gebhart/patrepeval huggingface dataset:
High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease. (1996)

Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. We constructed a plasmid containing a 5'-shortened human acid alpha-glucosidase cDNA driven by the cytomegalovirus promoter, as well as the aminoglycoside phosphotransferase and dihydrofolate reductase genes. Following transfection in dihydrofolate reductase-deficient Chinese hamster ovary cells, selection with Geneticin, and amplification with methotrexate, a cell line producing high levels of the alpha-glucosidase was established. In 48 hr, the cells cultured in Iscove's medium with 5 mM butyrate secreted 110-kDa precursor enzyme that accumulated to 91 micrograms.ml-1 in the medium (activity, > 22.6 mumol.hr-1.ml-1). This enzyme has a pH optimum similar to that of the mature form, but a lower Vmax and Km for 4-methylumbelliferyl-alpha-D-glucoside. It is efficiently taken up by fibroblasts from Pompe patients, restoring normal levels of acid alpha-glucosidase and glycogen. The uptake is blocked by mannose 6-phosphate. Following intravenous injection, high enzyme levels are seen in heart and liver. An efficient production system now exists for recombinant human acid alpha-glucosidase targeted to heart and capable of correcting fibroblasts from patients with Pompe disease.
Transducin Activation by Nanoscale Lipid Bilayers Containing One and Two Rhodopsins (2007)

Nanodiscs are nanometer scale planar membranes of controlled size that are rendered soluble in aqueous solution via an encircling amphipathic membrane scaffold protein "belt" (Bayburt, T. H., Grinkova, Y. V., and Sligar, S. G. (2002) Nano. Lett. 2, 853-856). Integral membrane proteins can be self-assembled into the Nanodisc bilayer with defined stoichiometry, which allows an unprecedented opportunity to investigate the nature of the oligomerization state of a G-protein-coupled receptor and its coupling to heterotrimeric G-proteins. We generated Nanodiscs having one and two rhodopsins present in the 10-nm-diameter lipid bilayer domain. Efficient transducin activation and isolation of a high affinity transducin-metarhodopsin II complex was demonstrated for a monodisperse and monomeric receptor. A population of Nanodiscs containing two rhodopsins was generated using an increased ratio of receptor to membrane scaffold protein in the self-assembly mixture. The two-rhodopsin population was isolated and purified by density gradient centrifugation. Interestingly, in this case, only one of the two receptors present in the Nanodisc was able to form a stable metarhodopsin II-G-protein complex. Thus there is clear evidence that a monomeric rhodopsin is capable of full coupling to transducin. Importantly, presumably due to steric interactions, it appears that only a single receptor in the Nanodiscs containing two rhodopsins can interact with G-protein. These results have important implications for the stoichiometry of receptor-G-protein coupling and cross talk in signaling pathways.
6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE: A METABOLIC SIGNALING ENZYME (1995)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Cycloxygenase-2 Inhibition Augments the Efficacy of a Cancer Vaccine (2006)

Tumor-derived cyclooxygenase-2 (COX-2) and its product, prostaglandin E2, exert strong immunoinhibitory effects that block dendritic cell function and CD4+ and CD8+ T-cell proliferation and function. We have shown previously that the addition of an oral COX-2 inhibitor to immunogene therapy using IFN-beta markedly augmented therapeutic efficacy in murine tumor models. In this study, we hypothesized that COX-2 inhibition might also augment an antitumor vaccination strategy. Mice bearing tumors derived from TC1 cells, a tumor line that expresses the human papillomavirus (HPV) E7 protein, were thus vaccinated with an adenoviral vector expressing HPV E7 protein (Ad.E7). This vaccine approach effectively generated E7-specific CD8+ cells and slowed the growth of small tumors but had little effect on large tumors. However, feeding mice with the COX-2 inhibitor, rofecoxib, restored the effectiveness of the vaccine against large tumors and prolonged survival. This effect was accompanied by a larger percentage of E7-specific CD8+ cells in the regional draining lymph nodes and a markedly increased number of tumor-infiltrating E7-specific CD8+ cells (as determined by flow cytometry) and total CD8+ T cells (as determined by immunohistochemical staining). Increased immunocyte trafficking was likely mediated by the generation of a Th1-type tumor microenvironment because COX-2 inhibition increased expression levels of mRNA for IFN-gamma, interleukin-12, IP-10, and MIG while lowering the expression of vascular endothelial growth factor within tumors. This study shows that the effectiveness of a cancer vaccine can be significantly improved by adding COX-2 inhibition.
Molecular Architecture and \nBiological Reactions (1946)

Answers to many basic problems of biology—nature of growth,&#13;\nmechanism of duplication of viruses and genes , action of enzymes,&#13;\nmechanism, of physiological activity of drugs, hormones, and vitamins, structure and action of nerve and brain tissue—may lie&#13;\nin knowledge of molecular structure and intermolecular reactions.
Multiple osteochondral arthroscopic grafting (mosaicplasty) for cartilage defects of the knee: Prospective study results at 2‐year follow‐up (2005)

Level IV, Case Series.
Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. (1974)

These combined data have permitted the conclusion that complement consumption was attributable to CRP complexes and that it proceeded via the classical pathway independent of the presence of specific antibody or immunoglobulin. The specificity of CRP for choline phosphatides and its capacity to activate the complement system are considered in relation to the possible functions of CRP in the inflammatory process.
Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma. (1997)

The GAGE family of tumor-associated antigens is present in a wide spectrum of human tumors but is highly restricted among normal tissues except to the testis. By reverse transcription-PCR, GAGE expression was detected in 55 of 67 neuroblastomas (NBs; 8 of 12 stage 1, 13 of 13 stage 2, 9 of 12 stage 3, 7 of 12 stage 4S, and 18 of 18 stage 4), 5 of 5 Ewing's and peripheral neuroectodermal tumors, and 11 of 11 tumor cell lines (9 NBs, 1 peripheral neuroectodermal tumor, and 1 melanoma). In contrast, 5 of 6 normal tissues (normal testis was positive), 18 of 18 NB-negative bone marrow (BM; 9 normal, 6 non-NB remission, and 3 stage-2 NB), and 9 of 10 NB-negative peripheral blood (PB; 9 normal and 1 stage 2B) were undetectable. In 18 patients with widespread NB under treatment, GAGE expression in paired samples of BM and PB was 89% concordant. Both correlated strongly with disease measured by conventional methods, including marrow histology or immunocytology, bone scan, meta-iodo-benzylguanidine scan, computed tomography/magnetic resonance imaging, and urine vanilly-mandelic acid/homovanillic acid. When serial samples from 14 patients with stage 4 NB were studied, BM from 7 of 7 patients at diagnosis and 14 of 14 patients (25 samples) on treatment were positive for GAGE. Thirteen patients were in continual remission off therapy, and their GAGE expression (12 BM and 9 PB) was undetectable at follow-up. When compared to molecular detection of tyrosine hydroxylase mRNA, GAGE may offer added sensitivity in detecting NB in both BM and PB. The GAGE family of antigens may be potential tumor markers of minimal residual disease.
Oral Hypoglycemic Agents (1989)

ORAL hypoglycemic agents are commonly prescribed drugs. In the United States they account for about 1 percent of all prescriptions.1 This review discusses the pharmacology, mechanisms of action, efficacy, safety, and recommended use of currently approved agents, as well as other agents that may become available in the near future.BackgroundDiabetes mellitus affects nearly 15 million people in the United States. About 15 percent have insulin-dependent diabetes (IDDM), which is believed to be caused by the autoimmune destruction of pancreatic islet beta cells.2 In such patients, insulin therapy is essential for life. About 80 percent of patients have non-insulin-dependent . . .
Biofilm Associated Urinary Tract Infections (1995)

Urinary tract infections (UTI) of the lower urinary tract are a common problem causing significant morbidity in females and males (Nickel 1990). Most of the causal organisms are Gram negative bacilli such as Escherichia coli and Proteus mirabilis, or Gram positive Enterococcus and Streptococcus spp., which have their reservoir in the gastrointestinal tract. The other major source of UTI pathogens is direct transmission through sexual activity. These organisms first colonize the introitus and the periurethral area before entering the bladder or prostate. There is an indigenous population of Gram positive, acid producing lactobacilli in this environment which under normal circumstances appears to enhance the urinary defence mechanisms and inhibit the successful progression of the enterics into the urethra and bladder (Chan et al. 1985; Reid et al. 1987, 1990a). When the balance between enteric uropathogens and host defences is upset, uropathogens are able to ascend through the urethra into the bladder, the prostate (in males) and less often into the kidneys where they colonize and cause infection. Usually only the bladder is infected giving rise to simple, uncomplicated acute cystitis. This condition is readily treated by several standard antibiotic regimes (Nickel 1990). Problems arise when this infection spreads from the bladder into other organs such as the kidneys (pyelonephritis) or prostate (prostatitis), or induces the formation of calculi (struvite urolithiasis: McLean et al. 1988, 1992). In these cases, significant tissue damage may occur, possibly causing permanent damage to renal function, which can be life threatening.
Meat flavor (1975)

The flavor of meat is due to a complex mixture of compounds produced by heating a heterogenous system containing nonodorous precursors and consists of volatile compounds with odor properties, nonvolatile compounds with taste and tactile properties, and potentiators and synergists. The chemistry of these compounds, their precursors, and the influence of enzymes found in muscle on the overall flavor of cooked meat are discussed. A short discussion on the flavor of ripened, dry sausages is also included.
Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1. (2006)

The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.
pH Measurement and titration (Mattock, G.) (1962)

ADVERTISEMENT RETURN TO ISSUEPREVBook and Media Revie...Book and Media ReviewNEXTpH Measurement and titration (Mattock, G.)Allen J. Bard Cite this: J. Chem. Educ. 1962, 39, 7, 377Publication Date (Print):July 1, 1962Publication History Received3 August 2009Published online1 July 1962Published inissue 1 July 1962https://doi.org/10.1021/ed039p377.1RIGHTS & PERMISSIONSArticle Views423Altmetric-Citations-LEARN 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 InReddit PDF (937 KB) Get e-Alerts Get e-Alerts
Polyolefin Matrixes with Permanent Antibacterial Activity:  Preparation, Antibacterial Activity, and Action Mode of the Active Species (2006)

Poly[2-(tert-butylamino)ethyl methacrylate] (PTBAEMA) belongs to a novel class of water-insoluble biocides. Dispersion of a poly(ethylene-co-butylene)-b-poly[2-(tert-butylamino)ethyl methacrylate] diblock copolymer (PEB-b-PTBAEMA) within low-density polyethylene (LDPE) imparts antimicrobial properties to the polyolefin as assessed by the viable cell counting method against Escherichia coli (E. coli). This diblock copolymer has been synthesized by atom transfer radical polymerization (ATRP) with a poly(ethylene-co-butylene) (PEB) oligomer end-capped by an activated bromide as a macroinitiator for the polymerization of 2-(tert-butylamino)ethyl methacrylate (TBAEMA). Morphological changes of E. coli bacteria in contact with modified LDPE have been observed by transmission and scanning electron microscopy and indicate that the diblock copolymer is bactericide rather than bacteriostatic. Finally, the action mode of the PEB-b-PTBAEMA copolymer more likely relies on the displacement of the Ca(2+) and/or Mg(2+) ions of the outer membrane of the bacteria, which is disorganized and finally disrupted.
The toxicological mode of action and the safety of synthetic amorphous silica—A nanostructured material (2012)

Synthetic amorphous silica (SAS), in the form of pyrogenic (fumed), precipitated, gel or colloidal SAS, has been used in a wide variety of industrial and consumer applications including food, cosmetics and pharmaceutical products for many decades. Based on extensive physico-chemical, ecotoxicology, toxicology, safety and epidemiology data, no environmental or health risks have been associated with these materials if produced and used under current hygiene standards and use recommendations. With internal structures in the nanoscale size range, pyrogenic, precipitated and gel SAS are typical examples of nanostructured materials as recently defined by the International Organisation for Standardisation (ISO). The manufacturing process of these SAS materials leads to aggregates of strongly (covalently) bonded or fused primary particles. Weak interaction forces (van der Waals interactions, hydrogen bonding, physical adhesion) between aggregates lead to the formation of micrometre (μm)-sized agglomerates. Typically, isolated nanoparticles do not occur. In contrast, colloidal SAS dispersions may contain isolated primary particles in the nano-size range which can be considered nano-objects. The size of the primary particle resulted in the materials often being considered as "nanosilica" and in the inclusion of SAS in research programmes on nanomaterials. The biological activity of SAS can be related to the particle shape and surface characteristics interfacing with the biological milieu rather than to particle size. SAS adsorbs to cellular surfaces and can affect membrane structures and integrity. Toxicity is linked to mechanisms of interactions with outer and inner cell membranes, signalling responses, and vesicle trafficking pathways. Interaction with membranes may induce the release of endosomal substances, reactive oxygen species, cytokines and chemokines and thus induce inflammatory responses. None of the SAS forms, including colloidal nano-sized particles, were shown to bioaccumulate and all disappear within a short time from living organisms by physiological excretion mechanisms with some indications that the smaller the particle size, the faster the clearance is. Therefore, despite the new nomenclature designating SAS a nanomaterial, none of the recent available data gives any evidence for a novel, hitherto unknown mechanism of toxicity that may raise concerns with regard to human health or environmental risks. Taken together, commercial SAS forms (including colloidal silicon dioxide and surface-treated SAS) are not new nanomaterials with unknown properties, but are well-studied materials that have been in use for decades.
Depyrogenation by endotoxin removal with positively charged depth filter cartridge. (1990)

Bacterial endotoxin, a major quality of parenteral pharmaceuticals, is negatively charged lipopolysaccharide (LPS). A depth filter chemically modified to carry positively charged functional groups is applied to remove endotoxin from aqueous solutions and buffers through charge interaction. The environmental conditions, such as pH and electrolytes, known to affect the efficiency of endotoxin removal by the filter were studied. The charge character of the solid filter was titrated potentiometrically. Other factors such as pyrogen concentration and flow rate were also studied. The effectiveness of depyrogenating the aqueous solution by endotoxin removal through charge interaction with the depth type filter cartridge is fully demonstrated. An optimized cartridge performance can be achieved by following the conditions illustrated in this report. A multi-cell cartridge capable of processing bulk volume of fluid at or over 5 GPM makes it an effective depyrogenating device for the pharmaceutical industry.
Navigation of Spacecraft on Deep Space Missions (1987)

Spacecraft which are sent on deep space missions to the planets must be accurately navigated in order to achieve the correct flight path. Navigation analysts use precise measurements and large computational software systems to determine a spacecraft's position throughout the mission and compute the velocity corrections for its guidance through space. When the spacecraft is launched into deep space on its voyage, it is impossible to know with great precision where it is headed. Imperfections in both the launch vehicle's terminal velocity and the uncertainty in the knowledge of the parameters which will affect the spacecraft trajectory contribute to errors in the predictions of the total flight path. Continuous navigation of the spacecraft achieves an ever-evolving prediction of its orbit from the reduction of radiometric and astrometric observations of the craft. Control of the spacecraft is achieved by computing and signalling to the craft a series of propulsive, velocity correction commands, which manoeuvre the craft to its desired course.
Manual for implementing residual radioactive material guidelines using RESRAD, Version 5.0 (1993)

This manual presents information for implementing US Department of Energy (DOE) guidelines for residual radioactive material. It describes the analysis and models used to derive site-specific guidelines for allowable residual concentrations of radionuclides in soil and the design and use of the RESRAD computer code for calculating doses, risks, and guideline values. It also describes procedures for implementing DOE policy for reducing residual radioactivity to levels that are as low as reasonably achievable. Two new pathways, radon inhalation and soil ingestion, have been added to RESRAD. Twenty-seven new radionuclides have also been added, and the cutoff half-life for associated radionuclides has been reduced to six months. Other major improvements to the RESRAD code include the ability to run sensitivity analyses, the addition of graphical output, user-specified dose factors, updated databases, an improved groundwater transport model, optional input of a groundwater concentration and a solubility constant, special models for tritium and carbon-14, calculation of cancer incidence risk, and the use of a mouse with menus.
Neuroform stent-assisted coiling of intracranial aneurysms: a 5 year single-center experience and follow-up (2009)

In treating complex intracranial aneurysms, the Neuroform stent-assisted coiling is a secure and effective technique.
Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials (2013)

Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot in the 1870s, is an age-related disorder that leads to degeneration of motor neurons. The disease begins focally in the central nervous system and then spreads relentlessly. The clinical diagnosis, defined by progressive signs and symptoms of upper and lower motor neuron dysfunction, is confirmed by electromyography. Additional testing excludes other conditions. The disease is heterogeneous, but most patients die of respiratory muscle weakness less than 3 years from symptom-onset. Like other age-related neurodegenerative diseases, ALS has genetic and environmental triggers. Of the five to 10% of cases that are inherited, mutations have been discovered for a high proportion. In addition to genetic factors, age, tobacco use, and athleticism may contribute to sporadic ALS, but important etiologies are unidentified for most patients. Complex pathophysiological processes, including mitochondrial dysfunction, aggregation of misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis, involve both motor neurons and surrounding glial cells. There is clinical and pathological overlap with other neurodegenerative diseases, particularly frontotemporal dementia. The mechanisms leading to disease propagation in the brain are a current focus of research. To date, one medication, riluzole, licensed in 1996, has been proved to prolong survival in ALS. Numerous clinical trials have so far been unable to identify another neuroprotective agent. Researchers now aim to slow disease progression by targeting known pathophysiological pathways or genetic defects. Current approaches are directed at muscle proteins such as Nogo, energetic balance, cell replacement, and abnormal gene products resulting from mutations. Until better understanding of the causes and mechanisms underlying progression lead to more robust neuroprotective agents, symptomatic therapies can extend life and improve quality of life. Palliative care programs such as hospice give emotional and physical support to patients and families throughout much of the disease course.