gebhart/patrepeval huggingface dataset:
Enhancement of the complement activating capacity of 17-1A mAb to overcome the effect of membrane-bound complement regulatory proteins on colorectal carcinoma (2002)

Adjuvant immunotherapy with 17-1A mAb directed against colorectal carcinoma is found to be effective in patients. However, 52 % of the patients treated with mAb 17-1A showed recurrence within 7 years. This high recurrence rate might be due to inhibition of complement activation by membrane-bound complement regulatory proteins (mCRP). The effect of these complement regulatory proteins might be reduced by blocking mCRP, or be overcome by activating more complement at the tumor cell membrane. In this study the complement-activating capacity of the 17-1A mAb was enlarged by conjugating it to cobra venom factor (CVF) or C3b. The most important C3 regulatory protein, CD55, was blocked using a bispecific mAb directed against the 17-1A / Ep-CAM antigen and CD55. Up to a 13-fold increase in C3 deposition was observed due to 17-1A-CVF and 17-1A-C3b, as compared to 17-1A. CD55 was shown to partly inhibit complement activation by these conjugates. The effect of the bispecific anti-17-1A / Ep-CAM*anti-CD55 mAb was compared with 17-1A conjugates with CVF or C3, and bispecific mAb were shown to be equally or more efficient in complement activation than the 17-1A-CVF or 17-1A-C3b conjugates. Therefore, 17-1A conjugates and anti-17-1A / EpCAM*anti-CD55 bispecific mAb may be promising immunotherapeutic agents for patients with colorectal cancer.
Comparison of Algorithms for the Localization of Focal Sources: Evaluation with simulated data and analysis of experimental data. (2002)

This paper presents a comparative study of the capabilities of five distributed linear solutions to accurately determine the position of single sources. Two recently developed inverse solutions, LAURA and EPIFOCUS are compared to the Minimum Norm, the column Weighted Minimum Norm and the Minimum Laplacian. The comparison is based on three figures of merit: 1) the number of sources with zero localization error, 2) the maximum localization error, and 3) the average localization error as a function of the source eccentricity. The best results in terms of the three figures of merit are obtained for EPIFOCUS and LAURA. We report for the first time a linear inverse solution (EPIFOCUS) capable of localizing all single sources with zero dipole localization error for a relatively low number of sensors (100). The robustness of EPIFOCUS is additionally evaluated in this paper with noisy synthetic data and experimental recordings in epileptic patients. It is concluded that EPIFOCUS is a robust method to localize single sources with the following advantages over single dipole localization: 1) It is computationally more efficient. 2) It is easily applicable to realistic head models (gray matter selected from MRI). 3) Sources are not restricted to be dipolar. The study described in the paper endorses an important theoretical conclusion: While it is possible to design linear solutions with optimal performance in the determination of the position of single sources, such performance is not warranted if multiple sources are simultaneously active. Consequently, lower dipole localization error is neither a sufficient nor a necessary condition for the performance of a linear inverse solution.
Optical pattern recognition for validation and security verification (1994)

We propose an idea for security verification of credit cards, passports, and other forms of identification so that they cannot easily be reproduced. A new scheme of complex phase/amplitude patterns that cannot be seen and cannot be copied by an intensity-sensitive detector such as a CCD camera is used. The basic idea is to permanently and irretrievably bond a phase mask to a primary identification amplitude pattern such as a fingerprint, a picture of a face, or a signature. Computer simulation results and tests of the proposed system are provided to verify that both the phase mask and the primary pattern are separately readable and identifiable in an optical processor or correlator.
Galanin: A Significant Role in Depression? (1998)

This paper describes a hypothesis that attempts to account for how changes in noradrenergic systems in the brain can affect depression-related behaviors and symptoms. It is hypothesized that increased activity of the locus coeruleus (LC) neurons, the principal norepinephrine (NE)-containing cells in the brain, causes release of galanin (GAL) in the ventral tegmentum (VTA) from LC axon terminals in which GAL is colocalized with NE. It is proposed that GAL release in VTA inhibits the activity of dopaminergic cell bodies in this region whose axons project to forebrain, thereby resulting in two of the principal symptoms seen in depression, decreased motor activation and decreased appreciation of pleasurable stimuli (anhedonia). The genesis of this hypothesis, which derives from studies using an animal model of depression, is described as well as recent data consistent with the hypothesis. The formulation proposed suggests that GAL antagonists may be of therapeutic benefit in the treatment of depression.
Extracellular matrix‐resident basic fibroblast growth factor: Implication for the control of angiogenesis (1991)

Despite the ubiquitous presence of basic fibroblast growth factor (bFGF) in normal tissues, endothelial cell proliferation in these tissues is usually very low, suggesting that bFGF is somehow sequestered from its site of action. Immunohistochemical staining revealed the localization of bFGF in basement membranes of diverse tissues, suggesting that the extracellular matrix (ECM) may serve as a reservoir for bFGF. Moreover, functional studies indicated that bFGF is an ECM component required for supporting endothelial cell proliferation and neuronal differentiation. We have found that bFGF is bound to heparan sulfate (HS) in the ECM and is released in an active form when the ECM-HS is degraded by heparanase expressed by normal and malignant cells (i.e. platelets, neutrophils, lymphoma cells). It is proposed that restriction of bFGF bioavailability by binding to ECM and local regulation of its release provide a novel mechanism for neovascularization in normal and pathological situations. The subendothelial ECM contains also tissue type- and urokinase type-plasminogen activators which participate in cell invasion and tissue remodeling. These results and studies on the properties of other ECM-immobilized enzymes (i.e. thrombin, plasmin, lipoprotein lipase) and growth factors (GM-CSF, IL-3, osteogenin), suggest that the ECM provides a storage depot for biologically active molecules which are thereby stabilized and protected. This may allow a more localized and persistent mode of action, as compared to the same molecules in a fluid phase.
Analysis of theYersinia pestisV Protein for the Presence of Linear Antibody Epitopes (1998)

The V protein expressed by pathogenic Yersinia pestis is an important virulence factor and protective immunogen. The presence of linear B-cell epitopes in the V protein was investigated by using a series of 17 overlapping linear peptides. Groups of 10 mice were immunized intraperitoneally with 30 microg of each peptide on days 0, 30, and 60. Although the V protein-specific antibody response to the peptides varied, most of the peptides elicited high antibody titers. The immunized mice were challenged subcutaneously with 60 50% lethal doses (LD50) (1 LD50 = 1.9 CFU) of a virulent Y. pestis strain, CO92. None of the peptide-immunized mice survived challenge. The animals immunized with the V protein were completely protected against challenge. The immunogenicity of some of the V peptides was increased by conjugating them to keyhole limpet hemocyanin. Only one peptide (encompassing amino acids 1 to 30) conjugate demonstrated some protection; the others were not protective. In additional experiments, V peptides that reacted well with sera from mice surviving Y. pestis infection were combined and used to immunize mice. Although the combined peptides appeared to be very immunogenic, they were not protective. Therefore, the protective B-lymphocyte epitope(s) in the V protein is most likely to be conformational.
Reversal of the Z- to B-Conformation of Poly(dA-dT)•Poly(dA-dT) Induced by Netropsin and Distamycin A (1996)

Poly(dA-dT) center dot poly(dA-dT) which adopts the Z-form at 5 M NaCl in presence of 95 mM Ni2+ions is reversed to the B-conformation by the nonintercalating drugs netropsin (Nt) and distamycin A (Dst). The drug-induced reversal from the Z-to B-form of poly(dA-dT) center dot poly(dA-dT) is evidenced by CD spectral changes at characteristic wavelengths around 295 nm and 248 nm. The drug-induced conformational transition is accompanied by a slow kinetic process. The results suggest the preference of these AT-specific drugs for the B-form and the inability of Nt and Dst to form a stable complex with the Z-form of poly(dA-dT) center dot poly(dA-dT).
Analysis of a multilevel multicell switch-mode power amplifier employing the "flying-battery" concept (2002)

This paper presents a novel switch-mode power amplifier based on a multicell multilevel circuit topology. The total output voltage of the system is formed by series connection of several switching cells having a low DC-link voltage. Therefore, the cells can be realized using modern low-voltage high-current power MOSFET devices and the DC link can easily be buffered by rechargeable batteries or "super" capacitors to achieve very high amplifier peak output power levels ("flying-battery" concept). The cells are operated in a phase-shifted interleaved pulsewidth-modulation mode, which, in connection with the low partial voltage of each cell, reduces the filtering effort at the output of the total amplifier to a large extent and, consequently, improves the dynamic system behavior. The paper describes the operating principle of the system, analyzes the fundamental relationships being relevant for the circuit design, and gives guidelines for the dimensioning of the control circuit. Furthermore, simulation results as well as results of measurements taken from a laboratory setup are presented.
Internet time synchronization: the network time protocol (1991)

The network time protocol (NTP), which is designed to distribute time information in a large, diverse system, is described. It uses a symmetric architecture in which a distributed subnet of time servers operating in a self-organizing, hierarchical configuration synchronizes local clocks within the subnet and to national time standards via wire, radio, or calibrated atomic clock. The servers can also redistribute time information within a network via local routing algorithms and time daemons. The NTP synchronization system, which has been in regular operation in the Internet for the last several years, is described, along with performance data which show that timekeeping accuracy throughout most portions of the Internet can be ordinarily maintained to within a few milliseconds, even in cases of failure or disruption of clocks, time servers, or networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Multi-column deep neural networks for image classification (2012)

Traditional methods of computer vision and machine learning cannot match human performance on tasks such as the recognition of handwritten digits or traffic signs. Our biologically plausible, wide and deep artificial neural network architectures can. Small (often minimal) receptive fields of convolutional winner-take-all neurons yield large network depth, resulting in roughly as many sparsely connected neural layers as found in mammals between retina and visual cortex. Only winner neurons are trained. Several deep neural columns become experts on inputs preprocessed in different ways; their predictions are averaged. Graphics cards allow for fast training. On the very competitive MNIST handwriting benchmark, our method is the first to achieve near-human performance. On a traffic sign recognition benchmark it outperforms humans by a factor of two. We also improve the state-of-the-art on a plethora of common image classification benchmarks.
Hypothesis for Vaccine Development: Protective Immunity to Enteric Diseases Caused by Nontyphoidal Salmonellae and Shigellae May Be Conferred by Serum IgG Antibodies to the O-Specific Polysaccharide of Their Lipopolysaccharides (1992)

Immunoprophylaxis for bacterial enteric diseases is hindered because the protective immune mechanism(s) against nontyphoidal salmonellae or shigellae in humans are not established. On the basis of the similarities between the clinical signs, epidemiology, pathogenesis, and pathology of as well as protective immunity to salmonellae and shigellae, we propose that serum IgG antibodies to the O-specific polysaccharide (O-SP) of their lipopolysaccharides (LPSs) will confer protective immunity to these two pathogens. Critical to this notion is that (1) the virulence of these two pathogens requires full expression of their LPS; (2) active or passive immunization with serum IgG O-SP antibodies confers protection of mice against Salmonella typhimurium (there are no comparable data for humans); and (3) in humans, convalescence from shigellosis confers type (O-SP) -specific protective immunity, and indirect evidence shows a correlation between the level of serum LPS antibodies and resistance to shigellosis. We designed conjugate vaccines to elicit high levels of long-lived serum IgG O-SP antibodies to nontyphoidal salmonellae and shigellae to test this hypothesis.
Optimally Porous and Biomechanically Compatible Scaffolds for Large-Area Bone Regeneration (2012)

Large-area or critical-sized bone defects pose a serious challenge in orthopedic surgery, as all current treatment options present with shortcomings. Bone tissue engineering offers a more promising alternative treatment strategy. However, this approach requires mechanically stable scaffolds that support homogenous bone formation throughout the scaffold thickness. Despite advances in scaffold fabrication, current scaffold-based techniques are unable to support uniform, three-dimensional bone regeneration, and are limited to only the scaffold surface in vitro and in vivo. This is mainly because of inadequate scaffold pore sizes (<200 μm) and accessible pore volume, and the associated limited oxygen diffusion and vascular invasion. In this study, we have adopted a method combining microsphere-sintering and porogen-leaching techniques to fabricate scaffolds with an increased accessible pore volume. Of the scaffolds developed, moderately porous poly(85 lactide-co-15 glycolide) (PLGA) microsphere scaffolds were selected as most advantageous, since they retain mechanical strength in the range of human cancellous bone and display a significantly higher accessible pore volume, which is attributed to an increased percentage of larger pores (i.e., size range 200-600 μm). Unlike control scaffolds with a limited pore size and an accessible pore volume, moderately porous scaffolds displayed increased oxygen diffusion, pre-osteoblast cell infiltration, proliferation, and survival throughout the entire scaffold. Furthermore, moderately porous PLGA microsphere scaffolds displayed enhanced and homogenous mineralization in vitro. Since these newly designed moderately porous scaffolds are weight bearing, are fully osteoconductive, and have the ability to support vascularization, they may serve as effective scaffolds for large-area bone defect repair/regeneration. In addition, this study demonstrates the ability to modulate scaffold porosity and, in turn, to develop oxygen tension-controlled matrices that are effective for large-area bone regeneration.
Recombinant Murine Granulocyte-Macrophage Colony-Stimulating Factor Augments Neutrophil Recovery and Enhances Resistance to Infections in Myelosuppressed Mice (1991)

The ability of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) to protect myelosuppressed mice against lethal infections was evaluated. In mice myelosuppressed by cyclophosphamide, subcutaneously administered rmGM-CSF was a potent stimulus of granulopoiesis by increasing the number of GM-CSF-responsive precursor cells in bone marrow followed by a profound neutrophilia. Neutrophil recovery was augmented by rmGM-CSF in a dose-dependent manner at daily doses of 0.6-5.0 micrograms/mouse. In addition, rmGM-CSF increased the functional activity of circulating neutrophils at similar doses. When rmGM-CSF was administered to neutropenic mice before experimentally induced Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections, it protected against these lethal infections, resulting in increased numbers of survivors. These data suggest that rmGM-CSF protects neutropenic mice from lethal infections, probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells.
Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1 (1999)

Almost any growth of tumors is to some extent associated with an inflammatory reaction which may be anti-tumorigenic by acting directly on tumor cells or protumorigenic cells presumably by inducing tumor-associated angiogenesis. In this study, we have analyzed the angiogenesis-inducing capacity of monocyte chemoattractant protein-1 (MCP-1), a key regulatory molecule of monocyte trafficking to sites of inflammation. MCP-1 was found to be potently angiogenic when implanted into rabbit cornea, exerting potency similar to the specific angiogenic vascular endothelial growth factor (VEGF)-A(121). MCP-1-induced angiogenesis in the cornea is associated with prominent recruitment of macrophages, whereas VEGF-A(121)-induced corneal angiogenesis is devoid of inflammatory cell recruitment. Based on these findings, we studied MCP-1 expression and macrophage recruitment in human invasive ductal mammary carcinomas in comparison with the physiological angiogenic processes in bovine ovarian corpus luteum. Macrophage recruitment was always associated with MCP-1 expression. High macrophage counts in mammary tumors corresponded with poor prognosis. In contrast, physiological ovarian angiogenesis was associated with only minimal inflammatory recruitment of macrophages. Our data show that MCP-1 is an indirect inflammation-associated inducer of angiogenesis and demonstrate distinct qualitative differences between tumor angiogenesis in human mammary tumors and physiological angiogenesis in the ovary.
The effect of C1 inhibitor on intestinal ischemia and reperfusion injury (2008)

Complement activation and neutrophil stimulation are two major components in events leading to ischemia and reperfusion (IR) injury. C1 inhibitor (C1INH) inhibits activation of each of the three pathways of complement activation and of the contact system. It is also endowed with anti-inflammatory properties that are independent of protease inhibition. The goal of these studies was to investigate the role and mechanism of C1INH in alleviating IR-induced intestinal injury. C57BL/6, C1INH-deficient (C1INH(-/-)), bradykinin type 2 receptor-deficient (Bk2R(-/-)), and C3-deficient mice (C3(-/-)) were randomized into three groups: sham operated control, IR, and IR + C1INH-treated groups. Ischemia was generated by occlusion of the superior mesenteric artery followed by reperfusion. C1INH or reactive center-cleaved inactive C1INH (iC1INH) was injected intravenously before reperfusion. IR resulted in intestinal injury in C57BL/6, C1INH(-/-), Bk2R(-/-), and C3(-/-) mice with significantly increased neutrophil infiltration into intestinal tissue. In each mouse strain, C1INH treatment reduced intestinal tissue injury and attenuated leukocyte infiltration compared with the untreated IR group. C1INH inhibited leukocyte rolling in the mesenteric veins of both C57BL/6 and C3-deficient mice subjected to IR. C1INH treatment also improved the survival rate of C57BL/6 and C1INH(-/-) mice following IR. Similar findings were observed in the IR animals treated with iC1INH. These studies emphasize the therapeutic benefit of C1INH in preventing intestinal injury caused by IR. In addition to the protective activities mediated via inhibition of the complement system, these studies indicate that C1INH also plays a direct role in suppression of leukocyte transmigration into reperfused tissue.
Occipital nerve stimulation for drug-resistant chronic cluster headache: long term follow-up up to 3 years (2009)

peer reviewed
Stable Electrolyte for High Voltage Electrochemical Double-Layer Capacitors (2016)

A simple electrolyte consisting of NaPF<sub>6</sub> salt in 1,2-dimethoxyethane (DME) can extend the voltage window of electric double-layer capacitors (EDLCs) to >3.5 V. DME does not passivate carbon electrodes at very negative potentials (near Na/Na<sup>+</sup>), extending the practical voltage window by about 1.0 V compared to standard, non-aqueous electrolytes based on acetonitrile. The voltage window is demonstrated in two- and three-electrode cells using a combination of electrochemical impedance spectroscopy (EIS), charge-discharge cycling, and measurements of leakage current. DME-based electrolytes cannot match the high conductivity of acetonitrile solutions, but they can satisfy applications that demand high energy density at moderate power. The conductivity of NaPF<sub>6</sub> in DME is comparable to commercial lithium-ion battery electrolytes and superior to most ionic liquids. Lastly, factors that limit the voltage window and EDLC energy density are discussed, and strategies to further boost energy density are proposed.
Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection (2005)

Infection with West Nile virus (WNV) causes a severe infection of the central nervous system (CNS) with higher levels of morbidity and mortality in the elderly and the immunocompromised. Experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. Here, we demonstrate that the complement system, a major component of innate immunity, controls WNV infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in solution and lysing WNV-infected cells. More decisively, mice that genetically lack the third component of complement or complement receptor 1 (CR1) and CR2 developed increased CNS virus burdens and were vulnerable to lethal infection at a low dose of WNV. Both C3-deficient and CR1- and CR2-deficient mice also had significant deficits in their humoral responses after infection with markedly reduced levels of specific anti-WNV immunoglobulin M (IgM) and IgG. Overall, these results suggest that complement controls WNV infection, in part through its ability to induce a protective antibody response.
Simulated bleeding--a forgotten disease in a land of plenty. (1996)

The human body is unable to synthesise Vitamin C and a diet deficient in Vitamin C leads to scurvy. Scurvy may mimic other medical conditions, like bleeding diasthesis or deep vein thrombosis, leading to delay in diagnosis and treatment, thus prolonging sufferings of patients. Often, scurvy could have been diagnosed if it is thought of and features of scurvy carefully looked for. Scurvy is easily treated with high dose of oral vitamin C. Recurrences may occur. Education of care providers cannot be overemphasised. We report three local cases of scurvy to highlight the existence of the disease in our modern society.