Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantification of Hox and Surfactant Protein-B Transcription during Murine Lung Development

Background: Genetic processes underlying fetal lung development and maturation are incompletely understood. Better knowledge of these processes would provide insights into the causes of lung malformations and prevention of respiratory distress syndrome and the potential adverse effects of glucocorticoids. Hox genes are involved in the lung branching morphogenesis and maturation of respiratory epithelium, but their expression pattern remains to be defined. Objectives: We hypothesized that genes involved in lung branching would be downregulated during early development, whereas those involved in maturation would be unchanged or upregulated. Methods: TaqMan real-time primers and probes were designed for all 39 murine Hox genes, and the murine SP-B gene and transcription profiles of these genes were obtained from whole lungs isolated at e14.5, e16.5, e18.5, e19.5 and postnatal days 1 and 20. Results:Hox genes in clusters A and B, specifically those between paralog groups 3 and 7, were the most represented, with Hoxa4 and Hoxa5 being the most highly transcribed. A wave of reduced transcription in 16 Hox genes, coincident with increased SP-B transcription, was observed with advancing gestation. Consistently high transcription of Hoxa5 from e14.5 to postnatal day 20 may indicate that sustained transcription is required for normal lung maturation. When e15.5 lungs were cultured with dexamethasone, Hoxb6, Hoxb7 and Hoxb8 levels were significantly upregulated, creating the potential for modulation of diverse downstream target genes. Conclusions: Improved understanding of the genetic processes underlying lung development afforded by our Q-PCR platform may allow development of more specific methods for inducing fetal lung maturation.
Lentiviral-Mediated Delivery of Mutant Huntingtin in the Striatum of Rats Induces a Selective Neuropathology Modulated by Polyglutamine Repeat Size, Huntingtin Expression Levels, and Protein Length

A new strategy based on lentiviral-mediated delivery of mutant huntingtin (htt) was used to create a genetic model of Huntington's disease (HD) in rats and to assess the relative contribution of polyglutamine (CAG) repeat size, htt expression levels, and protein length on the onset and specificity of the pathology. Lentiviral vectors coding for the first 171, 853, and 1520 amino acids of wild-type (19 CAG) or mutant htt (44, 66, and 82 CAG) driven by either the phosphoglycerate kinase 1 (PGK) or the cytomegalovirus (CMV) promoters were injected in rat striatum. A progressive pathology characterized by sequential appearance of ubiquitinated htt aggregates, loss of dopamine- and cAMP-regulated phosphoprotein of 32 kDa staining, and cell death was observed over 6 months with mutant htt. Earlier onset and more severe pathology occurred with shorter fragments, longer CAG repeats, and higher expression levels. Interestingly, the aggregates were predominantly located in the nucleus of PGK-htt171-injected rats, whereas they were present in both the nucleus and processes of CMV-htt171-injected animals expressing lower transgene levels. Finally, a selective sparing of interneurons was observed in animals injected with vectors expressing mutant htt. These data demonstrate that lentiviral-mediated expression of mutant htt provides a robust in vivo genetic model for selective neural degeneration that will facilitate future studies on the pathogenesis of cell death and experimental therapeutics for HD.
CFR-Working Paper NO . 06-04 Liquidity Commonality Beyond Best Prices

This paper investigates the commonality of liquidity in an open limit order book market. We find that commonality in liquidity becomes stronger the deeper we look into the limit order book. While commonality is only about 2% at the best prices, it increases up to about 20% inside the limit order book. Furthermore, we find strong time variation in commonality both on an intradaily basis and with the movement of the market return. Our study thus suggests that previous estimates of commonality do not hold for liquidity beyond best prices. Therefore, systematic liquidity risk in a limit order book market is much higher than previous evidence implies.
The leading edge during dorsal closure as a model for epithelial plasticity: Pak is required for recruitment of the Scribble complex and septate junction formation

Dorsal closure (DC) of the Drosophila embryo is a model for the study of wound healing and developmental epithelial fusions, and involves the sealing of a hole in the epidermis through the migration of the epidermal flanks over the tissue occupying the hole, the amnioserosa. During DC, the cells at the edge of the migrating epidermis extend Rac- and Cdc42-dependent actin-based lamellipodia and filopodia from their leading edge (LE), which exhibits a breakdown in apicobasal polarity as adhesions are severed with the neighbouring amnioserosa cells. Studies using mammalian cells have demonstrated that Scribble (Scrib), an important determinant of apicobasal polarity that functions in a protein complex, controls polarized cell migration through recruitment of Rac, Cdc42 and the serine/threonine kinase Pak, an effector for Rac and Cdc42, to the LE. We have used DC and the follicular epithelium to study the relationship between Pak and the Scrib complex at epithelial membranes undergoing changes in apicobasal polarity and adhesion during development. We propose that, during DC, the LE membrane undergoes an epithelial-to-mesenchymal-like transition to initiate epithelial sheet migration, followed by a mesenchymal-to-epithelial-like transition as the epithelial sheets meet up and restore cell-cell adhesion. This latter event requires integrin-localized Pak, which recruits the Scrib complex in septate junction formation. We conclude that there are bidirectional interactions between Pak and the Scrib complex modulating epithelial plasticity. Scrib can recruit Pak to the LE for polarized cell migration but, as migratory cells meet up, Pak can recruit the Scrib complex to restore apicobasal polarity and cell-cell adhesion.
Comparison of needle core biopsy and fine-needle aspiration for diagnostic accuracy in musculoskeletal lesions.

CONTEXT Needle core biopsy has been reported to be the choice of biopsy for musculoskeletal tumors. Fine-needle aspiration, on the other hand, has been widely accepted for nonmusculoskeletal tumors, but is only used in selected medical centers for musculoskeletal tumors. While fine-needle aspiration appears to have advantages to needle core biopsy in the aspects of simplicity and cost, the diagnostic accuracy should be the most critical parameter in determining the choice of biopsy. However, few studies comparing the diagnostic accuracy of these 2 biopsy methods have been performed. OBJECTIVE This study was designed to compare the diagnostic accuracy of fine-needle aspiration and needle core biopsy in musculoskeletal tumors. DESIGN Prospective study was performed in patients aged 10 years or older. Diagnostic accuracy was compared in 50 consecutive concurrent needle core biopsies and fine-needle aspirations of musculoskeletal lesions. RESULTS For primary musculoskeletal lesions, fine-needle aspiration achieved a diagnostic accuracy rate of 88% for nature of lesion, 64% for specific diagnosis, 78% for histologic grading, and 74% for histologic typing. Needle core biopsy achieved an accuracy rate of 93% for nature of lesions, 83% for specific diagnosis, 83% for histologic grading, and 90% for histologic typing. Both biopsy methods have a higher diagnostic accuracy rate for high-grade tumors than for low-grade or benign lesions in determining the nature, specific diagnosis, and histologic grading. CONCLUSIONS The needle core biopsy has a higher diagnostic accuracy than fine-needle aspiration in all aspects, including determining the nature of the tumor, establishing the histologic type and grade, and achieving a specific diagnosis.
Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Recurrence is one of the major causes of high mortality in ovarian cancer. However, the mechanism of ovarian cancer recurrence after chemotherapy has not been fully understood. In the present study, we investigated the effect of chemotherapy-induced tumor microenvironment on the proliferation of SKOV3 cells. We have shown that SKOV3 cells repopulated faster in the culture medium from apoptotic SKOV3 ovarian cancer cells after 24 h of etoposide phosphate (VP-16) treatment. We found that during apoptosis, cleaved caspase 3 could activate cytosolic calcium-independent phospholipase A2, which stimulated the release of arachidonic acid (AA) and triggered the production of prostaglandin E2 (PGE2). An increased level of phosphorylated focal adhesion kinase (FAK) subsequently facilitated the reproliferation of SKOV3 cells, and VP-16-induced repopulation effects were partially reversed by the FAK inhibitor PF562271. Furthermore, the plasma AA-to-PGE2 ratio and tumoral FAK expression of ovarian cancer patients after chemotherapy were significantly lower than those before chemotherapy. Taken together, our results indicate that chemotherapy-induced apoptotic cancer cells can produce PGE2-enriched microenvironment through caspase 3-mediated AA metabolic pathway, which could lead to the abnormal activation of FAK and eventually accelerate the repopulation of SKOV3 cells. Our study provides novel insight into a mechanism that may be utilized to prevent ovarian cancer recurrence in response to chemotherapy.
Force Application During Cochlear Implant Insertion: An Analysis for Improvement of Surgeon Technique

Highly invasive surgical procedures, such as the implantation of a prosthetic device, require correct force delivery to achieve desirable outcomes and minimize trauma induced during the operation. Improvement in surgeon technique can reduce the chances of excessive force application and lead to optimal placement of the electrode array. The fundamental factors that affect the degree of success for cochlear implant recipients are identified through empirical methods. Insertion studies are performed to assess force administration and electrode trajectories during implantations of the Nucleusreg 24 Contourtrade and Nucleusreg 24 Contour Advancetrade electrodes into a synthetic model of the human Scala Tympani, using associated methods. Results confirm that the advance off- stylet insertion of the soft-tipped contour advance electrode gives an overall reduction in insertion force. Analysis of force delivery and electrode positioning during cochlear implantation can help identify and control key factors for improvement of insertion method. Based on the findings, suggestions are made to enhance surgeon technique.
Capacity Achieving Peak Power Limited Probability Measures: Sufficient Conditions for Finite Discreteness

The problem of capacity achieving (optimal) input probability measures has been widely investigated for several channel models with constrained inputs. So far, no outstanding generalizations have been derived. This paper does a forward step in this direction, by introducing a set of new requirements, for the class of real scalar conditional output probability measures, under which the optimal input probability measure is shown to be discrete with a finite number of probability mass points, when peak power limited.
Aripiprazole for schizophrenia

Background Aripiprazole is an atypical antipsychotic that is reported to be effective in the treatment of schizophrenia. Aims To investigate the effects of aripiprazole on patients with schizophrenia and schizophrenia-like psychoses by conducting a systematic review of randomised controlled trials (RCTs). Method Database and manual searches and direct contact were used to identify relevant RCTs. Results We included 10 randomised controlled studies (involving a total of 4125 patients), but study attrition was large and the standard of data reporting was poor. Compared with placebo, aripiprazole treatment was associated with a significant decrease in relapse rates, increased compliance with the study protocol, and a decrease in prolactin levels below the expected values. Compared with risperidone, aripiprazole caused less elevation of prolactin levels and less prolongation of the average QTc interval. Conclusions Aripiprazole has been licensed despite the fact that few reliable data on this drug are publicly available. It may be effective for treatment of schizophrenia, but in terms of tolerability and global outcomes it shows little difference from existing antipsychotics.
Understanding Parkinsonian Handwriting Through a Computational Model of Basal Ganglia

Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease.
Myosins Move Speci fi c Organelles in Pollen Tubes and Are Required for Normal Fertility and Pollen Tube Growth in Arabidopsis 1 [ OPEN ]

Pollen tube growth is an essential aspect of plant reproduction because it is the mechanism through which nonmotile sperm cells are delivered to ovules, thus allowing fertilization to occur. A pollen tube is a single cell that only grows at the tip, and this tip growth has been shown to depend on actin filaments. It is generally assumed that myosin-driven movements along these actin filaments are required to sustain the high growth rates of pollen tubes. We tested this conjecture by examining seed set, pollen fitness, and pollen tube growth for knockout mutants of five of the six myosin XI genes expressed in pollen of Arabidopsis (Arabidopsis thaliana). Single mutants had little or no reduction in overall fertility, whereas double mutants of highly similar pollen myosins had greater defects in pollen tube growth. In particular, myo11c1 myo11c2 pollen tubes grew more slowly than wild-type pollen tubes, which resulted in reduced fitness compared with the wild type and a drastic reduction in seed set. Golgi stack and peroxisome movements were also significantly reduced, and actin filaments were less organized in myo11c1 myo11c2 pollen tubes. Interestingly, the movement of yellow fluorescent protein-RabA4d-labeled vesicles and their accumulation at pollen tube tips were not affected in the myo11c1 myo11c2 double mutant, demonstrating functional specialization among myosin isoforms. We conclude that class XI myosins are required for organelle motility, actin organization, and optimal growth of pollen tubes.
Micro-scale finite element analysis of stress concentrations in steel fiber composites under transverse loading

Steel fibers, with their high stiffness and high ductility, have a potential to provide a new range of properties in polymer composites, in comparison with carbon and glass fiber composites. However, the high stiffness contrast between the steel fiber and the polymer matrix plus the fiber’s non-circular cross-section are likely to generate high stress concentrations in a composite under transverse loading. In the present study, these stress concentrations are analyzed using finite element modeling and compared with the case of carbon and glass fiber composites. The study is performed for an isolated fiber and multiple fibers in hexagonal and random packings with 40% and 60% of fiber volume fractions. According to the results, in spite of a high contrast between the stiffness values of steel and glass fibers, no significant difference between the transverse stress concentrations was observed for steel and glass fibers in the hexagonal packing due to the difference in material properties. Differences in stress concentrations were noted for the case of randomly packed fibers. The polygonal cross-section of steel fibers was found to introduce extreme stress concentrations.
Efficient caching through stateful SDN in named data networking

Named data networking (NDN) is an innovative paradigm to provide content‐based services in future networks. As compared with legacy networks, naming of network packets and in‐network caching of content make NDN more feasible for content dissemination. However, the implementation of NDN requires drastic changes to the existing network infrastructure. One feasible approach is to use software‐defined networking (SDN), according to which the control of the network is delegated to a centralized controller, which configures the forwarding data plane. This approach leads to large signaling overhead and large end‐to‐end delays. In order to overcome these issues, we propose to enable NDN using a stateful data plane in the SDN network. In particular, we realize the functionality of an NDN node using a stateful SDN switch attached with a local cache for content storage and use OpenState to implement such an approach. In our solution, no involvement of the controller is required once the OpenState switch has been configured. We benchmark the performance of our solution against the traditional SDN approach considering several relevant metrics. Experimental results highlight the benefits of a stateful approach and of our implementation, which avoids signaling overhead and significantly reduces end‐to‐end delays.
Environmental monitoring of waterborne Campylobacter: evaluation of the Australian standard and a hybrid extraction-free MPN-PCR method

Campylobacter is the leading agent of diarrheal disease worldwide. This study evaluates a novel culture-PCR hybrid (MPN-PCR) assay for the rapid enumeration of Campylobacter spp. from estuarine and wastewater systems. To first evaluate the current, culture-based, Australian standard, an inter-laboratory study was conducted on 69 subsampled water samples. The proposed Most-Probable Number (MPN)-PCR method was then evaluated, by analysing 147 estuarine samples collected over a 2 year period. Data for 14 different biological, hydrological and climatic parameters were also collated to identify pathogen-environment relationships and assess the potential for method specific bias. The results demonstrated that the intra-laboratory performance of the MPN-PCR was superior to that of AS/NZS (σ = 0.7912, P < 0.001; κ = 0.701, P < 0.001) with an overall diagnostic accuracy of ~94%. Furthermore, the analysis of both MPN-PCR and AS/NZS identified the potential for the introduction of method specific bias during assessment of the effects of environmental parameters on Campylobacter spp. numbers.
Onset Coding Is Degraded in Auditory Nerve Fibers from Mutant Mice Lacking Synaptic Ribbons

Synaptic ribbons, found at the presynaptic membrane of sensory cells in both ear and eye, have been implicated in the vesicle-pool dynamics of synaptic transmission. To elucidate ribbon function, we characterized the response properties of single auditory nerve fibers in mice lacking Bassoon, a scaffolding protein involved in anchoring ribbons to the membrane. In bassoon mutants, immunohistochemistry showed that fewer than 3% of the hair cells' afferent synapses retained anchored ribbons. Auditory nerve fibers from mutants had normal threshold, dynamic range, and postonset adaptation in response to tone bursts, and they were able to phase lock with normal precision to amplitude-modulated tones. However, spontaneous and sound-evoked discharge rates were reduced, and the reliability of spikes, particularly at stimulus onset, was significantly degraded as shown by an increased variance of first-spike latencies. Modeling based on in vitro studies of normal and mutant hair cells links these findings to reduced release rates at the synapse. The degradation of response reliability in these mutants suggests that the ribbon and/or Bassoon normally facilitate high rates of exocytosis and that its absence significantly compromises the temporal resolving power of the auditory system.
An analytical study of peer-to-peer media streaming systems

Recent research efforts have demonstrated the great potential of building cost-effective media streaming systems on top of peer-to-peer (P2P) networks. A P2P media streaming architecture can reach a large streaming capacity that is difficult to achieve in conventional server-based streaming services. Hybrid streaming systems that combine the use of dedicated streaming servers and P2P networks were proposed to build on the advantages of both paradigms. However, the dynamics of such systems and the impact of various factors on system behavior are not totally clear. In this article, we present an analytical framework to quantitatively study the features of a hybrid media streaming model. Based on this framework, we derive an equation to describe the capacity growth of a single-file streaming system. We then extend the analysis to multi-file scenarios. We also show how the system achieves optimal allocation of server bandwidth among different media objects. The unpredictable departure/failure of peers is a critical factor that affects the performance of P2P systems. We utilize the concept of peer lifespan to model peer failures. The original capacity growth equation is enhanced with coefficients generated from peer lifespans that follow an exponential distribution. We also propose a failure model under arbitrarily distributed peer lifespan. Results from large-scale simulations support our analysis.
Construction and characterization of chromosomal insertional mutations of the Pseudomonas aeruginosa exoenzyme S trans-regulatory locus

Exoenzyme S is an ADP-ribosyltransferase produced by Pseudomonas aeruginosa. Synthesis of exoenzyme S depends on an intact trans-regulatory locus encoding three protein products, ExsC, ExsB, and ExsA. To identify the phenotype of ExsC, -B, and -A mutants in exoenzyme S production, specific insertional mutations with the streptomycin resistance-encoding omega interposon were introduced into cloned DNA and returned to the chromosomes of P. aeruginosa PA103, PAO1, and PAK. Southern blot analysis was used to confirm insertion of omega and resolution of vector sequences. Exoenzyme S expression was measured in parental and mutant derivatives by Western blot (immunoblot) analysis and ADP-ribosyltransferase activity measurement. A complete set of mutations were obtained in strains PAK and PAO1, but in strain PA103, only an insertion in the exsA coding region was identified. Southern blot analysis demonstrated that extensive duplication and rearrangement of the PA103 chromosomal trans-regulatory locus occurred when exsC::omega or exsB::omega recombination events were attempted. Exoenzyme S antigen was not detectable in the supernatant or lysate fractions of mutant strains by Western blot analysis. ADP-ribosyltransferase activity was detected in the lysate but not in the supernatant fractions of mutant derivatives. The general secretion pathway appeared to function normally in mutant strains, as elastase, exotoxin A, and phospholipase C were measured in the supernatants of parental and mutant strains. Several differences were noted when the extracellular protein profiles of parental strains were compared with similar samples from the insertional mutant strains. Some of these differences appeared to be unrelated to exoenzyme S. These data suggest that insertional inactivation of the exoenzyme S trans-regulatory locus may affect a subset of other extracellular proteins.