gebhart/patrepeval huggingface dataset:
Synthesis and Characterization of New Piperazine-Type Inhibitors for Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex I) (2008)

The mode of action of Deltalac-acetogenins, strong inhibitors of bovine heart mitochondrial complex I, is different from that of traditional inhibitors such as rotenone and piericidin A [Murai, M., et al. (2007) Biochemistry 46 , 6409-6416]. As further exploration of these unique inhibitors might provide new insights into the terminal electron transfer step of complex I, we drastically modified the structure of Deltalac-acetogenins and characterized their inhibitory action. In particular, on the basis of structural similarity between the bis-THF and the piperazine rings, we here synthesized a series of piperazine derivatives. Some of the derivatives exhibited very potent inhibition at nanomolar levels. The hydrophobicity of the side chains and their balance were important structural factors for the inhibition, as is the case for the original Deltalac-acetogenins. However, unlike in the case of the original Deltalac-acetogenins, (i) the presence of two hydroxy groups is not crucial for the activity, (ii) the level of superoxide production induced by the piperazines is relatively high, (iii) the inhibitory potency for the reverse electron transfer is remarkably weaker than that for the forward event, and (iv) the piperazines efficiently suppressed the specific binding of a photoaffinity probe of natural-type acetogenins ([ (125)I]TDA) to the ND1 subunit. We therefore conclude that the action mechanism of the piperazine series differs from that of the original Deltalac-acetogenins. The photoaffinity labeling study using a newly synthesized photoreactive piperazine ([ (125)I]AFP) revealed that this compound binds to the 49 kDa subunit and an unidentified subunit, not ND1, with a frequency of approximately 1:3. A variety of traditional complex I inhibitors as well as Deltalac-acetogenins suppressed the specific binding of [ (125)I]AFP to the subunits. The apparent competitive behavior of inhibitors that seem to bind to different sites may be due to structural changes at the binding site, rather than occupying the same site. The meaning of the occurrence of diverse inhibitors exhibiting different mechanisms of action is discussed in light of the functionality of the membrane arm of complex I.
Identification and characterisation of a cytotoxic porin-lipopolysaccharide complex from Campylobacter jejuni (1999)

A clinical isolate of Campylobacter jejuni, previously found to produce a toxin active in cell culture assays, was used for identification and characterisation of a cytotoxic porin-lipopolysaccharide (LPS) complex. This cytotoxic complex was isolated by high-performance liquid chromatography of crude concentrated culture supernate and DEAE-anion exchange chromatography. The complex had a toxic activity of 20.1 tissue culture dose50 (TCD50)/microg of protein for HEp-2 cells, 7.49 TCD50/microg of protein for HeLa cells and 1.87 TCD50/microg of protein for Chinese hamster ovary cells. Analysis by SDS-PAGE revealed a single protein band of 45 kDa and a high mol. wt carbohydrate moiety. The complex gave a positive result in the Limulus amoebocyte lysate test, indicating that the co-purifying carbohydrate was LPS, and had specificity for the lectins Galanthus nivalis agglutinin, Maackia amurensis agglutinin and Datura stramonium agglutinin. The cytotoxic activity associated with the complex was heat-labile at 70 degrees C, resistant to inactivation with trypsin and retained activity after treatment with sodium metaperiodate and the glycosidases neuraminidase and N-glycosidase F. Sequencing of the N-terminus of the protein component of the complex revealed 97% homology with the major outer-membrane porin protein from C. jejuni. The cytotoxic activity of the complex was neutralised by a polyclonal, homologous antiserum, which reacted on Western blot with the 45-kDa protein, but not by polyclonal antisera raised against a number of other bacterial toxins.
[Rule of antibody structure. Primary structure of a human monoclonal IgA-immunoglobulin (myeloma protein Tro). VII. Purification and characterization of the disulfide bridges]. (1979)

Myeloma Protein Tro has been isolated from the plasma of a myeloma patient. Monomeric IgA was separated from its polymer (by chromatography on Sephadex G-200). Both the forms were split with pepsin or cyanogen bromide and, if necessary, with thermolysin and subtilisin. The cystin-containing peptides were isolated from the hydrolysates by chromatography on Sephadex, ion-exchange columns, preparative paper chromatography, thin-layer chromatography, electrophoresis or by a combination of these methods. They were characterized by amino acid analyses and by determination of the N-terminal amino acids using the Dansyl-Edman procedure. Thus all the disulfide bridges of an IgA1 immunoglobulin could be established. The monomer has all together 48 cysteins, seven in each L- and seventeen in each H-chain; all these are covalently bonded by SS-bridges. Free SH-groups were not detected. The J-chain could only be identified serologically in the polymeric form of the protein. It is shown that the subunits of the polymers are covalently attached through either Cysl3, Cysl7 or both these residues of the H-chain.
Evaluation of Protein Solubility as an Indicator of Overprocessing Soybean Meal (1990)

Three experiments were conducted to compare urease activity (UA), orange G-binding capacity (OGBC), and protein solubility (PS) in a potassium-hydroxide solution of soybean meal (SBM) as indicators of overprocessing. In two additional experiments, amino-acid supplementation was employed in an attempt to overcome the growth depression associated with overheating SBM. Subsamples of commercially prepared lots of dehulled SBM were heated for varying periods of time in an autoclave at 121 C. In Experiments 1, 2, and 3, UA dropped to zero (pH change) after approximately 10 min of cooking. The assay was unable to differentiate between meals that were heated for longer periods. The OGBC of SBM was decreased by autoclaving. However, the narrow range of the orange G values that corresponded to degrees of heat treatment indicated that this test may be of limited value in identifying overprocessed SBM. By contrast, PS values decreased with each increase of autoclaving time, and did not approach zero even with 80 min of heating. Adding .2 % lysine either singly or in combination with .2% arginine or. 1% methionine, or both, totally overcame the growth depression due to overprocessing. The weight gains and feed conversions of broiler chicks were negatively correlated with autoclaving times in excess of 10 minutes. In all experiments, PS values more closely reflected the impaired chick performance from overheated SBM than UA or OGBC. The PS values below 70% suggested overprocessed SBM.
NAD+ glycohydrolase, an ecto-enzyme of calf spleen cells (1983)

By using a sensitive fluorimetric assay of NAD+ glycohydrolase (EC 3.2.2.6), we showed that calf spleen cells are able to hydrolyse 1,N6-etheno-NAD+ given in the medium. The observed rates of substrate hydrolysis and product accumulation in the medium are equivalent. Moreover, the splenocytes are able to cleave the nicotinamide-ribose bond of a water-soluble polymer of NAD+, and their NAD+ glycohydrolase activity is fully inhibited by a high-molecular-weight Blue Dextran. Selective permeation of the cellular membrane digitonin revealed an intracellular pool of NAD+ glycohydrolase, which accounts for 25% of the total activity. We conclude that NAD+ glycohydrolase associated with the splenocytes has the characteristics of an ecto-enzyme.
Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis (2011)

The long (2-day) interdialytic interval is a time of heightened risk among patients receiving hemodialysis. (Funded by the National Institutes of Health.).
Results of a prospective, randomized, multicenter study evaluating sacral neuromodulation with InterStim therapy compared to standard medical therapy at 6‐months in subjects with mild symptoms of overactive bladder (2014)

This study demonstrates superior objective and subjective success of SNM compared to SMT. SNM is shown to be a safe and effective treatment for OAB patients with mild to moderate symptoms. Neurourol. Urodynam. 34:224-230, 2015. © 2014 Wiley Periodicals, Inc.
Cell-free synthesis of stable isotope-labeled internal standards for targeted quantitative proteomics (2018)

High-sensitivity mass spectrometry approaches using selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) methods are powerful tools for targeted quantitative proteomics-based investigation of dynamics in specific biological systems. Both high-sensitivity detection of low-abundance proteins and their quantification using this technique employ stable isotope-labeled peptide internal standards. Currently, there are various ways for preparing standards, including chemical peptide synthesis, cellular protein expression, and cell-free protein or peptide synthesis. Cell-free protein synthesis (CFPS) or in vitro translation (IVT) systems in particular provide high-throughput and low-cost preparation methods, and various cell types and reconstituted forms are now commercially available. Herein, we review the use of such systems for precise and reliable protein quantification.
Learning Multiple Relative Attributes With Humans in the Loop (2014)

Semantic attributes have been recognized as a more spontaneous manner to describe and annotate image content. It is widely accepted that image annotation using semantic attributes is a significant improvement to the traditional binary or multiclass annotation due to its naturally continuous and relative properties. Though useful, existing approaches rely on an abundant supervision and high-quality training data, which limit their applicability. Two standard methods to overcome small amounts of guidance and low-quality training data are transfer and active learning. In the context of relative attributes, this would entail learning multiple relative attributes simultaneously and actively querying a human for additional information. This paper addresses the two main limitations in existing work: 1) it actively adds humans to the learning loop so that minimal additional guidance can be given and 2) it learns multiple relative attributes simultaneously and thereby leverages dependence amongst them. In this paper, we formulate a joint active learning to rank framework with pairwise supervision to achieve these two aims, which also has other benefits such as the ability to be kernelized. The proposed framework optimizes over a set of ranking functions (measuring the strength of the presence of attributes) simultaneously and dependently on each other. The proposed pairwise queries take the form of which one of these two pictures is more natural? These queries can be easily answered by humans. Extensive empirical study on real image data sets shows that our proposed method, compared with several state-of-the-art methods, achieves superior retrieval performance while requires significantly less human inputs.
Assessing the utility of 2.5% phenylephrine for diagnostic pupillary dilation (2017)

The addition of phenylephrine eye drops to tropicamide produced larger pupil dilation, but the magnitude of benefit was marginal and clinically insignificant in this young, healthy cohort. A single-dilating-agent regimen using tropicamide could be considered in routine clinical practice.
Insulin formulations--a review. (2002)

Although the improvement on insulin therapy since it was first conceived, it is still far from mimicking physiological secretion of pancreatic b-cells and research to find new insulin formulations and new routes of administration continues. Human biosynthetic insulin (rapid-acting, intermediate-acting and long-acting), produced by recombinant DNA technique, is currently available. The pharmacokinetic profile of rapid-acting insulin (regular) does not adequately reproduce the physiological post-prandial insulin response. This has led to the development of molecular analogues with slight modifications that prevent the spontaneous polymerisation underlying delayed absorption. Fast-acting analogues such as Lyspro and Aspart can be injected immediately before the meal, inducing a very fast and substantial peak of insulin, similar to that produced by b-cells, but have the disadvantage of short duration of action. For this reason, and because of the difficulty of obtaining sufficient basal insulin concentrations to control preprandial blood glucose levels with current long-acting insulins, analogues known as Glargine and Detemir have been synthesized. They have virtually no plasma peak and acts for about 24 h. These characteristics make it ideal to cover basal insulin requirement. With insulin analogues, it also seems possible to overcome the problem of intra- and inter-individual variability in absorption after subcutaneous injection. This variability is directly proportional to the duration of insulin action. Research into new routes of administration has led to production of inhaled insulin powder, soon to become commercially available. Insulin is absorbed through the lung alveoli. Trials to evaluate efficacy and toleration have shown that inhaled insulin has a similar kinetic profile to the fast-acting injected analogue and can therefore be used for mealtime requirement, combined with a single daily injection of long-acting insulin. Oral insulin is currently being studied in type 1 diabetes prevention with promising results.
Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas. (2010)

RPGR may regulate some complexes with NPHP proteins in the mammalian retina. The disruption of these complexes may contribute to the pathogenesis of retinal degeneration in X-linked RP and associated ciliary diseases.
Melanin‐concentrating hormone binding to mouse melanoma cells in vitro (1995)

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 was replaced by Phe and Val19 by Tyr. The resulting monoiodinated [125I] [Phe13,Tyr19]-MCH radioligand was biologically active and led to the discovery of high-affinity binding sites on mouse B16-F1, G4F and G4F-7 melanoma cells. Saturation binding analysis with G4F-7 cells revealed 1090 MCH receptors per cell and a KD of 1.18 x 10(-10) mol/l. Receptors for MCH were also found on rat PC12 phaeochromocytoma cells, human RE melanoma cells and COS-7 cells. Competition binding analyses with other peptides such as alpha-MSH, NPY and PACAP demonstrated that MCH receptor binding is specific. rANF(1-28) was found to be a weak competitor of MCH, indicating topological similarities between MCH and rANF(1-28) when interacting with MCH receptors.
Unraveling the Reactions of Nitric Oxide, Nitrite, and Hemoglobin in Physiology and Therapeutics (2006)

The ability of oxyhemoglobin to inhibit nitric oxide (NO)-dependent activation of soluble guanylate cyclase and vasodilation provided some of the earliest experimental evidence that NO was the endothelium-derived relaxing factor (EDRF). The chemical behavior of this dioxygenation reaction, producing nearly diffusion limited and irreversible NO scavenging, presents a major paradox in vascular biology: The proximity of large amounts of oxyhemoglobin (10 mmol/L) to the endothelium should severely limit paracrine NO diffusion from endothelium to smooth muscle. However, several physical factors are now known to mitigate NO scavenging by red blood cell encapsulated hemoglobin. These include diffusional boundaries around the erythrocyte and a red blood cell free zone along the endothelium in laminar flowing blood, which reduce reaction rates between NO and red cell hemoglobin by 100- to 600-fold. Beyond these mechanisms that reduce NO scavenging by hemoglobin within the red cell, 2 additional mechanisms have been proposed suggesting that NO can be stored in the red blood cell either as nitrite or as an S-nitrosothiol (S-nitroso-hemoglobin). The latter controversial hypothesis contends that NO is stabilized, transported, and delivered by intra-molecular NO group transfers between the heme iron and beta-93 cysteine to form S-nitroso-hemoglobin (SNO-Hb), followed by hypoxia-dependent delivery of the S-nitrosothiol in a process that links regional oxygen deficits with S-nitrosothiol-mediated vasodilation. Although this model has generated a field of research examining the potential endocrine properties of intravascular NO molecules, including S-nitrosothiols, nitrite, and nitrated lipids, a number of mechanistic elements of the theory have been challenged. Recent data from several groups suggest that the nitrite anion (NO2-) may represent the major intravascular NO storage molecule whose transduction to NO is made possible through an allosterically controlled nitrite reductase reaction with the heme moiety of hemoglobin. As subsequently understood, the hypoxic generation of NO from nitrite is likely to prove important in many aspects of physiology, pathophysiology, and therapeutics.
Fatty esters of cellulose from olive pomace and barley bran: Improved mechanical properties by metathesis crosslinking (2006)

Abstract Agricultural wastes such as olive pomace and barley bran have been transformed in plastic by esterification with fatty acid chlorides after acidic or alkaline delignification. These esterifications were carried out in homogenous solution DMA/LiCl by classical heating or microwave activation. The plastics obtained were characterized by IR and NMR spectra, and tested for their mechanical properties and potentiality of biodegradation. The mechanical properties were improved by olefin metathesis of undecylenic ester from olive cellulose. delignification. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 751–755, 2006
Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128 (2014)

MicroRNAs, the non-coding single-stranded RNA of 19-25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases.
Nanoflaky MnO2/carbon nanotube nanocomposites as anode materials for lithium-ion batteries (2010)

Caterpillar-like nanoflaky MnO2/carbon nanotube (CNT) nanocomposites are synthesized via a facile solution method. To build a three-dimensional hierarchy architecture, highly porous interconnected MnO2 nanoflakes are uniformly coated on the surface of the CNTs. As a promising anode material for lithium-ion batteries, the nanoflaky MnO2/CNT nanocomposite electrode exhibits a large reversible capacity of 801 mA h g−1 (∼1000 mA h g−1 can be attributed to the MnO2 porous layer alone) for the first cycle without capacity fade for the first 20 cycles and with a good rate capability. The superior electrochemical performance of the MnO2/CNT nanocomposite electrode compared to the pure MnO2 electrode can be attributed to its unique hierarchy architecture, which is able to provide fast lithium ion and electron transport and to accommodate a large volume change during the conversion reactions.
Resolution enhancement and improved data interpretation in electrostatic force microscopy (2001)

The electrostatic interaction between a model probe and a sample in a scanning probe microscope is analyzed. A simple model for a real experimental setup is proposed and solved by means of an appropriate approximation. In addition, a quantitative definition for resolution is presented. We find that generally the total force between tip and sample is dominated by contributions which are not confined to a nanometer-sized region under the tip apex. From our analysis we conclude that such a confinement is only obtained either with specially designed probes or by using the force gradient as signal source. We show that reliable experimental data acquired by local Kelvin probe microscopy can only be obtained if these considerations are taken into account. Finally, we propose an experimental setup which optimizes resolution and gives the correct local surface potential in the case of Kelvin probe microscopy.
Efficient Interstrand Excess Electron Transfer in PNA:DNA Hybrids (2002)

PNA:DNA strands were prepared containing a flavin electron donor and a thymine dimer acceptor, which gives a strand break upon single electron reduction. With these constructs, it was confirmed that an excess electron transfer through the base stack can be efficient in an interstrand fashion. The effect of an increased distance, a changed sequence, and stacking was explored.
The Molecular Biology of Cyanogenesis (2007)

The cyanogenic polymorphism in Trifolium repens L. (white clover) has been used as the basis of a study of the genetic control of cyanogenesis. The Ac locus controls the presence of two cyanoglucosides in white clover. Biochemical characterization of cyanoglucoside biosynthesis in plants containing different Ac alleles has shown that this is a complex locus which affects more than one step in the pathway. A study of the in vivo synthesis and processing of the cyanogenic beta-glucosidase (linamarase) of white clover led to the isolation of cDNA clones for this enzyme. The cloning strategy and structure of the cDNA clones is described. Together with biochemical and genetic data, these clones have been used to characterize the Li locus which controls linamarase activity in white clover. It has been shown that 'null' alleles of the Li locus result in very reduced levels of transcription of homologous mRNA sequences. The use of these cDNA clones to investigate the genomic organization of cyanogenesis genes in both white clover and other cyanogenic species is described, and their use in structural analysis of the cyanogenic beta-glucosidase is discussed.