gebhart/patrepeval huggingface dataset:
Invasion of the Central Nervous System by Cryptococcus neoformans Requires a Secreted Fungal Metalloprotease (2014)

Cryptococcus neoformans is a medically relevant fungal pathogen causing significant morbidity and mortality, particularly in immunocompromised individuals. An intriguing feature is its strong neurotropism, and consequently the hallmark of cryptococcal disease is a brain infection, cryptococcal meningoencephalitis. For C. neoformans to penetrate the central nervous system (CNS), it first breaches the blood-brain barrier via a transcellular pathway; however, the identities of fungal factors required for this transmigration remain largely unknown. In an effort to identify extracellular fungal proteins that could mediate interactions with the brain endothelium, we undertook a proteomic analysis of the extracellular proteome and identified a secreted metalloprotease (Mpr1) belonging to the M36 class of fungalysins. Here we found that Mpr1 promotes migration of C. neoformans across the brain endothelium and into the CNS by facilitating attachment of cryptococci to the endothelium surface, thus underscoring the critical role of M36 proteases in fungal pathogenesis.
Heparin Binds Endothelial Cell Growth Factor, the Principal Endothelial Cell Mitogen in Bovine Brain (1984)

Endothelial cell growth factor (ECGF), an anionic polypeptide mitogen, binds to immobilized heparin. The interaction between the acidic polypeptide and the anionic carbohydrate suggests a mechanism that is independent of ion exchange. Monoclonal antibodies to purified bovine ECGF inhibited the biological activity of ECGF in crude preparations of bovine brain. These data indicate that ECGF is the principal mitogen for endothelial cells from bovine brain, that heparin affinity chromatography may be used to purify and concentrate ECGF, and that the affinity of ECGF for heparin may have structural and perhaps biological significance.
Function of adenovirus E3 proteins and their interactions with immunoregulatory cell proteins (2004)

This manuscript will contain a brief review of adenovirus (Ad) biology including its structure and the spectrum of clinical diseases that it causes. Newer findings about the interactions of Ad early region 3 (E3) proteins with host proteins and signal transduction processes, which control the inflammatory response, will be described. Some of these processes affect the strategies for using Ads as vectors for gene therapy. There are many excellent reviews of some of these aspects 1. The history of the discoveries that led to the use of Ads as vectors as well as key experiments that resulted in improvements to various aspects of these systems have also been reviewed recently 2. The use of Ad E3 immunoregulatory genes to facilitate allogeneic transplantation and prevent autoimmune diabetes will be described.
Comment on ‘‘DNA plasmon’’ (1989)

Comment on the Letter by L. L. Van Zandt and V. K. Saxena, Phys. Rev. Lett. 61, 1788 (1988).Received 21 November 1988DOI:https://doi.org/10.1103/PhysRevLett.63.2316©1989 American Physical Society
Role of specific determinants in mannan of Candida albicans serotype A in adherence to human buccal epithelial cells (1992)

Candida albicans serotype A (C. albicans A) possesses a specific antigen, designated antigen 6, which resides in mannans on the cell surface. To determine the role of the mannan moiety of the C. albicans cell wall in adherence to buccal epithelial cells, we used antigen 6-deficient mutants which had been isolated by screening with an agglutinating monoclonal antibody against antigen 6 (MAb-6). 1H nuclear magnetic resonance spectral analysis of the purified mannans from the mutants showed a loss of the signals related to that beta-linkage of the side chains. Moreover, acetolyzed fragments of the mutant mannans showed a decreased amount of mannohexaose and mannopentaose. The mutant yeast cells exhibited significantly reduced ability to adhere both to exfoliated buccal epithelial cells and to a human buccal cell line. A number of strains of C. albicans A, C. tropicalis, and C. glabrata, all of which bear antigen 6, showed significantly higher adherence to the cell line than did those of C. albicans serotype B, which lack antigen 6. The whole mannan from the C. albicans A parent inhibited the adherence of C. albicans A to epithelial cells dose dependently, whereas mannan from a mutant strains did not. Moreover, C. albicans A treated with MAb-6 or polyclonal factor 6 serum showed reduced adherence. A close correlation was found between adhesive ability and agglutinability with MAb-6 in the C. albicans A parent, the antigenic mutants, and their spontaneous revertants. These results suggest that so far as mannan adhesion is concerned, serotype A-specific determinants are largely involved in the mechanisms of adherence of C. albicans A to human buccal epithelial cells.
Construction of viable deletion and insertion mutants of the Sabin strain of type 1 poliovirus: function of the 5' noncoding sequence in viral replication (1987)

A number of deletion and insertion sequences were introduced into the 5' noncoding sequence (742 nucleotides long) of the genome of the Sabin strain of type 1 poliovirus by using an infectious cDNA clone of the virus strain. The genomes of all three poliovirus serotypes contained highly homologous sequences (nucleotide positions 509 to 639) as well as highly variable sequences (positions 640 to 742) in the 5' noncoding region. The viability of mutant viruses was tested by transfecting mutant cDNA clones into African green monkey kidney cells and then estimating the plaque sizes displayed on the cells. The results suggested that the highly variable sequence next to the VP4 coding region did not play an important role, at least in the in vitro culture system used, that the loci of highly conserved nucleotide sequences were not always expected to be the genome regions essential for viral replication, that the sequence between positions 564 and 599 carried genetic information to maintain the efficiency of certain steps in viral replication, and that the sequence between positions 551 to 563 might play an essential role in viral replication. Four-base deletion or insertion mutations were introduced into relatively variable sequences in the genome region upstream of position 509. The results suggest that variable sequences do not always indicate that the corresponding genome regions are less important. Apparent revertants (large-plaque variants) were easily generated from one of the viable mutants with the small-plaque phenotype. The determination of nucleotide sequences of the revertant genomes revealed the second mutation site. The results suggested that the different loci at around positions 200 and 500 might specifically interact with each other. This interaction may result in the formation of a functional structure that influences the efficiency of certain steps in the viral replication.
C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Catalytic Enantioselective Carbonyl−Ene Reactions with Glyoxylate and Pyruvate Esters (2000)

The C2-symmetric complexes [Cu(S,S)-tert-butylbis(oxazolinyl)](SbF6)2 (2a), its bis(aquo) counterpart [Cu(S,S)-tert-butylbis(oxazolinyl)(H2O)2](SbF6)2 (4), and [Cu(S,S)-phenylbis(oxazolinyl)](OTf)2 (1c) have been shown to catalyze the enantioselective ene reaction between glyoxylate esters and various olefins. Monosubstituted, disubstituted, and trisubstituted olefins each react with ethyl glyoxylate in the presence of 0.2−10 mol % of catalysts 1, 2, and 4 to afford the ene products in good yield and enantioselectivity. Complex 2a has also been shown to catalyze the addition of 1,1-disubstituted olefins to methyl pyruvate in good yields (76−95%) and excellent enantioselectivies (≥98% ee). The synthetic utility of the glyoxylate−ene reaction was demonstrated by conversion of the resulting α-hydroxy ester into the corresponding methyl ester, free acid, Weinreb amide, and α-azido ester, all with no detectable racemization.
CD40/CD40 ligand interactions are required for T cell‐dependent production of interleukin‐12 by mouse macrophages (1996)

We have previously shown that T cell receptor-activated mouse T helper (Th)1 clones induce the production of interleukin (IL)-12 by splenic antigen-presenting cells (APC). Here, we show that the expression of CD40L by activated T cells is critical for T cell-dependent IL-12 production by mouse macrophages. IL-12 was produced in cultures containing alloreactive Th1 clones stimulated with allogeneic peritoneal macrophages, or in cultures of splenocytes stimulated with anti-CD3. Anti-CD40L monoclonal antibodies (mAb) inhibited the production of IL-12, but not IL-2, in these cultures by approximately 90% and had dramatic inhibitory effects on antigen-dependent proliferation of Th1 clones. In addition, both activated T cells and a Th1 clone derived from CD40L knockout mice failed to induce IL-12 production from splenic APC or peritoneal macrophages. Finally, macrophages cultured in the absence of T cells produced IL-12 upon stimulation with soluble recombinant CD40L in combination with either supernatants from activated Th1 clones or with interferon-gamma and granulocyte/macrophage colony-stimulating factor. Thus, both CD40L-dependent and cytokine-mediated signals from activated T cells are required to induce the production of IL-12 by macrophages. A blockade at the level of IL-12 production may explain, at least in part, the dramatic ability of anti-CD40L mAb to inhibit disease in animal models that are dependent upon the generation of a cell-mediated immune response. Moreover, a defect in T cell-dependent induction of IL-12 may contribute to the immune status of humans that lack functional CD40L.
TiO2inverse-opal electrode fabricated by atomic layer deposition for dye-sensitized solar cell applications (2010)

TiO2 inverse opals (TIO) fabricated by the atomic layer deposition (ALD) technique showed a superior infiltration result when compared to those fabricated by the conventional nanoparticles-infiltration method reported in previous studies. The ALD can achieve high filling fractions of more than ca. 96% of the maximum possible infiltration by conformal filling of 288, 390 and 510 nm opals, giving rise to high quality TIO. The photoelectrochemical performances of the ALD-fabricated TIO photoanodes of different sizes are investigated systematically for the first time in dye-sensitized solar cells (DSCs). When the TIO with a size of 288 nm was used as photoanode and indoline dye as a sensitizer in DSCs, the power conversion efficiency of the cell could attain 2.22% (Air Mass 1.5). It is found that the efficiency increases with decreasing lattice size of TIO electrode due to the larger surface area for dye loading. Owing to the selective reflectivity of the inverse opal, IPCE spectra of TIO electrodes revealed a strong wavelength dependence. Strategies relating to the characteristics of selective reflection and the design of composite photoanodes to enhance the efficiency of DSCs are discussed.
Potent Antibacterial Activities of Ag/TiO2Nanocomposite Powders Synthesized by a One-Pot Sol−Gel Method (2009)

The antimicrobial properties of Ag-based materials have been actively investigated recently. In such materials, control of the size of the Ag particles is critical to their bactericidal performance. A novel one-pot sol-gel scheme is described here. It incorporates room-temperature ionic liquids (RTILs) to synthesize Ag/TiO2 nanocomposite powders. The presence of RTILs is indispensable to the control of the size of the Ag particles. Highly dispersed, metallic Ag nanoclusters are formed on the TiO2 nanoparticle surface after calcination of the gel. The average cluster size of Ag can be controlled to be below 5 nm with high Ag loading (7.4 wt%). Antibacterial tests using 7.4 wt% Ag/TiO2 on 10(5) CFU/mL Escherichia coli (E. coli) strains incubated on Luria-Bertani (LB)/agar plates show that bacterial growth was inhibited by 98.8% at an Ag concentration of 1.2 microg/mL Complete inhibition was achieved at 2.4 microg(Ag)/mL. At this concentration, a 3.9 wt% Ag/TiO2 sample, with a smaller Ag cluster size (<3 nm), completely inhibited bacterial growth in a more populated E. coli community (approximately 3 x 10(6) CFU/mL). In fact, 1.6 microg/mL Ag suppressed bacterial growth by 99.9% with 3.9 wt% Ag/TiO2. Both the small Ag cluster size and the unique structure of TiO2 nanoparticles supporting highly dispersed Ag clusters are identified to be the sources of a superior bactericidal performance of the RTILs-derived Ag/TiO2.
Majorana modes and complex band structure of quantum wires (2013)

We describe Majorana edge states of a semi-infinite wire using the complex band structure approach. In this method the edge state at a given energy is built as a superposition of evanescent waves. It is shown that the superposition can not always satisfy the required boundary condition, thus restricting the existence of edge modes. We discuss purely 1D and 2D systems, focusing in the latter case on the effect of the Rashba mixing term.
Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function (2000)

The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHbeta subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases.
Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro (2010)

Mutations in WD repeat domain 36 gene (WDR36) play a causative role in some forms of primary open-angle glaucoma, a leading cause of blindness worldwide. WDR36 is characterized by the presence of multiple WD40 repeats and shows homology to Utp21, an essential protein component of the yeast small subunit (SSU) processome required for maturation of 18S rRNA. To clarify the functional role of WDR36 in the mammalian organism, we generated and investigated mutant mice with a targeted deletion of Wdr36. In parallel experiments, we used RNA interference to deplete WDR36 mRNA in mouse embryos and cultured human trabecular meshwork (HTM-N) cells. Deletion of Wdr36 in the mouse caused preimplantation embryonic lethality, and essentially similar effects were observed when WDR36 mRNA was depleted in mouse embryos by RNA interference. Depletion of WDR36 mRNA in HTM-N cells caused apoptotic cell death and upregulation of mRNA for BAX, TP53 and CDKN1A. By immunocytochemistry, staining for WDR36 was observed in the nucleolus of cells, which co-localized with that of nucleolar proteins such as nucleophosmin and PWP2. In addition, recombinant and epitope-tagged WDR36 localized to the nucleolus of HTM-N cells. By northern blot analysis, a substantial decrease in 21S rRNA, the precursor of 18S rRNA, was observed following knockdown of WDR36. In addition, metabolic-labeling experiments consistently showed a delay of 18S rRNA maturation in WDR36-depleted cells. Our results provide evidence that WDR36 is an essential protein in mammalian cells which is involved in the nucleolar processing of SSU 18S rRNA.
Stochastic models for the in silico simulation of synaptic processes (2008)

Specific presynaptic and postsynaptic mechanisms can be further analysed under various conditions, for instance by studying the presynaptic behaviour under repeated activations. The level of details of the description can be refined, for instance by further specifying the neurotransmitter generation and release steps. Taking advantage of the compositionality of the approach, an enhanced model could then be composed with other neural models, designed within the same framework, in order to obtain a more detailed and comprehensive model. In the long term, we are interested, in particular, in addressing models of synaptic plasticity, i.e. activity dependent mechanisms, which are the bases of memory and learning processes. More on the computer science side, we plan to follow some directions to improve the underlying computational model and the linguistic primitives it provides as suggested by the experiments carried out, e.g. by introducing a suitable notion of (spatial) locality.
An empirical comparison of evolution and coevolution for designing artificial neural network game players (2008)

In this paper, we compare two neuroevolutionary algorithms, namely standard NeuroEvolution (NE) and NeuroEvolution of Augmenting Topologies (NEAT), with three neurocoevolutionary algorithms, namely Symbiotic Adaptive Neuro-Evolution (SANE), Enforced Sub-Populations (ESP) and Evolving Efficient Connections (EEC). EEC is a novel neurocoevolutionary algorithm that we propose in this work, where the connection weights and the connection paths of networks are evolved separately. All these methods are applied to evolve players of two different board games. The results of this study indicate that neurocoevolutionary algorithms outperform neuroevolutionary algorithms for both domains. Our new method, especially, demonstrates that fully connected networks could generate noise which results in inefficient learning. The performance of standard NE model has been improved significantly through evolving connection weights and efficient connection paths in parallel in our method.
Determine Calibration Parameters with Satisfied Constraints for Coplanar Camera Calibration (2005)

Coplanar camera calibration is the process of determining a set of calibration parameters that describe the mapping between 2D control points and 2D image coordinates. However, the optimal solution for coplanar calibration can be obtained by solving a set of constrained optimization problem. This paper presents a technique to determine the calibration parameters for coplanar calibration, where a set of orthogonality constraints is fully satisfied. The solving of camera calibration consists of two steps. The first step is an estimating of calibration parameters using a closed form solution based on distortion free. In the second step, the parameters estimated in first step are iteratively improved by nonlinear optimization method, where the objective function is enforced to satisfy the constraints during optimization process. The computing of parameters is directly performed on computer image array by assuming that scale factor is equal to 1. Consequently, the image center can be simultaneously computed with the other parameters. The proposed technique is tested with a synthetic image that known distortion. The result shows that the proposed technique gives sufficient accuracy.
Programmable plasmid interference by the CRISPR-Cas system in Thermococcus kodakarensis (2013)

CRISPR-Cas systems are RNA-guided immune systems that protect prokaryotes against viruses and other invaders. The CRISPR locus encodes crRNAs that recognize invading nucleic acid sequences and trigger silencing by the associated Cas proteins. There are multiple CRISPR-Cas systems with distinct compositions and mechanistic processes. Thermococcus kodakarensis (Tko) is a hyperthermophilic euryarchaeon that has both a Type I-A Csa and a Type I-B Cst CRISPR-Cas system. We have analyzed the expression and composition of crRNAs from the three CRISPRs in Tko by RNA deep sequencing and northern analysis. Our results indicate that crRNAs associated with these two CRISPR-Cas systems include an 8-nucleotide conserved sequence tag at the 5' end. We challenged Tko with plasmid invaders containing sequences targeted by endogenous crRNAs and observed active CRISPR-Cas-mediated silencing. Plasmid silencing was dependent on complementarity with a crRNA as well as on a sequence element found immediately adjacent to the crRNA recognition site in the target termed the PAM (protospacer adjacent motif). Silencing occurred independently of the orientation of the target sequence in the plasmid, and appears to occur at the DNA level, presumably via DNA degradation. In addition, we have directed silencing of an invader plasmid by genetically engineering the chromosomal CRISPR locus to express customized crRNAs directed against the plasmid. Our results support CRISPR engineering as a feasible approach to develop prokaryotic strains that are resistant to infection for use in industry.
Toward a Global View of Alcohol, Tobacco, Cannabis, and Cocaine Use: Findings from the WHO World Mental Health Surveys (2008)

Globally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more recent cohorts, who also have higher levels of illegal drug use and extensions in the period of risk for initiation.
Diagnosis of multiple cancer types by shrunken centroids of gene expression (2002)

We have devised an approach to cancer class prediction from gene expression profiling, based on an enhancement of the simple nearest prototype (centroid) classifier. We shrink the prototypes and hence obtain a classifier that is often more accurate than competing methods. Our method of "nearest shrunken centroids" identifies subsets of genes that best characterize each class. The technique is general and can be used in many other classification problems. To demonstrate its effectiveness, we show that the method was highly efficient in finding genes for classifying small round blue cell tumors and leukemias.
Ion-beam assisted, electron-beam physical vapor deposition (1996)

Electron beam-physical vapor deposition (EB-PVD) is a relatively new technology that has overcome some of the difficulties associated with chemical vapor deposition, physical vapor deposition, and thermal spray processes. In the EB-PVD process, focused high-energy electron beams generated from electron guns are directed to melt and evaporate ingots, as well as preheat the substrate inside a vacuum chamber. By adding the assistance of ion beams to the process, coating density and adhesion are improved, while costs are reduced. This article describes physical vapor deposition and ion-beam processes, explains the advantages of EB-PVD, shows how ion beams optimize the benefits of EB-PVD, and enumerates a variety of applications.