gebhart/patrepeval huggingface dataset:
In vivo characterization of the type A and B vancomycin-resistant enterococci (VRE) VanRS two-component systems in Escherichia coli : A nonpathogenic model for studying the VRE signal transduction pathways (1998)

Escherichia coli reporter strains modeling the high-level type A and B vancomycin resistances of Enterococcus faecium BM4147 and Ent. faecalis have been developed to study the respective VanR-VanS two-component regulatory systems. PvanH-, PvanRa-, PvanY-, and PvanRb-lacZ fusions report on expression from the vancomycin-resistant enterococci promoters of the type A vanRSHAXYZ and type B vanRSYWHBX gene clusters. These strains also express from single-copy chromosomal genes vanRa, vanRb, or vanRSb behind their respective promoter (PvanRa or PvanRb) or vanSa or vanSb behind the rhamnose-inducible PrhaB. Results show that activation (phosphorylation) of the response regulator VanRa by its sensor kinase VanSa leads to transcriptional activation of both PvanH and PvanRa. Additionally, VanRb activates its cognate promoters PvanY and PvanRb, although this occurs only in the absence of VanSb and presumably is caused by VanRb phosphorylation by an unidentified endogenous E. coli kinase. Thus, VanSb interferes with activation of VanRb, probably by acting as a phospho-VanRb phosphatase. Although both VanRa and VanRb activate their cognate promoters, neither activates the heterologous PvanR, PvanH, or PvanY, arguing against the interchangeability of type A and B two-component regulatory switches in vancomycin-resistant enterococci. VanRa also is activated by the nonpartner kinase PhoR. Because this occurs in the absence of its inducing signal (Pi limitation), PhoR autophosphorylation apparently is regulated in vivo. Furthermore, the activation of VanRa caused by cross talk from PhoR in the absence of a signal allows distinction of cross talk from crossregulation as the latter, but not the former, responds to environmental cues.
Human Tumor Xenograft Efficacy Models (2010)

Mouse models of cancer have consistently been used to qualify new anticancer drugs for development of human clinical trials. The most used models are xenografts of human tumors grown in immunodeficient mice. Retrospective preclinical–clinical correlation studies indicate that xenograft models are very useful and the models continue to make contributions to critical clinical development choices. However, improvements must be made to increase their values. Here, we review the value and the limitations of xenograft models, and discuss how to enhance their role in developing new anticancer treatments.
Thermomechanical writing with an atomic force microscope tip (1992)

We have developed a new technique to perform fast, reliable nanoindentation of polymer surfaces for possible applications to high density data storage. In this technique, an infrared laser is focused on an atomic force microscope (AFM) tip, which is in contact with a transparent polymethyl methacrylate (PMMA) substrate. The heat from the tip softens the PMMA in the contact region, at which point the local tip pressure creates a pit. The pits range in size from several hundred angstroms to 1 μm, depending on the size of the laser pulse and the loading force on the tip. Pits have been made with pulses as short as 0.3 μs at loads of 10−7 N. By operating the AFM on a rotating disk, we have shown that the features can be written and read at frequencies up to at least 100 kHz.
Localization of Laminin α4-Chain in Developing and Adult Human Tissues (2002)

Recent studies suggest important functions for laminin-8 (Ln-8; alpha4beta1gamma1) in vascular and blood cell biology, but its distribution in human tissues has remained elusive. We have raised a monoclonal antibody (MAb) FC10, and by enzyme-linked immunoassay (EIA) and Western blotting techniques we show that it recognizes the human Ln alpha4-chain. Immunoreactivity for the Ln alpha4-chain was localized in tissues of mesodermal origin, such as basement membranes (BMs) of endothelia, adipocytes, and skeletal, smooth, and cardiac muscle cells. In addition, the Ln alpha4-chain was found in regions of some epithelial BMs, including epidermis, salivary glands, pancreas, esophageal and gastric glands, intestinal crypts, and some renal medullary tubules. Developmental differences in the distribution of Ln alpha4-chain were detected in skeletal muscle, walls of vessels, and intestinal crypts. Ln alpha4- and Ln alpha2-chains co-localized in BMs of fetal skeletal muscle cells and in some epithelial BMs, e.g., in gastric glands and acini of pancreas. Cultured human pulmonary artery endothelial (HPAE) cells produced Ln alpha4-chain as M(r) 180,000 and 200,000 doublet and rapidly deposited it to the growth substratum. In cell-free extracellular matrices of human kidney and lung, Ln alpha4-chain was found as M(r) 180,000 protein.
Large-scale synthesis and functional elements for the antimicrobial activity of defensins (2000)

Human neutrophil defensins, and their analogues incorporating anionic, hydrophobic or cationic residues at the N- and C-termini, were synthesized by solid-phase procedures. The synthetic defensins were examined for their microbicidal activity against Candida albicans, two Gram-negative bacteria (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) and two Gram-positive bacteria (Streptococcus gordonii and Streptococcus mutans). The human neutrophil peptide 1 (HNP1) and HNP2 were found to be potent candidacidal agents. HNP3, which differs by one amino acid at the N-terminus of its sequence, was totally inactive. The Gram-negative bacteria A. actinomycetemcomitans and P. gingivalis and the Gram-positive bacteria S. gordonii and S. mutans were insensitive to human defensins. However, the insertion of two basic residues, such as arginine, at both the N-terminus and the C-terminus of HNP2 significantly enhanced antifungal and antibacterial activity. The addition of anionic residues, such as aspartic acid, at the N- and C-termini rendered the molecule totally inactive. The presence of two hydrophobic amino acids, such as valine, at the N-terminus of HNP2 and of two basic arginine residues at its C-terminus resulted in molecules that were optimally active against these oral pathogens. The results suggest that the N- and C-terminal residues in defensin peptides are the crucial functional elements that determine their microbicidal potency. The three-dimensional structure of all defensins constitutes the same amphiphilic beta-sheet structure, with the polar face formed by the N- and C-terminal residues playing an important role in defining microbicidal potency and the antimicrobial spectrum. The enhanced microbicidal activity observed for defensin peptides with two basic residues at both the N- and C-termini could be due to optimization of the amphiphilicity of the structure, which could facilitate specific interactions with the microbial membranes.
Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide‐enhanced magnetic resonance imaging (2004)

Tracking of macrophages by MRI provides direct evidence of the immunomodulatory efficacy of FTY720 in the EAE model and correlates well with neurological symptoms and histology.
NH4Cl Treatment Prevents Tissue Calcification in Klotho Deficiency (2015)

Klotho, a cofactor in suppressing 1,25(OH)2D3 formation, is a powerful regulator of mineral metabolism. Klotho-hypomorphic mice (kl/kl) exhibit excessive plasma 1,25(OH)2D3, Ca(2+), and phosphate concentrations, severe tissue calcification, volume depletion with hyperaldosteronism, and early death. Calcification is paralleled by overexpression of osteoinductive transcription factor Runx2/Cbfa1, Alpl, and senescence-associated molecules Tgfb1, Pai-1, p21, and Glb1. Here, we show that NH4Cl treatment in drinking water (0.28 M) prevented soft tissue and vascular calcification and increased the life span of kl/kl mice >12-fold in males and >4-fold in females without significantly affecting extracellular pH or plasma concentrations of 1,25(OH)2D3, Ca(2+), and phosphate. NH4Cl treatment significantly decreased plasma aldosterone and antidiuretic hormone concentrations and reversed the increase of Runx2/Cbfa1, Alpl, Tgfb1, Pai-1, p21, and Glb1 expression in aorta of kl/kl mice. Similarly, in primary human aortic smooth muscle cells (HAoSMCs), NH4Cl treatment reduced phosphate-induced mRNA expression of RUNX2/CBFA1, ALPL, and senescence-associated molecules. In both kl/kl mice and phosphate-treated HAoSMCs, levels of osmosensitive transcription factor NFAT5 and NFAT5-downstream mediator SOX9 were higher than in controls and decreased after NH4Cl treatment. Overexpression of NFAT5 in HAoSMCs mimicked the effect of phosphate and abrogated the effect of NH4Cl on SOX9, RUNX2/CBFA1, and ALPL mRNA expression. TGFB1 treatment of HAoSMCs upregulated NFAT5 expression and prevented the decrease of phosphate-induced NFAT5 expression after NH4Cl treatment. In conclusion, NH4Cl treatment prevents tissue calcification, reduces vascular senescence, and extends survival of klotho-hypomorphic mice. The effects of NH4Cl on vascular osteoinduction involve decrease of TGFB1 and inhibition of NFAT5-dependent osteochondrogenic signaling.
Morpheme- and POS-based IBM1 and language model scores for translation quality estimation (2012)

We present a method we used for the quality estimation shared task of WMT 2012 involving IBM 1 and language model scores calculated on morphemes and POS tags. The IBM 1 scores calculated on morphemes and POS-4grams of the source sentence and obtained translation output are shown to be competitive with the classic evaluation metrics for ranking of translation systems. Since these scores do not require any reference translations, they can be used as features for the quality estimation task presenting a connection between the source language and the obtained target language. In addition, target language model scores of morphemes and POS tags are investigated as estimates for the obtained target language quality.
Advances in the measurement of red blood cell deformability: A brief review (2015)

Red blood cells (RBCs) exhibit a unique deformability, which enables them to change shape reversibly in response to an external force. The deformability of RBCs allows them to flow in microvessels while transporting oxygen and carbon dioxide. In this review, we discussed the major determinants of RBC deformability, which include cell geometry, internal viscosity, rheological properties of the membrane, osmotic pressure, calcium, nitric oxide, temperature, ageing, and depletion of adenosine triphosphate. Additionally, we highlighted the various methods and techniques used to measure RBC deformability. Individual cell analyses (pipette aspiration and optical tweezers) and bulk cell analyses (ektacytometry, multiple channels) were described and compared. Finally, we reviewed the correlation between RBC deformability and clinical outcomes such as diabetic microangiopathy.
Comparative lipidomics analysis of HIV-1 particles and their producer cell membrane in different cell lines (2012)

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that obtains its lipid envelope by budding through the plasma membrane of infected host cells. Various studies indicated that the HIV-1 membrane differs from the producer cell plasma membrane suggesting virus budding from pre-existing subdomains or virus-mediated induction of a specialized budding membrane. To perform a comparative lipidomics analysis by quantitative mass spectrometry, we first evaluated two independent methods to isolate the cellular plasma membrane. Subsequent lipid analysis of plasma membranes and HIV-1 purified from two different cell lines revealed a significantly different lipid composition of the viral membrane compared with the host cell plasma membrane, independent of the cell type investigated. Virus particles were significantly enriched in phosphatidylserine, sphingomyelin, hexosylceramide and saturated phosphatidylcholine species when compared with the host cell plasma membrane of the producer cells; they showed reduced levels of unsaturated phosphatidylcholine species, phosphatidylethanolamine and phosphatidylinositol. Cell type-specific differences in the lipid composition of HIV-1 and donor plasmamembranes were observed for plasmalogen-phosphatidylethanolamine and phosphatidylglycerol, which were strongly enriched only in HIV-1 derived from MT-4 cells. MT-4 cell-derived HIV-1 also contained dihydrosphingomyelin as reported previously, but this lipid class was also enriched in the host cell membrane. Taken together, these data strongly support the hypothesis that HIV-1 selects a specific lipid environment for its morphogenesis.
Quantification of fluorophore concentration in tissue-simulating media by fluorescence measurements with a single optical fiber (2003)

Quantifying fluorescent compounds in turbid media such as tissue is made difficult by the effects of multiple scattering and absorption of the excitation and emission light. The approach that we used was to measure fluorescence using a single 200-microm optical fiber as both the illumination source and the detector. Fluorescence of aluminum phthalocyanine tetrasulfonate (AlPcS4) was measured over a wide range of fluorophore concentrations and optical properties in tissue-simulating phantoms. A root-mean-square accuracy of 10.6% in AlPcS4 concentration was attainable when fluorescence was measured either interstitially or at the phantom surface. The individual effects of scattering, absorption, and the scattering phase function on the fluorescence signal were also studied by experiments and Monte Carlo simulations.
Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria (2007)

Structural and genetic studies on prokaryotic ribosomes have provided important insights into fundamental aspects of protein synthesis and translational control and its interaction with ribosomal drugs. Comparable mechanistic studies in eukaryotes are mainly hampered by the absence of both high-resolution crystal structures and efficient genetic models. To study the interaction of aminoglycoside antibiotics with selected eukaryotic ribosomes, we replaced the bacterial drug binding site in 16S rRNA with its eukaryotic counterpart, resulting in bacterial hybrid ribosomes with a fully functional eukaryotic rRNA decoding site. Cell-free translation assays demonstrated that hybrid ribosomes carrying the rRNA decoding site of higher eukaryotes show pronounced resistance to aminoglycoside antibiotics, equivalent to that of rabbit reticulocyte ribosomes, while the decoding sites of parasitic protozoa show distinctive drug susceptibility. Our findings suggest that phylogenetically variable components of the ribosome, other than the rRNA-binding site, do not affect aminoglycoside susceptibility of the protein-synthesis machinery. The activities of the hybrid ribosomes indicate that helix 44 of the rRNA decoding site behaves as an autonomous domain, which can be exchanged between ribosomes of different phylogenetic domains for study of function.
Do Soluble Cell Adhesion Molecules Play a Role in Endometriosis? (2000)

PROBLEM: Endometriosis is a chronic inflammatory disease associated with diverse immunologic disturbances. Cell adhesion molecules are essential for the development of immune and inflammatory reactions. This study was conducted to investigate whether or not serum and peritoneal levels of soluble cell adhesion molecules are altered in women with endometriosis. METHOD OF STUDY: The study group comprised five women with moderate‐to‐severe endometriosis. Eight healthy women with a normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples from both groups were analyzed for the soluble isoform of intercellular cell adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), endothelial selectin (sES), and platelet selectin (sPS). RESULTS: Serum levels of sICAM‐1 were significantly increased in women with endometriosis (median levels: 410.4 ng/mL; range: 233.9 ng/mL–598.4 ng/mL vs. 235.7 ng/mL; range: 187.4 ng/mL–323.7 ng/mL; P= 0.02). Although the levels of sVCAM‐1, sES, and sPS in both samples were higher in the study group, the differences did not reach significance. CONCLUSIONS: Our results suggest a role of ICAM‐1 in the pathophysiology of endometriosis. However, the role of other investigated cell adhesion molecules should be confirmed by further studies.
Symptoms of Tobacco Withdrawal (1991)

Smokers (n = 315) who wished to quit were randomly assigned in a double-blind manner to groups using either nicotine or placebo gum. Self-reported and observed symptoms of tobacco withdrawal were collected before cessation and at follow-ups of 1 to 2 weeks, 1 month, and 6 months. Self-reported and/or observed anger, anxiety, craving, difficulty concentrating, hunger, impatience, and restlessness were the most prominent symptoms of tobacco withdrawal. These symptoms had returned to precessation levels by 1 month except increased weight, hunger, and craving continued for 6 months in many smokers. Nicotine gum decreased most symptoms, including craving and hunger but not weight. Abstinent smokers with more intense withdrawal were not more likely to relapse. Abstinent smokers who gained more weight were less likely to relapse.
Prevention of Jarisch–Herxheimer Reactions by Treatment with Antibodies against Tumor Necrosis Factor α (1996)

Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.
Sensitive red protein calcium indicators for imaging neural activity (2016)

Abstract Genetically encoded calcium indicators (GECIs) allow measurement of activity in large populations of neurons and in small neuronal compartments, over times of milliseconds to months. Although GFP-based GECIs are widely used for in vivo neurophysiology, GECIs with red-shifted excitation and emission spectra have advantages for in vivo imaging because of reduced scattering and absorption in tissue, and a consequent reduction in phototoxicity. However, current red GECIs are inferior to the state-of-the-art GFP-based GCaMP6 indicators for detecting and quantifying neural activity. Here we present improved red GECIs based on mRuby (jRCaMP1a, b) and mApple (jRGECO1a), with sensitivity comparable to GCaMP6. We characterized the performance of the new red GECIs in cultured neurons and in mouse, Drosophila , zebrafish and C. elegans in vivo . Red GECIs facilitate deep-tissue imaging, dual-color imaging together with GFP-based reporters, and the use of optogenetics in combination with calcium imaging.
Serologic and Phenotypic Analysis of Blood Types Via Silicon Nanophotonics (2014)

Abstract Tens of millions of donor and patient samples are tested yearly to establish blood type compatibility between donor and recipient and to protect recipients from blood-borne infectious diseases. Blood type testing, particularly donor testing, is traditionally based in centralized clinical laboratories. However, current blood typing methods are encumbered by reagent availability, cost, technical training requirements, and time, placing a costly burden on the medical system. To address practical needs in blood typing, we have developed a multiplexed blood analysis platform using a low-cost and scalable silicon photonic biochip. This study investigates the use of silicon microring sensors to capture, detect, and quantify specific red blood cell (RBC) membrane antigens and anti-blood type antibodies from blood. To validate ABO blood phenotyping, microring resonators were streptavidin coated and functionalized with biotinylated anti-A IgM or biotinylated anti-B IgM antibodies. First, the response of anti-A/B functionalized microring resonators to characterized RBC membranes (RBC ghosts, 108 cells/ml) were measured in real-time (Figure 1). The biosensor arrays also exhibited minimal non-specific adsorption of RBC membrane fragments to the sensor surface. Microring resonators were shown to be suitable for identifying RBC ABO phenotype from donor blood samples. For ABO serologic analysis, silicon chips were functionalized with synthetic multivalent polymeric blood group antigens to serve as capture elements for circulating anti-ABO antibodies. Each chip also had sensors functionalized with biotinylated Protein A (btn-ProtA) and a biotinylated polyacrylamide polymer scaffold (btn-paa) to serve as on-chip positive and negative controls, respectively. The multiplexed biosensor chips were exposed to 100mL of plasma, followed by an anti-human-IgM antibody to enhance detection and quantification of antibodies bound to the surface. The resonance shift in each microring resonator was monitored over time, and the sensor response of the polymeric A and B blood group antigens was normalized to the control sensors. Figure 2 illustrates the levels of bound anti-A and anti-B for a panel of donor blood samples with varying ABO blood type, expressed as a relative shift in sensor resonance wavelength. These results demonstrate the detection of the naturally occurring' anti-A/B IgM antibodies for each respective ABO blood type. We have demonstrated that microring resonator biosensor arrays can quantitatively determine the donor ABO phenotypic and serologic status while incorporating on-chip controls for process standardization. Our work serves as proof-of-concept that a multiplexed silicon nanophotonics platform can rapidly detect both RBC antigens and anti-RBC antibodies in biological samples. This method has the potential for broad applicability in hematology and transfusion medicine for blood typing, quantitative monitoring of specific antibodies, and pathogen screening. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
Temporal Talbot effect in fiber gratings and its applications (1999)

We show that a temporal effect equivalent to the spatial Talbot effect (self-imaging) applies to the reflection of periodic pulse trains from linearly chirped fiber gratings (LCFG's). For specific input repetition periods the reflected signal is an exact replica of the input signal. Input repetition period values that give rise to this effect depend on the dispersion coefficient of the grating. We propose to use this effect as an alternative for dispersion measurement in LCFG's. Furthermore, by using the properties of the temporal Talbot effect, we can design linear passive devices (LCFG's) for use as frequency multipliers, able to multiply the repetition rate of a given pulse train.