gebhart/patrepeval huggingface dataset:
Unraveling Drug Penetration of Echinocandin Antifungals at the Site of Infection in an Intra-abdominal Abscess Model (2017)

Intra-abdominal candidiasis (IAC) is a prominent invasive fungal infection associated with high mortality. Prompt antifungal therapy and source control are crucial for successful treatment. Echinocandin antifungal drugs are first-line agents; however, their clinical effectiveness is highly variable, with known potential for breakthrough resistance, and little is known about drug exposure at the site of infection. Using matrix-assisted desorption ionization mass spectrometry imaging technology, we investigated the spatial and quantitative distribution in tissue lesions for two echinocandin drugs, micafungin and CD101, in a clinically relevant IAC mouse model. Drug accumulation within lesions was observed with both drugs at their humanized therapeutic doses. CD101, but not micafungin, accumulated in lesions at levels above the mutant prevention concentration of the infecting strain. These findings indicate that current echinocandin drugs are limited by penetration at the site of infection and have implications for clinical outcomes and emergence of resistance in patients with IAC.
Demonstration in Human Plasma of a Lectin Activity Analogous to that of Bovine Conglutinin (1987)

Evidence of the existence in human plasma of an activity analogous to that of bovine conglutinin is presented. The human plasma component was characterized antigenically and functionally. Human plasma was shown to agglutinate complement-coated erythrocytes in the presence of Ca2+, and this conglutination was inhibited by EDTA. The molecule also binds to complement-reacted solid phase IgG and to zymosan in the presence of Ca2+. The binding to complement is not inhibited by N-acetyl-D-mannosamine, but is inhibited by N-acetyl-D-glucosamine, as previously shown for bovine conglutinin. Antibodies raised against bovine conglutinin cross-react with the human protein. The plasma concentration of the conglutinin-like protein showed a high inter-individual variation between apparently healthy donors. Unlike bovine conglutinin, the human conglutinin activity could not be demonstrated in serum but only in plasma. The activity was more stable in plasma containing metal-ion chelators like EDTA and citrate than in heparin or hirudin plasma.
Comparison of LiFePO[sub 4] from Different Sources (2005)

The lithium iron phosphate chemistry is plagued by poor conductivity and slow diffusion in the solid phase. To alleviate these problems, various research groups have adopted different strategies, including decreasing the particle sizes, increasing the carbon content, and adding dopants. In this study, we obtained powders and/or electrodes from six different sources and used a combined model-experimental approach to compare the performance. Samples ranged from 0.4 to 15% "in situ" carbon. In addition, particle sizes varied by as much as an order of magnitude between samples. The study detailed in this manuscript allows us to provide insight into the relative importance of the conductivity of the samples compared to the particle size, the impact of having a distribution in particle sizes, and ideas for making materials to maximize the power capability of this chemistry.
Two Enteropathogenic Escherichia coli Type III Secreted Proteins, EspA and EspB, Are Virulence Factors (1998)

Enteropathogenic Escherichia coli (EPEC) belongs to a family of related bacterial pathogens, including enterohemorrhagic Escherichia coli (EHEC) O157:H7 and other human and animal diarrheagenic pathogens that form attaching and effacing (A/E) lesions on host epithelial surfaces. Bacterial secreted Esp proteins and a type III secretion system are conserved among these pathogens and trigger host cell signal transduction pathways and cytoskeletal rearrangements, and mediate intimate bacterial adherence to epithelial cell surfaces in vitro. However, their role in pathogenesis is still unclear. To investigate the role of Esp proteins in disease, mutations in espA and espB were constructed in rabbit EPEC serotype O103 and infection characteristics were compared to that of the wild-type strain using histology, scanning and transmission electron microscopy, and confocal laser scanning microscopy in a weaned rabbit infection model. The virulence of EspA and EspB mutant strains was severely attenuated. Additionally, neither mutant strain formed A/E lesions, nor did either one cause cytoskeletal actin rearrangements beneath the attached bacteria in the rabbit intestine. Collectively, this study shows for the first time that the type III secreted proteins EspA and EspB are needed to form A/E lesions in vivo and are indeed virulence factors. It also confirms the role of A/E lesions in disease processes.
Radioprotective and antioxidant action of caffeine: mechanistic considerations. (1996)

Caffeine, a major constituent of coffee and other beverages has significant abilities to scavenge highly reactive free radicals and excited states of oxygen and to protect crucial biological molecules against these species. This is one of the possible reasons why caffeine acts as a radioprotector against oxygen-dependent ('oxic') pathway of radiation damage and as an antimutagen/anticarcinogen under certain conditions. The possible physicochemical and molecular mechanisms of caffeine action are briefly reviewed in the light of the recent findings.
Studies inRed Blood Cell Preservation (1993)

Studies were conducted to examine whether an experimental additive solution (EAS-2) containing, in mM: 20 NH(4)Cl, 30 Na(2)HPO)4), 2 adenine, 110 dextrose, 55 mannitol, pH 7.15, would be useful to extend the storage shelf life of human RBCs. With 6 pairs of split units, ATP concentrations were better maintained for 12 weeks with EAS-2 than with Adsol® (1.8 vs. 1.1 µmol/gHb, respectively, p = 0.002). Autologous 24-hours 51Cr viability values for split units in the same donors were: on 6 paired units at 8 weeks, EAS-2 87.0±4.5%, Adsol 72.6±2.3%, p = 0.004; on 11 paired units at 9 weeks, EAS-2 79.5±7.1%, Adsol 68.2±10.1%, p = 0.0003. The data suggest that packed RBCs stored for 9 weeks with EAS-2 will be suitable for transfusion following the removal of supernatant with a single washing step.
A study of fiber-to-fiber losses in waveguide grating routers (1997)

Most of the waveguide grating router's loss comes from fiber coupling and star coupler. Our three-dimensional (3-D) models quantifies both losses. In addition, we study how various waveguide parameters affect the value and nonuniformity of this loss. Our optimization yields a design where the total fiber-to-fiber insertion loss can be reduced to 0.535 dB.
A simple, accurate method to calculate spread-spectrum multiple-access error probabilities (1992)

The exact calculation of error probabilities for direct-sequence spread-spectrum multiple-access (DS/SSMA) systems has been addressed in the literature. The exact calculation is computationally difficult, so emphasis has been on approximations and bounds. One particularly attractive approximation is to just use a signal-to-noise ratio in a Gaussian approximation, the 'standard approximation'. Unfortunately, that approximation is not generally accurate enough. An improved Gaussian approximation with good accuracy has recently been presented. The author derives an accurate Gaussian approximation which is also computationally very simple.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Eradication of Solid Human Breast Tumors in Nude Mice with an Intravenously Injected Light-Emitting Oncolytic Vaccinia Virus (2007)

Previously, we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, beta-galactosidase, and beta-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the viral genome, respectively. I.v. injections of GLV-1h68 (1x10(7) plaque-forming unit per mouse) into nude mice with established (approximately 300-500 mm3) s.c. GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity, and oncolytic efficacy. GLV-1h68 showed an enhanced tumor targeting specificity and much reduced toxicity compared with its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of IFN-stimulated genes (STAT-1 and IRF-7), cytokines, chemokines, and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.
Distinct Metabolomic Profiles of Papillary Thyroid Carcinoma and Benign Thyroid Adenoma (2015)

Papillary thyroid carcinoma (PTC) and benign thyroid adenoma (BTA) are the most common head and neck tumors. However, the metabolic differences between PTC and BTA have not been characterized. The aim of this study was to identify the metabolic profiles of these two types of tumors using a metabolomics approach. Tumors and adjacent nontumor specimens collected from 57 patients with PTC and 48 patients with BTA were profiled using gas chromatography-time-of-flight mass spectrometry and ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. A panel of 46 and 44 differentially expressed metabolites were identified in the PTC and BTA specimens, respetively, and compared with nontumor tissues. Common metabolic signatures, as characterized by increased glycolysis, amino acid metabolism, one carbon metabolism and tryptophan metabolism, were found in both types of tumors. Purine and pyrimidine metabolism was significantly elevated in the PTC specimens, and taurine and hypotaurine levels were also higher in the PTC tissues. Increased fatty acid and bile acid levels were found, especially in the BTA tissues. The metabolic profiles of the PTC and BTA tissues include both similar and remarkably different metabolites, suggesting the presence of common and unique mechanistic pathways in these types of tumors during tumorigenesis.
Effects of Beta Adrenergic Blockade on the Circulation, with Particular Reference to Observations in Patients with Hypertrophic Subaortic Stenosis (1964)

The circulatory effects of blocking the beta adrenergic receptors with Nethalide were studied in 10 patients with hypertrophic subaortic stenosis and in five postoperative subjects undergoing right heart catheterization. In the resting state, the heart rate and the rate of pressure development in the right ventricle diminished slightly, but cardiac index was not altered by the administration of Nethalide. These observations suggest that tonic sympathetic activity is not of major importance in basal subjects in the supine position. Nethalide attenuated the increase in heart rate and right ventricular dp/dt associated with exercise, and abolished the response of these two variables to the administration of isoproterenol. In the patients with hypertrophic subaortic stenosis Nethalide had little effect on the severity of the obstruction at rest, but reduced the intensification of the obstruction produced by exercise or isoproterenol. The possible clinical benefits of blocking the beta adrenergic receptors in these patients were discussed.
METHEMOGLOBINEMIA IN INFANCY (1950)

The purpose of this communication is to review the subject of methemoglobinemia in infancy and to add a report of a case of methemoglobinemia in neonatal life, resulting from the ingestion of well water containing large amounts of nitrates. Methemoglobinemia has been recognized as a disease entity for many years. Several authors have grouped the cases according to the chemical responsible for the disturbance, such as aniline dyes (wax crayons), bismuth subnitrate, potassium chlorate, nitrites, acetanilid and sulfonamide compounds. Methemoglobinemia has also been reported to occur in the following clinical syndromes: congenital or idiopathic methemoglobinemia,<sup>1</sup>Winckel's disease<sup>2</sup>and enterogenous cyanosis.<sup>3</sup> Interest in methemoglobinemia, as it occurs in infants, is only of recent date. In 1945, Comly<sup>4</sup>reported 2 cases of methemoglobinemia in early life and mentioned 19 others. He proposed that the high nitrate and nitrite content of well water used as a diluent for the
Rosiglitazone Induces Mitochondrial Biogenesis in Mouse Brain (2007)

Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain in an apolipoprotein (Apo) E isozyme-independent manner. Rosiglitazone induced both mitochondrial DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of mitochondrial biogenesis. Transcriptomics and proteomics analysis suggested the mitochondria produced in the presence of human ApoE3 and E4 were not as metabolically efficient as those in the wild type or ApoE knockout mice. Thus, we propose that PPARgamma agonism induces neuronal mitochondrial biogenesis and improves glucose utilization leading to improved cellular function and provides mechanistic support for the improvement in cognition observed in treatment of Alzheimer's patients with rosiglitazone.
The immunoglobulin heavy chain locus contains another B-cell-specific 3' enhancer close to the alpha constant region. (1993)

The transcription of immunoglobulin genes is controlled by variable region promoters and by enhancers, both of which are lymphoid specific. Because immunoglobulin genes are subject to an extremely complex regulation, we anticipated that there might be additional control elements for these genes. We therefore sought additional enhancers and demonstrate here that there is indeed another weak transcriptional enhancer just 3' to the mouse alpha constant region. This novel immunoglobulin enhancer is lymphoid specific and at two positions can bind members of the Oct family of transcription factors.
Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell (1997)

Epstein-Barr (EBV) is a powerful immortalizing virus for human B lymphocytes in vitro and is associated with several human neoplasias in vivo. Previously, we have shown that the majority of EBV-infected cells in the peripheral blood of healthy, persistently infected individuals do not express the activated phenotype, e.g., high levels of cell surface CD23 and CD80 (B7), characteristically expressed on in vitro-immortalized cells. Here, we show that > or = 90% of the CD23-, virus-infected cells in the peripheral blood are in G0 and therefore resting. The remaining cells may be G1 arrested, but we were unable to detect a significant number of cells traversing the S-G2-M stages of the cell cycle. The mRNA for LMP2A, but not EBNA1 originating from Qp, was readily detected in this population, and these cells appear competent in the processing and presentation of antigen by class I major histocompatibility complex. We propose that these resting B cells are the site of long-term latent persistence for EBV. We further propose that the persistence of the virus in a resting B7- B cell provides an important mechanism to escape immunosurveillance. The demonstration that EBV can persist latently in a resting B cell means that the immortalizing functions of EBV can be down regulated in a normal B cell. This conclusion has important implications for understanding and controlling EBV-associated neoplasia.
A Dual-Mode RF Power Harvesting System With an On-Chip Coil in 180-nm SOI CMOS for Millimeter-Sized Biomedical Implants (2018)

In this paper, we present a dual-mode power harvesting system for millimeter-sized biomedical implants that are immune to the variation of wireless link parameters and loading. The design includes a multistage full-wave voltage rectifier, a power management unit, and a low dropout voltage regulator. Depending on the received RF power level and the required power by the load, power delivery is conducted in a continuous or duty-cycled mode. The system is fabricated in 180-nm silicon on insulator (SOI) CMOS technology with an active area of 2.56 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> including an on-chip coil. RF power is transferred to the chip from a 2 × 2 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> coil through 10 mm of air at 434 MHz. The efficiency of the designed wireless link, which is the power transfer efficiency from the external coil to the on-chip coil, reaches up to 0.68% (-21.7 dB) at 10-mm separation through air. Keeping the transmitted RF power below 24 dBm, the system can provide a 1.08-V dc voltage for resistive loads larger than 20 kQ continuously over time. When the harvested power is not enough to drive the load continuously, the system operates in the duty-cycled mode. Measurement results show that the system can drive a 1-kQ load in the duty-cycled mode when the transmitted power level is 15 dBm.
Distinct changes in intranuclear lamin A/C organization during myoblast differentiation (2001)

Intranuclear lamin foci or speckles have been observed in various cell types. In order to explore the possibility of changes in internal lamin organization during muscle differentiation, we have examined the appearance of A-type lamin speckles that associate with RNA splicing factor speckles in C2C12 myoblasts and myotubes. Lamin speckles were observed in dividing myoblasts but disappeared early during the course of differentiation in postmitotic myocytes, and were absent in myotubes and muscle fibers. However, no changes were seen in the typical peripheral organization of lamins A/C or B1 or in RNA splicing factor speckles. Lamin speckles were also absent in quiescent myoblasts but reappeared as cells were reactivated to enter the cell cycle. These changes were not observed in other quiescent cell types. Immunoblot analysis indicated that the abundance and migration of lamins A and C was not altered in differentiated myoblasts. When myotube or quiescent myoblast nuclei were extracted with nucleases and detergent, a uniformly stained internal lamina was revealed, indicating that lamins A/C were antigenically masked in these cells, probably owing to structural reorganization of the lamina during differentiation or quiescence. Our results suggest that muscle cell differentiation is accompanied by regulated rearrangements in the organization of the A-type lamins.
Noninvasive arterial thrombus imaging with 99mTc monoclonal antifibrin antibody. (1992)

99mTc-labeled Fab' fragments of the T2G1s antibody are taken up specifically by acute arterial thrombi after intravenous injection. Uptake is progressive over a 2-hour period, and all thrombi are detected by radionuclide imaging at 2 hours. These results show that it is feasible to noninvasively detect arterial thrombi within 2 hours of formation.
Evaluation of Biomarker Discovery Approaches to Detect Protein Biomarkers of Acute Renal Allograft Rejection (2005)

Management of host responses to allografts by immunosuppressive therapy is the cornerstone of transplantation medicine, but it is still deficient in one important element: biomarkers that are readily accessible and predict the fate of the transplant early, specifically, and reliably. Using a Brown Norway (BN)-to-Lewis rat renal allograft model of kidney transplantation, this study aims at evaluating two proteomic approaches to discover biomarkers for acute rejection: SELDI-MS technology and 2D gel electrophoresis combined with mass spectrometry. Several novel potential serum biomarkers have been identified for follow up. Overall, the conclusion is that apparently at the serum protein level, dramatic changes only occur at a stage where kidney function is already severely affected. Multivariate analysis of serum profiles suggests that there is an ensemble of subtle changes, comprising a proteomic signature of acute rejection at an early stage, a more detailed evaluation of which might provide novel opportunities for the diagnosis of acute rejection. Profiling of the excreted proteins indicates that urine might even present the earliest signs of the rejection process.
Effects of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on serum lipids, lipoproteins and cholesterol ester transfer activity in primary hypercholesterolemic patients. (1995)

Effects of a combination therapy of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on lipid metabolism were investigated measuring a wide range of parameters in 42 patients with primary hypercholesterolemia. After a wash-out period patients were randomly allocated to 1 of the 2 groups, the fluvastatin-preceding group (G-1) and the niceritrol-preceding group (G-2). In G-1 fluvastatin monotherapy (30 mg/day) significantly decreased total cholesterol (TC) and LDL-cholesterol (LDL-C). There was no significant change in HDL-cholesterol (HDL-C), triglyceride (TG) and lipoprotein (a) (Lp(a)). Further effect in HDL-C and TG was observed after the addition of niceritrol (750 mg/day). On the other hand, in G-2, while niceritrol alone (750 mg/day) produced no significant change in TC, LDL-C, HDL-C, TG and Lp(a), the addition of fluvastatin (30 mg/day) reduced TC and LDL-C levels significantly. Cholesterol ester transfer (CET) activity was significantly reduced by niceritrol monotherapy. After the concomitant use of the 2 drugs CET activity was significantly reduced only in G-2. No significant change in lipoprotein lipase and hepatic triglyceride lipase activities were observed in the 2 groups at either point in time. No serious adverse effect was observed in this study. It is concluded that fluvastatin is an effective drug for lowering LDL-cholesterol and causes no adverse alteration in lipid metabolism. Combination with niceritrol at a dose of 750 mg/day dose not appear to augment or attenuate beneficial effects of fluvastatin.