gebhart/patrepeval huggingface dataset:
The Effect of Food on the Oral Bioavailability of Drugs: a Review of Current Developments and Pharmaceutical Technologies for Pharmacokinetic Control (2011)

Here we review the mediation of the food effects on drugs by pharmaceutical technologies. The pharmacokinetics of drugs are affected by the interaction of drugs with food, which changes drug physicochemical and physiological properties (food effects). Several pharmaceutical technologies may be used to control food effects. Drugs exhibit different patterns of solubilization depending on release formulations. Formulations such as nanoparticle, solid dispersion and cyclodextrin systems, may control the solubility and release of insoluble drugs. Other controlled-release technologies, such as osmotic-controlled release or colon-specific delivery systems may also control food effects. As the structure of drug candidates becomes more complex, different methods of investigation, such as in vitro and in vivo correlation and in silico simulation will be required to predict drug characteristics and food effects.
Macrophage inflammatory protein-1 alpha expression in interstitial lung disease. (1993)

Mononuclear phagocyte (M phi) recruitment and activation is a hallmark of a number of chronic inflammatory diseases of the lung, including sarcoidosis and idiopathic pulmonary fibrosis (IPF). We hypothesized that macrophage inflammatory protein-1 (MIP-1 alpha), a peptide with leukocyte activating and chemotactic properties, may play an important role in mediating many of the cellular changes that occur in sarcoidosis and IPF. In initial experiments, we demonstrated that human rMIP-1 alpha exerted chemotactic activities toward both polymorphonuclear leukocytes and monocytes, and these activities were inhibited by treatment with rabbit anti-human MIP-1 alpha antiserum. In support of the potential role of MIP-1 alpha in interstitial lung disease, we detected MIP-1 alpha in the bronchoalveolar lavage fluid of 22/23 patients with sarcoidosis (mean 443 +/- 76 pg/ml) and 9/9 patients with IPF (mean 427 +/- 81 pg/ml), whereas detectable MIP-1 alpha was found in only 1/7 healthy subjects (mean 64 +/- 64 pg/ml). In addition, we found a 2.5- and 1.8-fold increase in monocyte chemotactic activity in BALF obtained from patients with sarcoidosis and IPF respectively, as compared to healthy subjects, and this monocyte chemotactic activity, but not neutrophil chemotactic activity, was reduced by approximately 22% when bronchoalveolar lavage fluid from sarcoidosis and IPF patients were preincubated with rabbit antihuman MIP-1 alpha antibodies. To determine the cellular source(s) of MIP-1 alpha within the lung, we performed immunohistochemical analysis of bronchoalveolar lavage cell pellets, transbronchial biopsies, and open lung biopsies obtained from patients with IPF and sarcoidosis. Substantial expression of cell-associated MIP-1 alpha was detected in M phi, including both alveolar AM phi and interstitial M phi. In addition, interstitial fibroblasts within biopsies obtained from sarcoid and IPF patients also expressed immunoreactive MIP-1 alpha. Minimal to no detectable MIP-1 alpha was expressed in alveolar M phi from healthy subjects or interstitial cells in lung biopsy specimens obtained from patients undergoing thoracotomy for malignancy. Furthermore, pulmonary fibroblasts isolated from patients with IPF produced greater amounts of MIP-1 alpha after challenge with IL-1 beta than did similarly treated pulmonary fibroblasts recovered from patients without fibrotic lung disease. Our findings suggest that MIP-1 alpha is expressed in increased amounts within the airspace and interstitium of patients with sarcoidosis and IPF, and that this cytokine may be an important mediator of both M phi activation and recruitment that characterize these disease states.
Simple Route to Hydrophilic Microfluidic Chip Fabrication Using an Ultraviolet (UV)‐Cured Polymer (2007)

Abstract Herein, we introduce a simple route to fabricating hydrophilic microfluidic chips with an alternative material, a UV‐cured polyurethane‐related polymer, known as Norland Optical Adhesive (NOA 63). Conventionally, polydimethylsiloxane (PDMS) is widely used to fabricate microfluidic chips as an alternative to glass or SiO 2 because PDMS is easily molded and relatively cheap. However, despite these advantages, the hydrophobicity of PDMS entails critical problems when it is used in microfluidic chips because microchannels inside the microfluidic chips, which have extremely low surface tension, are difficult to fill with aqueous solution without an extra pumping system. To overcome these problems, significant efforts have been focused on developing procedures to change the PDMS surface to be hydrophilic. However, the resulting hydrophilicity is generally short‐lived and the modification procedures require cumbersome multi‐steps. In the present study, we demonstrate that microchannel‐molding and microfluidic chip construction are easier using NOA 63 than when using PDMS and that the hydrophilicity of the NOA surface, which is induced by treatment with O 2 plasma, lasts longer, for at least one month. Due to the longer lasting hydrophilicity, microchannels in NOA 63 microfluidic chips are spontaneously filled with solution by capillary reaction without any extra pumping over the period. The feasibility of NOA 63‐based microfabrication is verified by demonstrating NOA 63 microfluidic platforms with antibody‐immobilized beads for immunoassays.
Lippincott's Illustrated Reviews: Biochemistry (2004)

Lippicott's ilustrated reviews biochemistry , Lippicott's ilustrated reviews biochemistry , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی
Justice et dignité pour les chibanis (2012)

En 2009, trois associations toulousaines, la Case de Santé, le Centre d’initiatives et de ressources régionales autour du vieillissement des populations immigrées (CIRRVI) et le Tactikollectif, décident de regrouper leurs forces pour lancer un appel national afin de dénoncer les conditions de vie de nombreux immigrés âgés. Cette initiative trouvera un écho dans plusieurs villes de France et aboutira à la création du collectif « Justice et dignité pour les chibanis » (www.chibanis.org). 1 ,
In mice, proteinuria and renal inflammatory responses to albumin overload are strain-dependent (2005)

There are major strain differences in the proteinuria and renal inflammatory response of mice to albumin overload, which are not due to structural variation in the filtration barrier but possibly to functional differences in glomerular protein permeability.
Dissociation between bone resorption and bone formation in osteopenic transgenic mice (1998)

Bone mass is maintained constant in vertebrates through bone remodeling (BR). BR is characterized by osteoclastic resorption of preexisting bone followed by de novo bone formation by osteoblasts. This sequence of events and the fact that bone mass remains constant in physiological situation lead to the assumption that resorption and formation are regulated by each other during BR. Recent evidence shows that cells of the osteoblastic lineage are involved in osteoclast differentiation. However, the existence of a functional link between the two activities, formation and resorption, has never been shown in vivo. To define the role of bone formation in the control of bone resorption, we generated an inducible osteoblast ablation mouse model. These mice developed a reversible osteopenia. Functional analyses showed that in the absence of bone formation, bone resorption continued to occur normally, leading to an osteoporosis of controllable severity, whose appearance could be prevented by an antiresorptive agent. This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo.
High-level tryptophan accumulation in seeds of transgenic rice and its limited effects on agronomic traits and seed metabolite profile (2006)

Metabolic manipulation of plants to improve their nutritional quality is an important goal of plant biotechnology. Expression in rice (Oryza sativa L.) of a transgene (OASA1D) encoding a feedback-insensitive alpha subunit of rice anthranilate synthase results in the accumulation of tryptophan (Trp) in calli and leaves. It is shown here that the amount of free Trp in the seeds of such plants is increased by about two orders of magnitude compared with that in the seeds of wild-type plants. The total Trp content in the seeds of the transgenic plants was also increased. Two homozygous lines, HW1 and HW5, of OASA1D transgenic rice were generated for characterization of agronomic traits and aromatic metabolite profiling of seeds. The marked overproduction of Trp was stable in these lines under field conditions, although spikelet fertility and yield, as well as seed germination ability, were reduced compared with the wild type. These differences in agronomic traits were small, however, in HW5. In spite of the high Trp content in the seeds of the HW lines, metabolic profiling revealed no substantial changes in the amounts of other phenolic compounds. The amount of indole acetic acid was increased about 2-fold in the seeds of the transgenic lines. The establishment and characterization of these OASA1D transgenic lines have thus demonstrated the feasibility of increasing the Trp content in the seeds of rice (or of other crops) as a means of improving its nutritional value for human consumption or animal feed.
Isolation of a Crystalline Trypsin Inhibitor-Anticoagulant Protein from Pancreas1a (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation of a Crystalline Trypsin Inhibitor-Anticoagulant Protein from Pancreas1aLouis A. Kazal, Daniel S. Spicer, and Rose A. BrahinskyCite this: J. Am. Chem. Soc. 1948, 70, 9, 3034–3040Publication Date (Print):September 1, 1948Publication History Published online1 May 2002Published inissue 1 September 1948https://pubs.acs.org/doi/10.1021/ja01189a060https://doi.org/10.1021/ja01189a060research-articleACS PublicationsRequest reuse permissionsArticle Views330Altmetric-Citations252LEARN 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
Signaling Mechanisms Underlying the Release of Glucagon-Like Peptide 1 (2006)

Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response to a range of nutrients, hormones, and neurotransmitters. Its potency as an insulin secretagogue has led to pharmaceutical interest in developing strategies to enhance GLP-1 receptor activation in type 2 diabetes. A complementary approach, to stimulate endogenous release of GLP-1, would be facilitated by a better understanding of L-cell physiology. Using GLP-1–secreting cell lines such as GLUTag and STC-1, mechanisms underlying GLP-1 release have been identified at a single-cell level. A number of stimuli, including glucose and certain amino acids, result in membrane depolarization and Ca2+ entry through voltage-gated Ca2+ channels. Glucose triggers membrane depolarization both by closing ATP-sensitive potassium channels and because of its uptake by Na+-coupled glucose transporters. Whereas glutamine also triggers depolarization by Na+-coupled uptake, glycine opens Cl− channels on the surface membrane. A number of agents, including fatty acids and hormones, enhance GLP-1 secretion by acting at stages downstream of depolarization. Some of these target G protein–coupled receptors, triggering elevation of cAMP or release of Ca2+ from intracellular stores. Understanding these different pathways and how they could be targeted to maximize GLP-1 secretion may be a step toward developing therapeutic GLP-1 secretagogues.
Electrospinning jets and polymer nanofibers (2008)

In electrospinning, polymer nanofibers are formed by the creation and elongation of an electrified fluid jet. The path of the jet is from a fluid surface that is often, but not necessarily constrained by an orifice, through a straight segment of a tapering cone, then through a series of successively smaller electrically driven bending coils, with each bending coil having turns of increasing radius, and finally solidifying into a continuous thin fiber. Control of the process produces fibers with nanometer scale diameters, along with various cross-sectional shapes, beads, branches and buckling coils or zigzags. Additions to the fluid being spun, such as chemical reagents, other polymers, dispersed particles, proteins, and viable cells, resulted in the inclusion of the added material along the nanofibers. Post-treatments of nanofibers, by conglutination, by vapor coating, by chemical treatment of the surfaces, and by thermal processing, broaden the usefulness of nanofibers.
Pharmacokinetics of tobacco-specific N-nitrosamines. (1984)

Methods were developed to determine the biological half-life of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in Syrian golden hamsters and Fischer rats. The formation and elimination of 4-(N-nitrosomethylamino)-1-(-3-pyridyl)-1-butanol (NNA1), the major metabolite of NNK, was determined in the context of this study. The method consisted of extraction of the nitrosamine with ethyl acetate, elution through a Clin-Elut column, and concentration of the sample, followed by gas chromatography-thermal energy analysis. Biological half-lives of NNN, NNK and NNA1 in hamsters were found to be 0.77, 0.25 and 1.78 h, respectively; in rats they were 5.78, 1.78 and 3.56 h. These findings clearly indicate species differences in the pharmacokinetics associated with the distribution and elimination of the tobacco-specific N-nitrosamines.
Feasibility of Lipid Nanoparticles for Ocular Delivery of Anti-Inflammatory Drugs (2010)

Due to the multiple barriers imposed by the eye against the penetration of drugs, the ocular delivery and targeting are considered difficult to achieve. A major challenge in ocular drug therapy is to improve the poor bioavailability of topically applied ophthalmic drugs by overcoming the severe constraints imposed by the eye on drug absorption. One of the promising strategies nowadays is the use of colloidal carrier systems characterized by a submicron-meter size. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives to conventional and very popular ocular carrier systems, such as the nanoemulsions, liposomes, and polymeric nanoparticles. Nevertheless, taking into account the characteristics of the eye, morphometrical properties of the colloidal systems (e.g., average particle size and polydispersion) may represent a limiting factor for topical application without induced corneal irritation, being responsible for the selected system. This review article focuses on the application of lipid nanoparticles (SLN, NLC) as carriers for both non-steroidal and steroidal anti-inflammatory drugs for the treatment of ocular inflammatory disorders. Major benefits, as well as shortcomings, of ocular inflammation conditions are described, in particular upon management of inflammation induced by ocular surgery (e.g., cataracts, refractive surgery). Particular emphasis is given to the clinical choices currently available, while examining the most recent drugs that have been approved.
Generalized Unequal Error Protection LT Codes for Progressive Data Transmission (2012)

The original design of standard digital fountain codes assumes that the coded information symbols are equally important. In many applications, some source symbols are more important than others, and they must be recovered prior to the rest. Unequal Error Protection (UEP) designs are attractive solutions for such source transmissions. In this study, we introduce a more generalized design for the first universal fountain code design, LT codes, that makes it particularly suited for progressive bit stream transmissions. We apply the generalized LT codes to a progressive source and show that it has better UEP properties than other published results in the literature. For example, using the proposed generalization, we obtained up to 1.7dB PSNR gain in a progressive image transmission scenario over the two major UEP fountain code designs.
Subchronic and chronic effects of feeding of large amounts of acetaminophen in B6C3F1 mice. (1985)

N-Acetyl-p-aminophenol (acetaminophen) is one of the main metabolites of acetophenetidine (phenacetin), which was proved to be a carcinogen. Ishidate and Odashima have found that acetaminophen itself induced chromosomal aberrations in cultured Chinese hamster cells. The repair test by the rec-assay also gave a positive result (Kada et al., unpublished data). These results prompted us to perform an experiment of long-term administration of acetaminophen in B6C3F1 mice.During the preparation of this article Flaks and Flaks have reported that acetaminophen is tumorigenic in mice of the IF strain. The difference between results of the present study and the results obtained by Flaks and Flaks is briefly discussed.
THE EFFECTIVENESS OF ANTI-Ia-IMMUNOTOXINS IN THE SUPPRESSION OF MLR (1985)

The potential use of a mouse anti-Ia monoclonal antibody conjugated with a plant toxin as an immunosuppressive agent for organ transplantation was examined by studying the mixed lymphocyte reaction (MLR). In initial observations in a murine system utilizing strains A/J and C57B1/6 (B6), it was shown that a rich-toxin-conjugated anti-I-Ek monoclonal antibody (13.4-immunotoxin) would kill Ia-bearing cells of strain A/J (I-Ek)--but not of strain B6, the cells of which lack I-E determinants. Studies reported here demonstrated that 13.4-immunotoxin effectively removed stimulatory cells from the I-E-bearing spleen cells but had no effect on spleen cells lacking I-E determinants or responder lymph node cells (I-E+ or I-E-) similarly treated (i.e., 1 micrograms/10(6) cells). Taking advantage of the finding that such anti-I-E antibodies react with rat spleen cells bearing class II major histocompatibility complex molecules, we utilized these toxin-conjugated antibodies to inhibit MLR in rats. Assuming that the MLR is an in vitro representative of graft rejection, we suggest that such immunotoxins might be useful for pretreatment of organ allografts for transplantation across major histocompatibility barriers.
Imaging of fresh and aged venous thrombi in the dog with I-131 monoclonal antibody specific for the NH/sub 2/-terminal region of fibrin (1985)

An agent is needed for better visualization of aged thrombi by radionuclide imaging. Murine monoclonal antibody (Mab/T2GlS) specific for the NH/sub 2/-terminal region of human fibrin, does not react with fibrinogen. The authors purified this Mab from hybridoma clone culture medium by immunoaffinity chromatography using an Affi-Gel 10 column to which human fibrin was coupled; cross-reactivity with dog fibrin was confirmed by radioimmunoassay, using non-specific I-125 polyclonal murine IgG and the specific I-131 monoclonal antibody. The authors produced thrombi by two methods: (1) femoral venous ligation with injection of bovine thrombin (10 to 100 NIH units) and (2) transcatheter placement of Gianturco coils. When thrombi were one or 24 hours old, 100 ..mu..Ci of I-131-labeled fibrin-specific antibody were injected along with 50 ..mu..cI of I-125-labeled non-specific murine IgG for serial camera imaging and tissue radioassay. Thrombi one or 24 hours old were easily visualized on images 24 hours after antibody injection. At 48 hours, the thrombus concentration of the specific Mab was 17 times greater than the non-specific IgG. The thrombus/muscle concentration ratio was as high as 200 for the Mab and 14 for the non-specific IgG. These results suggest that this Mab may be useful for detecting spontaneous thromboembolismmore » clinically, because of its high affinity for human fibrin.« less
Factorized Convolutional Neural Networks (2017)

In this paper, we propose to factorize the convolutional layer to reduce its computation. The 3D convolution operation in a convolutional layer can be considered as performing spatial convolution in each channel and linear projection across channels simultaneously. By unravelling them and arranging the spatial convolutions sequentially, the proposed layer is composed of a low-cost single intra-channel convolution and a linear channel projection. When combined with residual connection, it can effectively preserve the spatial information and maintain the accuracy with significantly less computation. We also introduce a topological subdivisioning to reduce the connection between the input and output channels. Our experiments demonstrate that the proposed layers outperform the standard convolutional layers on performance/complexity ratio. Our models achieve similar performance to VGG-16, ResNet-34, ResNet-50, ResNet-101 while requiring 42x,7.32x,4.38x,5.85x less computation respectively.
Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes (1995)

The expression of certain MHC class I allotypes by potential target cells can inhibit NK cell-mediated cytotoxicity. We recently identified the NKB1 surface Ag, expressed on T and NK cell subsets, as a putative inhibitory receptor for HLA-B class I molecules possessing the Bw4 serologic epitope. NKB1 is a 70-kDa glycoprotein that after deglycosylation migrates as a 50-kDa protein as determined by SDS-PAGE. A cDNA encoding the NKB1 receptor was cloned from a NKB1+T cell cDNA library by expression in COS-7 cells using the anti-NKB1 mAb DX9. NKB1 is a member of the lg superfamily containing three lg-like domains in the extracellular region and is related to the recently identified family (p58/NKAT) of human NK and T cell surface molecules that appear to function as inhibitory receptors for HLA class I.
The fertility restorer gene, Rf2, for Lead Rice‐type cytoplasmic male sterility of rice encodes a mitochondrial glycine‐rich protein (2010)

Cytoplasmic male sterility (CMS) is associated with a mitochondrial mutation that causes an inability to produce fertile pollen. The fertility of CMS plants is restored in the presence of a nuclear-encoded fertility restorer (Rf) gene. In Lead Rice-type CMS, discovered in the indica variety 'Lead Rice', fertility of the CMS plant is restored by the single nuclear-encoded gene Rf2 in a gametophytic manner. We performed map-based cloning of Rf2, and proved that it encodes a protein consisting of 152 amino acids with a glycine-rich domain. Expression of Rf2 mRNA was detected in developing and mature anthers. An RF2-GFP fusion was shown to be targeted to mitochondria. Replacement of isoleucine by threonine at amino acid 78 of the RF2 protein was considered to be the cause of functional loss in the rf2 allele. As Rf2 does not encode a pentatricopeptide repeat protein, unlike a majority of previously identified Rf genes, the data from this study provide new insights into the mechanism for restoring fertility in CMS.