gebhart/patrepeval huggingface dataset:
The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment (2009)

It is widely accepted that alterations to cyclooxygenase-2 (COX-2) expression and the abundance of its enzymatic product prostaglandin E(2) (PGE(2)) have key roles in influencing the development of colorectal cancer. Deregulation of the COX-2/PGE(2) pathway appears to affect colorectal tumorigenesis via a number of distinct mechanisms: promoting tumour maintenance and progression, encouraging metastatic spread, and perhaps even participating in tumour initiation. Here, we review the role of COX-2/PGE(2) signalling in colorectal tumorigenesis and highlight its ability to influence the hallmarks of cancer--attributes defined by Hanahan and Weinberg as being requisite for tumorigenesis. In addition, we consider components of the COX-prostaglandin pathway emerging as important regulators of tumorigenesis; namely, the prostanoid (EP) receptors, 15-hydroxyprostaglandin dehydrogenase and the prostaglandin transporter. Finally, based on recent findings, we propose a model for the cellular adaptation to the hypoxic tumour microenvironment that encompasses the interplay between COX-2, hypoxia-inducible factor 1 and dynamic switches in beta-catenin function that fine-tune signalling networks to meet the ever-changing demands of a tumour.
Observations on the Orexigenic Hypothalamic Neuropeptide Y‐System in Neonatally Overfed Weanling Rats (1999)

Early postnatal overnutrition is a risk factor for obesity in juvenile and adult life. Underlying pathophysiological mechanisms are still unclear. Hypothalamic neuropeptides are decisively involved in the regulation of body weight and food intake. In this study, we investigated consequences of early postnatal overnutrition, as compared to normo-and undernutrition, on NPY within the arcuate nucleus and paraventricular nucleus (PVN). The normal litter size of Wistar rats was adjusted on the third day of life from 10 pups (normal litters, NL; normonutrition) to only three newborns (small litters, SL; overnutrition) or 18 pups per mother (large litters, LL; undernutrition). SL rats developed clear overweight until the day 21 of life (P<0.0001), as well as hyperleptinaemia (P<0.001), and hyperinsulinaemia (P<0.01). LL rats were underweight and had decreased leptin and insulin concentrations. Using radioimmunoassay, NPY contents were determined in hypothalamic micropunches, and immunocytochemistry for NPY was performed in serial hypothalamic sections on day 21 of life. While in the underweight, hypoleptinaemic, and hypoinsulinaemic LL rats increased concentrations of NPY in the arcuate nucleus and PVN were observed, no decrease in NPY content was found in the overweight, hyperleptinaemic, and hyperinsulinaemic SL rats. Moreover, the percentage of NPY-immunopositive neurones per total number of neurones was increased not only in the LL rats, but also in the SL rats. Since the NPY system is functionally mature already at this age, these findings might indicate an acquired resistance of the hypothalamic NPY system to increased levels of insulin and/or leptin in early postnatally overfed SL rats.
A Practical and Highly Active Ruthenium-Based Catalyst that Effects the Cross Metathesis of Acrylonitrile (2002)

The highest initiation rate of any reported ruthenium-based catalyst was found for the new olefin-metathesis catalyst [(H2IMes)(3-Br-py)2(Cl)2RuCHPh] (1), which was synthesized in one step from commercially available reagents. Complex 1 is highly efficient for the cross metathesis of acrylonitrile, which is generally a poor substrate for metathesis reactions (e.g., see scheme). Mes=2,4,6-trimethylphenyl. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z19775_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Synthesis, Structure, and Aggregation-Induced Emission of a Novel Lambda (Λ)-Shaped Pyridinium Salt Based on Tröger's Base (2007)

A novel Λ-shaped pyridinium salt 2,8-(6H,12H-5,11-methanodibenzo[b,f]diazocineylene)-di(p-ethenyl-N-methyl-pyridinium) ditosylate (abbreviated as DMDPS) based on Tröger's base was designed, synthesized and characterized. DMDPS exhibits a typical aggregation-induced emission (AIE) behavior that is virtually nonemissive in solution but highly luminescent in solid state. The difference between the structure and the optical properties of DMDPS and 1,4-phenyl-di(p-ethenyl-N-methyl-pyridinium) ditosylate (abbreviated as DPPS) are analyzed and compared. It is concluded that the loose stacking caused by twisted molecular configuration could reduce the distance-dependent intermolecular quenching effect to produce intense fluorescence in the aggregation state while the enantiomerization and/or the intramolecular vibrational motion which induce the nonradiative deactivation process could cause fluorescence quenching in the solution. As a water-soluble AIE-active material, DMDPS would have potential application in the area of optical and biological research.
Construction of non-covalent single-chain Fv dimers for hepatocellular carcinoma and their biological functions (2010)

we have generated scFv dimers by shortening a series of linkers to 3-5 amino acid residues in VH-linker-VL orientation, resulting in highly stable and affinity-improved dimeric molecules. These will become an attractive targeting moiety in immunotherapeutic and diagnostic applications for HCC.
Inhibition and reversal of denervation-induced atrophy by the β-agonist growth promoter, clenbuterol (1986)

Dietary administration of the growth promoter, clenbuterol, ameliorated denervation-induced atrophy in rat soleus muscles. In acutely denervated muscles the drug inhibited the appearance of atrophy, and in chronically denervated muscles the atrophy was almost fully reversed. Responses in slow twitch oxidative fibres were particularly marked.
Biometric Security for Cell Phones (2009)

Cell phones are already prime targets for theft. The increasing functionality of cell phones is making them even more attractive. With the increase of cell phone functionality including personal digital assistance, banking, e-commerce, remote work, internet access and entertainment, more and more confidential data is stored on these devices. What is protecting this confidential data stored on cell phones? Studies have shown that even though most of the cell phone users are aware of the PIN security feature more than 50% of them are not using it either because of the lack of confidence in it or because of the inconvenience. A large majority of those users believes that an alternative approach to security would be a good idea.
Superhydrophobicity of Biological and Technical Surfaces under Moisture Condensation: Stability in Relation to Surface Structure (2008)

The stability of superhydrophobic properties of eight plants and four technical surfaces in respect to water condensation has been compared. Contact and sliding angles were measured after application of water drops of ambient temperature (20 degrees C) onto cooled surfaces. Water evaporating from the drops condensed, due to the temperature difference between the drops and the surface, on the cooled samples, forming "satellite droplets" in the vicinity of the drops. Surface cooling to 15, 10, and 5 degrees C showed a gradual decrease of superhydrophobicity. The decrease was dependent on the specific surface architecture of the sample. The least decrease was found on hierarchically structured surfaces with a combination of a coarse microstructure and submicrometer-sized structures, similar to that of the Lotus leaf. Control experiments with glycerol droplets, which show no evaporation, and thus no condensation, were carried out to verify that the effects with water were caused by condensation from the drop (secondary condensation). Furthermore, the superhydrophobic properties after condensation on cooled surfaces from a humid environment for 10 min were examined. After this period, the surfaces were covered with spherical water droplets, but most samples retained their superhydrophobicity. Again, the best stability of the water-repellent properties was found on hierarchically structured surfaces similar to that of the Lotus leaf.
Erythromycin resistance by ribosome modification (1995)

Free access1 March 1995 Share on Erythromycin resistance by ribosome modificationAuthor: B WeisblumAuthors Info & AffiliationsDOI: https://doi.org/10.1128/aac.39.3.577 PDF/EPUB
The Mechanism of Inhibition of Antibody-Based Inhibitors of the Serine Protease MT-SP1 (2008)

Due to the conserved nature of protease active sites, it has been difficult to develop protease inhibitors that are both potent and specific. The vast majority of both small molecule and naturally-occuring protein protease inhibitors target the active site, and while potent, are often promiscuous. With the goal of developing novel classes of protease inhibitors that would be both potent and specific, a phage-displayed antibody library was panned against the cancer-associated protease membrane-type serine protease 1 (MT-SP1). Two inhibitors were discovered from the screen, and their mechanism of inhibition was further studied to understand the basis of their potency and specificity. \tA number of kinetic and biochemical experiments revealed that while the two inhibitors, E2 and S4, bound to the enzyme with different binding mechanisms, they were both competitive inhibitors of both small-molecule and macromolecular MT-SP1 substrates. Mutational analysis by alanine scanning of the surface loops surrounding the protease active site revealed that the antibodies made numerous contacts with these loops. The surface loops are sites of natural diversity among closely related serine proteases, and created the epitope that allowed for antibody specificity. Taken together, these results suggest that these antibody inhibitors gain a measure of potency by binding in the protease active site, and additional potency and specificity through interactions with the protease surface loops. These strategies could be adapted in efforts to develop specific inhibitors against other proteases.\tA structure of the Fab construct of E2 in complex with the protease domain of MT-SP1 was determined by x-ray crystallography. The structure revealed that the inhibitor has a novel mechanism of inhibition; it gains potency and specificity through interactions with the protease surface loops, and inhibits by binding a very large H3 loop in the active site in a catalytically non-competent manner. \tThe results here illustrate that antibodies can be effective inhibitors because they can bind to features that traditional protease inhibitors do not. These lessons can be used to guide the development of molecules that can specifically inhibit any protease.
Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity (2010)

This paper uses the measure of hemolysis to evaluate the toxicity of nonporous and porous silica nanoparticles with varied sizes and investigates the effects of porous structure and integrity on the nanoparticle-cell interaction. The results show that both nonporous and porous silica cause red blood cell membrane damage in a concentration- and size-dependent manner. In the case of mesoporous silica nanoparticles, the size-dependent hemolysis effect is only present when the nanoparticles have long-range ordered porous structure, revealing that pore structure is critical in cell-nanoparticle interactions. Mesoporous silica nanoparticles show lower hemolytic activity than their nonporous counterparts of similar size, likely due to fewer silanol groups on the cell-contactable surface of the porous silica nanoparticles. The extent of hemolysis by mesoporous silica nanoparticles increases as the pore structure is compromised by mild aging in phosphate-buffered solutions, initiating mesopore collapse. The pore integrity of mesoporous silica nanoparticles is examined by TEM, XRD, N(2) adsorption-desorption isotherms, and quantification of dissolved silica. In these nanoparticles, pore stability is clearly an important factor in determining the hemolytic activity; further work demonstrates that nanoparticle-induced hemolysis can be eliminated by modifying the silanol surface with a poly(ethylene glycol) coating.
Energy transfer in a bioluminescent system (1971)

Abstract Many (but not all) of the bioluminescent systems in coelenter‐ates involve energy transfer from an excited product molecule of the calcium activated photoprotein to a second species, the green fluorescent protein, with emission at 508 nm from its excited state. Although all the luminescent coelen‐terates studied possess photoproteins, not all of them have the green fluorescent protein. This green fluorescent molecule is localized in the luminescent cells; they can thus be easily distinguished by fluorescence microscopy. The active components occur in subcellular particles; these have been isolated in an active form by homogenization in isotonic (to sea water) salt solutions.
Medical therapy for pulmonary arterial hypertension (2007)

Recent advances in the understanding of pulmonary arterial hypertension have led to new therapeutic options, although the disease remains incurable and continues to cause substantial morbidity and mortality. Disease-specific therapies have been approved for use in the US, including epoprostenol and its various analogs, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. The use of combination therapy with agents from more than one of these drug classes is becoming increasingly common, although guidelines establishing optimal combinations are lacking. Meanwhile, potential future therapeutic options are actively being pursued.
NO mediates gastric relaxation after brief vagal stimulation in anesthetized dogs (1995)

In vitro studies showed that relaxations induced after vagal stimulation of the guinea pig stomach are mediated via nitric oxide (NO). The role of NO in canine gastric relaxation in response to vagal stimulation has as yet not been studied. The present study examined the influence of NG-nitro-L-arginine (L-NNA) on gastric relaxations after vagal nerve stimulation in the anesthetized dog. In beagle dogs (n = 7), the ventral and dorsal abdominal vagal nerves were connected to a pair of platinum electrodes. Gastric tone was measured by means of a barostat. Changes in gastric motility were measured with force transducers sutured on the fundus and the antrum. The cervical vagi were sectioned, and dogs were given atropine (0.2 mg/kg i.v.) and guanethidine (5 mg/kg i.v.). Electrical stimulation of the vagal trunks (19 V, 1-ms duration, for 15 s every 2 min, 1-30 Hz) induced frequency-dependent increases in volume. On the fundus, frequency-dependent relaxations could be observed (maximal effect at 5 mmHg and at 10 Hz). During electrical stimulation, the spontaneous antral contractions were completely blocked. After cessation of the stimulus, "rebound" contractions could be observed. L-NNA (5 mg/kg i.v.) completely blocked the increases in gastric volume and the relaxations on the fundus. On the antrum, however, contractions were observed during the electrical stimulation. L-Arginine (250 mg/kg i.v.) gradually restored the relaxations on electrical stimulation. This study demonstrates that NO mediates short-lasting vagally induced gastric relaxations in the anesthetized dog.
Combining GLP ‐1 receptor agonists with insulin: therapeutic rationales and clinical findings (2012)

Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose-dependent manner, thus conferring glycaemic control with a low incidence of hypoglycaemia. GLP-1RAs also promote weight loss, and have beneficial effects on markers of β cell function, lipid levels, blood pressure and cardiovascular risk markers. However, the durability of their effectiveness is unknown and, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose. In this review, the physiological and pharmacological rationale for using GLP-1RA and insulin therapies in combination is discussed, and data from clinical studies that have assessed the efficacy and safety of this treatment strategy are outlined.
Gestió de la diversitat a les organitzacions esportives. Un acostament crític (2004)

Mentre que les organitzacions publiques i comercials dels Estats Units, el Canada, Australia, Gran Bretanya i, de forma creixent, les de la Unio Europea, han incorporat el concepte de “gestio de la diversitat”, les organitzacions esportives, ben al contrari, han prestat poca atencio a aquest tema. De fet, s’han resistit a intentar de millorar la representacio de la dona i de les minories racials i etniques. Aquest article examina la idea de “gestio de la diversitat” a la llum de la creixent critica als seus objectius, que es fa evident tant a la literatura academica com a la del sector de la gestio. La bibliografia relacionada amb l’esport, encara que escassa, es exageradament positiva pel que fa al concepte de gestio de la diversitat, i anima les organitzacions esportives a plantejar-se els beneficis de la gestio de la diversitat, pero fent cas omis de la important critica de que aquesta esta sent objecte en l’actualitat. La gestio de la diversitat, tal com s’enten avui dia, contribuira poc a la millora de la representacio de la dona en els llocs de presa de decisions i de lideratge dintre de les organitzacions esportives (el mateix es podria dir sobre la raca/etnia i d’altres grups socials).
The Chemistry of Water Treatment Processes Involving Ozone, Hydrogen Peroxide and Ultraviolet Radiation (1987)

Abstract Advanced oxidation processes are defined as those which involve the generation of hydroxyl radicals in sufficient quantity to affect water purification. The theoretical and (practical yield of OH from O3 at high pH, 03/H202, O3/UV and H2O2/UV systems is reviewed. New data is presented which illustrates the importance of direct photolysis in the O3/UV process, the effect of the H202:03 ratio in the O3/H2O2 process, and the impact of the low extinction coefficient of H2O2 in the H202/UV process.
Antioxidants, Oxidative Stress, and Degenerative Neurological Disorders (1999)

Recently, clinical trials of several neurodegenerative diseases have increasingly targeted the evaluation of the effectiveness of various antioxidants. The results so far are encouraging but variable and thus confusing. Rationale for the possible clinical effectiveness of antioxidants in several degenerative conditions has arisen out of the many years of basic science generally showing that reactive oxygen species (ROS) and oxidative damage are important factors in the processes involved. Aging is one of the most significant risk factors for degenerative neurological disorders. Basic science efforts in our laboratory have centered on exploring the role of ROS and oxidative stress in neurodegenerative processes. The present review brings together some of the basic concepts we have learned by following this approach for the last 20 years and specifically the results we have obtained by following up on our serendipitous findings that a nitrone-based free radical trap, alpha-phenyl-tert-butylnitrone (PBN), has neuroprotective activity in several experimental neurodegenerative models. The mechanistic basis of the neuroprotective activity of PBN does not appear to rely on its general free radical trapping or antioxidant activity per se, but its activity in mediating the suppression of genes induced by pro-inflammatory cytokines and other mediators associated with enhanced neuroinflammatory processes. Neuroinflammatory processes, induced in part by pro-inflammatory cytokines, yield enhanced ROS and reactive nitric oxide species (RNS) as well as other unknown components that have neurotoxic properties. Neurotoxic amounts of RNS are formed by the activity of inducible nitric oxide synthase (iNOS). The demonstration of enhanced 3-nitro-tyrosine formation in affected regions of the Alzheimer's brain, in comparison to age-matched controls, reinforces the importance of neuroinflammatory processes. iNOS induction involves activation by phosphorylation of the MAP kinase p38 and can be induced in cultured astrocytes by IL-1beta or H2O2. The action of PBN and N-acetyl cysteine to suppress the activation of p38 was demonstrated in cultured astrocytes. The demonstration of activated p38 in neurons surrounding amyloid plaques in affected regions of the Alzheimer's brain attest to enhanced signal transduction processes in this neurodegenerative condition. The major themes of ROS and RNS formation associated with neuroinflammation processes and the suppression of these processes by antioxidants and PBN continue to yield promising leads for new therapies. Outcomes of clinical trials on antioxidants will become less confusing as more knowledge is amassed on the basic processes involved.
Collaborative feature learning from social media (2015)

Image feature representation plays an essential role in image recognition and related tasks. The current state-of-the-art feature learning paradigm is supervised learning from labeled data. However, this paradigm requires large-scale category labels, which limits its applicability to domains where labels are hard to obtain. In this paper, we propose a new data-driven feature learning paradigm which does not rely on category labels. Instead, we learn from user behavior data collected on social media. Concretely, we use the image relationship discovered in the latent space from the user behavior data to guide the image feature learning. We collect a large-scale image and user behavior dataset from Behance.net. The dataset consists of 1.9 million images and over 300 million view records from 1.9 million users. We validate our feature learning paradigm on this dataset and find that the learned feature significantly outperforms the state-of-the-art image features in learning better image similarities. We also show that the learned feature performs competitively on various recognition benchmarks.
Natural Diversity to Guide Focused Directed Evolution (2010)

Simultaneous multiple site-saturation mutagenesis was performed at four active-site positions of an esterase from Pseudomonas fluorescens to improve its ability to convert 3-phenylbutyric acid esters (3-PBA) in an enantioselective manner. Based on an appropriate codon choice derived from a structural alignment of 1751 sequences of alpha/beta-hydrolase fold enzymes, only those amino acids were considered for library creation that appeared frequently in structurally equivalent positions. Thus, the number of mutants to be screened could be substantially reduced while the number of functionally intact variants was increased. Whereas the wild-type esterase showed only marginal activity and poor enantioselectivity (E(true)=3.2) towards 3-PBA-ethyl ester, a significant number of hits with improved rates (up to 240-fold) and enantioselectivities (up to E(true)=80) were identified in these "smart" libraries.