gebhart/patrepeval huggingface dataset:
Activation of murine natural killer cells and macrophages by 8-bromoguanosine. (1988)

It has been shown that 8-bromoguanosine (8-BrGuo) activates T and B cells, but the underlying mechanism of this effect is not clear. We found that it also activates NK cells and macrophages by induction of IFN production. Culturing spleen cells with 8-BrGuo for 16 to 18 h induced cytotoxic activity to YAC cells. The cytotoxic cells expressed Qa-5, asialo-Gm-1, and NK-1.1 Ag. Similarly, preincubation of peptone-elicited peritoneal macrophages with 8-BrGuo induced macrophage cytolytic activity to P815 cells in an 18-h assay. Anti-IFN antibodies to IFN-alpha -beta and -gamma abolished these inductive events. Furthermore, elimination of asialo-Gm-1+ cells reduced the responses of NK and macrophages to 8-BrGuo, indicating that these cells possibly produce the IFN. We conclude from these observations that one biologic effect of 8-BrGuo is due to IFN production.
Molecular differences in the formation and structure of fine-stranded and particulate β-lactoglobulin gels (2000)

In order to reveal at a molecular level differences between fine-stranded and particulate gels, we present an Fourier transform infrared spectroscopic study of the thermal behavior of beta-lactoglobulin (beta-lg) in salt-free D(2)O solutions and low ionic strength at different pDs. Differences are found in the denaturation mechanism, in the unfolded state of the protein, in the aggregate formation, and in the strength of the intermolecular interactions. For fine-stranded gels (pD 2.8 and 7.8), heating induces the dissociation of the dimers into monomers. The protein undergoes extensive structural modifications before aggregation begins. Aggregation is characterized by the appearance of a new band attributed to intermolecular beta-sheets which is located in the 1613-1619 cm(-1) range. For particulate gels (pD 4.4 and 5.4), the protein structure is almost preserved up to 75-80 degrees C with no splitting of the dimers. The band characteristic of aggregation originates from the component initially located at 1623 cm(-1), suggesting that at the beginning of aggregation, globular beta-lg in the dimeric form associate to constitute oligomers with higher molecular mass. Aggregation may result in the association of globular slightly denatured dimers, leading to the formation of spherical particles rather than linear strands. The aggregation band is always located in the 1620-1623 cm(-1) range for particulate gels showing that hydrogen bonds are weaker for these aggregates than for fine-stranded ones. This has been related to a more extensive protein unfolding for fine-stranded gels that allows a closer alignment of the polypeptide chains, and then to the formation of much stronger hydrogen bonds. Small differences are also found in protein organization and in intermolecular hydrogen bond strength vs pD within the same type of gel. Protein conformation and protein-protein interactions in the gel state may be responsible of the specific macroscopic properties of each gel network. A coarse representation of the different modes of gelation is described.
Ocular Immune Privilege and the Impact of Intraocular Inflammation (2002)

Immune privilege, a characteristic of the internal compartments of the eye, is a physiologic mechanism that is designed to provide the eye with protection against pathogens while protecting the delicate visual axis from the sight-destroying potential of immunogenic inflammation. It is assumed that the presence of intraocular inflammation is incompatible with the existence of immune privilege. The validity of this assumption has been tested in four animal models of intraocular inflammation-systemic and local endotoxin-induced uveitis (EIU), mycobacterial adjuvant-induced uveitis (MAIU), and experimental autoimmune uveitis (EAU). Immune privilege was assessed in inflamed eyes by growth of intracamerally injected allogeneic tumor cells, by the capacity to support immune deviation following intracameral injection of antigen (ovalbumin, OVA), by assaying protein, leukocyte, and selected cytokine content of aqueous humor (AqH), and by capacity of inflamed AqH to suppress T cell activation in vitro. The results indicate that, irrespective of the type of inflammation, tumor cells formed progressively growing tumors in inflamed eyes. Moreover, OVA injected into the anterior chamber of eyes inflamed by MAIU and EAU failed to induce immune deviation. AqH from inflamed eyes reflected breakdown of the blood:ocular barrier as well as transient loss of its immunosuppressive properties. Immunosuppressive microenvironments routinely reemerged in inflamed eyes, and the immunosuppressive agent present under these circumstances in AqH was active TGF beta2. It is concluded that immune privilege is surprisingly resistant to abolition by intraocular inflammation, and that maintenance of immune privilege in the face of ongoing inflammation depends upon the emergence of progressive and partially different immunosuppressive mechanisms.
Human natural killer cells produce abundant macrophage inflammatory protein-1 alpha in response to monocyte-derived cytokines. (1996)

Once infected by obligate intracellular pathogens, monocytes/macrophages release cytokines that activate natural killer (NK) cells. NK cells in turn produce and secrete monocyte/macrophage activating factors such as interferongamma (IFN-gamma), which are important in the early control of these infections. Here we demonstrate that human NK cells are potent producers of another monocyte/macrophage-activating factor, macrophage inflammatory protein-1 alpha (MIP-1 alpha). Fresh NK cells produce negligible amounts of MIP-1 alpha after stimulation with the monocyte-derived cytokines IL-12, TNF-alpha, IL-1 beta, or IL-10, while stimulation with IL-15 alone results in modest MIP-1 alpha production. Abundant NK cell production MIP-1 alpha is seen after costimulation with IL-12 and IL-15, and is dose-dependent. Combinations of IL-12, with TNF-alpha, IL-1 beta, or IL-10 are substantially less effective inducers of MIP-1 alpha production by NK cells. NK cell MIP-1 alpha mRNA transcripts were detectable within 1 h after costimulation with IL-12 plus IL-15 and steadily increased over 24 h, with a concomitant increase in protein production detectable at 12 h. Resting NK cells constitutively express mRNA transcript for a MIP-1 alpha receptor, and costimulation with IL-12 and IL-15 upregulates its level of expression. Equilibrium binding studies with radioiodinated MIP-1 alpha were consistent with the induction of a single class of high affinity MIP-1 alpha receptors on NK cells costimulated with IL-12 and IL-15. Addition of exogenous MIP-1 alpha to resting NK cells did not enhance cytokine production, but did increase NK cytotoxic activity. The requirement for IL-15 as a critical cofactor for NK cell production MIP-1 alpha suggests a potentially unique role for this monocyte-derived cytokine in combination with IL-12. As MIP-1 alpha is known to potentiate the action of IFN-gamma on monocytes and to suppress human immunodeficiency virus replication, the NK cell's production of MIP-1 alpha may be important during the innate immune response to infection.
Orthogonal Self-Assembly on Colloidal Gold-Platinum Nanorods (1999)

The preparation of micrometer to nanometer-sized building blocks that can be selectively derivatized is reported here. Segmented multi-metal rods of controllable length (see Cover) were fabricated by electroplating in porous template membranes. Additionally it is shown how the surface chemistry of different parts within a single particle can be controlled by means of orthogonal self-assembly. Exploiting of the different reactivities of Pt and Au towards thiols and isocyanides leads to the observation of fluorescence from only the Au segments of the rods.
Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells (2000)

Enteroaggregative Escherichia coli (EAEC) is an emerging cause of acute and persistent diarrhea worldwide. EAEC infections are associated with intestinal inflammation and growth impairment in infected children, even in the absence of diarrhea. We previously reported that prototype EAEC strains rapidly induce IL-8 production by Caco-2 intestinal epithelial cells, and that this effect is mediated by a soluble, heat-stable factor released by these bacteria in culture. We herein report the cloning, sequencing, and expression of this biologically active IL-8-releasing factor from EAEC, and its identification as a flagellin that is unique among known expressed proteins. Flagella purified from EAEC 042 and several other EAEC isolates potently release IL-8 from Caco-2 cells; an engineered aflagellar mutant of 042 does not release IL-8. Finally, cloned EAEC flagellin expressed in nonpathogenic E. coli as a polyhistidine-tagged fusion protein maintains its proinflammatory activity. These findings demonstrate a major new means by which EAEC may cause intestinal inflammation, persistent diarrhea, and growth impairment that characterize human infection with these organisms. Furthermore, they open new approaches for diagnosis and vaccine development. This novel pathogenic mechanism of EAEC extends an emerging paradigm of bacterial flagella as inflammatory stimuli.
Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn (2000)

Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.
Successive interference cancelation amenable multiple access (SAMA) for future wireless communications (2014)

In this work, we introduce a novel multiple access scheme which is based on the joint design of the system signature matrix at the transmitter and the successive interference cancelation (SIC) based detector at the receiver. The symbols of the different users are judiciously spread in the frequency (space) domain, which can be effectively exploited by the SIC based technique, such as the iterative message-passing algorithm (MPA), to cancel the multi-user interference as well as to obtain diversity gain. Numerical results show that the non-orthogonal system based on the proposed successive interference cancelation amenable multiple access (SAMA) paradigm employing the iterative MPA achieves significant performances gain over the orthogonal one for the same spectral efficiency with affordable complexity.
Human glucokinase gene: isolation, structural characterization, and identification of a microsatellite repeat polymorphism. (1992)

The gene encoding human glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1), a major component of glucose sensing in pancreatic islet beta-cells, was isolated and characterized. The gene was shown by Southern blotting to exist as a single copy in the genome which mapped to chromosome 7p. It contained 12 exons including two tissue-specific first exons, one active in islet beta-cells (1B), and the other active in liver (1H), and one optional cassette exon which was expressed as a minor form in the liver. Thus the three previously reported isoforms of glucokinase mRNA were the result of tissue-specific activation of separate liver and islet promoters and subsequent alternative splicing events. Eleven exons, including 1H and the optional cassette exon 2A, were scattered over 16 kilobase (kb) in the genome, while exon 1B was separated from the rest by at least 20 kb. Although the islet promoter was found to lack a TATA box, a major transcript from the islet promoter was mapped 486 nucleotides upstream of the translation initiation site. The presence in the islet glucokinase promoter of the potential control element GCCACCAG, a homology of the regulatory element present in both human insulin (GCCACCGG) and rat insulin (GCCATCTG) genes, implied a possible tissue-specific regulatory role of this element. The liver promoter was found to contain a TATA box-like sequence, and transcription was initiated predominantly at 168 nucleotides upstream of the translation initiation site of the major isoform. A new highly polymorphic microsatellite, composed of a compound imperfect dinucleotide repeat [GT]15[GA]8CA[GA]7CA[GA]3AA[GA]2, was mapped 6 kb upstream of islet exon 1. A polymerase chain reaction-based assay was developed, and seven different sized alleles were identified in American Blacks. The sequence information reported here, along with the new polymorphic marker, will make it possible to clarify the molecular basis of potential glucokinase defects in noninsulin-dependent diabetes mellitus patients and may further elucidate the nature of genetic susceptibility to the development of this common metabolic disease.
The Glucose Oxidase Mechanism (1971)

Abstract The pH dependence of the steady state parameters of the glucose oxidase (EC 1.1.3.4, from Aspergillus niger) reaction was determined by O2-monitored experiments over the entire pH range from 3 to 10 at 25°, with d-glucose as substrate. The data were fitted to a three-parameter steady state rate equation and the significance of the steady state parameters was examined by stopped flow half-reaction and turnover measurements at the extremes of the pH range used. The major conclusions from these studies can be summarized as follows. 1. At low pH, in the presence of halide, the maximum turn-over number (kcat) is determined entirely by the rate of flavin reduction (k2) in the reductive half-reaction. Furthermore, substrate combines only with an unprotonated form of the oxidized enzyme and the reductive half-reaction can be represented as follows. H+ E0 (K1)/⇄/(H+) E0 + S (k1)/⇄/(k-1) E0 - S (k2)/→ Er + δ-lactone Since kcat and k2 are both specifically decreased by halides at low pH values, it is probable that the turnover rate in the low pH range is also limited by k2 in the absence of halide. The steady state absorption spectrum of E0 - S is indistinguishable from the spectrum of E0. This finding, together with the fact that removal of the 1-hydrogen from d-glucose is a ratelimiting process in flavin reduction is consistent with both a hydride transfer mechanism and with a flavin-glucose adduct mechanism in which this adduct is relatively unstable and never accumulates significantly as a kinetic intermediate. 2. The importance of k2 as a limiting first order process in turnover diminishes as the pH is raised. Thus, at pH 10 the major first order process in turnover is the breakdown of a species of oxidized enzyme, E'0, in the oxidative half-reaction. The rate of this process at pH 10.0 is 214 sec-1, whereas k2 has a value of 800 sec-1. 3. The reduced enzyme exists in two kinetically significant states of ionization, Er and Er-. The rapid reoxidation of Er with O2, to regenerate E0, is predominant at pH values less than 7. At pH values greater than 7, a much less rapid reaction of Er- with O2, leading to the formation of E'0-, becomes increasingly important. The species E'0- is unreactive with glucose and it is the conversion of a protonated form of E'0- to E0 which principally governs kcat at pH values greater than 7. We present a complete kinetic scheme describing the effects of pH and discuss the possible chemical significance of the species E'0.
Decisions with Multiple Objectives (1993)

Many of the complex problems faced by decision makers involve multiple conflicting objectives. This book describes how a confused decision maker, who wishes to make a reasonable and responsible choice among alternatives, can systematically probe his true feelings in order to make those critically important, vexing trade-offs between incommensurable objectives. The theory is illustrated by many real concrete examples taken from a host of disciplinary settings. The standard approach in decision theory or decision analysis specifies a simplified single objective like monetary return to maximise. By generalising from the single objective case to the multiple objective case, this book considerably widens the range of applicability of decision analysis.
Primary segmentation of auditory scenes (2002)

This work addresses the problem of separation of a complex auditory scene by humans, a process which is known as auditory scene analysis. From hierarchal point of view, auditory scene analysis can be described as grouping of auditory entities of one level to form entities of higher level of representation. One of the main difficulties in describing this hierarchal construct is to describe the first level of auditory representation i.e. the elementary auditory entities. This work defines auditory elementary units and describes a computational model for the formation of these units, each unit represents an independent acoustic component which is part of the outcome of one acoustic source. As elementary units are the first level of auditory analysis and serve as a basis for further grouping and formation of meaningful mental representation of auditory sources, this work should be seen as a first stage towards a more general model of auditory scene analysis which includes modeling of grouping processes of auditory elementary units.
Acute Phase Protein α1-Acid Glycoprotein Interacts with Plasminogen Activator Inhibitor Type 1 and Stabilizes Its Inhibitory Activity (2001)

alpha(1)-Acid glycoprotein, one of the major acute phase proteins, was found to interact with plasminogen activator inhibitor type 1 (PAI-1) and to stabilize its inhibitory activity toward plasminogen activators. This conclusion is based on the following observations: (a) alpha(1)-acid glycoprotein was identified to bind PAI-1 by a yeast two-hybrid system. Three of 10 positive clones identified by this method to interact with PAI-1 contained almost the entire sequence of alpha(1)-acid glycoprotein; (b) this protein formed complexes with PAI-1 that could be immunoprecipitated from both the incubation mixtures and blood plasma by specific antibodies to either PAI-1 or alpha(1)-acid glycoprotein. Such complexes could be also detected by a solid phase binding assay; and (c) the real-time bimolecular interactions monitored by surface plasmon resonance indicated that the complex of alpha(1)-acid glycoprotein with PAI-1 is less stable than that formed by vitronectin with PAI-1, but in both cases, the apparent K(D) values were in the range of strong interactions (4.51 + 1.33 and 0.58 + 0.07 nm, respectively). The on rate for binding of PAI-1 to alpha(1)-glycoprotein or vitronectin differed by 2-fold, indicating much faster complex formation by vitronectin than by alpha(1)-acid glycoprotein. On the other hand, dissociation of PAI-1 bound to vitronectin was much slower than that from the alpha(1)-acid glycoprotein, as indicated by 4-fold lower k(off) values. Furthermore, the PAI-1 activity toward urokinase-type plasminogen activator and tissue-type plasminogen activator was significantly prolonged in the presence of alpha(1)-acid glycoprotein. These observations suggest that the complex of PAI-1 with alpha(1)-acid glycoprotein can play a role as an alternative reservoir of the physiologically active form of the inhibitor, particularly during inflammation or other acute phase reactions.
[Differences in hemodynamic responses to dynamic exercise between borderline and sustained hypertension]. (1987)

To observe the effects of anatomical distribution of left ventricular hypertrophy (LVH) and the differences in blood pressure on cardiac function, borderline hypertensives (group A) and mild or moderate sustained hypertensives (group B) were studied at rest and during dynamic exercise and their results were compared with those of normal controls (group C). LVH was estimated by M-mode echocardiography, and cardiac function was assessed by radionuclide (RI) first pass and multigate methods. In each subjects, 0.5 watt/kg and 1.0 watt/kg loads of ergometer exercise were administered for 16 min in the supine position. The main results were as follows: 1. In borderline hypertension, there was significant hypertrophy of the interventricular septum, and the left ventricular mass index was greater than that in normal controls. 2. The cardiac index in borderline hypertension did not differ from that of normal controls, but that of sustained hypertension was significantly reduced. 3. Significant positive correlations were observed between blood pressure and the left ventricular mass index at rest and during exercise. 4. No difference in left ventricular ejection fraction (LVEF) at rest was observed among the three groups, but that in sustained hypertension during exercise was markedly less than that of the other groups. LVEF at 1.0 watt/kg load and delta LVEF correlated inversely with the left ventricular mass index. 5. Left ventricular end-systolic volume determined by an RI count method decreased significantly during exercise in normals and borderline hypertension, while that in sustained hypertension was not reduced during exercise. Accordingly, cardiac function in the latter group was judged to be impaired. 6. In borderline hypertension, regional LVEF in the septal portion was slightly reduced at rest and during exercise. This reduction might have been caused by an imbalance of hypertrophy between the septal and free wall portions. In sustained hypertension, regional septal LVEF was maintained at rest, but was markedly less during exercise as compared with the other groups. Regional LVEF in the free wall portion was similar in degree to that of LVEF at rest and during exercise in the three groups. 7. Though the peak filling rate (PFR) in borderline hypertension did not differ from that in controls, that of sustained hypertension was significantly reduced at rest and during exercise. Significant positive correlations were obtained between PFR and LVEF at rest and during exercise. In summary, elevated blood pressure at rest and during exercise was thought to be the most important causative factor of LVH in hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy (2005)

Uterine serous papillary cancer (USPC) represents a rare but highly aggressive variant of endometrial cancer, the most common gynecologic tumour in women. We used oligonucleotide microarrays that interrogate the expression of some 10 000 known genes to profile 10 highly purified primary USPC cultures and five normal endometrial cells (NEC). We report that unsupervised analysis of mRNA fingerprints readily distinguished USPC from normal endometrial epithelial cells and identified 139 and 390 genes that exhibited >5-fold upregulation and downregulation, respectively, in primary USPC when compared to NEC. Many of the genes upregulated in USPC were found to represent adhesion molecules, secreted proteins and oncogenes, such as L1 cell adhesion molecule, claudin-3 and claudin-4, kallikrein 6 (protease M) and kallikrein 10 (NES1), interleukin-6 and c-erbB2. Downregulated genes in USPC included SEMACAP3, ras homolog gene family, member I (ARHI), and differentially downregulated in ovarian carcinoma gene 1. Quantitative RT-PCR was used to validate differences in gene expression between USPC and NEC for several of these genes. Owing to its potential as a novel therapeutic marker, expression of the high-affinity epithelial receptor for Clostridium perfringens enterotoxin (CPE) claudin-4 was further validated through immunohistochemical analysis of formalin-fixed paraffin-embedded specimens from which the primary USPC cultures were obtained, as well as an independent set of archival USPC specimens. Finally, the sensitivity of primary USPC to the administration of scalar doses of CPE in vitro was also demonstrated. Our results highlight the novel molecular features of USPC and provide a foundation for the development of new type-specific therapies against this highly aggressive variant of endometrial cancer.