gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Transfection Biology of Novel Cationic Glycolipids for Use in Liposomal Gene Delivery (2001)

The molecular structure of the cationic lipids used in gene transfection strongly influences their transfection efficiency. High transfection efficiencies of non-glycerol-based simple monocationic transfection lipids with hydroxyethyl headgroups recently reported by us (Banerjee et al. J. Med. Chem. 1999, 42, 4292-4299) are consistent with the earlier observations that the presence of hydroxyl functionalities in the headgroup region of a cationic lipid contributes favorably in liposomal gene delivery. Using simple sugar molecules as the source of multiple hydroxyl functionalities in the headgroup region of the transfection lipids, we have synthesized four novel simple monocationic transfection lipids, namely, 1-deoxy-1-[dihexadecyl(methyl)ammonio]-D-xylitol (1), 1-deoxy-1-[methyl(ditetradecyl)ammonio]-D-arabinitol (2), 1-deoxy-1-[dihexadecyl(methyl)ammonio]-D-arabinitol (3) and 1-deoxy-1-[methyl(dioctadecyl)ammonio]-D-arabinitol (4), containing hydrophobic aliphatic tails and the hydrophilic arabinosyl or xylose sugar groups linked directly to the positively charged nitrogen atom. Syntheses, chemical characterizations, and the transfection biology of these novel transfection lipids 1-4 are described in this paper. Lipid 1, the xylosyl derivative, showed maximum transfection on COS-1 cells. All the lipids showed transfection with cholesterol as colipid and not with dioleoylphosphatidylethanolamine (DOPE). Radioactive quantitation of free and complexed DNA combined with ethidium bromide exclusion measurements suggest that though nearly 70% of the DNA exists as complexed DNA, the DNA may not have condensed as was observed with other cationic lipids. Presence of additional (more than two) hydroxyl functionalities in the headgroup of the cationic lipids appears to have improved the transfection efficiency and made these lipids less cytotoxic compared to two-hydroxyl derivatives.
Particulate Matter in Injectable Drug Products (2013)

Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations. <h3>Educational aims</h3> To understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation. To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey. To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children. To discuss when to treat PAP with whole-lung lavage and/or granulocyte–macrophage colony-stimulating factor, and review potential promising new therapies.
Development of rAAV2-CFTR: History of the First rAAV Vector Product to be Used in Humans (2016)

The first human gene therapy trials using recombinant adeno-associated virus (rAAV) vectors were performed in cystic fibrosis (CF) patients. Over 100 CF patients were enrolled in 5 separate trials of rAAV2-CFTR administration via nasal, endobronchial, maxillary sinus, and aerosol delivery. Recombinant AAV vectors were designed to deliver the CF transmembrane regulator (CFTR) gene and correct the basic CFTR defect by restoring chloride transport and reverting the upregulation of proinflammatory cytokines. However, vector DNA expression was limited in duration because of the low incidence of integration and natural airway epithelium turnover. In addition, repeated administration of AAV-CFTR vector resulted in a humoral immune response that prevented effective gene transfer from subsequent doses of vector. AAV serotype 2 was used in human trials before the comparison with other serotypes and determination that serotypes 1 and 5 not only possess higher tropism for the airway epithelium, but also are capable of bypassing the binding and trafficking processes-both were important hindrances to the effectiveness of rAAV2. Although rAAV-CFTR gene therapy does not appear likely to supplant newer small-molecule CFTR modulators in the near future, early work with rAAV-CFTR provided an important foundation for later use of rAAV in humans.
The OAuth 2.0 Internet of Things (IoT) Client Credentials Grant (2015)

As Internet of Things (IoT) deployments increase steadily the need for
a better user experience for handling the authentication and
authorization tasks in constrained environments increases. While
several technologies have been developed already that allow federated
access to protected resource the nature of IoT deployments requires
care with the limited resources available on many of these devices.
This document defines a new OAuth 2.0 authorization grant for the
interaction between constrained clients and resource servers to obtain
access tokens for access to protected resources. It does so by
leveraging prior work on OAuth 2.0, CoAP, and DTLS.
Modified Listeria bacteriophage lysin genes (ply) allow efficient overexpression and one-step purification of biochemically active fusion proteins (1996)

Listeria bacteriophage lytic enzymes are useful for in vitro applications such as rapid, gentle cell disruption, and they provide new approaches as selective antimicrobial agents for destruction of Listeria monocytogenes in contaminated foods. We describe here the amino-terminal modification of three cloned Listeria phage lysin genes (ply), resulting in fusion proteins with a 12-amino-acid leader containing six consecutive histidine residues. The recombinant enzymes retain their native specific activity and can be efficiently overproduced in Escherichia coli. By one-step metal chelate affinity chromatography, active lysins could be purified to more than 90% homogeneity.
Changes in chemical composition of tobacco lamina during senescence and curing. 1. Plastid pigments (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChanges in chemical composition of tobacco lamina during senescence and curing. 1. Plastid pigmentsHarold R. Burton and M. J. KasperbauerCite this: J. Agric. Food Chem. 1985, 33, 5, 879–883Publication Date (Print):September 1, 1985Publication History Published online1 May 2002Published inissue 1 September 1985https://pubs.acs.org/doi/10.1021/jf00065a028https://doi.org/10.1021/jf00065a028research-articleACS PublicationsRequest reuse permissionsArticle Views97Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Analysis of Tumor Growth Curves2 (1968)

Journal Article Analysis of Tumor Growth Curves Get access Lyle A. Dethlefsen, Lyle A. Dethlefsen Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. S. Prewitt, J. M. S. Prewitt Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. L. Mendelsohn M. L. Mendelsohn Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 40, Issue 2, February 1968, Pages 389–405, https://doi.org/10.1093/jnci/40.2.389 Published: 01 February 1968 Article history Received: 17 July 1967 Accepted: 06 September 1967 Published: 01 February 1968
A minimal gene set for cellular life derived by comparison of complete bacterial genomes. (1996)

The recently sequenced genome of the parasitic bacterium Mycoplasma genitalium contains only 468 identified protein-coding genes that have been dubbed a minimal gene complement [Fraser, C.M., Gocayne, J.D., White, O., Adams, M.D., Clayton, R.A., et al. (1995) Science 270, 397-403]. Although the M. genitalium gene complement is indeed the smallest among known cellular life forms, there is no evidence that it is the minimal self-sufficient gene set. To derive such a set, we compared the 468 predicted M. genitalium protein sequences with the 1703 protein sequences encoded by the other completely sequenced small bacterial genome, that of Haemophilus influenzae. M. genitalium and H. influenzae belong to two ancient bacterial lineages, i.e., Gram-positive and Gram-negative bacteria, respectively. Therefore, the genes that are conserved in these two bacteria are almost certainly essential for cellular function. It is this category of genes that is most likely to approximate the minimal gene set. We found that 240 M. genitalium genes have orthologs among the genes of H. influenzae. This collection of genes falls short of comprising the minimal set as some enzymes responsible for intermediate steps in essential pathways are missing. The apparent reason for this is the phenomenon that we call nonorthologous gene displacement when the same function is fulfilled by nonorthologous proteins in two organisms. We identified 22 nonorthologous displacements and supplemented the set of orthologs with the respective M. genitalium genes. After examining the resulting list of 262 genes for possible functional redundancy and for the presence of apparently parasite-specific genes, 6 genes were removed. We suggest that the remaining 256 genes are close to the minimal gene set that is necessary and sufficient to sustain the existence of a modern-type cell. Most of the proteins encoded by the genes from the minimal set have eukaryotic or archaeal homologs but seven key proteins of DNA replication do not. We speculate that the last common ancestor of the three primary kingdoms had an RNA genome. Possibilities are explored to further reduce the minimal set to model a primitive cell that might have existed at a very early stage of life evolution.
Simple in-line method to measure the dispersion of an optical system (1993)

We describe a simple in-line method to measure the dispersion of an optical system. The light beam passing through the optical system interferes with a reference beam in a spectrometer, and the resulting spectrum yields the quadratic and cubic dispersion terms of the system. We demonstrate this technique on an optical system made of grating pairs.
Nanostructures and porous silicon: activity at interfaces in sensors and photocatalytic reactors (2007)

Abstract Nanopore covered microporous porous silicon (PS) interfaces have been formed to provide an active scaffolding for the creation of sensor and microreactor configurations. Rapidly responding (≤2s), reversible, and sensitive (≤2 ppm), PS gas sensors, operating at room temperature, and based on a uniquely formed highly efficient electrical contract to the nanopore covered microporous array, are modified by introducing active nanoparticles to establish gas selectivity. In a complementary manner, active sites can be introduced for the purpose of forming a nanostructure based microreactor. Pulsing techniques and FFT analysis allow the gas response of the sensors to be measured, without saturation, and filtered on a drifting baseline to eliminate false positives and the effects of external noise. TiO 2– x N x visible light absorbing photocatalysts are introduced to quartz surfaces and to the PS structure for the purpose of creating a microreactor and subsequently to form the preconditioner for a solar pumped sensor. (© 2007 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Metabolic and health complications of obesity. (1990)

Overnutrition manifested by obesity has emerged as a major health problem in affluent countries. In spite of increased interest in fitness, obesity is on the increase in the United States. This is particularly so among children and adolescents. Although obesity is associated with many risk factors for diseases, the mechanisms whereby it enhances disease risk are not fully understood. Such an understanding is needed to develop strategies for management of these conditions. In this report we suggest that overnutrition produces clinical diseases only in individuals who already possess a metabolic weakness or "defect" in a given system. In the absence of such underlying defects, overnutrition, or obesity, is well tolerated. One of the most common consequences of obesity is dyslipidemia, that is, elevations of very low-density lipoprotein (VLDL) triglycerides and low-density lipoprotein (LDL) cholesterol and low concentrations of high-density lipoprotein (HDL) cholesterol. The major effect of overnutrition on lipoprotein metabolism is to stimulate the production of VLDL. For patients who have an underlying defect in lypolysis of VLDL triglycerides, hypertriglyceridemia will develop in the obese state. For those who have defective clearance of LDL, obesity will accentuate hypercholesterolemia. Both of these effects can be explained by overproduction of VLDL, due to obesity, combined with a genetic defect in clearance of VLDL or LDL. The mechanism whereby obesity causes a lowering of HDL cholesterol is uncertain, although it could enhance removal of HDL by an excess of adipose tissue. Another disease associated with obesity is cholesterol gallstones. The presence of obesity more than doubles the risk for gallstones. Two underlying factors increase the danger for gallstones: a deficiency of hepatic secretion of bile acids and a tendency for formation of cholesterol crystals in bile. Overnutrition promotes the synthesis of whole-body cholesterol, and the only route for excretion of this excess cholesterol is through the biliary tree.(ABSTRACT TRUNCATED AT 400 WORDS)
Th1 and Th2 responses regulate experimental lung granuloma development. (1996)

The pathogenesis of chronic interstitial lung disease is often characterized as an intense inflammatory response with accompanying fibroproliferation and deposition of extracellular matrix. Certain of these lung disorders share common characteristics, including an unknown etiology, ill defined mechanisms of initiation and maintenance, and end-stage fibrosis. Progressive pulmonary inflammation, as can occur in diseases such as idiopathic pulmonary fibrosis and end-stage sarcoidosis, is associated with substantial morbidity and mortality. Unfortunately, efficacious therapeutic options are not available for the treatment of these diseases, reflecting the limited scientific understanding of these disorders. However, it is likely that cytokine networks are operative in dictating the progression of these diseases. Recent studies show that various cytokines affect fibroblast activation, proliferation, and collagen deposition during the evolution of chronic fibrotic lung disease. In particular, gamma interferon suppresses such fibroblast activities as proliferation and collagen production, while interleukin-4 augments fibroblast growth and collagen production. Interestingly, these two mediators are the prototypic cytokines which functionally define either a Th1 or a Th2 response. Thus, experimental models of granulomatous lung inflammation, which are characterized by either a Th1 or a Th2 response, will be useful in delineating the mechanisms which maintain and resolve chronic granulomatous lung inflammation. These experimental systems will prove to be especially important as the degree of inflammation and fibroblast activation/proliferation during the pathogenesis of chronic pulmonary inflammation may be dependent upon a balance of Th1- and Th2-like cytokines which are expressed during the evolution of the disease.
Effect of stator chording and rotor skewing on performance of reluctance synchronous machine (2002)

Low torque ripple in electrical machines is generally required to reduce acoustic noise and mechanical resonance vibration. To design for low torque ripple, however, affects the average torque and the power rating of the machine. In this paper, the effect of stator winding chording and rotor skewing on the average torque, power factor, and torque ripple of the normal laminated, internal flux barrier rotor reluctance synchronous machine is investigated. The two-dimensional finite-element time-step method together with the basic machine equations are used in the analysis. It is shown that to design, in general, for low torque ripple and minimal effect on torque rating of the reluctance synchronous machine, full-pitch stator windings must be used, the rotor must be skewed by a stator slot pitch, and a low number of stator slots must be avoided.
Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways (2008)

T cell activation potently stimulates cellular metabolism to support the elevated energetic and biosynthetic demands of growth, proliferation, and effector function. We show that glucose uptake is limiting in T cell activation and that CD28 costimulation is required to allow maximal glucose uptake following TCR stimulation by up-regulating expression and promoting the cell surface trafficking of the glucose transporter Glut1. Regulation of T cell glucose uptake and Glut1 was critical, as low glucose prevented appropriate T cell responses. Additionally, transgenic expression of Glut1 augmented T cell activation, and led to accumulation of readily activated memory-phenotype T cells with signs of autoimmunity in aged mice. To further examine the regulation of glucose uptake, we analyzed CD28 activation of Akt, which appeared necessary for maximal glucose uptake of stimulated cells and which we have shown can promote Glut1 cell surface trafficking. Consistent with a role for Akt in Glut1 trafficking, transgenic expression of constitutively active myristoylated Akt increased glucose uptake of resting T cells, but did not alter Glut1 protein levels. Therefore, CD28 appeared to promote Akt-independent up-regulation of Glut1 and Akt-dependent Glut1 cell surface trafficking. In support of this model, coexpression of Glut1 and myristoylated Akt transgenes resulted in a synergistic increase in glucose uptake and accumulation of activated T cells in vivo that were largely independent of CD28. Induction of Glut1 protein and Akt regulation of Glut1 trafficking are therefore separable functions of CD28 costimulation that cooperate to promote glucose metabolism for T cell activation and proliferation.
Adsorption Kinetics of an Engineered Gold Binding Peptide by Surface Plasmon Resonance Spectroscopy and a Quartz Crystal Microbalance (2006)

The adsorption kinetics of an engineered gold binding peptide on gold surface was studied by using both quartz crystal microbalance (QCM) and surface plasmon resonance (SPR) spectroscopy systems. The gold binding peptide was originally selected as a 14-amino acid sequence by cell surface display and then engineered to have a 3-repeat form (3R-GBP1) with improved binding characteristics. Both sets of adsorption data for 3R-GBP1 were fit to Langmuir models to extract kinetics and thermodynamics parameters. In SPR, the adsorption onto the surface shows a biexponential behavior and this is explained as the effect of bimodal surface topology of the polycrystalline gold substrate on 3R-GBP1 binding. Depending on the concentration of the peptide, a preferential adsorption on the surface takes place with different energy levels. The kinetic parameters (e.g., K(eq) approximately 10(7) M(-1)) and the binding energy (approximately -8.0 kcal/mol) are comparable to synthetic-based self-assembled monolayers. The results demonstrate the potential utilization of genetically engineered inorganic surface-specific peptides as molecular substrates due to their binding specificity, stability, and functionality in an aqueous-based environment.
Add-back therapy use and its impact on LA persistence in patients with endometriosis (2010)

Among women using LA therapy for endometriosis, only 32% used any type of ABT, and these patients had significantly higher persistence and compliance with LA therapy compared to no ABT user group.
Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian subjects and in patients with falciparum malaria (1998)

Intravenous quinine pharmacokinetics in healthy Caucasians were similar to those reported for Nigerian or Thai subjects. At effective doses quinine causes considerable but reversible cochlear hearing losses in both healthy persons and in patients. Our findings do support the need for a loading dose. The fact that in malaria patients there was no correlation between body weight and quinine VD as calculated during the elimination phase renders questionable the usefulness of dosing quinine according to body weight.
In Situ Electrooxidation of Photobiological Hydrogen in a Photobioelectrochemical Fuel Cell Based on Rhodobacter sphaeroides (2005)

In this paper, we present a photobiological fuel cell that utilizes the metabolic activity of living cells of Rhodobacter sphaeroides for the generation of electricity based on the in situ oxidation of photobiological hydrogen. Organic acids and alcohols contained in synthetic media as well as in fermented media of Escherichia coli K 12 served as the proton donor source for the photobiological hydrogen production by R. sphaeroides. We demonstrate thatthe photobiological hydrogen is efficiently oxidized in the microbial medium at electrocatalytic electrodes coated with a platinum-poly(3,4-ethylenedioxythiophene) (Pt-PEDOT) bilayer composite. The experimental results are discussed in terms of current and power output, substrate, and solar conversion efficiency.