gebhart/patrepeval huggingface dataset:
Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy (2007)

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by mutation of the telomeric survival motor neuron 1 (SMN1) gene with retention of the centromeric SMN2 gene. We sought to establish whether the potent and specific hydroxamic acid class of histone deacetylase (HDAC) inhibitors activates SMN2 gene expression in vivo and modulates the SMA disease phenotype when delivered after disease onset. Single intraperitoneal doses of 10 mg/kg trichostatin A (TSA) in nontransgenic and SMA model mice resulted in increased levels of acetylated H3 and H4 histones and modest increases in SMN gene expression. Repeated daily doses of TSA caused increases in both SMN2-derived transcript and SMN protein levels in neural tissues and muscle, which were associated with an improvement in small nuclear ribonucleoprotein (snRNP) assembly. When TSA was delivered daily beginning on P5, after the onset of weight loss and motor deficit, there was improved survival, attenuated weight loss, and enhanced motor behavior. Pathological analysis showed increased myofiber size and number and increased anterior horn cell size. These results indicate that the hydroxamic acid class of HDAC inhibitors activates SMN2 gene expression in vivo and has an ameliorating effect on the SMA disease phenotype when administered after disease onset.
β-Methylation of the Phe7and Trp9Melanotropin Side Chain Pharmacophores Affects Ligand−Receptor Interactions and Prolonged Biological Activity (1997)

Topographically modified melanotropin side chain pharmacophore residues Phe7 and Trp9 in a cyclic peptide template (Ac-Nle4-c[Asp-His-Xaa7-Arg-Yaa9-Lys]-NH2) and Phe7 in a linear peptide template (Ac-Ser-Tyr-Ser-Nle4-Glu-His-Xaa7-Arg-Trp-Gly-Lys-Pro-Val-NH2) result in differences in potency and prolonged biological activity in the frog and lizard skin bioassays. These topographic modifications included the four isomers of beta-methylphenylalanine (beta-MePhe)7 and beta-methyltryptophan (beta-MeTrp)9 and the two isomers of 1,2,3,4-tetrahydro-beta-carboline (Tca)9 Modifications in the cyclic template resulted in up to a 1000-fold difference in potency for the beta-MePhe7 stereoisomeric peptides; up to a 476-fold difference in potency resulted for the beta-MeTrp9 peptides, and about a 50-fold difference between the Tca9-containing peptides. Up to a 40-fold difference in potency resulted for the beta-MePhe7 stereoisomeric peptides using the linear template in these assays. The relative potency ranking for modifications in the cyclic template of beta-MePhe7 were 2R,3S > 2S,3S = 2S,3R > 2R,3R in the frog assay and 2S,3R > 2R,3S > 2S,3S > 2R,3R in the lizard assay. The relative potencies for modifications in the cyclic template of beta-MeTrp9 were 2R,3S > 2R,3R > 2S,3S > > 2S,3R in the frog assay and 2S,3S = 2R,3R > 2R,3S > 2S,3R in the lizard assay. The relative potencies for modifications in the cyclic template of Tca9 were DTca > LTca in both assays. Significant differences in prolonged (residual) activities were also observed for these modified peptides and were dependent upon stereochemistry of the beta-methyl amino acid, peptide template, and bioassay system. Furthermore, comparisons of beta-MeTrp9 stereoisomeric peptides on the frog, lizard, and human MC1 receptors suggest that structure-activity relationships on both the classical frog and lizard skin bioassays do not necessarily predict corresponding SAR profiles for the human melanocortin receptors, indicating a remarkable species specificity of the MC1 receptor requirements.
Mutants at the 2-Fold Interface of Adeno-associated Virus Type 2 (AAV2) Structural Proteins Suggest a Role in Viral Transcription for AAV Capsids (2016)

Many viruses package enzymes within their capsids that assist in expressing their genomes postinfection, e.g., retroviruses. A number of nonenveloped viruses, including AAV, carry proteases that are needed for capsid maturation or for capsid modification during infection. We describe here what appears to be the first example of a nonenveloped viral capsid that appears to have a role in promoting transcription. A total of six mutants at the AAV capsid 2-fold interface were shown to have a severe defect in expressing their genomes, and the defect was at the level of mRNA accumulation. This suggests that AAV capsids have a novel role in promoting the transcription of the genomes that they have packaged. Since wt virions could not complement the mutant viruses, and the mutant viruses did not effectively inhibit wt gene expression, our results suggest that the capsid exerts its effect on transcription in cis.
Cyclosporin a and Vitamin D Metabolism: Studies in Patients with Psoriasis and in Rats (1994)

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxyvitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D. 2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day-1 kg-1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1-3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day-1 kg-1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day-1 kg-1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1-10 mumol/l) for 30 h or 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor. (1989)

A cDNA encoding a human macrophage migration inhibitory factor (MIF) was isolated, through functional expression cloning in COS-1 cells, from a cDNA library prepared from a lectin-stimulated T-cell hybridoma, T-CEMB. The 115-amino acid polypeptide encoded by the MIF cDNA (p7-1) was effectively released from the transfected COS-1 cells and yielded readily detectable MIF activity in the culture supernatant despite the apparent lack of a classical protein secretory sequence. Insertional mutational analysis and elution of MIF activity from polyacrylamide gel slices demonstrated that the Mr 12,000 protein with MIF activity released by the COS-1 cells is encoded by p7-1. The p7-1 cDNA hybridized with a 700-base mRNA expressed by Con-A-stimulated lymphocytes but not unstimulated lymphocytes. The availability of the MIF cDNA clone and recombinant MIF will facilitate the analysis of the role of this lymphokine in cell-mediated immunity, immunoregulation, and inflammation.
IL-21: An Executor of B Cell Fate (2009)

IL-21 is a type I cytokine that shares the common receptor gamma-chain with IL-2, IL-4, IL-7, IL-9, and IL-15. B cells are one of the lymphoid cell types whose development and function are regulated by IL-21. Depending on the interplay with costimulatory signals and on the developmental stage of a B cell, IL-21 can induce proliferation, differentiation into Ig-producing plasma cells, or apoptosis in both mice and humans. Alone and in combination with Th cell-derived cytokines IL-21 can regulate class switch recombination to IgG, IgA, or IgE isotypes, indicating its important role in shaping the effector function of B cells. This review highlights the role of IL-21 in B cell development, function, and disease and provides some perspectives on the future studies in this area.
Serum fibroblast growth factor-23 (FGF-23) levels are independently associated with left ventricular mass and myocardial performance index in maintenance haemodialysis patients (2010)

Plasma FGF-23 concentration is independently associated with LVMI and MPI in maintenance haemodialysis patients. Further prospective studies are needed to clarify whether increased serum FGF-23 level is a marker or a potential mechanism for left ventricular involvement in patients with end-stage renal disease.
Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial (2012)

ClinicalTrials.gov: NCT00254800.
The impact of fruit flavonoids on memory and cognition (2010)

There is intense interest in the studies related to the potential of phytochemical-rich foods to prevent age-related neurodegeneration and cognitive decline. Recent evidence has indicated that a group of plant-derived compounds known as flavonoids may exert particularly powerful actions on mammalian cognition and may reverse age-related declines in memory and learning. In particular, evidence suggests that foods rich in three specific flavonoid sub-groups, the flavanols, anthocyanins and/or flavanones, possess the greatest potential to act on the cognitive processes. This review will highlight the evidence for the actions of such flavonoids, found most commonly in fruits, such as apples, berries and citrus, on cognitive behaviour and the underlying cellular architecture. Although the precise mechanisms by which these flavonoids act within the brain remain unresolved, the present review focuses on their ability to protect vulnerable neurons and enhance the function of existing neuronal structures, two processes known to be influenced by flavonoids and also known to underpin neuro-cognitive function. Most notably, we discuss their selective interactions with protein kinase and lipid kinase signalling cascades (i.e. phosphoinositide-3 kinase/Akt and mitogen-activated protein kinase pathways), which regulate transcription factors and gene expression involved in both synaptic plasticity and cerebrovascular blood flow. Overall, the review attempts to provide an initial insight into the potential impact of regular flavonoid-rich fruit consumption on normal or abnormal deteriorations in cognitive performance.
I. Organ Culture of Amniochorionic Membrane In Vitro (1994)

The culture technique we propose is a simple organ explant system which maintains the morphology and autocrine/paracrine relationships within this tissue.
Novel Bacteriophage Lysin with Broad Lytic Activity Protects against Mixed Infection by Streptococcus pyogenes and Methicillin-Resistant Staphylococcus aureus (2013)

Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococcus [GrAS]) cause serious and sometimes fatal human diseases. They are among the many Gram-positive pathogens for which resistance to leading antibiotics has emerged. As a result, alternative therapies need to be developed to combat these pathogens. We have identified a novel bacteriophage lysin (PlySs2), derived from a Streptococcus suis phage, with broad lytic activity against MRSA, vancomycin-intermediate S. aureus (VISA), Streptococcus suis, Listeria, Staphylococcus simulans, Staphylococcus epidermidis, Streptococcus equi, Streptococcus agalactiae (group B streptococcus [GBS]), S. pyogenes, Streptococcus sanguinis, group G streptococci (GGS), group E streptococci (GES), and Streptococcus pneumoniae. PlySs2 has an N-terminal cysteine-histidine aminopeptidase (CHAP) catalytic domain and a C-terminal SH3b binding domain. It is stable at 50 °C for 30 min, 37 °C for >24 h, 4°C for 15 days, and -80 °C for >7 months; it maintained full activity after 10 freeze-thaw cycles. PlySs2 at 128 μg/ml in vitro reduced MRSA and S. pyogenes growth by 5 logs and 3 logs within 1 h, respectively, and exhibited a MIC of 16 μg/ml for MRSA. A single, 2-mg dose of PlySs2 protected 92% (22/24) of the mice in a bacteremia model of mixed MRSA and S. pyogenes infection. Serially increasing exposure of MRSA and S. pyogenes to PlySs2 or mupirocin resulted in no observed resistance to PlySs2 and resistance to mupirocin. To date, no other lysin has shown such notable broad lytic activity, stability, and efficacy against multiple, leading, human bacterial pathogens; as such, PlySs2 has all the characteristics to be an effective therapeutic.
Endocytosis of lysosomal alpha-galactosidase A by cultured fibroblasts from patients with Fabry disease. (1982)

The endocytosis of alpha-galactosidase A was studied in cultured fibroblasts from patients with Fabry disease. Alpha-galactosidase A was purified from human placenta by chromatography on concanavalin A-Sepharose, DEAE-cellulose, and N-epsilon-aminocaproyl-alpha-D-galactosylamine-Sepharose. Separation of the high-uptake form of the enzyme from the low-uptake form was accomplished by chromatography on ECTEOLA-cellulose. With the high-uptake form of the enzyme, the uptake was linear at low concentrations of enzyme and had a Kuptake of 0.01 U/ml of medium that corresponds to a Km of 5.0 x 10(-9) M. At high concentrations of enzyme, it became saturated. The high-uptake form could be converted to the low-uptake form by treatment with acid phosphatase. Mannose-6-P strongly inhibited the active uptake of the enzyme. Once taken up into the lysosomes of Fabry disease fibroblasts, alpha-galactosidase A activity was rapidly lost in the first 2 days of incubation at 37 degrees C, but was fairly stable for the next 6 days. The half-life of internalized alpha-galactosidase A activity was calculated to be 4 days. Crosslinking of the enzyme with hexamethylene diisocyanate did not increase the intracellular stability of alpha-galactosidase A activity.
Diclofenac is more effective for post-operative analgesia in patients undergoing lower abdominal gynecological surgeries: A comparative study (2014)

Injection diclofenac IM is more effective than paracetamol IV in terms of rescue analgesic requirement, but the combination of diclofenac IM and paracetamol IV provides no added advantage over diclofenac IM alone.
The G protein-coupled receptor identity of the frizzled proteins (2009)

Receptors of the Frizzled family initiate Wnt liganddependent signal transduction cascades controlling multiple steps in organism development and are highly conserved in animal evolution. Misactivation of the Wnt/ Frizzled signaling underlies many cases of cancerogenesis. Frizzled receptors possess seven transmembrane domains and their signaling depends on trimeric G proteins in various organisms. However, as Frizzled proteins constitute a distinct group within the superfamily of G protein-coupled receptors (GPCR), and as Frizzled signaling can apparently be G protein-independent in some experimental setups, the GPCR nature of Frizzled receptors has been questioned. Here we demonstrate that human Frizzled receptors can directly bind the trimeric Go protein in a pertussis toxin-sensitive manner. Furthermore, addition of Wnt ligands elicits Frizzled-dependent guanine nucleotide exchange on Go. An excess of secreted Frizzledrelated protein, a known antagonist of the Wnt/Frizzled pathways, inhibits Go activation, as does pretreatment of Go with pertussis toxin. These experiments provide a biochemical proof of the GPCR activities of Frizzled receptors. They also establish an in vitro assay of monitoring Frizzled activation by Wnt ligands, applicable for the high-throughput agonist/antagonist screening.
Kinetic and Affinity Predictions of a Protein-Protein Interaction Using Multivariate Experimental Design (2002)

We measured the influence of 14 mutations and 5 environmental variables (buffer perturbation) on the association and dissociation rate of a camel single domain antibody (cAb-Lys3) interacting with hen egg white lysozyme using a surface plasmon resonance-based biosensor. Based on this data set, we constructed quantitative predictive models for both kinetic (k(a) and k(d)) constants as for the affinity constant (K(d)). Mutations, after parameterization by quantitative descriptors, and buffers were selected using multivariate experimental design. These models were able to predict the corresponding parameters of four new variants of cAb-Lys3. Moreover, the models provide insights to the important chemical aspects of the interacting residues, which are difficult to deduce from the crystal structure. Our approach provides useful physicochemical information of protein-protein interactions in general. The information obtained from this kind of analysis complements and goes beyond that of conventional methods like alanine scanning and substitution by closely related amino acids. The mathematical modeling may contribute to a rational approach in the optimization of bio-molecules of biotechnological interest.
General Synthetic Method for Naphthyridines and Their N-Oxides Containing Isoquinolinic Nitrogen (1999)

Substituted naphthyridines containing isoquinolinic nitrogen were synthesized by the reaction of o-ethynylpyridinecarbaldehydes with ammonia. The synthesis of their N-oxides was also achieved by a basic cyclization reaction of the same pyridine derivatives via the corresponding oximes.
Building Hypermedia Applications: A Software Development Guide (1992)

Provides project leaders and programmers with the information they need for building PC and Macintosh hypermedia applications. The book covers both the technical details of application development as well as the project management requirements. Beginning with an examination of the strengths and potential uses of hypermedia, the book goes on to offer guidelines for obtaining system requirements, translating requirements into specifications, implementing rapid prototyping, achieving system integration, and testing and maintaining the application. Readers will also find specific advice for selecting and using off-the-shelf software and choosing the best hardware platform for their hypermedia applications.
Influence of PIL segment on solution properties of poly(N-isopropylacrylamide)-b-poly(ionic liquid) copolymer: micelles, thermal phase behavior and microdynamics (2012)

The assembly properties, thermal phase behavior and microdynamics of poly(NIPAM-b-BVImBr), poly(N-isopropylacrylamide)-b-poly(1-butyl-3-vinylimidazolium bromide), in aqueous solution are investigated by dynamic light scattering (DLS), turbidity measurements and FTIR spectroscopy in combination with two-dimensional correlation spectroscopy (2Dcos) and the perturbation correlation moving window (PCMW) technique. In particular, the influence of the introduction of the poly(BVImBr) segment on the solution properties of the block copolymer has attracted our attention: a core–shell micelle structure forms, consisting of a relatively hydrophobic core of poly(BVImBr) and a hydrophilic shell of PNIPAM; the phase transition temperature increases, due to one more step in the dehydration process originating from the alkyl side chains of the poly(1-butyl-3-vinylimidazolium bromide) (PIL) segment; what's more, a stronger hysteresis during the heating–cooling cycle, closely related to the recovery process, is observed. It reveals that the hydrogen bonds of CO⋯D–N among the micelles formed during heating are harder to remove, thus, the reconstruction of the CO⋯D–O–D hydrogen bonding and the recovery hydration process for the C–H groups during cooling are prevented due to the compact and regular micelle structure. More interestingly, the CO groups interact with the N–D groups at room temperature because of the existence of the micelle structure, which is regarded as intra-micelle hydrogen bonding; above the LCST, hydrogen bonds of the CO⋯D–N among the aggregated micelles called inter-micelle hydrogen bonding occur.
The synthesis and possible functions of virus-induced proteins in plants. (1988)

Plants reacting hypersensitively to virus infection accumulate proteins that exert their activity in the cytoplasm, the cell wall or the intercellular space of the leaf. The function of a number of these proteins is described and the expression and structure of genes encoding the extracellular proteins is discussed.
A Comparative Study of Wavelet Denoising of Surface Electromyographic Signals (2007)

This study intends to explore the wavelet denoising for optimal MUAP detection through the wavelet analysis of surface electromyographic (SEMG) signals. We first derive an estimator for signal to noise ratio and show that this estimator correlates to the quality of the reconstructed simulated signal. When applying this estimator to evaluate the SEMG signal, we find that the reconstructed signal is insensitive to the selection of denoising methods. This finding is further confirmed by the identical plots of those reconstructed SEMG data. In addition, the close correspondence of MUAP occurrences in the reconstructed signal and those in the original signal suggests that the denoising procedure can preserve the features of MUAP in the original SEMG signals.
Specific cloning of human DNA as yeast artificial chromosomes by transformation-associated recombination. (1996)

DNA molecules undergoing transformation into yeast are highly recombinogenic, even when diverged. We reasoned that transformation-associated recombination (TAR) could be employed to clone large DNAs containing repeat sequences, thereby eliminating the need for in vitro enzymatic reactions such as restriction and ligation and reducing the amount of DNA handling. Gently isolated human DNA was transformed directly into yeast spheroplasts along with two genetically marked (M1 and M2) linearized vectors that contained a human Alu sequence at one end and a telomere sequence at the other end (Alu-CEN-M1-TEL and Alu-M2-TEL). Nearly all the M1-selected transformants had yeast artificial chromosomes (YACs) containing human DNA inserts that varied in size from 70 kb to > 600 kb. Approximately half of these had also acquired the unselected M2 marker. The mitotic segregational stability of YACs generated from one (M1) or two (M1 and M2) vector(s) was comparable, suggesting de novo generation of telomeric ends. Since no YACs were isolated when rodent DNAs or a vector lacking an Alu sequence was used, the YACs were most likely the consequence of TAR between the repeat elements on the vector(s) and the human DNA. Using the BLUR13 Alu-containing vector, we demonstrated that human DNA could be efficiently cloned from mouse cells that contained a single human chromosome 16. The distribution of cloned DNAs on chromosome 16 was determined by fluorescence in situ hybridization. We propose that TAR cloning can provide an efficient means for generating YACs from specific chromosomes and subchromosome fragments and that TAR cloning may be useful for isolating families of genes and specific genes from total genome DNA.
Emission of photon echoes in a strongly scattering medium (2011)

We observe the two- and three-pulse photon echo emission from a scattering powder, obtained by grinding a Pr3+:Y2SiO5 rare earth doped single crystal. We show that the collective emission is coherently constructed over several grains. A well defined atomic coherence can therefore be created between randomly placed particles. Observation of photon echo on powders as opposed to bulk materials opens the way to faster material development. More generally, time-domain resonant four-wave mixing offers an attractive approach to investigate coherent propagation in scattering media.
[Study of the correlation between the expression level of asparagine synthetase and the outcome of children with acute lymphocytic leukemia]. (2008)

High expression of AS is associated with a poor outcome in ALL children.