gebhart/patrepeval huggingface dataset:
Environmental sources and transmission of Escherichia coli O157 in feedlot cattle. (2001)

A study was conducted in 2 feedlots in southern Alberta to identify environmental sources and management factors associated with the prevalence and transmission of Escherichia coli O157:H7. Escherichia coli O157:H7 was isolated in preslaughter pens of cattle from feces (0.8%), feedbunks (1.7%), water troughs (12%), and incoming water supplies (4.5%), but not from fresh total mixed rations. Fresh total mixed rations did not support the growth of E. coli O157:H7 and E. coli from bovine feces following experimental inoculation. Within a feedlot, the feces, water troughs, and feedbunks shared a few indistinguishable subtypes of E. coli O157:H7. A few subtypes were repeatedly isolated in the same feedlot, and the 2 feedlots shared a few indistinguishable subtypes. The prevalence of E. coli O157:H7 in water troughs of preslaughter cattle in 1 feedlot was associated with season, maximum climatic temperatures the week before sampling; total precipitation the week before sampling, and coliform and E. coli counts in the water trough.
Surveillance of Acute Rejection in Baboon Renal Transplantation by Elevation of Interferon-γ Inducible Protein-10 and Monokine Induced by Interferon-γ in Urine (2004)

This study shows an important correlation between urinary excretion of IP-10 and Mig and acute rejection in baboon kidney transplantation.
Cellular Targets for Activation by the E2F1 Transcription Factor Include DNA Synthesis- and G1/S-Regulatory Genes (1995)

Although a number of transfection experiments have suggested potential targets for the action of the E2F1 transcription factor, as is the case for many transcriptional regulatory proteins, the actual targets in their normal chromosomal environment have not been demonstrated. We have made use of a recombinant adenovirus containing the E2F1 cDNA to infect quiescent cells and then measure the activation of endogenous cellular genes as a consequence of E2F1 production. We find that many of the genes encoding S-phase-acting proteins previously suspected to be E2F targets, including DNA polymerase alpha, thymidylate synthase, proliferating cell nuclear antigen, and ribonucleotide reductase, are indeed induced by E2F1. Several other candidates, including the dihydrofolate reductase and thymidine kinase genes, were only minimally induced by E2F1. In addition to the S-phase genes, we also find that several genes believed to play regulatory roles in cell cycle progression, such as the cdc2, cyclin A, and B-myb genes, are also induced by E2F1. Moreover, the cyclin E gene is strongly induced by E2F1, thus defining an autoregulatory circuit since cyclin E-dependent kinase activity can stimulate E2F1 transcription, likely through the phosphorylation and inactivation of Rb and Rb family members. Finally, we also demonstrate that a G1 arrest brought about by gamma irradiation is overcome by the overexpression of E2F1 and that this coincides with the enhanced activation of key target genes, including the cyclin A and cyclin E genes.
Acetaminophen is an inhibitor of hepatic N-acetyltransferase 2 in vitro and in vivo (1998)

Slow acetylators of the polymorphic N-acetyltransferase 2 (NAT2, EC 2.3.1.5) suffer more often from side-effects of NAT-substrates than fast acetylators. Since concomitant administration of drugs may inhibit NAT2, we studied the influence of acetaminophen on NAT2 in human hepatic cytosol in vitro and in healthy individuals. In-vitro acetylation was assessed in liver homogenate of one fast and one slow acetylator using sulfamethazine as a test substrate. Acetaminophen competitively inhibited sulfamethazine acetylation in fast and slow acetylator liver samples with Ki values of acetaminophen of 2144 micromol/l and 712 micromol/l, respectively. In additional experiments, exposure of human liver cytosol to p-aminophenol, a putative precursor of acetaminophen in this reaction, revealed production of substantial amounts of acetaminophen, which indirectly suggests that acetaminophen may bind to the active site of NAT2. In-vivo acetylation was quantified with a urinary caffeine assay in 20 healthy volunteers at baseline and after repetitive oral administration of 1000 mg acetaminophen every 6 h for 1 day. The ratio of the acetylated caffeine metabolite acetyl-amino-6-formylamino-3-methyluracil to 1-methylxanthine was reduced by 30.9% (range 11.0-50.1%) in fast acetylators (n = 10) and by 19.3% (range 0.2-36.5%) in slow acetylators (n = 10). Acetaminophen, a widely used over-the-counter drug, which shares structural similarities with acetylated products, inhibits NAT2 both in vitro and in vivo. These findings suggest that even compounds which are not metabolized by NAT2 may inhibit the enzyme and reduce its metabolic capacity.
Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions. (1992)

We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.
Reduction imaging at 14 nm using multilayer-coated optics: Printing of features smaller than 0.1 μm (1990)

We demonstrate high resolution reduction imaging in the soft x-ray spectral region using multilayer-coated reflective optics. In particular, a Schwarzschild objective was used at 20:1 reduction with 14 nm radiation to image line and space features from a transmission mask onto a resist-coated silicon wafer with a resolution better than 0.1 μm. The mirrors of the objective were coated with Mo/Si multilayers to provide nearly 40% reflectance at near-normal incidence for the 14 nm radiation. Our results demonstrate that multilayer coatings are capable of enhancing the reflectance of optical components at soft x-ray wavelengths without significantly degrading their imaging performance.
Physiology and Pathophysiology of Purinergic Neurotransmission (2007)

This review is focused on purinergic neurotransmission, i.e., ATP released from nerves as a transmitter or cotransmitter to act as an extracellular signaling molecule on both pre- and postjunctional membranes at neuroeffector junctions and synapses, as well as acting as a trophic factor during development and regeneration. Emphasis is placed on the physiology and pathophysiology of ATP, but extracellular roles of its breakdown product, adenosine, are also considered because of their intimate interactions. The early history of the involvement of ATP in autonomic and skeletal neuromuscular transmission and in activities in the central nervous system and ganglia is reviewed. Brief background information is given about the identification of receptor subtypes for purines and pyrimidines and about ATP storage, release, and ectoenzymatic breakdown. Evidence that ATP is a cotransmitter in most, if not all, peripheral and central neurons is presented, as well as full accounts of neurotransmission and neuromodulation in autonomic and sensory ganglia and in the brain and spinal cord. There is coverage of neuron-glia interactions and of purinergic neuroeffector transmission to nonmuscular cells. To establish the primitive and widespread nature of purinergic neurotransmission, both the ontogeny and phylogeny of purinergic signaling are considered. Finally, the pathophysiology of purinergic neurotransmission in both peripheral and central nervous systems is reviewed, and speculations are made about future developments.
Rapid characterization of CRISPR-Cas9 protospacer adjacent motif sequence elements (2015)

To expand the repertoire of Cas9s available for genome targeting, we present a new in vitro method for the simultaneous examination of guide RNA and protospacer adjacent motif (PAM) requirements. The method relies on the in vitro cleavage of plasmid libraries containing a randomized PAM as a function of Cas9-guide RNA complex concentration. Using this method, we accurately reproduce the canonical PAM preferences for Streptococcus pyogenes, Streptococcus thermophilus CRISPR3 (Sth3), and CRISPR1 (Sth1). Additionally, PAM and sgRNA solutions for a novel Cas9 protein from Brevibacillus laterosporus are provided by the assay and are demonstrated to support functional activity in vitro and in plants.
On optimum combining at the mobile (1988)

Optimum combining for diversity antennas at the mobile is discussed. Effectively, the aim is to add the wanted signal vectors in a maximum ratio sense, while interferers are weighted so that their resultant is in a permanent deep fade. Even if there are not enough degrees of freedom available to accomplish this fully, an optimum solution can still be found. Many interpretations from conventional array technology do not apply to the mobile communications case and the mechanism of optimum combining for array branch signals rather than discrete spatial signals is reviewed. Physical interpretation of the formulation is emphasized throughout. Problems with the adaptive algorithm and its implementation are also identified. Sample matrix inversion is shown to be a likely algorithm to apply in vehicular mobile communications receivers. A worst case example gives an idea of the required computation rates.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Closed-Form Solution for Options with Stochastic Volatility with Applications to Bond and Currency Options (1993)

Journal Article A Closed-Form Solution for Options with Stochastic Volatility with Applications to Bond and Currency Options Get access Steven L. Heston Steven L. Heston Yale University Address correspondence to Steven L. Heston, Yale School of Organization and Management, 135 Prospect Street, New Haven, CT06511. Search for other works by this author on: Oxford Academic Google Scholar The Review of Financial Studies, Volume 6, Issue 2, April 1993, Pages 327–343, https://doi.org/10.1093/rfs/6.2.327 Published: 02 April 2015
First Synthesis of (±)-Basidifferquinone C, an Inducer for Fruiting-Body Formation inPolyporus arcularius (2009)

Basidifferquinones, isolated from Streptomyces sp., are potent inducers of fruiting-body formation in the basidiomycete, Polyporus arcularius. The first synthesis of (+/-)-basidifferquinone C was accomplished by starting from 3,5-dihydroxy-2-naphthoic acid.
Analysis of the codon 72 polymorphism of the TP53 gene in patients with endometriosis (2004)

Endometriosis is a benign gynaecologic disease that is associated with a certain risk for malignant degeneration. The disease has a genetic background, but the locations of possible genomic aberrations are still poorly clarified. In this context, the proline form of TP53 codon 72 polymorphism has been recently associated with the risk of developing endometriosis. In this case-control study, we aimed to investigate further the potential association between endometriosis and this polymorphism in order to evaluate whether this genetic variant may influence the susceptibility to the disease. Genomic DNA was obtained from a consecutive series of 303 Italian Caucasian women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. Endometriosis was defined according to the criteria of Holt and Weiss [Holt V and Weiss NS (2000) Recommendations for the design of epidemiologic studies of endometriosis. Epidemiol 11,654-659] for the definite disease. Subjects of similar age without laparoscopic evidence of the disease served as control group. Molecular analysis of TP53 codon 72 polymorphism was performed by PCR amplification. Endometriosis was documented in 151 women. We found no statistically significant difference in the distribution of TP53 codon 72 polymorphism genotypes between patients with and without endometriosis. The respective proportions of arginine homozygotes, heterozygotes and proline homozygotes were 55.6, 39.7 and 4.6% in the group with endometriosis and 59.9, 30.9 and 9.2% in the control group. Moreover, no statistically significant association was demonstrated between TP53 codon 72 polymorphism and the various clinical manifestations of the disease, although a non-significant tendency towards an increased frequency of the proline allele was observed in association with specific manifestations of the disease reflecting a more severe form. Our results suggest that the TP53 codon 72 polymorphism does not confer genetic susceptibility to endometriosis in the Italian population. However, a possible susceptibility role of this polymorphism in endometriosis development towards very severe forms cannot be ruled out.
WT1 induces expression of insulin-like growth factor 2 in Wilms' tumor cells. (1995)

The Wilms' tumor suppressor gene WT1 encodes a zinc finger transcription factor, whose expression inhibits the growth of the RM1 Wilms' tumor cell line. Transient transfection of WT1 constructs into 3T3 or 293 cells results in transcriptional repression of a number of cotransfected promoters containing the early growth response gene 1 consensus sequence. We now show that WT1 has properties of a transcriptional activator in RM1 cells, an effect that may be associated with the presence of a mutated p53 gene in these cells. Stable transfection of wild-type WT1 into RM1 cells results in induction of endogenous insulin-like growth factor 2 (IGF2) but not of other previously postulated WT1-target genes. The induction of IGF2 is dramatically enhanced by WT1 mutants encoding an altered transactivation domain. We conclude that IGF2 is a potentially physiological target gene for WT1 and that its induction may contribute to the growth-stimulating effects of WT1 variants.
A method for quantifying atrial fibrillation organization based on wave-morphology similarity (2002)

A new method for quantifying the organization of single bipolar electrograms recorded in the human atria during atrial fibrillation (AF) is presented. The algorithm relies on the comparison between pairs of local activation waves (LAWs) to estimate their morphological similarity, and returns a regularity index (rho) which measures the extent of repetitiveness over time of the detected activations. The database consisted of endocardial data from a multipolar basket catheter during AF and intraatrial recordings during atrial flutter. The index showed maximum regularity (rho = 1) for all atrial flutter episodes and decreased significantly when increasing AF complexity as defined by Wells (type I: rho = 0.75 +/- 0.23; type II: rho = 0.35 +/- 0.11; type III: rho = 0.15 +/- 0.08; P < 0.01). The ability to distinguish different AF episodes was assessed by designing a classification scheme based on a minimum distance analysis, obtaining an accuracy of 85.5%. The algorithm was able to discriminate among AF types even in presence of few depolarizations as no significant rho changes were observed by reducing the signal length down to include five LAWs. Finally, the capability to detect transient instances of AF complexity and to map the local regularity over the atrial surface was addressed by the dynamic and multisite evaluation of rho, suggesting that our algorithm could improve the understanding of AF mechanisms and become useful for its clinical treatment.
Structure–Activity Studies on Suramin Analogues as Inhibitors of NAD+‐Dependent Histone Deacetylases (Sirtuins) (2007)

Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomiasis and onchocerciasis. Suramin and diverse analogues exhibit a broad range of biological actions in vitro and in vivo, including, among others, antiproliferative and antiviral activity. Suramin derivatives usually target purinergic binding sites. Class III histone deacetylases (sirtuins) are amidohydrolases that require nicotinamide adenine dinucleotide (NAD(+)) as a cofactor for their catalytic mechanism(.) Deacetylation of the target proteins leads to a change in conformation and alters the activity of the proteins in question. Suramin was reported to inhibit human sirtuin 1 (SIRT1). We tested a diverse set of suramin analogues to elucidate the inhibition of the NAD(+)-dependent histone deacetylases SIRT1 and SIRT2 and discovered selective inhibitors of human sirtuins with potency in the two-digit nanomolar range. In addition, the structural requirements for the binding of suramin derivatives to sirtuins were investigated by molecular docking. The recently published X-ray crystal structure of human SIRT5 in complex with suramin and the human SIRT2 structure were used to analyze the interaction mode of the novel suramin derivatives.
Evoked Pain Analgesia in Chronic Pelvic Pain Patients Using Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation (2012)

Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain.
Randomized phase II trial of taxanes plus 5-fluorouracil for advanced gastric cancer (2005)

4149 Background: Taxanes (paclitaxel or docetaxel) has been shown to be effective in patients with advanced gastric cancer. We compared the combination of paclitaxel and 5-FU with the combination of docetaxel and 5-FU as first-line chemotherapy for metastatic or recurrent gastric cancer. Methods: We randomly assigned 74 chemotherapy-naïve patients to receive paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1, in combination with infusional 5-FU 500 mg/m2 daily for 5 days. Treatment was repeated every 3 weeks. Results: Of 36 patients in paclitaxel group and 38 in docetaxel group, 3 were ineligible or never received protocol therapy. After a median follow-up of 11 months, paclitaxel group showed, although statistically insignificant, better failure-free survival (4.8 months for paclitaxel group and 4.5 months for docetaxel group; P=0.71), overall survival (11.9 months v 9.2 months; P=0.06), and objective response rates (41.2% v 30.3%; P=0.07). Paclitaxel and 5-FU combination was associated with substantially less overall and grade 3/4 toxicities than docetaxel group (grade 3/4 toxicity in 26% v 39%; P=0.04). Of 298 cycles delivered, dose reduction was required less frequently in paclitaxel group (10/145 cycles v 33/153 cycles; P<0.01). Global quality of life was similar in both groups, but substantive differences in many symptom scores favored paclitaxel. Conclusions: Both paclitaxel and docetaxel in combination with 5-FU appear to have efficacy and manageable toxicity in patients with advanced gastric cancer. However, the combination of docetaxel and 5-FU suggests a trend towards better tolerability and efficacy. Further studies of this combination should be considered. No significant financial relationships to disclose.
Single-cell assays (2011)

This review presents an overview of literature that describes the applications of microfluidics to assay individual cells. We quantify the content of an individual mammalian cell, so that we can understand what criteria a single-cell assay must satisfy to be successful. We put in context the justification for single-cell assays and identify the characteristics that are relevant to single-cell assays. We review the literature from the past 24 months that describe the methods that use microfabrication-conventional or otherwise-and microfluidics in particular to study individual cells, and we present our views on how an increasing emphasis on three-dimensional cell culture and the demonstration of the first chemically defined cell might impact single-cell assays.
Production, specificity, and functionality of monoclonal antibodies to specific peptide–major histocompatibility complex class II complexes formed by processing of exogenous protein (1997)

Several unanswered questions in T cell immunobiology relating to intracellular processing or in vivo antigen presentation could be approached if convenient, specific, and sensitive reagents were available for detecting the peptide-major histocompatibility complex (MHC) class I or class II ligands recognized by alphabeta T cell receptors. For this reason, we have developed a method using homogeneously loaded peptide-MHC class II complexes to generate and select specific mAb reactive with these structures using hen egg lysozyme (HEL) and I-Ak as a model system. mAbs specific for either HEL-(46-61)-Ak or HEL-(116-129)-Ak have been isolated. They cross-react with a small subset of I-Ak molecules loaded with self peptides but can nonetheless be used for flow cytometry, immunoprecipitation, Western blotting, and intracellular immunofluorescence to detect specific HEL peptide-MHC class II complexes formed by either peptide exposure or natural processing of native HEL. An example of the utility of these reagents is provided herein by using one of the anti-HEL-(46-61)-Ak specific mAbs to visualize intracellular compartments where I-Ak is loaded with HEL-derived peptides early after antigen administration. Other uses, especially for in vivo tracking of specific ligand-bearing antigen-presenting cells, are discussed.
AAA+ Proteases: ATP-Fueled Machines of Protein Destruction (2011)

AAA+ family proteolytic machines (ClpXP, ClpAP, ClpCP, HslUV, Lon, FtsH, PAN/20S, and the 26S proteasome) perform protein quality control and are used in regulatory circuits in all cells. These machines contain a compartmental protease, with active sites sequestered in an interior chamber, and a hexameric ring of AAA+ ATPases. Substrate proteins are tethered to the ring, either directly or via adaptor proteins. An unstructured region of the substrate is engaged in the axial pore of the AAA+ ring, and cycles of ATP binding/hydrolysis drive conformational changes that create pulses of pulling that denature the substrate and translocate the unfolded polypeptide through the pore and into the degradation chamber. Here, we review our current understanding of the molecular mechanisms of substrate recognition, adaptor function, and ATP-fueled unfolding and translocation. The unfolding activities of these and related AAA+ machines can also be used to disassemble or remodel macromolecular complexes and to resolubilize aggregates.
Electroactive Surfactant Designed to Mediate Electron Transfer Between CdSe Nanocrystals and Organic Semiconductors (2003)

An electroactive pentathiophene surfactant containing a phosphonic acid head group was designed and shown to provide strong binding to the surface of a CdSe nanocrystal and facilitate charge transfer between the nanocrystal and an organic semiconducting matrix (see Figure). Incorporation into organic–inorganic heterojunction solar cells could improve the efficiency of these promising devices.