gebhart/patrepeval huggingface dataset:
Quantitative Measurement of Immunoglobulins and Free Light Chains Using Mass Spectrometry (2015)

Serum free light chain (sFLC) assays are well established in the diagnosis and monitoring of plasma cell disorders. However, current FLC immunoassays are subject to several analytical issues, which results in a lack of harmonized results. To facilitate sFLC standardization, we investigated the strengths and limitations of mass spectrometry as a novel technological platform for sFLC quantification. Stable isotope labeled reference peptides are added to serum samples for quantitation by selected reaction monitoring (SRM). The use of redundant peptide sets allows for quality control measures during data analysis. Measurements on serum provide information on intact immunoglobulins, but depletion of these intact molecules from the sera during sample processing permits the quantitation of sFLC. sFLC concentrations measured with SRM were comparable to those obtained by nephelometry and showed excellent linearity (r(2) > 0.99). In samples with high levels of sFLC, SRM data was more consistent with serum protein electrophoresis than nephelometric data and SRM is unaffected by antigen excess. The lower limits of quantitation were 3.8 and 2.7 mg/L for κ and λ sFLC. Errors due to polymorphic sequences were prevented by comparison of redundant peptide pairs. The application of stable isotope labeling combined with SRM can overcome many of the current potential analytical issues of sFLC analysis. We describe which hurdles still need to be taken to make SRM a robust and more accurate method for sFLC measurements.
The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol (2013)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C) concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.
Enrichment and analysis of RNA centered on ion pair reverse phase methodology (2006)

Here we describe a procedure for the rapid enrichment of RNA from cell extracts and the subsequent fractionation and analysis of the "small RNA" population by ion pair reverse phase chromatography. Solid phase extraction procedures have been developed utilizing nonporous alkylated poly(styrene-divinylbenzene) particles in conjunction with ion pair reagents to enrich total RNA. This approach facilitates the selective enrichment and separation of the relatively lower abundance small RNAs, from the more abundant higher molecular weight rRNA species. We also describe the application of monolithic capillaries in conjunction with ion pair reverse phase chromatography to bring increased sensitivity in the analysis of very low abundance RNAs. These approaches will simplify the biochemical analysis of this class of molecules, which are emerging as important regulators of global gene expression in higher organisms.
Induction of growth in kidney epithelial cells in culture by Na+. (1980)

The role of Na+ in the regulation of cell growth was examined in quiescent, high-density cultures of kidney epithelial cells of the BSC-1 line. The addition of NaCl to the medium increased the number of cells initiating DNA synthesis in a concentration-dependent manner after serum stimulation. In the presence of added NaCl, cells in confluent cultures grew to high density at an increased rate, whereas growth in sparse cultures was retarded. These results suggest that, in the presence of serum, Na+ can act as a mediator of the events that initiate cell proliferation.
An open study to determine the efficacy of blue light in the treatment of mild to moderate acne (2005)

Eight 10- or 20-minute treatments over 4 weeks with a narrowband blue light was found to be effective in reducing the number of inflamed lesions in subjects with mild to moderate acne. The treatment had little effect on the number of comedones. The onset of the effect was observable at the first assessment, at week 5, and maximal between weeks 8 and 12. Blue light phototherapy using a narrowband LED light source appears to be a safe and effective additional therapy for mild to moderate acne.
Regulation of the Catalytic Function of Coagulation Factor VIIa by a Conformational Linkage of Surface Residue Glu 154 to the Active Site (1999)

Coagulation factor VIIa is an allosterically regulated trypsin-like serine protease that initiates the coagulation pathways upon complex formation with its cellular receptor and cofactor tissue factor (TF). The analysis of a conformation-sensitive monoclonal antibody directed to the macromolecular substrate exosite in the VIIa protease domain demonstrated a conformational link from this exosite to the catalytic cleft that is independent of cofactor-induced allosteric changes. In this study, we identify Glu 154 as a critical surface-exposed exosite residue side chain that undergoes conformational changes upon active site inhibitor binding. The Glu 154 side chain is important for hydrolysis of scissile bond mimicking peptidyl p-nitroanilide substrates, and for inhibition of VIIa's amidolytic function upon antibody binding. This exosite residue is not linked to the catalytic cleft residue Lys 192 which plays an important role in thrombin's allosteric coupling to exosite I. Allosteric linkages between VIIa's active site and the cofactor binding site or between the cofactor binding site and the macromolecular substrate exosite were not influenced by mutation of Glu 154. Glu 154 thus only influences the linkage of the macromolecular substrate binding exosite to the catalytic center. These data provide novel evidence that allosteric regulation of VIIa's catalytic function involves discrete and independent conformational linkages and that allosteric transitions in the VIIa protease domain are not globally coupled.
An Evaluation of Receptor‐Mediated Gene Transfer Using Synthetic DNA‐Ligand Complexes (1994)

Receptor-mediated gene transfer is an attractive method for therapeutically correcting human genetic diseases since it permits the targeting of DNA to cellular receptors in specific tissues of adult animals. Genes introduced by this technique have been shown to be expressed in the target tissue for varying periods. However, to be useful for gene therapy, it is critical that both the chemical properties and physical interactions of the reagents involved in the design of the DNA delivery vehicle be rigorously characterized. In this review, we discuss the critical steps in the preparation of the DNA-ligand complex and the factors involved in the delivery and regulated expression of a transgene in animal tissues. The feasibility of using this technique for the therapeutic delivery of genes to mammalian tissues will also be evaluated.
Exploiting microbial hyperthermophilicity to produce an industrial chemical, using hydrogen and carbon dioxide (2013)

Microorganisms can be engineered to produce useful products, including chemicals and fuels from sugars derived from renewable feedstocks, such as plant biomass. An alternative method is to use low potential reducing power from nonbiomass sources, such as hydrogen gas or electricity, to reduce carbon dioxide directly into products. This approach circumvents the overall low efficiency of photosynthesis and the production of sugar intermediates. Although significant advances have been made in manipulating microorganisms to produce useful products from organic substrates, engineering them to use carbon dioxide and hydrogen gas has not been reported. Herein, we describe a unique temperature-dependent approach that confers on a microorganism (the archaeon Pyrococcus furiosus, which grows optimally on carbohydrates at 100°C) the capacity to use carbon dioxide, a reaction that it does not accomplish naturally. This was achieved by the heterologous expression of five genes of the carbon fixation cycle of the archaeon Metallosphaera sedula, which grows autotrophically at 73°C. The engineered P. furiosus strain is able to use hydrogen gas and incorporate carbon dioxide into 3-hydroxypropionic acid, one of the top 12 industrial chemical building blocks. The reaction can be accomplished by cell-free extracts and by whole cells of the recombinant P. furiosus strain. Moreover, it is carried out some 30°C below the optimal growth temperature of the organism in conditions that support only minimal growth but maintain sufficient metabolic activity to sustain the production of 3-hydroxypropionate. The approach described here can be expanded to produce important organic chemicals, all through biological activation of carbon dioxide.
A NOVEL AND EFFICIENT SYNTHESIS OF 4-PHENYL-2-CHLOROPYRIMIDINES FROM ACETOPHENONE CYANOIMINES (2002)

ABSTRACT A versatile and efficient 2 step synthesis of 4-phenyl-2-chloropyrimidines is described. The reaction proceeds by treatment of acetophenone cyanoimines under Vilsmeier–Haack conditions to give the target compounds in moderate yields.
Recent Advances in Video Based Document Processing: A Review (2012)

Extraction and recognition of text present in video has become a very popular research area in the last decade. Generally, text present in video frames is of different size, orientation, style, etc. with complex backgrounds, noise, low resolution and contrast. These factors make the automatic text extraction and recognition in video frames a challenging task. A large number of techniques have been proposed by various researchers in the recent past to address the problem. This paper presents a review of various state-of-the-art techniques proposed towards different stages (e.g. detection, localization, extraction, etc.) of text information processing in video frames. Looking at the growing popularity and the recent developments in the processing of text in video frames, this review imparts details of current trends and potential directions for further research activities to assist researchers.
Assembly of Trigonal and Tetragonal Prismatic Cages from Octahedral Metal Ions and a Flexible Molecular Clip (2007)

Reaction of a semirigid ligand with two octahedral metal ions with restricted coordination symmetry afforded metalated container complexes showing trigonal or tetragonal outer shapes and inner cavities.
Physical characterization of microporous poly(2‐hydroxyethyl methacrylate) gels (1981)

Poly(2-hydroxyethyl methacrylate)-(PHEMA) has been prepared by polymerizing in presence of different types of water-soluble additives, at various amounts, which were removed by swelling in water. Mechanical properties of swollen samples have been measured and analyzed by using the classical theory of rubber elasticity. Water permeability measurements were also performed to detect the presence of micropores and to determine the type of water transport. It has been shown that it's possible, using different types and amounts of additives, to obtain a wide range of physical properties of swollen PHEMA as required for various biomedical applications.
BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. (1998)

Combined with local irradiation, BEACOPP in one or both variants shows superior disease control compared with COPP/ABVD, with acceptable acute toxicity. Further follow-up is required to assess the effect of dosage and the effect on survival and late toxicities.
Design, Synthesis, and Application of Peptide Secondary Structure Mimetics (2002)

The secondary structure peptidomimetic approach is a rational way to develop novel nonpeptide pharmaceutical agents based upon biologically significant proteinaceous leads. A part of this approach elaborated in this laboratory over the past ten years is reviewed along with the recent developments in this field.
Analysis of p53-regulated gene expression patterns using oligonucleotide arrays (2000)

Oligonucleotide microarrays were employed to quantitate mRNA levels from a large number of genes regulated by the p53 transcription factor. Responses to DNA damage and to zinc-inducible p53 were compared for their transcription patterns in cell culture. A cluster analysis of these data demonstrates that genes induced by gamma radiation, UV radiation, and the zinc-induced p53 form distinct sets and subsets with a few genes in common to all these treatments. Cell type- or cell line-specific p53 responses were detected. When p53 proteins were induced with zinc, the kinetics of induction or repression of mRNAs from p53-responsive genes fell into eight distinct classes, five different kinetics of induction, and three different kinetics of repression. In addition, low levels of p53 in a cell induced or repressed only a subset of genes observed at higher p53 levels. The results of this study demonstrate that the nature of the p53 response in diverse mRNA species depends on the levels of p53 protein in a cell, the type of inducing agent or event, and the cell type employed. Of 6000 genes examined for p53 regulatory responses, 107 induced and 54 repressed genes fell into categories of apoptosis and growth arrest, cytoskeletal functions, growth factors and their inhibitors, extracellular matrix, and adhesion genes.
Synthesis and Antibacterial Activity of Fluorine-Containing Pyrimidinyl-sulfanilamide Derivatives (1967)

Twenty-one kinds of fluorine-containing pyrimidinylsulfanilamide derivatives, possessing CF3, CH2F, or CF3CH2O group in 2- or 4-position of the pyrimidine ring, were prepared, their pK values were measured, and their in vitro antibacterial activity was tested.
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. (1997)

Fluxes through intrahepatic glucose-producing metabolic pathways were measured in normal humans during overnight or prolonged (60 h) fasting. The glucuronate probe was used to measure the turnover and sources of hepatic UDP-glucose; mass isotopomer distribution analysis from [2-13C1]glycerol for gluconeogenesis and UDP-gluconeogenesis; [U-13C6]glucose for glucose production (GP) and the direct UDP-glucose pathway; and [1-2H1]galactose for UDP-glucose flux and retention in hepatic glycogen. After overnight fasting, GP (fluxes in milligram per kilogram per minute) was 2.19+/-0.09, of which 0.79 (36%) was from gluconeogenesis, 1.40 was from glycogenolysis, 0.30 was retained in glycogen via UDP-gluconeogenesis, and 0.17 entered hepatic UDP-glucose by the direct pathway. Thus, total flux through the gluconeogenic pathway (1.09) represented 54% of extrahepatic glucose disposal (2.02) and the net hepatic glycogen depletion rate was 0.93 (46%). Prolonging [2-13C1]glycerol infusion slowly increased measured fractional gluconeogenesis. In response to prolonged fasting, GP was lower (1. 43+/-0.06) and fractional and absolute gluconeogenesis were higher (78+/-2% and 1.11+/-0.07, respectively). The small but nonzero glycogen input to plasma glucose (0.32+/-0.03) was completely balanced by retained UDP-gluconeogenesis (0.31+/-0.02). Total gluconeogenic pathway flux therefore accounted for 99+/-2% of GP, but with a glycogen cycle interposed. Prolonging isotope infusion to 10 h increased measured fractional gluconeogenesis and UDP-gluconeogenesis to 84-96%, implying replacement of glycogen by gluconeogenic-labeled glucose. Moreover, after glucagon administration, GP (1.65), recovery of [1-2H1]galactose label in plasma glucose (25%) and fractional gluconeogenesis (91%) increased, such that 78% (0.45/0.59) of glycogen released was labeled (i.e., of recent gluconeogenic origin). In conclusion, hepatic gluconeogenic flux into glycogen and glycogen turnover persist during fasting in humans, reconciling inconsistencies in the literature and interposing another locus of control in the normal pathway of GP.
Action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of cAMP-response-element-binding protein (CREB) and p38 mitogen-activated protein (MAP) kinase in U937 monocytic cells (2000)

U937 monocytic cells are shown here to express a range of PDE4, cAMP-specific phosphodiesterase (PDE) isoenzymes: the long isoenzymes, PDE4A4, PDE4D5 and PDE4D3, plus the short isoenzyme, PDE4B2. These isoenzymes provide around 76% of the total cAMP PDE activity of U937 cells. The specific activities of the total PDE4A, PDE4B and PDE4D activities were 0.63±0.09, 8.8±0.2 and 34.4±2.9 pmol/min per mg of protein respectively. The PDE4 selective inhibitor, rolipram, inhibited immunopurified PDE4B and PDE4D activities similarly, with IC50 values of approx. 130 nM and 240 nM respectively. In contrast, rolipram inhibited immunopurified PDE4A activity with a dramatically lower IC50 value of around 3 nM. Rolipram increased phosphorylation of cAMP-response-element-binding protein (CREB) in U937 cells in a dose-dependent fashion, which implied the presence of both high affinity (IC50 value approx. 1 nM) and low affinity (IC50 value approx. 120 nM) components. Rolipram dose-dependently inhibited the interferon-γ (IFN-γ)-stimulated phosphorylation of p38 mitogen-activated protein (MAP) kinase in a simple monotonic fashion with an IC50 value of approx. 290 nM. On this basis, it is suggested that rolipram inhibition of PDE4A4 is involved in regulating CREB phosphorylation but not IFN-γ-stimulated p38 MAP kinase phosphorylation. PDE4A4 was also selectively activated by challenge of U937 cells with either bacterial lipopolysaccharide (LPS) or IFN-γ through a process which was attenuated by both wortmannin and rapamycin. It is proposed that the PDE4A4 isoform is involved in compartmentalized cAMP signalling responses in U937 monocytes.
L‐N‐Acetyl‐Cysteine Protection Against Cisplatin‐Induced Auditory Neuronal and Hair Cell Toxicity (2001)

Our in vitro studies have demonstrated that L-NAC protected both auditory neurons and hair cells from the toxic effects of cisplatin. Because it protects both of these inner ear structures, L-NAC may be potentially useful in protecting hearing, in general, from cisplatin-induced damage. In addition, L-NAC has low systemic and mucosal toxicity. It also has a low molecular weight that may allow it to readily cross the round window membrane. All these characteristics make it potentially suitable for transtympanic application for the prevention of the ototoxicity of cisplatin in vivo.
Direct Nanoimprinting of Metal Nanoparticles for Nanoscale Electronics Fabrication (2007)

One-step direct nanoimprinting of metal nanoparticles was investigated to fabricate nano-/microscale metallic structures such as nanodot and nanowire arrays. This was done at low temperatures and pressures, utilizing the low melting temperature and viscosity of metal nanoparticle solutions. Through precise control of the fluidic properties of the nanoparticle solution and the mold design, high-quality nanoscale features with no or negligible residual layer were nanoimprinted. Nanoscale electronic devices were also demonstrated, including nanowire resistors and nanochannel organic field effect transistors with an air-stable semiconducting polymer.
Systemic Toxicity of Diphtheria Toxin-Related Fragments (CRM26, CRM45), a Hormone-Toxin Hybrid Protein (TRH-CRM45), and Ricin A (1986)

As a preliminary step in evaluating the use of thyrotropin releasing hormone (TRH) linked to toxin fragments for systemic treatment of pituitary disease, we have examined the metabolic degradation, tissue distribution, renal excretion, and toxicity in rats of TRH-CRM45 which consists of TRH coupled to CRM45, a diphtheria toxin-related polypeptide. For comparison, we have similarly studied CRM45, CRM26 (a smaller diphtheria toxin-related fragment), and ricin A. All four proteins were found to concentrate in the kidney and liver relative to blood (in comparison to bovine serum albumin), tissue:plasma ratios for the kidney being much higher than those observed for the liver. Radioiodinated CRM45 and ricin A were rapidly cleared from the circulation with similar patterns. Systemic toxicity studies showed that at doses greater than 2 micrograms/100 g body wt (bw), CRM45 caused a decrease in growth rate and caused renal damage. CRM45 modified with 2-pyridyldithio(propionate) groups as well as TRH-CRM45 was significantly less toxic than CRM45, as was TRH-CRM45. CRM26 had no discernible effect on the growth rate of the animals. Ricin A, at a dose of 50 micrograms/100 g bw slowed the growth rate of rats, but specific liver or kidney damage could not be detected. These findings define an upper range of doses for possible therapeutic use.
Pig Embryonic Pancreatic Tissue as a Source for Transplantation in Diabetes (2009)

This novel protocol, comprising agents that simulate those approved for clinical use, offer an attractive approach for embryonic xenogeneic transplantation. Further studies in nonhuman primates are warranted.
Polymeric triple-shape materials (2006)

Shape-memory polymers represent a promising class of materials that can move from one shape to another in response to a stimulus such as heat. Thus far, these systems are dual-shape materials. Here, we report a triple-shape polymer able to change from a first shape (A) to a second shape (B) and from there to a third shape (C). Shapes B and C are recalled by subsequent temperature increases. Whereas shapes A and B are fixed by physical cross-links, shape C is defined by covalent cross-links established during network formation. The triple-shape effect is a general concept that requires the application of a two-step programming process to suitable polymers and can be realized for various polymer networks whose molecular structure allows formation of at least two separated domains providing pronounced physical cross-links. These domains can act as the switches, which are used in the two-step programming process for temporarily fixing shapes A and B. It is demonstrated that different combinations of shapes A and B for a polymer network in a given shape C can be obtained by adjusting specific parameters of the programming process. Dual-shape materials have already found various applications. However, as later discussed and illustrated by two examples, the ability to induce two shape changes that are not limited to be unidirectional rather than one could potentially offer unique opportunities, such as in medical devices or fasteners.