gebhart/patrepeval huggingface dataset:
Functional analyses of mouse ASK, an activation subunit for Cdc7 kinase, using conditional ASK knockout ES cells (2005)

ASK (activator of S phase kinase) is an activation subunit for mammalian Cdc7 kinase. We have generated mutant ES cell lines in which ASK can be conditionally inactivated. Upon loss of the ASK genes, the mutant ES cells rapidly cease cell growth. In keeping with its expected roles in activation of the essential S phase kinase, DNA synthesis is arrested and significant cell death is eventually induced in ASK-deficient cells, demonstrating essential roles of ASK for viability of ES cells. Using these mutant cells, we have set up a system where ASK molecules can be functionally dissected. In keeping with previous results from yeasts, conserved motif-M and motif-C were shown to be essential for in vivo functions of ASK, whereas a long C-terminal tail, found only in ASK-related molecules in higher eukaryotes, is not required. Unexpectedly, the motif-N, related to the BRCT motif and dispensable for viability in yeasts, is essential for the viability of ES cells. Further characterization reveals that motif-N is required for the maximum phosphorylation of MCM in cells, whereas the autophosphorylation activity of Cdc7 is not significantly affected by its loss. These results may suggest that motif-N of ASK may facilitate recruitment of substrates for Cdc7 kinase.
Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial (2013)

Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia.
Tunable Synthesis and Characterization of Oleo-Furan Sulfonate Surfactants from Renewable Furan and Fatty Acids (2018)

University of Minnesota Ph.D. dissertation. May 2018. Major: Chemical Engineering. Advisor: Paul Dauenhauer. 1 computer file (PDF); xiii, 139 pages.
A clinician's guide to X-linked hypophosphatemia (2011)

X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines, which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the Advances in Rare Bone Diseases Scientific Conference held at the NIH in October 2008. We briefly review the clinical and pathophysiologic features of the disorder and offer this guide in response to the conference recommendation, based on our collective accumulated experience in the management of this complex disorder.
The biology of fear- and anxiety-related behaviors. (2002)

Anxiety is a psychological, physiological, and behavioral state induced in animals and humans by a threat to well-being or survival, either actual or potential. It is characterized by increased arousal, expectancy, autonomic and neuroendocrine activation, and specific behavior patterns. The function of these changes is to facilitate coping with an adverse or unexpected situation. Pathological anxiety interferes with the ability to cope successfully with life challenges. Vulnerability to psychopathology appears to be a consequence of predisposing factors (or traits), which result from numerous gene-environment interactions during development (particularly during the perinatal period) and experience (life events), in this review, the biology of fear and anxiety will be examined from systemic (brain-behavior relationships, neuronal circuitry, and functional neuroanatomy) and cellular/molecular (neurotransmitters, hormones, and other biochemical factors) points of view, with particular reference to animal models. These models have been instrumental in establishing the biological correlates of fear and anxiety, although the recent development of noninvasive investigation methods in humans, such as the various neuroimaging techniques, certainly opens new avenues of research in this field. Our current knowledge of the biological bases of fear and anxiety is already impressive, and further progress toward models or theories integrating contributions from the medical, biological, and psychological sciences can be expected.
Inaccessible Pore Volume in Polymer Flooding (1972)

Abstract We have found that solutions of typical waterflooding polymers do not occupy all of the connected pore volume in porous media. The remainder of the pore volume is inaccessible to polymer. This inaccessible pore volume is occupied polymer. This inaccessible pore volume is occupied by water that contains no polymer, but is otherwise in equilibrium with the polymer solution. This allows changes in polymer concentration to be propagated through porous media more rapidly than propagated through porous media more rapidly than similar changes in salt concentration. At the front edge of a polymer bank the effect of inaccessible pore volume opposes the effect of adsorption and pore volume opposes the effect of adsorption and may completely remove it in some cases. This paper presents three experimental polymer floods showing the effect of inaccessible pore volume in the presence of varying amounts of adsorption. Results of these floods clearly show that about 30 percent of the connected pore volume in the rock samples used was not accessible to The polymer solutions. The changes required to include polymer solutions. The changes required to include inaccessible pore volume in mathematical models of polymer flow and in held prediction methods are discussed. Introduction One way of improving the mobility ratio during waterflooding operations is by addition of a water-soluble polymer to the flood water. Several different polymers have been proposed and a number of investigators have presented results on the behavior of these polymer solutions in porous media. In addition, mathematical models have been developed for predicting the field behavior of polymer flooding. In all these studies movement polymer flooding. In all these studies movement of the polymer bank through the reservoir rock is of great importance. One phenomenon that has been repeatedly observed in polymer flooding is the removal of polymer from solution by adsorption on the reservoir rock. As a polymer bank propagates through porous media, the polymer bank propagates through porous media, the front edge is gradually denuded of polymer. The amount of polymer lost from a bank may be large or small, depending on the nature of the polymer and rock surface. This loss of polymer must be measured and included in any realistic mathematical model of polymer behavior. It has been widely assumed that polymer behavior. It has been widely assumed that adsorption is the most significant factor causing polymer to propagate through porous media at a polymer to propagate through porous media at a velocity different from that of water. In this paper we present data that demonstrate that all of the pores may not be accessible to polymer molecules and that this "inaccessible polymer molecules and that this "inaccessible pore volume" can affect polymer propagation pore volume" can affect polymer propagation significantly. In addition to the experimental results, we discuss the changes in interpretation and in mathematical models that are required to include this phenomenon.
Resistance of severe combined immunodeficient mice to infection with Cryptosporidium parvum: the importance of intestinal microflora (1992)

Cryptosporidium parvum is a protozoan parasite which colonizes intestinal epithelium, causing transient diarrheal illness in immunocompetent hosts and severe chronic disease in immunocompromised hosts. We examined the resistance of severe combined immunodeficient mice, either bearing intestinal flora or germfree, to intestinal infection with C. parvum. Infection was not readily detected in flora-bearing adult severe combined immunodeficient mice until 5 to 7 weeks following oral challenge with C. parvum. In contrast, germfree adult severe combined immunodeficient mice were heavily infected 3 weeks following challenge. These data support the hypothesis that resistance of adult mice to C. parvum infection does not require a specific immune response but can be mediated by nonspecific mechanisms associated with the presence of intestinal flora.
Expansion of Immunostimulatory Dendritic Cells from Peripheral Blood of Patients with Cancer (1997)

Clinical investigators are keenly interested in the role of antigen-presenting cells (APCs) in the initiation of immune responses because of potential use of APCs in immune cell therapy. Pioneer studies in mammals by Steinman and coworkers have demonstrated that the specialized system of APCs is constituted by bone marrow-derived dendritic cells. Dendritic cells are distinguished by their unique ability to capture, process, and present antigens into peptide-HLA complexes to naive T lymphocytes and to deliver the costimulatory signal necessary for T-lymphocyte activation. In this article, we summarize the main experimental evidence supporting the hypothesis that individuals vaccinated with manipulated dendritic cells can mount tumor-specific humoral and cellular responses. This can lead to tumor regression as well as protective immunity to tumor growth in vivo.
Annealing effects on Czochralski grown Lu2Si2O7:Ce3+ crystals under different atmospheres (2008)

Cerium-doped lutetium pyrosilicate Lu2Si2O7:Ce3+ (LPS:Ce) single crystal samples grown via Czochralski method were annealed under air and H2 atmospheres from 350to1600°C. The x-ray excited luminescence spectra and UV as well as thermal stimulated luminescence spectra were measured. It was found that the luminescence efficiency after annealing in air at 1400°C was significantly enhanced compared to the unannealed samples. This phenomenon was suggested to be caused by the existence of some oxygen vacancies in the LPS:Ce crystals, and these oxygen vacancies can be effectively eliminated by means of annealing in air. Although the annealing will lead to the oxidization of cerium ions from Ce3+ ions to Ce4+, which is harmful to the luminescent efficiency, the annealing treatment does enhance the luminescent efficiency of LPS:Ce, without changing its luminescence mechanics.
Poly(aryleneethynylene)s:  Syntheses, Properties, Structures, and Applications (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPoly(aryleneethynylene)s: Syntheses, Properties, Structures, and ApplicationsUwe H. F. BunzView Author Information Department of Chemistry and Biochemistry, The University of South Carolina, Columbia, South Carolina 29208 Cite this: Chem. Rev. 2000, 100, 4, 1605–1644Publication Date (Web):March 14, 2000Publication History Received8 September 1999Published online14 March 2000Published inissue 1 April 2000https://pubs.acs.org/doi/10.1021/cr990257jhttps://doi.org/10.1021/cr990257jresearch-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views8547Altmetric-Citations1662LEARN 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 optionsGet e-Alertsclose SUBJECTS:Aromatic compounds,Catalysts,Hydrocarbons,Macromolecules,Polymers Get e-Alerts
Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model (1998)

IL-12 treatment of a murine transplantable breast carcinoma (HTH-K) led to tumour regression and cure which was related to the duration of treatment. We studied the sequential molecular and phenotypic changes in IL-12-treated tumours. IFN-gamma mRNA was detected 8 hr after the first treatment. mRNA expression for the IFN-gamma-inducible genes beta 2-microglobulin and indoleamine dioxygenase (IDO) was induced subsequently, together with the chemokine IP-10. IL-12-treated tumours had an abundant cellular infiltrate, consisting mainly of CD8+ T cells. mRNA for granzyme B and perforin also could be detected, suggesting that those cells were activated. After 7 days of daily therapy, tumours in IL-12-treated mice had a significant reduction in vasculature. Finally, the number of apoptotic tumour cells increased throughout IL-12 treatment. We compared the anti-tumour effects of IL-12 to those induced by IFN-gamma therapy, which caused initial tumour stasis but subsequent tumour progression. IFN-gamma induced beta 2-microglobulin and IDO over a 7-day period, but IP-10 was induced only transiently. IFN-gamma caused a lesser cellular infiltrate, a minor anti-angiogenic effect and a transient apoptotic effect. The success of IL-12 may be due to its ability to produce a distinct sequence of molecular and phenotypic changes in tumours, leading to an anti-tumour immune response, toxicity against tumour cells and an anti-angiogenic effect. Other cytokines, such as IFN-gamma, induce some, but not all, of these actions. Comparison of IL-12 and IFN-gamma suggests that sustained induction of IP-10 and activation of a resulting cellular infiltrate may be key changes in regressing tumours.
The Art and Science of Contemporary Drug Development (1972)

There are several recent thoughtful and highly instructive publications on drug research that treat extensively the problems associated with the design and discovery of new chemical entities (e.g., [1–4]). In addition, the rate of new drug discovery and the economics of research and development have been under close scrutiny, particularly since enactment of the 1962 amendments to the Food, Drug, and Cosmetic Act of 1938 in the United States [4–7]. Quite apart from the actual drug-discovery efforts of a pharmaceutical manufacturer are the equally difficult, vitally important, and costly activities involved in the developmental stages that lead to an approved, marketable product. Very little has been published on the details of this broad and complex subject.
IL-17 Mediated Inflammation Promotes Tumor Growth and Progression in the Skin (2012)

The mechanism for inflammation associated tumor development is a central issue for tumor biology and immunology and remains to be fully elucidated. Although IL-17 is implicated in association with inflammation mediated carcinogenesis, mechanisms are largely elusive. In the current studies, we showed that IL-17 receptor-A gene deficient (IL-17R-/-) mice were resistant to chemical carcinogen-induced cutaneous carcinogenesis, a well-established inflammation associated tumor model in the skin. The deficiency in IL-17R increased the infiltration of CD8+ T cells whereas it inhibited the infiltration of CD11b+ myeloid cells and development of myeloid derived suppressor cells. Inflammation induced skin hyperplasia and production of pro-tumor inflammatory molecules were inhibited in IL-17R-/- mice. We found that pre-existing inflammation in the skin increased the susceptibility to tumor growth, which was associated with increased development of tumor specific IL-17 producing T cells. This inflammation induced susceptibility to tumor growth was abrogated in IL-17R-/- mice. Finally, neutralizing IL-17 in mice that had already developed chemical carcinogen induced skin tumors could inhibit inflammation mediated tumor progression at late stages. These results demonstrate that IL-17 mediated inflammation is an important mechanism for inflammation mediated promotion of tumor development. The study has major implications for targeting IL-17 in prevention and treatment of tumors.
The Nrf2/ARE Pathway as a Potential Therapeutic Target in Neurodegenerative Disease (2008)

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce expression of a variety of cytoprotective and detoxification genes. Several of the genes commonly regulated by Nrf2 have been implicated in protection from neurodegenerative conditions. Work from several laboratories has uncovered the potential for Nrf2-mediated transcription to protect from neurodegeneration resulting from mechanisms involving oxidative stress. For this reason, Nrf2 may be considered a therapeutic target for conditions that are known to involve free radical damage. Because common mechanisms of neurodegeneration, such as mitochondrial dysfunction and build-up of reactive oxygen species, are currently being uncovered, targeting Nrf2 may be valuable in combating conditions with variable causes and etiologies. Most effectively to target this protein in neurodegenerative conditions, a description of the involvement of Nrf2 and potential for neuroprotection must come from laboratory models. Herein, we review the current literature that suggests that Nrf2 may be a valuable therapeutic target for neurodegenerative disease, as well as experiments that illustrate potential mechanisms of protection.
Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites (2002)

The cytokine macrophage migration inhibitory factor (MIF) has emerged to be an important regulator of the inflammatory response and is critically involved in the development of septic shock, arthritis, and glomerulonephritis. Although the biological activities of MIF are presumed to require a receptor-based mechanism of action, the protein is also a tautomerase and has a catalytically active N-terminal proline that is invariant in structurally homologous bacterial isomerases. This observation raises the possibility that MIF may exert its biological action via an enzymatic reaction. Physiologically relevant substrates for MIF have not been identified, nor have site-directed mutagenesis studies consistently supported the requirement for a functional catalytic site. Small molecule inhibitors of MIF's isomerase activity also have been developed, but none have been shown yet to inhibit MIF biological activity. We report herein that the iminoquinone metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), inhibits both the isomerase and the biological activities of MIF. The reaction between NAPQI and MIF is covalent and produces a NAPQI-modified MIF species with diminished cell binding activity and decreased recognition by anti-MIF mAb. These data are consistent with a model by which the NAPQI reacts with the catalytic Pro-1 of MIF to disrupt the integrity of epitope(s) critical to MIF's biological activity and point to the importance of the catalytic domain, but not the catalytic activity per se, in MIF function. These results also point to a powerful approach for the design of small molecule inhibitors of MIF based on interaction with its catalytic site and constitute an example of a pharmacophore capable of irreversibly inhibiting the action of a proinflammatory cytokine.
DeepQA Jeopardy! Gamification: A Machine-Learning Perspective (2014)

DeepQA is a large-scale natural language processing (NLP) question-and-answer system that responds across a breadth of structured and unstructured data, from hundreds of analytics that are combined with over 50 models, trained through machine learning. After the 2011 historic milestone of defeating the two best human players in the Jeopardy! game show, the technology behind IBM Watson, DeepQA, is undergoing gamification into real-world business problems. Gamifying a business domain for Watson is a composite of functional, content, and training adaptation for nongame play. During domain gamification for medical, financial, government, or any other business, each system change affects the machine-learning process. As opposed to the original Watson Jeopardy!, whose class distribution of positive-to-negative labels is 1:100, in adaptation the computed training instances, question-and-answer pairs transformed into true-false labels, result in a very low positive-to-negative ratio of 1:100 000. Such initial extreme class imbalance during domain gamification poses a big challenge for the Watson machine-learning pipelines. The combination of ingested corpus sets, question-and-answer pairs, configuration settings, and NLP algorithms contribute toward the challenging data state. We propose several data engineering techniques, such as answer key vetting and expansion, source ingestion, oversampling classes, and question set modifications to increase the computed true labels. In addition, algorithm engineering, such as an implementation of the Newton-Raphson logistic regression with a regularization term, relaxes the constraints of class imbalance during training adaptation. We conclude by empirically demonstrating that data and algorithm engineering are complementary and indispensable to overcome the challenges in this first Watson gamification for real-world business problems.
Self-contained powered knee and ankle prosthesis: Initial evaluation on a transfemoral amputee (2009)

This paper presents an overview of the design and control of a fully self-contained prosthesis, which is intended to improve the mobility of transfemoral amputees. A finite-state based impedance control approach, previously developed by the authors, is used for the control of the prosthesis during walking and standing. The prosthesis was tested on an unilateral amputee subject for over-ground walking. Prosthesis sensor data (joint angles and torques) acquired during level ground walking experiments at a self-selected cadence demonstrates the ability of the device to provide a functional gait similar to normal gait biomechanics. Battery measurements during level ground walking experiments show that the self-contained device provides over 4,500 strides (9.0 km of walking at a speed of 5.1 km/h) between battery charges.
Bioactivation and Cell Targeting of Semiconductor CdSe/ZnS Nanocrystals with Phytochelatin-Related Peptides (2004)

Synthetic phytochelatin-related peptides are used as an organic coat on the surface of colloidal CdSe/ZnS semiconductor nanocrystals synthesized from hydrophobic coordinating trioctyl phosphine oxide (TOPO) solvents. The peptides are designed to bind to the nanocrystals via a C-terminal adhesive domain. This adhesive domain, composed of multiple repeats of cysteines pairs flanked by hydrophobic 3-cyclohexylalanines, is followed by a flexible hydrophilic linker domain to which various bio-affinity tags can be attached. This surface coating chemistry results in small, buffer soluble, monodisperse peptide-coated nanoparticles with high colloidal stability and ensemble photophysical properties similar to those of TOPO-coated nanocrystals. Various peptide coatings are used to modulate the nanocrystal surface properties and to bioactivate the nanoparticles. CdSe/ZnS nanocrystals coated with biotinylated peptides efficiently bind to streptavidin and are specifically targeted to GPI-anchored avidin-CD14 chimeric proteins expressed on the membranes of live HeLa cells. This peptide coating surface chemistry provides a novel approach for the production of biocompatible photoluminescent nanocrystal probes.