gebhart/patrepeval huggingface dataset:
Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-κB with antimyeloma activity in vitro and in vivo (2008)

As multiple myeloma tumors universally dysregulate cyclin D genes we conducted high-throughput chemical library screens for compounds that induce suppression of cyclin D2 promoter transcription. The top-ranked compound was a natural triterpenoid, pristimerin. Strikingly, the early transcriptional response of cells treated with pristimerin closely resembles cellular responses elicited by proteosome inhibitors, with rapid induction of heat shock proteins, activating transcription factor 3 (ATF3), and CHOP. Enzymatic assays and immunoblotting confirm that pristimerin rapidly (< 90 minutes) and specifically inhibits chymotrypsin-like proteosome activity at low concentrations (< 100 nM) and causes accumulation of cellular ubiquitinated proteins. Notably, cytotoxic triterpenoids including pristimerin inhibit NF-kappaB activation via inhibition of IKK alpha or IKK beta, whereas proteosome inhibitors instead suppress NF-kappaB function by impairing degradation of ubiquitinated I kappaB. By inhibiting both IKK and the proteosome, pristimerin causes overt suppression of constitutive NF-kappaB activity in myeloma cells that may mediate its suppression of cyclin D. Multiple myeloma is exquisitely sensitive to proteosome or NF-kappaB pathway inhibition. Consistent with this, pristimerin is potently and selectively lethal to primary myeloma cells (IC(50) < 100 nM), inhibits xenografted plasmacytoma tumors in mice, and is synergistically cytotoxic with bortezomib--providing the rationale for pharmaceutical development of triterpenoid dual-function proteosome/NF-kappaB inhibitors as therapeutics for human multiple myeloma and related malignancies.
Histamine H4 Receptor Expression in Human Synovial Cells Obtained from Patients Suffering from Rheumatoid Arthritis (2005)

While histamine H4 receptor (H4R) has been implicated in immune system disturbances in different organ tissues, the presence and possible roles of H4R in synovial cells (SC) of rheumatoid arthritis (RA) patients has not previously been documented. This study conclusively evidences H4R expression in SC of RA patients by use of RT-PCR method. As RA consists mainly of immunological disturbances in SC of RA patients, this study's findings document a novel histamine action site, and opens potential new avenues to investigate mechanisms and to develop pharmacotherapeutic agents for the disease.
From Vinylidene Fluoride (VDF) to the Applications of VDF-Containing Polymers and Copolymers: Recent Developments and Future Trends (2009)

International audience
Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions. (1989)

Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second approximately 6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEV1 values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P less than 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness.
Synthesis and antitumor activity of cyclophosphamide analogs. 1. Benzo annulated cyclophosphamide and related systems (1975)

Synthesis of 2-[bis(2-chloroethyl)amino]-3,4-dihydro-2H-1,3,2-benzoxazaphosphorin 2-oxide (2), which is a benzo annulated analog of cyclophosphamide [2-bis(2-chloroethyl)aminotetrahydro-2H-1,3,2-oxazaphosphorin 2-oxide (1)], was carried out in order to test for possible increased antitumor activity relative to 1 due to the presence of an oxidatively reactive C-4 benzylic site in 2. A structural isomer of 2, 2-[bis(2-chloroethyl)amino]-1,4-dihydro-2H-3,1,2-benzoxazaphosphorin 2-oxide (3), and cognate systems 2-[bis(2-chloroethyl)amino]-1,2,3,4-tetrahydro-1,3,2-benzodiazaphosphorin 2-oxide (4) and 2-[bis(2-chloroethyl)amino]-4H-1,3,2-benzodioxaphosphorin 2-oxide (5) were also prepared for comparative purposes. In vivo antitumor evaluation in mice against L1210 lymphoid leukemia indicated no significant activity for compound 2. Compounds 3 and 4 were likewise found to be inactive and only marginal activity was exhibited by 5.
Electronically tunable distributed feedback lasers (1986)

The fabrication and performance characteristics of frequency tunable two-section distributed feedback lasers are reported. The lasers are of the double channel planar buried heterostructure type and utilize a second order grating for frequency selective feedback. The laser emits in a single frequency with a cw linewidth of ∼50 MHz. The single frequency output can be tuned by ∼2 Å by varying the current through one of the two sections. Electronically tunable sources of this type are potentially useful for coherent fiber transmission systems.
PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKaPredictions (2011)

In this study, we have revised the rules and parameters for one of the most commonly used empirical pKa predictors, PROPKA, based on better physical description of the desolvation and dielectric response for the protein. We have introduced a new and consistent approach to interpolate the description between the previously distinct classifications into internal and surface residues, which otherwise is found to give rise to an erratic and discontinuous behavior. Since the goal of this study is to lay out the framework and validate the concept, it focuses on Asp and Glu residues where the protein pKa values and structures are assumed to be more reliable. The new and improved implementation is evaluated and discussed; it is found to agree better with experiment than the previous implementation (in parentheses): rmsd = 0.79 (0.91) for Asp and Glu, 0.75 (0.97) for Tyr, 0.65 (0.72) for Lys, and 1.00 (1.37) for His residues. The most significant advance, however, is in reducing the number of outliers and removing unreasonable sensitivity to small structural changes that arise from classifying residues as either internal or surface.
Chemical synthesis of genes for human insulin. (1978)

A rapid chemical procedure has been developed and used for the synthesis of 29 oligodeoxyribonucleotides to build synthetic genes for human insulin. The gene for insulin B chain, 104 base pairs, and the one for A chain, 77 base pairs, were designed from the amino acid sequence of human polypeptides. They bear single-stranded cohesive termini for the EcoRI and BamHI restriction endonucleases and are designed to be inserted separately into a pBR322 plasmid. The synthetic fragments, deca- to pentadecanucleotides, were synthesized by a block phosphotriester method with trinucleotides as building blocks. Final purification was by high-performance liquid chromatography. All 29 oligonucleotides were pure and had the correct sequences.
Chick stem cells: Current progress and future prospects (2013)

Chick embryonic stem cells (cESCs) can be derived from cells obtained from stage X embryos (blastoderm stage); these have the ability to contribute to all somatic lineages in chimaeras, but not to the germ line. However, lines of stem cells that are able to contribute to the germ line can be established from chick primordial germ cells (cPGCs) and embryonic germ cells (cEGCs). This review provides information on avian stem cells, emphasizing different sources of cells and current methods for derivation and culture of pluripotent cells from chick embryos. We also review technologies for isolation and derivation of chicken germ cells and the production of transgenic birds.
Poly(A) Tail Recognition by a Viral RNA Element Through Assembly of a Triple Helix (2010)

Kaposi's sarcoma-associated herpesvirus produces a highly abundant, nuclear noncoding RNA, polyadenylated nuclear (PAN) RNA, which contains an element that prevents its decay. The 79-nucleotide expression and nuclear retention element (ENE) was proposed to adopt a secondary structure like that of a box H/ACA small nucleolar RNA (snoRNA), with a U-rich internal loop that hybridizes to and protects the PAN RNA poly(A) tail. The crystal structure of a complex between the 40-nucleotide ENE core and oligo(A)(9) RNA at 2.5 angstrom resolution reveals that unlike snoRNAs, the U-rich loop of the ENE engages its target through formation of a major-groove triple helix. A-minor interactions extend the binding interface. Deadenylation assays confirm the functional importance of the triple helix. Thus, the ENE acts as an intramolecular RNA clamp, sequestering the PAN poly(A) tail and preventing the initiation of RNA decay.
Ophthalmic Uses of a Thiol-Modified Hyaluronan-Based Hydrogel (2014)

<b>Significance:</b> Hyaluronic acid (HA, or hyaluronan) is a ubiquitous naturally occurring polysaccharide that plays a role in virtually all tissues in vertebrate organisms. HA-based hydrogels have wound-healing properties, support cell delivery, and can deliver drugs locally. <b>Recent Advances:</b> A few HA hydrogels can be customized for composition, physical form, and biomechanical properties. No clinically approved HA hydrogel allows for <i>in vivo</i> crosslinking on administration, has a tunable gelation time to meet wound-healing needs, or enables drug delivery. Recently, a thiolated carboxymethyl HA (CMHA-S) was developed to produce crosslinked hydrogels, sponges, and thin films. CMHA-S can be crosslinked with a thiol-reactive crosslinker or by oxidative disulfide bond formation to form hydrogels. By controlled crosslinking, the shape and form of this material can be manipulated. These hydrogels can be subsequently lyophilized to form sponges or air-dried to form thin films. CMHA-S films, liquids, and gels have been shown to be effective <i>in vivo</i> for treating various injuries and wounds in the eye in veterinary use, and are in clinical development for human use. <b>Critical Issues:</b> Better clinical therapies are needed to treat ophthalmic injuries. Corneal wounds can be treated using this HA-based crosslinked hydrogel. CMHA-S biomaterials can help heal ocular surface defects, can be formed into a film to deliver drugs for local ocular drug delivery, and could deliver autologous limbal stem cells to treat extreme ocular surface damage associated with limbal stem cell deficiencies. <b>Future Directions:</b> This CMHA-S hydrogel increases the options that could be available for improved ocular wound care, healing, and regenerative medicine.
Discovery of a Small Molecule Insulin Mimetic with Antidiabetic Activity in Mice (1999)

Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. Oral administration of L-783,281 to two mouse models of diabetes resulted in significant lowering in blood glucose levels. These results demonstrate the feasibility of discovering novel insulin receptor activators that may lead to new therapies for diabetes.
Synthesis of Novel N-1 (Allyloxymethyl) Analogues of 6-Benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, Emivirine) with Improved Activity Against HIV-1 and Its Mutants (2002)

This paper reports the synthesis and the antiviral activities of a series of 6-arylmethyl-1-(allyloxymethyl)-5-alkyluracil derivatives, which can be viewed as analogues of the anti-HIV-1 drug emivirine (formerly MKC-442) from which they differ in the replacement of the ethoxymethyl group with variously allyloxymethyl moieties. The most active compounds N-1 allyloxymethyl- and N-1 3-methylbut-2-enyl substituted 5-ethyl-6-(3,5-dimethylbenzyl)uracils (12 and 13) showed activity against HIV-1 wild-type in the picomolar range with selective index of greater than 5 x 10(6) and activity in the submicromolar range against the clinically important Y181C and K103N mutant strains known to be resistant to emivirine. Structure-activity relationship studies established a correlation between the anti-HIV-1 activity and the substitution pattern of the N-1 allyloxymethyl group.
Optimization flow control. I. Basic algorithm and convergence (1999)

We propose an optimization approach to flow control where the objective is to maximize the aggregate source utility over their transmission rates. We view network links and sources as processors of a distributed computation system to solve the dual problem using a gradient projection algorithm. In this system, sources select transmission rates that maximize their own benefits, utility minus bandwidth cost, and network links adjust bandwidth prices to coordinate the sources' decisions. We allow feedback delays to be different, substantial, and time varying, and links and sources to update at different times and with different frequencies. We provide asynchronous distributed algorithms and prove their convergence in a static environment. We present measurements obtained from a preliminary prototype to illustrate the convergence of the algorithm in a slowly time-varying environment. We discuss its fairness property.
Ionic‐Liquid‐Influenced Expeditious and Stereoselective Synthesis of Olefins (2007)

Abstract 1‐Butyl‐3‐methylimidazolium chloroaluminate, [bmim]Cl·.AlCl3 (molar fraction, N=0.67), ionic liquid has been used in combination with metallic Zn for the reductive coupling of carbonyl compounds to synthesize symmetrical olefins, with the Z‐isomer formed predominantly. The ionic liquid played a dual role of Lewis acid catalyst and solvent.
Nuclear Eukaryotic Initiation Factor 4e (Eif4e) Colocalizes with Splicing Factors in Speckles (2000)

The eukaryotic initiation factor 4E (eIF4E) plays a pivotal role in the control of protein synthesis. eIF4E binds to the mRNA 5' cap structure, m(7)GpppN (where N is any nucleotide) and promotes ribosome binding to the mRNA. It was previously shown that a fraction of eIF4E localizes to the nucleus (Lejbkowicz, F., C. Goyer, A. Darveau, S. Neron, R. Lemieux, and N. Sonenberg. 1992. Proc. Natl. Acad. Sci. USA. 89:9612-9616). Here, we show that the nuclear eIF4E is present throughout the nucleoplasm, but is concentrated in speckled regions. Double label immunofluorescence confocal microscopy shows that eIF4E colocalizes with Sm and U1snRNP. We also demonstrate that eIF4E is specifically released from the speckles by the cap analogue m(7)GpppG in a cell permeabilization assay. However, eIF4E is not released from the speckles by RNase A treatment, suggesting that retention of eIF4E in the speckles is not RNA-mediated. 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) treatment of cells causes the condensation of eIF4E nuclear speckles. In addition, overexpression of the dual specificity kinase, Clk/Sty, but not of the catalytically inactive form, results in the dispersion of eIF4E nuclear speckles.
A survey of potential problems and quality control in peptide synthesis by the fluorenylmethoxycarbonyl procedure. (1991)

The routine production of peptides by manual or automated solid-phase synthesis protocols has gained widespread usage among a variety of biological scientists as new synthetic procedures have been introduced over the past several years. We report here a detailed analysis of Fmoc synthesis procedures to identify problematic reactions and to evaluate analytical procedures for monitoring the quality of peptides during and after synthesis. The results of these studies demonstrate double additions of particular amino acids during single coupling cycles, frequent incomplete deblocking of peptides by standard piperidine reactions, and the failure of the Kaiser ninhydrin test to detect free amino groups of certain amino acids at the N-terminus of synthetic peptides. These results suggest the need for more careful monitoring of Fmoc synthesis reactions than previously recognized or recommended in standard protocols. We demonstrate the utility of plasma desorption mass spectrometry (PDMS) in analyzing peptide products and recommend a minimum sequence of analytical quality control including HPLC and PDMS.
Retinoic Acid Attenuates Rheumatoid Inflammation in Mice (2012)

Retinoic acid is the active vitamin A derivative and is well-known to have diverse immunomodulatory actions. In this study, we investigated the impact of all-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, on the development of arthritis and the pathophysiologic mechanisms by which ATRA might have antiarthritic effects in animal model of rheumatoid arthritis (RA; collagen-induced arthritis [CIA] in DBA/1J mice). We showed that treatment with ATRA markedly suppressed the clinical and histologic signs of arthritis in the CIA mice. It reduced the expression of IL-17 in the arthritic joints. Interestingly, Foxp3(+) regulatory T cells were markedly increased and IL-17-producing CD4(+) T cells (Th17 cells) were decreased in the spleens of ATRA-treated mice. In vitro treatment with ATRA induced the expression of Foxp3 and repressed the IL-17 expression in the CD4(+) T cells in mice. ATRA suppressed the production of total IgG and IgG2a in splenocytes that were stimulated by LPS. It also reduced serum levels of total IgG and IgG2 anti-collagen Abs and germinal center formation in CIA mice. In addition, the ATRA-treated mice showed decreased osteoclast formation in arthritic joints. Moreover, ATRA downregulated the expression of receptor activator of NF-κB ligand, the leading player of osteoclastogenesis, in the CD4(+) T cells and fibroblast-like synoviocytes from patients with RA. Furthermore, ATRA prevented both human monocytes and mice bone marrow-derived monocytes/macrophage cells from differentiating into osteoclasts. These data suggest ATRA might be an effective treatment modality for RA patients.
Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. (2005)

(177)Lu-DOTATOC therapy in patients with relapse after (90)Y-DOTATOC treatment is feasible, safe, and efficacious. No serious adverse events occurred.
Defining and Measuring Fatigue (1999)

In response to a long history of problems with defining and measuring fatigue, the University of Kansas School of Nursing established a Center for Biobehavioral Studies of Fatigue Management to facilitate the study of fatigue in diverse populations. The purpose of this article is to review past efforts to define and measure fatigue and the conceptual problems relevant to currently used measures of fatigue. Several distinct characteristics and corresponding measures of fatigue are identified and a definition and framework for the study of fatigue are discussed. Future research on fatigue must attend to the conceptual distinctions among various measures and the measures of fatigue most appropriate to the goals of a study.
Reduced Graphene Oxide Conjugated Cu2O Nanowire Mesocrystals for High-Performance NO2 Gas Sensor (2012)

Reduced graphene oxide (rGO)-conjugated Cu(2)O nanowire mesocrystals were formed by nonclassical crystallization in the presence of GO and o-anisidine under hydrothermal conditions. The resultant mesocrystals are comprised of highly anisotropic nanowires as building blocks and possess a distinct octahedral morphology with eight {111} equivalent crystal faces. The mechanisms underlying the sequential formation of the mesocrystals are as follows: first, GO-promoted agglomeration of amorphous spherical Cu(2)O nanoparticles at the initial stage, leading to the transition of growth mechanism from conventional ion-by-ion growth to particle-mediated crystallization; second, the evolution of the amorphous microspheres into hierarchical structure, and finally to nanowire mesocrystals through mesoscale transformation, where Ostwald ripening is responsible for the growth of the nanowire building blocks; third, large-scale self-organization of the mesocrystals and the reduction of GO (at high GO concentration) occur simultaneously, resulting in an integrated hybrid architecture where porous three-dimensional (3D) framework structures interspersed among two-dimensional (2D) rGO sheets. Interestingly, "super-mesocrystals" formed by 3D oriented attachment of mesocrystals are also formed judging from the voided Sierpinski polyhedrons observed. Furthermore, the interior nanowire architecture of these mesocrystals can be kinetically controlled by careful variation of growth conditions. Owing to high specific surface area and improved conductivity, the rGO-Cu(2)O mesocrystals achieved a higher sensitivity toward NO(2) at room temperature, surpassing the performance of standalone systems of Cu(2)O nanowires networks and rGO sheets. The unique characteristics of rGO-Cu(2)O mesocrystal point to its promising applications in ultrasensitive environmental sensors.
Nasal nitric oxide in man (1999)

The past decade has witnessed an explosion in the interest of biologists in the gas nitric oxide (NO). This highly reactive free radical, first considered only a noxious air pollutant, is produced in mammalian cells by specific enzymes and is believed to play a vital role in many biological events including regulation of blood flow, platelet function, immunity, and neurotransmission.1 2Direct measurement of NO in biological tissues is difficult to perform because this gas reacts rapidly with, for example, haemoglobin or other Fe2+-containing proteins. It is therefore often necessary to rely on indirect measurements in order to detect NO synthesis in vivo. Unlike the situation in most biological tissues where NO is rapidly destroyed, in the gas phase NO is fairly stable at low concentrations.3 NO produced in superficial structures of hollow organs will diffuse into the lumen and thus be detectable in gas collected from such organs.

The presence of NO in exhaled breath of humans was first demonstrated by Gustafsson et al in 1991.4Later studies clearly showed that, in healthy controls at rest, almost all NO found in exhaled air originates from the upper airways with only a minor contribution from the lower respiratory tract and the lungs.5-7 

The exact origin of the NO found in nasal air and the relative contribution from different sources within the nasal airways are not known. There are, however, some indications that favour the paranasal sinuses rather than the mucosa of the nasal cavity as a major source of nasal NO in adult healthy humans.8 Firstly, NO release in the sinuses is markedly reduced by intrasinus instillation of an NO synthase inhibitor (l-NAME) whereas nasal NO concentrations are only slightly reduced following intranasal administration of this inhibitor.9 Secondly, immunohistochemical and in …