gebhart/patrepeval huggingface dataset:
The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity (1995)

Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease if the central nervous system (CNS). Recently, the type I IFN, IFN-beta-1b was demonstrated to be a useful immunotherapy for MS. During treatment with IFN-beta-1b, toxicity at higher doses has been observed. IFN-tau, discovered for its role in the reproductive cycle, possesses all of the functions normally ascribed to the type I IFNs but lacks the toxicity normally associate with IFN treatment in vitro. We have examined the effects of IFN-tau treatment on experimental allergic encephalomyelitis (EAE), an animal model useful for the study of MS. EAE is a model of Ag-induced autoimmunity that can be modulated by bacterial superantigen to resemble the relapsing-remitting pattern of autoimmune disease observed in MS. IFN-tau was able to prevent development of EAE as effectively as IFN-beta but without associated toxicity such as lymphocyte suppression and weight loss. In addition, IFN-tau was able to prevent superantigen reactivation of EAE akin to the reduction in disease exacerbations observed in IFN-beta-1b treated MS patients. Mechanisms by which IFN-tau may prevent EAE include reduced proliferation in response to the autoantigen myelin basic protein and reduced TNF-alpha production. Thus, IFN-tau may prove to be a promising new IFN therapy for MS in light of its ability to prevent EAE and the lack of toxicity exhibited by this novel IFN.
Acute generalized microvascular injury by activated complement and hypoxia: the basis of the adult respiratory distress syndrome and multiple organ failure? (1986)

It has been suggested that generalized endothelial damage and permeability changes, induced by prolonged activation of the complement system and ensuing release of lysosomal enzymes, prostaglandins and toxic oxygen products, underlie the genesis of the Adult Respiratory Distress Syndrome (ARDS) and Multiple Organ Failure (MOF). The effects in New Zealand white rabbits were investigated of a 4 h infusion of activated complement and its combination with a short hypoxic episode on respiratory function, leukocyte count, platelet count and morphology of the lungs, heart, liver, kidney and spleen. Prolonged activation of the complement system induced hyperventilation with respiratory alkalosis and hypocapnia, depletion of granulocytes (PMN), and a variable accumulation PMN in the capillaries of all organs examined, in combination with interstitial, and, in the liver, cellular oedema. Electron microscopy of the lungs revealed degranulation of PMN, endothelial swelling and widening of the alveolar septa. The combination of hypoxia and systemic complement activation appeared to aggravate this microvascular injury with the occurrence of protein rich alveolar oedema and haemorrhage in the lungs and accumulation of PMN debris containing macrophages in the spleen. The alterations in respiratory function and pulmonary morphology in these rabbits, imitate the clinical and morphological characteristics of the early phase of ARDS. The inflammatory reaction, found in all other organs examined, might represent the early phase of MOF. If so, ARDS and MOF -- clinically closely interconnected syndromes -- might be interpreted as manifestations of the same syndrome and as the clinical expression of an uncontrolled whole body inflammation.
Antibacterial effects of knotwood extractives on paper mill bacteria (2004)

Hydrophilic knotwood extracts from 18 wood species were assessed in disc diffusion and liquid culture tests for antibacterial effects against three species of paper mill bacteria. The Pinus sylvestris, P. resinosa, P. contorta, and P. banksiana extracts decreased or inhibited bacterial growth. The susceptibility order was P. sylvestris > P. resinosa > P. contorta > P. banksiana, correlating with the concentrations of pinosylvin and pinosylvin monomethyl ether in these wood species. Also, Pseudotsuga menziesii and Thuja occidentalis extracts had a small inhibitory effect. The Gram-positive Bacillus coagulans was more susceptible to the extracts than the Gram-negative Burkholderia multivorans and Alcaligenes xylosoxydans. The main components in the Pinus knotwood extracts were pinosylvin monomethyl ether and pinosylvin, suggesting these to be the active components. Therefore, pure pinosylvin, pinosylvin monomethyl ether, and dihydro-pinosylvin monomethyl ether were also tested. All compounds showed antibacterial effects. However, higher concentrations were needed for these pure compounds than for the knotwood extracts. Pinosylvin had stronger antibacterial effects than pinosylvin monomethyl ether. This work shows that knotwood extracts, especially from Pinus species, have a potential for use as natural biocides in papermaking.
An ultrahigh‐speed optical waveform measurement method based on optical sampling with sum‐frequency generation (1993)

Abstract To realize a future high‐speed and ultralarge‐capacity optical transmission, it is indispensable to analyze the ultrahigh‐speed transmission characteristics of the entire system as well as functional circuits, devices and materials comprising the system. Evaluation of such a transmission characteristic requires ultrahigh‐speed optical waveform measurement method. In this paper, a new optical waveform measurement method called the sum frequency generation (SFG) optical sampling method is proposed. In this method, the SFG which is a second‐order nonlinear optical effect is used for all‐optically sampling the optical waveform to be measured (at the optical stage) by means of an ultrashort optical gate pulse. Hence, the bandwidth limitation of the optical receivers and the electronics can be eliminated. By means of this technique, accurate measurement without waveform distortions can be realized while high time resolution and high S/N ratios are maintained. In this paper, the theoretical performance of the present measurement technique is discussed and the measured results by the present method are presented.
Endothelial Dysfunction in Preeclampsia (1998)

Several years ago the hypothesis was advanced that alterations of endothelial function could explain much of the pathophysiology of preeclampsia. Since that time, extensive data have been generated to support the hypothesis. Markers of endothelial activation can be demonstrated in women with overt preeclampsia. More importantly, many of these markers precede clinically evident disease and disappear with resolution of the disease. The original postulate was that materials produced by the poorly perfused placenta, which is characteristic of preeclampsia, entered the systemic circulation and altered endothelial cell activity. This was proposed to change vascular sensitivity to circulating pressors, activate coagulation, and reduce vascular integrity resulting in the pathophysiological changes of preeclampsia. As data have accumulated it has become increasingly evident that the insult to the endothelium is neither toxicity nor nonspecific injury but rather can better be characterized as endothelial activation. Candidate molecules have been suggested but not established. It seems likely that the responsible agent(s) will not be unique molecules but rather usual molecules present in excessive amounts. The hypothesis has been expanded to invoke involvement of the maternal constitution in the generation of endothelial injury and injurants. This concept is stimulated by the observation that reduced placental perfusion per se is not sufficient to generate the maternal syndrome. Women with growth-restricted fetuses frequently are not preeclamptic. Placental bed biopsies from not only growth-restricted but also prematurely born infants demonstrate failure of the physiological remodeling of decidual vessels responsible for the reduced placental perfusion of preeclampsia. This has led to the concept that preeclampsia is secondary to an interaction of reduced placental perfusion and maternal factors. Interestingly these maternal factors, obesity, insulin resistance, black race, hypertension, and elevated plasma homocysteine concentration are all risk factors for atherosclerosis in later life.
Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis (2006)

The proteinase-activated receptors (PARs) are widely recognized for their modulatory properties of inflammation and neurodegeneration. We investigated the role of PAR2 in the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in mice. PAR2 expression was increased on astrocytes and infiltrating macrophages in human MS and murine EAE central nervous system (CNS) white matter (P < 0.05). Macrophages and astrocytes from PAR2 wild-type (WT) and knockout (KO) mice exhibited differential immune gene expression with PAR2 KO macrophages showing significantly higher interleukin 10 production after lipopolysaccharide stimulation (P < 0.001). PAR2 activation in macrophages resulted in the release of soluble oligodendrocyte cytotoxins (P < 0.01). Myelin oligodendrocyte glycoprotein-induced EAE caused more severe inflammatory gene expression in the CNS of PAR2 WT animals (P < 0.05), together with enhanced T cell proliferation and interferon gamma production (P < 0.05), compared with KO littermates. Indeed, PAR2 WT animals showed markedly greater microglial activation and T lymphocyte infiltration accompanied by worsened demyelination and axonal injury in the CNS compared with their PAR2 KO littermates. Enhanced neuropathological changes were associated with a more severe progressive relapsing disease phenotype (P < 0.001) in WT animals. These findings reveal previously unreported pathogenic interactions between CNS PAR2 expression and neuroinflammation with ensuing demyelination and axonal injury.
A perception‐driven autonomous urban vehicle (2008)

Abstract This paper describes the architecture and implementation of an autonomous passenger vehicle designed to navigate using locally perceived information in preference to potentially inaccurate or incomplete map data. The vehicle architecture was designed to handle the original DARPA Urban Challenge requirements of perceiving and navigating a road network with segments defined by sparse waypoints. The vehicle implementation includes many heterogeneous sensors with significant communications and computation bandwidth to capture and process high‐resolution, high‐rate sensor data. The output of the comprehensive environmental sensing subsystem is fed into a kinodynamic motion planning algorithm to generate all vehicle motion. The requirements of driving in lanes, three‐point turns, parking, and maneuvering through obstacle fields are all generated with a unified planner. A key aspect of the planner is its use of closed‐loop simulation in a rapidly exploring randomized trees algorithm, which can randomly explore the space while efficiently generating smooth trajectories in a dynamic and uncertain environment. The overall system was realized through the creation of a powerful new suite of software tools for message passing, logging, and visualization. These innovations provide a strong platform for future research in autonomous driving in global positioning system–denied and highly dynamic environments with poor a priori information. © 2008 Wiley Periodicals, Inc.
Micro-fabricated piezoelectric cantilever for atomic force microscopy (1996)

We successfully developed an atomic force microscope (AFM) with a batch-fabricated silicon cantilever with a pyramidal stylus. The high quality lead zirconate titanate (PZT) piezoelectric thin film allows simultaneously displacement sensing and actuating. The PZT thin film with a dielectric constant of 1000, a remanent polarization of 30 μC/cm2, and a piezoelectric constant of −100 pC/N, which are as high as those of bulk ceramics PZT, has been formed by sputtering at 400 °C and subsequent annealing at 650 °C. A Si(111) mono-atomic step whose height is 4 Å has been observed clearly in an AFM cyclic contact mode by a PZT-AFM lever as a displacement sensor. A PZT-AFM lever has been used as an actuator for z feedback positioning for AFM imaging of a compact disk pit.
Lesion formation and visualization using dual-mode ultrasound phased arrays (2002)

A 1 MHz spherical-section 64-element linear piezo-composite phased array and a supporting driving and data acquisition system were recently tested for use as a dual-mode high intensity focused ultrasound (HIFU) applicator system. In therapeutic mode, the array was shown to be capable of producing focal intensities in excess of 3500 W/cm/sup 2/ at its geometric center (100 mm radius of curvature). Imaging tests of quality assurance tissue-mimicking phantoms as well as computer simulations confirmed that the array has an oval-shaped imaging field of view (1xFOV) with nearly 50 dB, dynamic range extending from 70 to 120 mm in the axial direction and /spl plusmn/ 20 mm in the transverse direction. This is larger than its therapeutic operating field, which is defined as the region around the geometric focus where the loss in intensity gain is within 1 dB from the intensity gain at the geometric center. We have tested the array imaging capability in the visualization of the formation of discrete and volumetric lesions in freshly excised porcine liver samples. Experimental results clearly show that the enhancement of the tissue echogenicity at the lesion location is more pronounced in the harmonic images when compared to images at the fundamental. Results also clearly show that the harmonic imaging mode produces more accurate mapping of the lesion size and shape as determined by histologic evaluation.
Requirements for the synthesis of Boolean neural networks (1990)

The areas of investigation required to develop synthesis techniques for Boolean neural networks are discussed. Consideration is given to the problems of behavioral specification and to the lack of an analytic algebraic mapping between transformations within the hyper-state space and transformations within the function space of a network. Ways of identifying structure within both the behavior and functional architecture of classes of simple Boolean neural networks are suggested
Quantitative Determination of Factors Contributing to Doxorubicin Resistance in Multidrug-Resistant Cells (1989)

There is a large discrepancy between the changes in drug accumulation and the changes in drug cytotoxicity that accompany development of anthracycline resistance in multidrug-resistant cells. In our study, a quantitative relationship has been established between reversal of multidrug resistance by resistance modifiers and a concomitant decrease in intracellular levels of doxorubicin measured at equitoxic concentrations (IC50) in CHRC5 and 2780AD multidrug-resistant cells. (IC50 = concentration required for 50% growth inhibition.) We have demonstrated that resistance modifiers like verapamil and Ro 11-2933/001 act by increasing the effectiveness of intracellular doxorubicin, apparently by inducing redistribution of the drug from the cytoplasm to the nucleus of a multidrug-resistant cell, as shown by quantitative fluorescence microscopy. At complete reversal of resistance, as measured directly or inferred by extrapolation, the amount of intracellular doxorubicin at the IC50 as well as the ratio of nuclear doxorubicin to cytoplasmic doxorubicin were the same as those in sensitive cells. These results offer an explanation for the frequently observed discrepancies between drug accumulation and cytotoxicity and also show quantitatively that a decrease in drug accumulation and a change in intracellular drug distribution together are the only determinants of doxorubicin resistance in the multidrug-resistant cells studied.
Multifactorial Nature of Human Immunodeficiency Virus Disease: Implications for Therapy (1993)

The immunopathogenic mechanisms underlying human immunodeficiency virus (HIV) disease are extremely complex; the disease process is multifactorial with multiple overlapping phases. Viral burden is substantial and viral replication occurs throughout the entire course of HIV infection. Inappropriate immune activation and elevated secretion of certain cytokines compound the pathogenic process. Profound immunosuppression ultimately occurs together with a disruption of the microenvironment of the immune system, which is probably unable to regenerate spontaneously. Thus, therapeutic strategies in HIV disease must not be unidimensional, but rather must be linked to the complex pathogenic components of the disease and must address where feasible each of the recognized pathogenic processes for the possibility of therapeutic intervention.
Molecular Imaging with PET (2008)

The development of positron emission tomography (PET) imaging probes is necessary for molecular imaging. A review on some of the most important criteria necessary for a successful central nervous system (CNS) molecular probe has been discussed. A description on the radiolabeling strategies is given as well as on the most useful clinical PET radiopharmaceuticals that are useful for CNS and for the diagnosis of Alzheimer's disease. Furthermore, certain challenges on small animal PET imaging is also presented as well as its applications in rodent models of human brain diseases.
Lessons from Human Studies with Glucagon-Like Peptide-1: Potential of the Gut Hormone for Clinical Use (1997)

Glucagon-like peptide-1 (GLP-1) is a promising new therapeutic tool for the treatment of diabetes. Since the first reports describing its potent insulinotropic activity were published about a decade ago, knowledge of the incretin hormones, and GLP-1 in particular, has increased significantly. This timely volume summarizes what is now known about the molecular biology, physiology and pharmacology of GLP-1. Thorough coverage is given to the physiology of the hormone, including its generation, release and actions at pancreatic and extrapancreatic tissues. The intracellular mechanisms of GLP-1 are also described in detail. Discussion of the molecular biology includes the structure and functions of the genes coding for proglucagon and the GLP-1 receptor. A special feature of the book is the clinical information provided which includes data on the expression and release of GLP-1 and its potential use as a therapeutic agent for diabetes. Presenting the results of exciting new research, this book will be a valuable reference for endocrinologists, gastroenterologists, pharmacologists, physiologists and biochemists interested in this important hormone.
Role of residues 104, 164, 166, 238 and 240 in the substrate profile of PER-1 β-lactamase hydrolysing third-generation cephalosporins (1998)

The class A beta-lactamase PER-1, which displays 26% identity with the TEM-type extended-spectrum beta-lactamases (ESBLs), catalyses the hydrolysis of oxyimino-beta-lactams such as cefotaxime (CTX), ceftazidime (CAZ) and aztreonam (AZT). Molecular modelling was used to identify in PER-1 the amino acid residues corresponding to those found at positions 104, 164, 238 and 240 in the TEM-type ESBLs, which are critical for hydrolysis of oxyimino-beta-lactams. The function of these residues in PER-1 was assessed by site-directed mutagenesis. In this enzyme, residue 104 could be either a glutamine, an asparagine or a threonine. The Gln-->Gly mutation did not significantly affect the catalytic efficiency, while Asn-->Gly and Thr-->Glu resulted in a marked decrease in catalytic activity, probably due to the alteration of a hydrogen bond network connecting the putative Asn-104 residue to Asn-132 and Glu-166. Replacement of Ala-164 by Arg in PER-1 resulted in a mutant with no detectable activity, thus suggesting that Ala-164 is important for catalysis and stability of PER-1. Conversely, Ser-238-->Gly and Gly-240-->Glu had little effect on kcat and Km values. Finally, the replacement of the catalytic residue Glu-166 by an alanine resulted in a complete loss of activity for CTX and a marked decrease of kcat for CAZ and AZT. These results suggest that Glu-166 is an important residue in PER-1. However, residues other than Glu-166 could contribute in maintaining residual activity towards oxyimino-beta-lactams in the Ala-166 mutant.
Platinum-Catalyzed Tandem Indole Annulation/Arylation for the Synthesis of Diindolylmethanes and Indolo[3,2-b]carbazoles (2013)

Various diindolylmethanes were prepared from propargylic ethers and substituted indoles via a platinum-catalyzed tandem indole annulation/arylation cascade. The resulting diindolylmethanes could be converted to natural product malassezin by formylation or indolo[3,2-b]carbazoles by cyclization.
β-Lactamase Inhibitors Derived from Single-Domain Antibody Fragments Elicited in the Camelidae (2001)

Small, soluble single-domain fragments derived from the unique variable region of dromedary heavy-chain antibodies (VHHs) against enzymes are known to be potent inhibitors. The immunization of dromedaries with the TEM-1 and BcII beta-lactamases has lead to the isolation of such single-domain antibody fragments specifically recognizing and inhibiting those beta-lactamases. Two VHHs were isolated that inhibit TEM-1 and one BcII inhibiting VHH was identified. All inhibitory VHHs were tight-binding inhibitors. The 50% inhibitory concentrations were determined for all inhibitors and they were all in the same range as the enzyme concentration used in the assay. Addition of the VHHs to the TEM-1 beta-lactamase, expressed on the surface of bacteria, leads to a higher ampicillin sensitivity of the bacteria. This innovative strategy could generate multiple potent inhibitors for all types of beta-lactamases.
Transport and Pharmacological Properties of Nine Different Human Na,K-ATPase Isozymes (2000)

Na,K-ATPase plays a crucial role in cellular ion homeostasis and is the pharmacological receptor for digitalis in man. Nine different human Na,K-ATPase isozymes, composed of 3 alpha and beta isoforms, were expressed in Xenopus oocytes and were analyzed for their transport and pharmacological properties. According to ouabain binding and K(+)-activated pump current measurements, all human isozymes are functional but differ in their turnover rates depending on the alpha isoform. On the other hand, variations in external K(+) activation are determined by a cooperative interaction mechanism between alpha and beta isoforms with alpha2-beta2 complexes having the lowest apparent K(+) affinity. alpha Isoforms influence the apparent internal Na(+) affinity in the order alpha1 > alpha2 > alpha3 and the voltage dependence in the order alpha2 > alpha1 > alpha3. All human Na,K-ATPase isozymes have a similar, high affinity for ouabain. However, alpha2-beta isozymes exhibit more rapid ouabain association as well as dissociation rate constants than alpha1-beta and alpha3-beta isozymes. Finally, isoform-specific differences exist in the K(+)/ouabain antagonism which may protect alpha1 but not alpha2 or alpha3 from digitalis inhibition at physiological K(+) levels. In conclusion, our study reveals several new functional characteristics of human Na,K-ATPase isozymes which help to better understand their role in ion homeostasis in different tissues and in digitalis action and toxicity.