gebhart/patrepeval huggingface dataset:
Defense Strategies Against Hypoxia and Hypothermia (1986)

Because aerobic metabolic rates decrease in hypoxia-sensitive cells under oxygen-limiting conditions, the demand for glucose or glycogen for anaerobic glycolysis may rise drastically as a means of making up for the energetic shortfall. However, ion and electrical potentials typically cannot be sustained because of energy insufficiency and high membrane permeabilities; therefore metabolic and membrane functions in effect become decoupled. In hypoxia-tolerant animals, these problems are resolved through a number of biochemical and physiological mechanisms; of these metabolic arrest and stabilized membrane functions are the most effective strategies for extending tolerance to hypoxia. Metabolic arrest is achieved by means of a reversed or negative Pasteur effect (reduced or unchanging glycolytic flux at reduced O2 availability); and coupling of metabolic and membrane function is achievable, in spite of the lower energy turnover rates, by maintaining membranes of low permeability (probably via reduced densities of ion-specific channels). The possibility of combining metabolic arrest with channel arrest has been recognized as an intervention strategy. To date, the success of this strategy has been minimal, mainly because depression of metabolism through cold is the usual arrest mechanism used, and hypothermia in itself perturbs controlled cell function in most endotherms.
Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity. (1986)

CSF-1, a macrophage colony stimulating factor that causes proliferation and differentiation of progenitor cells, may also have effects on mature cells. Human peripheral blood monocytes were used to examine this possibility. Monocytes, separated from normal blood by density centrifugation and adherence, were incubated for 3 days with or without CSF-1 (1,000 U/ml, purified from the MIA PaCa pancreatic carcinoma line). The two groups of cells were then washed and tested for the ability, when induced, to produce several factors. When induced for 2 days with LPS and PMA, the monocytes produced a factor that was cytotoxic to L929 cells, and this factor was completely neutralized by polyclonal antibody to tumor necrosis factor. The cells preincubated with CSF-1 consistently produced an average of 12 times more of this factor than cells not exposed to CSF-1. Monocytes induced with LPS and PMA also produced a colony stimulating activity, as measured by colony formation when using mouse bone marrow. Cells preincubated with CSF-1, washed, and induced with LPS and PMA produced more than three times as much activity compared with control monocytes. When monocytes were induced with poly-I.C, 22-fold higher levels of interferon were produced by the cells exposed to CSF-1. These results show that CSF-1 has direct stimulating effects on mature human monocytes, and suggest that the macrophage growth factor may have clinical application in the treatment of infectious diseases and cancer.
Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. (1997)

The bimonthly regimen was more effective and less toxic than the monthly regimen and definitely increased the therapeutic ratio. However, there was no evidence of increased survival.
Three gonadotropin-releasing hormone genes in one organism suggest novel roles for an ancient peptide. (1995)

Gonadotropin-releasing hormone (GnRH) is known and named for its essential role in vertebrate reproduction. Release of this decapeptide from neurons in the hypothalamus controls pituitary gonadotropin levels which, in turn, regulate gonadal state. The importance of GnRH is underscored by its widespread expression and conservation across vertebrate taxa: five amino acids are invariant in all nine known forms, whereas two others show only conservative changes. In most eutherian mammals, only one form, expressed in the hypothalamus, is thought to exist, although in a recent report, antibody staining in developing primates suggests an additional form. In contrast, multiple GnRH forms and expression loci have been reported in many non-mammalian vertebrates. However, evidence based on immunological discrimination does not always agree with analysis of gene expression, since GnRH forms encoded by different genes may not be reliably distinguished by antibodies. Here we report the expression of three distinct GnRH genes in a teleost fish brain, including the sequence encoding a novel GnRH preprohormone. Using in situ hybridization, we show that this form is found only in neurons that project to the pituitary and exhibit changes in soma size depending on social and reproductive state. The other two GnRH genes are expressed in other, distinct cell populations. All three genes share the motif of encoding a polypeptide consisting of GnRH and a GnRH-associated peptide. Whereas the GnRH moiety is highly conserved, the GnRH-associated peptides are not, reflecting differential selective pressure on different parts of the gene. GnRH forms expressed in nonhypothalamic regions may serve to coordinate reproductive activities of the animal.
Synthesis of [Gly-1]RA-VII, [Gly-2]RA-VII, and [Gly-4]RA-VII. Glycine-Containing Analogues of RA-VII, an Antitumor Bicyclic Hexapeptide from Rubia Plants (2004)

Three analogues of RA-VII (1), an antitumor bicyclic hexapeptide from Rubia plants, were synthesized. Three analogues, [Gly-1]RA-VII (4), [Gly-2]RA-VII (5), and [Gly-4]RA-VII (6), in which one of the three alanine residues in 1 was replaced by a glycine residue, were prepared by linking of the cycloisodityrosine unit, obtained by degradation of 1, to three different glycine-containing tetrapeptides followed by macrocyclization. Of these three analogues, analogue 4 showed the highest cytotoxic activity. The NMR study revealed that in solution the conformer structures and their ratios of analogue 4 were very similar to those of natural peptide 1, suggesting that the methyl groups at Ala-2 and Ala-4 should be essential for producing the bioactive conformation, whereas that at D-Ala-1 is not essential.
Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics (2016)

MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development.
Towards automated georeferencing of Flickr photos (2010)

We explore the task of automatically assigning geographic coordinates to photos on Flickr. Using an approach based on k-medoids clustering and Naive Bayes classification, we demonstrate that the task is feasible, although high accuracy can only be expected for a portion of all photos. Based on this observation, we stress the importance of adaptive approaches that estimate locations at different granularities for different photos.
General Rules for Predicting Where a Catalytic Reaction Should Occur on Metal Surfaces:  A Density Functional Theory Study of C−H and C−O Bond Breaking/Making on Flat, Stepped, and Kinked Metal Surfaces (2003)

To predict where a catalytic reaction should occur is a fundamental issue scientifically. Technologically, it is also important because it can facilitate the catalyst's design. However, to date, the understanding of this issue is rather limited. In this work, two types of reactions, CH(4) <--> CH(3) + H and CO <--> C + O on two transition metal surfaces, were chosen as model systems aiming to address in general where a catalytic reaction should occur. The dissociations of CH(4) --> CH(3) + H and CO --> C + O and their reverse reactions on flat, stepped, and kinked Rh and Pd surfaces were studied in detail. We find the following: First, for the CH(4) <--> Ch(3) + H reaction, the dissociation barrier is reduced by approximately 0.3 eV on steps and kinks as compared to that on flat surfaces. On the other hand, there is essentially no difference in barrier for the association reaction of CH(3) + H on the flat surfaces and the defects. Second, for the CO <--> C + O reaction, the dissociation barrier decreases dramatically (more than 0.8 eV on Rh and Pd) on steps and kinks as compared to that on flat surfaces. In contrast to the CH(3) + H reaction, the C + O association reaction also preferentially occurs on steps and kinks. We also present a detailed analysis of the reaction barriers in which each barrier is decomposed quantitatively into a local electronic effect and a geometrical effect. Our DFT calculations show that surface defects such as steps and kinks can largely facilitate bond breaking, while whether the surface defects could promote bond formation depends on the individual reaction as well as the particular metal. The physical origin of these trends is identified and discussed. On the basis of our results, we arrive at some simple rules with respect to where a reaction should occur: (i) defects such as steps are always favored for dissociation reactions as compared to flat surfaces; and (ii) the reaction site of the association reactions is largely related to the magnitude of the bonding competition effect, which is determined by the reactant and metal valency. Reactions with high valency reactants are more likely to occur on defects (more structure-sensitive), as compared to reactions with low valency reactants. Moreover, the reactions on late transition metals are more likely to proceed on defects than those on the early transition metals.
Reversal of inflammation‐associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin (2007)

Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1-AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression.
RNA-Catalyzed Carbon-Carbon Bond Formation (2001)

RNA molecules with catalytic properties have been isolated by in vitro selection from combinatorial libraries. A broad range of chemical reactions can be catalyzed, and nucleic acids can accelerate bond formation between small organic substrates. The catalytic performance of nucleic acids can be enhanced by incorporation of additional functional groups. This minireview focuses on carbon-carbon bond formation accelerated by in vitro selected ribozymes.
Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. (1988)

We have previously described the application of an automated microculture tetrazolium assay (MTA) involving dimethyl sulfoxide solubilization of cellular-generated 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-formazan to the in vitro assessment of drug effects on cell growth (M.C. Alley et al., Proc. Am. Assoc. Cancer Res., 27:389, 1986; M.C. Alley et al., Cancer Res. 48:589-601, 1988). There are several inherent disadvantages of this assay, including the safety hazard of personnel exposure to large quantities of dimethyl sulfoxide, the deleterious effects of this solvent on laboratory equipment, and the inefficient metabolism of MTT by some human cell lines. Recognition of these limitations prompted development of possible alternative MTAs utilizing a different tetrazolium reagent, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] -2H- tetrazolium hydroxide (XTT), which is metabolically reduced in viable cells to a water-soluble formazan product. This reagent allows direct absorbance readings, therefore eliminating a solubilization step and shortening the microculture growth assay procedure. Most human tumor cell lines examined metabolized XTT less efficiently than MTT; however, the addition of phenazine methosulfate (PMS) markedly enhanced cellular reduction of XTT. In the presence of PMS, the XTT reagent yielded usable absorbance values for growth and drug sensitivity evaluations with a variety of cell lines. Depending on the metabolic reductive capacity of a given cell line, the optimal conditions for a 4-h XTT incubation assay were 50 micrograms of XTT and 0.15 to 0.4 microgram of PMS per well. Drug profiles obtained with representative human tumor cell lines for several standard compounds utilizing the XTT-PMS methodology were similar to the profiles obtained with MTT. Addition of PMS appeared to have little effect on the metabolism of MTT. The new XTT reagent thus provides for a simplified, in vitro cell growth assay with possible applicability to a variety of problems in cellular pharmacology and biology. However, the MTA using the XTT reagent still shares many of the limitations and potential pitfalls of MTT or other tetrazolium-based assays.
Degradation of Partially Oxidized Alginate and Its Potential Application for Tissue Engineering (2001)

Alginate has been widely used in a variety of biomedical applications including drug delivery and cell transplantation. However, alginate itself has a very slow degradation rate, and its gels degrade in an uncontrollable manner, releasing high molecular weight strands that may have difficulty being cleared from the body. We hypothesized that the periodate oxidation of alginate, which cleaves the carbon-carbon bond of the cis-diol group in the uronate residue and alters the chain conformation, would result in promoting the hydrolysis of alginate in aqueous solutions. Alginate, oxidized to a low extent (approximately 5%), degraded with a rate depending on the pH and temperature of the solution. This polymer was still capable of being ionically cross-linked with calcium ions to form gels, which degraded within 9 days in PBS solution. Finally, the use of these degradable alginate-derived hydrogels greatly improved cartilage-like tissue formation in vivo, as compared to alginate hydrogels.
Assessment of left atrial appendage function by transesophageal echocardiography. Implications for the development of thrombus. (1991)

We conclude that the LAA has a characteristic pattern of emptying in sinus rhythm. LAA thrombus formation in sinus rhythm and atrial fibrillation is associated with both poor LAA contraction and LAA dilation.
Printable Thin Film Supercapacitors Using Single-Walled Carbon Nanotubes (2009)

Thin film supercapacitors were fabricated using printable materials to make flexible devices on plastic. The active electrodes were made from sprayed networks of single-walled carbon nanotubes (SWCNTs) serving as both electrodes and charge collectors. Using a printable aqueous gel electrolyte as well as an organic liquid electrolyte, the performances of the devices show very high energy and power densities (6 W h/kg for both electrolytes and 23 and 70 kW/kg for aqueous gel electrolyte and organic electrolyte, respectively) which is comparable to performance in other SWCNT-based supercapacitor devices fabricated using different methods. The results underline the potential of printable thin film supercapacitors. The simplified architecture and the sole use of printable materials may lead to a new class of entirely printable charge storage devices allowing for full integration with the emerging field of printed electronics.
Gantenerumab: A Novel Human Anti-Aβ Antibody Demonstrates Sustained Cerebral Amyloid-β Binding and Elicits Cell-Mediated Removal of Human Amyloid-β (2012)

The amyloid-β lowering capacity of anti-Aβ antibodies has been demonstrated in transgenic models of Alzheimer's disease (AD) and in AD patients. While the mechanism of immunotherapeutic amyloid-β removal is controversial, antibody-mediated sequestration of peripheral Aβ versus microglial phagocytic activity and disassembly of cerebral amyloid (or a combination thereof) has been proposed. For successful Aβ immunotherapy, we hypothesized that high affinity antibody binding to amyloid-β plaques and recruitment of brain effector cells is required for most efficient amyloid clearance. Here we report the generation of a novel fully human anti-Aβ antibody, gantenerumab, optimized in vitro for binding with sub-nanomolar affinity to a conformational epitope expressed on amyloid-β fibrils using HuCAL(®) phage display technologies. In peptide maps, both N-terminal and central portions of Aβ were recognized by gantenerumab. Remarkably, a novel orientation of N-terminal Aβ bound to the complementarity determining regions was identified by x-ray analysis of a gantenerumab Fab-Aβ(1-11) complex. In functional assays gantenerumab induced cellular phagocytosis of human amyloid-β deposits in AD brain slices when co-cultured with primary human macrophages and neutralized oligomeric Aβ42-mediated inhibitory effects on long-term potentiation in rat brain. In APP751(swedish)xPS2(N141I) transgenic mice, gantenerumab showed sustained binding to cerebral amyloid-β and, upon chronic treatment, significantly reduced small amyloid-β plaques by recruiting microglia and prevented new plaque formation. Unlike other Aβ antibodies, gantenerumab did not alter plasma Aβ suggesting undisturbed systemic clearance of soluble Aβ. These studies demonstrated that gantenerumab preferentially interacts with aggregated Aβ in the brain and lowers amyloid-β by eliciting effector cell-mediated clearance.
Differential Regulation of Airway Epithelial Integrins by Growth Factors (1996)

The pattern of integrin expression on human airway epithelium changes significantly in injury or inflammation. In particular, two integrins, the fibronectin receptor, alpha 5 beta 1 and the fibronectin/tenascin receptor alpha v beta 6, are expressed at low or undetectable levels in normal airways in vivo but are induced in response to airway epithelial injury. We investigated the effects of various growth factors known to be present in the airways on the expression of constitutively expressed and inducible airway epithelial integrins using flow cytometry. In primary cultures of human airway epithelial cells, transforming growth factor-beta 1 (TGF beta 1) dramatically increased expression of alpha v beta 6 and essentially did not affect the expression of any other integrin, including alpha 5 beta 1. In contrast, epidermal growth factor (EGF) upregulated surface levels of both alpha v beta 6 and alpha 5 beta 1. Together, TGF beta 1 and EGF had an additive effect on alpha v beta 6 and alpha 5 beta 1 expression while increasing levels of alpha 2 beta 1 and decreasing expression of alpha 3 beta 1- and alpha 6-containing integrins. In contrast, the transformed airway epithelial cell line, BEAS-2B, expressed a markedly different repertoire of integrins. Integrin expression on BEAS-2B cells was not affected by any of the growth factors tested in this study. These results demonstrate that, in primary cultures of human airway epithelial cells, the pattern of integrin expression can be dramatically altered by growth factors. The inducible integrins, alpha v beta 6, and alpha 5 beta 1 are most subject to regulation by growth factors and expression of each of these can be differentially regulated. The differential regulation of the two principal fibronectin receptors on airway epithelial cells suggests that they may mediate different cellular responses to fibronectin.
Molecular restriction of anti-DNP antibodies induced by (DNP)2-gramicidin S. (1975)

The molecular properties of anti-DNP antibodies were studied in 80 rabbits hyperimmunized with (DNP)2-gramicidin S. Unimmunized animals or those previously skin-painted with DNFB were subjected to biweekly injections of (DNP)2-gramicidin S. Isoelectric focusing revealed that the spectrotypes of the anti-DNP antibodies fell into three classifications; monoclonal, 18 to 21%; biclonal, 21 to 30%; and restricted, 14 to 26%. In each immunization protocol 35% of the rabbits did not respond. Longer time periods and more intensive immunization were necessary to achieve and anti-DMP response than with conventional DNP-protein conjugates, with skin painting tending to shorten the overall response time. The anti-DNP responses were invariant with respect to affinity and isoelectric spectra regardless of the immunization protocol or degree of restriction. Chain reassociation studies on antibodies purified from the sera of rabbits displaying monoclonal spectrotypes provide additional evidence that such antibodies are biosynthetically homogeneous. These data support the concept that carrier complexity influences the heterogeneity of the anti-hapten response but strongly suggests that the genetics of an outbred population may be an overriding factor in controlling response heterogeneity.
A power conversion system for offshore wind parks (2008)

This article presents a power conversion system for offshore wind parks based on a high voltage generation, high frequency AC link with bidirectional switches and DC power collection and transmission to shore. All the converters are located in the nacelle of the wind turbines and the turbines are connected in series on the output side of the AC/DC converter and connected to shore without any further transformation stages. The electrical system, from the generator to the grid connection of the turbine, is modeled in PSCAD. The model consists of an induction machine, a 3-phase AC to single phase AC converter, a high frequency high power transformer and a full-bridge converter. The AC-AC converter is based on bidirectional switches with reverse-blocking IGBTs and the switches are controlled with a dedicated switching pattern. The simulations show that the switching pattern gives the expected square wave voltage from the AC-AC converter. The new converter topology is expected to reduce the converter losses due to fewer converter stages, the architecture of the reverse-blocking IGBT and the new switching pattern.