gebhart/patrepeval huggingface dataset:
Positional cloning of the wheat vernalization gene VRN1 (2003)

Winter wheats require several weeks at low temperature to flower. This process, vernalization, is controlled mainly by the VRN1 gene. Using 6,190 gametes, we found VRN1 to be completely linked to MADS-box genes AP1 and AGLG1 in a 0.03-centimorgan interval flanked by genes Cysteine and Cytochrome B5. No additional genes were found between the last two genes in the 324-kb Triticum monococcum sequence or in the colinear regions in rice and sorghum. Wheat AP1 and AGLG1 genes were similar to Arabidopsis meristem identity genes AP1 and AGL2, respectively. AP1 transcription was regulated by vernalization in both apices and leaves, and the progressive increase of AP1 transcription was consistent with the progressive effect of vernalization on flowering time. Vernalization was required for AP1 transcription in apices and leaves in winter wheat but not in spring wheat. AGLG1 transcripts were detected during spike differentiation but not in vernalized apices or leaves, suggesting that AP1 acts upstream of AGLG1. No differences were detected between genotypes with different VRN1 alleles in the AP1 and AGLG1 coding regions, but three independent deletions were found in the promoter region of AP1. These results suggest that AP1 is a better candidate for VRN1 than AGLG1. The epistatic interactions between vernalization genes VRN1 and VRN2 suggested a model in which VRN2 would repress directly or indirectly the expression of AP1. A mutation in the promoter region of AP1 would result in the lack of recognition of the repressor and in a dominant spring growth habit.
Multiple roles of pleckstrin homology domains in phospholipase Cβ function (2002)

Since their discovery almost 10 years ago pleckstrin homology (PH) domains have been identified in a wide variety of proteins. Here, we focus on two proteins whose PH domains play a defined functional role, phospholipase C (PLC)-beta(2) and PLCdelta(1). While the PH domains of both proteins are responsible for membrane targeting, their specificity of membrane binding drastically differs. However, in both these proteins the PH domains work to modulate the activity of their catalytic core upon interaction with either phosphoinositol lipids or G protein activators. These observations show that these PH domains are not simply binding sites tethered onto their host enzyme but are intimately associated with their catalytic core. This property may be true for other PH domains.
Cell “vision”: complementary factor of protein corona in nanotoxicology (2012)

Engineered nanoparticles are increasingly being considered for use as biosensors, imaging agents and drug delivery vehicles. Their versatility in design and applications make them an attractive proposition for new biological and biomedical approaches. Despite the remarkable speed of development in nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and the presentation of the proteins on their surface could lead to a different in vivo response than an uncoated particle. Here, in addition to protein adsorption, we are going to introduce concept of cell "vision", which would be recognized as another crucial factor that should be considered for the safe design of any type of nanoparticles that will be used in specific biomedical applications. The impact of exactly the same nanoparticles on various cells is significantly different and could not be assumed for other cells; the possible mechanisms that justify this cellular response relate to the numerous detoxification strategies that any particular cell can utilize in response to nanoparticles. The uptake and defence mechanism could be considerably different according to the cell type. Thus, what the cell "sees", when it is faced with nanoparticles, is most likely dependent on the cell type.
Glycosynthase Mutants of Endoglycosidase S2 Show Potent Transglycosylation Activity and Remarkably Relaxed Substrate Specificity for Antibody Glycosylation Remodeling (2016)

Glycosylation can exert a profound impact on the structures and biological functions of antibodies. Glycosylation remodeling using the endoglycosidase-catalyzed deglycosylation and transglycosylation approach is emerging as a promising platform to produce homogeneous glycoforms of antibodies, but the broad application of this method will require the availability of highly efficient glycosynthase mutants. We describe in this paper a systematic site-directed mutagenesis of an endoglycosidase from Streptococcus pyogenes of serotype M49 (Endo-S2) and the evaluation of the resulting mutants for their hydrolysis and transglycosylation activities. We found that mutations at the Asp-184 residue gave mutants that demonstrated significantly different properties, some possessed potent transglycosylation activity with diminished hydrolysis activity but others did not, which would be otherwise difficult to predict without the comparative study. In contrast to the previously reported Endo-S mutants that are limited to action on complex type N-glycans, the Endo-S2 glycosynthases described here, including D184M and D184Q, were found to have remarkably relaxed substrate specificity and were capable of transferring three major types (complex, high-mannose, and hybrid type) of N-glycans for antibody glycosylation remodeling. In addition, the Endo-S2 glycosynthase mutants were found to be much more active in general than the Endo-S mutants for transglycosylation. The usefulness of these Endo-S2 glycosynthase mutants was exemplified by an efficient glycosylation remodeling of two therapeutic monoclonal antibodies, rituximab and trastuzumab (Herceptin).
Vacuum deposited polymer films: Past, present, and future applications (1994)

Two extremely high rate processes have been developed for the vacuum deposition of polymer thin films. Dubbed the PML (for Polymer Multi-Layer) and LML (for Liquid Multi-Layer) processes, the PML technique was originally developed for the manufacture of polymer/aluminum surface mount capacitors while the LML method arose from a need to fabricate lithium polymer batteries. These processes have since been found to be compatible with most other vacuum deposition techniques in, integrated, in-line coating processes. Battelle has developed an extensive program, and a great deal of hardware, to pursue a wide variety of PML and LML applications which integrate these two process technologies with other, conventional, vacuum deposition methods. The historical development of the technologies is reviewed and the Battelle PML/LML facilities are described. Current Battelle work involving solar thermal control films, PML QWOTs, and polymer/metal high reflectors are also discussed. Battelle PML work that is just starting, involving non-linear optical materials/devices, lithium polymer battery fabrication, electrochromic devices, and polymer/oxide multilayers, is discussed as well.
12 (2012)

Introduction: Ventilator-associated pneumonia (VAP) is a leading HAI in ICUs despite improved patient care practices and advancements in endotracheal tube (ETT) designs. The ETT provides a conduit for bacterial access to the lower respiratory tract and a substratum for biofilm formation, both of which lead to VAP. A novel bio-inspired micro-topography may provide an alternative strategy for VAP prevention as it has been shown to reduce microbial attachment, migration and biofilm formation of several pathogens without the use of antimicrobial agents. Hypothesis: Micro-topography will reduce biofilm formation of VAP-associated pathogens in a medium mimicking the tracheal environment. Methods: To obtain mature Pseudomonas aeruginosa biofilms, patterned and un-patterned silicone samples (n=3) were immersed in arginine minimal medium with 2g/L porcine mucin and 400 mg/L oxacillin for 24hrs at 37°C. Four day Staphylococcus aureus biofilms developed in TSB media as described above. Experiments were completed in triplicate. Air-liquid interface P. aeruginosa biofilms grew on tilted samples (n=3) in mucin and oxacillin supplemented TSB. All samples were rinsed, fixed, dehydrated, and stained with propidium iodide. Image stacks were obtained in three pre-selected sites per sample by confocal laser scanning microscopy. Volumetric analysis was achieved by totaling biofilm area coverage in each z-stack and significance was assessed by student t-test or ANOVA models. Results: The micro-pattern reduced P. aeruginosa biofilm formation in a mucin-rich environment by an average of 58% (p<0.01) when compared to control surfaces. Four day S. aureus biofilms were reduced by an average of 67% (p=0.01). In an alternative model that simulates the air-liquid interface present on an ETT, P. aeruginosa biofilms were reduced by 44% (p<0.01). Conclusions: The micro-pattern surface modification inhibits the formation of P. aeruginosa biofilms in two models using a medium that mimics the tracheal environment. This pattern also reduces S. aureus biofilms, thereby demonstrating performance against two key VAP-associated species. These data suggest that the micro-pattern may prevent VAP without the use of antimicrobials if applied to the surface of an ETT.
LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation (2001)

Acute graft-versus-host disease (GVHD) and leukemic relapse remain the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT). Recent studies have demonstrated that the loss of gastrointestinal tract integrity, and specifically the translocation of LPS into the systemic circulation, is critical to the induction of cytokine dysregulation that contributes to GVHD. Using a mouse BMT model, we studied the effects of direct LPS antagonism on GVHD severity and graft-versus-leukemia (GVL) activity. Administration of B975, a synthetic lipid-A analogue from day 0 to day +6, reduced serum TNF-alpha levels, decreased intestinal histopathology, and resulted in significantly improved survival and a reduction in clinical GVHD, compared with control-treated animals. Importantly, B975 had no effect on donor T cell responses to host antigens in vivo or in vitro. When mice received lethal doses of P815 tumor cells at the time of BMT, administration of B975 did not impair GVL activity and resulted in significantly improved leukemia-free survival. These findings reveal a critical role for LPS in the early inflammatory events contributing to GVHD and suggest that a new class of pharmacologic agents, LPS antagonists, may help to prevent GVHD while preserving T cell responses to host antigens and GVL activity.
Recent advances in cardiovascular regenerative medicine: the induced pluripotent stem cell era (2008)

Induced pluripotent stem (iPS) cells have recently been established by transfecting mouse and human fibroblasts with the transcription factors Oct3/4, Sox2, Klf4 and c-Myc, known to be expressed at high levels in embryonic stem (ES) cells. These cells have great potential in regenerative medicine as they have the capacity to differentiate into all three germ layer-derived cells and are syngeneic. The differentiation of ES cells into cardiomyocytes mimics the early processes involved in heart development. Recent studies describe the contribution of various growth factors and corresponding inhibitors to heart development during embryogenesis. Bone morphogenetic proteins, Wnt protein and Notch signals play critical roles in heart development in a context- and time-dependent manner. Consistent with ES cells, the exposure of iPS cells to such growth factors is hypothesized to augment differentiation into cardiomyocytes. The combination of iPS cells and appropriate developmental signal information has the potential for providing the foundations for future regenerative medicine.
Follicular dendritic cell accessory activity crosses MHC and species barriers (2001)

Productive follicular dendritic cell (FDC)-B cell interactions appear to involve critical ligand-receptor interactions. Immune complexes (IC) on FDC activate complement and provide FDC with a complement-derived CD21 ligand (CD21L), which bind CD21, while antigen in the IC binds on the B cell-BCR. Further, FDC-FcgammaRIIB binds Fc regions of antibodies in IC and reduces coligation of BCR and FcgammaRIIB minimizing an inhibitor of B cell activation. Given that Fc receptors and complement receptors bind immunoglobulins and complement fragments of other species, we reasoned that FDC accessory activity should cross MHC and species barriers. This prediction was tested using memory lymphocytes from OVA-immune mice and TT-immune humans in combination with FDC from murine lymph nodes and human tonsils. Human and murine FDC converted IC into potent immunogens (specific antibody increased from background to thousands of ng / ml). MHC barriers did not restrict this activity and human FDC worked with murine lymphocytes and murine FDC worked with human lymphocytes. Furthermore, stimulation via MHC-dependent allogeneic or zenogeneic mechanisms did not promote antibody production by FDC. Polyclonal responses stimulated by lipopolysaccharide and pokeweed mitogen were also promoted (10 - 100-fold) and anti-CD21 blocked FDC activity. These results substantiate the hypothesis that FDC are necessary for strong recall responses and that FDC-CD21L is critical.
Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF (2005)

Toll-like receptors (TLRs) bind pathogen-specific ligands early in infection, initiating signaling pathways that lead to expression of multiple protective cellular genes. Many viruses have evolved strategies that block the effector mechanisms induced through these signaling pathways, but viral interference with critical proximal receptor interactions has not been described. We show here that the NS3/4A serine protease of hepatitis C virus (HCV), a virus notorious for its ability to establish persistent intrahepatic infection, causes specific proteolysis of Toll-IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF or TICAM-1), an adaptor protein linking TLR3 to kinases responsible for activating IFN regulatory factor 3 (IRF-3) and NF-kappaB, transcription factors controlling a multiplicity of antiviral defenses. NS3/4A-mediated cleavage of TRIF reduces its abundance and inhibits polyI:C-activated signaling through the TLR3 pathway before its bifurcation to IRF-3 and NF-kappaB. This uniquely broad mechanism of immune evasion potentially limits expression of multiple host defense genes, thereby promoting persistent infections with this medically important virus.
Analysis of T-Cell Receptor Gene Rearrangement and Expression in Human Natural Killer Clones (1985)

A series of clones of human natural killer (NK) cells was characterized with respect to expression of the Ti alpha and Ti beta genes of the T-cell receptor. T11+T3+ NK clones contained Ti alpha and Ti beta RNA transcripts and expressed disulfide-linked heterodimers, demonstrating the presence of a functional T-cell receptor. In contrast, T11+T3- NK clones expressed only 1.0-kilobase truncated Ti beta transcripts, without a Ti alpha transcript and no detectable surface Ti protein. Since previous studies demonstrated that Ti beta gene activation precedes Ti alpha gene activation in thymic ontogeny, the T11+T3- NK cells appear to be derived from T-lineage precursors.
LEAFY COTYLEDON2 encodes a B3 domain transcription factor that induces embryo development (2001)

The Arabidopsis LEAFY COTYLEDON2 (LEC2) gene is a central embryonic regulator that serves critical roles both early and late during embryo development. LEC2 is required for the maintenance of suspensor morphology, specification of cotyledon identity, progression through the maturation phase, and suppression of premature germination. We cloned the LEC2 gene on the basis of its chromosomal position and showed that the predicted polypeptide contains a B3 domain, a DNA-binding motif unique to plants that is characteristic of several transcription factors. We showed that LEC2 RNA accumulates primarily during seed development, consistent with our finding that LEC2 shares greatest similarity with the B3 domain transcription factors that act primarily in developing seeds, VIVIPAROUS1/ABA INSENSITIVE3 and FUSCA3. Ectopic, postembryonic expression of LEC2 in transgenic plants induces the formation of somatic embryos and other organ-like structures and often confers embryonic characteristics to seedlings. Together, these results suggest that LEC2 is a transcriptional regulator that establishes a cellular environment sufficient to initiate embryo development.
High power transcranial beam steering for ultrasonic brain therapy (2003)

A sparse phased array is specially designed for non-invasive ultrasound transskull brain therapy. The array is made of 200 single elements corresponding to a new generation of high power transducers developed in collaboration with Imasonic (Besançon, France). Each element has a surface of 0.5 cm2 and works at 0.9 MHz central frequency with a maximum 20 W cm(-2) intensity on the transducer surface. In order to optimize the steering capabilities of the array, several transducer distributions on a spherical surface are simulated: hexagonal, annular and quasi-random distributions. Using a quasi-random distribution significantly reduces the grating lobes. Furthermore, the simulations show the capability of the quasi-random array to electronically move the focal spot in the vicinity of the geometrical focus (up to +/- 15 mm). Based on the simulation study, the array is constructed and tested. The skull aberrations are corrected by using a time reversal mirror with amplitude correction achieved thanks to an implantable hydrophone, and a sharp focus is obtained through a human skull. Several lesions are induced in fresh liver and brain samples through human skulls, demonstrating the accuracy and the steering capabilities of the system.
Sensitivity of Human Immunodeficiency Virus Type 1 to the Fusion Inhibitor T-20 Is Modulated by Coreceptor Specificity Defined by the V3 Loop of gp120 (2000)

T-20 is a synthetic peptide that potently inhibits replication of human immunodeficiency virus type 1 by interfering with the transition of the transmembrane protein, gp41, to a fusion active state following interactions of the surface glycoprotein, gp120, with CD4 and coreceptor molecules displayed on the target cell surface. Although T-20 is postulated to interact with an N-terminal heptad repeat within gp41 in a trans-dominant manner, we show here that sensitivity to T-20 is strongly influenced by coreceptor specificity. When 14 T-20-naive primary isolates were analyzed for sensitivity to T-20, the mean 50% inhibitory concentration (IC(50)) for isolates that utilize CCR5 for entry (R5 viruses) was 0.8 log(10) higher than the mean IC(50) for CXCR4 (X4) isolates (P = 0. 0055). Using NL4.3-based envelope chimeras that contain combinations of envelope sequences derived from R5 and X4 viruses, we found that determinants of coreceptor specificity contained within the gp120 V3 loop modulate this sensitivity to T-20. The IC(50) for all chimeric envelope viruses containing R5 V3 sequences was 0.6 to 0.8 log(10) higher than that for viruses containing X4 V3 sequences. In addition, we confirmed that the N-terminal heptad repeat of gp41 determines the baseline sensitivity to T-20 and that the IC(50) for viruses containing GIV at amino acid residues 36 to 38 was 1.0 log(10) lower than the IC(50) for viruses containing a G-to-D substitution. The results of this study show that gp120-coreceptor interactions and the gp41 N-terminal heptad repeat independently contribute to sensitivity to T-20. These results have important implications for the therapeutic uses of T-20 as well as for unraveling the complex mechanisms of virus fusion and entry.
An End-to-End Compression Framework Based on Convolutional Neural Networks (2017)

Deep learning, e.g., convolutional neural networks (CNNs), has achieved great success in image processing and computer vision especially in high-level vision applications, such as recognition and understanding. However, it is rarely used to solve low-level vision problems such as image compression studied in this paper. Here, we move forward a step and propose a novel compression framework based on CNNs. To achieve high-quality image compression at low bit rates, two CNNs are seamlessly integrated into an end-to-end compression framework. The first CNN, named compact convolutional neural network (ComCNN), learns an optimal compact representation from an input image, which preserves the structural information and is then encoded using an image codec (e.g., JPEG, JPEG2000, or BPG). The second CNN, named reconstruction convolutional neural network (RecCNN), is used to reconstruct the decoded image with high quality in the decoding end. To make two CNNs effectively collaborate, we develop a unified end-to-end learning algorithm to simultaneously learn ComCNN and RecCNN, which facilitates the accurate reconstruction of the decoded image using RecCNN. Such a design also makes the proposed compression framework compatible with existing image coding standards. Experimental results validate that the proposed compression framework greatly outperforms several compression frameworks that use existing image coding standards with the state-of-the-art deblocking or denoising post-processing methods.
Optimization of the Coating Procedure for a High-Throughput 96-Blade Solid Phase Microextraction System Coupled with LC–MS/MS for Analysis of Complex Samples (2011)

Biocompatible C18-polyacrylonitrile (PAN) coating was used as the extraction phase for an automated 96-blade solid phase microextraction (SPME) system with thin-film geometry. Three different methods of coating preparation (dipping, brush painting, and spraying) were evaluated; the spraying method was optimum in terms of its stability and reusability. The high-throughput sample preparation was achieved by using a robotic autosampler that enabled simultaneous preparation of 96 samples in 96-well-plate format. The increased volume of the extraction phase of the C18-PAN thin film coating resulted in significant enhancement in the extraction recovery when compared with that of the C18-PAN rod fibers. Various factors, such as reusability, reproducibility, pH stability, and reliability of the coating were evaluated. The results showed that the C18-PAN 96-blade SPME coating presented good extraction recovery, long-term reusability, good reproducibility, and biocompatibility. The limits of detection and quantitation were in the ranges of 0.1-0.3 and 0.5-1 ng/mL for all four analytes.
SIKs control osteocyte responses to parathyroid hormone (2016)

Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.