gebhart/patrepeval huggingface dataset:
The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. (1995)

Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several "new" estrogens were found; alkylphenols, phthalates, some PCB congeners and hydroxylated PCBs, and the insecticides dieldrin, endosulfan, and toxaphene were estrogenic by the E-SCREEN assay. In addition, these compounds competed with estradiol for binding to the estrogen receptor and increased the levels of progesterone receptor and pS2 in MCF-7 cells, as expected from estrogen mimics. Recombinant human growth factors (bFGF, EGF, IGF-1) and insulin did not increase in cell yields. The aims of the work summarized in this paper were a) to validate the E-SCREEN assay; b) to screen a variety of chemicals present in the environment to identify those that may be causing reproductive effects in wildlife and humans; c) to assess whether environmental estrogens may act cumulatively; and finally d) to discuss the reliability of this and other assays to screen chemicals for their estrogenicity before they are released into the environment.
Technique for Producing Capillaries with Reproducible Orifice Diameters for Uniform Droplet Generation (1992)

A procedure is described for fabricating capillary orifice tips useful for the generation of uniform droplets. These generator tips operate at relatively low applied pressure, are relatively resistant to clogging, and incorporate orifice diameters reproducible to 1%. The method involves implanting a fused-silica capillary within a glass sleeve. When heated, the glass and fused silica wet to form a tight seal with no cracking caused by differences in thermal expansion. This technique permits the routine production of capillary tips with fixed orifice and outer diameters.
Use of a Soil Surfactant with Fungicides for Control of Fairy Ring Disease in Turfgrass (2008)

Fairy ring is the common name for a complex disease of turf encompassing the appearance of mushrooms, circles of stimulated grass, or rings of damaged or dead turfgrass maintained for lawns, athletic fields, or golf courses. Type-I fairy ring is especially destructive due to the development of water repellent or hydrophobic soil conditions and the subsequent decline and damage to the existing turfgrass. Fairy ring management strategies, particularly the control or suppression of Type-I fairy ring symptoms, has been inconsistent in effectiveness. The objective of this field study was to evaluate the efficacy of fungicides recommended for fairy ring control when applied alone and with a soil surfactant. This research was conducted on cool-season turfgrass in California in 2005, and in Pennsylvania in 2006. The same treatments were applied at both locations. The four fungicide treatments were evaluated at 620 g active ingredient (a.i.) azoxystrobin∙ha−1, 9757 g a.i. flutolanil∙ha−1, 310 g a.i polyoxin-D∙ha−1, or 558 g a.i. pyraclostrobin∙ha−1. Each fungicide was applied alone and in a tank-mix combination with the modified alkylated polyol soil surfactant (100 % concentration) at 19 L product∙ha−1. All treatments were applied at two water carrier volumes of 814 and 1628∙ L∙ha−1. At both locations, Type-I fairy ring symptoms were noticeably reduced in plots treated with fungicides plus soil surfactant at either water carrier volume versus plots treated with fungicides alone applied at 814 L water carrier ha−1. Therefore, the consistently best overall treatment for the control or suppression of Type-I fairy ring symptoms was fungicides plus soil surfactant at either water carrier volume. The application of plant protection products at the lower water volume is preferred by turfgrass managers and practitioners; thus the utility of soil surfactants applied with fungicides is a useful strategy for the chemical control of fairy ring in turf.
Design Aspects for the Development of Mixed-Metal Supramolecular Complexes Capable of Visible Light Induced Photocleavage of DNA (2003)

Mixed-metal supramolecular complexes that couple ruthenium or osmium based light absorbers to a central rhodium(III) core have been designed which photocleave DNA upon irradiation with visible light. The complexes [[(bpy)(2)Ru(dpp)](2)RhCl(2)](PF(6))(5), [[(bpy)(2)Os(dpp)](2)RhCl(2)](PF(6))(5), and [[(tpy)RuCl(dpp)](2)RhCl(2)](PF(6))(3), where bpy = 2,2'-bipyridine, tpy = 2,2':6',2' '-terpyridine, and dpp = 2,3-bis(2-pyridyl)pyrazine, all exhibit intense metal to ligand charge transfer (MLCT) based transitions in the visible but possess lower lying metal to metal charge transfer (MMCT) excited states. These supramolecular complexes with low lying MMCT states photocleave DNA when excited into their intense MLCT transitions. Structurally similar complexes without this low lying MMCT state do not exhibit DNA photocleavage, establishing the role of this MMCT state in the DNA photocleavage event. Design considerations necessary to produce functional DNA photocleavage agents are presented herein.
Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography (1999)

We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.
Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons (1999)

The efficiency of first-generation adenoviral vectors as gene delivery tools is often limited by the short duration of transgene expression, which can be related to immune responses and to toxic effects of viral proteins. In addition, readministration is usually ineffective unless the animals are immunocompromised or a different adenovirus serotype is used. Recently, adenoviral vectors devoid of all viral coding sequences (helper-dependent or gutless vectors) have been developed to avoid expression of viral proteins. In mice, liver-directed gene transfer with AdSTK109, a helper-dependent adenoviral (Ad) vector containing the human alpha(1)-antitrypsin (hAAT) gene, resulted in sustained expression for longer than 10 months with negligible toxicity to the liver. In the present report, we have examined the duration of expression of AdSTK109 in the liver of baboons and compared it to first-generation vectors expressing hAAT. Transgene expression was limited to approximately 3-5 months with the first-generation vectors. In contrast, administration of AdSTK109 resulted in transgene expression for longer than a year in two of three baboons. We have also investigated the feasibility of circumventing the humoral response to the virus by sequential administration of vectors of different serotypes. We found that the ineffectiveness of readministration due to the humoral response to an Ad5 first-generation vector was overcome by use of an Ad2-based vector expressing hAAT. These data suggest that long-term expression of transgenes should be possible by combining the reduced immunogenicity and toxicity of helper-dependent vectors with sequential delivery of vectors of different serotypes.
Simplified procedure for the routine isolation of Clostridium difficile from faeces. (1981)

The use of alcohol, at a final concentration of 50%, as a selective procedure for the isolation of Clostridium difficile was compared to a selective medium containing 250 microgram /ml of cycloserine and 10 microgram /ml of cefoxitin. Of 266 faecal samples 82 were shown to be positive by one or other method. Seventy-seven (94%) of these were detected by the selective agar (SA) and 72 (88%) by the alcohol procedure (AP). Ten samples (12%) were positive only by SA and five samples (6%) by AP only. The AP was further modified so that all manipulations prior to incubation were performed on the open bench. Of 18 positive samples, 18 (100%) were detected by SA and 16 (89%) by AP.
Solvent Extraction of Zinc from Strong Hydrochloric Acid Solution with Alamine336 (2009)

Solvent extraction reaction of Zn(II) by Alamine336 from strong HCl solution up to 10 M was identified by analyzing the data reported in the literature. The equilibrium constant of this reaction was estimated by considering the complex formation between zinc and chloride ion. The necessary thermodynamic parameters, such as equilibrium constant for the formation of complexes and the interaction parameters, were evaluated from the thermodynamic data reported in the literature. The following solvent extraction reaction and the equilibrium constant was obtained by considering the activity coefficients of solutes present in the aqueous phase with Bromley equation. <TEX>$Zn^{2+}\;2Cl^{-}\;+\;R_3NHCl_{org}\;=\;ZnCl_3R_3NH_{org},\;K_{ex}\;=\;6.33\;{\times}\;10^2$</TEX> There was a good agreement between measured and calculated distribution coefficients of Zn(II).
Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, as monotherapy in epidermal growth factor receptor (EGFR) amplified, recurrent glioblastoma (GBM). (2016)

2542 Background: Recurrent GBM (rGBM) has dismal prognosis. Almost 50% GBM tumors harbor amplified (amp) EGFR. ABT-414 is a tumor specific ADC combining an antibody targeting a unique conformation of EGFR (ABT-806) to a microtubule cytotoxin, monomethyl auristatin F (MMAF). Here we report the safety and efficacy of ABT-414 monotherapy at recommended phase 2 dose (RPTD) in EGFR amp, rGBM. Methods: M12-356 (NCT01800695) is an open-label, phase 1, 3-arm study: Arm A (ABT-414+radiation/temozolomide (TMZ) in newly diagnosed GBM (nGBM)), Arm B (ABT-414+TMZ in nGBM as adjuvant therapy, or in rGBM) and Arm C (ABT-414 monotherapy in rGBM). Each arm had an escalation cohort to determine the RPTD and an expansion cohort to establish the safety and preliminary efficacy at RPTD. Results of Arm C expansion cohort at 1.25 mg/kg RPTD (IV infusion) are shown here. Eligible patients (pts) were adults with KPS score ≥ 70, EGFR amp (confirmed centrally), rGBM, normal end-organ function and no prior bevacizumab. Results: As of January 7, 2016, 48 EGFR amp, rGBM pts were treated in this cohort. The median age was 59 years (range, 35-80). Most pts had prior therapies: 40% had 1, 48% had 2, 10% had ≥ 3 prior therapies. Most common treatment emergent adverse events (TEAEs) ( ≥ 25% pts) were blurred vision (60%), headache, photophobia (29% each), dry eye, eye pain, fatigue (27% each). The most common serious AE ( > 1 pt) was seizure (8%). Grade 3/4 TEAEs ( > 1 pt) were keratitis (15%), corneal epithelial microcysts (8%), hemiparesis, hyperglycemia, muscular weakness, seizure (6% each), blurred vision, ulcerative keratitis (4% each). No dose-limiting toxicities were reported. Best RANO responses of 44 pts with complete data were: 2 partial responses, 18 stable disease, 24 progressive disease. The 6-month progression-free survival (PFS6) estimate was 30% [95% CI = 17, 44]. Conclusions: ABT-414 monotherapy, at 1.25 mg/kg RPTD, displayed frequent yet reversible ocular toxicities. An encouraging tumor stability/response and PFS6 were observed in this highly refractory EGFR amp, rGBM. A global randomized trial of ABT-414, alone or with TMZ, vs. TMZ or lomustine, is underway in EGFR amp, rGBM (NCT02343406). Clinical trial information: NCT01800695.
The role of topical negative pressure in wound repair: Expression of biochemical markers in wound fluid during wound healing (2008)

The clinical effects of topical negative pressure therapy (TNP) on wound healing are well described in numerous articles. While the mechanism(s) of action are not completely understood, it is postulated that reduction of local and interstitial tissue edema, increased perfusion of the (peri-) wound area, changed bacterial composition, and mechanical stimulation of the woundbed contribute to the clinical success. Our hypothesis is that with the removal of excessive fluid, proteolytic enzymes negatively influencing the healing process are removed. Our aim was to assess whether the concentrations of albumin, matrixmetalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) were different between wounds treated with TNP and conventional gauze therapy. We analyzed wound fluid samples of 33 wounds treated with either TNP therapy (n=15) or conventional therapy (n=18) on albumin, pro- and activated MMP-9, TIMP-1, and the ratio of total MMP-9/TIMP-1. Albumin levels were found to increase significantly in acute wounds compared with chronic wounds; however, no difference could be found on comparing TNP with conventional therapy. We did find significantly lower levels of pro-MMP-9 and lower total MMP-9/TIMP-1 ratio in TNP-treated wounds during the follow-up of 10 days. These data strongly suggest that TNP therapy influences the microenvironment of the wound.
Development of Therapeutic-Grade Small Interfering RNAs by Chemical Engineering (2012)

Recent successes in clinical trials have provided important proof of concept that small interfering RNAs (siRNAs) indeed constitute a new promising class of therapeutics. Although great efforts are still needed to ensure efficient means of delivery in vivo, the siRNA molecule itself has been successfully engineered by chemical modification to meet initial challenges regarding specificity, stability, and immunogenicity. To date, a great wealth of siRNA architectures and types of chemical modification are available for promoting safe siRNA-mediated gene silencing in vivo and, consequently, the choice of design and modification types can be challenging to individual experimenters. Here we review the literature and devise how to improve siRNA performance by structural design and specific chemical modification to ensure potent and specific gene silencing without unwarranted side-effects and hereby complement the ongoing efforts to improve cell targeting and delivery by other carrier molecules.
An Adventurous Synthetic Journey with MNBA from Its Reaction Chemistry to the Total Synthesis of Natural Products (2013)

Abstract After initially establishing a novel cyclization reaction of ω-hydroxycarboxylic acids (seco-acids) using 4-trifluoromethylbenzoic anhydride (TFBA) and Lewis acid catalysts to form the corresponding lactones, we discovered a more advanced method for this transformation using 2-methyl-6-nitrobenzoic anhydride (MNBA) as a coupling reagent with nucleophilic catalysts. The latter lactonization is promoted by acyl-transfer catalysts, such as 4-(dimethylamino)pyridine (DMAP), 4-pyrrolidinylpyridine (PPY), and 4-(dimethylamino)pyridine N-oxide (DMAPO). (+)-Ricinelaidic acid lactone ((+)-2) was first synthesized by the TFBA-mediated cyclization with Lewis acid catalysts, while the threo-aleuritic acid lactone (20) was alternatively synthesized by the MNBA-mediated cyclization with acyl-transfer catalysts. Using this effective lactonization technology to form the ester linkage under mild conditions, we then demonstrated the preparation of various large-, medium-, and small-sized natural and unnatural lactones including (−)-cephalosporolide D ((−)-3), (−)-octalactin A ((−)-4), (−)-octalactin B ((−)-25), 2-epibotcinolide (49), (−)- and (+)-2-hydroxytetracosanolides ((−)-77 and (+)-77), (−)- and (+)-2-hydroxy-24-oxooctacosanolides ((−)-78 and (+)-78), (−)-tetrahydrolipstatin ((−)-THL, (−)-117), and the erythromycin A skeletons 103b, 103c, 104c, and 105b. The transition structures involved in the formation of the β-lactones from the corresponding 3-hydroxycarboxylic acids were then determined using DFT calculations at the B3LYP/6-31G*//B3LYP/6-31G* level, and the reactivity of several seco-acids was successfully predicted on the basis of the calculated thermodynamic properties of the transition structures.
Refractive height fields from single and multiple images (2012)

We propose a novel framework for reconstructing homogenous, transparent, refractive height-fields from a single viewpoint. The height-field is imaged against a known planar background, or sequence of backgrounds. Unlike existing approaches that do a point-by-point reconstruction - which is known to have intractable ambiguities - our method estimates and optimizes for the entire height-field at the same time. The formulation supports shape recovery from measured distortions (deflections) or directly from the images themselves, including from a single image. We report results for a variety of refractive height-fields showing significant improvement over prior art.
3,5,3′‐Triiodo‐L‐thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC‐1) towards a β‐cell‐Like phenotype (2005)

The thyroid hormone, 3,5,3'-Triiodo-L-thyronine (T3), is essential for growth, differentiation, and regulation of metabolic functions in multicellular organisms, although the specific mechanisms of this control are still unknown. In this study, treatment of a human pancreatic duct cell line (hPANC-1) with T3 blocks cell growth by an increase of cells in G(0)/G(1) cell cycle phase and enhances morphological and functional changes as indicated by the marked increase in the synthesis of insulin and the parallel decrease of the ductal differentiation marker cytokeratin19. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent increase in insulin and glut2 mRNA levels in response to T3. As last step of the acquisition of a beta-cell-like phenotype, we present evidence that thyroid hormones are able to increase the release of insulin into the culture medium. In conclusion, our results suggest, for the first time, that thyroid hormones induce cell cycle perturbations and play an important role in the process of transdifferentiation of a human pancreatic duct line (hPANC-1) into pancreatic-beta-cell-like cells. These findings have important implications in cell-therapy based treatment of diabetes and may provide important insights in the designing of novel therapeutic agents to restore normal glycemia in subjects with diabetes.
Extraction of high-resolution frames from video sequences (1996)

The human visual system appears to be capable of temporally integrating information in a video sequence in such a way that the perceived spatial resolution of a sequence appears much higher than the spatial resolution of an individual frame. While the mechanisms in the human visual system that do this are unknown, the effect is not too surprising given that temporally adjacent frames in a video sequence contain slightly different, but unique, information. This paper addresses the use of both the spatial and temporal information present in a short image sequence to create a single high-resolution video frame. A novel observation model based on motion compensated subsampling is proposed for a video sequence. Since the reconstruction problem is ill-posed, Bayesian restoration with a discontinuity-preserving prior image model is used to extract a high-resolution video still given a short low-resolution sequence. Estimates computed from a low-resolution image sequence containing a subpixel camera pan show dramatic visual and quantitative improvements over bilinear, cubic B-spline, and Bayesian single frame interpolations. Visual and quantitative improvements are also shown for an image sequence containing objects moving with independent trajectories. Finally, the video frame extraction algorithm is used for the motion-compensated scan conversion of interlaced video data, with a visual comparison to the resolution enhancement obtained from progressively scanned frames.
RNA expression patterns change dramatically in human neutrophils exposed to bacteria (2001)

A comprehensive study of changes in messenger RNA (mRNA) levels in human neutrophils following exposure to bacteria is described. Within 2 hours there are dramatic changes in the levels of several hundred mRNAs including those for a variety of cytokines, receptors, apoptosis-regulating products, and membrane trafficking regulators. In addition, there are a large number of up-regulated mRNAs that appear to represent a common core of activation response genes that have been identified as early-response products to a variety of stimuli in a number of other cell types. The activation response of neutrophils to nonpathogenic bacteria is greatly altered by exposure to Yersinia pestis, which may be a major factor contributing to the virulence and rapid progression of plague. Several gene clusters were created based on the patterns of gene induction caused by different bacteria. These clusters were consistent with those found by a principal components analysis. A number of the changes could be interpreted in terms of neutrophil physiology and the known functions of the genes. These findings indicate that active regulation of gene expression plays a major role in the neutrophil contribution to the cellular inflammatory response. Interruption of these changes by pathogens, such as Y pestis, could be responsible, at least in part, for the failure to contain infections by highly virulent organisms.