gebhart/patrepeval huggingface dataset:
Are resorbable implants about to become a reality? (2006)

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Site‐specific analysis of N‐glycans on haptoglobin in sera of patients with pancreatic cancer: A novel approach for the development of tumor markers (2008)

It was found in our previous studies that the concentration of fucosylated haptoglobin had increased in the sera of patients with pancreatic cancer (PC) compared to those of other types of cancer and normal controls. Haptoglobin, an acute phase protein, has four potential N-glycosylation sites, although it remains unknown which site is responsible for the change in fucosylated N-glycans. In the present study, site-specific N-glycan structures of haptoglobin in sera obtained from patients with PC or chronic pancreatitis (CP) were analyzed using liquid chromatography-electrospray ionization mass spectrometry. Mass spectrometry analyses demonstrated that concentrations of total fucosylated di-, tri- and tetra-branched glycans of haptoglobin increased in the sera of PC patients. Tri-antennary N-glycans containing a Lewis X-type fucose markedly increased at the Asn211 site of haptoglobin N-glycans. While fucosylated N-glycans derived from serum haptoglobin of patients with CP slightly increased, di-fucosylated tetra-antennary N-glycans were observed only at this site in PC patients, and were absent in the haptoglobin of normal controls and individuals with CP. Thus, the present study provides evidence that site-specific analyses of N-glycans may be useful as novel tumor markers for PC.
Nerve Injection of Viral Vectors Efficiently Transfers Transgenes into Motor Neurons and Delivers RNAi Therapy Against ALS (2009)

RNA interference (RNAi) mediates sequence-specific gene silencing, which can be harnessed to silencing disease-causing genes for therapy. Particularly suitable diseases are those caused by dominant, gain-of-function type of gene mutations. In these diseases, the mutant gene generates a mutant protein or RNA product, which possesses toxic properties that harm cells. By silencing the mutant gene, the toxicity can be lessened because the amount of the toxic product is lowered in cells. In this report, we tested RNAi therapy in a mouse model for amyotrophic lateral sclerosis (ALS), which causes motor neuron degeneration, paralysis, and death. We used a transgenic model that overexpresses mutant Cu, Zn superoxide dismutase (SOD1G93A), which causes ALS by a gained toxic property. We delivered RNAi using recombinant adenovirus (RAd) and adeno-associated virus serotype 2 (AAV2). We compared the efficiency of RNAi delivery between injecting the viral vectors into muscle and into nerve, and found that nerve injetion is more efficient in delivering RNAi to motor neurons. Based on this data, we conducted therapeutic trials in the mouse model and found that nerve injection of RAd, but not AAV2, at the disease onset had a modest therapeutic efficacy. These results highlight the potential and the challenges in delivering RNAi therapy by gene therapy.
Some factors modifying the expression of human strength (1961)

The maximal pull of forearm flexors was increased and, in some instances, decreased in predictable fashion by a loud noise, by the subject's own outcry, by certain pharmacologic agents (alcohol, adrenaline, and amphetamine), and by hypnosis. Significant average changes ranging from +26.5% to –31% were observed. An analysis of these data and that of others leads us to regard all performances short of the maximum limit, which is always imposed by the structure and prevailing physiologic state of the performing muscles, to be manifestations of acquired inhibitions that in turn are subject to disinhibition by pure Pavlovian procedures, by anesthetization of inhibitory mechanisms, or by pharmacologically induced symptoms serving as stimuli for disinhibition. Submitted on June 20, 1960
Intracellular gold nanoparticles enhance non-invasive radiofrequency thermal destruction of human gastrointestinal cancer cells (2008)

We demonstrate that GNPs 1) have no intrinsic cytotoxicity or anti-proliferative effects in two human cancer cell lines in vitro and 2) GNPs release heat in a focused external RF field. This RF-induced heat release is lethal to cancer cells bearing intracellular GNPs in vitro.
Exciplex emission and Auger process assistant green organic electrophosphorescence devices with very low doped level of iridium complex (2008)

We demonstrate efficient and simple structure phosphorescence organic light-emitting diodes, in which 4, 4', 4''-tris[3-methyl-pheny(phenyl)-amino]triphenyl -amine (m-MTDATA) and 4,7-diphenyl-1,10-phenanthroline (Bphen) are used as hole transport and electron transport layers, respectively, accompanied by 3 wt% fac-tris(2-phenylpyridine) iridium doped in 1,3,5-tris(N-phenylbenzimidazol-2-yl)-benzene (Ir : TPBi) as the emitting layer. As a result, a 29 lm W−1 peak power efficiency and 2.2 V turn-on voltage are achieved, respectively. The achievement of excellent electroluminescence (EL) properties was attributed to the contribution of exciplex formation at the interface of m-MTDATA/Ir : TPBi and the Auger-type two-step process of charge carrier injection. The competition between the interfacial exciplex and Ir-complex emissions in the EL processes was also discussed.
The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens (2006)

We used SEREX technology to identify novel tumour-associated antigens in patients with primary hepatocellular carcinoma and found serological responses to the polycomb group (PcG) protein BMI-1, which is overexpressed in a range of different tumour types. Further studies identified T-cell responses to both BMI-1 and another PcG protein, EZH2, in cancer patients and at relatively lower levels in some normal donors. We next identified several CD8+ T-cell epitopes derived from BMI-1 and EZH2 and demonstrated that EZH2-derived peptides elicited more significant interferon-gamma (IFN-gamma) release than BMI-1-derived peptides. That CD8(+) T cells were responsible for the observed responses was confirmed for EZH2 by both IFN-gamma capture assays and tetramer staining using an HLA-A0201-restricted, EZH2-derived YMSCSFLFNL (aa 666-674) epitope. The ability of YMSCSFLFNL (aa 666-674) to stimulate the in vitro expansion of specific T cells from peripheral blood lymphocytes was greatly enhanced when the CD25(+) T-cell population was depleted. EZH2-specific cytotoxic T lymphocyte clones specific for two HLA-A0201 epitopes were generated and found to recognise endogenously processed EZH2 in both HLA-matched fibroblasts and tumour cell lines. Given the widespread overexpression of PcG proteins in cancer and their critical role in oncogenesis, these data suggest that they may be useful targets for cancer immunotherapy.
Single Molecule Force Spectroscopy on Polysaccharides by Atomic Force Microscopy (1997)

Recent developments in piconewton instrumentation allow the manipulation of single molecules and measurements of intermolecular as well as intramolecular forces. Dextran filaments linked to a gold surface were probed with the atomic force microscope tip by vertical stretching. At low forces the deformation of dextran was found to be dominated by entropic forces and can be described by the Langevin function with a 6 angstrom Kuhn length. At elevated forces the strand elongation was governed by a twist of bond angles. At higher forces the dextran filaments underwent a distinct conformational change. The polymer stiffened and the segment elasticity was dominated by the bending of bond angles. The conformational change was found to be reversible and was corroborated by molecular dynamics calculations.
Free-flow electrophoresis with trapping by a transverse inhomogeneous field. (1991)

We propose an electrophoretic technique combining the use of a series of dielectric traps controlled by an ac electric field and conventional continuous field free-flow electrophoresis. From the theoretical model that we describe, one can expect, for DNA electrophoresis, an improvement of one to two orders of magnitude in the selectivities or experimental durations.
Circulating CD20 and CD52 in patients with non‐Hodgkin's lymphoma or Hodgkin's disease (2003)

The cell surface proteins CD20 and CD52 differ significantly in their structures and are expressed on the majority of B cells. Both circulating CD20 (cCD20) and circulating CD52 (cCD52) have been recently documented in patients with chronic lymphocytic leukaemia. A retrospective study to establish whether cCD20 and/or cCD52 were detectable in patients with lymphoma, and the clinical associations of these soluble antigens if detected, was conducted. cCD20 and cCD52 levels were analysed in a cohort of 65 patients with non-Hodgkin's lymphoma (NHL) and 37 with Hodgkin's disease (HD). Patients with NHL had elevated pretherapy levels of cCD20 and cCD52 compared with normal individuals. Patients with HD had significantly lower than normal pretherapy levels of both cCD20 and cCD52. cCD20 levels were marginally elevated post-therapy in NHL patients while in patients with HD, cCD20 levels remained significantly lower than normal after therapy. Serum cCD52 levels became significantly lower than normal post-therapy in NHL patients, and remained significantly lower than normal in HD patients. No predictive effects were found for pretherapy or post-therapy levels of cCD52 on survival for either cohort of patients. Post-therapy cCD20 levels independently highly correlated with survival in patients with NHL. Prospective evaluation will be required to establish if cCD20 and cCD52 may be used as biomarkers in the diagnosis, prognostic categorization, and monitoring of the clinical course in patients with lymphoma. The clinical significance of circulating antigen in patients receiving monoclonal antibody therapy directed against CD20 and/or CD52 warrants study.
Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS) (2011)

Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients. Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, < 10 mg/L). All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment. Canakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS. ClinicalTrials.gov: NCT00487708
Guanosine diphosphatase is required for protein and sphingolipid glycosylation in the Golgi lumen of Saccharomyces cerevisiae (1993)

Current models for nucleotide sugar use in the Golgi apparatus predict a critical role for the lumenal nucleoside diphosphatase. After transfer of sugars to endogenous macromolecular acceptors, the enzyme converts nucleoside diphosphates to nucleoside monophosphates which in turn exit the Golgi lumen in a coupled antiporter reaction, allowing entry of additional nucleotide sugar from the cytosol. To test this model, we cloned the gene for the S. cerevisiae guanosine diphosphatase and constructed a null mutation. This mutation should reduce the concentrations of GDP-mannose and GMP and increase the concentration of GDP in the Golgi lumen. The alterations should in turn decrease mannosylation of proteins and lipids in this compartment. In fact, we found a partial block in O- and N-glycosylation of proteins such as chitinase and carboxypeptidase Y and underglycosylation of invertase. In addition, mannosylinositolphosphorylceramide levels were drastically reduced.
A liquid crystal microlens obtained with a non-uniform electric field (1989)

Abstract A homogeneously aligned nematic liquid crystal cell with a hole-patterned electrode and with an indium-tin oxide (ITO-) coated counter-electrode has been prepared. A non-uniform electric field can be produced by the asymmetrical electrode structure. The liquid crystal director can be reoriented by applying a voltage across the electrodes, and this produces an axially symmetrical profile of the refractive index. This liquid crystal cell is expected to have a lens effect and so its optical properties have been investigated. The profile of the output light intensity was measured by using a detecting system with an optical fibre. Some relationships between the lens properties, the diameter of the hole and the thickness of the liquid crystal layer have been examined. The liquid crystal cell becomes a convex (converging) lens with a relatively low voltage. A focal length of several millimetres can be obtained by applying voltages of 3-4 V. As the applied voltage increases, the focal length becomes longer, and the cell changes to a concave (diverging) lens when a high voltage is applied (≳ 20 V). These properties are discussed from the viewpoint of the director orientation effects resulting from the non-uniform electric fields in the cell.
Global stabilization of nonlinear systems with uncertain structure (2005)

The global stabilization problem of nonlinear systems with uncertain structure is dealt with. Based on control Lyapunov function (CLF), a sufficient and necessary condition for Lyapunov stabilization is given. From the condition,several simply sufficient conditions for the globally asymptotical stability are deduced. A state feedback control law is designed to globally asymptotically stabilize the equilibrium of the closed system. Last, a simulation shows the effectiveness of the method.
A novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties (1988)

A novel toxin, tentatively named conotoxin GS (CGS), has been isolated from a marine snail, Conus geographus. CGS was found to exist as a single polypeptide chain, consisting of 34 amino acid residues, cross-linked by three disulfide bonds. Its amino acid sequence was shown to be Ala-Cys-Ser-Gly-Arg-Gly-Ser-Arg-Cys-Hyp-Hyp-Gln-Cys-Cys-Met-Gly-Leu-Arg- Cys-Gly - Arg-Gly-Asn-Pro-Gln-Lys-Cys-Ile-Gly-Ala-His-Gla-Asp-Val. In competition experiments, CGS inhibited the bindings of [3H]Lys-tetrodotoxin ([3H]Lys-TTX) and [3H]propionylconotoxin GIIIA to Electrophorus electricus electroplax membranes, with Ki values of 34 nM and 24 nM, respectively. The toxin inhibited the binding of [3H]Lys-TTX (1 nM) to rat skeletal muscle homogenates with an IC50 value of 880 nM but showed very little effect on this binding to the rat brain P2 fraction at 10 microM. These binding studies indicate that CGS belongs to the same group of Na channel inhibitors as TTX, STX (saxitoxin), and mu-conotoxins. Although CGS, like the mu-conotoxins, is a pharmacological probe for distinguishing between neuronal and muscle Na channel subtypes, the homology in the sequences of CGS and mu-conotoxins is very limited.
Efficient Targeted Next Generation Sequencing-Based Workflow for Differential Diagnosis of Alport-Related Disorders (2016)

Alport syndrome (AS) is an inherited type IV collagen nephropathies characterized by microscopic hematuria during early childhood, the development of proteinuria and progression to end-stage renal disease. Since choosing the right therapy, even before the onset of proteinuria, can delay the onset of end-stage renal failure and improve life expectancy, the earliest possible differential diagnosis is desired. Practically, this means the identification of mutation(s) in COL4A3-A4-A5 genes. We used an efficient, next generation sequencing based workflow for simultaneous analysis of all three COL4A genes in three individuals and fourteen families involved by AS or showing different level of Alport-related symptoms. We successfully identified mutations in all investigated cases, including 14 unpublished mutations in our Hungarian cohort. We present an easy to use unified clinical/diagnostic terminology and workflow not only for X-linked but for autosomal AS, but also for Alport-related diseases. In families where a diagnosis has been established by molecular genetic analysis, the renal biopsy may be rendered unnecessary.
Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle. (1980)

We used high-resolution two-dimensional electrophoresis to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.
Molecular mechanisms of erythrophagocytosis: Flow cytometric quantitation of in vitro erythrocyte phagocytosis by macrophages (1997)

A rapid, sensitive, and reproducible flow cytofluorimetric procedure is described for quantitation of erythrophagocytosis based on the use of red blood cells (RBCs) labeled with the fluorescent probe PKH-26. The procedure involves the following steps: i) incubation of PKH-26-labeled erythrocytes with macrophages, ii) removal of un-bound red blood cells, iii) lysis of membrane-bound RBCs, and iv) measurement of extent of phagocytosis by direct flow-cytometric analysis of intact macrophages. Each step was controlled by fluorescence microscopy. Use of fluorescent, instead of radio-labeled RBCs, makes the method more sensitive, rapid, and avoids radioactive hazards. Furthermore, this approach is multi-parametric and can distinguish different populations of macrophages with reference to their erythrophagocytic potential. This technology moreover, has broad applications from the initial step of contact (between effector and target cells to study the specific receptor mediated attachment) to the subsequent cascade of time-dependent changes resulting from that signal transduction.
Heat Resistance of Bacillus spp. Spores Isolated from Cow's Milk and Farm Environment (2001)

The aim of this study was to compare heat resistance of the spores of mesophile Bacillus spp. from raw milk (bulk tank milk and milk from individual cows) and farm environment (faeces, silage, litter, swabs from skin and udder) as related to their survival in heat-treated dairy products. Fifty-eight strains of 9 species of Bacillus were tested for termoresistance within the temperature range of 95 -135 C and various exposure times. The highest termoresistance was found in B. licheniformis spores, which survived the temperature of 135 C. Except for the spores B. coagulans and B. pumilus all remaining spores were able to germinate after heat treatment of up to 120 C. The greatest reduction of the spore numbers was found in B. cereus. The results indicate that some Bacillus spores may survive in milk even after heat treatment.
Synthesis, Oral Bioavailability and in vivo Activity of Acetal Derivatives of the Selective Antiherpesvirus Agent 9-(3-hydroxypropoxy) Guanine (BRL 44385) (1994)

Acyclic acetal derivatives of the selective antiherpesvirus agent 9-(3-hydroxypropoxy) guanine (BRL44385) and of its 2-aminopurine congener (BRL46720) have been prepared and evaluated in mice for oral delivery of BRL 44385. Guanine derivatives (6 a-c) were prepared via Mitsunobu condensation of an alcohol with a 9-hydroxy-6-methoxypurine (Harnden and Wyatt, 1990). Synthesis of derivatives of 2-aminopurine (10 a-d) was achieved by hydrogenolysis of 9-alkoxy-6-chloropurines, which were obtained either by reaction of an alkoxyamine with 4,6-dichloro-2,5-diformamidopyrimidine and subsequent ring closure or by Mitsunobu condensation of an alcohol with a 6-chloro-9-hydroxypurine. Following oral administration, 2-amino-9-[3-(iso-propoxymethyl)propoxy]-purine (10b, BRL 55792) was very well absorbed and provided high and prolonged concentrations of BRL44385 in the blood. In a cutaneous HSV-1 infection in the ear pinna of mice, orally dosed BRL 55792 was at least 3-fold more potent than both BRL44385 and Acyclovir in reduction of lesion severity.
[Double-blind comparison between amitriptyline Diffucaps and ordinary amitriptyline in sleep disorders of depressive origin]. (1975)

Within the conditions of the double-blind trial, it appears that long-acting amitriptyline (Diffucaps), given at the dosage of 25 mg at the evening meal, is more active and better tolerated than a dosage of 40 mg of ordinary amitriptyline at bedtime in depressive sleep disorders.
Prospects in Plant Genetic Engineering (1983)

The functional expression of a novel gene in a genetically engineered plant has not yet been reported. One major barrier in movement toward this goal is our limited understanding of the molecular bases of gene expression. Attempts to establish genetic engineering as a practical facet of plant breeding are also complicated by the fact that genes for most important plant characteristics have not yet been identified. However, the benefits to be gained from all aspects of plant improvement are stimulating research into both the development of plant transformation technology and the isolation and characterization of genes responsible for valuable traits. As scientists develop greater knowledge of plant molecular genetics, we can expect to see practical applications in such diverse areas as improvement of plant nutritional quality, decreases in fertilization requirements, and increases in resistance to environmental stresses and pathogens.
Halide-Induced Supramolecular Ligand Rearrangement (2004)

A novel reaction involving the halide-induced rearrangement of ligands within supramolecular Rh(I) complexes containing hemilabile ligands is presented. Three analogous bis- and trishemilabile ligands have been synthesized to construct bi- and trimetallic Rh(I) macrocyclic complexes. An intentionally added halide source results in the formal rotation of only one hemilabile ligand along the axis that is perpendicular to the plane defined by the aryl backbone of the hemilabile ligands. X-ray structures, as determined by X-ray crystallography, of key intermediates and products are presented.