gebhart/patrepeval huggingface dataset:
Fluorescence-Based Assays for Measuring Doxorubicin in Biological Systems (2016)

Detection and measurement of doxorubicin in biological systems, including body fluids, cells, and tissues, are instrumental in understanding the mechanisms of action of this widely used drug in treating cancer as well as in causing adverse effects. In this article, we, for the first time, characterized the use of fluorescence-based techniques, including fluorescence spectrometry, microscopy, and flow cytometry in measuring and/or detecting doxorubicin in biological systems, including cell lysates and cultured intact cells. We showed that doxorubicin has a maximum excitation and emission wavelength of 470 and 560 nm, respectively. The detection sensitivity by fluorescence spectrometry is less than 0.1 μM in buffers and cell lysates. Fluorescence microscopy demonstrated the readily detection of concentration-dependent accumulation of doxorubicin in cultured cells via either green or red fluorescence, but with green fluorescence showing a higher sensitivity of detection. Flow cytometry also revealed sensitive detection of doxorubicin accumulation in cell suspensions in a concentration-dependent manner. The readily and sensitive measurement and detection of doxorubicin by the above three fluorescence-based techniques has important implications in studying the cellular dynamics of doxorubicin in both cancer and normal cells under various experimental conditions.
Purification and Properties of Arginase from Soybean, Glycine max, Axes (1990)

Arginase (EC 3.5.3.1) was purified to homogeneity from cytosol of soybean, Glycine max, axes by chromatographic separations on Sephadex G-200, DEAE-sephacel, hydroxyapatite, and arginine-affinity columns. The molecular weight of the enzyme estimated by pore gradient gel electrophoresis was 240,000, while sodium dodecyl sulfate polyacrylamide gel electrophoresis gave a single band at the molecular weight of 60,000. The optimal pH for activity was 9.5 and the K(m) value was 83 millimolar. The enzyme was stimulated by polyamines such as putrescine.
Role of Chromium in Human Health and in Diabetes (2004)

Despite widespread use by patients with diabetes and anecdotal reports in the past regarding its efficacy, until recently, data in humans concerning chromium’s effects on insulin action in vivo or on cellular aspects of insulin action were scarce. Consequently, significant controversy still exists regarding the effect of chromium supplementation on parameters assessing human health. Furthermore, elucidating the cellular and molecular mechanisms by which chromium supplements affect carbohydrate metabolism in vivo is necessary before specific recommendations can be made regarding its routine use in the management of diabetes. This review focuses on providing current information about this trace mineral’s specific mechanisms of action and clinical trials in patients with diabetes.

Chromium, one of the most common elements in the earth’s crust and seawater, exists in our environment in several oxidation states, principally as metallic (Cr), trivalent (+3), and hexavalent (+6) chromium. The latter is largely synthesized by the oxidation of the more common and naturally occurring trivalent chromium and is highly toxic. Trivalent chromium, found in most foods and nutrient supplements, is an essential nutrient with very low toxicity.

The interest in chromium as a nutritional enhancement to glucose metabolism can be traced back to the 1950s, when it was suggested that brewer’s yeast contained a glucose tolerance factor (GTF) that prevented diabetes in experimental animals (1). This factor was eventually suggested to be a biologically active form of trivalent chromium that could substantially lower plasma glucose levels in diabetic mice (2). Interest regarding chromium administration in patients with diabetes was kindled by the observation in the 1970s that it truly was an essential nutrient required for normal carbohydrate metabolism. A patient receiving total parenteral nutrition (TPN) developed severe signs of diabetes, including weight loss and hyperglycemia that was refractory to increasing insulin dosing (3). Based on previous animal studies …
Novel Bifunctional Natriuretic Peptides as Potential Therapeutics (2008)

Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the promiscuous nature of CNP in this species. Interesting, the DNP tail alone had no effect on any NPR even though it is effective in vivo. To further increase the potency of CD-NP for NPR-A, we converted two different triplet sequences within the CNP ring to their corresponding residues in BNP. Both variants demonstrated increased affinity and full agonist activity for NPR-A, whereas one was as potent as any NPR-A activator known. In contrast to a previous report, we found that DNP binds the natriuretic peptide clearance receptor (NPR-C). However, none of the chimeric peptides bound NPR-C with significantly higher affinity than endogenous ligands. We suggest that bifunctional chimeric peptides represent a new generation of natriuretic peptide therapeutics.
Compacted DNA Nanoparticles Administered to the Nasal Mucosa of Cystic Fibrosis Subjects Are Safe and Demonstrate Partial to Complete Cystic Fibrosis Transmembrane Regulator Reconstitution (2004)

A double-blind, dose escalation gene transfer trial was conducted in subjects with cystic fibrosis (CF), among whom placebo (saline) or compacted DNA was superfused onto the inferior turbinate of the right or left nostril. The vector consisted of single molecules of plasmid DNA carrying the cystic fibrosis transmembrane regulator- encoding gene compacted into DNA nanoparticles, using polyethylene glycol-substituted 30-mer lysine peptides. Entry criteria included age greater than 18 years, FEV1 exceeding 50% predicted, and basal nasal potential difference (NPD) isoproterenol responses (> or = -5 mV) that are typical for subjects with classic CF. Twelve subjects were enrolled: 2 in dose level I (DLI) (0.8 mg DNA), 4 in DLII (2.67 mg), and 6 in DLIII (8.0 mg). The primary trial end points were safety and tolerability, and secondary gene transfer end points were assessed. In addition to routine clinical assessments and laboratory tests, subjects were serially evaluated for serum IL-6, complement, and C-reactive protein; nasal washings were taken for cell counts, protein, IL-6, and IL-8; and pulmonary function and hearing tests were performed. No serious adverse events occurred, and no events were attributed to compacted DNA. There was no association of serum or nasal washing inflammatory mediators with administration of compacted DNA. Day 14 vector polymerase chain reaction analysis showed a mean value in DLIII nasal scraping samples of 0.58 copy per cell. Partial to complete NPD isoproterenol responses were observed in eight subjects: one of two in DLI, three of four in DLII, and four of six in DLIII. Corrections persisted for as long as 6 days (1 subject to day 28) after gene transfer. In conclusion, compacted DNA nanoparticles can be safely administered to the nares of CF subjects, with evidence of vector gene transfer and partial NPD correction.
CisModification of the Steroid 21-Hydroxylase Gene Prevents Its Expression in the Y1 Mouse Adrenocortical Tumor Cell Line (1990)

The Y1 mouse adrenocortical tumor cell line retains the ability to synthesize and secrete steroids, but does not express steroid 21-hydroxylase (C21) and, therefore, does not produce 21-hydroxylated steroids. In this investigation the mechanisms underlying the loss of C21 activity in the Y1 cell line were explored. A 9-kilobase BglII fragment containing the C21 gene was cloned from the Y1 genome. This genomic clone directed the synthesis of C21 transcripts and 21-hydroxylated steroid products when transfected back into the Y1 cell line. As determined by restriction endonuclease digestions with MspI and HpaII, enzymes that distinguish between unmethylated and methylated CCGG sites, the endogenous C21 gene was extensively methylated in Y1 adrenal cells and in cells from other mouse tissues that do not normally express this gene. In contrast, the C21 gene was hypomethylated in primary cultures of mouse adrenal cells which normally synthesize large amounts of C21. The cloned C21 gene transfected into Y1 cells initially was unmethylated, but became extensively methylated with prolonged culture of the cells; prolonged culture of these transfectants also resulted in a loss of C21 expression. Loss of C21 expression in Y1 transfectants, however, temporally preceded the extensive methylation of the transfected C21 gene. Furthermore, treatment of Y1 cells with 5-azacytidine caused a demethylation of the endogenous C21 gene, but did not result in the recovery of C21 expression. These results indicate that Y1 cells contain a functional C21 gene that has been silenced by a reversible cis-modification event.(ABSTRACT TRUNCATED AT 250 WORDS)
Architectural support for high speed protection of memory integrity and confidentiality in multiprocessor systems (2004)

Recently there is a growing effort in both the architecture and the security community to create a hardware solution for authenticating system memory. As shown in the previous work, hardware-based memory authentication becomes a vital component for creating future trusted computing environments and digital rights protection. Almost all these prior work have focused on authenticating memory exclusively owned by a single processing element. However, in today's computing platforms, memory is often shared by multiple processing elements that support a shared system memory with a snooping cache coherence protocol. Authenticating shared memory is a new challenge to memory protection. In this paper, we present a secure and fast architecture for authenticating shared memory. In terms of incorporating memory authentication into the processor pipeline, we propose a new scheme called authentication speculative execution. Unlike the prior approaches, our scheme does not compromise security for performance. The novel ASE scheme is not only secure as it is combined with a onetime-pad (OTP) based memory encryption but also efficient to tolerate authentication latency by executing unauthenticated instructions speculatively. Results using modified RSIM running SPLASH2 benchmark show only 5% overhead in performance on dual and quad processor platforms. Furthermore, ASE shows 80% better performance on average over conservative nonspeculative execution based authentication schemes. The scheme is of practical use for both multiprocessor systems and uni-processor systems where memory is shared by one main processor and other co-processors on the system bus.
Kinematic Parameters to Evaluate Functional Performance of Sit-to-Stand and Stand-to-Sit Transitions Using Motion Sensor Devices: A Systematic Review (2014)

Clinicians commonly use questionnaires and tests based on daily life activities to evaluate physical function. However, the outcomes are usually more qualitative than quantitative and subtle differences are not detectable. In this review, we aim to assess the role of body motion sensors in physical performance evaluation, especially for the sit-to-stand and stand-to-sit transitions. In total, 53 full papers and conference abstracts on related topics were included and 16 different parameters related to transition performance were identified as potentially meaningful to explain certain disabilities and impairments. Transition duration is the most used to evaluate chair-related tests in real clinical settings. High-fall-risk fallers and frail subjects presented longer and more variable transition duration. Other kinematic parameters have also been highlighted in the literature as potential means to detect age-related impairments. In particular, vertical linear velocity and trunk tilt range were able to differentiate between different frailty levels. Frequency domain measures such as spectral edge frequency were also higher for elderly fallers. Lastly, approximate entropy values were larger for subjects with Parkinson's disease and were significantly reduced after treatment. This information could help clinicians in their evaluations as well as in prescribing a physical fitness program to correct a specific deficit.
Comparison of the Antinociceptive Effects of Pre- and Posttreatment with Intrathecal Morphine and MK801, an NMDA Antagonist, on the Formalin Test in the Rat (1992)

Current thinking emphasizes that protracted small afferent input can evoke mechanisms that mediate a significant potentiation of spinal nociceptive processing and that this facilitory component has a unique pharmacology. To investigate the behavioral parallels of this spinal facilitation, we evaluated the effects of pre- and post-treatment of intrathecal morphine (mu agonist) and MK801 (N-methyl-D-aspartate [NMDA] antagonist) on the formalin test. Intraplantar formalin resulted in a biphasic appearance of flinching behavior (phase 1 = 0-5 min; phase 2 = 10-60 min). Morphine and MK801 were administered intrathecally 15 min before formalin injection in the pretreatment study and 9 min after formalin injection in the posttreatment study. Pretreatment with intrathecal morphine produced comparable dose-dependent suppressions of the phase 1 and phase 2 behaviors (ED50 = 0.5 micrograms [95% CI = 0.3-0.9] and 0.3 micrograms [95% CI = 0.1-0.7], respectively). Posttreatment with morphine also resulted in comparable suppression of the phase 2 response (ED50 = 0.2 micrograms [95% CI = 0.1-0.3]). At the highest dose of intrathecal morphine (10 micrograms), an almost complete suppression of formalin-evoked behavior was observed. Pretreatment with MK801 inhibited the second-phase response more strongly than the first-phase response (ED50 = 1.6 micrograms [95% CI = 0.5-5.7] vs. 0.1 microgram [95% CI = 0.3 - 0.4], respectively). In contrast, posttreatment with the highest dose of MK801 had no effect on the phase 2 response.(ABSTRACT TRUNCATED AT 250 WORDS)
Isoxazole anthelmintics (1977)

&lt;p&gt;Chabazite zeolites with trimodal porosity (native micropores of the CHA framework, an additional network of larger micropores of ∼0.5 nm, and mesopores) were synthesized by adding diquarternary ammonium-type surfactant C&lt;sub&gt;22-4-4&lt;/sub&gt; cations and fluoride anions in the synthesis of SSZ-13 zeolite. The hierarchical SSZ-13 zeolites are fully crystalline and exhibit similar acidity as bulk SSZ-13 zeolite. The increased diffusion rate in the hierarchical SSZ-13, proven by uptake experiments of bulky molecules and selective staining by thiophene oligomers, resulted in much slower catalyst deactivation in the methanol-to-olefins (MTO) reaction. Confocal fluorescent images of spent hierarchical SSZ-13 zeolites reveal homogeneous distribution of carbonaceous deposits, indicating that the micropore space has been completely utilized during the MTO reaction. (Graph Presented).&lt;/p&gt;
Toward Understanding the Origin of Positive Effects of Ionic Liquids on Catalysis: Formation of More Reactive Catalysts and Stabilization of Reactive Intermediates and Transition States in Ionic Liquids (2010)

Over the past decade, ionic liquids have received a great deal of attention as a new means for catalyst immobilization. Large numbers of catalysts having polar or ionic character have been successfully immobilized in ionic liquids, thus allowing their recovery and recycling. However, catalyst immobilization is not the only benefit of ionic liquids in catalysis, of greater importance are the positive effects of ionic liquids on catalytic rates. In this Account, we highlight our work in elucidating the origin of the accelerating effects of ionic liquids in a range of catalytic reactions. Lewis acidic metal triflates often become much more reactive in ionic liquids containing noncoordinating anions as a result of "anion exchange." Consequently, the more electrophilic Lewis acidic species generated in situ accelerate the catalytic reactions dramatically. In some cases, highly reactive intermediates, such as vinyl cations, arenium cations, oxygen radical anions, and so forth, can be stabilized in the presence of ionic liquids, thus increasing the reactivity and selectivity of the reactions. Concerted processes such as S(N)2 and Diels-Alder reactions can also be accelerated through the cooperative activation of both the nucleophile and the electrophile by ionic liquids. In transition metal-catalyzed reactions, certain catalytically active oxidation states can be stabilized in ionic liquids against deactivation to catalytically inactive species. Thus it is clear that gaining an understanding of the origin of these "positive ionic liquid effects" is highly important, not only for predicting the effects of ionic liquids on other organic reactions but also for designing new catalytic reactions. Ionic liquids, by virtue of (typically) having a synthetically accessible carbon backbone, are amenable to tailoring by the organic chemist. Accordingly, their molecular structures can be subtly varied to give "tunable" properties, which can then be used to rationally examine the fundamental reasons that they accelerate catalyzed reactions. Although the origins of enhanced catalytic rates by ionic liquids have been elucidated in many areas, other undiscovered ionic liquid phenomena remain to be unearthed. Developing a better understanding of these modularly tunable liquid salts will foster new discoveries of catalytic reactions that are accelerated by ionic liquids as solvents or additives.
Randomized, double-blind trial of anti-interferon-?antibodies in rheumatoid arthritis (2001)

Antibodies to IFN-gamma could be a promising approach to treating RA, especially its treatment-resistant forms.
Transcranial electrical stimulation (tES – tDCS; tRNS, tACS) methods (2011)

Weak transcranial direct current stimulation (tDCS) with a homogenous DC field at intensities of around 1 mA induces long-lasting changes in the brain. tDCS can be used to manipulate brain excitability via membrane polarisation: cathodal stimulation hyperpolarises, while anodal stimulation depolarises the resting membrane potential, whereby the induced after-effects depend on polarity, duration and intensity of the stimulation. A variety of other parameters influence tDCS effects; co-application of neuropharmacologically active drugs may most impressively prolong or even reverse stimulation effects. Transcranial alternating stimulation (tACS) and random noise stimulation (tRNS) are used to interfere with ongoing neuronal oscillations and also finally produce neuroplastic effects if applied with appropriate parameters.
Toll-Like Receptor (TLR)2 and TLR4 Agonists Regulate CCR Expression in Human Monocytic Cells (2004)

Interactions between proinflammatory and cell maturation signals, and the pathways that regulate leukocyte migration, are of fundamental importance in controlling trafficking and recruitment of leukocytes during the processes of innate and adaptive immunity. We have investigated the molecular mechanisms by which selective Toll-like receptor (TLR)2 and TLR4 agonists regulate expression of CCR1 and CCR2 on primary human monocytes and THP-1 cells, a human monocytic cell line. We found that activation of either TLR2 (by Pam(3)CysSerLys(4)) or TLR4 (by purified LPS) resulted in down-modulation of both CCR1 and CCR2. Further investigation of TLR-induced down-modulation of CCR1 revealed differences in the signaling pathways activated, and chemokines generated, via the two TLR agonists. TLR2 activation caused slower induction of the NF-kappa B and mitogen-activated protein kinase signaling pathways and yet a much enhanced and prolonged macrophage-inflammatory protein 1 alpha (CC chemokine ligand 3) protein production, when compared with TLR4 stimulation. Enhanced macrophage-inflammatory protein 1 alpha production may contribute to the prolonged down-regulation of CCR1 cell surface expression observed in response to the TLR2 agonist, as preventing chemokine generation with the protein synthesis inhibitor cycloheximide, or CCR1 signaling with the receptor antagonist UCB35625, abolished TLR2- and TLR4-induced CCR1 down-modulation. This result suggests an autocrine pathway, whereby TLR activation can induce chemokine production, which then leads to homologous down-regulation of the cognate receptors. This work provides further insights into the mechanisms that regulate leukocyte recruitment and trafficking during TLR-induced inflammatory responses.
Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains (2007)

Glutamine-rich sequences exist in a wide range of proteins across multiple species. A subset of glutamine-rich sequences has been shown to form amyloid fibers implicated in human diseases. The physiological functions of these sequence motifs are not well understood, partly because of the lack of structural information. Here we have determined a high-resolution structure of a glutamine-rich domain from human histone deacetylase 4 (HDAC4) by x-ray crystallography. The glutamine-rich domain of HDAC4 (19 glutamines of 68 residues) folds into a straight alpha-helix that assembles as a tetramer. In contrast to most coiled coil proteins, the HDAC4 tetramer lacks regularly arranged apolar residues and an extended hydrophobic core. Instead, the protein interfaces consist of multiple hydrophobic patches interspersed with polar interaction networks, wherein clusters of glutamines engage in extensive intra- and interhelical interactions. In solution, the HDAC4 tetramer undergoes rapid equilibrium with monomer and intermediate species. Structure-guided mutations that expand or disrupt hydrophobic patches drive the equilibrium toward the tetramer or monomer, respectively. We propose that a general role of glutamine-rich motifs be to mediate protein-protein interactions characteristic of a large component of polar interaction networks that may facilitate reversible assembly and disassembly of protein complexes.