gebhart/patrepeval huggingface dataset:
Tell me a story: using short fiction in teaching law and bioethics. (1997)

For some years now, I have been experimenting with the use of short fiction in my upper-level class on Biomedical Ethics and the Law. Biomedical ethics a subject nourished by stories. One can almost chart the course of legal progress in bioethics by invoking the names of the leading characters: Karen Quinlan,1 Nancy Cruzan,2 Baby M.3 It these people and their problems, and the often conflicting wishes of the people who love and care for them, that capture students' imagination and make bioethics such a compelling field of study. The family of Nancy Cruzan, for example, generously allowed themselves to be featured in a Frontline program so affecting that my students always choke up when viewing it. (A particularly instructive moment for law students when the lower court's opinion handed to the Cruzan family at home and they are left alone to puzzle out where the important stuff is and who actually won.) Donald Cowart, now called Dax, a burn victim who was treated against his will, the subject of two documentaries,4 numerous essays,5 and at least one book.6
Efficient Genome Engineering of Toxoplasma gondii Using CRISPR/Cas9 (2014)

Toxoplasma gondii is a parasite of humans and animals, and a model for other apicomplexans including Plasmodium spp., the causative agents of malaria. Despite many advances, manipulating the T. gondii genome remains labor intensive, and is often restricted to lab-adapted strains or lines carrying mutations that enable selection. Here, we use the RNA-guided Cas9 nuclease to efficiently generate knockouts without selection, and to introduce point mutations and epitope tags into the T. gondii genome. These methods will streamline the functional analysis of parasite genes and enable high-throughput engineering of their genomes.
Randomized Forced Titration to Different Doses of Technosphere® Insulin Demonstrates Reduction in Postprandial Glucose Excursions and Hemoglobin A1c in Patients with Type 2 Diabetes (2008)

This study demonstrated that, over 11 weeks, TI plus basal insulin glargine is well tolerated and results in dose-dependent reductions in postprandial glucose and HbA1c levels.
The miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation of mouse embryonic cardiomyocytes (2012)

MicroRNAs (miRNAs) have gradually been recognized as regulators of embryonic development; however, relatively few miRNAs have been identified that regulate cardiac development. A series of recent papers have established an essential role for the miRNA-17-92 (miR-17-92) cluster of miRNAs in the development of the heart. Previous research has shown that the Friend of Gata-2 (FOG-2) is critical for cardiac development. To investigate the possibility that the miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation in mouse embryonic cardiomyocytes we initially used bioinformatics to analyze 3' untranslated regions (3'UTR) of FOG-2 to predict the potential of miR-17-92 to target it. We used luciferase assays to demonstrate that miR-17-5p and miR-20a of miR-17-92 interact with the predicted target sites in the 3'UTR of FOG-2. Furthermore, RT-PCR and Western blot were used to demonstrate the post-transcriptional regulation of FOG-2 by miR-17-92 in embryonic cardiomyocytes from E12.5-day pregnant C57BL/6J mice. Finally, EdU cell assays together with the FOG-2 rescue strategy were employed to evaluate the effect of proliferation on embryonic cardiomyocytes. We first found that the miR-17-5p and miR-20a of miR-17-92 directly target the 3'UTR of FOG-2 and post-transcriptionally repress the expression of FOG-2. Moreover, our findings demonstrated that over-expression of miR-17-92 may inhibit cell proliferation via post-transcriptional repression of FOG-2 in embryonic cardiomyocytes. These results indicate that the miR-17-92 cluster regulates the expression of FOG-2 protein and suggest that the miR-17-92 cluster might play an important role in heart development.
Analyzing the functions of large glycoconjugates through the dissipative properties of their absorbed layers using the gel-forming mucin MUC5B as an example (2008)

Glyconjugates such as mucins, proteoglycans, and polysaccharides form the structural basis of protective cell-surface layers. In particular gel-forming mucins define a zone between the epithelial cell layer and the environment. Such molecules are of extreme molecular weight 5-100 x 10(6) and size (Rg 20-300 nm). On this account their biochemistry is inseparable from their physical biochemistry. Combining laser light scattering and quartz crystal mass balance with dissipation methods (QCM-D) we have investigated the properties of the MUC5B mucin and its cognate fragments when bound to a hydrophobic surface. MUC5B forms the basis of gels responsible for the protection of the oral cavity, lung, and cervical canal surfaces. Here we show, by analyzing dissipative interactions of hydrophobic, gold, and polystyrene surfaces, with the intact MUC5B molecule, its reduced subunits, and glycosylated tryptic fragments (obtained after reduction), the formation of 40- to 100-nm-thick highly structured, hydrated interfaces. These interfaces are dominated in their geometry and dissipative properties by the negatively charged carbohydrate-rich domains of the molecule, the naked protein domains being responsible for attachment. These carbohydrate-rich surfaces have well-defined absorptive properties and permit the entry and entrapment of albumin-coated micro-beads into the absorbed layer at and below a size of 60 nm. However beads larger than 100 nm are completely excluded from the surfaces. These absorptive phenomena correlate with large changes in film dissipation and thus may not only be important in biological functions, e.g. binding viruses, but could also be informative to the surfaces (often ciliated) onto which such mucus films are attached.
Reproductive hazards in the workplace (1980)

RETURN TO ISSUEPREVNewsNEXTReproductive hazards in the workplaceGovernment and companies are at odds over approaches to worker protection, mainly because of differences in interpretation of the problemREBECCA L. RAWLSView Author Information C&EN, WashingtonCite this: Chem. Eng. News 1980, 58, 7, 35–37Publication Date (Print):February 18, 1980Publication History Published online7 November 2010Published inissue 18 February 1980https://pubs.acs.org/doi/10.1021/cen-v058n007.p035https://doi.org/10.1021/cen-v058n007.p035newsACS PublicationsCopyright © 1980 American Chemical SocietyArticle Views10Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
μ-Conotoxin KIIIA Derivatives with Divergent Affinities versus Efficacies in Blocking Voltage-Gated Sodium Channels (2010)

The possibility of independently manipulating the affinity and efficacy of pore-blocking ligands of sodium channels is of interest for the development of new drugs for the treatment of pain. The analgesic mu-conotoxin KIIIA (KIIIA), a 16-residue peptide with three disulfide bridges, is a pore blocker of voltage-gated sodium channels, including neuronal subtype Na(V)1.2 (K(d) = 5 nM). At saturating concentrations, KIIIA incompletely blocks the sodium current of Na(V)1.2, leaving a 5% residual current (rI(Na)). Lys7 is an important residue: the K7A mutation decreases both the efficacy (i.e., increases rI(Na) to 23%) and the affinity of the peptide (K(d) = 115 nM). In this report, various replacements of residue 7 were examined to determine whether affinity and efficacy were inexorably linked. Because of their facile chemical synthesis, KIIIA analogues that had as a core structure the disulfide-depleted KIIIA[C1A,C2U,C9A,C15U] (where U is selenocysteine) or ddKIIIA were used. Analogues ddKIIIA and ddKIIIA[K7X], where X represents one of nine different amino acids, were tested on voltage-clamped Xenopus oocytes expressing rat Na(V)1.2 or Na(V)1.4. Their affinities ranged from 0.01 to 36 muM and rI(Na) values from 2 to 42%, and these two variables appeared to be uncorrelated. Instead, rI(Na) varied inversely with side chain size, and remarkably charge and hydrophobicity appeared to be inconsequential. The ability to manipulate a mu-conopeptide's affinity and efficacy, as well as its capacity to interfere with subsequent tetrodotoxin binding, greatly expands its scope as a reagent for probing sodium channel structure and function and may also lead to the development of mu-conotoxins as safe analgesics.
Synthesis of the minor fetal hemoglobin Fic in colonies of erythropoietic precursors isolated from human umbilical cord blood (1982)

The biosynthesis of the minor hemoglobin FIc, which contains acetylated gamma chains, and the major hemoglobin Fo was studied during erythroid cell differentiation and maturation in cultures of erythroid precursors isolated from five human umbilical cord blood samples. A gradual decrease in the synthesis of Hb FIc was observed during the maturation of the erythroid cells when cultured from 7 to 15 days. The synthesis of Hb Fo did not show a consistent change; however, the relative synthesis of Hb FIc was the highest in the 7-day-old colonies and decreased at day 15 to levels observed in the reticulocytes. The addition of sodium butyrate, which is known to promote histone acetylation, significantly increased the synthesis of Hb FIc in 7-day-old colonies.
Bacteriotherapy Using Fecal Flora (2004)

The intestinal flora may play a key role in the pathogenesis of certain gastrointestinal (GI) diseases. Components of bowel flora such as Lactobacillus acidophilus and Bifidobacterium bifidus have long been used empirically as therapeutic agents for GI disorders. More complex combinations of probiotics for therapeutic bacteriotherapy have also recently become available, however the most elaborate mix of human-derived probiotic bacteria is, by definition, the entire fecal flora. Fecal bacteriotherapy uses the complete normal human flora as a therapeutic probiotic mixture of living organisms. This type of bacteriotherapy has a longstanding history in animal health and has been used sporadically against chronic infections of the bowel, especially as a treatment of last resort for patients with severe Clostridium difficile syndromes including recurrent diarrhea, colitis, and pseudomembranous colitis. Encouraging results have also been observed following infusions of human fecal flora in patients with inflammatory bowel disease, irritable bowel syndrome, and chronic constipation. The therapeutic use of fecal bacteriotherapy is reviewed here and possible mechanisms of action and potential applications explored. Published reports on fecal bacteriotherapy are few in number, and detail the results of small uncontrolled open studies and case reports. Nevertheless, given the promising clinical responses, formal research into fecal bacteriotherapy is now warranted.
Determining an author's native language by mining a text for errors (2005)

In this paper, we show that stylistic text features can be exploited to determine an anonymous author's native language with high accuracy. Specifically, we first use automatic tools to ascertain frequencies of various stylistic idiosyncrasies in a text. These frequencies then serve as features for support vector machines that learn to classify texts according to author native language.
Chemokine-mediated angiogenesis: an essential link in the evolution of airway fibrosis? (2005)

Angiogenesis may be an important factor in the development of fibrotic lung disease. Prior studies have strongly suggested a role for angiogenic vascular remodeling in pulmonary fibrosis, and emerging evidence indicates that new vessel formation is critical in airway fibrosis. Bronchiolitis obliterans syndrome is a fibrotic occlusion of distal airways that is largely responsible for the morbidity and mortality of patients after lung transplantation. In this issue, Belperio et al. demonstrate a role for CXC chemokine receptor 2 in the regulation of angiogenesis-mediated airway fibroproliferation (see the related article beginning on page 1150). By integrating an understanding of neovascularization into the study of events that occur between inflammation and fibrosis, it becomes increasingly possible to rationally design therapies that can halt conditions of maladaptive fibrosis.
Terpenoid Metabolism in Wild-Type and Transgenic Arabidopsis Plants[W] (2003)

Volatile components, such as terpenoids, are emitted from aerial parts of plants and play a major role in the interaction between plants and their environment. Analysis of the composition and emission pattern of volatiles in the model plant Arabidopsis showed that a range of volatile components are released, primarily from flowers. Most of the volatiles detected were monoterpenes and sesquiterpenes, which in contrast to other volatiles showed a diurnal emission pattern. The active terpenoid metabolism in wild-type Arabidopsis provoked us to conduct an additional set of experiments in which transgenic Arabidopsis overexpressing two different terpene synthases were generated. Leaves of transgenic plants constitutively expressing a dual linalool/nerolidol synthase in the plastids (FaNES1) produced linalool and its glycosylated and hydroxylated derivatives. The sum of glycosylated components was in some of the transgenic lines up to 40- to 60-fold higher than the sum of the corresponding free alcohols. Surprisingly, we also detected the production and emission of nerolidol, albeit at a low level, suggesting that a small pool of its precursor farnesyl diphosphate is present in the plastids. Transgenic lines with strong transgene expression showed growth retardation, possibly as a result of the depletion of isoprenoid precursors in the plastids. In dual-choice assays with Myzus persicae, the FaNES1-expressing lines significantly repelled the aphids. Overexpression of a typical cytosolic sesquiterpene synthase resulted in the production of only trace amounts of the expected sesquiterpene, suggesting tight control of the cytosolic pool of farnesyl diphosphate, the precursor for sesquiterpenoid biosynthesis. This study further demonstrates the value of Arabidopsis for studies of the biosynthesis and ecological role of terpenoids and provides new insights into their metabolism in wild-type and transgenic plants.
Tumor antigens defined by cloned immunological probes are highly polymorphic and are not detected on autologous normal cells. (1989)

We have isolated UV light-induced and spontaneous tumors along with nonmalignant cells and tissues from each host. CD8+ CTL clones generated to a number of highly immunogenic UV-induced tumors did not react with autologous normal fibroblasts nor with autologous second tumors. Using up to 25 independently induced tumors as targets, these CTL clones were found to be uniquely specific for the particular tumor used for immunization even when multiple tumors isolated from the same animals were used as targets. In addition to this extensive antigenic diversity of independently induced tumors, we found that a single cancer cell can express multiple independent antigens that were uniquely expressed on the tumor but were not detectable on autologous nonmalignant fibroblasts. A poorly immunogenic spontaneous tumor was also found to express an antigen that was uniquely specific for the immunizing tumor in that it was absent from any of 25 other tumors tested. This antigen was recognized by a mAb and not detected on autologous nonmalignant fibroblasts or on an autologous second spontaneous tumor. These findings demonstrate that syngeneic CTL clones or mAbs can define unique antigens on UV-induced or spontaneous tumors. The use of autologous nonmalignant fibroblast targets made it unlikely that these antigens were widely expressed on normal cells. The availability of cloned immunological probes to antigens on tumors isolated with autologous normal cells will allow a reliable identification of the genetic origins of unique antigens on experimentally induced and spontaneous tumors and permit a decisive answer to whether these unique antigens are encoded by normal genes or by genes that have undergone somatic mutations; i.e., whether these antigens are truly tumor specific.
Assembling Heterocycle-Tethered C-Glycosyl and α-Amino Acid Residues via 1,3-Dipolar Cycloaddition Reactions (2004)

The 1,3-dipolar cycloadditions of C-glycosyl nitrile oxides and acetylenes to an alkyne and an azide, respectively, bearing a masked glycinyl moiety furnished disubstituted isoxazoles and triazoles. Unveiling the glycinyl group in these cycloadducts afforded C-glycosyl alpha-amino acids in which the two bioactive entities were tethered through rigid five-membered heterocycles. Optimized entries to the same compounds involved the use of unmasked but protected alkyne- and azide-containing amino acids as the partners of 1,3-dipolar cycloadditions.
Oxidation Behavior of Silicon and Carbon in Molten Iron-Carbon-Silicon Alloys with Carbon Dioxide (2001)

Desiliconization of molten Fe-Si-C alloy is important to keep basicity of slag higher in the dephosphorization process and to minimize total slag generation rate in steelmaking process. However, there is a desiliconization limit because competitive decarburization reaction proceeds as silicon content of metal decreases. Therefore development of an effective method that promotes desiliconization without decarburization is desired. Oxidation behavior of silicon and carbon in molten Fe-C-Si alloys with CO2 is investigated mainly at 1573K in this study. Desiliconization limit with CO2 at 1573K is [mass%Si]=9.1×10-4 under the conditions of aC=1, aSiO2=1 and PCO2=1 atm and silicon in metal can be removed up to [mass%Si]=1.3×10-3 in the present experiment. However, in order to remove silicon to a desired level, it is necessary to remove formed SiO2 from the metal bath because SiO2 is reduced with carbon in the melt and Si is remelted into metal. Overall rate constant of silicon oxidation under the condition of aC=1 is about 3.1×10-5 m/s and is independent of CO2 flow rate. Overall rate constants of simultaneous carbon and silicon oxidation under the condition of PCO2=1 are 4.0×10-6 m/s and 5.0×10-6 m/s, respectively and the rate constant for silicon is smaller than that under the condition of aC=1. It is inferred simultaneous oxidation of carbon and silicon causes some retarding effects on the advance of each reaction.
Autophagy, an Achilles’ heel AKTing against cancer? (2009)

Akt has emerged as an attractive cancer therapeutic target with a central role in cell survival, growth, proliferation and metabolism.A key to the clinical success of Akt inhibitors is the maximal possible antitumor efficacy achievable without intolerable side effects. In our recent work, we show that although Akt inhibition does not always induce a clear apoptotic response, autophagy is a more readily detectable response to pan-Akt knockdown or selective small molecule inhibitors of the PI3K/Akt pathway. Autophagy isa catabolic process of bulk lysosomal degradation and recycling of cytoplasmic material and organelles, which can provide a temporary survival mechanism for cells under stress conditions, but can also make cells vulnerable to several forms of cell death under specific circumstances. We hypothesize that autophagy induced by Akt inhibition may sensitize tumor cells to agents targeting the later steps of this lysosomal degradation process. Indeed, agents that interfere with the lysosomal degradation function could precipitate cell death when combined with Akt inhibition and promote complete tumor remissions in preclinical models. These findings suggest that manipulating the autophagic response may be a promising strategy to increase the therapeutic efficacy of Akt inhibitors.
Palliative Uses of Methylphenidate in Patients With Cancer: A Review (2002)

PURPOSE: Cancer is, unfortunately, often a terminal disease. The goal of therapy for many patients with cancer is palliation of symptoms common at the end of life, including pain, depression, and cognitive dysfunction. Methylphenidate is a psychostimulant most commonly used in the treatment of attention deficit hyperactivity disorder. In this report, we review the use of methylphenidate in the palliative care of patients with cancer. METHODS: This review was written on the basis of a computerized literature search of Medline. We considered all English language publications from 1966 to present using the following key words: methylphenidate, palliative care, and cancer. Forty-nine articles were identified as being relevant for this review. RESULTS: On the basis of this review, we came to the conclusion that methylphenidate is used to ameliorate opioid-induced somnolence, to augment the analgesic effects of opioids, to treat depression, and to improve cognitive function in patients with cancer. CONCLUSION: The medical literature supports the palliative use of methylphenidate in the care of patients with cancer. Further placebo-controlled trials are needed to elucidate the precise role that methylphenidate will have in providing symptom relief to dying patients.
Endoscopic laser coagulation in the management of severe twin‐to‐twin transfusion syndrome (1998)

The results of this multicentre study are similar to those in our original report on the first 45 cases. In comparison with serial amniodrainage, the survival rate may be similar, but the handicap rate in survivors appears much lower. This study stresses the need for a prospective study comparing these two techniques.
RECOMBINANT LIPOPROTEINS: Implications for Structure and Assembly of Native Lipoproteins (1986)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
Counting primary loops in polymer gels (2012)

Much of our fundamental knowledge related to polymer networks is built on an assumption of ideal end-linked network structure. Real networks invariably possess topological imperfections that negatively affect mechanical properties; modifications of classical network theories have been developed to account for these defects. Despite decades of effort, there are no known experimental protocols for precise quantification of even the simplest topological network imperfections: primary loops. Here we present a simple conceptual framework that enables primary loop quantification in polymeric materials. We apply this framework to measure the fraction of primary loop junctions in trifunctional PEG-based hydrogels. We anticipate that the concepts described here will open new avenues of theoretical and experimental research related to polymer network structure.
STRAND SEPARATION AND SPECIFIC RECOMBINATION IN DEOXYRIBONUCLEIC ACIDS: BIOLOGICAL STUDIES (1960)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.