gebhart/patrepeval huggingface dataset:
SCREENING OF TOXIC COMPOUNDS IN MAMMALIAN CELL CULTURES (1983)

The cytotoxic concentrations of about 100 randomly selected drugs and chemicals, tested on HeLa cells in the MIT-24 system and/or in primary cultures of fetal chicken cells, were compared with the lethal doses and/or concentrations of the agents in the mouse and in man. Most agents (80%) had a similar toxicity in vitro and in vivo, suggesting a lethal interference in man with basal functions common to all specialized human tissues as well as cultured cells, i.e., basal cytotoxicity. This high frequency of basally cytotoxic agents opens possibilities for screening chemicals for toxicity and for studying cytotoxic mechanisms with a standard battery of a few appropriate cell tests. This battery may be used in three ways: (1) to study cytotoxic mechanisms of all chemicals, and apply the resulting knowledge to understanding toxicity in man of basally cytotoxic agents; (2) to supplement conventional animal tests in acute toxicity test programs; (3) to screen chemicals and extracts for their potential basal cytotoxicity. To validate these ideas and to select suitable tests for the battery, results from cytotoxicity tests on a wide variety of chemicals in several in vitro systems must be compared with one another and with the toxicity of the agents in animals and man.
Parameters contributing to efficient ion generation in aerosol MALDI mass spectrometry (2007)

The Bioaerosol Mass Spectrometry (BAMS) system was developed for the real-time detection and identification of biological aerosols using laser desorption ionization. Greater differentiation of particle types is desired; consequently MALDI techniques are being investigated. The small sample size ( approximately 1 microm3), lack of substrate, and ability to simultaneously monitor both positive and negative ions provide a unique opportunity to gain new insight into the MALDI process. Several parameters known to influence MALDI molecular ion yield and formation are investigated here in the single particle phase. A comparative study of five matrices (2,6-dihydroxyacetophenone, 2,5-dihydroxybenzoic acid, alpha-cyano-4-hydroxycinnamic acid, ferulic acid, and sinapinic acid) with a single analyte (angiotensin I) is presented and reveals effects of matrix selection, matrix-to-analyte molar ratio, and aerosol particle diameter. The strongest analyte ion signal is found at a matrix-to-analyte molar ratio of 100:1. At this ratio, the matrices yielding the least and greatest analyte molecular ion formation are ferulic acid and alpha-cyano-4-hydroxycinnamic acid, respectively. Additionally, a significant positive correlation is found between aerodynamic particle diameter and analyte molecular ion yield for all matrices. SEM imaging of select aerosol particle types reveals interesting surface morphology and structure.
An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices (2017)

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression, but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments that halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS). Although PCLS production from IPF explants is possible, IPF explants are rare and typically represent end-stage disease. Here we present a novel model of early fibrosis-like changes in human PCLS derived from patients without ILD/IPF using a combination of profibrotic growth factors and signaling molecules (transforming growth factor-β, tumor necrosis factor-α, platelet-derived growth factor-AB, and lysophosphatidic acid). Fibrotic-like changes of PCLS were qualitatively analyzed by histology and immunofluorescence and quantitatively by water-soluble tetrazolium-1, RT-qPCR, Western blot analysis, and ELISA. PCLS remained viable after 5 days of treatment, and fibrotic gene expression (<i>FN1</i>, <i>SERPINE1</i>, <i>COL1A1</i>, <i>CTGF</i>, <i>MMP7</i>, and <i>ACTA2)</i> increased as early as 24 h of treatment, with increases in protein levels at 48 h and increased deposition of extracellular matrix. Alveolar epithelium reprogramming was evident by decreases in surfactant protein C and loss of <i>HOPX</i> In summary, using human-derived PCLS, we established a novel ex vivo model that displays characteristics of early fibrosis and could be used to evaluate novel therapies and study early-stage IPF pathomechanisms.
Adiabatic mode coupling between SiGe photonic devices and SOI waveguides (2012)

We describe the coupling between optical modes of silicon-on-insulator SOI waveguides and Ge/SiGe quantum well modulators using an eigenmode expansion method. Laterally tapered features in the epitaxial layers are investigated for adiabatic optical coupling, and we find that there is a critical width range of the Ge/SiGe structure of 200-300 nm, where the taper angle should be minimised. We identify optimised taper profiles, which, for 1-μm-wide waveguides, allow the length of an adiabatic taper to be reduced from 250 μm for a simple linear profile to 40 μm for the optimised structure.
Functional extensions of Dip Pen NanolithographyTM: active probes and microfluidic ink delivery (2005)

Dip Pen Nanolithography (DPN™) is an important technique for nanotechnology and a fundamental new tool for studying the consequences of miniaturization. In this scanning probe technique a sharp tip is coated with a functional molecule (the 'ink') then brought into contact with a surface where it deposits ink via a water meniscus. The DPN process is a direct-write pattern transfer technique with nanometer resolution and is inherently general with respect to usable inks and substrates, including biomolecules such as proteins and oligonucleotides. We present functional extensions of the basic DPN process by showing multiple active probes along with the ability to load different inks onto probe tips. We present the fabrication process and characterization of thermomechanically actuated probes that use the bimorph effect to induce deflection of individual cantilevers as well as the integration of these probes with control electronics and an interface module. As an additional improvement to DPN functionality, we developed the capability to write with different inks on the probe array, permitting the fabrication of multicomponent nanodevices in one writing session. For this purpose, we fabricate passive microfluidic devices and present the microfluidic behavior and ink loading performance of these components.
Corynebacterial Protein Kinase G Controls 2-Oxoglutarate Dehydrogenase Activity via the Phosphorylation Status of the OdhI Protein (2006)

A novel regulatory mechanism for control of the ubiquitous 2-oxoglutarate dehydrogenase complex (ODH), a key enzyme of the tricarboxylic acid cycle, was discovered in the actinomycete Corynebacterium glutamicum, a close relative of important human pathogens like Corynebacterium diphtheriae and Mycobacterium tuberculosis. Based on the finding that a C. glutamicum mutant lacking serine/threonine protein kinase G (PknG) was impaired in glutamine utilization, proteome comparisons led to the identification of OdhI as a putative substrate of PknG. OdhI is a 15-kDa protein with a forkhead-associated domain and a homolog of mycobacterial GarA. By using purified proteins, PknG was shown to phosphorylate OdhI at threonine 14. The glutamine utilization defect of the delta pknG mutant could be abolished by the additional deletion of odhI, whereas transformation of a delta odhI mutant with a plasmid encoding OdhI-T14A caused a defect in glutamine utilization. Affinity purification of OdhI-T14A led to the specific copurification of OdhA, the E1 subunit of ODH. Because ODH is essential for glutamine utilization, we assumed that unphosphorylated OdhI inhibits ODH activity. In fact, OdhI was shown to strongly inhibit ODH activity with a Ki value of 2.4 nM. The regulatory mechanism described offers a molecular clue for the reduced ODH activity that is essential for the industrial production of 1.5 million tons/year of glutamate with C. glutamicum. Moreover, because this signaling cascade is likely to operate also in mycobacteria, our results suggest that the attenuated pathogenicity of mycobacteria lacking PknG might be caused by a disturbed tricarboxylic acid cycle.
Protecting Your Idea: Think Twice before Seeing Your Patent Attorney (1995)

The actual advantages and need of patenting ideas by any firm or researcher are identified. It is shown that that patents are not desirable in all conditions and are required only when the product requires some sort of control and integration of processes.
Urokinase-type Plasminogen Activator-induced Monocyte Adhesion Requires a Carboxyl-terminal Lysine and cAMP-dependent Signal Transduction (1995)

Urokinase-type plasminogen activator (u-PA) or its amino-terminal fragment (ATF) containing the u-PA receptor (u-PAR) binding domain, is known to promote monocyte adhesion. In the present study, U937 monocyte adhesion to a plastic surface was used to investigate the mechanism of its promotion by u-PA and ATF. Adhesion was found to be inhibited by cycloheximide or actinomycin D, implicating protein synthesis and gene expression in u-PA-induced monocyte adhesion. Adhesion was prevented by 2'-deoxyadenosine 3'-monophosphate, indicating that a cAMP-dependent pathway of signal transduction was involved. This concept was supported by the complementary finding that u-PA-induced adhesion was greatly promoted by forskolin, cholera toxin, or 8-bromo-cAMP, which by themselves induced little adhesion. Furthermore, similar to many other cAMP-dependent activities, cGMP diminished u-PA-induced adhesion. When u-PA or ATF was treated with immobilized carboxypeptidase B, its proadhesive effect was abolished, implicating the involvement of carboxyl-terminal lysine residues (Lys158 on u-PA and Lys135 on ATF). Moreover, when a carboxyl-terminal lysine analog was added, the proadhesive effect of carboxypeptidase B-treated u-PA or ATF was restored. In conclusion, the present study indicates that u-PA- or ATF-induced monocyte adhesion involves cAMP-dependent signal transduction, which is triggered by u-PAR binding. It is also critically dependent on the presence of a carboxyl-terminal lysine.
Assessment of bone condition by acoustic emission technique: A review (2009)

The paper deals with the review of acoustic emission technique in biomedical field. The review is done with the aim to provide an overview of the use of AE technique in biomedical field, mainly concentrated on the AE behavior of bone under different loading conditions, its dependence on strain rate, in osteoporosis, monitoring the fracture healing process of bone. The overall conclusion from the review was that almost all the studies in bone indicated that the initial AE occurs only in the plastic region and just prior to yield. That means the use of AE technique for clinical application cannot be considered as a safe technique, but the early occurrence of AE events from callus promises the application of AE technique for monitoring the fracture healing process. The negligible effect of soft tissues on AE response of bone promises AE to become a non-invasive method for assessment of bone condition.
Identification of the Mismatch Negativity in the Responses of Individual Listeners (2000)

The mismatch negativity (MMN) was recorded from normal adults in three stimulus conditions: two contrast conditions and a control condition in which standard and deviant stimuli were identical. Averaged waveforms were analyzed by examiners blind to the evoking stimulus condition. Hit rates, a false alarm rate, and d' values were determined based on the number of MMNs identified in each condition. Hit rates were low and the false alarm rate was relatively high, resulting in unacceptably small d' values. The relationship between MMN findings and corresponding behavioral discrimination data for individual listeners was not systematic. Factors that may contribute to ambiguity and error in MMN data analysis are discussed.
Human recombinant apolipoprotein E redirects lipopolysaccharide from Kupffer cells to liver parenchymal cells in rats In vivo. (1997)

Chylomicrons have been shown to protect mice and rats against a lethal dose of lipopolysaccharide and may serve as a therapeutic means to protect against endotoxemia. However, the requisite of isolation from human lymph hampers pharmaceutical application. Recently, we developed recombinant chylomicrons from commercially available lipids and human recombinant apolipoprotein E. The current study explored the effectiveness of these apoE-enriched emulsions in redirecting LPS from Kupffer cells to liver parenchymal cells. Upon injection into rats, 125I-LPS rapidly and specifically associated with the liver (64.3+/-3.1% of the injected dose) and spleen (4.1+/-0.7%). The uptake of LPS by the spleen was four- to fivefold reduced upon incubation with the apoE-enriched emulsion or free apoE (P < 0.0001), but not with emulsion alone or Lipofundin. Within the liver, 125I-LPS mainly associated with Kupffer cells. The uptake by Kupffer cells was eight- to ninefold reduced by the apoE-enriched emulsion or apoE alone (P < 0.01), and a 19.6-fold increased uptake ratio by liver parenchymal cells over Kupffer cells was observed. The emulsion without apoE had no effect on the in vivo kinetics of LPS. LPS interacted selectively with the apoE moiety of the recombinant chylomicron. Emulsion-associated and free apoE bound approximately two molecules of LPS, possibly by its exposed hydrophilic domain involving arginine residues. We anticipate that the protecting effect of endogenous chylomicrons against LPS-induced endotoxemia may result from the apoE moiety and that human recombinant apoE may serve as a therapeuticum to protect against endotoxemia.
Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence (2007)

The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) inhibits hematopoietic stem cell (HSC) expansion, interferes with HSC self-renewal and compromises the ability of HSC to reconstitute hematopoiesis. We have investigated mechanisms by which TNFalpha suppresses hematopoiesis using the genomic instability syndrome Fanconi anemia mouse model deficient for the complementation-group-C gene (Fancc). Examination of senescence makers, such as senescence-associated beta-galactosidase, HP1-gamma, p53 and p16(INK4A) shows that TNFalpha induces premature senescence in bone marrow HSCs and progenitor cells as well as other tissues of Fancc-/- mice. TNFalpha-induced senescence correlates with the accumulation of reactive oxygen species (ROS) and oxidative DNA damage. Neutralization of TNFalpha or deletion of the TNF receptor in Fancc-/- mice (Fancc-/-;Tnfr1-/-) prevents excessive ROS production and hematopoietic senescence. Pretreatment of TNFalpha-injected Fancc-/- mice with a ROS scavenger significantly reduces oxidative base damage, DNA strand breaks and senescence. Furthermore, HSCs and progenitor cells from TNFalpha-treated Fancc-/- mice show increased chromosomal aberrations and have an impaired oxidative DNA-damage repair. These results indicate an intimate link between inflammatory reactive oxygen species and DNA-damage-induced premature senescence in HSCs and progenitor cells, which may play an important role in aging and anemia.
Cycling Probe Technology with RNase H Attached to an Oligonucleotide (1996)

A streptavidin-RNase H gene fusion was constructed by cloning the Thermus thermophilus RNase H coding sequence in the streptavidin expression vector pTSA18F. The gene was expressed in Escherichia coli, and the resulting fusion protein was purified to apparent homogeneity. The fusion protein was shown to have a molecular weight of 128 kDa and to consist of four subunits. Furthermore, heat treatment of the fusion enzyme showed that it was stable as a tetramer at 65 degrees C. The fusion enzyme was shown to have both biotin binding and RNase H catalytic properties. Using cycling probe technology (CPT), the fusion enzyme was compared to the native RNase H with a biotinylated probe at different ratios of probe:enzyme and varying amounts of synthetic target DNA. At a ratio of 1:1, the fusion enzyme was active in CPT, but the native enzyme was not; both enzymes were active at a 1:5000 ratio of probe:enzyme. The fusion enzyme was further tested using biotinylated and non-biotinylated probes and was shown to be active at a 1:1 ratio with the biotinylated probe but not with the non-biotinylated probe. These experiments show that through binding of the streptavidin-RNase H fusion enzyme to the biotinylated probe, the efficiency of the cycling probe reaction is enhanced.
Mitochondrial decay in hepatocytes from old rats: Membrane potential declines, heterogeneity and oxidants increase (1997)

Mitochondrial function during aging was assessed in isolated rat hepatocytes to avoid the problem of differential lysis when old, fragile mitochondria are isolated. Rhodamine 123, a fluorescent dye that accumulates in mitochondria on the basis of their membrane potential, was used as a probe to determine whether this key function is affected by aging. A marked fluorescent heterogeneity was observed in hepatocytes from old (20-28 months) but not young (3-5 months) rats, suggesting age-associated alterations in mitochondrial membrane potential, the driving force for ATP synthesis. Three distinct cell subpopulations were separated by centrifugal elutriation; each exhibited a unique rhodamine 123 fluorescence pattern, with the largest population from old rats having significantly lower fluorescence than that seen in young rats. This apparent age-associated alteration in mitochondrial membrane potential was confirmed by measurements with radioactive tetraphenylphosphonium bromide. Cells from young rats had a calculated membrane potential of -154 mV, in contrast to that of the three subpopulations from old rats of -70 mV (the largest population), -93 mV, and -154 mV. Production of oxidants was examined using 2',7'dichlorofluorescin, a dye that forms a fluorescent product upon oxidation. The largest cell subpopulation and a minor one from old animals produced significantly more oxidants than cells from young rats. To investigate the molecular cause(s) for the heterogeneity, we determined the levels of an age-associated mtDNA deletion. No significant differences were seen in the three subpopulations, indicating that the mitochondrial decay is due to other mutations, epigenetic changes, or both.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS (1935)

Experiments on the sensitization of guinea pigs with simple chemical compounds are described. Positive effects were obtained by the administration of small quantities, namely fractions of milligrams, with 1:2:4 chlorodinitrobenzene, p-nitrosodimethylaniline, 1:2:4 trinitrobenzene, picryl chloride, four dichlorodinitrobenzenes, and a number of other aromatic compounds. Several substances chemically similar to those enumerated gave negative results. The first named compound is known to produce hypersensitiveness in human beings, a large number of cases having been observed in factory workers. The mechanism of these effects is discussed.
Ellipsometric method for separate measurements of n and d of a transparent film (1975)

This paper describes an ellipsometric method that enables separate measurements of refractive index n and thickness d of a transparent film at an arbitrary angle of incidence and thus facilitates optical monitoring of a growing film. The method is useful for homogeneous transparent films deposited on a transparent substrate.
Carotid Endarterectomy: The Gold Standard (1996)

Carotid endarterectomy has been firmly established as the gold standard of therapy for symptomatic and asymptomatic patients with severe carotid stenosis, provided surgical complication rates are within prescribed limits. The procedure-related risk of stroke/death should be &lt; 3% in asymptomatic patients and &lt; 6% in symptomatic patients. New investigational therapies such as balloon angioplasty and stenting for carotid stenosis should be evaluated against the same standard.
Adenomatous Polyposis Coli (APC)-independent Regulation of β-Catenin Degradation via a Retinoid X Receptor-mediated Pathway (2003)

Beta-catenin is a component of stable cell adherent complexes whereas its free form functions as a transcription factor that regulate genes involved in oncogenesis and metastasis. Free beta-catenin is eliminated by two adenomatous polyposis coli (APC)-dependent proteasomal degradation pathways regulated by glycogen synthase kinase 3beta (GSK3 beta) or p53-inducible Siah-1. Dysregulation of beta-catenin turnover consequent to mutations in critical genes of the APC-dependent pathways is implicated in cancers such as colorectal cancer. We have identified a novel retinoid X receptor (RXR)-mediated APC-independent pathway in the regulation of beta-catenin. In this proteasomal pathway, RXR agonists induce degradation of beta-catenin and RXR alpha and repress beta-catenin-mediated transcription. In vivo, beta-catenin interacts with RXR alpha in the absence of ligand, but RXR agonists enhanced the interaction. RXR agonist action was not impaired by GSK3 beta inhibitors or deletion of the GSK3 beta-targeted sequence from beta-catenin. In APC- and p53-mutated colorectal cancer cells, RXR agonists still inactivated endogenous beta-catenin via RXR alpha. Interestingly, deletion of the RXR alpha A/B region abolished ligand-induced beta-catenin degradation but not RXR alpha-mediated transactivation. RXR alpha-mediated inactivation of oncogenic beta-catenin paralleled a reduction in cell proliferation. These results suggest a potential role for RXR and its agonists in the regulation of beta-catenin turnover and related biological events.
Elimination of tumor by CD47/PD-L1 dual-targeting fusion protein that engages innate and adaptive immune responses (2017)

The host immune system generally serves as a barrier against tumor formation. Programmed death-ligand 1 (PD-L1) is a critical "don't find me" signal to the adaptive immune system, whereas CD47 transmits an anti-phagocytic signal, known as the "don't eat me" signal, to the innate immune system. These and similar immune checkpoints are often overexpressed on human tumors. Thus, dual targeting both innate and adaptive immune checkpoints would likely maximize anti-tumor therapeutic effect and elicit more durable responses. Herein, based on the variable region of atezolizumab and consensus variant 1 (CV1) monomer, we constructed a dual-targeting fusion protein targeting both CD47 and PD-L1 using "Knobs-into-holes" technology, denoted as IAB. It was effective in inducing phagocytosis of tumor cells, stimulating T-cell activation and mediating antibody-dependent cell-mediated cytotoxicity in vitro. No obvious sign of hematological toxicity was observed in mice administered IAB at a dose of 100 mg/kg, and IAB exhibited potent antitumor activity in an immune-competent mouse model of MC38. Additionally, the anti-tumor effect of IAB was impaired by anti-CD8 antibody or clodronate liposomes, which implied that both CD8+ T cells and macrophages were required for the anti-tumor efficacy of IAB and IAB plays an essential role in the engagement of innate and adaptive immune responses. Collectively, these results demonstrate the capacity of an elicited endogenous immune response against tumors and elucidate essential characteristics of synergistic innate and adaptive immune response, and indicate dual blockade of CD47 and PD-L1 by IAB may be a synergistic therapy that activates both innate and adaptive immune response against tumors.