gebhart/patrepeval huggingface dataset:
Direct toxic effect of the radiocontrast agent diatrizoate on renal proximal tubule cells (1987)

The pathophysiology of radiocontrast agent-induced acute renal failure is presently unclear. To test for a possible direct deleterious effect of diatrizoate, a commonly used radiocontrast agent, on renal tubule cells, suspensions enriched in rabbit proximal tubule segments were incubated with sodium diatrizoate. After these manipulations, a variety of well-established metabolic parameters to quantitate the extent of cell injury were measured. Diatrizoate sodium (25 mM) produced significant declines in tubule K+, ATP, and total adenine nucleotide (TAN) contents, significant decreases in tubule basal and uncoupled respiratory rates, and a significant increase in tubule Ca2+ content, demonstrating the development of cell injury induced by diatrizoate. These effects were dose related and were progressive with increasing incubation time from 97.5 to 157.5 min. The effects of N-methylglucosamine (meglumine) on renal tubule cell viability was also evaluated. Meglumine is a low molecular weight amino-substituted cationic compound and is commonly added to radiocontrast dye solutions. Meglumine (25 mM) had significant effects to lower tubule K+ content and to decrease both tubule basal and uncoupled respiratory rates. These alterations were slightly additive to diatrizoate in that meglumine diatrizoate produced greater alterations in tubule-metabolic parameters compared to diatrizoate sodium. A period of 22.5 min of hypoxia also caused deleterious changes in each of these quantitative indices of cell viability, and diatrizoate potentiated the degree of hypoxia-induced cell injury. These results demonstrate that the radiocontrast agent, diatrizoate, is directly toxic to renal proximal tubule cells. Meglumine, a cation added to diatrizoate containing radiocontrast solutions, also had a moderate toxic effect on renal epithelial cells and added to the toxicity of diatrizoate. Diatrizoate also aggravated the degree of cell injury induced by a 22.5-min period of hypoxia. These experiments thus provide evidence for a direct toxic effect of diatrizoate on proximal renal tubule cells which was additive to hypoxic cell injury.
Actin mRNA localizes in the absence of protein synthesis. (1990)

Actin mRNA is localized in chicken embryo fibroblasts to the distal regions of leading lamellae, but not within the ruffling edges. In this investigation we have addressed the role of actin translation in this process. The translocation of actin mRNA to the cell periphery was studied by monitoring the distribution of actin mRNA in cells during spreading. Within 90 min, actin mRNA moved from a perinuclear to a peripheral distribution. Formation of lamellipodia preceded actin mRNA localization, indicating that localization is not a prerequisite for this event. Neither puromycin (which dissociates ribosomes from mRNA) nor cycloheximide (which stabilizes ribosomes on mRNA) had any effect on this movement of actin mRNA. Anchoring of actin mRNA was studied using cells with peripherally localized actin mRNA. No change in actin mRNA localization was observed for 30 min in the same inhibitors. These data indicate that the presence of the nascent polypeptide is not necessary for translocation of actin mRNA to the cell periphery, or anchoring at that site. This suggests that the mRNA contains information concerning its spatial distribution within the cytoplasm.
Studies on the assembly and secretion of fibrinogen. (1991)

cDNAs of fibrinogen A alpha and gamma chains were individually subcloned into a eukaryotic expression vector by using the polymerase chain reaction. Triple cotransfection into COS cells of the two plasmids together with a B beta chain expression plasmid, constructed as described previously (Danishefsky, K.J., Hartwig, R., Banerjee, D., and Redman, C. (1990) Biochim. Biophys. Acta 1048, 202-208), resulted in the secretion of complete fibrinogen into the media and the formation of four additional intracellular complexes which we also showed to be present in the hepatocyte cell line Hep 3B. The complexes, which have Mr = 232, 150, 135, and 128 (x 10(-3) conform with the Mr expected for A alpha B beta gamma 2, B beta gamma 2 and gamma 3, respectively. A A mechanism of assembly is proposed based on the assumption that all these complexes are precursors of complete fibrinogen. Each of the expressed fibrinogen chains in transfected COS cells interacts noncovalently with binding protein (BiP, GRP 78), but not to the same extent; gamma chain binds less BiP than the A alpha and B beta chains. Assembly of fibrinogen is not absolutely required for its secretion. In addition to complete fibrinogen, the conditioned media of hepatocytes and of transfected COS cells contained free A alpha, free gamma, and two of the above-mentioned complexes, A alpha gamma 2 and A alpha B beta gamma 2.
The Immune Response to Pneumococcal Proteins during Experimental Human Carriage (2002)

Colonization of the nasopharynx is the initial step in all infections caused by Streptococcus pneumoniae. The antibody response to carriage was examined in an experimental model of human colonization in healthy adults. Asymptomatic colonization was detected in 6/14 subjects and continued for up to 122 d. Susceptibility to carriage did not correlate with total serum immunoglobulin (Ig)G to the homotypic capsular polysaccharide. All of the colonized subjects, in contrast, developed a serum IgG and secretory IgA response to a 22 kD protein, whereas 7 of 8 subjects who did not become colonized had preexisting antibody to this protein. Analysis of the 22 kD protein identified it as the NH(2)-terminal region of pneumococcal surface protein A (PspA). Our findings provide evidence for the role of antibody to this protein fragment in preventing pneumococcal carriage by humans.
Semantic Image Segmentation via Deep Parsing Network (2015)

This paper addresses semantic image segmentation by incorporating rich information into Markov Random Field (MRF), including high-order relations and mixture of label contexts. Unlike previous works that optimized MRFs using iterative algorithm, we solve MRF by proposing a Convolutional Neural Network (CNN), namely Deep Parsing Network (DPN), which enables deterministic end-to-end computation in a single forward pass. Specifically, DPN extends a contemporary CNN architecture to model unary terms and additional layers are carefully devised to approximate the mean field algorithm (MF) for pairwise terms. It has several appealing properties. First, different from the recent works that combined CNN and MRF, where many iterations of MF were required for each training image during back-propagation, DPN is able to achieve high performance by approximating one iteration of MF. Second, DPN represents various types of pairwise terms, making many existing works as its special cases. Third, DPN makes MF easier to be parallelized and speeded up in Graphical Processing Unit (GPU). DPN is thoroughly evaluated on the PASCAL VOC 2012 dataset, where a single DPN model yields a new state-of-the-art segmentation accuracy.
Brain Enolases as Specific Markers of Neuronal and Glial Cells (1978)

There are three distinct enolase isoenzymes in brain; neuron-specific enolase (NSE), formerly referred to as neuron-specific protein, which is specifically localized in neurons, a nonneuronal enolase (NNE), and a third hybrid form. Light microscopy with immunocytochemical techniques has permitted localization of non-neuronal enolase. The NNE is located in glial cells with no staining of endothelial cells or neurons. Thus, NSE and NNE can be used as specific metabolic markers for neurons and glial cells, respectively.
HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSION (2006)

The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen-regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago. Since the identification of EPO as the humoral regulator of red blood cell production and the cloning of the EPO gene, considerable progress has been made in understanding the regulation of EPO gene expression. This has finally led to the identification of a widespread cellular oxygen-sensing mechanism. Central to this mechanism is the transcription factor complex hypoxia-inducible factor (HIF)-1. The abundance and activity of HIF-1, a heterodimer of an alpha- and beta-subunit, is predominantly regulated by oxygen-dependent post-translational hydroxylation of the alpha-subunit. Non-heme ferrous iron containing hydroxylases use dioxygen and 2-oxoglutarate to specifically target proline and an asparagine residue in HIF-1alpha. As such, the three prolyl hydroxylases (prolyl hydroxylase domain-containing protein (PHD) 1, PHD2 and PHD3) and the asparagyl hydroxylase (factor inhibiting HIF (FIH)-1) act as cellular oxygen sensors. In addition to erythropoiesis, HIF-1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases. In addition to the tight regulation by oxygen tension, temporal and tissue-specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney.
5′ Unlocked Nucleic Acid Modification Improves siRNA Targeting (2013)

Optimization of small interfering RNAs (siRNAs) is important in RNA interference (RNAi)-based therapeutic development. Some specific chemical modifications can control which siRNA strand is selected by the RNA-induced silencing complex (RISC) for gene silencing. Intended strand selection will increase potency and reduce off-target effects from the unintended strand. Sometimes, blocking RISC loading of the unintended strand leads to improved intended strand-silencing potency, but the generality of this phenomenon is unclear. Specifically, unlocked nucleic acid (UNA) modification of the 5' end of canonical (i.e., 19+2) siRNAs abrogates gene silencing of the modified strand, but the fate and potency of the unmodified strand has not been investigated. Here, we show that 5' UNA-modified siRNAs show improved silencing potency of the unmodified strand. We harness this advantageous property in a therapeutic context, where a limited target region in a conserved HIV 5' long terminal repeat U5 region would otherwise yield siRNAs with undesired strand selection properties and poor silencing. Applying 5' UNA modification to the unintended sense (S) strand of these otherwise poorly targeted siRNAs dramatically improves on-target silencing by the intended antisense (AS) strand in pNL4-3.luciferase studies. This study highlights the utility of 5' UNA siRNA modification in therapeutic contexts where siRNA sequence selection is constrained.Molecular Therapy-Nucleic Acids (2013) 2, e103; doi:10.1038/mtna.2013.36; published online 2 July 2013.
Sequence-Specific Knockdown of EWS-FLI1 by Targeted, Nonviral Delivery of Small Interfering RNA Inhibits Tumor Growth in a Murine Model of Metastatic Ewing's Sarcoma (2005)

The development of effective, systemic therapies for metastatic cancer is highly desired. We show here that the systemic delivery of sequence-specific small interfering RNA (siRNA) against the EWS-FLI1 gene product by a targeted, nonviral delivery system dramatically inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. The nonviral delivery system uses a cyclodextrin-containing polycation to bind and protect siRNA and transferrin as a targeting ligand for delivery to transferrin receptor-expressing tumor cells. Removal of the targeting ligand or the use of a control siRNA sequence eliminates the antitumor effects. Additionally, no abnormalities in interleukin-12 and IFN-alpha, liver and kidney function tests, complete blood counts, or pathology of major organs are observed from long-term, low-pressure, low-volume tail-vein administrations. These data provide strong evidence for the safety and efficacy of this targeted, nonviral siRNA delivery system.
Free-space quantum-key distribution (1998)

A working free-space quantum key distribution (QKD) system has been developed and tested over a 205-m indoor optical path at Los Alamos National Laboratory under fluorescent lighting conditions. Results show that free-space QKD can provide a secure real-time key distribution between parties who have a need to communicate secretly.
Expression of CD74 by AML blasts and cell lines, and enhanced in vitro cytotoxicity of anti-CD74 antibody after interferon-gamma (IFN-γ) treatment. (2010)

6576 Background: CD74 (DR-associated invariant chain) is expressed alone or with DR in a wide range of hematologic cancers and solid tumors. Humanized anti-CD74 mAb, milatuzumab (Immunomedics, Morris Plains, NJ), exhibits direct cytotoxicity for NHL, CLL and MM cell lines, and is in clinical evaluation for therapy of NHL, MM and CLL. Also, CD74 is induced by interferons in multiple cancer cell lines. Here we report an evaluation of CD74 expression and function in AML, and the effect of CD74 upregulation by treatment with IFN-γ on the cytotoxicity of milatuzumab for AML cell lines. Methods: CD74 expression in bone marrow biopsy (BMB) specimens from non-M3 AML patients was evaluated by immunohistochemistry and, for the 3 human AML cell lines, by flow cytometry, with/without permeabilization and with/without IFN-γ (40 and 200 U/mL). These cell lines were also tested in proliferation assays for responses to milatuzumab, with/without IFN-γ. Results: In 13/14 BMB specimens, there was moderate to strong CD74 expression by leukemic blasts, which was mostly intracellular, usually with a perinuclear distribution. Three AML cell lines also showed moderate to strong expression of CD74, which was mostly intracellular. WithoutIFN-g, surface expression of CD74 was present, but IFN-γ treatment of these 3 lines resulted in upregulation of surface CD74 by 69-117%. Much higher levels of intracellular CD74 were observed in all 3 lines, with and without IFN-γ. IFN- γ induced intracellular CD74 in all 3 lines (from 85%-868%). In 2/3 lines, IFN-γ increased milatuzumab-mediated growth inhibition (23.7 to 44.8% and -3.9 to 30.9%, respectively). Conclusions: CD74 is expressed in AML patient specimens and in AML cell lines, with the majority of CD74 expression found intracellularly. Cell surface and cytoplasmic expression of CD74 were upregulated in AML lines after IFN-γ exposure. This increased expression resulted in increased cytotoxicity of the anti-CD74 mAb, milatuzumab, in 2/3 AML lines. Thus, AML is another cancer type where combined IFN-γ and milatuzumab treatment may be useful. Supported in part by NIH grant PO1- CA103985. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunomedics, Inc. Immunomedics, Inc.
The Study on N Genome of Leymus Species (1994)

Leymus Hochst. is a perennial genus of Triticeae. All species in Leymus have the genomes NX. The genome N is from the genus Psathyrostachys. Two Psathyrostachys species, diploid P. huashanica Keng ex Kuo and P. juncea (Fische.) Nevski (2n= 14), were hybridized with allotetraploid, Leymus secalinus (Georgi.) Tzvelev and L. multicaulis (Kar. & Kir.) Tzvelev. Meiotic behavior of the synthetic hybrids was studied. The chromosome pairings indicated that one L. secalinus genome and one L. multicaulis genome were closely homologous with both P. huashanica and P. juncea genomes. The data of genomic analysis in the hybrids of P. huashanica crossed with L. secalinus and L. multicaulis are so similar to those in the hybrids of P. juncea crossed with L. secalinus and L. multicaulis, there is no significant difference between them. Both P. huashanica and P. juncea are possible donors of the N genome of L. secalinus and L. multicaulis.
Reconfigurable MEMS-enabled frequency selective surfaces (2002)

A technique for designing reconfigurable frequency selective surfaces using microelectromechanical systems (MEMS) technology is presented. A method of moments simulation technique for analysing these periodic structures has been used to predict the tunability using this technique. Fabricated and measured results verify the concept of tunability.
Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. (1994)

The accumulation of assembled holoenzymes composed of regulatory D-type cyclins and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting for progression through the G1 phase of the cell cycle in mammalian fibroblasts. Both the synthesis and assembly of D-type cyclins and cdk4 depend upon serum stimulation, but even when both subunits are ectopically overproduced, they do not assemble into complexes in serum-deprived cells. When coexpressed from baculoviral vectors in intact Sf9 insect cells, cdk4 assembles with D-type cyclins to form active protein kinases. In contrast, recombinant D-type cyclin and cdk4 subunits produced in insect cells or in bacteria do not assemble as efficiently into functional holoenzymes when combined in vitro but can be activated in the presence of lysates obtained from proliferating mammalian cells. Assembly of cyclin D-cdk4 complexes in coinfected Sf9 cells facilitates phosphorylation of cdk4 on threonine 172 by a cdk-activating kinase (CAK). Assembly can proceed in the absence of this modification, but cdk4 mutants which cannot be phosphorylated by CAK remain catalytically inactive. Therefore, formation of the cyclin D-cdk4 complex and phosphorylation of the bound catalytic subunit are independently regulated, and in addition to the requirement for CAK activity, serum stimulation is required to promote assembly of the complexes in mammalian cells.
Self‐assembly and recrystallization of bacterial S‐layer proteins at silicon supports imaged in real time by atomic force microscopy (2003)

The self-assembly of bacterial surface-layer (S-layer) proteins (SbpA of Bacillus sphaericus CCM 2177) at silicon supports (hydrophobic, non-plasma-treated and hydrophilic, O2 plasma-treated silicon supports) was imaged in real time by atomic force microscopy (AFM). A closed mosaic layer consisting of small crystals (less than 200 nm in diameter) was formed at a hydrophobic silicon support, whereas a coherent crystalline lattice consisting of large domains (2-10 micro m in size) was generated at O2 plasma-treated, hydrophilic silicon wafers. The structure of the formed layers was a monolayer (9 nm in height) at the hydrophobic silicon and a bilayer (15 nm in height) at the hydrophilic silicon. In situ AFM measurements confirmed the importance of ionic bonds in the formation of crystalline SbpA layers at silicon supports. Rupture of the protein subunits with a metal chelator from the crystalline lattice of SbpA was visualized in situ by AFM. The stability of solid-supported SbpA layers could be enhanced by cross-linking the S-layers with amino-amino or amino-carboxyl group directed cross-linkers.
A segmented radiofrequency-only quadrupole collision cell for measurements of ion collision cross section on a triple quadrupole mass spectrometer (1997)

The gas collision cell of a triple quadrupole mass spectrometer has been modified to consist of ten short quadrupole rod segments that allow an axial field to be applied to the cell in order to make measurements of ion mobility. The radiofrequency (rf)-quadrupole field provides effective radial confinement that greatly reduces diffusional losses at low pressure. The mobilities of mass-selected ions from an ionspray source have been measured at a pressure of 8 × 10−3 torr at electric fields of 0. 1 to 3 V/cm, and used to calculate the collision cross sections of the ions. The measured cross sections compare well with those measured by other techniques.
Modern Clinical Research on LSD (2017)

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT<sub>2A</sub> receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.
Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension (2011)

Nitric oxide (NO) and reactive oxygen species (ROS) play important roles in blood pressure regulation via the modulation of the autonomic nervous system, particularly in the central nervous system (CNS). In general, accumulating evidence suggests that NO inhibits, but ROS activates, the sympathetic nervous system. NO and ROS, however, interact with each other. Our consecutive studies and those of others strongly indicate that an imbalance between NO bioavailability and ROS generation in the CNS, including the brain stem, activates the sympathetic nervous system, and this mechanism is involved in the pathogenesis of neurogenic aspects of hypertension. In this review, we focus on the role of NO and ROS in the regulation of the sympathetic nervous system within the brain stem and subsequent cardiovascular control. Multiple mechanisms are proposed, including modulation of neurotransmitter release, inhibition of receptors, and alterations of intracellular signaling pathways. Together, the evidence indicates that an imbalance of NO and ROS in the CNS plays a pivotal role in the pathogenesis of hypertension.