gebhart/patrepeval huggingface dataset:
Oxidation of Methionine Residues to Methionine Sulfoxides Does Not Decrease Potential Antiatherogenic Properties of Apolipoprotein A-I (2000)

The initial stage of oxidation of high density lipoproteins (HDL) is accompanied by the lipid hydroperoxide-dependent, selective oxidation of two of the three Met residues of apolipoprotein A-I (apoA-I) to Met sulfoxides (Met(O)). Formation of such selectively oxidized apoA-I (i.e. apoA-I(+32)) may affect the antiatherogenic properties of HDL, because it has been suggested that Met(86) and Met(112) are important for cholesterol efflux and Met(148) is involved in the activation of lecithin:cholesterol acyl transferase (LCAT). We therefore determined which Met residues were oxidized in apoA-I(+32) and how such oxidation of apoA-I affects its secondary structure, the affinity for lipids, and its ability to remove lipids from human macrophages. We also assessed the capacity of discoidal reconstituted HDL containing apoA-I(+32) to act as substrate for LCAT, and the dissociation of apoA-I and apoA-I(+32) from reconstituted HDL. Met(86) and Met(112) were present as Met(O), as determined by amino acid sequencing and mass spectrometry of isolated peptides derived from apoA-I(+32). Selective oxidation did not alter the alpha-helicity of lipid-free and lipid-associated apoA-I as assessed by circular dichroism, and the affinity for LCAT was comparable for reconstituted HDL containing apoA-I or apoA-I(+32). Cholesteryl ester transfer protein mediated the dissociation of apoA-I more readily from reconstituted HDL containing apoA-I(+32) than unoxidized apoA-I. Also, compared with native apoA-I, apoA-I(+32) had a 2- to 3-fold greater affinity for lipid (as determined by the rate of clearance of multilamellar phospholipid vesicles) and its ability to cause efflux of [(3)H]cholesterol, [(3)H]phospholipid, and [(14)C]alpha-tocopherol from lipid-laden human monocyte-derived macrophages was significantly enhanced. By contrast, no difference was observed for cholesterol and alpha-tocopherol efflux to lipid-associated apolipoproteins. Together, these results suggest that selective oxidation of Met residues enhances rather than diminishes known antiatherogenic activities of apoA-I, consistent with the overall hypothesis that detoxification of lipid hydroperoxides by HDL is potentially antiatherogenic.
Neural correlates of the LSD experience revealed by multimodal neuroimaging (2016)

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
Diagnosis and treatment of low back pain (2006)

Low back pain is a considerable health problem in all developed countries and is most commonly treated in primary healthcare settings. It is usually defined as pain, muscle tension, or stiffness localised below the costal margin and above the inferior gluteal folds, with or without leg pain (sciatica). The most important symptoms of non-specific low back pain are pain and disability. The diagnostic and therapeutic management of patients with low back pain has long been characterised by considerable variation within and between countries among general practitioners, medical specialists, and other healthcare professionals.1 2 w1 Recently, a large number of randomised clinical trials have been done, systematic reviews have been written, and clinical guidelines have become available. The outlook for evidence based management of low back pain has greatly improved. This review presents the current state of science regarding the diagnosis and treatment of low back pain.

We used the Cochrane Library to identify relevant systematic reviews that evaluate the effectiveness of conservative, complementary, and surgical interventions. Medline searches were used to find other relevant systematic reviews on diagnosis and treatment of low back pain, with the keywords “low back pain”, “systematic review”, “meta-analysis”, “diagnosis”, and “treatment”. Our personal files were used for additional references. We also checked available clinical guidelines and used Clinical Evidence as source for clinically relevant information on benefits and harms of treatments.3 4

Most of us will experience at least one episode of low back pain during our life. Reported lifetime prevalence varies from 49% to 70% and point prevalences from 12% to 30% are reported in Western countries.w2 w3

The diagnostic process is mainly focused on the triage of patients with specific or non-specific low back pain. Specific low back pain is defined as symptoms caused by a specific pathophysiological mechanism, such …
Distinct Kinetics for Binding of the CD46 and SLAM Receptors to Overlapping Sites in the Measles Virus Hemagglutinin Protein (2002)

Measles virus (MV) is a human pathogen using two distinct cell surface receptors for entry into host cells. We present here a comparative analysis for binding of the MV receptors CD46 and SLAM to the measles virus hemagglutinin protein (MVH, Edmonston strain). Soluble monomeric and dimeric MVH variants were prepared in mammalian cells and their conformation assessed using a panel of monoclonal antibodies. The two receptor molecules specifically bound to the MVH protein with distinct binding modes. The association rate (k(a)) for SLAM binding to MVH was very low ( approximately 3000 m(-1)s(-1)), about 20 times lower that the k(a) determined for CD46 binding. However, SLAM bound tighter to the virus protein than CD46, as revealed by a 5-fold lower dissociation rate (k(d), approximately 1.5 x 10(-3) s(-1)). These data suggest that the SLAM receptor binds to a less accessible and more hydrophobic surface on MVH than the CD46 receptor, as illustrated in a binding model. Despite the differences in kinetics, receptor competition binding experiments revealed that they recognize overlapping sites in MVH. Indeed, a panel of anti-MVH monoclonal antibodies equally inhibited binding of both receptor molecules. The similar immune reactivity of the two receptor binding sites suggests that the shift in receptor usage by MV may not be driven by immune responses.
Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis (1998)

The murine Bmp8a and Bmp8b genes are tightly linked on mouse chromosome 4 and have similar expression during reproduction. Previous studies have shown that targeted mutagenesis of Bmp8b causes male infertility due to germ cell degeneration. To investigate the function of Bmp8a, we have inactivated the gene by homologous recombination. Heterozygous and homozygous Bmp8a mutants reveal normal embryonic and postnatal development. Despite high levels of Bmp8a expression in the deciduum, homozygous mutant females have normal fertility, suggesting that the gene is not essential for female reproduction. Bmp8a and Bmp8b are expressed in similar patterns in male germ cells. Unlike homozygous Bmp8btm1 mutants, homozygous Bmp8atm1 males do not show obvious germ cell defects during the initiation of spermatogenesis. However, germ cell degeneration is observed in 47% of adult homozygous Bmp8atm1 males, establishing a role of Bmp8a in the maintenance of spermatogenesis. A small proportion of the mating homozygous Bmp8atm1 males also show degeneration of the epididymal epithelium, indicating a novel role for BMPs in the control of epididymal function.
Sequence and structure of Clp P, the proteolytic component of the ATP-dependent Clp protease of Escherichia coli. (1990)

The ATP-dependent Clp protease of Escherichia coli contains two dissimilar components: the Clp A regulatory polypeptide, with two ATP binding sites and intrinsic ATPase activity, and the Clp P subunit, which contains the proteolytic active site. The DNA sequence of the clpP gene predicts a protein of 207 amino acids (Mr 21,679), which is in close agreement with the size determined by sodium dodecyl sulfate-gel electrophoresis of purified Clp P. Clp P has a native Mr of approximately 240,000, and electron micrographs of the protein show superimposed disk-like structures with a central cavity, similar in appearance to purified proteasomes from eukaryotic cells. Clp P is synthesized with a 14-amino acid leader which is rapidly cleaved in vivo to yield the 193-amino acid protein which has activity in vitro. The clpP gene is at 10 min on the E. coli map, close to that for the ATP-dependent Lon protease of E. coli and far from the gene for clpA. Primer extension experiments indicate that transcription initiates immediately upstream of the coding region for Clp P, with a major transcription start at 120 bases in front of the start of translation. Insertion mutations in clpP have been isolated and transferred to the chromosome; strains devoid of Clp P are viable in the presence or absence of Lon protease. Mutations in clpP stabilize the same Clp A-beta-galactosidase fusion protein specifically stabilized by clpA mutations, providing the first genetic evidence that Clp A and Clp P act together in vivo.
Diffusion NMR Spectroscopy in Supramolecular and Combinatorial Chemistry: An Old Parameter—New Insights (2004)

Intermolecular interactions in solution play an important role in molecular recognition, which lies at the heart of supramolecular and combinatorial chemistry. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for simultaneously measuring diffusion coefficients of multicomponent systems. The diffusion coefficient reflects the effective size and shape of a molecular species. Applications of this technique include the estimation of association constants and mapping the intermolecular interactions in multicomponent systems as well as investigating aggregation, ion pairing, encapsulation, and the size and structure of labile systems. Diffusion NMR spectroscopy can also be used to virtually separate mixtures and screen for specific ligands of different receptors, and may assist in finding lead compounds.
PMMA Microspheres for Intradermal Implantation: Part I. Animal Research (1991)

In search of a biocompatible implant for the correction of small deficiencies within the dermal corium as in wrinkles and acne scars, polymethylmethacrylate (PMMA) microspheres, 10 to 63 microns in diameter, were dispersed in Tween 80 medium and injected intradermally and subdermally into the abdominal skin of rats. Histological examination of specimens for up to 7 months revealed a modest tissue reaction, forming a delicate fibrous capsule around each individual microsphere within 4 months. Foreign body giant cells were seen rarely (in up to 1.5% of all cells). No break-down, corrosion, or phagocytosis of the spheres was observed at 7 months. The Tween 80 dispersion medium did not produce any histologically detectable reaction. Because PMMA products (Paladon, Palacos) have been used in medicine for almost 50 years without causing biological degradation or cancer, the material may be applied safely in the form of microspheres (Arteplast) in corium and subcutis of human patients with wrinkles or acne scars.
VirtualBox: bits and bytes masquerading as machines (2008)

Reconfiguring your existing system to do something new is painful. Using VirtualBox is not.
First Korean Case of Infantile Hypophosphatasia with Novel Mutation in ALPL and Literature Review. (2016)

Hypophosphatasia is a rare hereditary disorder characterized by defective bone and tooth mineralization and deficiency of tissue non-specific alkaline phosphatase activity. The prognosis for the infantile form is poor, with approximately 50% of patients dying within the first year of life from respiratory failure. We describe the clinical and biochemical findings as well as the molecular analysis of a Korean boy with infantile hypophosphatasia and present a literature review. A 1-month-old boy visited the clinic because of poor feeding, frequent vomiting, hypotonia, and failure to thrive from birth. Laboratory tests revealed high total calcium, low phosphorous, low alkaline phosphatase, low parathyroid hormone, and normal 25-hydroxyvitamin D. Intravenous hydration with normal saline was started, and dietary calcium intake was restricted. Skeletal X-rays showed a markedly increased distance of the anterior fontanelle, impaired mineralization, and rachitic changes in the metaphyses. By Sanger sequencing of the ALPL gene, we identified two heterozygous variants, including a missense (c.334G>A; p.Gly112Ser) and a nonsense (c.1039C>T; p.Gln347*) variant. The c.334G>A (p.Gly112Ser) variant had previously been reported in a patient with lethal type hypophosphatasia, while the nonsense c.1039C>T (p.Gln347*) variant was novel. In the current case, the accurate diagnosis and prompt intervention-including dietary calcium intake restriction, tracheostomy to prevent progression to respiratory failure, and fundoplication with gastrostomy to ensure the administration of adequate calories-seemed to play an important role for avoiding preventable morbidity and premature mortality.
Comparative resistance of the 20S and 26S proteasome to oxidative stress (1998)

Oxidatively modified ferritin is selectively recognized and degraded by the 20S proteasome. Concentrations of hydrogen peroxide (H2O2) higher than 10 micromol/mg of protein are able to prevent proteolytic degradation. Exposure of the protease to high amounts of oxidants (H2O2, peroxynitrite and hypochlorite) inhibits the enzymic activity of the 20S proteasome towards the fluorogenic peptide succinyl-leucine-leucine-valine-tyrosine-methylcoumarylamide (Suc-LLVY-MCA), as well as the proteolytic degradation of normal and oxidant-treated ferritin. Fifty per cent inhibition of the degradation of the protein substrates was achieved using 40 micromol of H2O2/mg of proteasome. No change in the composition of the enzyme was revealed by electrophoretic analysis up to concentrations of 120 micromol of H2O2/mg of proteasome. In further experiments, it was found that the 26S proteasome, the ATP- and ubiquitin-dependent form of the proteasomal system, is much more susceptible to oxidative stress. Whereas degradation of the fluorogenic peptide, Suc-LLVY-MCA, by the 20S proteasome was inhibited by 50% with 12 micromol of H2O2/mg, 3 micromol of H2O2/mg was enough to inhibit ATP-stimulated degradation by the 26S proteasome by 50%. This loss in activity could be followed by the loss of band intensity in the non-denaturing gel. Therefore we concluded that the 20S proteasome was more resistant to oxidative stress than the ATP- and ubiquitin-dependent 26S proteasome. Furthermore, we investigated the activity of both proteases in K562 cells after H2O2 treatment. Lysates from K562 cells are able to degrade oxidized ferritin at a higher rate than non-oxidized ferritin, in an ATP-independent manner. This effect could be followed even after treatment of the cells with H2O2 up to a concentration of 2mM. The lactacystin-sensitive ATP-stimulated degradation of the fluorogenic peptide Suc-LLVY-MCA declined, after treatment of the cells with 1mM H2O2, to the same level as that obtained without ATP stimulation. Therefore, we conclude that the regulation of the 20S proteasome by various regulators takes place during oxidative stress. This provides further evidence for the role of the 20S proteasome in the secondary antioxidative defences of mammalian cells.
Impact of Intrauterine Growth Retardation and Body Proportionality on Fetal and Neonatal Outcome (1990)

Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)
Manipulating Cellular Activities Using an Ultrasound–Chemical Hybrid Tool (2017)

We developed an ultrasound-chemical hybrid tool to precisely manipulate cellular activities. A focused ultrasound coupled with gas-filled microbubbles was used to rapidly trigger the influx of membrane-impermeable chemical dimerizers into living cells to regulate protein dimerization and location without inducing noticeable toxicity. With this system, we demonstrated the successful modulation of phospholipid metabolism triggered by a short pulse of ultrasound exposure. Our technique offers a powerful and versatile tool for using ultrasound to spatiotemporally manipulate the cellular physiology in living cells.
Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice (2011)

The role of the Notch signaling pathway in tumor development is complex, with Notch1 functioning either as an oncogene or as a tumor suppressor in a context-dependent manner. To further define the role of Notch1 in tumor development, we systematically surveyed for tumor suppressor activity of Notch1 in vivo. We combined the previously described Notch1 intramembrane proteolysis-Cre (Nip1::Cre) allele with a floxed Notch1 allele to create a mouse model for sporadic, low-frequency loss of Notch1 heterozygosity. Through this approach, we determined the cell types most affected by Notch1 loss. We report that the loss of Notch1 caused widespread vascular tumors and organism lethality secondary to massive hemorrhage. These findings reflected a cell-autonomous role for Notch1 in suppressing neoplasia in the vascular system and provide a model by which to explore the mechanism of neoplastic transformation of endothelial cells. Importantly, these results raise concerns regarding the safety of chronic application of drugs targeting the Notch pathway, specifically those targeting Notch1, because of mechanism-based toxicity in the endothelium. Our strategy also can be broadly applied to induce sporadic in vivo loss of heterozygosity of any conditional alleles in progenitors that experience Notch1 activation.
Bundling Decisions by a Multiproduct Monopolist with Incomplete Information (1983)

This paper analyzes bundling decisions of a rnultiproduct monopolist facing uncertain&#13;\ndemand. The monopolist sells his products using an auction mechanism and the market is&#13;\nanalyzed as a game with incomplete information in which the buyers as well as the seller&#13;\nare strategic agents. With a small number of buyers, a profit maximizing seller will bundle&#13;\nall his output. This makes buyers uniformly worse off compared to the case where the same&#13;\nmonopolist does not bundle, in the sense that any buyer is worse off regardless of his&#13;\ndemand for the monopolist's outputs. With a larger number of buyers, the seller will have a&#13;\ntendency to unbundle his output and "high-demand" buyers are worse off than they would&#13;\nbe if the monopolist bundled his output. "Low-demand" buyers. on the other hand. are&#13;\nalways better off when the monopolist unbundles his output, regardless of the number of&#13;\ncompeting buyers. Despite the fact that "high demand" buyers are the typical purchasers&#13;\nof the monopolist's output, the net effect of increasing the number of buyers is greater&#13;\nmarket efficiency since bundling creates market inefficiencies both ex post and ex ante.
Effect of the E4 region on the persistence of transgene expression from adenovirus vectors (1997)

The utility of adenovirus vectors for gene therapy is limited by the transience of expression that has been observed in various in vivo models. Immunological responses to viral targets can eliminate transduced cells and cause the loss of transgene expression. We previously described the characterization of an E4 modified adenovirus, Ad2E4ORF6, which is replication defective in cotton rats. We reasoned that gene transfer vectors based on Ad2E4ORF6 would have a reduced potential for viral gene expression in vivo which might be beneficial for achieving persistence of transgene expression. E1 replacement vectors expressing the cystic fibrosis transmembrane regulator or beta-galactosidase were constructed as series of vectors that differed with respect to the E4 region. Vectors containing a wild-type E4 region, E4 open reading frame 6, or a complete E4 deletion were compared in the lungs of BALB/c mice for persistence of expression. Results obtained with nude mice indicate that nonimmunological factors have a major influence on the longevity of transgene expression. Expression was transient from the E1a promoter with all vectors but persisted from the cytomegalovirus promoter only with a vector containing a wild-type E4 region. Transience of expression did not correlate with the disappearance of vector DNA, suggesting that promoter down-regulation may be involved. Coinfection studies indicate an E4 product(s) could be supplied in trans to allow persistent expression from the cytomegalovirus promoter. In summary, the choice of promoter is important for achieving persistence of expression; in addition, some promoters are highly influenced by the context of the vector backbone.