gebhart/patrepeval huggingface dataset:
[A new inclusion complex of silibinin and beta-cyclodextrins: in vitro dissolution kinetics and in vivo absorption in comparison with traditional formulations]. (1992)

The very low bioavailability of silybinin, the main constituent of silymarin, so far prevented the development of an oral pharmaceutical specialty based on this active ingredient. To overcome this difficulty, an inclusion complex between Silybinin and beta-Cyclodextrin was prepared. The new complex was compared in vitro tests (dissolution rate) and in a in vivo test (rat bile elimination) with silybinin, silymarin and one traditional formulation based on silybinin. The results show a dramatic increase in the dissolution rate of the complex (> 90% within 5 min) respect to the silybinin that confirm to be practically insoluble (< 5%). The in vivo results agree with the dissolution rates; after administration of the silybinin complex p.o., the silybinin concentration in the rat bile was near 20 times more than after administration of silybinin as is or in a traditional formulation. In the last two cases, the silybinin concentration was even 6 times less than after administration of the same amount of silymarin. These data show that the beta-CD complex solved the problem of the bioavailability of silybinin which, in the traditional formulation utilised as reference, proved to be not bioavailable.
Protection of Intellectual Property Rights in Computers and Computer Programs: Recent Developments (1982)

Disappearance of acetic acid was quantified to determine whether removal of this acid from the reticulorumen is altered when ruminal acetic acid concentrations are elevated. Ruminally fistulated beef steers (n = 3 per experiment; BW = 320 +/- 9 kg) were fed eight times daily a 46% corn-based concentrate:54% mixed hay diet to meet maintenance energy requirements (3.5 kg of DM/d). In situ production of acetic acid, determined by pulsed-continuous infusion of [1-14C]acetic acid, was 530 mmol/h (CV = 12%). Disappearance from the reticulorumen (i.e., presumed absorption) was 460 mmol/h (CV = 2%) or 87% (CV = 2%) of ruminal production. Variation is described within an operational steady state. Acetic acid concentrations were increased by continuous infusion of unlabeled acetic acid into the reticulorumen. Ruminal disappearance (mmol/h) increased when this simulated production was elevated up to and exceeding in situ rates reported previously (530 to 2,700 mmol/h). These data suggest that two-thirds to three-fourths of ruminal acetate production disappeared across the reticuloruminal wall when concentration was elevated; the complement exited from the rumen with the liquid phase. The reticulorumen has an additional capacity to remove acetic acid; however, it does so with an apparent reduced efficiency at higher production rates. Liquid out-flow may affect the efficiency of reticuloruminal disappearance. Sites distal to the rumen become quantitatively important when ruminal acetic acid concentrations are increased.
Paraoxonase and coronary heart disease (1998)

Paraoxonase (PON1) hydrolyses organophosphate insecticides and nerve gases and is responsible for determining the selective toxicity of these compounds in mammals. Human PON1 has two genetic polymorphisms giving rise to amino-acid substitutions at positions 55 and 192. The 192 polymorphism is the major determinant of the PON1 activity polymorphism towards organophosphates. However, the 55 polymorphism also modulates activity. Ex vivo, the PON1 polymorphisms are important in determining the capacity of HDL to protect LDL against oxidative modification in vitro and this may explain the relationship between the PON1 alleles and coronary heart disease in case-control studies. In recent case-control studies serum PON1 concentration and activity were also found to be decreased in coronary heart disease (CHD) independent of the PON1 polymorphism, and in diabetes serum PON1 specific activity decrease is also independent of the PON1 genetic polymorphism. HDL from transgenic mice lacking PON1 fails to protect LDL against oxidative modification. Thus PON1 may be a determinant of resistance to the development of atherosclerosis by protecting lipoproteins against oxidative modification, perhaps by hydrolysing phospholipid and cholesteryl-ester hydroperoxides.
Mucosal Administration of Ag85B-ESAT-6 Protects against Infection with Mycobacterium tuberculosis and Boosts Prior Bacillus Calmette-Guerin Immunity (2006)

We have examined the intranasal administration of a vaccine against Mycobacterium tuberculosis (M.tb) consisting of the mucosal adjuvant LTK63 and the Ag Ag85B-ESAT-6. Vaccination with LTK63/Ag85B-ESAT-6 gave a strong and sustained Th1 response mediated by IFN-gamma-secreting CD4 cells, which led to long-lasting protection against tuberculosis, equivalent to that observed with bacillus Calmette-Guérin (BCG) or Ag85B-ESAT-6 in dimethyldioctadecylammonium bromide/monophosphoryl lipid A. Because a crucial element of novel vaccine strategies is the ability to boost BCG-derived immunity, we also tested whether LTK63/Ag85B-ESAT-6 could act as a BCG booster vaccine in BCG-vaccinated mice. We found that vaccinating with LTK63/Ag85B-ESAT-6 strongly boosted prior BCG-stimulated immunity. Compared with BCG-vaccinated nonboosted mice, we observed that infection with M.tb led to a significant increase in anti-M.tb-specific CD4 T cells in the lungs of LTK63/Ag85B-ESAT-6-boosted animals. This correlated with a significant increase in the protection against M.tb in LTK63/Ag85B-ESAT-6-boosted mice, compared with BCG-vaccinated animals. Thus, LTK63/Ag85B-ESAT-6 represents an efficient preventive vaccine against tuberculosis with a strong ability to boost prior BCG immunity.
Carbon footprint in water sector. Case study for Bucharest (2017)

Climate change has become one of the most difficult problems facing the environment. Global warming is caused by social activities, such as burning fossil fuels and abrupt changes in land use, with severe consequences on human settlements worldwide. Judging by the way it manifests, global warming is a major problem facing urban centers of all sizes. Urban areas are the main sources of greenhouse gas (GHG) emissions, of which 72% of the total GHG emitted consists of carbon dioxide, 18% methane gas and 9% nitrous oxide. Carbon dioxide emissions play the most crucial factor in global warming and they are increasing each year almost 3% each year. The Intergovernmental Panel on Climate Change (IPCC) has developed a methodology to estimate the GHGs emissions including the water sector.
The discovery of labile methyl esters on proliferating cell nuclear antigen by MS/MS (2006)

The post-translational modification of proliferating cell nuclear antigen (PCNA) has been implicated in modulating its function for over 20 years. With multiple interacting partners, PCNA is involved in processes ranging from DNA replication and repair to cell cycle control and apoptosis. The ability of PCNA to distinguish between specific binding partners in different tasks is currently of intense interest, and several post-translational modifications have been reported to modulate its function. Unfortunately, these reports have produced contradictory information on the type(s) of modification present on the molecule. Here we report a detailed structural analysis of a single acidic PCNA isoform, cancer-specific polyferating nuclear anitgen (csPCNA), isolated from breast cancer cells by 2D-PAGE and LC-MS/MS. With this approach we fully characterized the csPCNA isoform and confidently identified a single post-translational modification, methyl esterification. Interestingly, the methyl esters consistently localized to 15 specific glutamic and aspartic acid residues of csPCNA. The methyl esterification of csPCNA represents a novel type of post-translational modification in mammalian cells that could ultimately hold the key towards unlocking its diverse functions.
A phase I clinical and pharmacokinetic study of tipifarnib in combination with docetaxel in patients with advanced solid malignancies (2007)

Although the high incidence of febrile neutropenia necessitated a multiple scheduling adaptation of tipifarnib compared to the original protocol, the apparent lack of mutual pharmacokinetic interactions, the ability to coadminister tipifarnib and docetaxel near single-agent MTDs, and suggestive evidence of efficacy make this drug combination attractive for further examination.
Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. (1990)

We studied 2254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase to determine whether graft-versus-leukemia (GvL) reactions are important in preventing leukemia recurrence after bone marrow transplantation. Four groups were investigated; recipients of non-T-cell depleted allografts without graft-versus-host disease (GvHD), recipients of non-T-cell depleted allografts with GvHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants compared with recipients of non-T-cell depleted allografts without GvHD, Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = 0.03), chronic (relative risk, 0.43, P = 0.01), and both acute and chronic GvHD (relative risk 0.33, P = 0.0001). These data support an anti-leukemia effect of GvHD. AML patients receiving identical twin transplants had an increased probability of relapse (relative risk 2.58, P = 0.008) compared to allograft recipients without GvHD supporting an anti-leukemia effect of allografts independent of GvHD. CML patients receiving T-cell depleted transplants without GvHD had a higher probability of relapse (relative risk 6.91, P = 0.0001) than recipients of non-T-cell depleted allografts without GvHD. These data support an antileukemia effect independent of GvHD altered by T-cell depletion. These results indicate that much of the anti-leukemia effect of bone marrow transplants is related to immune factors rather than high-dose chemotherapy and/or radiation.
Morbidity Profiles of Centenarians: Survivors, Delayers, and Escapers (2003)

These results suggest there may be multiple routes to achieving exceptional longevity and that there are sex differences according to which route is taken. These routes represent different phenotypes and thus likely different genotypes of centenarians. The identification of three types of centenarians, Survivors, Delayers, and Escapers, provides direction for future study into the factors that determine exceptional longevity.
Lanna Style (2014)

Abstract Just as spirit shrines, in their enactment of margin-center dynamics, acted as microcosms for how Chiang Mai elites positioned themselves vis-à-vis the forest, notions of charismatic potential outlined in the religious practices of Northern Thai spirit mediums have uncanny parallels in how Chiang Mai is positioned vis-à-vis Bangkok. Here, a nationalist-inflected “culture,” made manifest in architecture, film depictions, and other aesthetic representations, serves to replace the possessing spirit in determining progressive potential. Culture brokers represent Northern Thailand in a certain, Orientalized in ways that highlight Chiang Mai’s own marginality as well as its attractive potential. Recast not as a center, but as a periphery brimming with prosperous potential, Chiang Mai becomes malleable, feminized, and open to appropriation.
Materials selection and residual solvent retention in biodegradable electrospun fibers (2007)

Abstract Electrospun tissue engineering scaffolds provide mechanical support to seeded cells that populate the structure while depositing specific extracellular matrix components. The potent sterilizing agent 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) is often used in electrospinning investigations involving biologically‐derived polymers. Surprisingly, there has been no study of solvent retention versus composition even though materials selection should influence organic solvent content. We developed a method quantifying HFIP retention following electrospinning of gelatin, polycaprolactone (PCL), and PCL‐gelatin blends using electro‐spray mass spectroscopy. The acetone content of acetone‐spun PCL was also established. Pure gelatin fiber contained as much as 1600 ppm of HFIP. In contrast, little acetone or HFIP was detected in 100% PCL. Gelatin clearly has a greater affinity for HFIP than PCL and materials selection has a strong influence on the amount of retained solvent. Vacuum + heat treatment at 37 and 45ºC reduced [HFIP] to 10 and 5.6 ppm, respectively, levels having no demonstrated effects on mammalian cell viability. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Requirement for a Peptidoglycan Recognition Protein (PGRP) in Relish Activation and Antibacterial Immune Responses in Drosophila (2002)

Components of microbial cell walls are potent activators of innate immune responses in animals. For example, the mammalian TLR4 signaling pathway is activated by bacterial lipopolysaccharide and is required for resistance to infection by Gram-negative bacteria. Other components of microbial surfaces, such as peptidoglycan, are also potent activators of innate immune responses, but less is known about how those components activate host defense. Here we show that a peptidoglycan recognition protein, PGRP-LC, is absolutely required for the induction of antibacterial peptide genes in response to infection in Drosophila and acts by controlling activation of the NF-kappaB family transcription factor Relish.
Qualitative and quantitative evaluation of Simon™, a new CE‐based automated Western blot system as applied to vaccine development (2012)

Many CE-based technologies such as imaged capillary IEF, CE-SDS, CZE, and MEKC are well established for analyzing proteins, viruses, or other biomolecules such as polysaccharides. For example, imaged capillary isoelectric focusing (charge-based protein separation) and CE-SDS (size-based protein separation) are standard replacement methods in biopharmaceutical industries for tedious and labor intensive IEF and SDS-PAGE methods, respectively. Another important analytical tool for protein characterization is a Western blot, where after size-based separation in SDS-PAGE the proteins are transferred to a membrane and blotted with specific monoclonal or polyclonal antibodies. Western blotting analysis is applied in many areas such as biomarker research, therapeutic target identification, and vaccine development. Currently, the procedure is very manual, laborious, and time consuming. Here, we evaluate a new technology called Simple Western™ (or Simon™) for performing automated Western analysis. This new technology is based on CE-SDS where the separated proteins are attached to the wall of capillary by a proprietary photo activated chemical crosslink. Subsequent blotting is done automatically by incubating and washing the capillary with primary and secondary antibodies conjugated with horseradish peroxidase and detected with chemiluminescence. Typically, Western blots are not quantitative, hence we also evaluated the quantitative aspect of this new technology. We demonstrate that Simon™ can quantitate specific components in one of our vaccine candidates and it provides good reproducibility and intermediate precision with CV <10%.
Apoptosis of leukemic cells accompanies reduction in intracellular pH after targeted inhibition of the Na+/H+exchanger (2000)

The Na(+)/H(+) exchanger isoform 1 (NHE1) is primarily responsible for the regulation of intracellular pH (pH(i)). It is a ubiquitous, amiloride-sensitive, growth factor-activatable exchanger whose role has been implicated in cell-cycle regulation, apoptosis, and neoplasia. Here we demonstrate that leukemic cell lines and peripheral blood from primary patient leukemic samples exhibit a constitutively and statistically higher pH(i) than normal hematopoietic tissue. We then show that a direct correlation exists between pH(i) and cell-cycle status of normal hematopoietic and leukemic cells. Advantage was taken of this relationship by treating leukemic cells with the Na(+)/H(+) exchanger inhibitor, 5-(N, N-hexamethylene)-amiloride (HMA), which decreases the pH(i) and induces apoptosis. By incubating patient leukemic cells in vitro with pharmacologic doses of HMA for up to 5 hours, we show, using flow cytometry and fluorescent ratio imaging microscopy, that when the pH(i) decreases, apoptosis-measured by annexin-V and TUNEL methodologies-rapidly increases so that more than 90% of the leukemic cells are killed. The differential sensitivity exhibited between normal and leukemic cells allows consideration of NHE1 inhibitors as potential antileukemic agents. (Blood. 2000;95:1427-1434)
Regulation of Lymphocyte Function by PPARγ: Relevance to Thyroid Eye Disease‐Related Inflammation (2008)

Thyroid eye disease (TED) is an autoimmune condition in which intense inflammation leads to orbital tissue remodeling, including the accumulation of extracellular macromolecules and fat. Disease progression depends upon interactions between lymphocytes and orbital fibroblasts. These cells engage in a cycle of reciprocal activation which produces the tissue characteristics of TED. Peroxisome proliferator‐activated receptor‐ γ (PPAR γ ) may play divergent roles in this process, both attenuating and promoting disease progression. PPAR γ has anti‐inflammatory activity, suggesting that it could interrupt intercellular communication. However, PPAR γ activation is also critical to adipogenesis, making it a potential culprit in the pathological fat accumulation associated with TED. This review explores the role of PPAR γ in TED, as it pertains to crosstalk between lymphocytes and fibroblasts and the development of therapeutics targeting cell‐cell interactions mediated through this signaling pathway.
Dried Blood Spot Specimens Are a Suitable Alternative Sample Type for HIV-1 Viral Load Measurement and Drug Resistance Genotyping in Patients Receiving First-Line Antiretroviral Therapy (2012)

Our results indicate that DBS specimens could be used for surveys to monitor HIVDR prevention failure in resource-limited settings.
Activation of Neural and Pluripotent Stem Cell Signatures Correlates with Increased Malignancy in Human Glioma (2011)

The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal- and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.
Hedgehog pathway activation in human transitional cell carcinoma of the bladder (2012)

We observed constitutive activation of the Hh pathway in most NMIBC and about 50% of MIBC. We also found that some protein-coding genes and miRNAs involved in the Hh pathway may have prognostic value at the individual level.
Supramolecular Assembly of Amelogenin Nanospheres into Birefringent Microribbons (2005)

Although both tooth enamel and bone are composed of organized assemblies of carbonated apatite crystals, enamel is unusual in that it does not contain collagen nor does it remodel. Self-assembly of amelogenin protein into nanospheres has been recognized as a key factor in controlling the oriented and elongated growth of carbonated apatite crystals during dental enamel biomineralization. We report the in vitro formation of birefringent microribbon structures that were generated through the supramolecular assembly of amelogenin nanospheres. These microribbons have diffraction patterns that indicate a periodic structure of crystalline units along the long axis. The growth of apatite crystals orientated along the c axis and parallel to the long axes of the microribbons was observed in vitro. The linear arrays (chains) of nanospheres observed as intermediate states before the microribbon formation give an important indication as to the function of amelogenin in controlling the oriented growth of apatite crystals during enamel mineralization.
The Human Estrogen Receptor-α Is a Ubiquitinated Protein Whose Stability Is Affected Differentially by Agonists, Antagonists, and Selective Estrogen Receptor Modulators (2001)

The human estrogen receptor alpha-isoform (ERalpha) is a nuclear transcription factor that displays a complex pharmacology. In addition to classical agonists and antagonists, the transcriptional activity of ERalpha can be regulated by selective estrogen receptor modulators, a new class of drugs whose relative agonist/antagonist activity is determined by cell context. It has been demonstrated that the binding of different ligands to ERalpha results in the formation of unique ERalpha-ligand conformations. These conformations have been shown to influence ERalpha-cofactor binding and, therefore, have a profound impact on ERalpha pharmacology. In this study, we demonstrate that the nature of the bound ligand also influences the stability of ERalpha, revealing an additional mechanism by which the pharmacological activity of a compound is determined. Of note we found that although all ERalpha-ligand complexes can be ubiquitinated and degraded by the 26 S proteasome in vivo, the mechanisms by which they are targeted for proteolysis appear to be different. Specifically, for agonist-activated ERalpha, an inverse relationship between transcriptional activity and receptor stability was observed. This relationship does not extend to selective estrogen receptor modulators and pure antagonists. Instead, it appears that with these compounds, the determinant of receptor stability is the ligand-induced conformation of ERalpha. We conclude that the different conformational states adopted by ERalpha in the presence of different ligands influence transcriptional activity directly by regulating cofactor binding and indirectly by modulating receptor stability.
Acceptor specificity of GDP-Fuc:Galβ1→4GlcNAc-R α3-fucosyltransferase VI (FucT VI) expressed in insect cells as soluble, secreted enzyme (1997)

As an extension of previous study (de Vries et al., 1995, J. Biol. Chem., 270, 8712-8722) the acceptor specificity of recombinant FucT VI, expressed in insect cells as soluble enzyme, and purified from the growth medium by affinity chromatography, was analyzed toward a broad panel of oligosaccharide and glycoprotein substrates. It was found that FucT VI effectively utilizes any type-2-chain based structure (Gal beta 1-->4GlcNAc-R). Neutral as well as sialylated structures are fucosylated with high efficiency. To identify polar groups on acceptors that function in enzyme binding, deoxygenated substrate analogs were tested as acceptors. FucT VI had an absolute requirement for a hydroxyl at C-6 of galactose in addition to the accepting hydroxyl at C-3. Thus, FucT VI, although different from FucT III, IV, and V in acceptor properties, seems to bind the acceptor in a similar way.