gebhart/patrepeval huggingface dataset:
Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. (1984)

The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. The aim of the present investigation was to clarify whether the Ki-67 nuclear antigen is restricted in its expression to certain phases of the cell cycle. All experiments consistently showed that the Ki-67 nuclear antigen is present in S, G2, and M phase, but is absent in G0. However, the results concerning Ki-67 antigen expression in G1 phase varied: cells passing the early events of mitogen triggered transition from G0 to G1, i.e., G1T and first G1A, lacked the Ki-67 nuclear antigen, whereas G1 cells after mitosis were constantly Ki-67-positive. This result suggests that after mitosis cells might not follow the same metabolic pathways as G0 cells do when entering G1 for the first time. Therefore, we suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle. Because our data show that the Ki-67 nuclear antigen is present throughout the cell cycle, immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
Evaluation of the Nonneoplastic Pathology in Tumor Nephrectomy Specimens (2006)

Pathologic changes in nonneoplastic renal parenchyma of nephrectomy specimens for renal tumors and the significance of these changes with regard to the outcome of contralateral kidney function have not been studied previously. We examined the nonneoplastic renal parenchymal changes in 110 consecutive tumor nephrectomy specimens, and we correlated our findings with patients' clinical information. The material was examined for the presence of any glomerular, tubulointerstitial, or vascular pathology. In our analysis, only about 10% of cases had unremarkable renal parenchyma and vasculature. A further 28% of cases had unremarkable parenchyma, but some degree of vascular sclerosis was noted. The remaining cases (>60%) had evident pathologic abnormalities, most commonly related to vascular disease or diabetes mellitus. Regardless of the type of renal cancer they have, the majority of our cases can be placed in one of three principal groups: 1) unremarkable kidney parenchyma, with or without vascular sclerosis (38%); 2) parenchymal scarring and marked vascular changes, including cases of atheroembolic disease, and chronic thrombotic microangiopathy (28%); and 3) changes related to diabetes mellitus, such as glomerular hypertrophy, mesangial expansion, and diffuse glomerulosclerosis (24%). Follow-up data on serum creatinine 6 months postoperatively were available in a third of our patients. Patients with severe histopathologic findings (parenchymal scarring with >20% global glomerulosclerosis and advanced diffuse diabetic glomerulosclerosis) showed a significant change in serum creatinine from the preoperative period to 6 months after radical nephrectomy (P=0.001), indicative of progressive worsening of renal function; this change is significantly greater than that seen in patients with unremarkable renal parenchyma (P=0.01). We conclude that adequate examination of nonneoplastic renal parenchyma is an important tool in recognizing patients at risk for progressive renal disease after nephrectomy and could be an essential step in providing early preventive and treatment measures and better medical care of patients undergoing nephrectomy for neoplastic processes.
A Mobile IPv6 Firewall Traversal Scheme Integrating with AAA (2006)

Recently, mobile IPv6 has been standardized to provide seamless roaming for mobile users in IPv6 network. However, current IP networks are predominantly based on IPv4 technology and most of the firewalls have been designed for these networks. These firewalls will interfere in the smooth operation of mobile IPv6 and can be a detriment to deployment. In this paper, we propose a mobile IPv6 firewall traversal scheme integrating with AAA protocol. By defining several diameter extension messages between the AAA server and firewall, the firewall policies can be adjusted dynamically to provide the mobile IPv6 entities with transparent communication. The solution requires neither any modification of mobile IPv6 protocol nor to add special network components. Furthermore, the scheme is based on hierarchical network model and taking AAA factors into consideration. Therefore, it suits the operation mode of many service providers as well
Lifetime- and Color-Tailored Fluorophores in the Micro- to Millisecond Time Regime (2000)

We report the development of compound dyes which have tunable emission wavelengths, from 520 to 680 nm, and simultaneously tunable excited-state lifetimes, ranging from 50 to 500 μs. Future work is expected to extend these ranges yet further. The compound dyes are made of a lanthanide donor with a millisecond lifetime, which transfers energy to an acceptor with nanosecond lifetime, the latter made from an organic fluorophore. By varying the distance between the two, energy transfer from donor to acceptor results in a variable donor lifetime and emission, primarily from the acceptor. Emission color of the complex is therefore determined by choice of acceptor, and the lifetime decay of acceptor emission following an excitation pulse is determined by the donor's lifetime, which feeds the acceptor's delayed emission. By utilizing both the time-domain and wavelength-domain, these probes have the potential for quadratically increasing the number of detectable probes on a single sample.
Reduction in Mortality in Subjects With Homozygous Familial Hypercholesterolemia Associated With Advances in Lipid-Lowering Therapy (2011)

Lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia.
HER2-positive breast cancer: beyond trastuzumab. (2010)

The outlook for patients with HER2-positive breast cancer was revolutionized by the development of trastuzumab (Herceptin), a humanized murine monoclonal antibody. Use of this agent led to improved overall survival when it was added to chemotherapy for the treatment of metastatic breast cancer. Improved understanding of mechanisms of resistance to trastuzumab has facilitated the development of novel agents for HER2-positive breast cancer, and also resulted in superior outcomes when added to chemotherapy in the adjuvant setting. This review explores the use of several such agents, including lapatinib (Tykerb), HSP90 inhibitors, T-DM1, and other tyrosine kinase inhibitors. Emerging data from trials of these agents indicate that the HER2 pathway remains a valid therapeutic target following disease progression on trastuzumab, and suggest a promising role for combined HER2 blockade with two or more agents.
A new flash memory management for flash storage system (2003)

Proposes a new way of managing flash memory space for flash memory-specific file systems based on a log-structured file system. Flash memory has attractive features such as non-volatility and fast I/O speed, but it also suffers from an inability to update in place, and limited usage cycles. These drawbacks require many changes to conventional storage (file) management techniques. Our focus is on lowering the cleaning cost and evenly utilizing flash memory cells while maintaining a balance between these two often-conflicting goals. The cleaning efficiency is enhanced by dynamically separating cold data and non-cold data. The second goal, cycle leveling, is achieved to the degree where the maximum difference between erase cycles is below the error range of the hardware. Simulation results show that the proposed method has a significant benefit over naive methods: a maximum of 35% reduction in the cleaning cost with evenly-spread writes across segments.
Safety and efficacy of investigator‐prescribed BeneFIX® prophylaxis in children less than 6 years of age with severe haemophilia B (2010)

Prophylaxis is increasingly prescribed in treatment of haemophilia and its benefit is believed to be most significant for the youngest patients as haemophilic arthropathy may be prevented if prophylaxis is initiated prior to recurrent haemarthroses. While clinical prophylaxis data are readily available for haemophilia A, analogous data for haemophilia B are relatively limited. A prospective clinical study of recombinant factor IX (BeneFIX; rFIX), designed to allow investigator prescribed prophylaxis according to customary practices, was conducted in children <6 years old with severe haemophilia B. Nearly all children were prescribed prophylaxis (22/25; 88%) for all or part of their study participation. Favourable efficacy and safety profiles were reported. Routine prophylaxis with 1 or 2 rFIX infusions per week over an average of greater than 6 months of therapy resulted in near complete prevention of spontaneous breakthrough haemorrhages (<1 per year), with most children (77%) having none, including seven patients (32%) who had no bleeding episodes at all. Haemorrhages in joints were less common than those outside joints (27% vs. 73% of haemorrhages). In a patient population that included children with multiple prior haemarthroses, 68% of children had no joint bleeding. Breakthrough haemorrhages resolved with 1 or 2 infusions in 89% of episodes. The absence of changes in prophylaxis infusion schedules suggests that 1 or 2 rFIX infusion(s) per week were well-tolerated by these young patients, including those with (41%) and without (59%) central venous access devices. Safety was established by the low incidence of treatment-related adverse events.
G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms General subjects (2017)

AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences.Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents.Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells.Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled G-quadruplex Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
Dynamic contrast‐enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti‐angiogenic therapy in a xenograft model of glioblastoma multiforme (2002)

Findings demonstrate that tumor vascular permeability and tumor growth can be inhibited by neutralization of endogenous VEGF and suggest that angiogenesis with the maintenance of endothelial hyperpermeability requires the presence of VEGF within the tissue microenvironment. Changes in tumor vessel permeability and tumor volumes as measured by contrast-enhanced MRI provide an assay that could prove useful for clinical monitoring of anti-angiogenic therapies in brain tumors.
MILESTONES IN THE HISTORY OF THE MENINGOCOCCUS (1956)

This paper cites the most significant findings in the development of present day knowledge of the meningococcus (Neisseria meningitidis). It is pointed out that advances have occurred stepwise, each step involving approximately a decade. These decades are discussed in turn: the period of classification, the development of serum therapy, epidemiology and biology, chemotherapy and resistance, and finally transduction and genetic recombination. Future trends in research on the meningococcus are pointed out.
DNA Sequencing up to 1300 Bases in Two Hours by Capillary Electrophoresis with Mixed Replaceable Linear Polyacrylamide Solutions (2000)

This paper presents results on ultralong read DNA sequencing with relatively short separation times using capillary electrophoresis with replaceable polymer matrixes. In previous work, the effectiveness of mixed replaceable solutions of linear polyacrylamide (LPA) was demonstrated, and 1000 bases were routinely obtained in less than 1 h. Substantially longer read lengths have now been achieved by a combination of improved formulation of LPA mixtures, optimization of temperature and electric field, adjustment of the sequencing reaction, and refinement of the base-caller. The average molar masses of LPA used as DNA separation matrixes were measured by gel permeation chromatography and multiangle laser light scattering. Newly formulated matrixes comprising 0.5% (w/w) 270 kDa and 2% (w/w) 10 or 17 MDa LPA raised the optimum column temperature from 60 to 70 degrees C, increasing the selectivity for large DNA fragments, while maintaining high selectivity for small fragments as well. This improved resolution was further enhanced by reducing the electric field strength from 200 to 125 V/cm. In addition, because sequencing accuracy beyond 1000 bases was diminished by the low signal from G-terminated fragments when the standard reaction protocol for a commercial dye primer kit was used, the amount of these fragments was doubled. Augmenting the base-calling expert system with rules specific for low peak resolution also had a significant effect, contributing slightly less than half of the total increase in read length. With full optimization, this read length reached up to 1300 bases (average 1250) with 98.5% accuracy in 2 h for a single-stranded M13 template.
Cellular Synthesis of Synchronous Sequential Machines (1972)

A method of synthesizing sequential machines using identical cells arranged in arrays is described. The array is connected in a regular pattern and can be designed to include features such as redundancy and programmability. Minimal synthesis is also discussed.
Amino acid residues lining the chloride channel of the cystic fibrosis transmembrane conductance regulator. (1994)

The cystic fibrosis transmembrane conductance regulator forms a chloride channel that is regulated by phosphorylation and intracellular ATP levels. The structure of the channel-forming domains is undetermined. To identify the residues lining this channel we substituted cysteine, one at a time, for 9 consecutive residues (91-99) in the M1 membrane-spanning segment. The cysteine substitution mutants were expressed in Xenopus oocytes. We determined the accessibility of the engineered cysteine to charged, sulfhydryl-specific methanethiosulfonate reagents added extracellularly. We assume that, among residues in membrane-spanning segments, only those lining the channel will be accessible to react with these hydrophilic reagents and that such a reaction would irreversibly alter conduction through the channel. Only the cysteines substituted for Gly-91, Lys-95, and Gln-98 were accessible to the reagents. We conclude that these residues are in the channel lining. The periodicity of these residues is consistent with an alpha-helical secondary structure.
Characterization and analysis of a novel glycoprotein from snake venom using liquid chromatography‐electrospray mass spectrometry and Edman degradation (1999)

An N-linked glycosylation in a novel C-lectin protein from snake venom was observed by Edman degradation and liquid chromatography-electrospray mass spectrometry. The peptides obtained by trypsin cleavage were analyzed to confirm the amino acid sequence and Asn5 was found to be the N-glycosylation site. The result was further confirmed by N-glycosidase digestion. In addition, the protein and tryptic peptides with and without glycan chain were characterized by mass spectrometry according to the mass difference. The glycopeptide obtained from proteolytic digestion was analyzed and the glycoforms were identified as high-mannose type by tandem MS coupled with alpha-mannosidase digestion. An oxidized Met residue was detected and located in the protein by mass spectrometry.
Increase in urokinase plasminogen activator mRNA synthesis in human carcinoma cells is a primary effect of the potent tumor promoter, phorbol myristate acetate. (1986)

The effect of tumor promoters and growth factors on the synthesis of urokinase and urokinase mRNA in human carcinoma cells has been investigated. In urokinase-producing human carcinoma cells (A1251), a 20-40-fold increase in urokinase mRNA level is obtained after treatment with 10 nM phorbol myristate acetate (PMA), a smaller effect (two- to fourfold) with 2 ng/ml platelet-derived growth factor (PDGF) and no effect with epidermal growth factor (EGF) (up to 50 nM). After treatment with PMA, urokinase mRNA level increases already at 30 min peaking 2-4 h thereafter. Cell line A431, which has an abnormally high number of EGF receptors, shows the same response to PMA, but also responds to EGF (two- to fourfold increase in mRNA). The kinetics are similar to those of A1251. Nuclear transcription experiments show that the PMA-induced increase in urokinase mRNA is due to increased synthesis. The protein synthesis inhibitor, cycloheximide (10 micrograms/ml), also increases the level of urokinase mRNA. When both cycloheximide and PMA are used, super-induction is observed. This result may indicate that a short-lived protein negatively regulates the level of urokinase. The different efficiency of the effectors (PMA and PDGF better than EGF) and their kinetics, as well as the effect of cycloheximide on urokinase mRNA synthesis, (a) are reminiscent of the effect of PDGF and PMA on competence phase genes (Kelly, K., B.H. Cochran, C.D. Stiles, and P. Leder, 1983, Cell, 35: 603-610), (b) demonstrate that the synthesis of urokinase is part of the early cellular response to these factors, and (c) provide a preliminary insight in the overproduction of urokinase by primary malignant tumors and transformed cells in culture.
Cloning of a Wound Inducible Lycopersicon esculentum Cytochrome P450 Gene and Lack of Regeneration of Transgenic Plants with Sense or Antisense Constructs (2002)

A Lycopersicon esculentum Mill. (tomato) cDNA clone with high similarity to a Nicotiana plumbaginifolia Viv. (tobacco) cytochrome P450 gene was isolated using 5' and 3' rapid amplification of cDNA ends (RACE). The isolated cDNA (GenBank Accession No. AF249329) has an open reading frame of 1494 base pairs (bp) and encodes a protein of 498 amino acids with 75% identity to the N. plumbaginifolia cytochrome P450 ( CYP72A2 ) and 45% to a Catharanthus roseus G. Don (Madagaskar periwinkle) CYP72A1 protein sequence. By Southern-blot analysis, one or two highly homologous genes were detected in the L. esculentum genome. Expression of the cloned P450 gene was regulated by circadian rhythm and enhanced by wounding. Leaf transcripts were detected in the light but not dark. Highest transcript levels were observed 3 hours after mechanical wounding. No increase in expression was seen in response to applications of zeatin as with the N. plumbaginifolia gene. Of the tissues analyzed, shoot tips and young leaves and fruit had the highest detectable transcript levels. Attempts to transform more than 1400 cotyledon explants of L. esculentum with sense or antisense CYP72A2 gene constructs produced no transgenic plants.
Performance Characteristics of Solid Lithium‐Aluminum Alloy Electrodes (1976)

Lithium‐aluminum alloy electrodes have shown a great deal of promise for meeting the performance requirements of negative electrodes in batteries for off‐peak energy storage in utility networks and for vehicle propulsion. To develop negative electrodes that meet the cell performance goals, the effects of a number of variables on the lithium‐aluminum electrode performance were determined. Investigations were conducted to determine the effects of volume fraction electrolyte in the electrode, electrode thickness, fabrication technique, lithium concentration in the Li‐Al alloy, and current collector in the electrode. Electrochemically formed Li‐Al electrodes that are 0.32 cm thick, have an electrolyte volume fraction of 0.2 in the charged state, and contain about 2 weight percent stainless steel wire current collector have demonstrated the performance goals for the negative electrodes in a electric automobile battery. For electrode thicknesses ≥0.64 cm, vibratorily loaded pyrometallurgical Li‐Al electrodes with porous metallic current collectors have demonstrated the highest lithium utilization and capacity density over a wide range of discharge current densities and have met the performance goals for negative electrodes in a off‐peak energy storage battery.
Molecular Docking of Potential Inhibitors for Influenza H7N9 (2015)

As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a threat to the public health, due to its high lethality and pathogenicity. Furthermore, H7N9 has already generated various mutations such as neuraminidase R294K mutation which could make the anti-influenza oseltamivir less effective or ineffective. In this regard, it is urgent to develop new effective anti-H7N9 drug. In this study, we used the general H7N9 neuraminidase and oseltamivir-resistant influenza virus neuraminidase as the acceptors and employed the small molecules including quercetin, chlorogenic acid, baicalein, and oleanolic acid as the donors to perform the molecular docking for exploring the binding abilities between these small molecules and neuraminidase. The results showed that quercetin, chlorogenic acid, oleanolic acid, and baicalein present oseltamivir-comparable high binding potentials with neuraminidase. Further analyses showed that R294K mutation in neuraminidase could remarkably decrease the binding energies for oseltamivir, while other small molecules showed stable binding abilities with mutated neuraminidase. Taken together, the molecular docking studies identified four potential inhibitors for neuraminidase of H7N9, which might be effective for the drug-resistant mutants.
Digital processing of high-resolution electrocardiograms--detection of His-Purkinje activity from the body surface. (1988)

Article Digital Processing of High-Resolution Electrocardiograms — Detection of His-Purkinje Activity from the Body Surface - Digitale Auswertung hochauflösender Elektrokardiogramme - Ableitung der His-Purkinje-Aktivität von der Körperoberfläche was published on January 1, 1988 in the journal Biomedical Engineering / Biomedizinische Technik (volume 33, issue 10).