gebhart/patrepeval huggingface dataset:
THE ROLE OF COMPLEMENT AND COMPLEMENT RECEPTORS IN INDUCTION AND REGULATION OF IMMUNITY (1998)

Covalent attachment of activated complement C3 (C3d) to antigen links innate and adaptive immunity by targeting antigen to follicular dendritic cells (FDC) and B cells via specific receptors CD21 and CD35. Recent characterization of knockout mice deficient in complement components C3, C4, or the receptors CD21 and CD35 as well as biochemical studies of the CD21/CD19/Tapa-1 coreceptor on B cells have helped to elucidate the mechanism of complement regulation of both B-1 and B-2 lymphocytes. Interestingly, natural antibody of the adaptive immune system provides a major recognition role in activation of the complement system, which in turn enhances activation of antigen-specific B cells. Enhancement of the primary and secondary immune response to T-dependent antigens is mediated by coligation of the coreceptor and the B cell antigen receptor, which dramatically increases follicular retention and B cell survival within the germinal center. Most recent evidence suggests that complement also regulates elimination of self-reactive B cells, as breeding of mice that are deficient in C4 or CD21/CD35 with the lupus-prone strain of lpr mice demonstrates an exacerbation of disease due to an increase in autoantibodies.
B-Cell Activating Factor as a Cancer Biomarker and Its Implications in Cancer-Related Cachexia (2015)

B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF's proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia.
The Role of Brushite and Octacalcium Phosphate in Apatite Formation (1992)

Studies of apatite mineral formation are complicated by the possibility of forming several calcium phosphate phases. The least soluble, hydroxyapatite (HAP), is preferentially formed under neutral or basic conditions. In more acidic solutions phases such as dicalcium phosphate dihydrate (Brushite, DCPD) and octacalcium phosphate (OCP) are often found. Even under ideal HAP precipitation conditions the precipitates are generally nonstoichiometric, suggesting the formation of calcium-deficient apatites. Both DCPD and OCP have been implicated as possible precursors to the formation of apatite. This may occur by the initial precipitation of DCPD and/or OCP followed by transformation to a more apatitic phase. Although DCPD and OCP are often detected during in vitro crystallization, in vivo studies of bone formation rarely show the presence of these acidic calcium phosphate phases. In the latter case the situation is more complicated, since a large number of ions and molecules are present that can be incorporated into the crystal lattice or adsorbed at the crystallite surfaces. In biological apatite, DCPD and OCP are usually detected only during pathological calcification where the pH is often relatively low. In normal in vivo calcifications these phases have not been found, suggesting the involvement of other precursors or the formation of an initial amorphous calcium phosphate phase (ACP) followed by transformation to apatite.
Mobilization of capillary endothelium in vitro induced by effectors of angiogenesis in vivo. (1983)

An assay to measure endothelial cell mobilization on a gelatin substratum has been developed. Utilization of the gelatin-agarose and Boyden chamber assays established that: (a) fragments or extracts of corneas treated with several effectors of angiogenesis in vivo acquired the capacity to mobilize the capillary endothelium in vitro; (b) this mobilization was selective for the capillary endothelium; endothelium from aorta and fibroblasts from human skin or rabbit cornea were unresponsive; and (c) among the effectors of angiogenesis utilized alone; i.e., without the intermediary action of the cornea, none were able to mobilize the capillary endothelium in vitro, except for the heparin-copper complex. The data are interpreted to indicate that new formation of capillaries in vivo is the end result of a cascade of events of which heparin and copper are important components.
In vitro selection of molecular beacons (2003)

While molecular beacons are primarily known as biosensors for the detection of nucleic acids, it has proven possible to adapt other nucleic acid binding species (aptamers) to function in a manner similar to molecular beacons, yielding fluorescent signals only in the presence of a cognate ligand. Unfortunately, engineering aptamer beacons requires a detailed knowledge of aptamer sequence and structure. In order to develop a general method for the direct selection of aptamer beacons we have first developed a selection method for molecular beacons. A pool of random sequence DNA molecules were immobilized via a capture oligonucleotide on an affinity column, and those variants that could be released from the column by a target oligonucleotide were amplified. After nine rounds of selection and amplification the elution characteristics of the population were greatly improved. A fluorescent reporter in the selected beacons was located adjacent to a DABCYL moiety in the capture oligonucleotide; addition of the target oligonucleotide led to release of the capture oligonucleotide and up to a 17-fold increase in fluorescence. Signaling was specific for the target oligonucleotide, and occurred via a novel mechanism, relative to designed molecular beacons. When the target oligonucleotide is bound it can form a stacked helical junction with an intramolecular hairpin in the selected beacon; formation of the intramolecular hairpin in turn leads to release of the capture oligonucleotide. The ability to select molecular beacons may prove useful for identifying available sites on complex targets, such as mRNAs, while the method for selection can be easily generalized to other, non-nucleic acid target classes.
Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium. (1996)

Thrombospondin-1 (TSP1), a multifunctional extracellular matrix glycoprotein, has been shown to suppress the angiogenic response in vivo and in vitro. We hypothesized that TSP1 might play a role in the inhibition of capillary morphogenesis during the endometrial cycle and examined its expression in 46 human endometrial specimens. Our results show that the expression of TSP1 in the endometrium is (a) cycle-dependent, (b) associated with periods of low capillary growth, and (c) regulated by progesterone. TSP1 protein was identified in the basement membrane of capillaries of the functional endometrium during the secretory phase. Abundant expression of TSP1 mRNA in the secretory phase was also detected by in situ hybridization, in contrast to the low levels seen in the proliferative phase. These findings were confirmed by Northern analysis of proliferative and secretory endometrium. Transcripts for TSP1 were observed predominantly in stromal cells, but signal was also detected in some endothelial and smooth muscle cells. Since the proliferation of endometrial tissue is regulated by steroid hormones, we tested the effects of estrogen and progesterone on TSP1 expression by stromal cells isolated from human endometrium. We found that levels of TSP1 mRNA and protein were increased after incubation with progesterone. Maximal stimulation of mRNA was observed after 8 h of treatment with 10-50 microM progesterone, and the effect was suppressed by the progesterone antagonist RU-486. Induction by progesterone was cell-specific and equivalent to the stimulation mediated by PDGF. Finally, the levels of TSP1 present in progesterone-stimulated cultures were sufficient to inhibit the migration of endothelial cells in vitro; this effect was nullified by anti-TSP antibodies. We therefore propose that the production of TSP1 at later stages of the endometrial cycle is linked to the inhibition of vessel formation and that TSP1 expression is progesterone-dependent in this tissue.
Calcium channel blockers and stroke. (2005)

The most frequent indication for Calcium Channel Blockers (CCBs) is their use as antihypertensive agents for primary or secondary stroke prevention. Hypertension contributes to virtually all mechanisms of stroke, of atherothrombotic, lacunar, cardioembolic and intraparenchymal hemorrhage types. In comparison with the rather univocal mechanisms underlying coronary artery or peripheral artery disease, the variable mechanisms of stroke are the main reason explaining not only the different impact of vascular risk factors, but also the different effects of drugs given for prevention. In an acute stroke setting, lowering blood pressure is potentially harmful, especially if it is carried out using short-acting dihydropyridine derivatives. Some CCBs, such as nicardipine, are preferred in certain conditions (including acute thrombolysis). In stroke, CCBs may also play a role as neuroprotectants. Then twofold effect--against vessel wall changes and as neuroprotectants (after ischemia or degenerative insults)--make this class of drugs of interest for their possible application in the setting of dementias, particularly that of vascular dementia. Some CCBs have been tested and are of benefit when used for preventing or treating cerebral vasospasm after subarachnoid hemorrhage. CCBs must be considered effective in preventing stroke in hypertensive patients. In comparison with other antihypertensive agents, their effects are similar to or even better than those exerted by other drugs. This may be due to the fact that stroke includes different types, with differing underlying pathophysiological mechanisms. The anti-atherosclerotic properties of CCBs may be useful in preventing the atherothrombotic type of stroke at the large pre-cerebral artery level. Dihydropyridinic derivatives may play a selective role in relation to small-vessel disease of the brain, which leads to multiple stroke-associated conditions, including lacunar infarct, intra-cerebral hemorrhage and subcortical vascular dementia. Oral nimodipine is recommended in the prevention/treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). CCBs, particularly nimodipine, may be of some benefit in vascular or mixed degenerative and vascular dementia or, taking into account subtypes, more selectively in subcortical vascular dementia. In this setting, CCBs may contribute toward reducing the risk of recurrent stroke in patients who are usually at high risk of recurrence.
ASA Physical Status Classifications (1978)

The American Society of Anesthesiologists' (ASA) Physical Status Classification was tested for consistency of use by a questionnaire sent to 304 anesthesiologists. They were requested to classify ten hypothetical patients. Two hundred fifty-five (77.3 percent) responded to two mailings. The mean number of patients rated consistently was 5.9. Four patients elicited wide ranges of responses. Age, obesity, previous myocardial infarction, and anemia provoked controversy. There was no significant difference in responses from different regions of the country. Academic anesthesiologists rated a greater number identical than did those in private practice (P less than 0.01). There was no difference in ratings between those who used the classification for billing purposes and those who did not. The ASA Physical Status Classification is useful but suffers from a lack of scientific precision.
Discovery of Mixed Pharmacology Melanocortin-3 Agonists and Melanocortin-4 Receptor Tetrapeptide Antagonist Compounds (TACOs) Based on the Sequence Ac-Xaa1-Arg-(pI)DPhe-Xaa4-NH2 (2017)

The centrally expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been studied as possible targets for weight management therapies, with a preponderance of studies focusing on the MC4R. Herein, a novel tetrapeptide scaffold [Ac-Xaa<sup>1</sup>-Arg-(pI)DPhe-Xaa<sup>4</sup>-NH<sub>2</sub>] is reported. The scaffold was derived from results obtained from a MC3R mixture-based positional scanning campaign. From these results, a set of 48 tetrapeptides were designed and pharmacologically characterized at the mouse melanocortin-1, -3, -4, and -5 receptors. This resulted in the serendipitous discovery of nine compounds that were MC3R agonists (EC<sub>50</sub> < 1000 nM) and MC4R antagonists (5.7 < pA<sub>2</sub> < 7.8). The three most potent MC3R agonists, 18 [Ac-Arg-Arg-(pI)DPhe-Tic-NH<sub>2</sub>], 1 [Ac-His-Arg-(pI)DPhe-Tic-NH<sub>2</sub>], and 41 [Ac-Arg-Arg-(pI)DPhe-DNal(2')-NH<sub>2</sub>] were more potent (EC<sub>50</sub> < 73 nM) than the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH<sub>2</sub>. This template contains a sequentially reversed "Arg-(pI)DPhe" motif with respect to the classical "Phe-Arg" melanocortin signaling motif, which results in pharmacology that is first-in-class for the central melanocortin receptors.
Ionic Conductance Changes in Lobster Axon Membrane When Lanthanum Is Substituted for Calcium (1966)

The trivalent rare earth lanthanum was substituted for calcium in the sea water bathing the exterior of an "artificial node" of a lobster axon in a sucrose gap. It caused a progressive rise in threshold, and a decrease in the height of the action potential as well as in its rates of rise and fall. Prolonged application produced an excitation block. Voltage-clamp studies of the ionic currents showed that the time courses of the ionic conductance changes for both sodium and potassium were increased. Concurrently, the potentials at which the conductance increases occurred were shifted to more positive inside values for the La+++ sea water. These effects resemble changes resulting from a high external calcium concentration. Over and above this, La+++ also causes a marked reduction in the maximum amount of conductance increase following a depolarizing potential step. Membrane action potentials similar to those observed experimentally in the La+++ solution have been computed with appropriate parameter changes in the Hodgkin-Huxley equations.
Nucleotide sequence of the streptolysin O (SLO) gene: structural homologies between SLO and other membrane-damaging, thiol-activated toxins (1987)

The complete nucleotide sequence of a cloned streptolysin O (SLO) gene and the amino acid sequence of SLO, predicted from the DNA sequence, are reported. SLO contains a single cysteine residue located close to the C terminus of the molecule and shares extensive structural homologies with other thiol-activated toxins, which allow us to predict functionally important features.
Current and emerging concepts in tumour metastasis (2010)

Disseminated cancer accounts for most deaths due to malignancy. Despite this, research has focused predominantly on tumour development and progression at the primary site. Recently, attention has shifted towards the field of tumour metastasis. Several new and exciting concepts that have emerged in the past few years may shed light on this complex area. The established canonical theory of tumour metastasis, as a process emerging from a stepwise accumulation of genetic events fuelled by clonal evolution, has been challenged. New evidence suggests that malignant cells can disseminate at a much earlier stage than previously recognized in tumourigenesis. These findings have direct relevance to clinical practice and shed new light on tumour biology. Gene-profiling studies support this theory, suggesting that metastatic ability may be an innate property shared by the bulk of cells present early in a developing tumour mass. There is a growing recognition of the importance of host factors outside the primary site in the development of metastatic disease. The role of the 'pre-metastatic niche' is being defined and with this comes a new understanding of the function of bone marrow-derived progenitor cells in directing the dissemination of malignant cells to distant sites. Current research has highlighted the crucial roles played by non-neoplastic host cells within the tumour microenvironment in regulating metastasis. These new concepts have wide-ranging implications for our overall understanding of tumour metastasis and for the development of cancer therapeutics.
An architecture for managing application services over global networks (2002)

This paper proposes a novel approach for providing end-to-end management of application services that have been deployed over large IP networks. A key feature of the proposed architecture is that it can be implemented as enhancements to existing, commercial network management platforms, thus allowing network service providers to offer new functionality by leveraging existing, deployed infrastructures.
Platelet and leucocyte activation in childhood sickle cell disease: association with nocturnal hypoxaemia (2000)

We hypothesized that vaso-occlusive events in childhood sickle cell disease (SCD) may relate to inflammatory cell activation as well as interactions between sickle erythrocytes and vascular endothelium. Peripheral blood was examined from 24 children with SCD, of whom 12 had neurological sequelae and seven had frequent painful crises, and 10 control subjects. Platelet (CD62P and CD40L expression) and granulocyte (CD11b expression) activation and levels of platelet-erythrocyte and platelet-granulocyte complexes were determined by flow cytometry. Platelets (P = 0.019), neutrophils (P = 0.02) and monocytes (P = 0.001) were more activated and there were increased platelet-erythrocyte complexes (P = 0.026) in SCD patients compared with controls. Platelet-granulocyte complexes were not raised. There were no differences between the different groups of SCD. As hypoxia activates monocytes, platelets and endothelial cells and causes sickling of SCD erythrocytes, we also investigated 20 SCD patients with overnight pulse oximetry. Minimum overnight saturation correlated with the level of platelet-erythrocyte complexes (Spearman's rho -0.668, P < 0.02), neutrophil CD11b (Spearman's rho -0.466, P = 0.038) and monocyte CD11b (Spearman's rho -0.652, P = 0. 002). These findings provide important clues about the mechanism by which SCD patients may become predisposed to vaso-occlusive events.
Oxidative Stress as a Major Culprit in Kidney Disease in Diabetes (2008)

It is postulated that localized tissue oxidative stress is a key component in the development of diabetic nephropathy. There remains controversy, however, as to whether this is an early link between hyperglycemia and renal disease or develops as a consequence of other primary pathogenic mechanisms. In the kidney, a number of pathways that generate reactive oxygen species (ROS) such as glycolysis, specific defects in the polyol pathway, uncoupling of nitric oxide synthase, xanthine oxidase, NAD(P)H oxidase, and advanced glycation have been identified as potentially major contributors to the pathogenesis of diabetic kidney disease. In addition, a unifying hypothesis has been proposed whereby mitochondrial production of ROS in response to chronic hyperglycemia may be the key initiator for each of these pathogenic pathways. This postulate emphasizes the importance of mitochondrial dysfunction in the progression and development of diabetes complications including nephropathy. A mystery remains, however, as to why antioxidants per se have demonstrated minimal renoprotection in humans despite positive preclinical research findings. It is likely that the utility of current study approaches, such as vitamin use, may not be the ideal antioxidant strategy in human diabetic nephropathy. There is now an increasing body of data to suggest that strategies involving a more targeted antioxidant approach, using agents that penetrate specific cellular compartments, may be the elusive additive therapy required to further optimize renoprotection in diabetes.
A novel Apaf-1–independent putative caspase-2 activation complex (2002)

Caspase activation is a key event in apoptosis execution. In stress-induced apoptosis, the mitochondrial pathway of caspase activation is believed to be of central importance. In this pathway, cytochrome c released from mitochondria facilitates the formation of an Apaf-1 apoptosome that recruits and activates caspase-9. Recent data indicate that in some cells caspase-9 may not be the initiator caspase in stress-mediated apoptosis because caspase-2 is required upstream of mitochondria for the release of cytochrome c and other apoptogenic factors. To determine how caspase-2 is activated, we have studied the formation of a complex that mediates caspase-2 activation. Using gel filtration analysis of cell lysates, we show that caspase-2 is spontaneously recruited to a large protein complex independent of cytochrome c and Apaf-1 and that recruitment of caspase-2 to this complex is sufficient to mediate its activation. Using substrate-binding assays, we also provide the first evidence that caspase-2 activation may occur without processing of the precursor molecule. Our data are consistent with a model where caspase-2 activation occurs by oligomerization, independent of the Apaf-1 apoptosome.
Membrane Proteins: From Sequence to Structure (1994)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
Microarray Analysis of Microbial Virulence Factors (2001)

Hybridization with oligonucleotide microchips (microarrays) was used for discrimination among strains of Escherichia coli and other pathogenic enteric bacteria harboring various virulence factors. Oligonucleotide microchips are miniature arrays of gene-specific oligonucleotide probes immobilized on a glass surface. The combination of this technique with the amplification of genetic material by PCR is a powerful tool for the detection of and simultaneous discrimination among food-borne human pathogens. The presence of six genes (eaeA, slt-I, slt-II, fliC, rfbE, and ipaH) encoding bacterial antigenic determinants and virulence factors of bacterial strains was monitored by multiplex PCR followed by hybridization of the denatured PCR product to the gene-specific oligonucleotides on the microchip. The assay was able to detect these virulence factors in 15 Salmonella, Shigella, and E. coli strains. The results of the chip analysis were confirmed by hybridization of radiolabeled gene-specific probes to genomic DNA from bacterial colonies. In contrast, gel electrophoretic analysis of the multiplex PCR products used for the microarray analysis produced ambiguous results due to the presence of unexpected and uncharacterized bands. Our results suggest that microarray analysis of microbial virulence factors might be very useful for automated identification and characterization of bacterial pathogens.
A Survey of Hardware Trojan Taxonomy and Detection (2010)

Editor's note:Today's integrated circuits are vulnerable to hardware Trojans, which are malicious alterations to the circuit, either during design or fabrication. This article presents a classification of hardware Trojans and a survey of published techniques for Trojan detection.