gebhart/patrepeval huggingface dataset:
World-to-Digital-Microfluidic Interface Enabling Extraction and Purification of RNA from Human Whole Blood (2014)

Digital microfluidics (DMF) is a powerful technique for simple and precise manipulation of microscale droplets of fluid. This technique enables processing and analysis of a wide variety of samples and reagents and has proven useful in a broad range of chemical, biological, and medical applications. Handling of "real-world" samples has been a challenge, however, because typically their volumes are greater than those easily accommodated by DMF devices and contain analytes of interest at low concentration. To address this challenge, we have developed a novel "world-to-DMF" interface in which an integrated companion module drives the large-volume sample through a 10 μL droplet region on the DMF device, enabling magnet-mediated recovery of bead-bound analytes onto the device as they pass through the region. To demonstrate its utility, we use this system for extraction of RNA from human whole blood lysates (110-380 μL) and further purification in microscale volumes (5-15 μL) on the DMF device itself. Processing by the system was >2-fold faster and consumed 12-fold less reagents, yet produced RNA yields and quality fully comparable to conventional preparations and supporting qRT-PCR and RNA-Seq analyses. The world-to-DMF system is designed for flexibility in accommodating different sample types and volumes, as well as for facile integration of additional modules to enable execution of more complex protocols for sample processing and analysis. As the first technology of its kind, this innovation represents an important step forward for DMF, further enhancing its utility for a wide range of applications.
Epipolarization Microscopic Immunogold Assay: a Combination of Immunogold Silver Staining, Enzyme-Linked-Immunosorbent Assay and Epipolarization Microscopy (1995)

We describe a new immunoassay which combines an immunosorbent assay, immunogold silver staining and epipolarization microscopy. Our new assay procedure features multiple samples on a single microscope slide, and high sensitivity of epipolarization microscope for detection of silver-enhanced colloidal gold as a final immunoassay product. We call the new immunoassay "on slide immunogold assay" (OSIGA). This new method uses biotinylated antibody and streptavidin-gold reaction with silver enhancement technique. With OSIGA it is possible to investigate 30 samples on a single microscopic slide. Our preliminary studies used 10-20 microliter samples and detected nanogram quantities of a standardized protein solution. Unlike enzyme linked immunosorbent assay (ELISA), which has a limited time for reading the final color products, the OSIGA specimens can be dried or resin mounted for longer storage and future reference.
The silver halide photographic process (1988)

Abstract The light-sensitive elements of conventional photographic materials are crystallites principally of the bromide or chloride salts of silver. Certain chemical modifications employing sulphur and gold compounds are used to maximize the response, and organic dyes are adsorbed to provide sensitivity throughout the visible spectrum. Absorption of a few photons results in the reductive formation of one or more clusters of silver or gold atoms on the surface. These clusters act as catalysts to promote further reduction of the host crystallites during photographic development. The success of the system depends upon the particular physical properties of the silver halides, such as their bonding and electron structure, the dielectric properties, the point defect structure, and the electronic transport characteristics. These are all reviewed, and the ways in which they interact to lead to the favourable photodecomposition are followed in some detail. A nucleation-and-growth mechanism operates to provide several of the favourable features of the process, and the chemical treatments used optimize the competition between these desirable steps and the unwanted recombination of electronic carriers.
Chemical Vapor Deposition Process on the ZSM-5(010) Surface as Investigated by Molecular Dynamics (1999)

The molecular dynamics (MD) method was applied to investigate a chemical vapor deposition process on the ZSM-5(010) surface. Si(OH)4 molecules were placed on the ZSM-5(010) surface, and MD simulation was performed for 12 ps. We observed the formation and evaporation of H2O molecules over the ZSM-5(010) surface. It indicates that the surface chemical reactions such as Si(OH)4 + HO-[ZSM-5] → Si(OH)3−O-[ZSM-5] + H2O, Si(OH)3−O-[ZSM-5] + Si(OH)3−O-[ZSM-5] → [ZSM-5]-O−Si(OH)2−O−Si(OH)2−O-[ZSM-5] + H2O and others, take place during the MD simulation. The formation of new Si−O−Si bonds was also observed on the surface, indicating the crystal growth of the ZSM-5(010) surface. Moreover, the constructed SiO2 layer was not amorphous, but inherited the ZSM-5 structure, keeping the 10-membered ring and (010) oriented configuration. Hence, we confirmed that the MD method was effective for reproducing and investigating the chemical vapor deposition process on zeolite surfaces on an atomic scale.
Pepitope: epitope mapping from affinity-selected peptides (2007)

http://pepitope.tau.ac.il/
Induction of Therapeutic Antitumor Immunity by In Vivo Administration of a Lentiviral Vaccine (2005)

Direct in vivo administration of a lentiviral vaccine has been shown to transduce dendritic cells (DCs) in order to induce antigen-specific CD8+ T cell responses, but the efficacy of antitumor immunity has not been reported. In this study we tested whether direct in vivo administration of a lentiviral vaccine can induce selfantigen- based therapeutic antitumor immunity in murine tumor models. Lentiviral vector (LV) transduced DCs efficiently in vitro and was able to transduce DCs in vivo. LV-transduced DCs effectively presented antigens to T cells. Compared with a naked DNA tyrosinase-related protein-2 (TRP2)-heat shock protein-70 (hsp70) vaccine, the TRP2-specific interferon-gamma-producing CD8+ T cell response was augmented by direct in vivo administration of an LV-TRP2hsp70 vaccine, which induced significant therapeutic antitumor immunity in subcutaneous B16 and subcutaneous GL-26 models. Moreover, in vivo administration of an LV-NeuEDhsp70 vaccine induced significant therapeutic antitumor immunity against spontaneous breast tumors in a BALB/c- Neu transgenic model. Our observations indicate that direct in vivo administration of a lentiviral vaccine not only enhances antigen-specific CD8+ T cell responses, but also generates significant therapeutic antitumor activities.
Molecular Determinants of Species Specificity in the Coronavirus Receptor Aminopeptidase N (CD13): Influence of N-Linked Glycosylation (2001)

Aminopeptidase N (APN), a 150-kDa metalloprotease also called CD13, serves as a receptor for serologically related coronaviruses of humans (human coronavirus 229E [HCoV-229E]), pigs, and cats. These virus-receptor interactions can be highly species specific; for example, the human coronavirus can use human APN (hAPN) but not porcine APN (pAPN) as its cellular receptor, and porcine coronaviruses can use pAPN but not hAPN. Substitution of pAPN amino acids 283 to 290 into hAPN for the corresponding amino acids 288 to 295 introduced an N-glycosylation sequon at amino acids 291 to 293 that blocked HCoV-229E receptor activity of hAPN. Substitution of two amino acids that inserted an N-glycosylation site at amino acid 291 also resulted in a mutant hAPN that lacked receptor activity because it failed to bind HCoV-229E. Single amino acid revertants that removed this sequon at amino acids 291 to 293 but had one or five pAPN amino acid substitution(s) in this region all regained HCoV-229E binding and receptor activities. To determine if other N-linked glycosylation differences between hAPN, feline APN (fAPN), and pAPN account for receptor specificity of pig and cat coronaviruses, a mutant hAPN protein that, like fAPN and pAPN, lacked a glycosylation sequon at 818 to 820 was studied. This sequon is within the region that determines receptor activity for porcine and feline coronaviruses. Mutant hAPN lacking the sequon at amino acids 818 to 820 maintained HCoV-229E receptor activity but did not gain receptor activity for porcine or feline coronaviruses. Thus, certain differences in glycosylation between coronavirus receptors from different species are critical determinants in the species specificity of infection.
Analysis of brain lipids by high performance thin-layer chromatography and densitometry. (1983)

We have devised a high performance thin-layer chromatography (HPTLC) densitometry method to resolve the major lipid classes of brain tissue. We used DEAE-Sephadex column chromatography to separate the total lipid into neutral and acidic lipid fractions. The lipid fractions were then spotted on separate HPTLC plates and chromatographed in one dimension using two solvent systems. Quantitation was by in situ densitometry with absolute amounts of the lipid classes determined from co-chromatographed standards. An internal standard was also used to improve the precision. The individual lipid classes of rat whole brain, human brain gray and white matter, rat and bovine myelin, and bovine oligodendroglia were quantitated. Human brain phosphatidylethanolamine plasmalogen was also quantitated. Sensitivity was increased by using the cupric acetate charring reagent, which we found to be more sensitive than the conventional sulfuric acid-dichromate reagent. Total lipid (less than 400 micrograms) was quantitated from 5 mg of tissue wet weight. The limit of detection, on HPTLC, for the individual lipid classes was below 20 ng.
A Rationale for Discipline-Based Art Education (1989)

Developing and implementing a DBAE program is both time and ener gy consuming, this writer admits. However, he says, the results make the effort more than worthwhile.
Expression of c-myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential (1989)

The expression of oncogenes (c-myc, c-fos, c-Ki-ras, c-Ha-ras, and p53) was examined by Northern blot analysis using freshly isolated human colorectal and gastric cancers and noncancerous portions as the controls. Remarkably high levels of c-myc expression were found in colorectal cancers (eight of 11), but not in gastric cancers. High levels of c-myc expression were also detected in colorectal polyps and in metastatic liver tumors. In colorectal polyps, the transcript levels significantly correlated with the histologic malignancy and the size. In contrast, neither c-fos nor c-Ki-ras was overexpressed in colorectal and gastric cancers, and transcripts of c-Ha-ras and p53 were not evident in any tissue examined. In light of these observations the c-myc expression may be specifically associated with the evolution of colorectal cancer as well as progression and maintenance stages, hence may prove to be a useful marker to evaluate the malignant potential of colorectal polyps.
Structural Origin of the High Affinity of a Chemically Evolved Lanthanide‐Binding Peptide (2004)

Playing tag with terbium: New hydrophobic contacts and ligating amino acids are revealed in the 2.0-Å resolution X-ray crystal structure of a chemically evolved 17-residue lanthanide-binding peptide complexed with a Tb3+ ion (see ribbon diagram). The crystal structure agrees well with luminescence-lifetime measurements in solution, which indicate that no first-shell-coordinating water molecules are present in the complex. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460028_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. (1988)

Schwann cells have a unique role in regulating the growth of axons during regeneration and presumably during development. Here we show that Schwann cells are the best substrate yet identified for promoting process growth in vitro by peripheral motor neurons. To determine the molecular interactions responsible for Schwann cell regulation of axon growth, we have examined the effects of specific antibodies on process growth in vitro, and have identified three glycoproteins that play major roles. These are the Ca2+-independent cell adhesion molecule (CAM), L1/Ng-CAM; the Ca2+-dependent CAM, N-cadherin; and members of the integrin extracellular matrix receptor superfamily. Two other CAMs present on neurons and/or Schwann cells-N-CAM and myelin-associated glycoprotein-do not appear to be important in regulating process growth. Our results imply that neuronal growth cones use integrin-class extracellular matrix receptors and at least two CAMs--N-cadherin and L1/Ng-CAM-for growth on Schwann cells in vitro and establish each of these glycoproteins as a strong candidate for regulating axon growth and guidance in vivo.
Antifungal Therapeutic Drug Monitoring: Established and Emerging Indications (2008)

The successful management of invasive fungal infections continues to pose a difficult challenge to clinicians. As the population of at-risk immunocompromised patients increases, the incidence of invasive mycosis has risen in parallel (57). Despite recent advances in antifungal pharmacology, the morbidity and mortality due to invasive fungal infections remain unacceptably high.

Numerous factors determine the outcome of these infections, including the host immune state, pathogen variables including drug susceptibility, location of the infection, timing of diagnosis relative to initiation of antifungal therapy, management of the infection source (e.g., surgery or vascular catheter removal), and effective administration of the appropriate dose of the most potent and safe antifungal drug (Fig. ​(Fig.1).1). Few of these variables are under the control of the clinician. The choices of antifungal drug and dosing regimen are among the factors which the clinician can dictate. However, even if the appropriate drug and regimen are initiated, drug exposure at the site of infection may be inadequate due to pharmacokinetic variability and may contribute to treatment failure. Conversely, antifungal exposures may exceed those anticipated and may result in toxicity. Many antifungal drugs exhibit marked variability in drug blood concentrations due to inconsistent absorption, metabolism, elimination, or interaction with concomitant medications. An understanding of the pharmacokinetics and pharmacodynamics of these drugs has been demonstrated to be important to optimize drug choice and dosing regimen design. One tool to detect drug exposures outside of the therapeutic window is monitoring of drug concentration in blood. The utility of this tool to inform drug choice and dosing decisions is being increasingly explored.



FIG. 1.

Determinants for outcome of invasive mycoses.



Several factors must be considered in determining the role of therapeutic drug monitoring in patient management (32, 86, 88). An accurate, rapid, and cost-effective drug assay must be readily available to the clinician. Two pharmacological features then determine the relevance of monitoring of concentrations of drug in blood. The foremost variable is an unpredictable drug dose-exposure relationship. Next, there must be a clear relationship between concentrations of drug in blood and either toxicity or treatment efficacy. Consideration of these pharmacological variables for available antifungal compounds is the focus of this review.
3D printing of new biobased unsaturated polyesters by microstereo-thermal-lithography (2014)

New micro three-dimensional (3D) scaffolds using biobased unsaturated polyesters (UPs) were prepared by microstereo-thermal-lithography (μSTLG). This advanced processing technique offers indubitable advantages over traditional printing methods. The accuracy and roughness of the 3D structures were evaluated by scanning electron microscopy and infinite focus microscopy, revealing a suitable roughness for cell attachment. UPs were synthesized by bulk polycondensation between biobased aliphatic diacids (succinic, adipic and sebacic acid) and two different glycols (propylene glycol and diethylene glycol) using fumaric acid as the source of double bonds. The chemical structures of the new oligomers were confirmed by proton nuclear magnetic resonance spectra, attenuated total reflectance Fourier transform infrared spectroscopy and matrix assisted laser desorption/ionization-time of flight mass spectrometry. The thermal and mechanical properties of the UPs were evaluated to determine the influence of the diacid/glycol ratio and the type of diacid in the polyester's properties. In addition an extensive thermal characterization of the polyesters is reported. The data presented in this work opens the possibility for the use of biobased polyesters in additive manufacturing technologies as a route to prepare biodegradable tailor made scaffolds that have potential applications in a tissue engineering area.
A murine cytokine fusion toxin specifically targeting the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor on normal committed bone marrow progenitor cells and GM-CSF-dependent tumor cells (1995)

A fusion protein was synthesized consisting of the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mGM-CSF hybrid gene was cloned into a vector under the control of an inducible promoter and the protein expressed in Escherichia coli. After induction, a protein was purified from inclusion bodies in accord with the deduced molecular weight of DT390 mGM-CSF. Cell-free studies of the adenosine diphosphate-ribosylating activity of DT390 mGM-CSF showed results that were similar to those of native DT. The DT390 mGM-CSF immunotoxin inhibited FDCP2.1d, a murine myelomonocytic tumor line expressing the GM-CSF receptor with an IC50 (concentration inhibiting 50% activity) of 5 x 10(-11) mol/L. The fusion toxin was specifically cytotoxic and directed by the GM-CSF portion of the molecule because addition of a monoclonal antibody directed against GM-CSF inhibited its ability to kill the cell line. Cell lines that do not express GM-CSF receptor were not inhibited by the fusion toxin. DT390 mGM-CSF was also able to specifically inhibit normal committed bone marrow (BM) progenitor cells as measured in clonal colony-forming unit granulocyte-macrophage assays. Together, these findings indicate that DT390 mGM-CSF may be useful as a novel tool for purging BM of contaminating leukemia cells or in vivo for eliminating residual leukemia cells. Also, it can be used to determine whether committed and/or noncommitted BM progenitor cells express the GM-CSF receptor.
Condensed Heteroaromatic Ring Systems. XXI. Synthesis of Pyrrolo(2,3-d)pyrimidines and Pyrrolo(3,2-d)pyrimidines. (1993)

Pyrrolo[2, 3-d]pyrimidines and pyrrolo[3, 2-d]pyrimidines were synthesized in high yields by the palladiumcatalyzed reaction of 4-acetylamino-5-bromopyrimidines and 5-acetylamino-4-iodopyrimidines with (Z)-1-ethoxy-2-(tributylstannyl)ethene followed by cyclization under acidic conditions.
Coronavirus and Pasteurella Infections in Bovine Shipping Fever Pneumonia and Evans' Criteria for Causation (2000)

Respiratory tract infections with viruses and Pasteurella spp. were determined sequentially among 26 cattle that died during two severe epizootics of shipping fever pneumonia. Nasal swab and serum samples were collected prior to onset of the epizootics, during disease progression, and after death, when necropsies were performed and lung samples were collected. Eighteen normal control cattle also were sampled at the beginning of the epizootics as well as at weekly intervals for 4 weeks. Respiratory bovine coronaviruses (RBCV) were isolated from nasal secretions of 21 and 25 cattle before and after transport. Two and 17 cattle nasally shed Pasteurella spp. before and after transport, respectively. RBCV were isolated at titers of 1 x 10(3) to 1.2 x 10(7) PFU per g of lung tissue from 18 cattle that died within 7 days of the epizootics, but not from the lungs of the remaining cattle that died on days 9 to 36. Twenty-five of the 26 lung samples were positive for Pasteurella spp., and their CFU ranged between 4.0 x 10(5) and 2.3 x 10(9) per g. Acute and subacute exudative, necrotizing lobar pneumonia characterized the lung lesions of these cattle with a majority of pneumonic lung lobes exhibiting fibronecrotic and exudative changes typical of pneumonic pasteurellosis, but other lung lobules had histological changes consisting of bronchiolitis and alveolitis typical of virus-induced changes. These cattle were immunologically naive to both infectious agents at the onset of the epizootics, but those that died after day 7 had rising antibody titers against RBCV and Pasteurella haemolytica. In contrast, the 18 clinically normal and RBCV isolation-negative cattle had high hemagglutinin inhibition antibody titers to RBCV from the beginning, while their antibody responses to P. haemolytica antigens were delayed. Evans' criteria for causation were applied to our findings because of the multifactorial nature of shipping fever pneumonia. This analysis identified RBCV as the primary inciting cause in these two epizootics. These viruses were previously not recognized as a causative agent in this complex respiratory tract disease of cattle.
Niacin stimulates adiponectin secretion through the GPR109A receptor (2009)

Niacin (nicotinic acid) has recently been shown to increase serum adiponectin concentrations in men with the metabolic syndrome. However, little is known about the mechanism(s) by which niacin regulates the intracellular trafficking and secretion of adiponectin. Since niacin appears to exert its effects on lipolysis through receptor (GPR109A)-dependent and -independent pathways, the purpose of this investigation was to examine the role of the recently identified GPR109A receptor in adiponectin secretion. Initial in vivo studies in rats demonstrated that niacin (30 mg/kg po) acutely increases serum adiponectin concentrations, whereas it decreases NEFAs. Further in vitro studies demonstrated an increase in adiponectin secretion and a decrease in lipolysis in primary adipocytes following treatment with niacin or beta-hydroxybutyrate (an endogenous ligand of the GPR109A receptor), but these effects were blocked when adipocytes were pretreated with pertussis toxin. Niacin had no effect on adiponectin secretion or lipolysis in 3T3-L1 adipocytes, which have limited cell surface expression of the GPR109A receptor. To further substantiate these in vitro findings, wild-type and GPR109A receptor knockout mice were administered a single dose of niacin or placebo, and serum was obtained for the determination of adiponectin and NEFA concentrations. Serum adiponectin concentrations increased and serum NEFAs decreased in the wild-type mice within 10 min following niacin administration. However, niacin administration had no effect on adiponectin and NEFA concentrations in the GPR109A receptor knockout mice. These results demonstrate that the GPR109A receptor plays an important role in the dual regulation of adiponectin secretion and lipolysis.