gebhart/patrepeval huggingface dataset:
Overview of the LDL receptor: relevance to cholesterol metabolism and future approaches for the treatment of coronary heart disease (2009)

Overview of the LDL receptor: relevance to cholesterol metabolism and future approaches for the treatment of coronary heart disease William R Lagor, John S MillarDepartment of Pharmacology, Institute for Translational Research and Therapeutics, University of Pennsylvania, Philadelphia, PA, USAAbstract: Since the discovery of the low-density lipoprotein (LDL) receptor over 30 years ago manipulation of its activity has been pursued through dietary and pharmacological means with the goal of reducing LDL cholesterol levels. This has proven to be one of the most widely implemented and beneficial interventions to reduce LDL cholesterol levels and the incidence of cardiovascular death. This review provides an overview of the LDL receptor and its role in regulating whole body cholesterol homeostasis and LDL cholesterol levels. New findings on regulation of the LDL receptor are discussed and how they can be used to develop novel therapeutics to reduce cardiovascular risk.Keywords: VLDL, statins, pcsk9, cardiovascular disease
Evolution of the Phytochrome Gene Family and Its Utility for Phylogenetic Analyses of Angiosperms (1995)

Sarah Mathews, Matt Lavin, Robert A. Sharrock, Evolution of the Phytochrome Gene Family and Its Utility for Phylogenetic Analyses of Angiosperms, Annals of the Missouri Botanical Garden, Vol. 82, No. 2 (1995), pp. 296-321
Identification of 3α-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation (1995)

In addition to E mu, several elements downstream of the IgH cluster, i.e. 3' of the C alpha gene, are involved in regulating IgH gene rearrangement and expression. This entire downstream regulatory region was shown to be deleted in the mutant myeloma cell line, LP1.2. The deletion encompasses approximately 34 kb and is presumably responsible for the reduced levels of IgH expression in this cell line. An additional regulatory element, included in the LP1.2 deletion, was identified by investigation of a DNase I hypersensitivity site located approximately 33 kb downstream of the alpha gene and present in pre-B and plasma cells. This novel IgH gene enhancer element, termed 3' alpha-hs4, is capable of activity throughout B cell development. Transient transfection of 3' alpha-hs4 in a CAT reporter gene construct shows transcriptional enhancement activity approximating that of E mu in S194 plasmacytoma and M12.4.1 and A-20 B cell lines; while in a pre-B cell line, 18-81, the average activity is 25% that of E mu. Enhancer activity was localized to an 800 bp fragment. The activity of 3' alpha-hs4 is orientation independent and appears to be B cell specific. Tight regulation of 3' alpha-hs4 is inferred from its variable activity in different plasmacytoma cell lines and within the pre B cell line, 18-81.
Transformation of Kluyveromyces fragilis (1984)

For the transformation of the yeast species Kluyveromyces fragilis, we have constructed a vector containing a bacterial kanamycin resistance (Kmr) gene, the TRP1 gene of Saccharomyces cerevisiae, and an autonomously replicating sequence of Kluyveromyces lactis called KARS2 . By utilizing the method based on treatment by alkali cations and with the Kmr gene as the selective marker, a wild-type strain of K. fragilis was transformed to resistance against the antibiotic G418 . In the transformed cell the plasmid replicates autonomously. The same plasmid could also be used to transform S. cerevisiae trp1 mutant to Trp+. Thus, KARS2 of K. lactis enables the vector to replicate in K. fragilis, K. lactis, and S. cerevisiae, whereas ARS1 of S. cerevisiae allows autonomous replication only in S. cerevisiae.
Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis (1995)

Aging men develop a significant loss of muscle strength that occurs in conjunction with a decline in serum testosterone concentrations. We investigated the effects of testosterone administration to six healthy men [67 +/- 2 (SE) yr] on skeletal muscle protein synthesis, strength, and the intramuscular insulin-like growth factor I (IGF-I) system. Elderly men with serum testosterone concentrations of 480 ng/dl or less were given testosterone injections for 4 wk to produce serum concentrations equal to those of younger men. During testosterone administration muscle strength (isokinetic dynamometer) increased in both right and left hamstring and quadricep muscles as did the fractional synthetic rate of muscle protein (stable-isotope infusion). Ribonuclease protection assays done on total RNA from muscle showed that testosterone administration increased mRNA concentrations of IGF-I and decreased mRNA concentrations of insulin-like growth factor binding protein-4. We conclude that increasing testosterone concentrations in elderly men increases skeletal muscle protein synthesis and strength. This increase may be mediated by stimulation of the intramuscular IGF-I system.
Dynamic coating using methylcellulose and polysorbate 20 for nondenaturing electrophoresis of proteins on plastic microchips (2007)

A dynamic coating using methylcellulose (MC) and a nonionic detergent (polysorbate 20) was developed, which controlled protein adsorption onto the surface of microchannels on a microchip made of poly(methyl methacrylate) (PMMA). Optimum concentration of polysorbate 20 in combination with the range of MC concentrations controlled the protein adsorption onto the microchannel surface, and increased the solubility of the protein samples while facilitating the injection of high concentrations of MC solutions into the microchannels. Higher concentrations of nonionic detergent increased the EOF mobility as opposed to the electrophoretic mobility and caused the electrophoresis to fail. Nondenaturing microchip electrophoresis of protein samples with molecular masses ranging from 20 to 100 kDa were completed in 100 s. Also, successful separation of a BSA sample and its complex with anti-BSA mAb ( 220 kDa) was achieved on a PMMA microchip. The separation exhibited high reproducibility in both migration time (RSD = 1%) and peak area (RSD = 10-15%).
Nasopharyngeal Flora in the First Three Years of Life in Normal and Otitis-Prone Children (1991)

Nasopharyngeal carriage of the three major middle ear pathogens (Streptococcus pneumoniae, nontypeable Hemophilus influenzae, and Moraxella catarrhalis) was evaluated prospectively in a group of 110 children followed up for the first 3 years of life. The findings suggested that nasopharyngeal carriage of middle ear pathogens increases significantly during respiratory illness among the general population of young children; however, otitis-prone children demonstrated a tendency to carry nontypeable H influenzae at an unusually high rate even during health. This propensity to carry nontypeable H influenzae might explain why nontypeable H influenzae is a major cause of recurrent or chronic otitis media.
Pivotal Role of Electrophilicity in Glutathione S-Transferase Induction by tert-Butylhydroquinone (2003)

Although the induction of glutathione S-transferase (GST) activity by tert-butylhydroquinone (tBHQ) has been well-documented in several cell culture systems and rodent experiments, the exact mechanism responsible for its inducibility is still not thoroughly understood. To more precisely define the molecular mechanism of GST induction by tBHQ, we examined the one-electron oxidation and glutathione (GSH) reaction potentials of tBHQ as compared to its analogue, 2,5-di-tert-butylhydroquinone (DtBHQ). tBHQ and DtBHQ showed similar one-electron oxidation potentials, including free radical quenching (antioxidant), oxidative conversion of both compounds to a benzoquinone form, and Cu(2+)-dependent superoxide generation. On the other hand, the reduced GSH level was observed by the addition of tBHQ, but not DtBHQ, suggesting that tBHQ acts as an electrophile while DtBHQ does not. The data were consistent with the observation that tBHQ more potently induced the GSTP1 gene expression in RL34 cells than DtBHQ did. Moreover, we indeed detected the GSH-tBHQ conjugates in the cells exposed to tBHQ using an electrochemical detector-high-performance liquid chromatography technique. Thus, we conclude that an electrophilic quinone oxidation product that reacts with intracellular nucleophiles including protein thiol or GSH plays a major role in the GSTP1 gene expression.
Acute Manic Psychosis Following the Dermal Application of

N

,

N

-Diethyl-M-Toluamide (deet) in an Adult (1986)

Extensive animal testing and 30 years of human experience have established the general safety of DEET when applied episodically to skin or bedclothes. Local and systemic toxic and allergic reactions to DEET have been observed in man. Three weeks prior to admission, for the purpose of self-medication, a 30 year old man began daily applications of the insect repellant, DEET followed by a 1-2 hour period in a light-bulb heated box. Sedation and incoherence were noted for short periods following each application session. Aggressiveness and psychotic ideation led to hospital admission where he displayed psychomotor hyperactivity, rapid and pressured speech, tangentiality, flight of ideas, and grandiose delusions. Treatment was begun with haloperidol. Clinical improvement was complete within 6 days, atypical for classic endogenous mania. Drug and metabolites were identified in the urine more than 2 weeks after the last drug application.
Light-Regulated and Cell-Specific Expression of Tomato rbcS-gusA and Rice rbcS-gusA Fusion Genes in Transgenic Rice (1993)

A previously isolated rice (Oryza sativa) rbcS gene was further characterized. This analysis revealed specific sequences in the 5' regulatory region of the rice rbcS gene that are conserved in rbcS genes of other monocotyledonous species. In transgenic rice plants, we examined the expression of the beta-glucuronidase (gusA) reporter gene directed by the 2.8-kb promoter region of the rice rbcS gene. To examine differences in the regulation of monocotyledonous and dicotyledonous rbcS promoters, the activity of a tomato rbcS promoter was also investigated in transgenic rice plants. Our results indicated that both rice and tomato rbcS promoters confer mesophyll-specific expression of the gusA reporter gene in transgenic rice plants and that this expression is induced by light. However, the expression level of the rice rbcS-gusA gene was higher than that of the tomato rbcS-gusA gene, suggesting the presence of quantitative differences in the activity of these particular monocotyledonous and dicotyledonous rbcS promoters in transgenic rice. Histochemical analysis of rbcS-gusA gene expression showed that the observed light induction was only found in mesophyll cells. Furthermore, it was demonstrated that the light regulation of rice rbcS-gusA gene expression was primarily at the level of mRNA accumulation. We show that the rice rbcS gene promoter should be useful for expression of agronomically important genes for genetic engineering of monocotyledonous species.
A concept for RSVP over Diffserv (2002)

Currently two approaches to provide quality of service in the Internet are being discussed. An early one is the Resource Reservation Protocol, RSVP, (IETF RFC 2205) based on an end to end approach. Recent and ongoing activities in the IETF's Differentiated Service Working Group are focused on methods for providing quality of service in backbones. This paper presents a concept for the integration of both integrated and differentiated services, describes a prototype implementation, and presents evaluation results. Additionally the paper discusses business aspects arising from this service translation.
A biological, immunological and physico-chemical comparison of the current clinical batches of the recombinant FSH preparations Gonal-F and Puregon (2000)

The immunopotency and in-vitro biopotency of clinical batches of Gonal-F((R)) and Puregon((R)) (recombinant human follicle stimulating hormones) were compared and their carbohydrate chains investigated for charge heterogeneity and internal carbohydrate complexity. Immunopotency (IU/pmol) for both Gonal-F and Puregon was 0.35 +/- 0.01 and biopotency (ED(50), pmol/l) was similar, being 7.3 +/- 0.6 and 5.4 +/- 0.2 respectively. Charge distributions were essentially the same with no difference either in median isoelectric point (pI) (between 4.26 and 4.50), or in the bulk of material fractionated between pI 4 and 5 (66.0 +/- 1.8% Gonal-F and 72.0 +/- 1.8% Puregon). However, there were minor differences in charge at extremes of pI, Gonal-F being slightly more acidic: 18.2% Gonal-F versus 9.8% Puregon at pI 3.5-4.0 (P: = 0.03) and 6.7% Gonal-F versus 10.7% Puregon at pI 5.0-5.5 (P: = 0.03). Carbohydrate complexity was the same: 9.3 versus 10.9 (complex), 76.6 versus 78.6 (intermediate) and 14.1 versus 10.5% (simple). In summary, Gonal-F and Puregon have similar immunopotency, in-vitro biopotency and internal carbohydrate complexity, differing slightly in charge heterogeneity, Gonal-F having more acidic glycoforms. We conclude them to be intrinsically very similar, expecting no difference in clinical efficacy on the basis of respective structure.
Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model. (1997)

The intestinal epithelium represents the major barrier to absorption of orally administered drugs and peptides into the systemic circulation. Entry of molecules through the paracellular pathway is restricted by tight junctions. We have previously reported that these structures can be modulated by Zonula occludens toxin (Zot). In the present report, we show that Zot reversibly increases rabbit intestinal permeability to insulin by 72% (P = 0.034) and immunoglobulins by 52% (P = 0.04) in vitro. When tested in vivo, Zot induced a 10-fold increase of insulin absorption in both the rabbit jejunum and ileum, whereas no substantial changes were detected in the colon. Similar results were obtained with immunoglobulins, whereby Zot induced twofold and sixfold increases of IgG absorption in the jejunum and ileum, respectively. In diabetic rats, bioavailability of oral insulin coadministered with Zot was sufficient to lower serum glucose concentrations to levels comparable to those obtained after parenteral injection of the hormone. The survival time of diabetic animals chronically treated with oral insulin + Zot was comparable to that observed in parenterally treated rats. These studies offer an innovative strategy for the oral delivery of drugs and proteins normally not absorbed through the intestine.
[Morphological study on the role of ICC-like cells in detrusor neuro-modulation of rat urinary bladder]. (2008)

Morphological study indicated that ICC-like cells in rat urinary bladder may play an important role in detrusor neuromodulation. Further study on function will be helpful for elucidating the mechanism of bladder neuromodulation clearly.
Inverse halftoning using wavelets (2002)

This paper introduces a new approach to inverse halftoning using nonorthogonal wavelets. The distinct features of this wavelet-based approach are: a) edge information in the highpass wavelet images of a halftone is extracted and used to assist inverse halftoning, b) cross-scale correlations in the multiscale wavelet decomposition are used for removing background halftoning noise while preserving important edges in the wavelet lowpass image, c) experiments show that our simple wavelet-based approach outperforms the best results obtained from inverse halftoning methods published in the literature, which are iterative in nature.
Scaling Hetero-Epitaxy from Layers to Three-Dimensional Crystals (2012)

Quantum structures made from epitaxial semiconductor layers have revolutionized our understanding of low-dimensional systems and are used for ultrafast transistors, semiconductor lasers, and detectors. Strain induced by different lattice parameters and thermal properties offers additional degrees of freedom for tailoring materials, but often at the expense of dislocation generation, wafer bowing, and cracks. We eliminated these drawbacks by fast, low-temperature epitaxial growth of Ge and SiGe crystals onto micrometer-scale tall pillars etched into Si(001) substrates. Faceted crystals were shown to be strain- and defect-free by x-ray diffraction, electron microscopy, and defect etching. They formed space-filling arrays up to tens of micrometers in height by a mechanism of self-limited lateral growth. The mechanism is explained by reduced surface diffusion and flux shielding by nearest-neighbor crystals.
Estimating the dose variation in a volume of interest with explicit consideration of patient geometric variation (2000)

A method to measure the effects of internal organ motion and deformation and patient setup error on cumulative dose variation in a volume of interest is proposed. The method uses multiple CT scans and electronic portal images of a single patient to numerically simulate dose-volume effects over the entire course of the patient's external beam treatment. The results are expressed in the form of a novel dose-volume histogram, called an expected dose-volume histogram (EDVH).
Liposome‐mediated DNA vaccination (1997)

Numerous reports have indicated that intramuscular injection of antigen‐coding naked plasmid DNA can trigger humoral and cell‐mediated protective immunity against infection. This follows DNA uptake by muscle fibres, leading to the expression and extracellular release of the antigen. Here it is shown for the first time that intramuscular immunization of mice with pRc/CMV HBS (encoding the S region of hepatitis B antigen; HBsAg) entrapped into positively charged (cationic) liposomes leads to greatly improved humoral and cell‐mediated immunity. These cationic liposome‐entrapped DNA vaccines generate titres of anti‐HBsAg IgG 1 antibody isotype in excess of 100‐fold higher and increased levels of both IFN‐γ and IL‐4 when compared with naked DNA or DNA complexed with preformed similar (cationic) liposomes. It is likely that immunization with liposome‐entrapped plasmid DNA involves antigen‐presenting cells locally or in the regional draining lymph nodes.
Memristors and Superconducting Quantum Interference Filters in RF Systems (2013)

&lt;p&gt;Complex nonlinear dynamical systems have been appeared in many fields of science and engineering. We are curious about two specific instances of those systems. Those two instances connect memristors and Josephson junctions to the electromagnetic fields. The first instance investigated microstrip patch antenna embedding dual memristors. This hybrid system produces broadband radiation in a narrow band radiation structure. The second one studies the novel ultra-sensitive magnetic field receiver implemented by superconducting quantum interference filters (SQIFs).&lt;/p&gt;&lt;p&gt;For the first instance, we notice that memristor has been proposed as the fourth passive element. We start with investigating the circuit model of this memristive element. Then, we embedded this circuit model into an EM radiation structure. We first report an efficient broadband electromagnetic radiation from a narrowband microstrip patch antenna. The directly modulated microstrip patch antenna system with dual memristors is calculated by using an integrated full-wave finite-difference time-domain solver and an embedded SPICE3 solver. Nonlinear transient electromagnetic responses are analyzed. The radiation frequency spectrum demonstrates the broadband radiation performance from the narrowband antenna system. We predict that the conceptual challenge of high frequency memristors will stimulate pioneering work in the fields of microwave and memristors.&lt;/p&gt;&lt;p&gt;For the second one, we predict that superconducting quantum interference filters (SQIFs) might play a key role in future quantum wireless communication systems. We analyze the dynamic behavior of this large-scale 2D DC SQIF (two-dimensional superconducting direct current quantum interference filter) array in a dynamic electromagnetic environment. The investigation under this framework starts from the SPICE circuit description of a RCSJ (resistively and capacitively shunted junction) model of a Josephson junction and then extends to the 2D SQIF with few device parameters. We separate the interface and the implementation of 2D DC SQIF. This approach can significantly improve circuit-level design efficiency of 2D SQIF array and ultimately allows us to accelerate the hybrid design with an electromagnetic radiation structure. Our findings on the average voltage response of this device offer compelling evidence that the bias static magnetic field plays a key role in designing an effective far-field magnetic field sensor. Since this device can function as both a robust and sensitive low noise pre-amplifier as well as a receiving antenna which only senses the magnetic field component of far-field electromagnetic wave signals, we call it magnetic-antenna or B-antenna. We believe that our research not only directly benefits the sensor design for Information Operations/Signals Intelligence (IO/SIGINT) applications in Very High Frequency/Ultra High Frequency (VHF/UHF) bands, but also opens new dimension of novel ultra-sensitive receiving antenna technology.&lt;/p&gt;
Complexes of Plasmid DNA with Basic Domain 47-57 of the HIV-1 Tat Protein Are Transferred to Mammalian Cells by Endocytosis-mediated Pathways (2003)

Arginine-rich peptides, penetratins, as part of a number of cellular and viral proteins, can penetrate across plasma membrane directly, without participation of endocytosis. We show that one of penetratins, the basic domain 47-57 of human immunodeficiency virus, type 1, transcription factor Tat (Tat peptide), is able to interact with plasmid DNA electrostatically. These interactions result in formation of polyelectrolytic complexes at various negative/positive charge ratios of plasmid DNA and Tat peptide. Plasmid DNA is capable of binding to Tat peptide up to 1.7-fold excess of the complex positive charge. The DNA-Tat complexes can be used for delivery of plasmid DNA into mammalian cells. Transfection efficacy of cultured cells by DNA-Tat complexes is stimulated by free Tat peptide, most likely because it protects DNA-Tat complexes from disruption by anionic proteoglycans of cellular surface. Our data strongly argue in favor of the endocytosis-dependent mechanism of DNA-Tat complex uptake by mammalian cells similarly to internalization of complexes of plasmid DNA with other polycationic carriers. Moreover, different cell lines use different endocytosis-mediated pathways for DNA-Tat complex internalization. Intravenous injections to mice of DNA-Tat complexes in comparison with injections of naked DNA showed an inhibitory effect of DNA-Tat complex positive charge on expression of transferred gene. A low level of foreign gene expression in the liver of mice injected intravenously with positively charged DNA-Tat complexes is accounted for by inactivation of DNA-Tat complexes in the bloodstream due to their interactions with serum albumin. These data should be taken into account in an attempt to develop versatile gene delivery systems based on penetratin application for human disease therapy.