gebhart/patrepeval huggingface dataset:
Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux (2004)

Copper is known to play a role in iron recycling from macrophages. To examine whether cellular copper status affects expression of the iron exporter ferroportin-1 (FPN1), J774 macrophage cells were exposed to 10-100 microM CuSO(4) for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose- and time-dependent manner. After 20 h, 100 microM CuSO(4) up-regulated FPN1 transcript levels approximately 13-fold compared to untreated controls. Induction was detected 8 h after copper treatment was initiated and markedly increased thereafter. A corresponding increase in FPN1 protein levels was observed upon copper treatment. Induction of J774 cell FPN1 expression by copper was also associated with a dose-dependent increase in (59)Fe release after erythrophagocytosis of labeled red blood cells. Thus, a previously uncharacterized role for copper in the regulation of macrophage iron recycling is suggested by the induction of FPN1 gene expression and iron efflux by this metal.
Phase II Study of the MEK1/MEK2 Inhibitor Trametinib in Patients With Metastatic BRAF -Mutant Cutaneous Melanoma Previously Treated With or Without a BRAF Inhibitor (2012)

Trametinib was well tolerated. Significant clinical activity was observed in BRAF-inhibitor-naive patients previously treated with chemotherapy and/or immunotherapy. Minimal clinical activity was observed as sequential therapy in patients previously treated with a BRAF inhibitor. Together, these data suggest that BRAF-inhibitor resistance mechanisms likely confer resistance to MEK-inhibitor monotherapy. These data support further evaluation of trametinib in BRAF-inhibitor-naive BRAF-mutant melanoma, including rarer forms of BRAF-mutant melanoma.
CD137 Accurately Identifies and Enriches for Naturally Occurring Tumor-Reactive T Cells in Tumor (2013)

Our findings reveal a role for the TNFR-family member CD137 in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of TILs, thus rationalizing its agonistic engagement in vivo and its use in TIL selection for adoptive immunotherapy trials.
A Comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in Pulmonary Neuroendocrine Tumors (2009)

Typical bronchial carcinoids showed higher and more selective uptake of (68)Ga-DOTATATE than of (18)F-FDG. Atypical carcinoids and higher grades had less (68)Ga-DOTATATE avidity but were (18)F-FDG-avid.
Structure of the periplasmic component of a bacterial drug efflux pump (2004)

Multidrug resistance among Gram-negative bacteria is conferred by three-component membrane pumps that expel diverse antibiotics from the cell. These efflux pumps consist of an inner membrane transporter such as the AcrB proton antiporter, an outer membrane exit duct of the TolC family, and a periplasmic protein known as the adaptor. We present the x-ray structure of the MexA adaptor from the human pathogen Pseudomonas aeruginosa. The elongated molecule contains three linearly arranged subdomains; a 47-A-long alpha-helical hairpin, a lipoyl domain, and a six-stranded beta-barrel. In the crystal, hairpins of neighboring MexA monomers pack side-by-side to form twisted arcs. We discuss the implications of the packing of molecules within the crystal. On the basis of the structure and packing, we suggest a model for the key periplasmic interaction between the outer membrane channel and the adaptor protein in the assembled drug efflux pump.
Production of recombinant L-leucine dehydrogenase fromBacillus cereus in pilot scale using the runaway replication systemE. coli[piet98] (2000)

A method for the production of recombinant L-leucine dehydrogenase from Bacillus cereus in pilot scale is described employing the temperature induced runaway replication vector pIET98 and the Escherichia coli host strain BL21. Fed-batch cultivation using a semi-synthetic high-cell densitiy medium was adjusted in 5-L scale to yield a constant growth rate of 0,17 h(-1) and a final cell concentration of 27 g dry weight/L by exponentially increasing the nutrient supply. Runaway replication and thus, LeuDH expression was induced during the feeding phase by increasing the cultivation temperature to 41 degrees C yielding a specific enzyme activity of 110 U/mg, which corresponds to 30% of the soluble cell protein. The cultivation was terminated when the dissolved oxygen content fell below 10% saturation. The final volume activity was 600,000 U/L cultivation. No change in growth, cell density, or expression activity was observed scaling up the cultivation volume to 200 L. Thus, 120,000,000 units L-leucine dehydrogenase were obtained from one cultivation. The purification of L-leucine dehydrogenase to homogeneity was carried out by heat denaturation, liquid-liquid extraction, gel filtration, and anion-exchange chromatography to give pure enzyme in 65% yield. The integrity of the recombinant enzyme was tested measuring the molecular weight and determining the N-terminal amino acid sequence.
Discrimination among morphine, saline and naltrexone in rhesus monkeys receiving morphine subchronically (1994)

Discriminative control was established among morphine, saline and naitrexone in rhesus monkeys receiving morphine every other day. Three hours prior to sessions subjects received saline or 3.2 mg/kg morphine; immediately prior to sessions they received saline or 0.01 mg/kg of naitrexone. There were dose-related generalizations to each training condition: morphine generalized to the morphine plus saline lever; small doses of naitrexone reversed effects of morphine and larger doses occasioned responding on the morphine plus naitrexone lever; in one monkey still larger doses occasioned responding on the saline plus saline lever. When saline was administered 3h earlier, naitrexone had no effect in one subject and occasioned responding on the morphine plus naitrexone lever in a second subject. Nalbuphine substituted for morphine plus saline in one monkey and for morphine plus naitrexone in a second monkey; ketamine did not substitute for either training drug. That stimulus control was established between no drug and a combination of morphine and naitrexone suggests the latter condition did not represent the absence of morphine. In addition to demonstrating stimulus control for three conditions in rhesus monkeys, the current study suggests opioid antagonists might have novel discriminative stimulus effects at opioid receptors even under conditions where signs of withdrawal are not evident.
Distinct Activation Patterns of Idioventricular Rhythms and Sympathetically‐Induced Ventricular Tachycardias in Dogs with Atrioventricular Block (1992)

To investigate mechanisms of ventricular impulse formation in response to sympathetic stimulation in the healthy canine heart in situ, we compared the patterns of ventricular activation during the idioventricular rhythms arising after complete atrioventricular (AV) block and ventricular tachycardias induced by RSG or LSG stimulation. Isochronal maps were generated by computer from 116-127 unipolar electrograms recorded from the entire ventricular epicardium in 15 open chest, anesthetized dogs. In eight of these, bipolar electrograms were recorded with plunge electrodes from 11 selected endocardial sites located below epicardial breakthrough areas. Intracardiac recordings from the His-Purkinje system were made with electrode catheters. After electrograms were recorded during sinus rhythm, complete AV block was induced by injecting formaldehyde into the AV node and idioventricular rhythms occurred spontaneously at a rate of 37 +/- 12 beats/min (mean +/- SD, n = 25). During idioventricular rhythms, endocardial activation preceded the earliest epicardial breakthrough, which occurred in either the right anterior paraseptal region, antero-apical left ventricle, or postero-apical left ventricle. These sites were consistent with a focal origin in the subendocardial His-Purkinje system. Total epicardial activation times lasted for 47 +/- 13 msec (n = 40). Idioventricular rhythms were suppressed by overdrive pacing (intermittent trains of ten beats with decremental cycle length from 500 to 200 msec) or by intravenous calcium infusion (to plasma levels of 10.1-15.2 mM). Right or left stellate ganglion stimulation increased idioventricular rhythm rates (to 52 +/- 13 beats/min, n = 28) and also induced, in all preparations, ventricular tachycardias that had significantly faster rates (189 +/- 55 beats/min, n = 27, P less than 0.005). Ventricular fibrillation was induced after brief runs of ventricular tachycardia in five of the preparations. During ventricular tachycardias, epicardial activation occurred on the right ventricular outflow tract or the postero-lateral wall of the left ventricle, and preceded endocardial activation in 50% of cases. Total epicardial activation times (103 +/- 29 beats/min) were significantly longer than during idioventricular rhythms (P less than 0.005). Ventricular tachycardias displayed overdrive excitation at critical pacing cycle lengths (360-280 msec) and were not suppressed by calcium infusion. Thus, differential mechanisms of impulse formation with distinct localizations can be elicited from healthy ventricular myocardium.
Modulation of Renal Disease in MRL/ lpr Mice Genetically Deficient in the Alternative Complement Pathway Factor B (2000)

In systemic lupus erythematosus, the renal deposition of complement-containing immune complexes initiates an inflammatory cascade resulting in glomerulonephritis. Activation of the classical complement pathway with deposition of C3 is pathogenic in lupus nephritis. Although the alternative complement pathway is activated in lupus nephritis, its role in disease pathogenesis is unknown. To determine the role of the alternative pathway in lupus nephritis, complement factor B-deficient mice were backcrossed to MRL/lpr mice. MRL/lpr mice develop a spontaneous lupus-like disease characterized by immune complex glomerulonephritis. We derived complement factor B wild-type (B+/+), homozygous knockout (B-/-), and heterozygous (B+/-) MRL/lpr mice. Compared with B+/- or B+/+ mice, MRL/lpr B-/- mice developed significantly less proteinuria, less glomerular IgG deposition, and decreased renal scores as well as lower IgG3 cryoglobulin production and vasculitis. Serum C3 levels were normal in the B-/- mice compared with significantly decreased levels in the other two groups. These results suggest that: 1) factor B plays an important role in the pathogenesis of glomerulonephritis and vasculitis in MRL/lpr mice; and 2) activation of the alternative pathway, either by the amplification loop or by IgA immune complexes, has a prominent effect on serum C3 levels in this lupus model.
Kinematic transformations for remotely-actuated planar continuum robots (2002)

We consider a class of robotic manipulators generally termed "hyper-redundant". Specifically, we seek to examine some of the kinematic properties of "continuum" hyper-redundant robots. Unlike the case with rigid-link robots, there is no commonly accepted formula for describing continuum robot kinematics. Although these manipulators are continuously flexible, they are actuated with a finite number of actuators. We discuss two possible options for mapping desired infinite-dimensional robot shapes to the finite-dimensional actuator space, using "natural" and "wavelet" decompositions. We compare and contrast these kinematic descriptions, illustrating how the wavelet decomposition can simplify the inverse kinematics for redundant planar continuum robots.
The use of carbon fiber implants in anterior cruciate ligament surgery. (1985)

In cruciate ligament surgery where carbon fibers have been placed within the synovial cavity of the knee joint, an inadequate biologic response occurs that leads to failure of the implant and fragmentation within the joint. This paper describes in detail the operative technique of one surgeon (A.E.S.) of placing a collagen-coated carbon fiber implant through the retrosynovial route of the anterior cruciate ligament. It also describes the clinical and arthroscopic follow-up evaluations of four consecutive cases by an independent surgeon (P.F.). The results confirm the contention that when the carbon fibers are placed either within the remnants of the original ligament or within a sheath of fascia lata and maintained in the retrosynovial situation, no carbon debris appears within the joint cavity, and a normal-looking cruciate ligament results.
Race and the Response to Adrenergic Blockade with Carvedilol in Patients with Chronic Heart Failure (2001)

The benefit of carvedilol was apparent and of similar magnitude in both black and nonblack patients with heart failure.
Mutagenesis of the regulatory domain of phenylalanine hydroxylase (2001)

The regulatory domain of phenylalanine hydroxylase (PAH, EC ) consists of more than 100 amino acids at the N terminus, the removal of which significantly activates the enzyme. To study the regulatory properties controlled by the N terminus, a series of truncations and site-specific mutations were made in this region of rat PAH. These enzymes were expressed highly in Escherichia coli and purified through a pterin-conjugated Sepharose affinity column. The removal of the first 26 amino acids of the N terminus increased the activity by about 20-fold, but removal of the first 15 amino acids increased the activity by only 2-fold. Replacing serine-29 of rat PAH with cysteine from the same site of human PAH increased the activity by more than 4-fold. Mutation of serine to other amino acids with varying side chains: alanine, methionine, leucine, aspartic acid, asparagine, and arginine also resulted in significant activation, indicating a serine-specific inhibitory effect. But these site-specific mutants showed 30--40% lower activity when assayed with 6-methyl-5,6,7,8-tetrahydropterin. Stimulation of hydroxylase activity by preincubation of the enzyme with phenylalanine was inversely proportional to the activation state of all these mutants. Combined with recent crystal structures of PAH [Kobe, B. et al. (1999) Nat. Struct. Biol. 6, 442-448; and Erlandsen, H., Bjorgo, E., Flatmark, T. & Stevens, R. C. (2000) Biochemistry 39, 2208-2217], these data suggest that residues 16-26 have a controlling regulatory effect on the activity by interaction with the dihydroxypropyl side chain of (6R)-5,6,7,8-tetrahydrobiopterin. The serine/cysteine switch explains the difference in regulatory properties between human and rat PAH. The N terminus as a whole is important for maintaining rat PAH in an optimum catalytic conformation.
Role of breast milk in acquisition of cytomegalovirus infection: recent advances (2006)

Abstract Purpose of review Congenital infection with cytomegalovirus is a major cause of disability in newborns. Recently, there has been increased emphasis on the study of postnatally acquired cytomegalovirus infection. One route by which cytomegalovirus infections are acquired in newborns is via consumption of breast milk from cytomegalovirus-seropositive, lactating mothers. The purpose of this review is to summarize recent studies of breast-milk-acquired cytomegalovirus infections in newborns, particularly in low-birth-weight premature infants. Recent findings Nearly all cytomegalovirus-seropositive women will reactivate and shed cytomegalovirus during lactation, as demonstrated by sensitive polymerase chain reaction techniques, as well as by viral culture of breast milk. A substantial proportion of infants exposed to cytomegalovirus in breast milk will acquire a primary cytomegalovirus infection. Although acquisition of cytomegalovirus by this route is seldom of consequence in healthy term infants, cytomegalovirus infections in low-birth-weight premature infants have been demonstrated to cause symptomatic illness, including hepatitis, neutropenia, thrombocytopenia, and a ‘sepsis-like’ state. Summary Cytomegalovirus is commonly shed in human milk, and cytomegalovirus-seropositive women can transmit this infection via breast-feeding. The benefits of breast-feeding greatly outweigh the minimal risk, if any, of infections transmitted to term infants. Caution is warranted, however, in low-birth-weight premature infants, who are at increased risk of cytomegalovirus disease. Interventions to screen breast milk, or to attempt to render breast milk noninfectious through treatments such as freezing, may be warranted in high-risk premature infants.
Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin (2013)

4-1BB agonist antibody treatment induces a population of KLRG1(+) T cells that infiltrate melanoma tumors. We investigated the origin and function of these cells, as well as their place within established T cell paradigms. We find that these T cells, particularly the CD4 lineage, represent a novel phenotype characterized by enhanced, multipotent cytotoxicity. Distinct from described polarities, this T cell phenotype is driven by the T-box transcription factor Eomesodermin. Formation of this phenotype requires 4-1BB signaling on both T and antigen-presenting cells and the resulting production of the cytokines IL-27, IL-15, and IL-10. Furthermore, we find CD4(+) T cells bearing the signature features of this phenotype in the livers of mice infected with both bacterial and viral intracellular pathogens, suggesting a role for these cells in infectious immunity. These T cells constitute a novel phenotype that resolves multiple questions associated with 4-1BB activation, including how 4-1BB enhances tumor-specific cytotoxicity and how 4-1BB can promote tumor immunity while repressing autoimmunity.
Structure−Activity Study of Brassinin Derivatives as Indoleamine 2,3-Dioxygenase Inhibitors (2005)

A screen of indole-based structures revealed the natural product brassinin to be a moderate inhibitor of indoleamine 2,3-dioxygenase (IDO), a new cancer immunosuppression target. A structure-activity study was undertaken to determine which elements of the brassinin structure could be modified to enhance potency. Three important discoveries have been made, which will impact future IDO inhibitor development: (i) The dithiocarbamate portion of the brassinin lead is a crucial moiety, which may be binding to the heme iron of IDO; (ii) an indole ring is not necessary for IDO inhibition; and (iii) substitution of the S-methyl group of brassinin with large aromatic groups provides inhibitors that are three times more potent in vitro than the most commonly used IDO inhibitor, 1-methyl-tryptophan.
Evidence for an accessory component that increases the affinity of the erythropoietin receptor. (1993)

Evidence for an accessory component that can modify the affinity of the erythropoietin (Epo) receptor is presented. Dihydrofolate reductase (DHFR)-deficient Chinese hamster ovary (CHO) cells were transfected with a plasmid containing the Epo receptor cDNA (derived from murine erythroleukemia cells with only low affinity receptors) and DHFR cDNA. The cells expressed both high and low affinity receptors. Upon amplification with methotrexate (MTX), only the number of low affinity receptors increased, suggesting that there was a constitutively expressed cellular component in CHO cells that can increase Epo receptor affinity. Further support for this hypothesis was provided by our finding that fusion of IW 201 cells, which have only low affinity receptors, with nontransfected CHO cells, which have no Epo receptors, resulted in high affinity binding sites for Epo.
Using Different Drift Gases To Change Separation Factors (α) in Ion Mobility Spectrometry (1999)

The use of different drift gases to alter separation factors (alpha) in ion mobility spectrometry has been demonstrated. The mobility of a series of low molecular weight compounds and three small peptides was determined in four different drift gases. The drift gases chosen were helium, argon, nitrogen, and carbon dioxide. These drift gases provide a range of polarizabilities and molecular weights. In all instances, the compounds showed the greatest mobility in helium and the lowest mobility in carbon dioxide; however the percentage change of mobility for each compound was different, effectively changing the alpha value. The alpha value changes were primarily due to differences in drift gas polarizability but were also influenced by the mass of the drift gas. In addition, gas-phase ion radii were calculated in each of the different drift gases. These radii were then plotted against drift gas polarizability producing linear plots with r2 values greater than 0.99. The intercept of these plots provides the gas-phase radius of an ion in a nonpolarizing environment, whereas the slope is indicative of the magnitude of the ion's mobility change related to polarizability. It therefore, should be possible to separate any two compounds that have different slopes with the appropriate drift gas.
Non-Photolithographic Methods for Fabrication of Elastomeric Stamps for Use in Microcontact Printing (1996)

This paper describes several methods that generate patterned relief structures for casting the elastomeric stamps required in microcontact printing (μCP). The relief structures include the following: (1) patterns etched in thin films of silver (200 nm thick) with printed SAMs of hexadecanethiolate as resists; (2) patterned polymeric structures assembled on the surface of a thin film of silver (or gold) that has been patterned with SAMs of hexadecanethiolate; and (3) polystyrene microspheres assembled on a flat surface. Commercial diffraction gratings were also useful as masters. Microcontact printing with poly(dimethylsiloxane) stamps cast from these relief structures was used in combination with selective wet etching to generate patterns in thin films of silver and gold. Although some of these techniques used photolithography once in fabricating the initial masters, they could produce patterns more complex than those on the initial masters. These procedures provide a convenient route to moderately complex patterns with feature sizes ranging from ∼100 nm to ∼100 μm.
Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion Through Simultaneous Suppression of Cdkn1a and Cdkn2a in Mice (2014)

Our results show that expansion of hepatic stem/progenitor cells requires Ring1B-mediated epigenetic silencing of Cdkn1a and Cdkn2a, demonstrating that Ring1B simultaneously regulates multiple CDKIs in tissue stem/progenitor cells.
Synthesis and structure-activity relationships of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines with antirhinovirus activity (1989)

A series of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines where the 2-substituent was H, F, Cl, CF3, CH3, CH2CH3, NH2, NHCH3, N(CH3)2, SCH3, or SO2CH3 was synthesized and tested for antirhinovirus activity to evaluate the effect of 2-substituents on antiviral activity. Intuitive and quantitative structure-activity relationship (QSAR) analysis showed that optimum antirhinovirus serotype 1B activity was associated with 9-benzylpurines that contained a C-2 lipophilic, electron-withdrawing substituent. The most active compound, 6-(dimethylamino)-9-(4-methylbenzyl)-2-(trifluoromethyl)-9H-purine (14), had an IC50 = 0.03 microM against serotype 1B, but its activity against 18 other serotypes was not uniform; the IC50s ranged over 260-fold.
Managing Insect Resistance to Bacillus thuringiensis Toxins (1992)

Bacillus thuringiensis (B.t.) delta-endotoxins provide an alternative to chemical insecticides for controlling many species of pest insects. Recent biotechnological developments offer the promise of even greater use of B.t. toxins in genetically transformed pest-resistant crops. However, the discovery that insects can adapt to these toxins raises concerns about the long-term usefulness of B.t. toxins. Several methods for managing the development of resistance to B.t. toxins have been suggested, but none of these approaches offer clear advantages in all situations.