gebhart/patrepeval huggingface dataset:
AspergillusGalactomannan Enzyme Immunoassay and Quantitative PCR for Diagnosis of Invasive Aspergillosis with Bronchoalveolar Lavage Fluid (2004)

Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in hematopoietic stem cell transplant patients. Diagnosis requires microbiological or histopathologic demonstration of the organism in tissues; however, cultivation of Aspergillus species from respiratory secretions has low diagnostic sensitivity. Assays to detect Aspergillus antigen or DNA in bronchoalveolar lavage (BAL) fluid could facilitate earlier diagnosis, thereby guiding optimal therapy and obviating the need for additional costly and potentially morbid diagnostic evaluation. We evaluated the performance of a galactomannan enzyme immunoassay (GM EIA; Bio-Rad) by using a range of index cutoffs to define positivity and a quantitative PCR (qPCR) assay for the detection of Aspergillus species from BAL samples of patients with proven and probable IPA (case patients; n = 49) and without IPA (control patients; n = 50). The sensitivity of the GM EIA was 61% with an index cutoff of 1.0 and 76% with an index cutoff of 0.5; the corresponding specificities were 98 and 94%, respectively. The sensitivity and specificity of qPCR assay were 67 and 100%, respectively. The sensitivity with 22 culture-negative BAL specimens from patients with IPA was 41% for GM EIA with an index cutoff of 1.0, 59% for GM EIA with an index cutoff of 0.5, and 36% for qPCR assay. GM EIA indices and DNA quantities corresponded to BAL fungal burdens, with culture-positive samples having larger amounts of antigen and DNA compared to culture-negative samples. GM EIA and qPCR assay add to the sensitivity of BAL for diagnosing IPA in high-risk patients, with excellent specificity. Adjunctive use of these tests may reduce dependence on invasive diagnostic procedures.
P53 Mediates the Apoptotic Response to GTP Depletion after Renal Ischemia-Reperfusion (2003)

Ischemic injury to the kidney is characterized in part by nucleotide depletion and tubular cell death in the form of necrosis or apoptosis. GTP depletion was recently identified as an important inducer of apoptosis during chemical anoxia in vitro and ischemic injury in vivo. It has also been shown that GTP salvage with guanosine prevented apoptosis and protected function. This study investigates the role of p53 in mediating the apoptotic response to GTP depletion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion. p53 protein levels increased significantly in the medulla over 24 h post-ischemia. The provision of guanosine inhibited the increase in p53. Pifithrin-alpha, a specific inhibitor of p53, mimicked the effects of guanosine. It had no effect on necrosis, yet it prevented apoptosis and protected renal function. Pifithrin-alpha was protective when given up to 14 h after the ischemic insult. The effects of pifithrin-alpha on p53 included inhibition of transcriptional activation of downstream p53 targets like p21 and Bax and inhibition of p53 translocation to the mitochondria. Similar results were obtained in cultured renal tubular cells. It is concluded that p53 is an important mediator of apoptosis during states of GTP depletion. Inhibitors of p53 should be considered in the treatment of ischemic renal injury.
PROTEIN ISOLATE FROM HIGH‐PROTEIN OATS: PREPARATION, COMPOSITION AND PROPERTIES (1977)

ABSTRACT An alkaline extraction process was developed to produce protein isolates and starch from defatted flour or defatted groats of high‐protein oats. Optimum extraction was at pH 9.2 in 0.02N sodium hydroxide with a solid:solvent ratio of 1:6. The defatted flour was extracted with sodium hydroxide solution, and bran was removed by screening the alkaline dispersion. After centrifuging the slurry that passed through the screen, the alkaline supernatant was adjusted to pH 5.0 to yield a precipitate (protein isolate) and supernatant. The defatted groats were first extracted with water followed by two sodium hydroxide extractions. Bran was removed by screening the second alkaline dispersion, and protein isolate was precipitated from the first alkaline extract at pH 5.7. Protein content (nitrogen × 6.25) of the isolate varied between 94 and 103% and accounted for 53–67% of total protein from defatted flour or groats. The isolate contained from 3.4–4.0g lysine and 2.2–4.2g total sulfur amino acids per 16g nitrogen. Minimum nitrogen solubility of the isolates was 3–4% near pH 5.5, and solubility was 78–83% near pH 2.2. All protein isolates had good hydration capacity (2.9–3.9) and two of the isolates had good emulsifying activity (around 50%) and good emulsion stability (near 50%).
Angiogenesis in multiple myeloma (2001)

Angiogenesis 1is felt to be important for the progression of most malignant neoplasms, including multiple myeloma. These images are from four patients with newly diagnosed multiple myeloma and demonstrate the presence of numerous microvessels in the bone marrow (400× magnification). Immunohistochemical staining for microvessels was performed using a monoclonal antibody against CD34. Studies have shown that bone marrow microvessels are significantly increased in myeloma compared with monoclonal gammopathy of undetermined significance. This increased angiogenesis correlates with the proliferative activity of plasma cells and is associated with poor prognosis.
Estrogen receptor α mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen (1999)

Estrogen is an important vasoprotective molecule that causes the rapid dilation of blood vessels by activating endothelial nitric oxide synthase (eNOS) through an unknown mechanism. In studies of intact ovine endothelial cells, 17beta-estradiol (E2) caused acute (five-minute) activation of eNOS that was unaffected by actinomycin D but was fully inhibited by concomitant acute treatment with specific estrogen receptor (ER) antagonists. Overexpression of the known transcription factor ERalpha led to marked enhancement of the acute response to E2, and this was blocked by ER antagonists, was specific to E2, and required the ERalpha hormone-binding domain. In addition, the acute response of eNOS to E2 was reconstituted in COS-7 cells cotransfected with wild-type ERalpha and eNOS, but not by transfection with eNOS alone. Furthermore, the inhibition of tyrosine kinases or mitogen-activated protein (MAP) kinase kinase prevented the activation of eNOS by E2, and E2 caused rapid ER-dependent activation of MAP kinase. These findings demonstrate that the short-term effects of estrogen central to cardiovascular physiology are mediated by ERalpha functioning in a novel, nongenomic manner to activate eNOS via MAP kinase-dependent mechanisms.
Rosiglitazone improves contextual fear conditioning in aged rats (2004)

Experimental, clinical, and epidemiologic studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) are beneficial in Alzheimer's disease and other neuroinflammatory processes. One possible mechanism is an interaction with peroxisome proliferator-activated receptors (PPARs). We examined the effect of a specific PPARgamma agonist, rosiglitazone, on contextual fear conditioning in aged rats. Male rats (20-months-old) were administered rosiglitazone in the diet for 2 months prior to behavioral testing. Young control and aged rats fed rosiglitazone froze significantly more than did the aged control rats in a hippocampal-dependent fear conditioning task. Rosiglitazone had no effect hippocampal interleukin-1beta levels, markers of oxidative damage, and NMDA receptor expression. Therefore, activation of PPARgamma prevented age-related deficits in hippocampal function.
Sterol composition of rapeseed varieties introduced in Bulgaria. (2009)

MAREKOV, I., B. DAMYANOVA, S. MOMCHILOVA, M. ZLATANOV, G. ANTOVA, M. ANGELOVAROMOVA and T. NENKOVA, 2009. Sterol composition of rapeseed varieties introduced in Bulgaria. Bulg. J. Agric. Sci., 15: 119-122 The composition of glyceride oils isolated from the seeds of 6 rapeseed varieties introduced in Bulgaria was investigated focusing on the biologically active substances: sterols and sterol esters. Sterols in the glyceride oils were found to be totally 3 g.kg-1 including 2 g.kg-1 free sterols and 1 g.kg-1 esterified sterols. β-Sitosterol predominated in both free and esterified sterols, being respectively 658–790 g.kg-1 and 471–700 g.kg-1, followed by campesterol and stigmasterol. Oleic acid (609–768 g.kg-1) was the main component among the fatty acids of the sterol esters, followed by palmitic acid (72–144 g.kg-1).
Control of tumor progression by maintenance of apoptosis (1996)

The ability to induce multiple apoptotic regressions of an androgen-dependent tumor cell population by repeated cycles of androgen withdrawal and replacement may be advantageous in therapeutic strategies aimed at delaying or preventing tumor progression. With greater insight into factors that either initiate or limit apoptosis, more efficient application of intermittent therapy might be achieved, especially if methods could be devised to increase the length or number of treatment cycles. Both calreticulin and clusterin represent proteins with a potential role in the regulation of apoptosis. Calreticulin may inhibit target gene transcription by interacting with steroid hormone receptors, thereby masking their DNA-binding sites and triggering the onset of the apoptotic process. Clusterin, on the other hand, is a membrane-stabilizing protein that appears to be involved in limiting the autophagic lysis of epithelial cells during apoptosis. Also, the increasing tendency for nuclear localization of clusterin after androgen withdrawal may preserve the nuclear environment, limiting the lethal effect of treatment. Thus, tumor progression, characterized by the loss of apoptotic potential, appears to be linked in part to the inappropriate activation of the TRPM-2 gene, which accounts for the constitutive expression of clusterin. © 1996 Wiley-Liss, Inc.
Epilepsy in the Elderly (2008)

There are many unique characteristics in elderly patients with epilepsy. The incidence of seizure in this age group is the highest of any age group and continues to increase as people live longer. Etiology of seizures is different than for adults and includes cerebrovascular disease, dementia, closed head injury, and metabolic encephalopathies. The elderly patient with epilepsy most often presents with complex partial seizures that have a higher recurrence rate than the younger population. The seizures are often difficult to diagnose since they present with atypical symptoms, particularly prolonged postictal symptoms, including memory lapses, confusion, altered mental status, and inattention. There are also therapeutic challenges due to age-related changes in pharmacokinetics, including variations in absorption, distribution, metabolism, and excretion. These must be considered when selecting antiepileptic drug (AED) therapy to avoid harmful side effects. In addition, several of the AEDs have drug-drug interactions, a problem potentially exacerbated in this population of patients due to the use of medications for comorbid conditions.
Building Block Approach to the Construction of Long-Lived Osmium(II) and Ruthenium(II) Multimetallic Complexes Incorporating the Tridentate Bridging Ligand 2,3,5,6-Tetrakis(2-pyridyl)pyrazine (1996)

Two classes of synthetically useful bimetallic complexes of the form [(tpy)M(tpp)RuCl(3)](PF(6)) and [(tpy)M(tpp)Ru(tpp)](PF(6))(4) have been prepared and their spectroscopic and electrochemical properties investigated (tpy = 2,2':6',2"-terpyridine, tpp = 2,3,5,6-tetrakis(2-pyridyl)pyrazine, and M = Ru(II) or Os(II)). Synthetic methods have been developed for the stepwise construction of tpp-bridged systems using a building block approach. In all four complexes, the tpp that serves as the bridging ligand is the site of localization of the lowest unoccupied molecular orbital (LUMO). The nature of the HOMO (highest occupied molecular orbital) varies depending upon the components present. In the systems of the type [(tpy)M(tpp)RuCl(3)](PF(6)), the ruthenium metal coordinated to tpp and three chlorides is the easiest to oxidize and is the site of localization of the HOMO. In contrast, for the [(tpy)M(tpp)Ru(tpp)](PF(6))(4) systems, the HOMO is based on the metal, M, that is varied, either Ru or Os. This gives rise to systems which possess a lowest lying excited state that is always a metal-to-ligand charge transfer state involving tpp but can be tuned to involve Os or Ru metal centers in a variety of coordination environments. The synthetic variation of the components within this framework has allowed for understanding the spectroscopic and electrochemical properties. Bimetallic systems incorporating this tpp ligand have long-lived excited states at room temperature (lifetimes of ca. 100 ns). The bimetallic system [(tpy)Ru(tpp)Ru(tpp)](PF(6))(4) has a longer excited state lifetime than the monometallic system from which it was constructed, [(tpy)Ru(tpp)](PF(6))(2). Details of the spectroscopic and electrochemical studies are reported herein.
Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells (2002)

Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.
Synthesis and vesicle formation from novel pseudoglyceryl dimeric lipids. Evidence of formation of widely different membrane organizations with exceptional thermotropic properties (1997)

Eight new bis-cationic dimeric lipids 2a–h have been synthesized; TEM of their aqueous dispersions confirmed the vesicle formation and from the thermal, spectroscopic, DLS and XRD studies it has been revealed that they form three different kinds of membranous aggregate depending on the m-value.
Role of cell type-specific promoters in the developmental regulation of T1, an interleukin 1 receptor homologue. (1995)

Murine T1, an orphan receptor related to interleukin 1 receptors, exhibits a bimodal expression in mouse development. The molecular analysis of cultured cell lines now reveals the contribution of alternate promoters of the T1 gene to its differential expression. In nonhemopoietic cell types, where T1 synthesis in vivo is restricted to organogenesis and neoplasia, a recently characterized AP-1-dependent promoter directs a proliferation-associated expression of the gene. In hemopoietic cells, which express the T1 receptor throughout ontogenesis in vivo, T1 gene activity is driven by a novel serum factor-independent, constitutive promoter. The tissue-specific use of constitutive versus growth factor-dependent alternate promoters thus directs the permanent activity of the T1 gene in hemopoietic tissue versus the developmentally restricted expression of the gene in nonhemopoietic tissues in vivo.
A conserved MYB transcription factor involved in phosphate starvation signaling both in vascular plants and in unicellular algae (2001)

Plants have evolved a number of adaptive responses to cope with growth in conditions of limited phosphate (Pi) supply involving biochemical, metabolic, and developmental changes. We prepared an EMS-mutagenized M(2) population of an Arabidopsis thaliana transgenic line harboring a reporter gene specifically responsive to Pi starvation (AtIPS1::GUS), and screened for mutants altered in Pi starvation regulation. One of the mutants, phr1 (phosphate starvation response 1), displayed reduced response of AtIPS1::GUS to Pi starvation, and also had a broad range of Pi starvation responses impaired, including the responsiveness of various other Pi starvation-induced genes and metabolic responses, such as the increase in anthocyanin accumulation. PHR1 was positionally cloned and shown be related to the PHOSPHORUS STARVATION RESPONSE 1 (PSR1) gene from Chlamydomonas reinhardtii. A GFP::PHR1 protein fusion was localized in the nucleus independently of Pi status, as is the case for PSR1. PHR1 is expressed in Pi sufficient conditions and, in contrast to PSR1, is only weakly responsive to Pi starvation. PHR1, PSR1, and other members of the protein family share a MYB domain and a predicted coiled-coil (CC) domain, defining a subtype within the MYB superfamily, the MYB-CC family. Therefore, PHR1 was found to bind as a dimer to an imperfect palindromic sequence. PHR1-binding sequences are present in the promoter of Pi starvation-responsive structural genes, indicating that this protein acts downstream in the Pi starvation signaling pathway.
A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. (2000)

Fasting hyperinsulinemia is a widely used surrogate measure of insulin resistance and predicts type 2 diabetes in various populations. Whether fasting hyperinsulinemia predicts diabetes independent of insulin resistance is unknown. In 319 Pima Indians with normal glucose tolerance, fasting plasma insulin concentration and insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp) were inversely related, but at any given M, there was substantial variation, with some subjects being hyperinsulinemic and others being hypoinsulinemic relative to their degree of insulin sensitivity. In 262 of the 319 subjects followed prospectively over 6.4 +/- 3.9 years, a high fasting plasma insulin concentration was a significant independent predictor of diabetes, in addition to low M and low acute insulin response (AIR) (intravenous glucose challenge). In 161 of the 319 subjects with follow-up measurements of M and AIR (5.1 +/- 3.9 years), a high relative fasting plasma insulin concentration predicted a decline in AIR but not in M before the onset of diabetes. The adjusted fasting plasma insulin concentration was a familial trait (heritability of 0.52) and in a genome-wide scan, there was suggestive evidence of linkage (logarithm of odds score 1.77) to a region on chromosome 3q, which harbors the gene encoding GLUT2. These results provide the first prospective evidence in humans that fasting hyperinsulinemia itself has a primary role in the pathogenesis of diabetes, independent of insulin resistance. Whether amelioration of basal insulin hypersecretion will prevent diabetes remains to be elucidated.
Extrachromosomal elements in tobacco plastids. (1994)

The plastid genome of higher plants is a circular double-stranded DNA molecule which is present in multiple identical copies. We report here an 868-bp plastid DNA minicircle, NICE1, that formed in tobacco (Nicotiana tabacum) plastids during transformation, as an unexpected product of homologous recombination. Such extrachromosomal elements are normally absent in plastids of higher plants. We have constructed shuttle plasmids containing NICE1 sequences which are maintained extrachromosomally when reintroduced into plastids by particle bombardment. Furthermore, recombination between homologous sequences in the shuttle plasmids and the main plastid genome occurs. Recombination products were characterized after recovery of the shuttle plasmids in Escherichia coli and of recombinant plastid genomes in the progeny of transformed plants. Our findings indicate that shuttle plasmids can be used to engineer plastid genes without concomitant integration of foreign DNA and to recover plastid mutations in E. coli.
Fluorescence labeling of the C‐terminus of proteins with a puromycin analogue in cell‐free translation systems (1999)

We have developed a new method for the C-terminus-specific fluorescence labeling of proteins. This method is based on the experimental finding that a fluorescent puromycin analogue at lower concentrations bonds efficiently to the C-terminus of mature proteins in cell-free translation systems using mRNA without a stop codon. This labeling is performed under moderate conditions and its labeling efficiency is in the range of 50-95%. Here we demonstrate a protein-protein interaction assay using fluorescence polarization measurement. This labeling method should also be useful for other rapid molecular interaction assays without purification of the labeled proteins, such as fluorescence correlation spectroscopy.
A Generalized Path Integral Control Approach to Reinforcement Learning (2010)

With the goal to generate more scalable algorithms with higher efficiency and fewer open parameters, reinforcement learning (RL) has recently moved towards combining classical techniques from optimal control and dynamic programming with modern learning techniques from statistical estimation theory. In this vein, this paper suggests to use the framework of stochastic optimal control with path integrals to derive a novel approach to RL with parameterized policies. While solidly grounded in value function estimation and optimal control based on the stochastic Hamilton-Jacobi-Bellman (HJB) equations, policy improvements can be transformed into an approximation problem of a path integral which has no open algorithmic parameters other than the exploration noise. The resulting algorithm can be conceived of as model-based, semi-model-based, or even model free, depending on how the learning problem is structured. The update equations have no danger of numerical instabilities as neither matrix inversions nor gradient learning rates are required. Our new algorithm demonstrates interesting similarities with previous RL research in the framework of probability matching and provides intuition why the slightly heuristically motivated probability matching approach can actually perform well. Empirical evaluations demonstrate significant performance improvements over gradient-based policy learning and scalability to high-dimensional control problems. Finally, a learning experiment on a simulated 12 degree-of-freedom robot dog illustrates the functionality of our algorithm in a complex robot learning scenario. We believe that Policy Improvement with Path Integrals (PI 2) offers currently one of the most efficient, numerically robust, and easy to implement algorithms for RL based on trajectory roll-outs.