gebhart/patrepeval huggingface dataset:
Ca2+ entry via AMPA/KA receptors and excitotoxicity in cultured cerebellar Purkinje cells (1994)

Initial studies of glutamate receptors activated by kainate (KA) found them to be Ca2+ impermeable. Activation of these receptors was thought to produce Ca2+ influx into neurons only indirectly by Na(+)-dependent depolarization. However, Ca2+ entry via AMPA/KA receptors has now been demonstrated in several neuronal types, including cerebellar Purkinje cells. We have investigated whether such Ca2+ influx is sufficient to induce excitotoxicity in cultures of cerebellar neurons enriched for Purkinje cells. Agonists at non-NMDA receptors induced Ca2+ influx in the majority of these cells, as measured by whole-cell voltage clamp and by fura-2 [Ca2+]i microfluorimetry. To assess excitotoxicity, neurons were exposed to agonists for 20 min and cell survival was evaluated by a fluorescence assay 24 hr later. KA (100 microM) reduced neuronal survival relative to controls to 43 +/- 3% when applied in Na(+)-containing solution and to 45 +/- 3% in Na(+)-free solution. This toxicity was blocked completely by CNQX but only slightly by 100 microM Cd2+ and 50 microM D-(-)-2-amino-5-phosphonovaleric acid. Both Purkinje neurons and non-Purkinje cell types present in the cultures were similarly vulnerable to toxic KA exposure, but the population marked by KA-induced Co2+ uptake was selectively diminished by the excitotoxicity. Na(+)-independent excitotoxicity could also be induced by domoate, AMPA, or glutamate. Compared to KA, NMDA was relatively ineffective in inducing cell death. Most of the KA-induced excitotoxicity could be blocked by removal of extracellular Ca2+ during the KA exposure and for a 5 min period thereafter. Furthermore, antagonists of the Ca(2+)-activated enzymes nitric oxide synthase and calpain significantly reduced the KA-induced cell death. These results show that non-NMDA receptor activation can cause excitotoxicity in cerebellar Purkinje neurons by mechanisms not involving Na+ influx, but rather depending on direct Ca2+ permeation and activation of Ca(2+)- dependent enzymatic processes.
Electrochemical Biosensors for Detection of Biological Warfare Agents (2003)

Abstract This review discusses current development in electrochemical biosensors for detection of biological warfare agents. This could include bacteria, viruses and toxins that are aerosoled deliberately in air, food or water to spread terrorism and cause disease or death to humans, animals or plants. The rapid and unequivocal detection and identification of biological warfare agents is a major challenge for any government including military, health and other government agents. Reliable, specific characterization and identification of the microorganism from sampling location, either air, water, soil or others is required. This review will survey different types of electrochemical biosensors has been developed based on the following: i) Immunosensors ii) PCR (DNA base Sensor) iii) Bacteria or whole cell sensor and iv) Enzyme sensor. This article gives an overview of electrochemical biosensor for detection of biological warfare agents. Electrochemical biosensors have the advantages of sensitivity, selectivity, to operate in turbid media, and amenable to miniaturization. Recent developments in immunofiltration, flow injection, and flow‐through electrochemical biosensors for bacteria, viruses, and toxin detection are reviewed. The current research and development in biosensors for biological warfare agents detection is of interest to the public as well as to the defense is also discussed.
A model-based reasoning architecture for system-level fault diagnosis (2008)

This dissertation presents a model-based reasoning architecture with a two fold purpose: to detect and classify component faults from observable system behavior, and to generate fault propagation models so as to make a more accurate estimation of current operational risks. It incorporates a novel approach to system level diagnostics by addressing the need to reason about low-level inaccessible components from observable high-level system behavior. In the field of complex system maintenance it can be invaluable as an aid to human operators.&#13;\n&#13;\nThe first step is the compilation of the database of functional descriptions and associated fault-specific features for each of the system components. The system is then analyzed to extract structural information, which, in addition to the functional database, is used to create the structural and functional models. A fault-symptom matrix is constructed from the functional model and the features database. The fault threshold levels for these symptoms are founded on the nominal baseline data. Based on the fault-symptom matrix and these thresholds, a diagnostic decision tree is formulated in order to intelligently query about the system health. For each faulty candidate, a fault propagation tree is generated from the structural model. Finally, the overall system health status report includes both the faulty components and the associated at risk components, as predicted by the fault propagation model.
In-Situ Combustion Handbook -- Principles and Practices (1999)

No abstract prepared.
Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system (1994)

The analysis of mutant alleles at the Wnt-1 locus has demonstrated that Wnt-1-mediated cell signalling plays a critical role in development of distinct regions of the embryonic central nervous system (CNS). To determine how these signals participate in the formation of the CNS, we have ectopically expressed this factor in the spinal cord under the control of the Hoxb-4 Region A enhancer. Ectopic Wnt-1 expression causes a dramatic increase in the number of cells undergoing mitosis in the ventricular region and a concomitant ventricular expansion. Although this leads to consistent changes in the relative proportions of dorsal and ventral regions, Wnt-1 does not appear to act as a primary patterning signal. Rather, our experiments indicate that Wnt-1 can act as a mitogen in the developing CNS.
A Syntactic Approach for Handwritten Mathematical Formula Recognition (1984)

Mathematical formulas are good examples of two-dimensional patterns as well as pictures or graphics. The use of syntactic methods is useful for interpreting such complex patterns. In this paper we propose a system for the interpretation of 2-D mathematic formulas based on a syntactic parser. This system is able to recognize a large class of 2-D mathematic formulas written on a graphic tablet. It starts the parsing by localization of the ``principal'' operator in the formula and attempts to partition it into subexpressions which are similarly analyzed by looking for a starting character. The generalized parser used in the system has been developed in our group for continuous speech recognition and picture interpretation.
Reconfigurable platforms and the challenges for large-scale implementations of spiking neural networks (2008)

FPGA devices have witnessed popularity in their use for the rapid prototyping of biological Spiking Neural Network (SNNs) applications, as they offer the key requirement of reconfigurability. However, FPGAs do not efficiently realise the biological neuron/synaptic models. Also their routing structures cannot accommodate the high levels of neuron inter-connectivity inherent in complex SNNs. This paper highlights and discusses the current challenges of implementing large scale SNNs on reconfigurable FPGAs. The paper presents a novel Field Programmable Neural Network (FPNN) architecture incorporating low power analogue synapse and a network on chip architecture for SNN routing and configuration. Initial results are presented.
Active Specific Immunotherapy of Melanoma with Allogeneic Cell Lysates Rationale, Results, and Possible Mechanisms of Actiona (1993)

Since 1985, we have conducted clinical trials with a therapeutic melanoma vaccine (melanoma theraccine). Mechanical lysates of two melanoma cell lines chosen for their complementary characteristics were combined with the adjuvant DETOX and injected subcutaneously on weeks 1, 2, 3, 4, and 6 for one or two courses and then monthly in patients with objective clinical responses. Of 106 patients, 20 had objective clinical regression of tumor masses, 5 with complete responses. The median duration of response was 21 months. Twelve patients lived at least 2 years, with a median survival of nearly 3 years. Two of them are free of disease for > 2 and > 6 years, respectively. However, it was not necessary to achieve complete remissions to cause an increase in survival, and most of the long-surviving patients have one or more (stable) residual nodules. The pace of the disease process was clearly slowed in those individuals. A rise in the level of cytotoxic T-lymphocyte precursors in the blood (pTC) correlated with clinical response. Only those patients who had a rise in pTC had a remission. In addition to "classical" CD8+ Tc, CD4+ Tc were cloned from the blood of immunized patients. Melanoma-specific Tc of both types that killed autologous melanoma but not matched lymphoblastoid cells were detected. Allogeneic melanoma cell lines were also killed, with mainly HLA-A2/28 and HLA-B12/44/45 degenerate restriction. CD4+ Tc were restricted by HLA Class I antigens, as judged by their killing of HLA Class II-negative melanomas and blocking by anti-class I antibodies. Other CD4+ clones were blocked by both anti-HLA Class I or anti-Class II MHC monoclonal antibodies, and only two were blocked only by anti-HLA Class II. Immunohistory revealed CD4+ and CD8+ T cells in lesions under rejection, but the predominant cells were macrophages, suggesting delayed-type hypersensitivity as a possible mechanism. Clinical responses were found most often in patients with HLA-A2/28, -B12/44/45, and -C3, particularly when two or more of those alleles were present. This may have been due either to (1) similarity of MHC antigens between one of the immunizing melanomas and the patient's melanoma or (2) the intrinsic importance of these MHC molecules in presenting melanoma-associated antigens to Tc in vivo. IFN-alpha 2 b salvaged 8 of 18 patients who failed with the theraccine, regardless of MHC phenotype, perhaps through upregulation of MHC and tumor epitopes on the autochthonous tumor.
Clinical Use of Anti‐Vascular Endothelial Growth Factor Monoclonal Antibodies in Metastatic Colorectal Cancer (2008)

Abstract Vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor and has been identified as an important target of cancer therapy. Blocking endothelial cell VEGF activity inhibits tumor angiogenesis; normalizes tumor vasculature, facilitating improved chemotherapy delivery; and prevents the recruitment of progenitor cells from the bone marrow. Bevacizumab, the only United States Food and Drug Administration (FDA)-approved anti-VEGF agent, is a monoclonal antibody that inhibits the binding of VEGF to VEGF receptors. The addition of bevacizumab to standard first- and second-line chemotherapy regimens for the treatment of metastatic colorectal cancer improves overall and progression-free survival times and increases the time to disease progression. Studies are evaluating bevacizumab as adjuvant therapy. The optimal bevacizumab dosage is unknown, but 5 mg/kg every 2 weeks is currently recommended for initial therapy. A surrogate efficacy marker is needed to optimize bevacizumab use, both for dose and patient selection; the clinical applicability of several surrogate efficacy markers is being evaluated. Generally, bevacizumab is well tolerated; however, several serious adverse effects that may occur (e.g., hypertensive crisis) can usually be appropriately prevented or managed. Although current recommendations suggest the administration of the first bevacizumab dose over 90 minutes to prevent infusion-related hypersensitivity reactions, recent study results show that 5 and 10 mg/kg can safely be administered over 10 and 20 minutes, respectively. Whether the addition of bevacizumab to metastatic colorectal cancer treatment regimens is a cost-effective treatment option is unknown; health economic studies are needed. When used for FDA-approved indications or for off-label indications being evaluated in select clinical trials, Medicare reimburses for bevacizumab therapy.
Three-Dimensional Model of the Melt-Blowing Process (2003)

A model has been developed that can predict the three-dimensional motion of a fiber as it is being formed below a melt-blowing die. The model involves the simultaneous solution of the momentum, energy, and continuity equations. The model equations are solved numerically with both Newtonian and viscoelastic constitutive equations. Predicted parameters include fiber attenuation, vibration frequency, vibration amplitude, temperature, and stress. The predicted results compare favorably with previously published experimental data.
Coding assignments of double-stranded RNA segments of SA 11 rotavirus established by in vitro translation (1980)

The segmented double-stranded (ds) RNA genome of the simian rotavirus SA 11, after denaturation, can be translated in a cell-free protein synthesizing system. Of the 11 genome segments, 9 can be resolved on polyacrylamide gels and thus could be individually isolated and translated, providing a means of identifying the polypeptide encoded by each segment. On the basis of electrophoretic mobility of products in sodium dodecyl sulfate-polyacrylamide gels, the probable gene-coding assignments of dsRNA segments 1 to 6 were determined. RNA segments 1 to 4 code for polypeptides I1, I2, I3, and I4, respectively; segment 5 codes for a polypeptide very similar in mobility to a minor polypeptide present in SA 11-infected cells, O1A; and segment 6 codes for the major inner-capsid polypeptide I5.
The Heparin Binding Domain of Insulin-Like Growth Factor Binding Protein (IGFBP)-3 Increases Susceptibility of IGFBP-3 to Proteolysis (1999)

IGFBP-3 proteolysis clears IGFBP-3 from body fluids and increases IGF bioavailability. As shown here, native human IGFBP-3 was cleaved by proteases in media conditioned by hamster and insect cells. This proteolysis was less pronounced for IGFBP-3 containing a mutated heparin binding domain, and was prevented by purifying IGFBP-3 on an IGF-I affinity column in the presence of 2 M sodium chloride, suggesting that the responsible protease(s) binds the IGFBP-3 heparin binding domain. To determine if any human proteases act this way, we first studied plasma prekallikrein since it can copurify with IGFBP-3, and found: 1) [125]IGFBP-3 binds to prekallikrein immobilized either on nitrocellulose or on immunocapture plates; 2) the IGFBP-3 heparin binding domain participates in forming the IGFBP-3/prekallikrein complex; 3) the binary IGFBP-3/prekallikrein complex can bind IGF-I to form a ternary complex; and 4) activation of prekallikrein to alpha-kallikrein by Factor XIIa resulted in proteolysis of bound IGFBP-3. This work suggests: 1) cleavage of IGFBP-3 by a protease may be aided by the ability of the protease zymogen to directly bind the IGFBP-3 heparin binding domain; and 2) direct binding of protease zymogens to IGFBP-3 may explain some instances where IGFBP-3 is preferentially proteolyzed in the presence of other IGFBPs.
Depletion of CXCR2 Inhibits Tumor Growth and Angiogenesis in a Murine Model of Lung Cancer (2004)

The Glu-Leu-Arg(+) (ELR(+)) CXC chemokines are potent promoters of angiogenesis and have been demonstrated to induce a significant portion of nonsmall cell lung cancer-derived angiogenic activity and support tumorigenesis. ELR(+) CXC chemokines share a common chemokine receptor, CXCR2. We hypothesized that CXCR2 mediates the proangiogenic effects of ELR(+) CXC chemokines during tumorigenesis. To test this postulate, we used syngeneic murine Lewis lung cancer (LLC; 3LL, H-2(b)) heterotopic and orthotopic tumor model systems in C57BL/6 mice replete (CXCR2(+/+)) and deficient in CXCR2 (CXCR2(-/-)). We first demonstrated a correlation of the expression of endogenous ELR(+) CXC chemokines with tumor growth and metastatic potential of LLC tumors. Next, we found that LLC primary tumors were significantly reduced in growth in CXCR2(-/-) mice. Moreover, we found a marked reduction in the spontaneous metastases of heterotopic tumors to the lungs of CXCR2(-/-) mice. Morphometric analysis of the primary tumors in CXCR2(-/-) mice demonstrated increased necrosis and reduced vascular density. These findings were further confirmed in CXCR2(+/+) mice using specific neutralizing Abs to CXCR2. The results of these studies support the notion that CXCR2 mediates the angiogenic activity of ELR(+) CXC chemokines in a preclinical model of lung cancer.
Visual search: The role of peripheral information measured using gaze-contingent displays (2006)

Two of the factors limiting progress in understanding the mechanisms of visual search are the difficulty of controlling and manipulating the retinal stimulus when the eyes are free to move and the lack of an ideal observer theory for fixation selection during search. Recently, we developed a method to precisely control retinal stimulation with gaze-contingent displays (J. S. Perry & W. S. Geisler, 2002), and we derived a theory of optimal eye movements in visual search (J. Najemnik & W. S. Geisler, 2005). Here, we report a parametric study of visual search for sine-wave targets added to spatial noise backgrounds that have spectral characteristics similar to natural images (the amplitude spectrum of the noise falls inversely with spatial frequency). Search time, search accuracy, and eye fixations were measured as a function of target spatial frequency, 1/f noise contrast, and the resolution falloff of the display from the point of fixation. The results are systematic and similar for the two observers. We find that many aspects of search performance and eye movement pattern are similar to those of an ideal searcher that has the same falloff in resolution with retinal eccentricity as the human visual system.
Optimization within a unified transformation framework (1996)

Programmers typically want to write scientific programs in a high level language with semantics based on a sequential execution model. To execute efficiently on a parallel machine, however, a program typically needs to contain explicit parallelism and possibly explicit communication and synchronization. So, we need compilers to convert programs from the first of these forms to the second. There are two basic choices to be made when parallelizing a program. First, the computations of the program need to be distributed amongst the set of available processors. Second, the computations on each processor need to be ordered. My contribution has been the development of simple mathematical abstractions for representing these choices and the development of new algorithms for making these choices. I have developed a new framework that achieves good performance by minimizing communication between processors, minimizing the time processors spend waiting for messages from other processors, and ordering data accesses so as to exploit the memory hierarchy. This framework can be used by optimizing compilers, as well as by interactive transformation tools. The state of the art for vectorizing compilers is already quite good, but much work remains to bring parallelizing compilers up to the same standard. The main contribution of my work can be summarized as improving this situation by replacing existing ad hoc parallelization techniques with a sound underlying foundation on which future work can be built. (Also cross-referenced as UMIACS-TR-96-93)
Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains (2015)

By non-covalent association after proteolytic cleavage, the pro-domains modulate the activities of the mature growth factor domains across the transforming growth factor-β family. In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9·pro-domain complexes have equivalent biological activities as the BMP9 mature ligand dimers. By using real-time surface plasmon resonance, we could demonstrate that either binding of pro-domain-complexed BMP9 to type I receptor activin receptor-like kinase 1 (ALK1), type II receptors, co-receptor endoglin, or to mature BMP9 domain targeting antibodies leads to immediate and complete displacement of the pro-domains from the complex. Vice versa, pro-domain binding by an anti-pro-domain antibody results in release of the mature BMP9 growth factor. Based on these findings, we adjusted ELISA assays to measure the protein levels of different BMP9 variants. Although mature BMP9 and inactive precursor BMP9 protein were directly detectable by ELISA, BMP9·pro-domain complex could only be measured indirectly as dissociated fragments due to displacement of mature growth factor and pro-domains after antibody binding. Our studies provide a model in which BMP9 can be readily activated upon getting into contact with its receptors. This increases the understanding of the underlying biology of BMP9 activation and also provides guidance for ELISA development for the detection of circulating BMP9 variants.
Treatment of Recurrent <i>Clostridium difficile</i> Diarrhea. (2006)

Treatment of recurrent <i>Clostridium difficile</i>-associated diarrhea can be challenging. Once patients develop recurrent disease, further episodes are common and can continue for months or even a year or more. Treatment begins with a repeat standard 10-day course of antibiotics, followed by tapering and/or pulsing of the antibiotic dose. Probiotics can also be useful, particularly the nonpathogenic yeast <i>Saccharomyces boulardii</i>. Stool reconstitution via fecal enemas, colonoscopy, and nasogastric tubes have been performed to restore normal colonic flora. Additional approaches under investigation, such as vaccination against <i>C. difficile</i>, show encouraging preliminary results.
Comprehensible Visualization for Augmented Reality (2009)

This article presents interactive visualizations to support the comprehension of spatial relationships between virtual and real world objects for Augmented Reality (AR) applications. To enhance the clarity of such relationships we discuss visualization techniques and their suitability for AR. We apply them on different AR applications with different goals, e.g. in X-Ray vision or in applications which draw a user's attention to an object of interest. We demonstrate how Focus and Context (F+C) visualizations are used to affect the user's perception of hidden or nearby objects by presenting contextual information in the area of augmentation. We discuss the organization and the possible sources of data for visualizations in Augmented Reality and present cascaded and multi level F+C visualizations to address complex, cluttered scenes that are inevitable in real environments. This article also shows filters and tools to interactively control the amount of augmentation. It compares the impact of real world context preserving to a pure virtual and uniform enhancement of these structures for augmentations of real world imagery. Finally this paper discusses the stylization of sparse object representations for AR to improve X-Ray vision.