gebhart/patrepeval huggingface dataset:
Activation of TRAP/Mediator Subunit TRAP220/Med1 Is Regulated by Mitogen-Activated Protein Kinase-Dependent Phosphorylation (2005)

The TRAP/Mediator coactivator complex serves as a molecular bridge between gene-specific activators and RNA polymerase II. TRAP220/Med1 is a key component of TRAP/Mediator that targets the complex to nuclear hormone receptors and other types of activators. We show here that human TRAP220/Med1 is a specific substrate for extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) family. We demonstrate that ERK phosphorylates TRAP220/Med1 in vivo at two specific sites: threonine 1032 and threonine 1457. Importantly, we found that ERK phosphorylation significantly increases the stability and half-life of TRAP220/Med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription. Furthermore, ERK phosphorylates TRAP220/Med1 in a cell cycle-dependent manner, resulting in peak levels of expression during the G(2)/M phase of the cell cycle. ERK phosphorylation of ectopic TRAP220/Med1 also triggered shuttling into the nucleolus, thus suggesting that ERK may regulate TRAP220/Med1 subnuclear localization. Finally, we observed that ERK phosphorylation of TRAP220/Med1 stimulates its intrinsic transcriptional coactivation activity. We propose that ERK-mediated phosphorylation is a regulatory mechanism that controls TRAP220/Med1 expression levels and modulates its functional activity.
Fungal identification using a Bayesian classifier and the Warcup training set of internal transcribed spacer sequences (2016)

Fungi are key organisms in many ecological processes and communities. Rapid and low cost surveys of the fungal members of a community can be undertaken by isolating and sequencing a taxonomically informative genomic region, such as the ITS (internal transcribed spacer), from DNA extracted from a metagenomic sample, and then classifying these sequences to determine which organisms are present. This paper announces the availability of the Warcup ITS training set and shows how it can be used with the Ribosomal Database Project (RDP) Bayesian Classifier to rapidly and accurately identify fungi using ITS sequences. The classifications can be down to species level and use conventional literature-based mycological nomenclature and taxonomic assignments.
Expression and pharmacological characterization of a stimulatory subtype of adenosine receptor in fetal chick ventricular myocytes. (1992)

Ventricular and atrial myocytes cultured from chick embryos 14 days in ovo were used as model systems to study cardiac adenosine receptors. In membranes of ventricular cultures, blocking of the A1-adenosine receptor pathway by the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or by pertussis toxin treatment of the myocyte resulted in a significant adenosine agonist-mediated stimulation of the adenylate cyclase activity. The maximal increases in adenylate cyclase activity caused by the equipotent or the A2-adenosine receptor-selective agonists (from 52.1 +/- 3% to 63 +/- 10% [mean +/- SEM]) were significantly greater than those caused by the A1-selective agonists (from 11 +/- 5% to 34.6 +/- 7%) (p less than 0.01, by t test, n = 4-8). However, in membranes of atrial myocytes, when A1-subtype had been blocked, the various adenosine agonists had no effect on the adenylate cyclase activity. Whether the stimulatory adenylate cyclase-coupled adenosine receptor is also capable of stimulating contractility in the intact ventricular myocyte was next investigated. In ventricular but not in atrial cells, the various adenosine agonists caused an increase in the contractile amplitude in the presence of DPCPX or in myocytes preexposed to pertussis toxin. The increase in contraction amplitude caused by each agonist was expressed as percent of maximum (maximum is the increase in contractility caused by 2.4 mM calcium). In the pertussis toxin-treated myocyte, the maximal increases caused by the equipotent or A2-agonists (NECA, MECA, CV-1808, and CGS21680, from 49.6 +/- 3% to 52.5 +/- 6%, n = 8-12) were significantly greater than those elicited by the A1-agonists (2-CADO, S-PIA, R-PIA, and DCCA, from 12 +/- 4% to 37 +/- 3%, n = 8) (p less than 0.05, by t test). These data demonstrated that a stimulatory adenosine receptor, likely the A2-adenosine receptor, was present on the ventricular but not the atrial myocytes and was linked directly to a stimulation of the cardiac contractility. The functional effects mediated by the A1-subtype became manifested in the presence of isoproterenol, as evidence by an inhibition of the isoproterenol-stimulated increases in adenylate cyclase activity and in cardiac contractility by adenosine agonists. Thus, both subtypes of adenosine receptors, each mediating opposing responses, were present on the ventricular myocytes, whereas only the A1-subtype was found in the atria. The presence of a stimulatory functional A2-adenosine receptor may help explain the absence of a direct negative inotropic response to adenosine in the ventricle.
Evidence for a stromal-epithelial “lactate shuttle” in human tumors (2011)

Recently, we proposed a new mechanism for understanding the Warburg effect in cancer metabolism. In this new paradigm, cancer-associated fibroblasts undergo aerobic glycolysis, and extrude lactate to "feed" adjacent cancer cells, which then drives mitochondrial biogenesis and oxidative mitochondrial metabolism in cancer cells. Thus, there is vectorial transport of energy-rich substrates from the fibroblastic tumor stroma to anabolic cancer cells. A prediction of this hypothesis is that cancer-associated fibroblasts should express MCT4, a mono-carboxylate transporter that has been implicated in lactate efflux from glycolytic muscle fibers and astrocytes in the brain. To address this issue, we co-cultured MCF7 breast cancer cells with normal fibroblasts. Interestingly, our results directly show that breast cancer cells specifically induce the expression of MCT4 in cancer-associated fibroblasts; MCF7 cells alone and fibroblasts alone, both failed to express MCT4. We also show that the expression of MCT4 in cancer-associated fibroblasts is due to oxidative stress, and can be prevented by pre-treatment with the anti-oxidant N-acetyl-cysteine. In contrast to our results with MCT4, we see that MCT1, a transporter involved in lactate uptake, is specifically upregulated in MCF7 breast cancer cells when co-cultured with fibroblasts. Virtually identical results were also obtained with primary human breast cancer samples. In human breast cancers, MCT4 selectively labels the tumor stroma, e.g., the cancer-associated fibroblast compartment. Conversely, MCT1 was selectively expressed in the epithelial cancer cells within the same tumors. Functionally, we show that overexpression of MCT4 in fibroblasts protects both MCF7 cancer cells and fibroblasts against cell death, under co-culture conditions. Thus, we provide the first evidence for the existence of a stromal-epithelial lactate shuttle in human tumors, analogous to the lactate shuttles that are essential for the normal physiological function of muscle tissue and brain. These data are consistent with the "reverse Warburg effect," which states that cancer-associated fibroblasts undergo aerobic glycolysis, thereby producing lactate, which is utilized as a metabolic substrate by adjacent cancer cells. In this model, "energy transfer" or "metabolic-coupling" between the tumor stroma and epithelial cancer cells "fuels" tumor growth and metastasis, via oxidative mitochondrial metabolism in anabolic cancer cells. Most importantly, our current findings provide a new rationale and novel strategy for anti-cancer therapies, by employing MCT inhibitors.
Differential requirements of novel A1PiZ degradation deficient (ADD)genes in ER-associated protein degradation (2003)

In the eukaryotic cell, a protein quality control process termed endoplasmic reticulum-associated degradation (ERAD) rids the ER of aberrant proteins and unassembled components of protein complexes that fail to reach a transport-competent state. To identify novel genes required for ERAD, we devised a rapid immunoassay to screen yeast lacking uncharacterized open reading frames that were known targets of the unfolded protein response (UPR), a cellular response that is induced when aberrant proteins accumulate in the ER. Six genes required for the efficient degradation of the Z variant of the alpha1-proteinase inhibitor (A1PiZ), a known substrate for ERAD, were identified, and analysis of other ERAD substrates in the six A1PiZ-degradation-deficient (add) mutants suggested diverse requirements for the Add proteins in ERAD. Finally, we report on bioinformatic analyses of the new Add proteins, which will lead to testable models to elucidate their activities.
Stimulation of tumor growth by recombinant human insulin-like growth factor-I (IGF-I) is dependent on the dose and the level of IGF-I receptor expression. (1998)

The insulin-like growth factors (IGF) I and II regulate metabolism, mitogenesis, differentiation, and apoptosis. The therapeutic uses of IGF-I have been discussed extensively; however, excessive activity of the IGF ligands and IGF-I receptor has been suggested as a factor in tumorigenesis. The inhibition of apoptosis by IGF-I is believed to be particularly important for the stimulation of tumor growth. This study examined whether systemic recombinant human IGF-I (rhIGF-I) therapy affects the growth of fibrosarcomas derived from fibroblasts expressing the IGF-I receptor at high or naturally occurring densities (1.9 x 10(5) compared with 1.6 x 10(4) IGF-I receptors/cell) in athymic nude mice. Treatment with 4 or 10 mg/kg rhIGF-I resulted in a marked reduction in the tumor latency and stimulated the growth of fibrosarcomas that overexpressed the IGF-I receptor. The latency and growth of fibrosarcomas expressing parental levels of the IGF-I receptor were not affected by rhIGF-I therapy. Analysis of mitosis by histone H3 mRNA in situ hybridization and of apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling assay indicated that rhIGF-I-stimulated tumor growth was associated with a marked increase in mitogenesis; however, there was no evidence for any significant effect on apoptosis. These data imply that: (a) systemic rhIGF-I can stimulate the growth of tumors directly by stimulating mitosis; and (b) a reasonable level of IGF-I receptor expression is required for stimulation of tumor growth by systemic rhIGF-I.
Pulsus Alternans (1996)

Figure 1. Physical examination of two patients with severe left ventricular failure revealed pulsus alternans in the radial pulse. Pulsus alternans is a physical finding characterized by a regular alternation of the force of the arterial pulse. It almost invariably indicates the presence of severe left ventricular systolic dysfunction.Panel A shows a simultaneous electrocardiogram (ECG), phonocardiogram, and carotid-pulse tracing in a 64-year-old man with an ejection fraction of 15 percent due to dilated cardiomyopathy. Alternating strong and weak beats are seen in the carotid pulse tracing that corresponded to an alternation of approximately 40 mm Hg in the systolic . . .
Relation of Donor Age and Preexisting Coronary Artery Disease on Angiography and Intracoronary Ultrasound to Later Development of Accelerated Allograft Coronary Artery Disease (1997)

Heart donors with angiographic evidence of preexisting coronary artery disease and older donors are more likely to develop new allograft coronary artery disease by 3 years. However, there is no difference in survival or freedom from ischemic events between younger and older donors at a mean follow-up of 3.8 years.
&alpha;&alpha;&ndash;Crosslinked Hemoglobin: Was Failure Predicted by Preclinical Testing? (2000)

In 1998, Baxter Healthcare announced that it was abandoning its product, diaspirin-crosslinked hemoglobin (DCLHb), the first 'blood substitute' to complete all phases of human trials. The company announced that the phase III (pivotal) trials in humans had resulted in an unexpectedly high survival in a group of patients serving as controls for those who received their product in a trauma setting. It is not possible to quantitate the time, efforts and money that were expended in the course of developing this product, from 1985 to 1998. It is rumored that the giant healthcare company had expended more than a half billion dollars on this product, not to mention the investment in the same product by the US Army, the National Institutes of Health and many independent university-based scientists. The disappointment was profound and far-reaching. Although the threat of HIV transmission by banked blood has all but disappeared in the developed world, still the bulk of the world's population faces blood shortages, which this product and its future generations might have helped alleviate. Only Baxter and the Food and Drug Administration may forever know key elements of the history of development of this product. However, because the US Army decided to make its version of the product widely available to scientists, there is a substantial published record, contributed to by both Baxter and independent scientists. Examination of this record leads to the conclusion that there is no single reason for failure. However, it shows that the characteristic hemodynamic response caused by alphaalphaHb increased vascular resistance, and probably eliminates its potential as a red cell substitute. Newer solutions that overcome this limitation should fare better in clinical development when this problem is overcome.
The effect of food on the pharmacokinetics of oral fluralaner in dogs (2014)

Fluralaner is absorbed to a considerable extent in fasted and fed dogs. Administration of fluralaner chewable tablets with food significantly increases bioavailability.
New Gelatin-Based Hydrogels via Enzymatic Networking (2002)

New types of hydrogels have been obtained starting from high bloom purified gelatin A, alone or in mixtures with hyaluronan and with a hyaluronan derivative bearing primary amino groups, by transglutaminase-catalyzed cross-linking. The reticulation process, carried out adopting two different temperature protocols, and the ensuing materials have been characterized in terms of rheologically estimated gel times, equilibrium swelling in water and in phosphate buffer solution (PBS), and rigidity modulus. Main structural and conformational factors governing the physicochemical properties and the possible application of the new hydrogels are discussed.
Cloning and Sequence of cDNAs for an Intracellular Acid Invertase from Etiolated Hypocotyls of Mung Bean and Expression of the Gene during Growth of Seedlings (1992)

Etiolated seedlings of mung bean (Vigna radiata) contain two forms (a heterodimer of 30-kDa and 38-kDa subunits and a 70-kDa monomeric form) of soluble intracellular acid invertase [Arai et al. Plant Cell Physiol. (1991) 32: 1291–1298]. A cDNA for the heterodimeric form was cloned and its nucleotide sequence was determined. The heterodimeric form was synthesized as a single polypeptide with a long leader sequence of 101 amino acids. A sequence resembling a signal peptide, of about 60 amino acids was present at the N-terminus. The extent of similarity in terms of nucleotide and amino acid sequences to carrot acid invertase, the only plant invertase for which the primary structure is known, was 51.1% and 49.6%, respectively. RNA blot analysisshowed that a transcript of the gene for acid invertase appeared within 6 h of imbibition of seeds and was accumulated at maximal levels between 9 and 15 h. The time course of the expression of the gene for acid invertase was markedly different from that of the invertase activity itself, and expression of the gene occurred much earlier than the appearance of the enzymatic activity in hypocotyls. The reason for the absence of a correlation between enzymatic activity and the level of the transcript is discussed.
Targeted transposition at the vestigial locus of Drosophila melanogaster. (1994)

Targeted transposition is the replacement of one P element with another. We are exploiting this unique property of P elements to study the complex regulatory domain of the Dopa decarboxylase (Ddc) gene in Drosophila melanogaster. P element constructs targeted to the same site in the genome will be subjected to the same position effect. This allows the subtle effects typical of most mutations in the Ddc regulatory region to be measured in the absence of the variable influences of position effects which are associated with the current method of germline transformation. We have investigated some of the parameters affecting targeted transposition of a Ddc transposon, P[Ddc], into a P element allele at the vestigial locus. These events were detected by an increased mutant vg phenotype. The location of the donor transposon in cis or in trans to the target had little effect on the frequency of targeting. Likewise, the mobility of different donor elements, as measured by their rate of transposition to a different chromosome, varied nearly 20-fold, while the rate of targeted transposition was very similar between them. All targeted alleles were precise replacements of the target P element by P[Ddc], but in several cases the donor was inserted in the opposite orientation. The targeted alleles could be described as the result of a replicative, conversion-like event.
Anomalous conductivity zones in electrophoresis. III. Experimental tests of the theory (1983)

Abstract An assumption used in developing the basic theory, that ionic retardation factors are substantially independent of solute concentration, is tested and found valid. The results of electrophoresis through 15% polyacrylamide gels are found to be in agreement with the theory. Zones of altered concentration appear in the presence of spermine tetrahydrochloride, sodium phosphate buffer (pH 7.2) or Tris‐HCl (pH 7.0). The use of ionic retardation factors and transport numbers deduced from conductivity measurements leads to correct prediction of the sign of concentration change in each case. The direction and velocity of migration of a low‐concentration boundary can also be predicted, together with associated changes in pH. Further confirmation comes from a detailed analysis of published work on electrophoresis through sucrose gradients. The theoretical treatment is suitable for application to other systems (such as isoelectric focusing and isotachophoresis) where a gel is used as a stabilizing medium, and where effects of the kind discussed may produce unexpected distubances.
X-ray Phase-Contrast Imaging and Metrology through Unified Modulated Pattern Analysis (2017)

We present a method for x-ray phase-contrast imaging and metrology applications based on the sample-induced modulation and subsequent computational demodulation of a random or periodic reference interference pattern. The proposed unified modulated pattern analysis (UMPA) technique is a versatile approach and allows tuning of signal sensitivity, spatial resolution, and scan time. We characterize the method and demonstrate its potential for high-sensitivity, quantitative phase imaging, and metrology to overcome the limitations of existing methods.
Increasing Register File Immunity to Transient Errors (2005)

Transient errors are a major reason for system downtime in many systems. In prior research, the register file has largely been neglected, but since it is accessed very frequently, the probability of transient errors is high. These errors can quickly spread to different parts of the system, and cause an application crash or silent data corruption. The paper addresses the reliability of register files in superscalar processors. We propose to duplicate actively used physical registers in unused physical registers. If the protection mechanism (parity or ECC) used for the primary copy indicates an error, the duplicate can provide the data, as long as it is not corrupted. We implement two strategies based on register duplication. In the "conservative strategy", we limit ourselves with the given register usage behavior, and duplicate register contents only on otherwise unused registers. Consequently, there is no impact on the original performance when there is no error, except for the protection mechanism used for the primary copy. Experiments with two different versions of this strategy show that, with the more powerful conservative scheme, 78% of the accesses are to the physical registers with duplicates. The "aggressive strategy" sacrifices some performance to increase the number of register accesses with duplicates. It does so by marking the registers not used for a long time as "dead" and using them for duplicating actively used registers. Experiments with this strategy indicate that it takes the fraction of reliable register accesses to 84%, and degrades the overall performance by only 0.21% on average.
Carbon-Binding Designer Proteins that Discriminate between sp2- and sp3-Hybridized Carbon Surfaces (2013)

Robust and simple strategies to directly functionalize graphene- and diamond-based nanostructures with proteins are of considerable interest for biologically-driven manufacturing, biosensing, and bioimaging. Here, we identify a new set of carbon-binding peptides that vary in overall hydrophobicity and charge and engineer two of these sequences (Car9 and Car15) within the framework of E. coli thioredoxin 1 (TrxA). We develop purification schemes to recover the resulting TrxA derivatives in a soluble form and conduct a detailed analysis of the mechanisms that underpin the interaction of the fusion proteins with carbonaceous surfaces. Although equilibrium quartz crystal microbalance measurements show that TrxA::Car9 and TrxA::Car15 have similar affinities for sp(2)-hybridized graphitic carbon (Kd = 50 and 90 nM, respectively), only the latter protein is capable of dispersing carbon nanotubes. Further investigation by surface plasmon resonance and atomic force microscopy reveals that TrxA::Car15 interacts with sp(2)-bonded carbon through a combination of hydrophobic and π-π interactions but that TrxA::Car9 exhibits a cooperative mode of binding that relies on a combination of electrostatics and weaker π stacking. Consequently, we find that TrxA::Car9 binds equally well to sp(2)- and sp(3)-bonded (diamondlike) carbon particles whereas TrxA::Car15 is capable of discriminating between the two carbon allotropes. Our results emphasize the importance of understanding both bulk and molecular recognition events when exploiting the adhesive properties of solid-binding peptides and proteins in technological applications.