gebhart/patrepeval huggingface dataset:
An alternative view of the proposed alternative activities of hemopexin (2011)

Abstract Hemopexin is a plasma protein that plays a well‐established biological role in sequestering heme that is released into the plasma from hemoglobin and myoglobin as the result of intravascular or extravascular hemolysis as well as from skeletal muscle trauma or neuromuscular disease. In recent years, a variety of additional biological activities have been attributed to hemopexin, for example, hyaluronidase activity, serine protease activity, pro‐inflammatory and anti‐inflammatory activity as well as suppression of lymphocyte necrosis, inhibition of cellular adhesion, and binding of divalent metal ions. This review examines the challenges involved in the purification of hemopexin from plasma and in the recombinant expression of hemopexin and evaluates the questions that these challenges and the characteristics of hemopexin raise concerning the validity of many of the new activities proposed for this protein. As well, an homology model of the three‐dimensional structure of human hemopexin is used to reveal that the protein lacks the catalytic triad that is characteristic of many serine proteases but that hemopexin possesses two highly exposed Arg‐Gly‐Glu sequences that may promote interaction with cell surfaces.
The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain. (1994)

Nitric oxide (NO) synthases contain FAD, FMN, heme, and (6R)-5,6,7,8-tetrahydro-L-biopterin as prosthetic groups. We have characterized the pteridine-binding site of purified brain NO synthase, using 3H-labeled (6R)-5,6,7,8-tetrahydro-L-biopterin as radioligand. Association of [3H]tetrahydrobiopterin followed second-order kinetics (kon = 1.3 x 10(6) M-1 min-1), the dissociation reaction was reversible and first-order (koff = 3.2 x 10(-1) min-1), yielding a kinetic KD of 0.25 microM. Binding of the radioligand was competitively antagonized by several pteridine derivatives with the following order of potency (KI): 7,8-dihydro-L-biopterin (2.2 microM), (6S)-5,6,7,8-tetrahydro-L-biopterin (19 microM), (6R,S)-6-methyl-5,6,7,8-tetrahydropterin (240 microM), and 6,7-dimethyl-5,6,7,8-tetrahydropterin (> 1 mM). The affinity of NO synthase for tetrahydrobiopterin was increased 6-fold in the presence of 0.1 mM L-arginine (KD = 37 nM), and, conversely, tetrahydrobiopterin enhanced the affinity of the enzyme for 3H-labeled NG-nitro-L-arginine about 2-fold. 7-Nitroindazole, which presumably binds to the heme group of NO synthase, competitively inhibited binding of [3H]tetrahydrobiopterin and [3H]NG-nitro-L-arginine with similar Ki values (0.1 microM). Functional as well as binding studies revealed that 7-nitroindazole was competitive with both L-arginine and tetrahydrobiopterin. Our data indicate that brain NO synthase exhibits a highly specific binding site for (6R)-5,6,7,8-tetrahydro-L-biopterin, which allosterically interacts with the substrate domain and may be located proximal to the prosthetic heme group of NO synthase.
Stereochemical Surprises in the Lewis Acid-Mediated Allylation of Isatins (2010)

The BF3·OEt2-mediated allylation of isatin with an α-chiral allylic stannane is diastereo- and enantioselective. Conversely, allylation of any substituted isatin employing the identical protocol is not diastereoselective at all and only enantioselective for the major diastereomer having syn relative configuration. The anti isomer is, however, formed in almost racemic form. Both absolute and relative configurations are unambiguously secured by X-ray analysis of major isomers, and the stereochemical assignment of the other 3-substituted 3-hydroxy oxindoles is based on similar NMR spectroscopic characteristics. The remarkable observations are rationalized by an acyclic transition state model.
Freeze-fracture replica electron microscopy combined with sds digestion for cytochemical labeling of integral membrane proteins: Application to the immunogold labeling of intercellular junctional complexes (1995)

We propose a new electron microscopic method, the sodium dodecylsulphate (SDS)-digested freeze-fracture replica labeling technique, to study the two-dimensional distribution of integral membrane proteins in cellular membranes. Unfixed tissue slices were frozen with liquid helium, freeze-fractured, and replicated in a platinum/carbon evaporator. They were digested with 2.5% SDS to solubilize unfractured membranes and cytoplasm. While the detergent dissolved unfractured membranes and cytoplasm, it did not extract fractured membrane halves. After SDS-digestion, the platinum/carbon replicas, along with attached cytoplasmic and exoplasmic membrane halves, were processed for cytochemical labeling, followed by electron microscopic observation. As an initial screening, we applied this technique to the immunogold labeling of intercellular junction proteins: connexins (gap junction proteins), occludin (tight junction protein), desmoglein (desmosome protein), and E-cadherin (adherens junction protein). The immunogold labeling was seen superimposed on the image of a fracture face visualized by platinum/carbon shadowing. The immunoreaction was specific, and only the structures where the proteins were expected were labeled. For instance, anti-occludin immunogold complexes were observed immediately adjacent to the tight junction strands on the protoplasmic and exoplasmic fracture faces. No significant levels of gold label were associated with non-tight-junctional regions of plasma membranes. The procedures of the SDS-digested freeze-fracture replica labeling and its potential significance are discussed.
Interleukin-1 receptor antagonist: effectiveness against interleokin-1 fever (1992)

Conscious cats were used to examine the effectiveness of the interleukin-1 receptor antagonist against the fever induced by interleukin-1 and endotoxin. Although inactive by itself, the antagonist (three 1-micrograms bolus injections at 10-min intervals), injected into the third ventricle, attenuated the febrile response to a subsequent intracerebroventricular bolus of interleukin-1. The rise in prostaglandin E2 levels in cerebrospinal fluid, which is a characteristic feature of fever, was curtailed as well. The interleukin-1 antagonist had little or no inhibitory effect on the response to an intracerebroventricular bolus of endotoxin, even though a higher dose was employed (2-micrograms bolus injections given three times at 10-min intervals and six times at 30-min intervals, respectively, before and after endotoxin administration). At either dosage, the intracerebroventricular antagonist was completely ineffective against an intravenous bolus injection of interleukin-1 or endotoxin and both fever and prostaglandin E2 elevation developed unabated. We conclude that brain receptors mediating the pyrogenic action of centrally injected interleukin-1 are susceptible to the antagonist. The same receptors, however, are seemingly not activated by systemic pyrogens. Our findings are consistent with the concept of circulating interleukin-1 acting outside the blood-brain barrier in the normal sequence of fever.
Motilin and Infantile Colic (1990)

Two hundred and nineteen infants, consecutively born, took part in a prospective study of infantile colic from birth to 12 weeks of age. The prevalence of infantile colic in this group was 17.4%. S-motilin was studied in 78 term infants (19 with and 59 without infantile colic) at birth (cord blood), at one day, and at 6 and 12 weeks of age, respectively. Basal motilin levels were raised both in cord blood (p less than 0.01) and in blood from neonates (p less than 0.001) who developed colic as well as in 6 week (p less than 0.05) and in 12-week-old infants with colic (p less than 0.01). Formula-fed infants with colic had higher basal motilin levels than formula-fed controls at 6 and 12 weeks of age (p less than 0.05). Breast-fed infants with colic had higher basal motilin levels than breast-fed controls at 12 weeks of age (p less than 0.05). The raised levels of motilin from the first day of life in infants who develop infantile colic might indicate that the gastrointestinal tract is affected in infants with infantile colic, before any symptoms of colic appear.
Fluorescent protein marker lines in maize: generation and applications (2013)

Fluorescent proteins (FP) have significantly impacted the way that we study plants in the past two decades. In the post-genomics era, these FP tools are in higher demand by plant scientists for studying the dynamics of protein localization, function, and interactions, and to translate sequence information to biological knowledge that can benefit humans. Although FP tools have been widely used in the model plant Arabidopsis, few FP resources have been developed for maize, one of the most important food crops worldwide, and an ideal species for genetic and developmental biology research. In an effort to provide the maize and cereals research communities with a comprehensive set of FP resources for different purposes of study, we generated more than 100 stable transformed maize FP marker lines, which mark most compartments in maize cells with different FPs. Additionally, we are generating driver and reporter lines, based on the principle of the pOp-LhG4 transactivation system, allowing specific expression or mis-expression of any gene of interest to precisely study protein functions. These marker lines can be used not only for static protein localization studies, but will be useful for studying protein dynamics and interactions using kinetic microscopy methods, such as fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and fluorescence resonance energy transfer (FRET).
Beyond Cholesterol (1989)

IT is now well established that hypercholesterolemia is an important cause of coronary heart disease, and clinical intervention studies have demonstrated the therapeutic value of correcting hypercholesterolemia.1 , 2 The National Cholesterol Education Program has been instituted on the basis of these findings.3 From that ambitious program we can anticipate the development of progressively better methods of reducing plasma cholesterol levels and therefore even further decreases in mortality from coronary heart disease. However, no matter how successfully we deal with hypercholesterolemia, coronary heart disease will not disappear, because a high cholesterol level is by no means the only causative factor. At any . . .
Vector bending sensors based on fibre Bragg gratings inscribed by infrared femtosecond laser (2005)

A direction-sensitive bend sensor in standard singlemode fibre is demonstrated for the first time based on an axially-offset fibre Bragg grating, directly written by an infrared femtosecond laser.
Interleukin-1-beta, interleukin-6, and interferon-gamma in suction blister fluids of involved and uninolved skin and in sera of psoriatic patients. (1994)

Interleukin-1-beta (IL-1-beta), Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) were measured by enzyme immunoassay (EIA) methods in blister fluids (BFs) obtained from both involved (ISBF) and non-involved skin (USBF) and in sera from 14 psoriatic patients. The same determinations were carried out in 14 sera and in 5 suction blister fluids from 14 normal subjects. IL-6 was always detectable in all skin fluids and in 3 psoriasis sera. IL-1-beta was measured only in 5 ISBFs and in 5 sera from the same patients. IFN-gamma was present in 11 ISBFs, in 5 USBFs and in 5 sera. The analysis of the levels found in the samples shows: 1) a local production of these cytokines, 2) the presence of detectable amounts of IL-6 and IFN-gamma in USBFs, and 3) a significant correlation between the IL-6 levels in the ISBFs and erythema score.
24.4L: Late‐News Paper : A 13.0‐inch AM‐OLED Display with Top Emitting Structure and Adaptive Current Mode Programmed Pixel Circuit (TAC) (2001)

Abstract A device structure and a driving method were developed to design large‐scale active matrix organic light‐emitting diode (AM‐OLED) display with good gray scale uniformity and high aperture ratio. With these technologies, we developed a full color 13.0‐inch SVGA AM‐OLED display, the largest OLED display ever reported to date. These technologies will open up the OLED applications to larger size displays such as desktop monitors and TVs.
Eyes for relighting (2004)

The combination of the cornea of an eye and a camera viewing the eye form a catadioptric (mirror + lens) imaging system with a very wide field of view. We present a detailed analysis of the characteristics of this corneal imaging system. Anatomical studies have shown that the shape of a normal cornea (without major defects) can be approximated with an ellipsoid of fixed eccentricity and size. Using this shape model, we can determine the geometric parameters of the corneal imaging system from the image. Then, an environment map of the scene with a large field of view can be computed from the image. The environment map represents the illumination of the scene with respect to the eye. This use of an eye as a natural light probe is advantageous in many relighting scenarios. For instance, it enables us to insert virtual objects into an image such that they appear consistent with the illumination of the scene. The eye is a particularly useful probe when relighting faces. It allows us to reconstruct the geometry of a face by simply waving a light source in front of the face. Finally, in the case of an already captured image, eyes could be the only direct means for obtaining illumination information. We show how illumination computed from eyes can be used to replace a face in an image with another one. We believe that the eye not only serves as a useful tool for relighting but also makes relighting possible in situations where current approaches are hard to use.
The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells (2013)

This study aimed to compare epithelial cells derived from human embryonic stem cells (hESCs) to human ameloblast-lineage cells (ALCs), as a way to determine their potential use as a cell source for ameloblast regeneration. Induced by various concentrations of bone morphogenetic protein 4 (BMP4), retinoic acid (RA) and lithium chloride (LiCl) for 7 days, hESCs adopted cobble-stone epithelial phenotype (hESC-derived epithelial cells (ES-ECs)) and expressed cytokeratin 14. Compared with ALCs and oral epithelial cells (OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs. ES-ECs were compared with human fetal skin epithelium, human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well. ALCs had relatively high expression levels of cytokeratin 76, which was also found to be upregulated in ES-ECs. Based on the present study, with the similarity of gene expression with ALCs, ES-ECs are a promising potential cell source for regeneration, which are not available in erupted human teeth for regeneration of enamel.
Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain (2004)

Multiple lines of evidence implicate beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Abeta is involved remain unclear. Addition of Abeta to the extracellular space can be neurotoxic. Intraneuronal Abeta42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Abeta42 localized by immunoelectron microscopy to, and accumulated with aging in, the outer membranes of multivesicular bodies, especially in neuronal processes and synaptic compartments. We now demonstrate that primary neurons from Tg2576 mice recapitulate the in vivo localization and accumulation of Abeta42 with time in culture. Furthermore, we demonstrate that Abeta42 aggregates into oligomers within endosomal vesicles and along microtubules of neuronal processes, both in Tg2576 neurons with time in culture and in Tg2576 and human AD brain. These Abeta42 oligomer accumulations are associated with pathological alterations within processes and synaptic compartments in Tg2576 mouse and human AD brains.
Distinct WNT Pathways Regulating AER Formation and Dorsoventral Polarity in the Chick Limb Bud (1998)

The apical ectodermal ridge (AER) is an essential structure for vertebrate limb development. Wnt3a is expressed during the induction of the chick AER, and misexpression of Wnt3a induces ectopic expression of AER-specific genes in the limb ectoderm. The genes beta-catenin and Lef1 can mimic the effect of Wnt3a, and blocking the intrinsic Lef1 activity disrupts AER formation. Hence, Wnt3a functions in AER formation through the beta-catenin/LEF1 pathway. In contrast, neither beta-catenin nor Lef1 affects the Wnt7a-regulated dorsoventral polarity of the limb. Thus, two related Wnt genes elicit distinct responses in the same tissues by using different intracellular pathways.
Intelligent Agents for Web-based Tasks: An Advice-Taking Approach (1998)

We present and evaluate an implemented system with which to rapidly and easily build intelligent software agents for Web-based tasks. Our design is centered around two basic functions: ScoreThisLink and ScoreThisPage. If given highly accurate such functions, standard heuristic search would lead to efficient retrieval of useful information. Our approach allows users to tailor our system&amp;apos;s behavior by providing approximate advice about the above functions. This advice is mapped into neural network implementations of the two functions. Subsequent reinforcements from the Web (e.g., dead links) and any ratings of retrieved pages that the user wishes to provide are, respectively, used to refine the link- and pagescoring functions. Hence, our architecture provides an appealing middle ground between nonadaptive agent programming languages and systems that solely learn user preferences from the user&amp;apos;s ratings of pages. We describe our internal representation of Web pages, the major predicates ...
The Nitric Oxide Hypothesis of Migraine and Other Vascular Headaches (1995)

The molecular mechanisms of migraine pain remain to be determined. Our studies of glyceryl trinitrate (GTN)-induced and histamine-induced headaches have led us to propose that nitric oxide (NO) may be the causative molecule in migraine pain. We also propose that substances capable of inducing experimental vascular headache do so with NO as the common mediator. Finally, we suggest that drugs with antimigraine activity inhibit NO and the cascade of intracellular reactions triggered by NO. We believe these observations provide new insight into the mechanisms of vascular headache. The importance of NO as a potential initiator of the migraine attack indicates new directions for the pharmacological treatment of migraine and other vascular headaches.
Hepatitis E Virus: cDNA Cloning and Expression (1992)

Viral hepatitis E is endemic, frequently provoking epidemic outbreaks in many developing countries. We have attempted to clone the viral genome and to develop an antibody assay system. A lambda gt11 cDNA library was constructed from the bile juice containing putative causative viruses and was immunoscreened by the antisera obtained from patients and monkeys infected with hepatitis E. Three virus-specific clones were isolated and were revealed to overlap one another in sequence, with 1,459 nucleotides in total length. These clones direct the synthesis of polypeptides probably having common immunological epitope(s). Immunoplaque assay revealed the occurrence of antibodies against this epitope in the sera from experimental monkeys with the convalescent phase and from patients of Myanmar, Nepal and India. The data indicate that the cDNA fragments are useful for immunodiagnosis of hepatitis E.
CCL3 (MIP-1α) plasma levels and the risk for disease progression in chronic lymphocytic leukemia (2010)

B-cell receptor (BCR) signaling has been inferred as an important mechanism for disease progression in chronic lymphocytic leukemia (CLL) and other B-cell malignancies. In response to BCR activation, CLL cells secrete the chemokine CCL3, which fosters interactions between CLL cells and the leukemia microenvironment. CCL3 secretion correlates with expression of the 70-kDa ζ-associated protein (ZAP-70) and responsiveness of the CLL clone to BCR stimulation. Here, we measured CCL3 plasma levels by enzyme-linked immunosorbent assay (ELISA) in 351 CLL patients and examined CCL3 levels for associations with established prognostic markers and time from diagnosis to initial therapy. We found that CCL3 plasma concentrations were strongly associated with established prognostic markers. In a Cox proportional hazards regression model, CCL3 as well as established prognostic markers (immunoglobulin heavy chain variable-region mutation status, CD38 or ZAP-70 cytogenetics, clinical stage) were significantly associated with time to treatment. Multivariable analysis revealed that CCL3 (hazard ratio [HR] = 2.33, P < .0001), advanced clinical stage (HR = 2.75, P = .0025), poor risk cytogenetics (del 17p, HR = 2.38; del11q, HR = 2.36, P = .001), and CD38 expression (HR = 1.43, P = .023) were independent prognostic markers. Collectively, CCL3 is a novel, robust, and independent prognostic marker in CLL that can easily and reliably be measured by ELISA. CCL3 therefore should become useful for risk assessment in patients with CLL.
Adenovirus-Mediated Somatic Genome Editing of Pten by CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses (2015)

CRISPR/Cas9 derived from the bacterial adaptive immunity pathway is a powerful tool for genome editing, but the safety profiles of in vivo delivered Cas9 (including host immune responses to the bacterial Cas9 protein) have not been comprehensively investigated in model organisms. Nonalcoholic steatohepatitis (NASH) is a prevalent human liver disease characterized by excessive fat accumulation in the liver. In this study, we used adenovirus (Ad) vector to deliver a Streptococcus pyogenes-derived Cas9 system (SpCas9) targeting Pten, a gene involved in NASH and a negative regulator of the PI3K-AKT pathway, in mouse liver. We found that the Ad vector mediated efficient Pten gene editing even in the presence of typical Ad vector-associated immunotoxicity in the liver. Four months after vector infusion, mice receiving the Pten gene-editing Ad vector showed massive hepatomegaly and features of NASH, consistent with the phenotypes following Cre-loxP-induced Pten deficiency in mouse liver. We also detected induction of humoral immunity against SpCas9 and the potential presence of an SpCas9-specific cellular immune response. Our findings provide a strategy to model human liver diseases in mice and highlight the importance considering Cas9-specific immune responses in future translational studies involving in vivo delivery of CRISPR/Cas9.