gebhart/patrepeval huggingface dataset:
Chromium and polyphenols from cinnamon improve insulin sensitivity (2008)

Naturally-occurring compounds that have been shown to improve insulin sensitivity include Cr and polyphenols found in cinnamon (Cinnamomon cassia). These compounds also have similar effects on insulin signalling and glucose control. The signs of Cr deficiency are similar to those for the metabolic syndrome and supplemental Cr has been shown to improve all these signs in human subjects. In a double-blind placebo-controlled study it has been demonstrated that glucose, insulin, cholesterol and HbA1c are all improved in patients with type 2 diabetes following Cr supplementation. It has also been shown that cinnamon polyphenols improve insulin sensitivity in in vitro, animal and human studies. Cinnamon reduces mean fasting serum glucose (18-29%), TAG (23-30%), total cholesterol (12-26%) and LDL-cholesterol (7-27%) in subjects with type 2 diabetes after 40 d of daily consumption of 1-6 g cinnamon. Subjects with the metabolic syndrome who consume an aqueous extract of cinnamon have been shown to have improved fasting blood glucose, systolic blood pressure, percentage body fat and increased lean body mass compared with the placebo group. Studies utilizing an aqueous extract of cinnamon, high in type A polyphenols, have also demonstrated improvements in fasting glucose, glucose tolerance and insulin sensitivity in women with insulin resistance associated with the polycystic ovary syndrome. For both supplemental Cr and cinnamon not all studies have reported beneficial effects and the responses are related to the duration of the study, form of Cr or cinnamon used and the extent of obesity and glucose intolerance of the subjects.
The Relationship Between Powder Inhaler Resistance and Peak Inspiratory Conditions in Healthy Volunteers — Implications for In Vitro Testing (1993)

Despite the fact that powder inhaler devices have been available for over 3 decades there is still very little fundamental information as to how powder inhaler design interacts with the airway dynamics of patients. This paper documents the results of human volunteer investigations designed to elucidate this interaction. These data indicates that if 'maximum' inhalation effort is employed the flow rate attained through an inhaler is controlled by the maximum pressure drop developed by the chest muscles. If a moderate or 'comfortable' effort is used, however, the relationship is more complex. An equation for defining the 'respirable fraction' of an inhalation aerosol cloud as a function of inhalation flow rate is also proposed.
Biomaterials for Sensors, Fuel Cells, and Circuitry (2002)

Bioelectronics is a rapidly progressing interdisciplinary research field that aims to integrate biomolecules and electronic elements into functional systems (1,2). Biomolecules offer unique building blocks for such devices. The ability to control the shape and structure of biomolecules, such as proteins and DNA, and the evolution-optimized chemical functions of biomaterials including binding, catalysis, ion-pumping and self-assembly, make biomolecules attractive building blocks for functional devices. Hybrid systems formed by the integration of biomolecules with electronic elements, such as electrodes, or transistors enable the electronic read-out detection of biomolecular functions, the transformation of biocatalyzed processes into electrical power, and the templating of nanosized circuitry. Future applications of bioelectronic systems may include computation devices and prosthetic units. This article covers many aspects of the new field of bioelectronics.
Preferential hydrogenation of aldehydes and ketones. (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticlePreferential hydrogenation of aldehydes and ketones.Takeshi Ohkuma, Hirohito Ooka, Takao Ikariya, and Ryoji NoyoriCite this: J. Am. Chem. Soc. 1995, 117, 41, 10417–10418Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October 1995https://doi.org/10.1021/ja00146a041RIGHTS & PERMISSIONSArticle Views4678Altmetric-Citations321LEARN 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 InReddit PDF (313 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Characterization of mutations in ATP8B1 associated with hereditary cholestasis (2004)

Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1-3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened.
Synthesis of New Arylhydroxymethylphosphinic Acids and Derivatives (2003)

International audience
FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver (2013)

Many aspects of intercellular communication are mediated through "sending" and "receiving" packets of information via the secretion and subsequent receptor-mediated detection of biomolecular species including cytokines, chemokines, and even metabolites. Recent evidence has now established a new modality of intercellular communication through which biomolecular species are exchanged between cells via extracellular lipid vesicles. A particularly important class of extracellular vesicles is exosomes, which is a term generally applied to biological nanovesicles ~30-200 nm in diameter. Exosomes form through invagination of endosomes to encapsulate cytoplasmic contents, and upon fusion of these multivesicular endosomes to the cell surface, exosomes are released to the extracellular space and transport mRNA, microRNA (miRNA) and proteins between cells. Importantly, exosome-mediated delivery of such cargo molecules results in functional modulation of the recipient cell, and such modulation is sufficiently potent to modulate disease processes in vivo. It is possible that such functional delivery of biomolecules indicates that exosomes utilize native mechanisms (e.g., for internalization and trafficking) that may be harnessed by using exosomes to deliver exogenous RNA for therapeutic applications. A complementary perspective is that understanding the mechanisms of exosome-mediated transport may provide opportunities for "reverse engineering" such mechanisms to improve the performance of synthetic delivery vehicles. In this review, we summarize recent progress in harnessing exosomes for therapeutic RNA delivery, discuss the potential for engineering exosomes to overcome delivery challenges and establish robust technology platforms, and describe both potential challenges and advantages of utilizing exosomes as RNA delivery vehicles.
Design and Synthesis of 2‘,3‘-Dideoxy- 2‘,3‘-didehydro-β-l-cytidine (β-l-d4C) and 2‘,3‘-Dideoxy-2‘,3‘-didehydro-β-l-5- fluorocytidine (β-l-Fd4C), Two Exceptionally Potent Inhibitors of Human Hepatitis B Virus (HBV) and Potent Inhibitors of Human Immunodeficiency Virus (HIV) in Vitro (1996)

ADVERTISEMENT RETURN TO ISSUELetterNEXTDesign and Synthesis of 2',3'-Dideoxy- 2',3'-didehydro-β-l-cytidine (β-l-d4C) and 2',3'-Dideoxy-2',3'-didehydro-β-l-5- fluorocytidine (β-l-Fd4C), Two Exceptionally Potent Inhibitors of Human Hepatitis B Virus (HBV) and Potent Inhibitors of Human Immunodeficiency Virus (HIV) in VitroTai-Shun Lin, Mei-Zhen Luo, Mao-Chin Liu, Yong-Lian Zhu, Elizabeth Gullen, Ginger E. Dutschman, and Yung-Chi ChengView Author Information Department of Pharmacology and The Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8066 Cite this: J. Med. Chem. 1996, 39, 9, 1757–1759Publication Date (Web):April 26, 1996Publication History Received13 November 1995Published online26 April 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm950836qhttps://doi.org/10.1021/jm950836qrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views745Altmetric-Citations106LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Antimicrobial agents,Genetics,Pharmaceuticals,Toxicity,Viruses Get e-Alerts
Experimental transmission of a granulocytic form of the tribe Ehrlichieae by Dermacentor variabilis and Amblyomma americanum to dogs (1990)

Transstadial transmission of granulocytic Ehrlichieae in dogs was attempted using ticks, Amblyomma americanum and Dermacentor variabilis. Ticks were exposed by feeding as nymphs on acutely infected pups; adult ticks then fed to repletion on susceptible adult dogs that were monitored daily for signs of infection. Evidence of transmission was not observed in control dogs or in those exposed to D variabilis. In contrast, dogs exposed to A americanum developed serologic or clinical evidence of infection, but organisms were not seen in blood smears until corticosteroids were administered, causing recrudescence and accompanying parasitemia. At 12 days after subinoculation of blood obtained from donor adult dogs, before corticosteroids were administered, a febrile response, thrombocytopenia, and appearance of morulae in neutrophilic granulocytes were observed in 2 susceptible recipient dogs.
Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. (2003)

HPV-16 infection is associated with a significant increased risk for oropharyngeal cancer but not oral cavity cancer. Furthermore, HPV-16 infection does not appear to be more common in never-smokers than ever-smokers with SCCHN.
Uncertainty and Sensitivity Analyses of a Decision Analytic Model for Posteradication Polio Risk Management (2008)

Decision analytic modeling of polio risk management policies after eradication may help inform decisionmakers about the quantitative tradeoffs implied by various options. Given the significant dynamic complexity and uncertainty involving posteradication decisions, this article aims to clarify the structure of a decision analytic model developed to help characterize the risks, costs, and benefits of various options for polio risk management after eradication of wild polioviruses and analyze the implications of different sources of uncertainty. We provide an influence diagram of the model with a description of each component, explore the impact of different assumptions about model inputs, and present probability distributions of model outputs. The results show that choices made about surveillance, response, and containment for different income groups and immunization policies play a major role in the expected final costs and polio cases. While the overall policy implications of the model remain robust to the variations of assumptions and input uncertainty we considered, the analyses suggest the need for policymakers to carefully consider tradeoffs and for further studies to address the most important knowledge gaps.
Inversion of Reflection Seismograms by Differential Semblance Analysis: Algorithm Structure and Synthetic Examples (1992)

Seismograms predicted from acoustic or elastic earth models depend very nonlinearly on the long wavelength components of velocity. This sensitive dependence demands the use of special variational principles in waveform-based inversion algorithms. The differential semblance variational principle is well-suited to velocity inversion by gradient methods, since its objective function is smooth and convex over a large range of velocity models. An extension of the adjoint state technique yields an accurate estimate of the differential semblance gradient. Nonlinear conjugate gradient iteration is quite successful in locating the global differential semblance minimum, which is near the ordinary least squares global minimum when coherent data noise is small. Several examples based on the 2D primaries-only acoustic model illustrate features of the method and its performance.
Effect of heat treatment on the properties and structure of TiO 2 nanotubes: phase composition and chemical composition (2010)

Abstract Titanium oxide (TiO 2 ) nanotubes prepared by electrolytic anodisation of a titanium electrode have been systematically heat treated to control the conversion of the as‐prepared amorphous structure to nanocrystalline anatase and rutile. Raman spectroscopy revealed that the temperature of calcination is critical in determining the structure and crystallinity of the titania. X‐ray Photoelectron Spectroscopy analysis shows the as‐prepared film to consist mainly of oxide, although a small amount of fluoride contamination remains from the electrolyte. Organic components from post‐anodising cleaning treatments were also present. Fluorine ions are gradually ejected from the anodic layer during annealing and the fluorine concentration is negligible in samples that are heat treated above 400 °C. Choosing the appropriate annealing temperature allows the structure to be made up of defined proportions of anatase and rutile with a reduced contamination of species from the electrolyte or organic solvents. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Alteration of growth responses in established cardiac pressure overload hypertrophy in rats with aortic banding. (1995)

We examined the acute effects of elevated wall stress, norepinephrine, and angiotensin II on cardiac protein synthesis as well as protooncogene expression in hearts with established pressure overload left ventricular hypertrophy. Isolated rat hearts with chronic hypertrophy (LVH) were studied 12 wk after ascending aortic banding when systolic function was fully maintained. New protein synthesis (incorporation of [3H]phenylalanine [Phe]) was analyzed in isolated perfused rat hearts after a 3-h protocol; c-fos, c-jun, c-myc, and early growth response gene-1 (EGR-1) mRNA levels (Northern blot) were studied over a time course from 15 to 240 min of perfusion. Under baseline conditions (i.e., before mechanical or neurohormonal stimulation), [3H]-Phe-incorporation (280 nmoles/gram protein/h) and protooncogene mRNA levels were similar in age-matched control and LVH hearts. However, hearts with chronic LVH were characterized by a markedly blunted or absent [3H]-Phe-incorporation after acute imposition of isovolumic systolic load (90 mmHg/gram left ventricle), as well as norepinephrine (10(-6)M), or angiotensin II infusion (10(-8)M plus prazosin 10(-7)M) compared with nonhypertrophied control hearts. Similarly, stimulation of LVH hearts with acute systolic load or norepinephrine was associated with a significantly blunted increase of protooncogene mRNA levels relative to control hearts. The blunted induction of c-fos mRNA in LVH hearts was not due to feedback inhibition, since cycloheximide perfusion of hearts exposed to elevated wall stress further increased the differences between age-matched control and LVH hearts. The data suggest that acute molecular growth responses to mechanical or neurohormonal stimulation are altered in rat hearts with established LVH relative to nonhypertrophied control hearts. This alteration of molecular adaptations in hearts with compensatory hypertrophy may prevent inappropriate excess cardiac growth in response to mechanical and neurohormonal stimuli.
Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease (2011)

Iron isomaltoside 1000 was clinically well tolerated, safe and effective. This new intravenous iron may offer a further valuable choice in treating the anemia of CKD.
A rat knock out model of human familial adenomatous polyposis (2006)

4844 Humans with mutations in the Adenomatous Polyposis Coli (APC) gene get hundreds to thousands of adenomas in the colon and develop colorectal cancer, however current mouse models of human intestinal cancer, including the ApcMin model developed at the McArdle Laboratory, develop lesions primarily in the small intestine and have never been observed to metastasize. We have generated a rat knock out of Apc in which the animals develop primarily colonic tumors by 90 days of age. We have termed this allele Pirc for polyposis in rat colon. Our group has recently developed the technology to knock out rat genes of interest through mutagenesis with N-ethyl-N-nitrosourea (ENU). We screened 2530 base pairs of exon 15 of the rat Apc gene from genomic DNA in the offspring of mutagenized Fisher-344 inbred rats using a universal vector gap repair yeast truncation assay (Biotechniques. 2004 Sep;37(3):383-8). Screening of 1360 progeny yielded a single mutant with an A to T transversion changing a lysine to a stop codon at amino acid position 1137. Upon abstract submission the founder male is 260 days old, remains fertile, and has successfully transmitted the mutation to 60 progeny. Ten of the resulting mutant N1 animals were brother-sister mated and their offspring confirmed that the ApcPirc allele is homozygous lethal. Necropsy of six N1 ApcPirc heterozygotes, three at 90 days and three at 130 days of age, identified an average of 6 visible adenomatous polyps in the colon, while six wild type age-matched littermates were tumor-free. Histological immunofluorescence staining of four of the tumors for β-catenin confirmed the tumor-associated relocalization of β-catenin from the lateral membrane to the cytoplasm and nucleus. The affected animals showed neither visible lesions nor β-catenin relocalization in the small intestine. Pirc/+ animals treated somatically with ENU at 2 weeks of age develop in excess of 100 microadenomas in the distal small intestine and colon by 60 days post injection. No lesions were seen in the ENU treated non-carriers. ApcPirc was successfully crossed to Wistar-Furth and intercrossing of the F1 carriers determined that the ApcPirc allele was homozygous lethal in the F2 progeny. Ongoing studies include the examination of tumor number and distribution in older carrier N1 and F1 animals as well as the effects of a high fat diet on N1 animals. The primary localization of tumors to the colon recapitulates human intestinal cancer, addressing one of the major drawbacks of ApcMin and other mouse models that have a primarily small-intestinal distribution. The colonic phenotype and longer life span of the ApcPirc rat combined with the growing resources of rat genetics, genomics and biology indicate that the rat may be an advantageous model for human tumor progression and experimental treatment of colon cancer.
Reexpression of LSAMP inhibits tumor growth in a preclinical osteosarcoma model (2014)

The high frequency and the specificity of the deletion indicate that it is important for the development of osteosarcomas. The deletion targets the tumor suppressor LSAMP, and based on the functional evidence, the tumor suppressor function of LSAMP is most likely exerted by reducing the proliferation rate of the tumor cells, possibly by indirectly upregulating one or more of the genes HES1, CTAG2 or KLF10. To our knowledge, this study describes novel functions of LSAMP, a first step to understanding the functional role of this specific deletion in osteosarcomas.
Direct Observation of Tube-Like Motion of a Single Polymer Chain (1994)

Tube-like motion of a single, fluorescently labeled molecule of DNA in an entangled solution of unlabeled lambda-phage DNA molecules was observed by fluorescence microscopy. One end of a 16- to 100-micrometer-long DNA was attached to a 1-micrometer bead and moved with optical tweezers. The molecule was stretched into various conformations having bends, kinks, and loops. As the polymer relaxed, it closely followed a path defined by its initial contour. The relaxation time of the disturbance caused by the bead was roughly 1 second, whereas tube-like motion in small loops persisted for longer than 2 minutes. Tube deformation, constraint release, and excess chain segment diffusion were also observed. These observations provide direct evidence for several key assumptions in the reptation model developed by de Gennes, Edwards, and Doi.