gebhart/patrepeval huggingface dataset:
A new generation of magnetoencephalography: Room temperature measurements using optically-pumped magnetometers (2017)

Advances in the field of quantum sensing mean that magnetic field sensors, operating at room temperature, are now able to achieve sensitivity similar to that of cryogenically cooled devices (SQUIDs). This means that room temperature magnetoencephalography (MEG), with a greatly increased flexibility of sensor placement can now be considered. Further, these new sensors can be placed directly on the scalp surface giving, theoretically, a large increase in the magnitude of the measured signal. Here, we present recordings made using a single optically-pumped magnetometer (OPM) in combination with a 3D-printed head-cast designed to accurately locate and orient the sensor relative to brain anatomy. Since our OPM is configured as a magnetometer it is highly sensitive to environmental interference. However, we show that this problem can be ameliorated via the use of simultaneous reference sensor recordings. Using median nerve stimulation, we show that the OPM can detect both evoked (phase-locked) and induced (non-phase-locked oscillatory) changes when placed over sensory cortex, with signals ~4 times larger than equivalent SQUID measurements. Using source modelling, we show that our system allows localisation of the evoked response to somatosensory cortex. Further, source-space modelling shows that, with 13 sequential OPM measurements, source-space signal-to-noise ratio (SNR) is comparable to that from a 271-channel SQUID system. Our results highlight the opportunity presented by OPMs to generate uncooled, potentially low-cost, high SNR MEG systems.
Physico-chemical properties of biofilms (2000)

A review with 61 refs. Microorganisms in aggregates such as flocs, film, and sludge do not only display biochem. and biol., but also phys. and physico-chem. properties. Among these are mech. stability, binding of water, diffusion, sorption, mass transport and optical properties, and friction resistance. These properties are chiefly caused by the extracellular polymeric substances (EPS) which fill the space between the cells and account for a considerable proportion of the org. carbon content of biofilms. The EPS consist not only of polysaccharides but also of considerable amts. of protein; nucleic acids and lipids are also found in the EPS. Above all, the EPS form the morphol. and internal structure of biofilms, including surface pores and channels. The EPS provide a matrix which allows the cells to maintain their position for a much longer period of time compared to the planktonic mode. This facilitates the formation of synergistic microconsortia of different species which can perform orchestrated degrdn. processes. Mech. stability of biofilms includes aspects such as sloughing of the biomass in biofilm reactors, resulting in possibly adverse effects to the process. On the other hand, when biofilms have to be removed as biofouling layers, it is the cohesive and adhesive forces which have to be overcome. Three types of weak interactions have to be considered, viz. hydrogen bonds, electrostatic interactions, and van der Waals interactions. As EPS contain many groups capable of different forms of these interactions, the binding force between macromols. is multiplied by the no. of interacting groups, which increases the overall binding force by several orders of magnitude. Interactions between extracellular enzymes and polysaccharides are known which stabilize the enzymes and possibly enhance their activity.
Insulin-like growth factor I receptors in normal and neoplastic human endometrium. (1990)

Insulin-like growth factor I (IGF-I) binding sites were characterized in normal and neoplastic endometrium. The characteristics of the endometrial IGF-I receptor are similar to those reported for other tissues. The binding of 125I-IGF-I to the endometrial membranes is saturable and time, temperature, and pH dependent. The 125I-IGF-I binding activity to the membranes obtained from differentiated and undifferentiated adenocarcinoma as well as sarcoma of the endometrium was significantly higher (P less than 0.05) when compared to the binding activity of the membranes obtained from normal endometrium. The Scatchard analysis of the competitive binding data of both normal and neoplastic endometrium revealed linear plots. This indicated a single class binding site for IGF-I with equilibrium dissociation constants (Kd) of 5.0, 6.8, 6.94, and 6.88 nM for normal, differentiated, and undifferentiated adenocarcinoma, and sarcoma of the endometrium, respectively. Therefore, the differences observed in 125I-IGF-I binding between normal and neoplastic endometrial membranes was due to an increase in the number of IGF-I binding sites and not to a change in receptor binding affinity. Autoradiograms from affinity labelling studies revealed a band corresponding to Mr 132,000 subunit of the receptor which is characteristic of the type I receptor reported for other tissues. A dimer of the alpha subunit (Mr 263,000) was also observed in all four categories of endometrial tissue. Additionally, autoradiograms obtained from sarcoma of the endometrium revealed a Mr 40,000 band that was only displaced by IGF-I and IGF-II peptides but not by the monoclonal antibody alpha IR-3 to the type I receptor. These suggest that the band is representative of the IGF-I or IGF-II binding protein. A similar band was not observed in the other tissues. The results show that the human endometrium contains high affinity IGF-I or IGF-II binding sites. The fact that IGF-I binding activity was significantly higher for neoplastic endometrium suggests that IGF-I may play an important role on supporting the growth of this neoplastic tissue.
Sickle Cell Biomechanics (2010)

As the predominant cell type in blood, red blood cells (RBCs) and their biomechanical properties largely determine the rheological and hemodynamic behavior of blood in normal and disease states. In sickle cell disease (SCD), mechanically fragile, poorly deformable RBCs contribute to impaired blood flow and other pathophysiological aspects of the disease. The major underlying cause of this altered blood rheology and hemodynamics is hemoglobin S (HbS) polymerization and RBC sickling under deoxygenated conditions. This review discusses the characterization of the biomechanical properties of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology of the disease.
Recombinant interferon-? therapy in patients with follicular lymphoma (1998)

Recombinant IFN-alpha is safe and effective when given in conjunction with standard chemotherapeutic regimens in selected patients with follicular NHL, and may especially benefit patients with minimal residual disease after induction chemotherapy.
Fluorolabeling of antibody variable domains with green fluorescent protein variants: application to an energy transfer-based homogeneous immunoassay (2000)

A site-specific and efficient fluorolabeling of antibody variable regions with green fluorescent protein (GFP) variants and its application to an energy transfer-based homogeneous fluoroimmunoassay (open sandwich FIA) were attempted. Two chimeric proteins, Trx-V(H)-EBFP and Trx-V(L)-EGFP, consisting of V(H) and V(L) fragments of anti-hen egg lysozyme (HEL) antibody HyHEL-10 and two GFP color variants, EBFP and EGFP, respectively, were designed to be expressed in cytoplasm of trxB - mutant Escherichia coli as fusions with thioredoxin from E.coli The mixture of two proteins could be purified with HEL-affinity chromatography, retaining sufficient intrinsic fluorescence and binding activity to HEL. A significant increase in fluorescence resonance energy transfer (FRET) dependent on HEL concentration was observed, indicating the reassociation of the V(H) and V(L) domains of these chimeric proteins due to co-existing antigen. With this open sandwich FIA, an HEL concentration of 1-100 microg/ml could be non-competitively determined. The assay could be performed in a microplate format and took only a few minutes to obtain a sufficient signal after simple mixing of the chimeric proteins with samples. This represents the first demonstration that the FRET between GFP variants is applicable to homogeneous immunoassay.
Targeting of Macrophage Activity by Adenovirus-Mediated Intragraft Overexpression of TNFRp55-Ig, IL-12p40, and vIL-10 Ameliorates Adenovirus-Mediated Chronic Graft Injury, whereas Stimulation of Macrophages by Overexpression of IFN-γ Accelerates Chronic Graft Injury in a Rat Renal Allograft Model (2003)

Adenovirus (Ad)-mediated gene transfer of immunoregulatory molecules prevents acute allograft rejection. It is here analyzed for the first time whether this approach may prevent the development of chronic renal allograft injury in rats. Renal allografts (F344-->Lewis rat) were ex vivo transduced in group I with control Ad-construct, group II with three different therapeutic Ad-constructs expressing the immunoregulatory molecules vIL-10, TNFRp55-Ig, and IL-12p40, and group III with AdIFN-gamma. Group IV served as untreated controls. Control grafts (IV) showed increasing proteinuria during the 24-wk follow-up. Chronic graft injury was accelerated by Ad-control (I) and even more by AdIFN-gamma (III). All rats carrying the AdIFN-gamma-transduced grafts died within 12 to 13 wk by advanced chronic renal failure associated with strong immune cell infiltration and immune gene expression. By contrast, the Ad-therapy group II showed less inflammation and improved graft histology and function if compared with the groups I and III. Moreover, significantly less infiltrating ED-1(+) macrophages and an improved histologic score even if compared with untreated controls (IV) was observed. However, after disappearance of therapeutic gene expression, group II showed increasing proteinuria probably as result of late T cell activation to the Ad-encoded proteins. Ex vivo transduction of allografts with Ad-control or even more AdIFN-gamma expression promotes intragraft inflammation and chronic graft injury. Targeting macrophage activation by a cocktail of therapeutic genes improved the results. These data support the pathogenetic role of cytokines in chronic graft injury; however, they also show the limitations of the Ad-mediated gene transfer.
Release of simian virus 40 virions from epithelial cells is polarized and occurs without cell lysis (1989)

We have investigated the process of release of simian virus 40 (SV40) virions from several monkey kidney cell lines. High levels of virus release were observed prior to any significantly cytopathic effects in all cell lines examined, indicating that SV40 utilizes a mechanism for escape from the host cell which does not involve cell lysis. We demonstrate that SV40 release was polarized in two epithelial cell types (Vero C1008 and primary African green monkey kidney cells) grown on permeable supports; release of virus occurs almost exclusively at apical surfaces. In contrast, equivalent amounts of SV40 virions were recovered from apical and basal culture fluids of nonpolarized CV-1 cells. SV40 virions were observed in large numbers on apical surfaces of epithelial cells and in cytoplasmic smooth membrane vesicles. The sodium ionophore monensin, an inhibitor of vesicular transport, was found to inhibit SV40 release without altering viral protein synthesis or infectious virus production.
Biochemical Pathways Leading to Collagen Deposition in Pulmonary Fibrosis (1985)

Fibrosis in the lung is well described histologically. There is destruction of the normal architecture with the appearance of inflammatory cells and connective tissue components, particularly collagen. Biochemical evidence for an increased deposition of collagen in man has been demonstrated in patients with both acute and chronic forms of pulmonary fibrosis. Studies of collagen metabolism in man are equivocal but there is convincing evidence for an increased synthesis rate in animal models of pulmonary fibrosis. Collagen degradation has been little studied but may be important, given the recent evidence indicating quite rapid turnover of lung collagen and a decreased degradation of collagen in experimental disease. The distribution of collagen types has been studied in man, where there is some evidence for the production of type III collagen in the early active phase of disease with a preponderance of type I collagen in the late stages. The cellular mechanisms leading to these changes are uncertain but the alveolar macrophage may play a central role, since it is capable of releasing factors which expand the fibroblast population as well as attracting new fibroblasts to the site of injury. These pathways are described for what is essentially the normal physiological response of scar formation, which has pathological consequences in the lung, a tissue requiring thin membranes at its epithelial and endothelial surfaces, in order to perform its main function of gas exchange.
Interleukin-1 receptor antagonist in normal and psoriatic epidermis. (1992)

The objective of these studies was to characterize the IL-1 inhibitory activity present in normal and psoriatic epidermis from clinically stable lesions. Fractionation of normal epidermal cytosol on a molecular sizing column failed to reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs indicated that both the IL-1 receptor antagonist (IL-1ra) and IL-1 alpha were present in overlapping peaks. Further fractionation of the normal epidermal cytosol by anion exchange chromatography separated these two molecules, revealing the IL-1 inhibitory bioactivity of the IL-1ra molecule. Similar studies on psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity and IL-1ra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic cytosol was neutralized by a mAb specific for IL-1ra. The ratio of IL-1ra to IL-1 alpha proteins was significantly increased in involved psoriatic skin compared with normal skin. By Western blot analysis this IL-1ra was approximately 20 kD, slightly larger than monocyte-derived IL-1ra and equivalent to an intracellular variant of IL-1ra expressed by keratinocytes. Polymerase chain reaction indicated the presence of mRNA for both forms of IL-1ra in normal epidermis, with both forms increased in psoriatic-involved skin. Immunofluorescence studies revealed the IL-1ra protein to be concentrated in the stratum granulosum of normal skin and in the basal-midbasal layers of psoriatic epidermis. These results suggest that the balance between intracellular IL-1ra and IL-1 alpha may be an important influence on keratinocyte growth and/or differentiation, as well as on the inflammatory potential of IL-1 in injured skin.
Comprehensive review of JAK inhibitors in myeloproliferative neoplasms (2012)

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as 'BCR-ABL1-negative' MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in 'BCR-ABL1-negative' MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate- to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.
Femtosecond photonic viral inactivation probed using solid-state nanopores (2018)

We report on detection of virus inactivation using femtosecond laser radiation by measuring the&#13;\nconductance of a solid state nanopore designed for detecting single particles. Conventional methods&#13;\nof assaying for viral inactivation based on plaque forming assays require 24–48 h for bacterial growth.&#13;\nNanopore conductance measurements provide information on morphological changes at a single&#13;\nvirion level.We show that analysis of a time series of nanopore conductance can quantify the detection&#13;\nof inactivation, requiring only a few minutes from collection to analysis. Morphological changes were&#13;\nverified by dynamic light scattering. Statistical analysis maximizing the information entropy provides&#13;\na measure of the log reduction value. This work provides a rapid method for assaying viral inactivation&#13;\nwith femtosecond lasers using solid-state nanopores.
High Expression of HER3 Is Associated with a Decreased Survival in Gastric Cancer (2008)

HER3 overexpression is strongly associated with tumor progression and poor prognosis of patients with gastric cancer. It may become a new prognostic factor and a target of treatment.
Inhibition Effect of Amaryllidaceae Alkaloids, Lycorine and Lycoricidinol on Macrophage TNF-α Production (2001)

We previously demonstrated that Amaryllidaceae alkaloids, lycorine and lycoricidinol, inhibit induction of apoptosis by calprotectin derived from neutrophils, and that the latter alkaloid showed suppression in rat adjuvant-induced arthritis model. These findings suggest that the alkaloids have a modulating activity against inflammatory reaction. To explore further the mechanism of the suppression for inflammation, we studied the effect of the alkaloids on macrophage tumor necrosis factor (TNF-alpha) production in vitro, since TNF-alpha is recognized as a pivotal cytokine to regulate inflammation. As a result of this study, lycorine and lycoricidinol inhibited TNF-alpha production of murine macrophages stimulated with lipopolysaccharide (ID50 were 0.2 microgram/ml and 0.002 microgram/ml, respectively). The inhibition was also observed in macrophages treated by Gram-positive bacteria, Enterococcus faecalis. Both lycorine and lycoricidinol reportedly have inhibitory activity for protein biosynthesis. Although the inhibition of TNF-alpha production by lycoricidinol was mainly due to the inhibition of protein biosynthesis, lycorine showed inhibition against TNF-alpha production at lower concentrations than the case that they inhibited 35S-Cysteine/35S-Methionine incorporation into macrophages. These facts suggest that the inhibition of TNF-alpha production is not due to the inhibitory activity against protein translation at least at lower concentrations. From these results, it was concluded that these alkaloids exert inhibitory effects not only on neutrophil apoptosis-inducing protein, calprotectin, but also on macrophage TNF-alpha production.
Polarization-dependent optical gain characteristics of delta-strained quantum wells for semiconductor optical amplifiers (2000)

Polarization sensitivity of quantum-well structures with delta-strained layers is investigated by numerical analysis. The effects of delta-strained layers on optical gains are very sensitive to the location and the number of the layers. Among the various structures investigated, the quantum well with two delta-strained layers has the least polarization sensitivity for wide wavelength and injected carrier density ranges.
Disorders of glucose metabolism in sleep apnea (2005)

Sleep is a complex behavioral state that occupies one-third of the human life span. Although viewed as a passive condition, sleep is a highly active and dynamic process. The sleep-related decrease in muscle tone is associated with an increase in resistance to airflow through the upper airway. Partial or complete collapse of the airway during sleep can lead to the occurrence of apneas and hypopneas during sleep that define the syndrome of sleep apnea. Sleep apnea has become pervasive in Western society, affecting approximately 5% of adults in industrialized countries. Given the pandemic of obesity, the prevalence of Type 2 diabetes mellitus and metabolic syndrome has also increased dramatically over the last decade. Although the role of sleep apnea in cardiovascular disease is uncertain, there is a growing body of literature that implicates sleep apnea in the pathogenesis of altered glucose metabolism. Intermittent hypoxemia and sleep fragmentation in sleep apnea can trigger a cascade of pathophysiological events, including autonomic activation, alterations in neuroendocrine function, and release of potent proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6. Epidemiologic and experimental evidence linking sleep apnea and disorders of glucose metabolism is reviewed and discussed here. Although the cause-and-effect relationship remains to be determined, the available data suggest that sleep apnea is independently associated with altered glucose metabolism and may predispose to the eventual development of Type 2 diabetes mellitus.
Contributions of a Finite Element Model for the Geometric Optimization of an Implantable Bioartificial Pancreas (2002)

The extravascular implantation of islets of Langerhans immunoprotected within a permselective membrane is a promising method to treat diabetes mellitus. However, oxygen limitation due to purely diffusive solute transport was considered to provoke tissue necrosis and graft failure. We built a solute transport model based on a finite element method aiming at optimizing the hollow fiber geometry. With a low islet density, the influence of oxygen axial flux inside the fiber was underlined and a characteristic length for oxygen supply was introduced. This study allowed the conclusion that islet density must be adapted to the fiber diameter chosen for implantation.
Studies on the Inactivation of Bovine Liver Enoyl-CoA Hydratase by (Methylenecyclopropyl)formyl-CoA:  Elucidation of the Inactivation Mechanism and Identification of Cysteine-114 as the Entrapped Nucleophile (2001)

The inhibitory properties of (methylenecyclopropyl)formyl-CoA (MCPF-CoA), a metabolite derived from a natural amino acid, (methylenecyclopropyl)glycine, against bovine liver enoyl-CoA hydratase (ECH) were characterized. We have previously demonstrated that MCPF-CoA specifically targets ECHs, which catalyze the reversible hydration of alpha,beta-unsaturated enoyl-CoA substrates to the corresponding beta-hydroxyacyl-CoA products. Here, we synthesized (R)- and (S)-diastereomers of MCPF-CoA to examine the stereoselectivity of this inactivation. Both compounds were shown to be competent inhibitors for bovine liver ECH with nearly identical second-order inactivation rate constants (k(inact)/K(I)) and partition ratios (k(cat)/k(inact)), indicating that the inactivation is nonstereospecific with respect to ring cleavage. The inhibitor, upon incubation with bovine liver ECH, labels a tryptic peptide, ALGGGXEL, near the active site of the protein, where X is the amino acid that is covalently modified. Cloning and sequence analysis of bovine liver ECH gene revealed the identity of the amino acid residue entrapped by MCPF-CoA as Cys-114 (mature sequence numbering). On the basis of gHMQC (gradient heteronuclear multiple quantum coherence) analysis with [3-(13)C]-labeled MCPF-CoA, the ring cleavage is most likely induced by the nucleophilic attack at the terminal carbon of the exomethylene group (C(2)'). We propose a plausible inactivation mechanism that involves relief of ring strain and is consistent with examples found in the literature. In addition, these studies provide important clues for future design of more efficient and selective inhibitors to control and/or regulate fatty acid metabolism.