gebhart/patrepeval huggingface dataset:
Assessment of an EIA for measuring human serum erythropoietin as compared with RIA and an in‐vitro bioassay (1992)

A recently developed enzyme-linked immunosorbent assay (EIAZ, ELISA) using two murine monoclonal anti-erythropoietin antibodies was compared with a radioimmunoassay (RIA) and a commercial in-vitro bioassay, EPOS, for measuring serum erythropoietin (Epo) in humans. Specificity and validity for Epo-EIA and the other two assays were examined. The serum Epo in normal subjects was 18 +/- 12 mU/ml (mean +/- SD, n = 80) for EIA compared with 22.5 +/- 18.5 mU/ml (n = 20) for RIA and 136 +/- 132 mU/ml (n = 14) for the bioassay. The serum Epo concentrations in normals and patients were highly comparable between EIA and RIA for Epo (P less than 0.01, r = 0.95). Epo concentrations by the EIA for normal female and male subjects were 20.5 +/- 13 and 16.5 +/- 10 mU/ml, respectively. Epo levels in patients with secondary polycythaemia or autoimmune haemolytic anaemia were significantly higher than normal subjects by the three methods. Epo levels in patients with chronic renal failure were within the normal range. By the EPOS bioassay, the Epo concentrations of normals and patients with renal failure were significantly higher than expected (136 +/- 132 and 447 +/- 273, respectively). Due to its inherent design, the EPOS bioassay possibly measures bone marrow proliferative activity in response to other serum growth regulators besides erythropoietin and was found to be unsuitable for clinical assessment of Epo. We concluded that the new EIA and RIA were similarly sensitive, reliable and accurate for measurement of serum Epo. The EIA method has the advantage of being less time consuming, more convenient and avoids the use of a radioisotope.
Migration of Monocytes/Macrophages In Vitro and In Vivo Is Accompanied by MMP12-dependent Tunnel Formation and by Neovascularization (2002)

Migration of cells within tissues often requires the proteolytic destruction of the extracellular matrix (ECM).There is a large body of evidence that shows the involvement of matrix degrading enzymes, in particular the metalloproteases (MMP) and their inhibitors (TIMPS), inmany physiological and pathological processes related tocell movement in general (Amorino et al. 1998; Hiraokaet al. 1998; Murphy and Gavrilovic 1999; Shapiro 1999;Stetler-Stevenson 1999; Levine et al. 2000) and to angiogenesis in particular (Werb et al. 1999; Moldovan et al.2000; Libby and Schonbeck 2001). However, the fate ofthe tracks created within the matrix by migrating cells(Fig. 1a), which we called tunnels (Moldovan et al. 2000;Moldovan 2002), remain largely unexplored. Do they really exist? How long do they survive after a cell movesaway? Do they collapse, are they passively filled by otherproteins, or is there an active mechanism of tissue repairbehind the migrating cells...
Rapidly switchable matrix-assisted laser desorption/ionization and electrospray quadrupole-time-of-flight mass spectrometry for protein identification (2000)

We describe a new interface for a prototype quadrupole-quadrupole-time-of-flight (TOF) mass spectrometer (Centaur, Sciex) that allows rapid switching between electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) modes of operation. Instrument performance in both modes is comparable (i.e., resolution approximately 10,000 FWHM, mass accuracy <10 ppm, sensitivity approximately 1 fmol) because the ion source is decoupled from the TOF mass analyzer by extensive gas collisions in the quadrupole stages of the instrument. The capacity to obtain side-by-side high quality ESI and MALDI mass spectra from a single proteolytic mixture greatly facilitates the identification of proteins and elucidation of their primary structures. Improved strategies for protein identification result from this ability to measure spectra using both ionization modes in the same instrument and to perform MS/MS on singly charged as well as multiply charged ions. Examples are provided to demonstrate the utility and performance of the modified instrument.
Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D Inhibitors Demonstrating Alternative Complement Pathway Inhibition in Vivo (2017)

The highly specific S1 serine protease factor D (FD) plays a central role in the amplification of the complement alternative pathway (AP) of the innate immune system. Genetic associations in humans have implicated AP activation in age-related macular degeneration (AMD), and AP dysfunction predisposes individuals to disorders such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The combination of structure-based hit identification and subsequent optimization of the center (S)-proline-based lead 7 has led to the discovery of noncovalent reversible and selective human factor D (FD) inhibitors with drug-like properties. The orally bioavailable compound 2 exerted excellent potency in 50% human whole blood in vitro and blocked AP activity ex vivo after oral administration to monkeys as demonstrated by inhibition of membrane attack complex (MAC) formation. Inhibitor 2 demonstrated sustained oral and ocular efficacy in a model of lipopolysaccharide (LPS)-induced systemic AP activation in mice expressing human FD.
Nondestructive assessment of the severity of occlusal caries lesions with near-infrared imaging at 1310 nm (2010)

The high transparency of dental enamel in the near-infrared (NIR) at 1310 nm can be exploited for imaging dental caries without the use of ionizing radiation. The objective of this study is to determine whether the lesion contrast derived from NIR imaging in both transmission and reflectance can be used to estimate lesion severity. Two NIR imaging detector technologies are investigated: a new Ge-enhanced complementary metal-oxide-semiconductor (CMOS)-based NIR imaging camera, and an InGaAs focal plane array (FPA). Natural occlusal caries lesions are imaged with both cameras at 1310 nm, and the image contrast between sound and carious regions is calculated. After NIR imaging, teeth are sectioned and examined using polarized light microscopy (PLM) and transverse microradiography (TMR) to determine lesion severity. Lesions are then classified into four categories according to lesion severity. Lesion contrast increases significantly with lesion severity for both cameras (p<0.05). The Ge-enhanced CMOS camera equipped with the larger array and smaller pixels yields higher contrast values compared with the smaller InGaAs FPA (p<0.01). Results demonstrate that NIR lesion contrast can be used to estimate lesion severity.
A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma (2004)

Since 601A>G alters the potency of LTD4 and this variant allele may be associated with resistance to asthma, it is possible that modulation of the CYSLTR2 may be useful in asthma pharmacotherapy.
CHAPTER X (2009)

The genius of this composer was peculiarly sensitive to rhythmical expression, and features analogous to those of Greek music are not uncommon with him. In the first subject of the great posthumous D minor quartet, we undoubtedly have two examples of crousis, in the single foot which occurs twice over in bars 19 and 25, the bars in which the first violin and violoncello utter four crotchets on the note A. And what a deliciously fresh effect these isolated and apparently interpolated bars give, though to the superficial observer they seem to occur at random in the midst of four-bar phrases. Again, in the opening bars of the C major symphony, the unison passage for the horns is in two distinct tripodies, followed by a sort of sigh on the final dipody of the Greeklike period 3 + 3 + 2. In the Andante con moto of the Unfinished Symphony, after the introductory two feet, the melody enters on the violins with a 5 + 5 + 3 period, in the midst of which the two introductory bars are repeated as a crousis: could anything be more Greek in its symmetry, its grace, and its avoidance of the commonplace?
A Randomized Placebo-Controlled Trial of Sustained-Release Amitriptyline in Primary Fibromyalgia (1996)

AbstractObjectives: The objective of this study was to evaluate the efficacy and safety of a sustained-release preparation of amitriptyline, taken once daily, in patients with primary fibromyalgia [FS]. Methods: Forty-six patients were evaluated at one and two months in a double-blind placebo-controlled study. The primary evaluation of the outcome of therapy was based on the comparison of the "clinically meaningful response rate in the two treatment groups. Results: At four weeks, five of the 24 patients receiving amitriptyline [A] [21%, 95% CI 7.1%-42.4%] and none of the 22 patients receiving placebo [P] [95% CI 0-15.4%] were responders [P = 0.050]; at eight weeks there were 14 P58%, 95% CI 36.6-77.9%] responders in group A and none in group P [(%% CI 0-15.4%] [P < 0.001]. Adverse events were observed in Group A only and were minor. Conclusion: Sustained-release amitriptyline may be beneficial in the treatment of some FS patients.KEYWORDS: FibromyalgiaAmitriptyline
Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants (2006)

Abnormal findings on MRI at term equivalent in very preterm infants strongly predict adverse neurodevelopmental outcomes at two years of age. These findings suggest a role for MRI at term equivalent in risk stratification for these infants.
The Viral Load of Epstein–Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma (2011)

Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL.
Humanized hemato-lymphoid system mice (2015)

Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment.
Vascular Endothelial Growth Factor in Pulmonary Hypertension (1996)

The best studied of the endothelial cell specific growth factors, VEGF, is present in alveolar and bronchial epithelial cells, in vascular smooth muscle cells, and in macrophages. The gene encoding VEGF is abundantly present in lung tissue and is induced by short-term and long-term hypoxia, as well as by prostacyclin, prostaglandin E2, and cyclic AMP. In the case of prostaglandin-stimulated gene upregulation protein kinase A (PKA) is involved. Suramin, an inhibitor of growth factor receptor binding inhibits the development of chronic hypoxic pulmonary hypertension in rats. Further evidence is necessary to link VEGF with pulmonary hypertensive vascular remodeling. This requires the development of antibodies directed against VEGF or against VEGF receptors and gene transfection or antisense strategies.
Fabry Disease Mimicking Hypertrophic Cardiomyopathy: Genetic Screening Needed for Establishing the Diagnosis in Women (2010)

This is the first report of systematic mutation screening of GLA in HCM patients without sarcomere gene mutations. GLA mutations were found in 3/90 (3%) of HCM families and in 2/20 (10%) of females without sarcomere-gene mutations. None of the probands presented other indices of Fabry disease. This, in combination with putative reversibility of cardiac changes by enzyme replacement therapy, supports systematic testing for Fabry disease. Enzyme measurements are sufficient in men, but genetic testing is needed in women.
Evaluating a new method for maintaining body temperature during OPCAB and robotic procedures. (2006)

The Allon Thermowrap system significantly out-performed conventional techniques in achieving and maintaining normothermia during off-pump and robotic procedures.
Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis (2003)

Effector T cell responses can be modulated by competing positive or negative signals transduced by natural killer (NK) cell receptors. This raises the possibility that dominant T cell stimulation might promote autoimmune reactions. In rheumatoid arthritis (RA), the severity of autoimmune and inflammatory joint disease correlates with large numbers of CD4+CD28- T cells, which are scarce in healthy individuals. For poorly defined reasons, these T cells are autoreactive, implying that they may contribute to disease manifestations. CD4+CD28- T cells in peripheral blood and synovial tissue of RA patients were found to express NKG2D, a costimulatory receptor that is absent on normal CD4 T cells. NKG2D was induced by tumor necrosis factor alpha and IL-15, which are abundant in inflamed synovia and RA patient sera. RA synoviocytes aberrantly expressed the stress-inducible MIC ligands of NKG2D, which stimulated autologous CD4+CD28- T cell cytokine and proliferative responses. Peripheral blood serum samples of RA patients contained substantial amounts of synoviocyte-derived soluble MICA, which failed to induce down-modulation of NKG2D because of the opposing activity of tumor necrosis factor alpha and IL-15. These results suggest that a profound dysregulation of NKG2D and its MIC ligands may cause autoreactive T cell stimulation, thus promoting the self-perpetuating pathology in RA and possibly other autoimmune diseases.
Immune Complexes in Urine and Serum of Patients with Bladder Cancer (1984)

The urine and/or serum of 43 patients with bladder cancer was tested for the presence of immune complexes. Immune complexes were present more frequently in the urine (38 per cent) than in the serum (23 per cent). Urinary immune complexes were elevated in 10 per cent of the patients with no tumor (group 1), 25 per cent with superficial neoplasms (group 2) and 89 per cent with infiltrating or metastatic disease (group 3), which compared favorably to elevated serum immune complexes in 20, 25 and 33 per cent of the patients, respectively. The incidence of urinary immune complexes was statistically significant when compared in patients with and without active tumors (p less than 0.03), and when group 3 patients were compared to those in group 1 or 2 (p less than 0.01 and p less than 0.03, respectively). Unlike serum immune complexes urinary immune complexes appeared to correlate with the presence and stage of bladder cancer.
Brunenders: a partially attenuated historic poliovirus type I vaccine strain (2015)

Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.
Novel Regulation of Parkin Function through c-Abl-Mediated Tyrosine Phosphorylation: Implications for Parkinson's Disease (2011)

Mutations in parkin, an E3 ubiquitin ligase, are the most common cause of autosomal-recessive Parkinson's disease (PD). Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl links parkin to sporadic forms of PD via tyrosine phosphorylation. Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in striatum of adult C57BL/6 mice. Activated c-Abl was found in the striatum of PD patients. Concomitantly, parkin was tyrosine-phosphorylated, causing loss of its ubiquitin ligase and cytoprotective activities, and the accumulation of parkin substrates, AIMP2 (aminoacyl tRNA synthetase complex-interacting multifunctional protein 2) (p38/JTV-1) and FBP-1.STI-571, a selective c-Abl inhibitor, prevented tyrosine phosphorylation of parkin and restored its E3 ligase activity and cytoprotective function both in vitro and in vivo. Our results suggest that tyrosine phosphorylation of parkin by c-Abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic PD. Moreover, inhibition of c-Abl offers new therapeutic opportunities for blocking PD progression.
Redefining the role(s) of endothelial αvβ3-integrin in angiogenesis (2014)

For nearly two decades now, the RGD (Arg-Gly-Asp)-binding αvβ3-integrin has been a focus of anti-angiogenic drug design. These inhibitors are well-tolerated, but have shown only limited success in patients. Over the years, studies in β3-integrin-knockout mice have shed some light on possible explanations for disappointing clinical outcomes. However, studying angiogenesis in β3-integrin-knockout mice is a blunt tool to investigate β3-integrin's role in pathological angiogenesis. Since establishing our laboratory at University of East Anglia (UEA), we have adopted more refined models of genetically manipulating the expression of the β3-integrin subunit. The present review will highlight some of our findings from these models and describe how data from them have forced us to rethink how targeting αvβ3-integrin expression affects tumour angiogenesis and cancer progression. Revisiting the fundamental biology behind how this integrin regulates tumour growth and angiogenesis, we believe, is the key not only to understanding how angiogenesis is normally co-ordinated, but also in success with drugs directed against it.
Multifunctional Carbon Nanotube Yarns by Downsizing an Ancient Technology (2004)

By introducing twist during spinning of multiwalled carbon nanotubes from nanotube forests to make multi-ply, torque-stabilized yarns, we achieve yarn strengths greater than 460 megapascals. These yarns deform hysteretically over large strain ranges, reversibly providing up to 48% energy damping, and are nearly as tough as fibers used for bulletproof vests. Unlike ordinary fibers and yarns, these nanotube yarns are not degraded in strength by overhand knotting. They also retain their strength and flexibility after heating in air at 450 degrees C for an hour or when immersed in liquid nitrogen. High creep resistance and high electrical conductivity are observed and are retained after polymer infiltration, which substantially increases yarn strength.
Counting sperm does not add up any more: time for a new equation? (2007)

Although sperm dysfunction is the single most common cause of infertility, we have poor methods of diagnosis and surprisingly no effective treatment (excluding assisted reproductive technology). In this review, we challenge the usefulness of a basic semen analysis and argue that a new paradigm is required immediately. We discuss the use of at-home screening to potentially improve the diagnosis of the male and to streamline the management of the sub-fertile couple. Additionally, we outline the recent progress in the field, for example, in proteomics, which will allow the development of new biomarkers of sperm function. This new knowledge will transform our understanding of the spermatozoon as a machine and is likely to lead to non-ART treatments for men with sperm dysfunction.
Current Issues in the Diagnosis and Management of Dementia (2003)

Aging, memory loss, Alzheimer's disease, and other forms of dementia assume increasing importance to patients, physicians, and society as our population becomes older. Mild cognitive impairment, topography and semiology of dementia syndromes, reversible forms of dementia, dementia therapy, driving, genetic testing of patients and family members, and caregiver risk are reviewed.
Neutralization of respiratory syncytial virus by individual and mixtures of F and G protein monoclonal antibodies (1988)

We identified several types of neutralization effected by F and G protein monoclonal antibodies (MAbs) reacted individually or as mixtures against respiratory syncytial virus (RSV). Neutralizing activity was identified by a microneutralization test in which virus replication was determined by enzyme immunoassay. Complete neutralization was seen only with MAbs against the F protein. Strain-specific neutralization, complete neutralization against some strains of RSV, and no neutralization against other strains were seen with an additional MAb against the F protein. Partial neutralization, virus replication significantly reduced but still present, and no neutralization were seen with MAbs against both the F and G proteins. Enhanced neutralization, enhanced efficacy of neutralization, or increased neutralizing titer with a mixture of two MAbs over that for the individual MAbs was seen with all MAbs against the F protein and all but three MAbs against the G protein. Most (10 of 13) of the MAbs that exhibited neutralizing activity reacted with some but not all strains of RSV in an enzyme immunoassay. The epitopes corresponding to these 10 MAbs probably contribute to the strain-specific component of the neutralizing antibody response to RSV. Our results suggest that interpretation of RSV neutralization with MAbs is complex and that studies of such neutralization should include mixtures of MAbs and multiple RSV strains.
Characteristics of an Adult Population With Newly Diagnosed Type 2 Diabetes (2001)

Although both onset groups were on average obese, the inverse linear relationship of obesity and age of diabetes onset that we observed suggests that obesity is a continuous risk rather than a threshold risk for diabetes onset. Both onset groups had a high prevalence of cardiovascular disease risk factors.