT), and breast cancer risk. The model predicts a decrease in the relative risk of breast cancer of 3% per unit increase in BMI (kg/m2) for premenopausal women and an increase in the relative risk of 4% per unit increase in BMI for postmenopausal women who are not HRT users. When comparing postmenopausal women who use estrogen-only HRT to postmenopausal women who do not use HRT, the model predicts an increased risk of breast cancer associated with use of estrogen that diminishes with increasing BMI, with a relative risk of 1.6 for women with BMI of 18, 1.2 for women with BMI of 25, and 1.0 for women with BMI ≥ 30. Model predictions agree with data from five major epidemiological studies.
Molecular Plasticity in the Rat Auditory Brainstem: Modulation of Expression and Distribution of Phosphoserine, Phospho-CREB and TrkB after Noise Trauma

We induced acoustic trauma by applying click stimuli of 130 dB (SPL) for 30 min to one ear of adult rats. This treatment resulted in an instant and permanent threshold shift of 96 dB in the affected ear. A massive reduction of cochlear nerve fibers in the ventral cochlear nucleus (VCN) was demonstrated by tracing them from the cochlea of rats that survived acoustic overstimulation for 1 year or longer. In the auditory brainstem, we observed a deprivation-dependent appearance of fibers positive for tyrosine receptor kinase B in the ipsilateral VCN between day 3 and day 21 after trauma and an increase in phosphoserine immunostaining in the neuropil of the ipsilateral VCN and in neurons of the contralateral lateral superior olive during the first 30 days after trauma. Immunoreactivity for the cAMP response element binding protein in its phosphorylated form was transiently depressed in the ipsilateral inferior colliculus immediately after trauma and was elevated as late as 7 months after trauma in the ipsilateral VCN. Apparently, a unilateral acoustic overstimulation entails specific regulations of the activity of plasticity-associated molecules through phosphorylation and includes changes to neurotrophin signaling between neurons of the auditory brainstem.
Animal models in addiction research

Recently, various addiction problems have spread in the world, and the situation is growing serious. Addiction is a condition that results when individuals ingest an addictive substance or perform a specific action that can be pleasurable but the continuous use or act of which becomes compulsive and interferes with ordinary life responsibilities. It is very important to clarify the mechanisms underlying addiction, but there are still many unclear points. Animal studies have been crucial in understanding the biology and pathophysiology of drug addiction. In recent years, although self-administration tests and conditioned place preference tests have been widely used as drug-dependence evaluation methods, intracranial self-stimulation (ICSS) method that electrically stimulate the medial forebrain bundle (lateral hypothalamic region) of the mesolimbic dopamine system could be also useful tools that can provide different insights in drug dependency assessment. In this symposium, we would like to discuss the advantage and disadvantage of ICSS method in drug dependence research and reward-system neural network analysis, in light of previous research and recent trends using the ICSS method. Young Scientists Symposium1
Nitrogen Eosinophils for Generating Reactive Characterization of Pathways Available to Oxide-Derived Oxidants in Severe Asthma: Eosinophils Are a Major Source of Nitric

Eosinophil recruitment and enhanced production of NO are characteristic features of asthma. However, neither the ability of eosinophils to generate NO-derived oxidants nor their role in nitration of targets during asthma is established. Using gas chro-matography-mass spectrometry we demonstrate a 10-fold increase in 3-nitrotyrosine (NO 2 Y) content, a global marker of protein modiﬁcation by reactive nitrogen species, in proteins recovered from bronchoalveolar lavage of severe asthmatic patients (480 6 198 m mol/mol tyrosine; n 5 11) compared with nonasthmatic subjects (52.5 6 40.7 m mol/mol tyrosine; n 5 12). Parallel gas chromatography-mass spectrometry analyses of bronchoalveolar lavage proteins for 3-bromotyrosine (BrY) and 3-chlorotyrosine (ClY), selective markers of eosinophil peroxidase (EPO)- and myeloperoxidase-catalyzed oxidation, respectively, demonstrated a dramatic preferential formation of BrY in asthmatic (1093 6 457 m mol BrY/mol tyrosine; 161 6 88 m mol ClY/mol tyrosine; n 5 11 each) compared with nonasthmatic subjects (13 6 14.5 m mol BrY/mol tyrosine; 65 6 69 m mol ClY/mol tyrosine; n 5 12 each). Bronchial tissue from individuals who died of asthma demonstrated the most intense anti-NO 2 Y immunostaining in epitopes that colocalized with eosinophils. Although eosinophils from normal subjects failed to generate detectable levels of NO, NO 2 2 , NO 3 2 , or NO 2 Y, tyrosine nitration was promoted by eosinophils activated either in the presence of physiological levels of NO 2 2 or an exogenous NO source. At low, but not high (e.g., > 2 m M/min), rates of NO ﬂux, EPO inhibitors and catalase markedly attenuated aromatic nitration. These results identify eosinophils as a major source of oxidants during asthma. They also demonstrate that eosinophils use distinct mechanisms for generating NO-derived oxidants and identify EPO as an enzymatic source of nitrating intermediates in eosinophils. The Journal of Immunology, 2001, 166: 5763–5772. than neutrophils at promoting aromatic nitration reactions
Neuroprotective Effects of Vanillyl Alcohol in Gastrodia elata Blume Through Suppression of Oxidative Stress and Anti-Apoptotic Activity in Toxin-Induced Dopaminergic MN9D Cells

Gastrodia elata Blume (GE) has long been used in oriental countries as a traditional herbal medicine to relieve symptoms associated with neurological ailments such as vertigo, general paralysis and epilepsy. In this study, we have investigated the effects of GE extracts and its major bioactive components on 1-methyl-4-phenylpyridinium (MPP+)-treated MN9D dopaminergic cells, a classic in vitro model for Parkinson’s disease (PD). We found that vanillyl alcohol effectively inhibited the cytotoxicity and improved cell viability in MPP+-induced MN9D dopaminergic cells. The underlying mechanisms of vanillyl alcohol action were also studied. Vanillyl alcohol attenuated the elevation of reactive oxygen species (ROS) levels, decreased in the Bax/Bcl-2 ratio and poly (ADP-ribose) polymerase proteolysis. These results indicate that vanillyl alcohol protected dopaminergic MN9D cells against MPP+-induced apoptosis by relieving oxidative stress and modulating the apoptotic process and is therefore a potential candidate for treatment of neurodegenerative diseases such as Parkinson’s disease.