gebhart/patrepeval huggingface dataset:
Gold Nanoparticle-Based Miniaturized Nanomaterial Surface Energy Transfer Probe for Rapid and Ultrasensitive Detection of Mercury in Soil, Water, and Fish (2007)

Contamination of the environment with mercury has been an important concern throughout the world for decades. Exposure to high Hg levels can be harmful to the brain, heart, kidneys, lungs, and immune system of humans of all ages. Driven by the need to detect trace amounts of mercury in environmental samples, here we present a miniaturized, inexpensive, and battery-operated ultrasensitive gold nanoparticle-based nanomaterial surface energy transfer probe for screening mercury levels in contaminated soil, water, and fish which has excellent sensitivity (2 ppt) and selectivity for Hg(II) over competing analytes, with the largest fluorescence enhancement to date for sensing Hg(II) in environmental samples (1100-fold). The sensitivity of our probe to detect mercury level in soil, water, and fish is about 2-3 orders of magnitude higher than the EPA standard limit. We demonstrate that our probe is suitable to screen the amount of mercury in different fish, shellfish, and water samples from various commercial sources.
Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia (2014)

In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3Kδ, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade ≥3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.
MRI of tumor angiogenesis (2007)

Angiogenesis has long been established as a key element in the pathophysiology of tumor growth and metastasis. Increasingly, new molecularly targeted antiangiogenic drugs are being developed in the fight against cancer. These drugs bring with them a need for an accurate means of diagnosing tumor angiogenesis and monitoring response to treatment. Imaging techniques can offer this in a noninvasive way, while also providing functional information about the tumor. Among the many clinical imaging techniques available, MRI alone can provide relatively good spatial resolution and specificity, without ionizing radiation and with limited side effects. Arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging techniques can be employed to confer indirect measures of angiogenesis, such as blood flow and blood volume, without the need for external contrast agents. Dynamic contrast-enhanced (DCE)-MRI is rapidly emerging as a standard method for directly measuring angiogenesis during angiogenesis-inhibitor drug trials. As macromolecular MR contrast agents become available, they will inevitably be utilized in the assessment of tumor perfusion and vessel permeability. Meanwhile, technological advances have made imaging at a molecular level a possibility. They have brought the potential to directly target MR contrast agents to markers of angiogenesis, such as the alpha(v)beta(3) integrin. Before this is used clinically, however, substantial gains in sensitivity brought about by improved coils, pulse sequences, and contrast agents will be needed. Herein we discuss the techniques currently available for MRI of angiogenesis, along with their respective advantages and disadvantages, and what the future holds for this evolving field of imaging.
JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells (2012)

Chronic aristolochic acid nephropathy (CAAN) is a chronic and progressive tubulointerstitial nephropathy characterized by extensive interstitial fibrosis. Aristolochic acid (AA) could induce overexpression of transforming growth factor-β1 (TGF-β1) in a human renal proximal tubule epithelial cells line (HKC), which has been implicated in the pathogenesis of CAAN. The present studies in HKC cells showed 1) AA could activate JNK in time- and dose-dependent manners and JNK inhibitor SP600125 could inhibit AA-induced TGF-β1 promoter activity and TGF-β1 synthesis; 2) AA-induced JNK activation and TGF-β1 synthesis were significantly inhibited by kinase-inactive mutants of MEKK4, MKK4, or MKK7; 3) AA could upregulate luciferase activity derived by a wild-type TGF-β1 promoter, but not by an AP-1 binding-deficient TGF-β1 promoter; and 4) AA could upregulate expression of c-Fos, phospho-c-Jun, and phospho-ATF2. The above data suggest AA-induced TGF-β1 overexpression in HKC cells may be mainly mediated by the JNK signaling pathway. Both the upstream kinases of JNK including MEKK4, MKK4, and MKK7, and the downstream transcription factor of JNK, AP-1, may also participate in this process.
Anions, the Reporters of Structure in Ionic Liquids (2012)

In this work we compare the role that different anions play in the structure function S(q) for a set of liquids with the same cation. It is well established that because of their amphiphilic nature and their often larger size, cations play a fundamental role in the structural landscape of ionic liquids. On the other hand, it is often atoms in the anions that display the largest X-ray form factors and therefore play a very significant role as reporters of structure in small- and wide-angle X-ray scattering (SAXS/WAXS)-type experiments. For a set of liquids with similar topological landscape, how does S(q) change when the anionic scattering is deemphasized? Also, how do we computationally recover the typical length scale of important and perhaps universal ionic liquid structural features such as charge alternation when these are experimentally inaccessible from S(q) because of interference cancellations? We answer these questions by studying three different tetrapentylammonium-based liquids with the I(-), PF6(-) and N(CN)2(-) anions.
An antigen-independent contact mechanism as an early step in T cell-proliferative responses to dendritic cells. (1989)

Dendritic cells bearing antigen efficiently aggregate and stimulate antigen-specific T cells. We describe an experimental model in which an initial, apparently antigen-independent binding step is followed by ligation of the TCR. The model is the polyclonal response to mAb to the CD3 portion of the TCR complex. Epidermal and thymic dendritic cells utilize low levels of Fc receptors to present the anti-CD3 mAb and induce mitogenesis. Within 3 h of coculture, most of the dendritic cells have formed clusters with the resting T lymphocytes, and these clusters are the site for subsequent DNA synthesis and cell growth. However, the binding of dendritic cells to T cells proceeds as efficiently in the absence of anti-CD3 as in its presence, and anti-FcR mAb does not block. CD3 and Fc receptors are essential for the subsequent mitogenesis response in dendritic-T cell clusters. Because an exogenous ligand for the TCR does not seem to be required for the extensive polyclonal clustering of resting lymphocytes to dendritic cells, we suggest that an antigen-independent mechanism mediates the initial interaction. This clustering seems essential for T cell growth since we do not detect, in two-chamber experiments, soluble lymphocyte-activating factors that originate from dendritic-T cell aggregates and that activate anti-CD3-coated T cells.
17α-hydroxyprogesterone Caproate for the Prevention of Preterm Delivery (2006)

Within our baseline assumptions, 17alpha-hydroxyprogesterone caproate was associated with cost-savings when used for the prevention of preterm deliveries in women with prior preterm deliveries.
Polyurethane cationomers. I. Structure‐property relationships (1990)

Abstract Polyether polyurethane cationomers are prepared using poly (tetramethylene oxide) of molecular weight 2000 as soft segments, N ‐methyl‐diethanolamine as chain extender, glycolic acid as quaternization agent, methyl ethyl ketone as solvent, and three different diisocyanates. The three diisocyanates are 4,4′‐diphenylenemethylene diisocyanate (MDI), hexamethylene diisocyanate (HDI), and toluene diisocyanate (TDI). Properties of the films cast from solutions of the three series of ionomers are studied by infrared spectroscopy, dynamic mechanical analysis, thermogravimetric analysis, differential scanning calorimetry, wide angle x‐ray diffraction, and tensile elongation testing. In the un‐ionized and ionized systems, the hard segments exhibit disordered and ordered arrangements, respectively. Ionization disrupts the order and produces increased cohesion in the hard domains, which have opposing effects on the tensile elongation properties. In the MDI and TDI systems, cohesion is predominant, leading to an increased tensile strength and modulus and decreased elongation at break. But in the HDI system, the disruption of the order is predominant, leading to decreased tensile strength and only insignificant reduction in the elongation at break. In the TDI system, the tensile strength is rather low, which is attributed to the poor order in the hard domains resulting from the high content of the asymmetric 2,4‐isomer of the urethane.
Temporal-difference methods and Markov models (1993)

The relation between temporal-difference training methods and Markov models is explored. This relation is derived from a new perspective, and in this way the particular association between conventional temporal-difference methods and first-order Markov models is explained. The authors then derive a generalization of temporal-difference methods that is suitable for Markov models of higher order. Several issues related to the performance of mismatched temporal-difference methods (i.e., the performance when the temporal-difference method is not specifically designed to match the order of the Markov model) are investigated numerically.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modeling of Galvanostatic Charge and Discharge of the Lithium/Polymer/Insertion Cell (1993)

The galvanostatic charge and discharge of a lithium anode/solid polymer separator/insertion cathode cell is modeled using concentrated solution theory. The model is general enough to include a wide range of polymeric separator materials, lithium salts, and composite insertion cathodes. Insertion of lithium into the active cathode material is simulated using superposition, thus greatly simplifying the numerical calculations. Variable physical properties are permitted in the model. The results of a simulation of the charge/discharge behavior of the system are presented. Criteria are established to assess the importance of diffusion in the solid matrix and transport in the electrolyte. Consideration is also given to various procedures for optimization of the utilization of active cathode material.
Computer Analysis of Sequence Data (1994)

DNA sequencing has become increasingly efficient over the years, resulting in an enormous increase in the amount of data gener ated. In recent years, the focus of sequencing has shifted, from being th
Passive sweat collection and colorimetric analysis of biomarkers relevant to kidney disorders using a soft microfluidic system (2019)

The rich range of biomarkers in sweat and the ability to collect sweat in a non-invasive manner create interest in the use of this biofluid for assessments of health and physiological status, with potential applications that range from sports and fitness to clinical medicine. This paper introduces two important advances in recently reported classes of soft, skin-interfaced microfluidic systems for sweat capture and analysis: (1) a simple, broadly applicable means for collection of sweat that bypasses requirements for physical/mental exertion or pharmacological stimulation and (2) a set of enzymatic chemistries and colorimetric readout approaches for determining the concentrations of creatinine and urea in sweat, throughout ranges that are physiologically relevant. The results allow for routine, non-pharmacological capture of sweat for patient populations, such as infants and the elderly, that cannot be expected to sweat through exercise, and they create potential opportunities in the use of sweat for kidney disease screening/monitoring. Studies on human subjects demonstrate these essential capabilities, with quantitative comparisons to standard methods. The results expand the range of options available in microfluidic sampling and sensing of sweat for disease diagnostics and health monitoring.
Squeezing with a flux-driven Josephson parametric amplifier (2013)

Josephson parametric amplifiers (JPA) are promising devices for applications in circuit quantum electrodynamics and for studies on propagating quantum microwaves because of their good noise performance. In this work, we present a systematic characterization of a flux-driven JPA at millikelvin temperatures. In particular, we study in detail its squeezing properties by two different detection techniques. With the homodyne setup, we observe the squeezing of vacuum fluctuations by superposing signal and idler bands. For a quantitative analysis, we apply dual-path cross-correlation techniques to reconstruct the Wigner functions of various squeezed vacuum and thermal states. At 10 dB signal gain, we find 4.9 ± 0.2 dB squeezing below the vacuum. In addition, we discuss the physics behind squeezed coherent microwave fields. Finally, we analyze the JPA noise temperature in the degenerate mode and find a value smaller than the standard quantum limit for phase-insensitive amplifiers.
2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists (1993)

Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pKi values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pKi 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 microgram/kg i.v.), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.
Cytocompatibility studies of an in situ photopolymerized thermoresponsive hydrogel nanoparticle system using human aortic smooth muscle cells (2008)

We have been investigating thermoresponsive hydrogel nanoparticle composite networks to develop photopolymerized hydrogels to deliver drugs for prevention of restenosis after angioplasty. These composite systems can form a gel under physiological conditions and release drugs in response to temperature changes. Our novel system, consisting of poly(N-isopropylacrylamide) thermoresponsive nanoparticles, photo cross-linker poly(ethylene glycol) diacrylate, and UV photoinitiator, 2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone-1-one (Irgacure 2959), would be photopolymerized in situ in the presence of UV light. The focus of this study was to evaluate the effects of photoinitiator and UV exposure on human aortic smooth muscle cells (HASMCs). We found that the exposure to UV light did not significantly affect the cellular survival within doses required for photopolymerization. The photoinitiator was cytocompatible at low concentrations (< or = 0.015% w/v); however, cytotoxicity increased with increasing photoinitiator concentrations. In addition, free radicals formed in the presence of a photoinitiator and UV light caused significant levels of cell death. An antioxidant (free radical scavenger), ascorbic acid, added to the cell media, significantly improved relative cell survival but increased the hydrogel gelation time. Finally, HASMC survival when exposed to all potential cytotoxic components was also evaluated by exposing HASMCs to media incubated with our composite hydrogels. In summary, our studies show that the photoinitiator and free radicals are responsible for the cytotoxicity on HASMCs, and the addition of antioxidants can significantly reduce these harmful effects.
The pathophysiology of acute coronary syndromes (2000)

V irtually all regional acute myocardial infarcts are caused by thrombosis developing on a culprit coronary atherosclerotic plaque. The very rare exceptions to this are spontaneous coronary artery dissection, coronary arteritis, coronary emboli, coronary spasm, and compression by myocardial bridges. Thrombosis is also the major initiating factor in unstable angina, particularly when rest pain is recent and increasing in severity. Necropsy studies suggest that a new thrombotic coronary event underlies 50-70% of sudden deaths caused by ischaemic heart disease.
Factors affecting α,‐1,2 glucooligosaccharide synthesis by Leuconostoc mesenteroides NRRL B‐1299 dextransucrase (2001)

The optimization of alpha-1,2 glucooligosaccharide (GOS) synthesis from maltose and sucrose by Leuconostoc mesenteroides NRRL B-1299 dextransucrase was achieved using experimental design and consecutive analysis of the key parameters. An increase of the pH of the reaction from 5.4 to 6.7 and of the temperature from 25 to 40 degrees C significantly favored alpha-1,2 GOS synthesis, thanks to a significant decrease of the side reactions, i.e., dextran and leucrose synthesis. These positive effects were not sufficient to compensate for the decrease of enzyme stability caused by the use of high pH and temperature. However, the critical parameters were the sucrose to maltose concentration ratio (S/M) and the total sugar concentration (TSC). Alpha1,2 GOS synthesis was favored at high S/M ratios. But using these conditions also led to an increase of side reactions which could be modulated by choosing the appropriate TSC. Finally, with S/M = 4 and TSC = 45% w/v, dextran and leucrose productions were limited and the final alpha-1,2 GOS yield reached 56.7%, the total GOS yield being 88%.
Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor in hamsters (1999)

These results suggest that TR has antifibrotic potential in vivo and may be useful in the treatment of fibrotic diseases where increased TGF-beta is associated with excess collagen accumulation.
Rapid identification of rough Brucella isolates by a latex coagglutination assay with the 25-kilodalton outer membrane protein and rough-lipopolysaccharide-specific monoclonal antibodies (1997)

A latex coagglutination assay was developed to identify rough (R) isolates of Brucella. Latex beads were coated, via protein A, with either an anti-Brucella rough-lipopolysaccharide (R-LPS) monoclonal antibody (MAb) or an anti-Brucella 25-kDa outer membrane protein (Omp25) MAb. Slide agglutination tests were done for 68 strains of Brucella spp., including type strains of all biovars as well as field isolates. Latex beads coated with MAb to R-LPS coagglutinated only R strains, whereas latex beads coated with MAb to Omp25 coagglutinated all the R Brucella isolates except Brucella ovis. Coagglutination was easier to read than agglutination with rabbit R-Brucella-specific antiserum. Thus, this assay accurately differentiates B. ovis from other R Brucella isolates. The latex coagglutination assay can substitute, to advantage, for the current anti-Brucella (R) rabbit monospecific serum.
Overexpression of activating transcription factor 5 in human rectal cancer (2011)

The aim of this study was to investigate the relationship between the expression of activating transcription factor 5 (ATF5) and clinicopathological features in human rectal cancer. Relative quantitative real-time RT-PCR and immunohistochemical staining were used to detect ATF5 mRNA and protein expression in 92 paired samples of rectal cancer and distant normal tissues. Immunohistochemical staining of the matched rectal tissue samples revealed that the positive expression rate of the ATF5 protein in rectal cancer was significantly higher compared to that in the normal tissue. Furthermore, the expression of ATF5 in poorly differentiated cancers was higher compared to that in well to moderately differentiated cancers (P=0.013). However, there was no significant association between ATF5 protein expression and patient age, gender, histological tumor type, cell differentiation, invasive depth, lymph node metastasis or distant metastasis (P>0.05). However, to our surprise, there was no difference in the relative mRNA expression levels of ATF5 between normal tissues and rectal cancers. Our findings indicate that overexpression of ATF5 protein may be an important biomarker of the degree of malignancy, and increased expression may be related to the post-transcriptional regulation of ATF5 in rectal cancer tissues.
Tissue‐specific expression of splice variants of the mouse voltage‐gated calcium channel α2/δ subunit (1996)

Five different splice variants of mouse alpha2/delta subunit isoforms (alpha2a-e), which arose from various combinations of three alternatively spliced regions, were cloned with a combination of cDNA library screening and RT-PCR. Expression patterns and relative abundance of the various isoforms in mouse tissues were determined with an RNAse protection assay. Skeletal muscle and brain expressed single isoforms, alpha2a and alpha2b, respectively; however, the cardiovascular system expressed all five isoforms. Heart expressed mainly isoforms alpha2c and alpha2d while, in contrast to other species, aorta expressed predominantly alpha2a, the 'skeletal muscle' isoform. Smooth muscle-containing tissues expressed alpha2d and alpha2e. Thus, alpha2/delta isoforms are restricted in their tissue expression, suggesting an important functional role for the differentially spliced variants.