gebhart/patrepeval huggingface dataset:
Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization (2017)

We propose a technique for producing `visual explanations' for decisions from a large class of Convolutional Neural Network (CNN)-based models, making them more transparent. Our approach - Gradient-weighted Class Activation Mapping (Grad-CAM), uses the gradients of any target concept (say logits for `dog' or even a caption), flowing into the final convolutional layer to produce a coarse localization map highlighting the important regions in the image for predicting the concept. Unlike previous approaches, Grad- CAM is applicable to a wide variety of CNN model-families: (1) CNNs with fully-connected layers (e.g. VGG), (2) CNNs used for structured outputs (e.g. captioning), (3) CNNs used in tasks with multi-modal inputs (e.g. visual question answering) or reinforcement learning, without architectural changes or re-training. We combine Grad-CAM with existing fine-grained visualizations to create a high-resolution class-discriminative visualization, Guided Grad-CAM, and apply it to image classification, image captioning, and visual question answering (VQA) models, including ResNet-based architectures. In the context of image classification models, our visualizations (a) lend insights into failure modes of these models (showing that seemingly unreasonable predictions have reasonable explanations), (b) outperform previous methods on the ILSVRC-15 weakly-supervised localization task, (c) are more faithful to the underlying model, and (d) help achieve model generalization by identifying dataset bias. For image captioning and VQA, our visualizations show even non-attention based models can localize inputs. Finally, we design and conduct human studies to measure if Grad-CAM explanations help users establish appropriate trust in predictions from deep networks and show that Grad-CAM helps untrained users successfully discern a `stronger' deep network from a `weaker' one even when both make identical predictions. Our code is available at https: //github.com/ramprs/grad-cam/ along with a demo on CloudCV [2] and video at youtu.be/COjUB9Izk6E.
Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy (2018)

CYD-TDV protected against severe VCD and hospitalization for VCD for 5 years in persons who had exposure to dengue before vaccination, and there was evidence of a higher risk of these outcomes in vaccinated persons who had not been exposed to dengue. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers, NCT00842530 , NCT01983553 , NCT01373281 , and NCT01374516 .).
Monomeric Monocyte Chemoattractant Protein-1 (MCP-1) Binds and Activates the MCP-1 Receptor CCR2B (1998)

To address the role of dimerization in the function of the monocyte chemoattractant protein-1, MCP-1, we mutated residues that comprise the core of the dimerization interface and characterized the ability of these mutants to dimerize and to bind and activate the MCP-1 receptor, CCR2b. One mutant, P8A*, does not dimerize. However, it has wild type binding affinity, stimulates chemotaxis, inhibits adenylate cyclase, and stimulates calcium influx with wild type potency and efficacy. These data suggest that MCP-1 binds and activates its receptor as a monomer. In contrast, Y13A*, another monomeric mutant, has a 100-fold weaker binding affinity, is a much less potent inhibitor of adenylate cyclase and stimulator of calcium influx, and is unable to stimulate chemotaxis. Thus Tyr13 may make important contacts with the receptor that are required for high affinity binding and signal transduction. We also explored whether a mutant, [1+9-76]MCP-1 (MCP-1 lacking residues 2-8), antagonizes wild type MCP-1 by competitive inhibition, or by a dominant negative mechanism wherein heterodimers of MCP-1 and [1+9-76]MCP-1 bind to the receptor but are signaling incompetent. Consistent with the finding that MCP-1 can bind and activate the receptor as a monomer, we demonstrate that binding of MCP-1 in the presence of [1+9-76]MCP-1 over a range of concentrations of both ligands fits well to a simple model in which monomeric [1+9-76]MCP-1 functions as a competitive inhibitor of monomeric MCP-1. These results are crucial for elucidating the molecular details of receptor binding and activation, for interpreting mutagenesis data, for understanding how antagonistic chemokine variants function, and for the design of receptor antagonists.
Homocysteine attenuates endothelial haem oxygenase‐1 induction by nitric oxide (NO) and hypoxia (2001)

The disrupted metabolism of homocysteine (Hcy) causes hyperhomocysteinemia, a condition associated with the impairment of nitric oxide (NO) bio-availability, tissue hypoxia and increased risk of vascular disease. Here, we examined how Hcy modulates the induction of the stress protein haem oxygenase-1 (HO-1) evoked by NO releasing agents and hypoxia in vascular endothelial cells. We found that Hcy (0.5 mM) markedly reduced the increase in haem oxygenase activity and HO-1 protein expression induced by sodium nitroprusside (SNP, 0.5 mM) but did not affect HO-1 activation mediated by S-nitroso-N-acetyl-penicillamine. Cells pre-treated with Hcy followed by addition of fresh medium containing SNP still exhibited an augmented haem oxygenase activity. Interestingly, high levels of Hcy were also able to abolish hypoxia-mediated HO-1 expression in a concentration-dependent manner. These novel findings indicate that hyperhomocysteinemia interferes with crucial signaling pathways required by cells to respond and adapt to stressful conditions.
Enhancement of Memory in Alzheimer Disease With Insulin and Somatostatin, but Not Glucose (1999)

These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD.
Excessive genomic DNA copy number variation in the Li–Fraumeni cancer predisposition syndrome (2008)

DNA copy number variations (CNVs) are a significant and ubiquitous source of inherited human genetic variation. However, the importance of CNVs to cancer susceptibility and tumor progression has not yet been explored. Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited disorder characterized by a strikingly increased risk of early-onset breast cancer, sarcomas, brain tumors and other neoplasms in individuals harboring germline TP53 mutations. Known genetic determinants of LFS do not fully explain the variable clinical phenotype in affected family members. As part of a wider study of CNVs and cancer, we conducted a genome-wide profile of germline CNVs in LFS families. Here, by examining DNA from a large healthy population and an LFS cohort using high-density oligonucleotide arrays, we show that the number of CNVs per genome is well conserved in the healthy population, but strikingly enriched in these cancer-prone individuals. We found a highly significant increase in CNVs among carriers of germline TP53 mutations with a familial cancer history. Furthermore, we identified a remarkable number of genomic regions in which known cancer-related genes coincide with CNVs, in both LFS families and healthy individuals. Germline CNVs may provide a foundation that enables the more dramatic chromosomal changes characteristic of TP53-related tumors to be established. Our results suggest that screening families predisposed to cancer for CNVs may identify individuals with an abnormally high number of these events.
Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses (2015)

Neuraminidase (NA) is an influenza virus enzymatic protein that cleaves sialic acid linkages on infected cell surfaces, thus facilitating viral release and contributing to viral transmission and mucus infection. In currently available inactivated or live, attenuated influenza vaccines based on the antigenic content of hemagglutinin proteins, vaccine efficacy can be contributed partly through NA-elicited immune responses. We investigated the NA immunity of different recombinant NA (rNA) proteins associated with pH1N1 and H5N1 viruses. Our results indicate that H5N1 rNA immunization induced more potent cross-protective immunity than pH1N1 rNA immunization, and three mutated residues, I149V, I365T, and S366N, near the NA enzyme active site(s) are linked to enhanced cross-reactive NA-inhibiting antibodies against heterologous and heterosubtypic influenza A viruses. These findings provide useful information for the development of an NA-based universal influenza vaccine.
New chemotherapeutic strategies for soft tissue sarcomas (1999)

Advanced soft-tissue sarcomas are still incurable in the vast majority of patients. The currently available standard methods of treatment such as surgery, radiation therapy, and chemotherapy have a very modest impact on the natural history of advanced soft tissue sarcomas. Nevertheless, until new strategies become widely available and applicable to this disease, we are obligated to optimize the current resources and make the best use of these modalities. We discuss the approaches of standard chemotherapy used in a dose-intensive fashion (especially in high-risk patients at an earlier stage), attempts to find new drugs with activity in this disease, and tests of the concepts of anti-angiogenic and differentiation therapy. To improve cure rates, patients and physicians must be encouraged to participate in multidisciplinary clinical trials.
CEDIA, a new homogeneous immunoassay system. (1986)

Genetic engineering of beta-galactosidase (EC 3.2.1.23) has led to the development of a new homogeneous assay system, CEDIA. The Z gene of the lac operon of Escherichia coli encodes a large enzymatically inactive polypeptide that spontaneously aggregates and folds to form active beta-galactosidase. Using recombinant DNA techniques, we have been able to engineer beta-galactosidase protein into a large polypeptide (an enzyme acceptor, EA) and a small polypeptide (an enzyme donor, ED). The EAs and EDs are both enzymatically inactive, but spontaneously associate to form enzymatically active tetramers. In the assay, hapten or analyte is attached to an ED, and an analyte-specific antibody is used to inhibit the spontaneous assembly of active enzyme. Analyte in a patient's serum competes with the analyte in the analyte-ED conjugate for antibody, modulating the amount of beta-galactosidase formed. The signal generated by enzyme substrates is directly proportional to the analyte concentrations in the patient's serum. We describe quick (5-15 min) colorimetric tests for digoxin, requiring no serum pretreatments or predilutions and suitable for use with centrifugal and random-access analyzers.
Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model (2000)

40-kHz US at low intensity markedly accelerates fibrinolysis and also improves tissue perfusion and reverses acidosis, effects that would be beneficial in treatment of acute thrombosis.
A microfluidic-based hydrodynamic trap: design and implementation (2011)

We report an integrated microfluidic device for fine-scale manipulation and confinement of micro- and nanoscale particles in free-solution. Using this device, single particles are trapped in a stagnation point flow at the junction of two intersecting microchannels. The hydrodynamic trap is based on active flow control at a fluid stagnation point using an integrated on-chip valve in a monolithic PDMS-based microfluidic device. In this work, we characterize device design parameters enabling precise control of stagnation point position for efficient trap performance. The microfluidic-based hydrodynamic trap facilitates particle trapping using the sole action of fluid flow and provides a viable alternative to existing confinement and manipulation techniques based on electric, optical, magnetic or acoustic force fields. Overall, the hydrodynamic trap enables non-contact confinement of fluorescent and non-fluorescent particles for extended times and provides a new platform for fundamental studies in biology, biotechnology and materials science.
Layered representation for motion analysis (2002)

Standard approaches to motion analysis assume that the optic flow is smooth; such techniques have trouble dealing with occlusion boundaries. The image sequence can be decomposed into a set of overlapping layers, where each layer's motion is described by a smooth flow field. The discontinuities in the description are then attributed to object opacities rather than to the flow itself, mirroring the structure of the scene. A set of techniques is devised for segmenting images into coherently moving regions using affine motion analysis and clustering techniques. It is possible to decompose an image into a set of layers along with information about occlusion and depth ordering. The techniques are applied to a flower garden sequence. The scene can be analyzed into four layers, and, the entire 30-frame sequence can be represented with a single image of each layer, along with associated motion parameters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulatory T Cells Control Immune Responses through Their Non-Redundant Tissue Specific Features (2013)

Regulatory T cells (Treg) are needed in the control of immune responses and to maintain immune homeostasis. Of this subtype of regulatory lymphocytes, the most potent are Foxp3 expressing CD4+ T cells, which can be roughly divided into two main groups; natural Treg cells (nTreg), developing in the thymus, and induced or adaptive Treg cells (iTreg), developing in the periphery from naïve, conventional T cells. Both nTreg cells and iTreg cells have their own, non-redundant roles in the immune system, with nTreg cells mainly maintaining tolerance toward self-structures, and iTreg developing in response to externally delivered antigens or commensal microbes. In addition, Treg cells acquire tissue specific features and are adapted to function in the tissue they reside. This review will focus on some specific features of Treg cells in different compartments of the body.
Characterization of replication-competent retroviruses from nonhuman primates with virus-induced T-cell lymphomas and observations regarding the mechanism of oncogenesis (1994)

Rapidly progressive T-cell lymphomas were observed in 3 of 10 rhesus monkeys several months after autologous transplantation of enriched bone marrow stem cells that had been transduced with a retroviral vector preparation containing replication-competent virus (R. E. Donahue, S. W. Kessler, D. Bodice, K. McDonagh, C. Dunbar, S. Goodman, B. Agricola, E. Byrne, M. Raffeld, R. Moen, J. Bacher, K. M. Zsebo, and A. W. Nienhuis, J. Exp. Med. 176:1124-1135, 1992). The animals with lymphoma appeared to be tolerant to retroviral antigens in that their sera lacked antibodies reactive with viral proteins and contained 10(4) to 10(5) infectious virus particles per ml. By molecular cloning and DNA sequencing, we have now demonstrated that the serum from one of the monkeys contained a replication-competent retrovirus that arose by recombination between vector and packaging encoding sequences (vector/helper [V/H] recombinant) in the producer clone used for transduction of bone marrow stem cells. Southern blot analysis demonstrated 14 or 25 copies of this genome per cell where present in two animals. The genome of a second replication-competent virus was also recovered by molecular cloning; it arose by recombination involving the genome of the V/H recombinant and endogenous murine retroviral genomes in the producer clone. Twelve copies of this amphotropic virus/mink cell focus-forming virus genome were present in tumor DNA of one animal, but it was not found in tumor DNA of the other two animals with lymphoma. Southern blot analysis of DNA from various tissues demonstrated common insertion site bands in several samples of tumor DNA from one animal, suggesting clonal origin of the lymphoma. Our data are most consistent with a pathogenic mechanism in which chronic productive retroviral infection allowed insertional mutagenesis of critical growth control genes, leading to cell transformation and clonal tumor evolution.
Large Polycrystalline Silicon Grains Prepared by Excimer Laser Crystallization of Sputtered Amorphous Silicon Film with Process Temperature at 100 °C (2007)

Large polycrystalline silicon (poly-Si) grains with a diameter of 1.8 µm are successfully prepared by excimer laser crystallization (ELC) of a sputtered amorphous silicon (α-Si) film at a maximum process temperature of 100 °C. By pulsed DC magnetron sputtering, α-Si is deposited on a non-structured oxidized wafer. It is found that the α-Si film deposited with a bias is easily ablated during ELC, even at an energy density below the super lateral growth (SLG) region. However, the α-Si film deposited without a bias can endure an energy density well beyond the SLG region without ablation. This zero-bias sputtered α-Si film with a high compressive stress has a low Ar content and a high density, which is beneficial for the suppression of ablation. Large grains with a petal-like shape can be obtained in a wide energy density window, which can be a result from some fine crystallites in the α-Si matrix. These large grains with a low process temperature are promising for the direct formation of system circuits as well as a high-quality display on a plastic foil.
FetalRHDgenotyping in maternal serum during the first trimester of pregnancy (2002)

Fetal RHD genotype determination is useful in the management of sensitized RhD-negative pregnant women. It can be ascertained early during pregnancy by chorionic villus sampling (CVS) or amniocentesis. However, these procedures are invasive, resulting both in an increased risk of fetal loss and in an increased severity of immunization due to fetomaternal haemorrhage. A reliable determination of RHD genotype by fetal DNA analysis in maternal serum during the first trimester of pregnancy is reported in this study. One hundred and six sera from RhD-negative pregnant women were obtained during the first trimester of pregnancy. These sera were tested for the presence of RHD gene using a new real-time polymerase chain reaction assay and the results compared with those obtained later in pregnancy on amniotic fluid cells and by RHD serology of the new-born. All sera from women carrying a RhD-positive fetus (n = 62) gave positive results for RHD gene detection and sera from women carrying a RhD-negative fetus (n = 40) were negative. The high level of accuracy of fetal RHD genotyping obtained in this study could enable this technique to be offered on a routine basis for the management of RhD-negative patients during the first trimester of pregnancy.
A conserved tryptophan in pneumolysin is a determinant of the characteristics of channels formed by pneumolysin in cells and planar lipid bilayers (1998)

Pneumolysin is one of the family of thiol-activatable, cytolytic toxins. Within these toxins the amino acid sequence Trp-Glu-Trp-Trp is conserved. Mutations made in this region of pneumolysin, residues 433-436 inclusive, did not affect cell binding or the formation of toxin oligomers in the target cell membrane. However, the mutations did affect haemolysis, leakage of low-molecular-mass metabolites from Lettre cells and the induction of conductance channels across planar lipid bilayers. Of eight modified pneumolysins examined, Trp-433-->Phe showed the smallest amount of haemolysis or leakage (less than 5% of wild type). Pneumolysin-induced leakage from Lettre cells was sensitive to inhibition by bivalent cations but the extent of inhibition varied depending on the modification. Leakage by the mutant Trp-433-->Phe was least sensitive to cation inhibition. The ion-conducting channels formed across planar lipid bilayers exhibit small (less than 30 pS), medium (30 pS-1 nS) and large (more than 1 nS) conductance steps. Small- and medium-sized channels were preferentially closed by bivalent cations. In contrast with wild-type toxin, which formed predominantly small channels, the modified toxin Trp-433-->Phe formed large channels that were insensitive to cation-induced closure. Polysaccharides of molecular mass more than 15 kDa inhibited haemolysis by wild-type toxin, but polysaccharide of up to 40 kDa did not prevent haemolysis by Trp-433-->Phe. Electron microscopy revealed that Trp-433-->Phe formed oligomeric arc and ring structures with dimensions identical with those of wild-type toxin, and that the ratio of arcs to rings formed was the same for wild-type toxin and the Trp-433-->Phe variant. We conclude that the change Trp-433-->Phe affects channel formation at a point subsequent to binding to the cell membrane and the formation of oligomers, and that the size of arc and ring structures revealed by electron microscopy does not reflect the functional state of the channels.
<title>Image fusion using geometrical features</title> (1992)

This paper describes a new approach to register images obtained from different modalities. Differential operators in scale space are used to extract geometric features from the images corresponding to similar structures. The resulting feature images may be matched by minimizing some function of the distances between the features in the respective images. Our first application concerns matching of brain images. We discuss a differential operator that produces ridge-like feature images from which the center curve of the cranium is easily extracted in CT and MRI. Results of the performance of these operators in 2-D matching tasks are presented. In addition, the potential of this approach for multimodality matching of 3-D medical images is illustrated by the striking similarity of the ridge images extracted from CT and MR images by the 3-D version of the operator.
Harmonics load signature recognition by wavelets transforms (2002)

Power quality has become an important concern both to the utilities and their customers. End user equipment is often more sensitive to disturbances that exist both on the supplying power system and within the customer facilities. Power quality embraces problems caused by harmonics, over or under-voltages, or supply discontinuities. Harmonics are caused by all sorts of nonlinear loads. In order to fully understand the problems caused by harmonics pollution, an effective means of identifying sources of power harmonics is important. The authors used fuzzy numbers for harmonics signature recognition. In this paper, the authors have made use of new developments in wavelets so that each type of current waveform polluted with power harmonics can well be represented by a normalised energy vector consisting of five elements. Furthermore, a mixture of harmonics load can also be represented by a corresponding vector. This paper describes the mathematics and algorithms for arriving at the vectors, forming a strong foundation for real-time harmonics signature recognition, in particular useful to the re-structuring of the whole electric power industry.