Miracle-dz/UniFAR-FTUs huggingface dataset:
Interglandular cytogenetic heterogeneity detected by comparative genomic hybridization in pancreatic cancer.

The aim of this study is to explore the mechanisms of intratumoral cytogenetic heterogeneity (ICH) in pancreatic cancer. Using comparative genomic hybridization (CGH) analysis, we investigated interglandular variation in 20 primary invasive ductal adenocarcinomas of the pancreas. Three or four adjacent neoplastic glands were individually microdissected from a tumor specimen. Extracted DNA from each gland was amplified by degenerate oligonucleotide primed-PCR, followed by CGH. In addition, DNA index (DI) was measured by laser scanning cytometry in each case. CGH profiles displayed a wide variety of differences between glands within the same tumor in all cases, i.e., interglandular cytogenetic heterogeneity was distinct in pancreatic cancers. In this study, genetic changes detected in all regions of a tumor were classified as "region-independent" alterations, whereas changes seen in at least one, but not all regions were designated as "region-dependent" alterations, which resulted in ICH. The degree of ICH, which was manifested as the ratio of these two types of alterations, correlated closely with DI (Spearman rho = 0.842; P = 0.0002). Therefore, DI might be a surrogate marker for ICH. These results suggest that with tumor progression, ICH and DNA aneuploidy result from the successive appearance of region-dependent alterations attributable to chromosomal instability in tumor cells. Our data support a concept of individual cell heterogeneity in pancreatic cancer.
A Projective Invariant for Textures

Image texture analysis has received a lot of attention in the past years. Researchers have developed many texture signatures based on texture measurements, for the purpose of uniquely characterizing the texture. Existing texture signatures, in general, are not invariant to 3D transforms such as view-point changes and non-rigid deformations of the texture surface, which is a serious limitation for many applications. In this paper, we introduce a new texture signature, called the multifractal spectrum (MFS). It provides an efficient framework combining global spatial invariance and local robust measurements. The MFS is invariant under the bi-Lipschitz map, which includes view-point changes and non-rigid deformations of the texture surface, as well as local affine illumination changes. Experiments demonstrate that the MFS captures the essential structure of textures with quite low dimension.
First Odin sub-mm retrievals in the tropical upper troposphere: ice cloud properties

More accurate global measurements of the amount of ice in thicker clouds are needed to validate atmospheric models and sub-mm radiometry can be an important com- ponent in this respect. A cloud ice retrieval scheme for the first such instrument in space, Odin-SMR, is presented here. Several advantages of sub-mm observations are shown, such as low influence of particle shape and orientation, and a high dynamic range of the retrievals. In the case of Odin-SMR, only cloud ice above 12.5 km can be measured. The present retrieval scheme gives a detection threshold of about 4 g/m 2 above 12.5 km and does not saturate even for thickest ob- served clouds (>500 g/m 2 ). The main retrieval uncertainties are the assumed particle size distribution and cloud inhomo- geneity effects. The overall retrieval accuracy is estimated to be 75%. The retrieval error is judged to have large random components and to be significantly lower than this value for averaged results, but high fixed errors can not be excluded. However, a firm lower value can always be pro- vided. Initial results are found to be consistent with simi- lar Aura MLS retrievals, but show important differences to corresponding data from atmospheric models. This first re- trieval algorithm is limited to lowermost Odin-SMR tangent altitudes, and further development should improve the detec- tion threshold and the vertical resolution. It should also be possible to decrease the retrieval uncertainty associated with cloud inhomogeneities by detailed analysis of other data sets.
Simultaneous Pathoproteomic Evaluation of the Dystrophin-Glycoprotein Complex and Secondary Changes in the mdx-4cv Mouse Model of Duchenne Muscular Dystrophy

In skeletal muscle, the dystrophin-glycoprotein complex forms a membrane-associated assembly of relatively low abundance, making its detailed proteomic characterization in normal versus dystrophic tissues technically challenging. To overcome this analytical problem, we have enriched the muscle membrane fraction by a minimal differential centrifugation step followed by the comprehensive label-free mass spectrometric analysis of microsomal membrane preparations. This organelle proteomic approach successfully identified dystrophin and its binding partners in normal versus dystrophic hind limb muscles. The introduction of a simple pre-fractionation step enabled the simultaneous proteomic comparison of the reduction in the dystrophin-glycoprotein complex and secondary changes in the mdx-4cv mouse model of dystrophinopathy in a single analytical run. The proteomic screening of the microsomal fraction from dystrophic hind limb muscle identified the full-length dystrophin isoform Dp427 as the most drastically reduced protein in dystrophinopathy, demonstrating the remarkable analytical power of comparative muscle proteomics. Secondary pathoproteomic expression patterns were established for 281 proteins, including dystrophin-associated proteins and components involved in metabolism, signalling, contraction, ion-regulation, protein folding, the extracellular matrix and the cytoskeleton. Key findings were verified by immunoblotting. Increased levels of the sarcolemmal Na+/K+-ATPase in dystrophic leg muscles were also confirmed by immunofluorescence microscopy. Thus, the reduction of sample complexity in organelle-focused proteomics can be advantageous for the profiling of supramolecular protein complexes in highly intricate systems, such as skeletal muscle tissue.
Risperidone Irreversibly Binds to and Inactivates the h5-HT7 Serotonin Receptor

Risperidone displays a novel mechanism of antagonism of the h5-HT7 receptor. Pretreatment of the cells with 5 or 20 nM risperidone, followed by removal of the drug from the media, renders the 5-HT7 receptors unresponsive to 10 μM 5-HT for at least 24 h. Thus, risperidone seems to be producing a rapid, long-lasting inactivation of the h5-HT7 receptor. Whole-cell radioligand binding studies indicate that risperidone interacts in an irreversible or pseudo-irreversible manner with the h5-HT7 receptor, thus producing the inactivation. Internalization of the h5-HT7 receptor was not detected by monitoring green fluorescent protein-labeled fluorescent forms of the h5-HT7 receptor exposed to 20 nM risperidone. Ten other antagonists were tested for h5-HT7-inactivating properties, and only 9-OH-risperidone and methiothepin were found to demonstrate the same anomalous properties as risperidone. These results indicate that the h5-HT7 receptor may possess unique structural features that allow certain drugs to induce a conformation resulting in an irreversible interaction in the intact membrane environment. This may indicate that the h5-HT7 receptor is part of a subfamily of G-protein-coupled receptors (GPCRs) possessing this property or that many GPCRs have the potential to be irreversibly blocked, but only select drugs can induce this effect. At the very least, the possibility that highly prescribed drugs, such as risperidone, are irreversibly antagonizing GPCR function in vivo is noteworthy.
Transglutaminase 2, a Novel Regulator of Eicosanoid Production in Asthma Revealed by Genome-Wide Expression Profiling of Distinct Asthma Phenotypes

Background A frequent manifestation of asthma, exercise-induced bronchoconstriction (EIB), occurs in 30–50% of asthmatics and is characterized by increased release of inflammatory eicosanoids. The objective of this study was to identify genes differentially expressed in EIB and to understand the function of these genes in the biology of asthma. Methodology/Principal Findings Genome-wide expression profiling of airway leukocytes and epithelial cells obtained by induced sputum was conducted in two groups of subjects with asthma with and without EIB (n = 7 per group), at baseline and following exercise challenge. Based on the results of the gene expression study, additional comparisons were made with a normal control group (n = 10). Localization studies were conducted on epithelial brushings and biopsies from an additional group of asthmatics with EIB (n = 3). Genes related to epithelial repair and mast cell infiltration including β-tryptase and carboxypeptidase A3 were upregulated by exercise challenge in the asthma group with EIB. A gene novel to asthma pathogenesis, transglutaminase 2 (TGM2), was the most differentially expressed at baseline between the groups. In vivo studies confirmed the increased expression of TGM2 in airway cells and airway lining fluid, and demonstrate that TGM2 is avidly expressed in the asthmatic airway epithelium. In vitro studies using recombinant human enzymes reveal that TGM2 augments the enzymatic activity of secreted phospholipase A2 (PLA2) group X (sPLA2-X), an enzyme recently implicated in asthma pathogenesis. Conclusions/Significance This study found that TGM2, a mediator that is novel to asthma pathogenesis, is overexpressed in asthmatic airways and functions to increase sPLA2-X enzymatic activity. Since PLA2 serves as the first rate-limiting step leading to eicosanoid formation, these results suggest that TGM2 may be a key initiator of the airway inflammatory cascade in asthma.
Exploration of Novel Inhibitors for Bruton’s Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation

Bruton’s tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in many cellular signaling pathways. B cell malignancies are dependent on BCR signaling, thus making BTK an efficient therapeutic target. Over the last few years, significant efforts have been made in order to develop BTK inhibitors to treat B-cell malignancies, and autoimmunity or allergy/hypersensitivity but limited success has been achieved. Here in this study, 3D QSAR pharmacophore models were generated for Btk based on known IC50 values and experimental energy scores with extensive validations. The five features pharmacophore model, Hypo1, includes one hydrogen bond acceptor lipid, one hydrogen bond donor, and three hydrophobic features, which has the highest correlation coefficient (0.98), cost difference (112.87), and low RMS (1.68). It was further validated by the Fisher’s randomization method and test set. The well validated Hypo1 was used as a 3D query to search novel Btk inhibitors with different chemical scaffold using high throughput virtual screening technique. The screened compounds were further sorted by applying ADMET properties, Lipinski’s rule of five and molecular docking studies to refine the retrieved hits. Furthermore, molecular dynamic simulation was employed to study the stability of docked conformation and to investigate the binding interactions in detail. Several important hydrogen bonds with Btk were revealed, which includes the gatekeeper residues Glu475 and Met 477 at the hinge region. Overall, this study suggests that the proposed hits may be more effective inhibitors for cancer and autoimmune therapy.
Asymmetric Al-free active region laser structure for high-brightness tapered lasers at 975 nm

We have realized an asymmetric laser structure at 975 nm, based on an Al-free active region. The quantum wells are located near the p-cladding, so that most of the waveguide is n-type, which allows for reduced optical losses and series resistance. On uncoated broad-area lasers, we have obtained very low optical losses of 0.4 cm-1, together with a high internal quantum efficiency of close to 100%. Based on this structure, we have realized index-guided tapered lasers delivering 1.3W CW, with a narrow far-field angle of 2.5° (FWHM) and 5.8° (at 1/e2) in the slow axis, and a good beam propagation ratio M2 = 1.6. The lasers reach a high maximum wall-plug efficiency of 56%. These tapered lasers deliver a maximum power of 1.5W CW with M2 < 3. The results on the asymmetric structure are compared with those of a symmetric laser structure.
Implementing IEEE 1641 - using a complete system

This year, new products have been introduced onto a Royal Air Force (RAF) test system, which provide an integrated IEEE 1641 development and run-time system. The program involved the integration of Commercial of the Shelf (COTS) products to provide a facility to enable the creation of a TPS using 1641 signal definitions, through to the running of the test program using established instruments and driver software. This paper discusses the process involved in achieving the objectives from the point of view of the TPS developer and integrator, and will cover the complete process, from requirements capture, via TPS integration, to program operation and results verification. The paper will also outline the lessons learned and the resulting feedback to the COTS product developers and 1641 working groups.
Interior Fracture Mechanism Analysis and Fatigue Life Prediction of Surface-Hardened Gear Steel under Axial Loading

The interior defect-induced fracture of surface-hardened metallic materials in the long life region has become a key issue on engineering design. In the present study, the axial loading test with fully reversed condition was performed to examine the fatigue property of a surface-carburized low alloy gear steel in the long life region. Results show that this steel represents the duplex S-N (stress-number of cycles) characteristics without conventional fatigue limit related to 107 cycles. Fatigue cracks are all originated from the interior inclusions in the matrix region due to the inhabitation effect of carburized layer. The inclusion induced fracture with fisheye occurs in the short life region below 5 × 105 cycles, whereas the inclusion induced fracture with fine granular area (FGA) and fisheye occurs in the long life region beyond 106 cycles. The stress intensity factor range at the front of FGA can be regarded as the threshold value controlling stable growth of interior long crack. The evaluated maximum inclusion size in the effective damage volume of specimen is about 27.29 μm. Considering the size relationships between fisheye and FGA, and inclusion, the developed life prediction method involving crack growth can be acceptable on the basis of the good agreement between the predicted and experimental results.
Control of Medium-Voltage AC Motor Drive for Wide Speed Range Using Modular Multilevel Converter

For the application of variable speed drive, submodule capacitors of the modular multilevel converter (MMC) suffer from large voltage fluctuations at low frequencies. This paper presents a control technique that regulates this fluctuation to a constant value at all speeds with rated load torque. Transformerless configuration of this drive is as follows. An MMC is used as a front-end converter and is directly connected to the grid. It keeps the grid current sinusoidal and is in phase with the grid voltage. It generates regulated dc current at the output. Another MMC, connected in cascade with the earlier one, drives a three-phase induction motor. Therefore, the input to this rear-end MMC is constant dc current, the output is variable magnitude and frequency voltage source that drives the motor. This paper proposes a control strategy for this drive. The proposed control method and its performance have been analyzed and verified through experimental results in this paper.
Data Fusion of Visible/Near-infrared Spectroscopy and Spectral Scattering for Apple Quality Assessment

Visible/near-infrared (VNIR) spectroscopy and spectral scattering are based on different sensing principles, and they have shown different abilities for predicting apple fruit firmness and soluble solids content (SSC). Hence the two techniques could work synergistically to improve the quality prediction of apples. In this research, VNIR spectroscopic and spectral scattering data for the wavelength range of 460–1,100 nm were collected for 6,631 apples of ‘Delicious', 'Golden Delicious' and 'Jonagold' cultivars during the 2009 and 2010 harvest seasons and for three months after the refrigerated air storage. Partial least squares models were developed for each sensor and their combination to predict the fruit firmness and SSC for both single-year and cross-year data sets. The spectral scattering technique generally performed better in predicting firmness, whereas the VNIR technique was superior for prediction of SSC. Overall, the data fusion of the two sensors produced significant improvements (p<0.05) for prediction of the firmness and SSC than individual sensors. Cross-year prediction results for firmness and SSC were lower, compared with prediction results for each year. However, the cross-year prediction model for SSC was more robust and less sensitive to the harvest-year effect, compared to the firmness prediction model. Sensor fusion can provide more robust and accurate firmness and SSC assessment for apples.
Learning complex output representations in connectionist parsing of spoken language

Due to robustness, learnability and ease of integration of different information sources, connectionist parsing systems have proven to be applicable for parsing spoken language, However, most proposed connectionist parsers do not compute and represent complex structures. These parsers assign only a very limited structure to a given input string. For spoken language translation and data base access, more detailed syntactic and semantic representation is needed. In the present paper, the authors show that arbitrary linguistic features and arbitrary complex tree structures can indeed also be learned by a connectionist parsing system. <<ETX>>
Predictable Dynamics in the S&P 500 Index Options Implied Volatility Surface

One key stylized fact in the empirical option pricing literature is the existence of an implied volatility surface (IVS). The usual approach consists of fitting a linear model linking the implied volatility to the time to maturity and the moneyness, for each cross section of options data. However, recent empirical evidence suggests that the parameters characterizing the IVS change over time. In this paper we study whether the resulting predictability patterns in the IVS coefficients may be exploited in practice. We propose a two-stage approach to modeling and forecasting the S&P 500 index options IVS. In the first stage we model the surface along the cross-sectional moneyness and time-to-maturity dimensions, similarly to Dumas et al. (1998). In the second-stage we model the dynamics of the cross-sectional first-stage implied volatility surface coefficients by means of vector autoregression models. We find that not only the S&P 500 implied volatility surface can be successfully modeled, but also that its movements over time are highly predictable in a statistical sense. We then examine the economic significance of this statistical predictability with mixed findings. Whereas profitable delta-hedged positions can be set up that exploit the dynamics captured by the model under moderate transaction costs and when trading rules are selective in terms of expected gains from the trades, most of this profitability disappears when we increase the level of transaction costs and trade multiple contracts off wide segments of the IVS. This suggests that predictability of the time-varying S&P 500 implied volatility surface may be not inconsistent with market efficiency.
The Role of Broca's Area in Sentence Comprehension

The role of Broca's area in sentence processing has been debated for the last 30 years. A central and still unresolved issue is whether Broca's area plays a specific role in some aspect of syntactic processing (e.g., syntactic movement, hierarchical structure building) or whether it serves a more general function on which sentence processing relies (e.g., working memory). This review examines the functional organization of Broca's area in regard to its contributions to sentence comprehension, verbal working memory, and other multimodal cognitive processes. We suggest that the data are consistent with the view that at least a portion of the contribution of Broca's area to sentence comprehension can be attributed to its role as a phonological short-term memory resource. Furthermore, our review leads us to conclude that there is no compelling evidence that there are sentence-specific processing regions within Broca's area.
Prospect Theory Explains Newsvendor Behavior: The Role of Reference Points

Current understanding in operations management is that prospect theory, as a theory of decision making under uncertainty, cannot systematically explain the ordering behavior observed in experiments on the newsvendor problem. We suggest this is because the newsvendor’s reference point is assumed to be the status quo, i.e., zero payoff. We propose an alternative based on newsvendor’s salient payoffs and show that prospect theory can, in fact, account for experimental results. This paper was accepted by Serguei Netessine, operations management.
Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent

The purpose of this study was to synthesize biocompatible polyvinylpyrrolidone (PVP)-coated iron oxide (PVP-IO) nanoparticles and to evaluate their efficacy as a magnetic resonance imaging (MRI) contrast agent. The PVP-IO nanoparticles were synthesized by a thermal decomposition method and characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and a superconducting quantum interface device (SQUID). The core size of the particles is about 8–10 nm and the overall size is around 20–30 nm. The measured r2 (reciprocal of T2 relaxation time) and r2* (reciprocal of T2* relaxation time) are 141.2 and 338.1 (s mM)−1, respectively. The particles are highly soluble and stable in various buffers and in serum. The macrophage uptake of PVP-IO is comparable to that of Feridex as measured by a Prussian blue iron stain and phantom study. The signal intensity of a rabbit liver was effectively reduced after intravenous administration of PVP-IO. Therefore PVP-IO nanoparticles are potentially useful for T2-weighted MR imaging.
Cold Shock Domain Family Members YB-1 and MSY4 Share Essential Functions during Murine Embryogenesis

ABSTRACT Three cold shock domain (CSD) family members (YB-1, MSY2, and MSY4) exist in vertebrate species ranging from frogs to humans. YB-1 is expressed throughout embryogenesis and is ubiquitously expressed in adult animals; it protects cells from senescence during periods of proliferative stress. YB-1-deficient embryos die unexpectedly late in embryogenesis (embryonic day 18.5 [E18.5] to postnatal day 1) with a runting phenotype. We have now determined that MSY4, but not MSY2, is also expressed during embryogenesis; its abundance declines substantially from E9.5 to E17.5 and is undetectable on postnatal day 1(adult mice express MSY4 in testes only). Whole-mount analysis revealed similar patterns of YB-1 and MSY4 RNA expression in E11.5 embryos. To determine whether MSY4 delays the death of YB-1-deficient embryos, we created and analyzed MSY4-deficient mice and then generated YB-1 and MSY4 double-knockout embryos. MSY4 is dispensable for normal development and survival, but the testes of adult mice have excessive spermatocyte apoptosis and seminiferous tubule degeneration. Embryos doubly deficient for YB-1 and MSY4 are severely runted and die much earlier (E8.5 to E11.5) than YB-1-deficient embryos, suggesting that MSY4 indeed shares critical cellular functions with YB-1 in the embryonic tissues where they are coexpressed.