gebhart/patrepeval huggingface dataset:
Authentication in distributed systems (1991)

We describe a theory of authentication and a system that implements it. Our theory is based on the notion of principal and a "speaks for" relation between principals. A simple principal either has a name or is a communication channel; a compound principal can express an adopted role or delegation of authority. The theory explains how to reason about a principal's authority by deducing the other principals that it can speak for; authenticating a channel is one important application. We use the theory to explain many existing and proposed mechanisms for security. In particular, we describe the system we have built. It passes principals efficiently as arguments or results of remote procedure calls, and it handles public and shared key encryption, name lookup in a large name space, groups of principals, loading programs, delegation, access control, and revocation.
Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential. (1986)

It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each m...
Neurosteroids Involved in Regulating Inhibition in the Inferior Colliculus (2006)

Fast inhibitory neurotransmission in the brain is largely mediated by the gamma-aminobutyric acid-type A (GABA(A)) receptor. The 3alpha,5alpha-reduced neurosteroids (e.g., allopregnanolone) are the most potent endogenous modulators of the GABA(A) receptor. Although it is known that 3alpha,5alpha-reduced neurosteroid levels change during stress or depression and over the estrus cycle, a basic physiological role consistent with their pharmacological action remains elusive. We used the unique architecture of the auditory midbrain to reveal a role for 3alpha,5alpha-reduced neurosteroids in regulating inhibitory efficacy. After blocking the massive GABAergic projection from the dorsal nucleus of the lateral lemniscus (DNLL) to the contralateral central nucleus of the inferior colliculus (ICC) in anesthetized rats, a reactive increase in the efficacy of other inhibitory circuits in the ICC (separable because of the dominant ear that drives each circuit) was demonstrated with physiological measures-single-neuron activity and a neural-population-evoked response. This effect was prevented by blocking 3alpha,5alpha-reduced neurosteroid synthesis with a 5alpha-reductase inhibitor: finasteride. Immunohistochemistry confirmed that the DNLL blockade induced an increase in 3alpha,5alpha-reduced neurosteroids in the contralateral ICC. This study shows that when GABAergic inhibition is reduced, the brain compensates within minutes by locally increasing synthesis of neurosteroids, thereby balancing excitatory and inhibitory inputs in complex neural circuits.
Bridging the gap between optical fibers and silicon photonic integrated circuits (2014)

We present a rigorous approach for designing a highly efficient coupling between single mode optical fibers and silicon nanophotonic waveguides based on diffractive gratings. The structures are fabricated on standard SOI wafers in a cost-effective CMOS process flow. The measured coupling efficiency reaches -1.08 dB and a record value of -0.62 dB in the 1550 nm telecommunication window using a uniform and a nonuniform grating, respectively, with a 1 dB-bandwidth larger than 40 nm.
The Nuclear Receptor PPARγ and Immunoregulation: PPARγ Mediates Inhibition of Helper T Cell Responses (2000)

The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors belonging to the nuclear receptor superfamily. Until recently, the genes regulated by PPARs were those believed to be predominantly associated with lipid metabolism. Recently, an immunomodulatory role for PPAR gamma has been described in cells critical to the innate immune system, the monocyte/macrophage. In addition, evidence for an antiinflammatory role of the PPAR gamma ligand, 15-deoxy-Delta 12,14-PGJ2 (15d-PGJ2) has been found. In the present studies, we demonstrate, for the first time, that murine helper T cell clones and freshly isolated splenocytes express PPAR gamma 1. The PPAR gamma expressed is of functional significance in that two ligands for PPAR gamma, 15d-PGJ2 and a thiazolidinedione, ciglitazone, mediate significant inhibition of proliferative responses of both the T cell clones and the freshly isolated splenocytes. This inhibition is mediated directly at the level of the T cell and not at the level of the macrophage/APC. Finally, we demonstrate that the two ligands for PPAR gamma mediate inhibition of IL-2 secretion by the T cell clones while not inhibiting IL-2-induced proliferation of such clones. The demonstration of the expression and function of PPAR gamma in T cells reveals a new level of immunoregulatory control for PPARs and significantly increases the role and importance of PPAR gamma in immunoregulation.
Gene Therapy for SCID-X1: Focus on Clinical Data (2011)

A recent report by Gaspar et al. summarizes the clinical long-term follow-up (LTFU) of 10 patients presenting with X-linked severe combined immunodeficiency (SCID-X1) who were treated with first-generation gamma-retroviral vectors to reconstitute the expression of the interleukin-2 receptor common γ-chain (IL2RG) in autologous hematopoietic cells.1 As in a related study of nine patients conducted by Hacein-Bey-Abina et al.,2 the children enrolled in this study had no human leukocyte antigen–matched donor, thus reducing the safety and effectiveness of an allogeneic stem cell transplant.
Impaired IL-18 processing protects caspase-1–deficient mice from ischemic acute renal failure (2001)

We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1 beta and IL-18, were protected against ischemic acute renal failure (ARF). Caspase-1(-/-) mice developed less ischemic ARF as judged by renal function and renal histology. These animals had significantly reduced blood urea nitrogen and serum creatinine levels and a lower morphological tubular necrosis score than did wild-type mice with ischemic ARF. Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1(-/-) mice from ARF. In wild-type animals, we found that ARF causes kidney IL-18 levels to more than double and induces the conversion of the IL-18 precursor to the mature form. This conversion is not observed in caspase-1(-/-) ARF mice or sham-operated controls. We then injected wild-type mice with IL-18-neutralizing antiserum before the ischemic insult and found a similar degree of protection from ARF as seen in caspase-1(-/-) mice. In addition, we observed a fivefold increase in myeloperoxidase activity in control mice with ARF, but no such increase in caspase-1(-/-) or IL-18 antiserum-treated mice. Finally, we confirmed histologically that caspase-1(-/-) mice show decreased neutrophil infiltration, indicating that the deleterious role of IL-18 in ischemic ARF may be due to increased neutrophil infiltration.
GROWTH FACTOR RECEPTOR TYROSINE KINASES (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Cytokines as Mediators of Neuroinflammation in Experimental Autoimmune Encephalomyelitis (2018)

Cytokines play a pivotal role in maintaining homeostasis of the immune system and in regulation of the immune response. Cytokine dysregulation is often associated with development of various pathological conditions, including autoimmunity. Recent studies have provided insights into the cytokine signaling pathways that are involved not only in pathogenesis of autoimmune neuroinflammatory disorders, such as multiple sclerosis, but also in neurodegenerative states, for example, Alzheimer's disease. Understanding the exact molecular mechanisms of disease pathogenesis and evaluation of relevant experimental animal models are necessary for development of effective therapeutic approaches.
Modification of the C terminus of cecropin is essential for broad-spectrum antimicrobial activity (1993)

Cecropin A is a naturally occurring peptide with bactericidal activity against gram-negative and gram-positive bacteria. Production of large quantities of bactericidal peptides that are similar in structure and activity to cecropin A has been achieved by combining recombinant DNA techniques and techniques and chemical modification. Expression of the bactericidal peptide in Escherichia coli was accomplished through the formation of a fusion protein. The 5' end of the L-ribulokinase gene was fused to a single copy of a synthetic gene encoding cecropin A. A methionine codon was engineered between the two genes, and a methionylglycine extension was introduced at the C terminus of cecropin A. Cyanogen bromide treatment of the fusion protein yielded cecropin A with a C-terminal homoserine. The recombinant cecropin A with a homoserine at the C terminus did not kill most gram-positive bacteria tested. However, recombinant cecropin A with a chemically modified C terminus has antimicrobial activity similar to that of cecropin produced by cecropia pupae.
Klotho Deficiency Causes Vascular Calcification in Chronic Kidney Disease (2010)

Soft-tissue calcification is a prominent feature in both chronic kidney disease (CKD) and experimental Klotho deficiency, but whether Klotho deficiency is responsible for the calcification in CKD is unknown. Here, wild-type mice with CKD had very low renal, plasma, and urinary levels of Klotho. In humans, we observed a graded reduction in urinary Klotho starting at an early stage of CKD and progressing with loss of renal function. Despite induction of CKD, transgenic mice that overexpressed Klotho had preserved levels of Klotho, enhanced phosphaturia, better renal function, and much less calcification compared with wild-type mice with CKD. Conversely, Klotho-haploinsufficient mice with CKD had undetectable levels of Klotho, worse renal function, and severe calcification. The beneficial effect of Klotho on vascular calcification was a result of more than its effect on renal function and phosphatemia, suggesting a direct effect of Klotho on the vasculature. In vitro, Klotho suppressed Na(+)-dependent uptake of phosphate and mineralization induced by high phosphate and preserved differentiation in vascular smooth muscle cells. In summary, Klotho is an early biomarker for CKD, and Klotho deficiency contributes to soft-tissue calcification in CKD. Klotho ameliorates vascular calcification by enhancing phosphaturia, preserving glomerular filtration, and directly inhibiting phosphate uptake by vascular smooth muscle. Replacement of Klotho may have therapeutic potential for CKD.
Modulation of Lipid‐Induced ER Stress by Fatty Acid Shape (2010)

Exposure of pancreatic β cells to long-chain saturated fatty acids (SFA) induces a so-called endoplasmic reticulum (ER) stress that can ultimately lead to cell death. This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER stress. Here we demonstrate that the tendency of a free fatty acid (FFA) to reduce SFA toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double bonds and nature of the isomers (cis or trans). Interestingly, potent FFA act as building blocks for phospholipid synthesis and help to restore an optimal membrane organization, compatible with ER function and normal protein trafficking.
A Comparison of the Neutralizing Properties of Monoclonal and Polyclonal Antibodies to Human Interferon Alpha (1984)

Specific polyclonal antisera to human interferon-alpha 1 (HuIFN-alpha 1), human interferon-alpha 2 (HuIFN-alpha 2) and human lymphoblastoid interferon (HuIFN-alpha Ly Namalwa) have been raised in rabbits and sheep. The antisera raised against HuIFN-alpha 1 and HuIFN-alpha 2 strongly neutralized the antiviral activity of their homologous IFN-alpha subtypes, but were less active against the heterologous IFN-alpha subtypes and preparations containing mixtures of IFN-alpha subtypes, e.g. human leukocyte interferon (HuIFN-alpha Le). Antisera raised against HuIFN-alpha Ly Namalwa strongly neutralized the antiviral activity of all IFN-alpha-containing preparations and showed weak cross-reactivity with human interferon-beta (HuIFN-beta). Neither anti-HuIFN-alpha 1 nor anti-HuIFN-alpha 2 could be demonstrated to neutralize the antiviral activity of HuIFN-beta. A number of monoclonal antibodies to HuIFN-alpha 2 have been prepared and these were found to neutralize HuIFN-alpha 2 antiviral activity to varying degrees, but not to neutralize the heterologous subtype HuIFN-alpha 1, preparations containing mixtures of IFN-alpha subtypes or HuIFN-beta.
Molecular cascades that mediate the influence of inflammation on epilepsy (2011)

Experimental evidence strongly indicates a significant role for inflammatory and immune mediators in initiation of seizures and epileptogenesis. Here we will summarize data supporting the involvement of IL-1β, TNF-α and toll-like receptor 4 in seizure generation and the process of epileptogenesis. The physiological homeostasis and control over brain immune response depends on the integrity of the blood-brain barrier, transforming growth factor (TGF)-β signaling and leukocyte migration. To what extent targeting the immune system is successful in preventing epileptogenesis, and which signaling pathway should be beleaguered is still under intensive research.
Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. (1993)

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two cytokines that are secreted by activated T cells and have similar effects on monocytes and B cells. We describe a mutant form of human interleukin-4 (hIL-4) that competitively antagonizes both hIL-4 and human interleukin-13 (hIL-13). The amino acid sequences of IL-4 and IL-13 are approximately 30% homologous and circular dichroism (CD) spectroscopy shows that both proteins have a highly alpha-helical structure. IL-13 competitively inhibited binding of hIL-4 to functional human IL-4 receptors (called hIL-4R) expressed on a cell line which responds to both hIL-4 and IL-13. Binding of hIL-4 to an hIL-4 responsive cell line that does not respond to IL-13, and binding of hIL-4 to cloned IL-4R ligand binding protein expressed on heterologous cells, were not inhibited by IL-13. hIL-4 bound with approximately 100-fold lower affinity to the IL-4R ligand binding protein than to functional IL-4R. The mutant hIL-4 antagonist protein bound to both IL-4R types with the lower affinity. The above results demonstrate that IL-4 and IL-13 share a receptor component that is important for signal transduction. In addition, our data establish that IL-4R is a complex of at least two components one of which is a novel affinity converting subunit that is critical for cellular signal transduction.
The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium (2011)

Valproic acid (VPA) is the most widely prescribed epilepsy treatment worldwide, but its mechanism of action remains unclear. Our previous work identified a previously unknown effect of VPA in reducing phosphoinositide production in the simple model Dictyostelium followed by the transfer of data to a mammalian synaptic release model. In our current study, we show that the reduction in phosphoinositide [PtdInsP (also known as PIP) and PtdInsP(2) (also known as PIP(2))] production caused by VPA is acute and dose dependent, and that this effect occurs independently of phosphatidylinositol 3-kinase (PI3K) activity, inositol recycling and inositol synthesis. In characterising the structural requirements for this effect, we also identify a family of medium-chain fatty acids that show increased efficacy compared with VPA. Within the group of active compounds is a little-studied group previously associated with seizure control, and analysis of two of these compounds (nonanoic acid and 4-methyloctanoic acid) shows around a threefold enhanced potency compared with VPA for protection in an in vitro acute rat seizure model. Together, our data show that VPA and a newly identified group of medium-chain fatty acids reduce phosphoinositide levels independently of inositol regulation, and suggest the reinvestigation of these compounds as treatments for epilepsy.
RESULTS FROM THE BES (2000)

Results from the BES for the past decade, such as τ mass measurement, measurements of f D s and f D , studies of ξ(2230) and ψ(2s) physics, R scan, and so on, are summarized.
TRANSCRIPTIONAL CONTROL OF MUSCLE DEVELOPMENT BY MYOCYTE ENHANCER FACTOR-2 (MEF2) PROTEINS (1998)

Metazoans contain multiple types of muscle cells that share several common properties, including contractility, excitability, and expression of overlapping sets of muscle structural genes that mediate these functions. Recent biochemical and genetic studies have demonstrated that members of the myocyte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)-box transcription factors play multiple roles in muscle cells to control myogenesis and morphogenesis. Like other MADS-box proteins, MEF2 proteins act combinatorially through protein-protein interactions with other transcription factors to control specific sets of target genes. Genetic studies in Drosophila have also begun to reveal the upstream elements of myogenic regulatory hierarchies that control MEF2 expression during development of skeletal, cardiac, and visceral muscle lineages. Paradoxically, MEF2 factors also regulate cell proliferation by functioning as endpoints for a variety of growth factor-regulated intracellular signaling pathways that are antagonistic to muscle differentiation. We discuss the diverse functions of this family of transcription factors, the ways in which they are regulated, and their mechanisms of action.
Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation (2007)

The discovery of the ubiquitin system was awarded with the Nobel Prize in Chemistry in 2004. Labeling of intracellular proteins for degradation by a multienzymatic complex, called the proteasome, was identified as the main function of this system. Subsequently, it was discovered that the attachment of ubiquitin to proteins can modify their function without degradation. Finally, a number of other molecules were recognized to be conjugated to proteins in a manner similar to ubiquitin and were henceforth called ubiquitin-like proteins. This review provides an overview of this class of molecules and its implication for function, subcellular location, and half-life of proteins.
Monoclonal antibodies selective for α‐synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α‐synuclein transgenic mice with the disease‐causing A30P mutation (2013)

Inclusions of intraneuronal alpha-synuclein (α-synuclein) can be detected in brains of patients with Parkinson's disease and dementia with Lewy bodies. The aggregation of α-synuclein is a central feature of the disease pathogenesis. Among the different α-synuclein species, large oligomers/protofibrils have particular neurotoxic properties and should therefore be suitable as both therapeutic and diagnostic targets. Two monoclonal antibodies, mAb38F and mAb38E2, with high affinity and strong selectivity for large α-synuclein oligomers were generated. These antibodies, which do not bind amyloid-beta or tau, recognize Lewy body pathology in brains from patients with Parkinson's disease and dementia with Lewy bodies and detect pathology earlier in α-synuclein transgenic mice than linear epitope antibodies. An oligomer-selective sandwich ELISA, based on mAb38F, was set up to analyze brain extracts of the transgenic mice. The overall levels of α-synuclein oligomers/protofibrils were found to increase with age in these mice, although the levels displayed a large interindividual variation. Upon subcellular fractionation, higher levels of α-synuclein oligomers/protofibrils could be detected in the endoplasmic reticulum around the age when behavioral disturbances develop. In summary, our novel oligomer-selective α-synuclein antibodies recognize relevant pathology and should be important tools to further explore the pathogenic mechanisms in Lewy body disorders. Moreover, they could be potential candidates both for immunotherapy and as reagents in an assay to assess a potential disease biomarker.
Adenovirus As An Integrating Vector (2002)

Recombinant adenoviral vectors have served as one of the most efficient gene delivery vehicles in vivo thus far. Multiply attenuated or completely gutless adenoviral vectors have been developed to achieve long-term gene expression in animal models by overcoming cellular immunity against de novo synthesized adenoviral proteins. However, since adenovirus lacks native integration machinery, the goal of gene therapy obtaining permanent expression cannot be realized with current adenoviral vector systems. Recent studies have shown that replication-incompetent adenoviral vectors randomly integrate into host chromosomes at frequencies of 0.001-1% of infected cells. To improve the integration frequencies of adenoviral vectors, a variety of hybrid vectors combining the highly efficient DNA delivery of adenovirus with the integrating machinery of retroviruses, adeno-associated viruses, and transposons, have been emerging. These hybrid vectors have shown promise, at least in in vitro systems. Furthermore, adenoviral vectors have shown potential as gene targeting vectors. These developments should eventually lead to more effective gene therapy vectors that can transduce a myriad of cell types stably in vivo.
Surface markers on human b and t lymphocytes. VI. Cytotoxicity against cell lines as a functional marker for lymphocyte subpopulations (1975)

The spontaneous lymphocyte mediated cytotoxicity (SLMC) of cells from normal donors against 19 different established cell lines was analysed. All normal lymphocytes were cytotoxic in all combinations tested in a17h 51-Cr release assay. ALMC was found to be mediated by a minor subpopulation of lymphocytes with Fc/C3 receptors. Non-cytotoxic SRBC binding T-lymphocytes could be induced to become cytotoxic by the addition of Con A to the incubation medium. SLMC and lectin-induced cytotoxicity were briefly characterized. It is argued that SLMC is a non-specific non-immunological reaction which must be taken into consideration when lymphocytes from cancer patients are tested against tumour-cell lines in vitro. Futhermore, SLMC and letin-induced cytotoxicity are proposed as functional markers for Fc/C3-binding lymphocytes and SRBC binding lymphocytes respectively.