gebhart/patrepeval huggingface dataset:
P-selectin-deficient mice are protected from PAF-induced shock, intestinal injury, and lethality (1997)

In a previous study, we showed that anti-CD11b or anti-CD18 antibody markedly attenuated platelet-activating factor (PAF)-induced shock and intestinal necrosis in rats, whereas anti-P-selectin anti-body was ineffective. Here we used genetically altered mice to study the mechanism of PAF in mice. We found that P-selectin-deficient mice are completely protected from the adverse effects of PAF with no mortality or intestinal injury and only mild hemoconcentration and transient hypotension. In contrast, CD18- or intercellular adhesion molecule 1 (ICAM-1)-deficient mice were not protected from PAF-induced tissue injury and death. However, when ICAM-1-, but not CD18-, deficient mice were pretreated with fucoidin, the adverse effects of PAF were markedly reduced; survival was 100%, although hypotension still developed. Neutrophil-depleted mice were protected from PAF-induced intestinal injury but still developed hypotension and hemoconcentration. PAF increases peripheral blood neutrophil counts, probably by inducing granulopoiesis, since neutrophil-depleted mice still showed granulocytosis 60 min after PAF. Thus P-selectin plays an important role in PAF-induced injury in mice, and the selectins and the integrin-ICAM-1 system work in concert to mediate the inflammatory response to PAF in vivo.
Indexing without invariants in 3D object recognition (1999)

We present a method of indexing 3D objects from single 2D images. The method does not rely on invariant features. This allows a richer set of shape information to be used in the recognition process. We also suggest the kd-tree as an alternative indexing data structure to the standard hash table. This makes hypothesis recovery more efficient in high-dimensional spaces, which are necessary to achieve specificity in large model databases. Search efficiency is maintained in these regimes by the use of best-bin first search. Neighbors recovered from the index are used to generate probability estimates, local within the feature space, which are then used to rank hypotheses for verification. On average, the ranking process greatly reduces the number of verifications required. Our approach is general in that it can be applied to any real-valued feature vector. In addition, it is straightforward to add to our index information from real images regarding the true probability distributions of the feature groupings used for indexing.
Combining markers with and without the limit of detection (2013)

In this paper, we consider the combination of markers with and without the limit of detection (LOD). LOD is often encountered when measuring proteomic markers. Because of the limited detecting ability of an equipment or instrument, it is difficult to measure markers at a relatively low level. Suppose that after some monotonic transformation, the marker values approximately follow multivariate normal distributions. We propose to estimate distribution parameters while taking the LOD into account, and then combine markers using the results from the linear discriminant analysis. Our simulation results show that the ROC curve parameter estimates generated from the proposed method are much closer to the truth than simply using the linear discriminant analysis to combine markers without considering the LOD. In addition, we propose a procedure to select and combine a subset of markers when many candidate markers are available. The procedure based on the correlation among markers is different from a common understanding that a subset of the most accurate markers should be selected for the combination. The simulation studies show that the accuracy of a combined marker can be largely impacted by the correlation of marker measurements. Our methods are applied to a protein pathway dataset to combine proteomic biomarkers to distinguish cancer patients from non-cancer patients.
The Toll/interleukin-1 receptor domain: a molecular switch for inflammation and host defence (2000)

The pro-inflammatory cytokine interleukin-1 (IL-1) signals via the Type-I IL-1 receptor (IL-1RI), inducing an increase in the expression of many genes with roles in immunity and inflammation. The signalling pathways involve two adapter proteins, MyD88 and Tollip, which via two IL-1 receptor-associated kinases (IRAK and IRAK-2) activate transcription factors such as nuclear factor-kappa B and protein kinases such as p38 mitogen-activated protein kinase. A role for the low-molecular-mass G-proteins Rac, Ras and Rap in these processes has also been indicated. IL-1RI is the founder of a diverse superfamily of receptors, which all share a cytosolic domain, termed the Toll/IL-1 receptor (TIR) domain. The superfamily can be divided broadly into three subgroups. The first of these is most similar to IL-1RI and includes the receptor for IL-18 and the Th2 cell regulator T1/ST2. The second subgroup is most similar to the Drosophila melanagaster protein Toll and includes Toll-like receptor 2 (TLR2), which is required for host defence against Gram-positive bacteria and fungi, and TLR4, which is required for lipopolysaccharide responsiveness, and thus is involved in host defence against Gram-negative bacteria. There are also a number of TLRs in plants and insects, all involved in host defence. The third subgroup contains non-receptor proteins which possess a TIR domain and are cytosolic. MyD88 is a member, and it presumably complexes with IL-1RI via a TIR-TIR interaction. The other two members are proteins encoded by the vaccinia virus, A46R and A52R, which block TIR-dependent signalling. This receptor superfamily therefore appears to play a central role in inflammation and host defence against infection, pointing to the TIR domain as a critical molecular player in the innate immune response.
Functional studies of the heart during a 24-hour preservation using a new autoperfusion preparation. (1991)

Serial cardiac function studies were carried out during a 24-hour preservation in a new autoperfusion multiorgan preparation using adult Yorkshire swine (n = 8). The heart was removed with the lungs, liver, pancreas, duodenum, and both kidneys while they were still perfused by the heart and oxygenated by the lungs. The organs were placed in a 32 degrees C bath solution containing lactated Ringer's, heparin, and neomycin. Fresh blood and a solution containing glucose (10%) with potassium chloride (2 gm/L), calcium chloride (1 gm/L), heparin sodium (100 mg/L), mannitol (12.5 gm/L), insulin (100 U/L), metronidazole hydrochloride (500 mg/L), penicillin (1,000,000 U/L), and methylprednisolone (250 mg/L) were given slowly through the portal vein. A fat emulsion 2 ml, methylprednisolone 30 mg, and heparin sodium 20 mg were given through the portal vein every 2 hours. No inotropic drugs were used. Aortic systolic pressures ranged from 79 to 97 mm Hg; the aortic diastolic pressures ranged from 44 to 61 mm Hg. Central venous pressures ranged from 0.4 to 2.0 mm Hg, and the heart rate was 69 to 81 beats/min. Left ventricular maximum dp/dt ranged from 1405 to 1836 mm Hg/sec, and maximum dp/dt/p ranged from 17.0 to 26.2 (sec-1). Aortic blood flow ranged from 1.2 to 1.6 L/min, and systemic resistance ranged from 33 to 53 U. Lactic acid decreased from 8.15 to 2.80 mmol/L. Myocardium wet/dry weight ratio after preservation averaged 5.13 (vs 5.09 for control). These results suggest that the heart may be preserved up to 24 hours with minimal change in function with this new autoperfusion preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
Use of transcriptional repressors to stabilize plasmid copy number of transcriptional fusion vectors (1985)

Strong promoters cloned into transcriptional fusion vectors can adversely affect plasmid copy number. In this study, we investigated the use of transcriptional repressors, lacI and tetR, to stabilize the copy number of plasmids containing the lacUV5 and tetA promoters, respectively. Repression of these promoters was found to prevent plasmid copy number variation. Transcriptional strength of these promoters, when cloned into transcriptional fusion vectors, was determined by measuring the rate of synthesis after derepression with inducer. By using this approach, promoter strength can be accurately measured in vivo, without the need to compensate for copy number variation.
Study of innovative electric machines for high efficiency vehicular traction applications (2013)

This thesis collects some of the work accomplished during the PhD research activity focused on the study of special electric machines for vehicle traction applications. The work is divided into due parts. The rst part is mainly technological and covers some studies and experimental activities concerning new technical solutions to solve some common issues in operation of electric motors for automotive use, namely ux weakening and cogging torque. The second part has a more theoretical nature and focuses on some methods for electric machine modeling and analysis which has been developed to facilitate the study and design optimizations carried out during the PhD research work.&#13;\nThe chapters in the rst part address the following topics:&#13;\n1. Development and testing of an interior-permanent-magnet motor prototype fully conceived, designed and manufactured at the University of Trieste to implement a new concept of flux weakening system at high speeds. The concept has been also protected through a pending patent.&#13;\n2. Multi-objective design optimization of an interior permanent magnet reluctance-assisted synchronous motor for the automotive industry.&#13;\nThe design optimization was meant to support an industrial development project which is still in progress so no prototype has been built yet.&#13;\n3. Study of a new optimized magnetic wedge design capable of reducing cogging torque in automotive propulsion motors having open stator slots.&#13;\nThe second part proposes some analytical and numerical results that have been worked out to approach the modeling and optimization of various kinds of permanent magnet synchronous motors. The main problem to which these chapters try to answer is to nd suciently fast but accurate methods for permanent magnet analysis without time-consuming finite-element transient analysis. The proposed methods have been successfully integrated into design optimization programs used in the industrial environment in the development of innovative electric machines not only for the automotive industry.
An in vitro polysome display system for identifying ligands from very large peptide libraries. (1994)

We have used an in vitro protein synthesis system to construct a very large library of peptides displayed on polysomes. A pool of DNA sequences encoding 10(12) random decapeptides was incubated in an Escherichia coli S30 coupled transcription/translation system. Polysomes were isolated and screened by affinity selection of the nascent peptides on an immobilized monoclonal antibody specific for the peptide dynorphin B. The mRNA from the enriched pool of polysomes was recovered, copied into cDNA, and amplified by the polymerase chain reaction (PCR) to produce template for the next round of in vitro synthesis and selection. A portion of the amplified template from each round was cloned into a filamentous phagemid vector to determine the specificity of peptide binding by phage ELISA and to sequence the DNA. After four rounds of affinity selection, the majority of clones encoded peptides that bound specifically to the antibody and contained a consensus sequence that is similar to the known epitope for the antibody. Synthetic peptides corresponding to several of these sequences have binding affinities ranging from 7 to 140 nM. The in vitro system described here has the potential to screen peptide libraries that are three to six orders of magnitude larger than current biological peptide display systems.
A new ultrasonic process for a renewal of aortic valve decalcification (2006)

This new approach of ultrasonic aortic valve decalcification gives good in vitro results which allow to consider a clinical evaluation of this procedure.
Flow oriented linear dichroism to probe protein orientation in membrane environments (2002)

The first page of this article is displayed as the abstract.
In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance (2009)

We previously showed that incorporating target sequences for the hematopoietic-specific microRNA miR-142 into an antigen-encoding transgene prevents antigen expression in antigen-presenting cells (APCs). To determine whether this approach induces immunologic tolerance, we treated mice with a miR-142-regulated lentiviral vector encoding green fluorescent protein (GFP), and subsequently vaccinated the mice against GFP. In contrast to control mice, no anti-GFP response was observed, indicating that robust tolerance to the transgene-encoded antigen was achieved. Furthermore, injection of the miR-142-regulated vector induced a population of GFP-specific regulatory T cells. Interestingly, an anti-GFP response was observed when microRNA miR-122a was inserted into the vector and antigen expression was detargeted from hepatocytes as well as APCs. This demonstrates that, in the context of lentiviral vector-mediated gene transfer, detargeting antigen expression from professional APCs, coupled with expression in hepatocytes, can induce antigen-specific immunologic tolerance.
Comparison of the therapeutic effects of human and mouse adipose-derived stem cells in a murine model of lipopolysaccharide-induced acute lung injury (2013)

Treatment with hASCs or mASCs significantly attenuated LPS-induced acute lung injury in mice. These results suggest a potential benefit for using an ASC-based therapy to treat clinical ALI and may possibly prevent the development of acute respiratory distress syndrome (ARDS).
Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment (2002)

Most lymphomas that involve the central nervous system are B-cell neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in the cerebrospinal fluid (CSF) in patients with primary central nervous system lymphoma; however, the CSF levels of rituximab are approximately 0.1% of serum levels associated with therapeutic activity in patients with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is a frequent complication of non-Hodgkin lymphoma, we have conducted an analysis of the safety and pharmacokinetics of direct intrathecal administration of rituximab using cynomolgus monkeys. No significant acute or delayed toxicity, neurologic or otherwise, was detected. Pharmacokinetic analysis suggests that drug clearance from the CSF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent lymphomatous meningitis will be implemented based on these findings.
Protective Effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration (2004)

Clinical trials of several neurodegenerative diseases have increasingly targeted the evaluation of various antioxidants' effectiveness. The human diet contains several thousand phytochemicals, many of which have significant bioactivities. Vitamin C, a naturally occurring antioxidant, is known to reduce the risk of neurodegenerative disorders such as Alzheimer's disease. Quercetin, one of the major flavonoids in some fruits and vegetables, has much stronger antioxidative and anticarcinogenic activities than vitamin C. Therefore, we investigated the protective effects of quercetin on hydroxy peroxide-induced neurodegeneration. To determine the protective effects, PC12 cells were preincubated with quercetin and vitamin C before H(2)O(2) treatment for 2 h. Results showed that cell viability was clearly improved with quercetin, and quercetin showed a higher protective effect than vitamin C. Because oxidative stress is known to increase neuronal cell membrane breakdown, we further investigated lactate dehydrogenase and trypan blue exclusion assays. We observed that quercetin decreased oxidative stress-induced neuronal cell membrane damage more than vitamin C. These results suggest that quercetin, in addition to many other biological benefits, contributes significantly to the protective effects of neuronal cells from oxidative stress-induced neurotoxicity, such as Alzheimer disease.
A highly sensitive affinity-column-mediated immunometric assay, as exemplified by digoxin. (1984)

We describe a highly sensitive heterogeneous enzyme-linked immunoassay in which digoxin is used as the model analyte. An excess of enzyme-labeled monovalent antibody is incubated with sample containing the analyte such that all analyte is rapidly and quantitatively bound. Excess antibody that does not acquire a antigen in its binding site is rapidly removed from the mixture by passage through a porous affinity column containing immobilized analyte (or analog), present in vast excess. Only the labeled monovalent antibody that possesses an antigen in its binding site elutes from the column in the unbound fraction. The label present in this fraction is then quantified. Such an assay is extremely sensitive and obviates the limitations imposed by antibody affinity constants on homogeneous and competitive heterogeneous immunoassays. This assay can be performed rapidly and is readily amenable to automation.
Removal of magnetoencephalographic artifacts with temporal signal‐space separation: Demonstration with single‐trial auditory‐evoked responses (2008)

Magnetic interference signals often hamper analysis of magnetoencephalographic (MEG) measurements. Artifact sources in the proximity of the sensors cause strong and spatially complex signals that are particularly challenging for the existing interference-suppression methods. Here we demonstrate the performance of the temporally extended signal space separation method (tSSS) in removing strong interference caused by external and nearby sources on auditory-evoked magnetic fields-the sources of which are well established. The MEG signals were contaminated by normal environmental interference, by artificially produced additional external interference, and by nearby artifacts produced by a piece of magnetized wire in the subject's lip. After tSSS processing, even the single-trial auditory responses had a good-enough signal-to-noise ratio for detailed waveform and source analysis. Waveforms and source locations of the tSSS-reconstructed data were in good agreement with the responses from the control condition without extra interference. Our results demonstrate that tSSS is a robust and efficient method for removing a wide range of different types of interference signals in neuromagnetic multichannel measurements.
Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity (2013)

Recent studies have underscored the importance of memory T cells in mediating protective immunity against pathogens and cancer. Pharmacological inhibition of regulators that mediate T cell differentiation promotes the differentiation of activated CD8(+) T cells into memory cells. Nonetheless, pharmacological agents have broad targets and can induce undesirable immunosuppressive effects. Here, we tested the hypothesis that aptamer-targeted siRNA inhibition of mTOR complex 1 (mTORC1) function in CD8(+) T cells can enhance their differentiation into memory T cells and potentiate antitumor immunity more effectively than the pharmacologic inhibitor rapamycin. To specifically target activated cells, we conjugated an siRNA targeting the mTORC1 component raptor to an aptamer that binds 4-1BB, a costimulatory molecule that is expressed on CD8(+) T cells following TCR stimulation. We found that systemic administration of the 4-1BB aptamer-raptor siRNA to mice downregulated mTORC1 activity in the majority of CD8(+) T cells, leading to the generation of a potent memory response that exhibited cytotoxic effector functions and enhanced vaccine-induced protective immunity in tumor-bearing mice. In contrast, while treatment with the general mTORC1 inhibitor rapamycin also enhanced antigen-activated CD8(+) T cell persistence, the cytotoxic effector functions of the reactivated memory cells were reduced and the alloreactivity of DCs was diminished. Consistent with the immunological findings, mice treated with rapamycin, but not with 4-1BB aptamer-raptor siRNA, failed to reject a subsequent tumor challenge.
Scalable Tensor Decompositions for Multi-aspect Data Mining (2008)

Modern applications such as Internet traffic, telecommunication records, and large-scale social networks generate massive amounts of data with multiple aspects and high dimensionalities. Tensors (i.e., multi-way arrays) provide a natural representation for such data. Consequently, tensor decompositions such as Tucker become important tools for summarization and analysis. One major challenge is how to deal with high-dimensional, sparse data. In other words, how do we compute decompositions of tensors where most of the entries of the tensor are zero. Specialized techniques are needed for computing the Tucker decompositions for sparse tensors because standard algorithms do not account for the sparsity of the data. As a result, a surprising phenomenon is observed by practitioners: Despite the fact that there is enough memory to store both the input tensors and the factorized output tensors, memory overflows occur during the tensor factorization process. To address this intermediate blowup problem, we propose Memory-Efficient Tucker (MET). Based on the available memory, MET adaptively selects the right execution strategy during the decomposition. We provide quantitative and qualitative evaluation of MET on real tensors. It achieves over 1000X space reduction without sacrificing speed; it also allows us to work with much larger tensors that were too big to handle before. Finally, we demonstrate a data mining case-study using MET.
Light-Sheet-Based Fluorescence Microscopy for Three-Dimensional Imaging of Biological Samples (2013)

In modern biology, most optical imaging technologies are applied to two-dimensional cell culture systems; that is, they are used in a cellular context that is defined by hard and flat surfaces. However, a physiological context is not found in single cells cultivated on coverslips. It requires the complex three-dimensional (3D) relationship of cells cultivated in extracellular matrix (ECM) gels, tissue sections, or in naturally developing organisms. In fact, the number of applications of 3D cell cultures in basic research as well as in drug discovery and toxicity testing has been increasing over the past few years. Unfortunately, the imaging of highly scattering multicellular specimens is still challenging. The main issues are the limited optical penetration depth, the phototoxicity, and the fluorophore bleaching. Light-sheet-based fluorescence microscopy (LSFM) overcomes many drawbacks of conventional fluorescence microscopy by using an orthogonal/azimuthal fluorescence arrangement with independent sets of lenses for illumination and detection. The basic idea is to illuminate the specimen from the side with a thin light sheet that overlaps with the focal plane of a wide-field fluorescence microscope. Optical sectioning and minimal phototoxic damage or photobleaching outside a small volume close to the focal plane are intrinsic properties of LSFM. We discuss the basic principles of LSFM and methods for the preparation, embedding, and imaging of 3D specimens used in the life sciences in an implementation of LSFM known as the single (or selective) plane illumination microscope (SPIM).
Experimental importance sampling using a 3-section PMD emulator with programmable DGD elements (2003)

We experimentally employ importance sampling techniques using three programmable differential group delay (DGD) elements to obtain rare polarization mode dispersion (PMD) events with probabilities as low as 10/sup -24/ with only 1000 random samples. Our method does not require deterministic control of the polarization coupling between sections.