gebhart/patrepeval huggingface dataset:
RESPONSES OF CRITERION VARIABLES TO DIFFERENT SUPPLEMENTAL DOSES OF L-CARNITINE L-TARTRATE (2007)

L-carnitine L-tartrate (LCLT) supplementation beneficially affects markers of postexercise metabolic stress and muscle damage. However, to date, no study has determined the dose response of LCLT to elicit such responses. Therefore, the purpose of this study was to determine the effects of different doses of LCLT on criterion variables previously shown to be responsive to LCLT supplementation. Eight healthy men (22 +/- 3 y, 174 +/- 5 cm, 83.0 +/- 15.3 kg) were supplemented with 0 g, 1 g, and 2 g of LCLT for 3 weeks and then performed a bout of resistance exercise (5 sets of 15-20 repetition maximum with a 2-min rest between sets) with associated blood draws. This procedure was performed in a balanced, randomized, repeated measures design. Serum carnitine concentrations increased (p < or = 0.05) following the 1 g and 2 g doses, with the 2-g dose providing the highest carnitine concentrations. The 1- and 2-g doses reduced postexercise serum hypoxanthine, serum xanthine oxidase, serum myoglobin, and perceived muscle soreness. In conclusion, both the 1- and 2-g doses were effective in mediating various markers of metabolic stress and of muscle soreness. Use of LCLT appears to attenuate metabolic stress and the hypoxic chain of events leading to muscle damage after exercise.
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver (2002)

Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element-binding proteins (SREBPs).SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1-4).In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles.The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice.These studies form the subject of this review.
Topical application of the immunosuppressant tacrolimus accelerates carcinogenesis in mouse skin (2003)

Caution and careful surveillance are required with regard to skin lesions in patients treated with tacrolimus for prolonged periods.
Evaluating delivery point reliability performance for network configurations (2003)

The reliability of an electric or telecommunication network configuration is a measure of its ability to continuously meet the demands of all its points of delivery. Customers who have processes that are highly susceptible to sustained and momentary interruptions in their supply network configuration are significantly affected in their ability to produce end products and maintain processes. This paper presents a reliability method based on Bayes theorem to evaluate the reliability at individual delivery points within a given electric utility network configuration. The reliability characteristics of the components of the network are defined by their respective failure rate and repair/replacement rates. The primary advantage of Bayes theorem over other methodologies is the retention of the network configuration and the ability to impose various operating constraints during the recovery of the network from component outages. This paper clearly reveals that the reliability levels at individual points of delivery can vary significantly depending upon the reliability of the power supplies serving a given network configuration.
Light emission by magnetic and electric dipoles close to a plane interface I Total radiated power (1977)

Expressions for the total power radiated by magnetic and electric dipoles of arbitrary orientation located in a medium 1 at distance z0 from the interface to a homogeneous or planar stratified medium 2 are derived. A relation between the normalized powers radiated by magnetic and electric dipoles is established. For a homogeneous loss-free medium 2, curves of the normalized powers L(z0)/L∞ radiated by magnetic and electric dipoles versus the normalized distance z0/λ1 are presented for different values of the relative refractive index n = n2/n1 as the only parameter. The computer calculations are compared with analytical expressions derived for small and large distances. For n &gt; 1, the contribution of the evanescent waves to the radiated power is calculated separately. We show that the classical results for the normalized radiated power yield the correct normalized spontaneous emission rates from an excited atomic state for electric and magnetic dipole transitions, respectively. We point out that the results for the electric dipole also give the change of the total power scattered by a small dielectric scattering particle when it is placed close to an interface.
Metabolic and psychophysiologic studies of cannabidiol-hexobarbital interaction (1980)

Cannabidiol (CBD), 600 mg/day orally for 5 to 12 days, inhibited hexobarbital metabolism in ten subjects. Hexobarbital oral clearance was 36% lower and apparent volume of distribution was 35% smaller, with no change in half-life during CBD. In four subjects who received intravenous and oral hexobarbital, systemic clearance was 36% lower while bioavailability was 10% greater during CBD. Hexobarbital increased fatigue and tremor, impaired eye-tracking performance, and altered the electroencephalogram. Hexobarbital effects were not affected by CBD. Inhibition of metabolism of other drugs should be considered when large amounts of CBD are taken or when CBD is used for therapy.
Use of HIV as a gene transfer vector. (2009)

Despite the extensive research efforts over the past 25 years that have focused on HIV, there is still no cure for AIDS. However, tremendous progress in the understanding of the structure and biology of the HIV virus led to the development of safe and potent HIV-based transgene delivery vectors. These genetic vehicles are referred to as lentiviral vectors. They appear to be better suited for particular applications, such as transgene delivery into stem cells, compared to other viral- and non-viral vectors. This is because Lentivirus-based vectors can efficiently infect nondividing and slowly dividing cells. In the present review article, the current state of understanding of HIV-1 is discussed and the main characteristics that had an impact on vector design are outlined. A historical view on the vector concept is presented to facilitate discussion of recent results in vector engineering in a broader context. Subsequently, a state of the art overview concerning vector construction and vector production is given. This review also touches upon the subject of lentiviral vector safety and related topics that can be helpful in addressing this issue are discussed. Finally, examples of Lentivirus-based gene delivery systems and their applications are presented, with emphasis on animal transgenesis and human gene therapy.
BAFF selectively enhances the survival of plasmablasts generated from human memory B cells (2003)

The generation of Ig-secreting cells (ISCs) from memory B cells requires interactions between antigen-specific (Ag-specific) B cells, T cells, and dendritic cells. This process must be strictly regulated to ensure sufficient humoral immunity while avoiding production of pathogenic autoantibodies. BAFF, a member of the TNF family, is a key regulator of B cell homeostasis. BAFF exerts its effect by binding to three receptors - transmembrane activator of and CAML interactor (TACI), B cell maturation antigen (BCMA), and BAFF receptor (BAFF-R). To elucidate the contribution of BAFF to the differentiation of B cells into ISCs, we tracked the fate of human memory B cells stimulated with BAFF or CD40L. BAFF and CD40L significantly increased the overall number of surviving B cells. This was achieved via distinct mechanisms. CD40L induced proliferation of nondifferentiated blasts, while BAFF prevented apoptosis of ISCs without enhancing proliferation. The altered responsiveness of activated memory B cells to CD40L and BAFF correlated with changes in surface phenotype such that expression of CD40 and BAFF-R were reduced on ISCs while BCMA was induced. These results suggest BAFF may enhance humoral immunity in vivo by promoting survival of ISCs via a BCMA-dependent mechanism. These findings have wide-ranging implications for the treatment of human immunodeficiencies as well as autoimmune diseases.
An Attenuated LC16m8 Smallpox Vaccine: Analysis of Full-Genome Sequence and Induction of Immune Protection (2005)

The potential threat of smallpox bioterrorism has made urgent the development of lower-virulence vaccinia virus vaccines. An attenuated LC16m8 (m8) vaccine was developed in 1975 from the Lister strain used in the World Health Organization smallpox eradication program but was not used against endemic smallpox. Today, no vaccines can be tested with variola virus for efficacy in humans, and the mechanisms of immune protection against the major intracellular mature virion (IMV) and minor extracellular enveloped virion (EEV) populations of poxviruses are poorly understood. Here, we determined the full-genome sequences of the m8, parental LC16mO (mO), and grandparental Lister (LO) strains and analyzed their evolutionary relationships. Sequence data and PCR analysis indicated that m8 was a progeny of LO and that m8 preserved almost all of the open reading frames of vaccinia virus except for the disrupted EEV envelope gene B5R. In accordance with this genomic background, m8 induced 100% protection against a highly pathogenic vaccinia WR virus in mice by a single vaccination, despite the lack of anti-B5R and anti-EEV antibodies. The immunogenicity and priming efficacy with the m8 vaccine consisting mainly of IMV were as high as those with the intact-EEV parental mO and grandparental LO vaccines. Thus, mice vaccinated with 10(7) PFU of m8 produced low levels of anti-B5R antibodies after WR challenge, probably because of quick clearance of B5R-expressing WR EEV by strong immunity induced by the vaccination. These results suggest that priming with m8 IMV provides efficient protection despite undetectable levels of immunity against EEV.
High mobility group protein 1 preferentially conserves torsion in negatively supercoiled DNA (1989)

HMG 1 is known to bind to a variety of DNAs and to unwind nicked and closed circular DNA. We now report evidence that it has a significantly higher unwinding angle on negatively supercoiled DNA than on the other torsional forms. The degree of unwinding observed on nicked circular DNA depends on the purity of the HMG 1 preparation used. HMG 1 from CM-Sephadex has an unwinding angle of 28.8 degrees, compared to 7.2 degrees for the purer preparation obtained from Mono S, suggesting that contaminating strand-separating activity is removed by the additional purification step. The subsequent studies on closed circular forms of DNA were all performed using the purer HMG 1. After preincubation of highly negatively supercoiled DNA (sigma = -0.040) with HMG 1, the DNA-protein mixture was relaxed with Escherichia coli topoisomerase I. At molar ratios of less than 100:1 (HMG 1 to DNA), negatively supercoiled DNA displays a dose-dependent change in the linking number, indicating an unwinding angle of 57.6 degrees. HMG 1 protects 50% of highly negatively supercoiled DNA from E. coli topoisomerase I at a molar ratio of 100:1, and protects all supercoils at a molar ratio of 200:1, indicating saturation of the DNA at this concentration. HMG 1 also protects highly negatively supercoiled DNA from calf thymus topoisomerase I, with an apparent unwinding angle of 57.6 degrees. Moderately negatively supercoiled DNA (sigma = -0.018), but not moderately positively supercoiled DNA (sigma = +0.011), competes for the protective effect of HMG 1 on highly negatively supercoiled DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Absence of progesterone receptor associated with secondary breast cancer in postmenopausal women (1999)

The relationship between expression of receptors for oestrogen and progesterone (ER and PR) and disease progression in breast cancer was investigated by comparing immunocytochemical determinations of ER and PR in fine needle aspirates from primary and secondary breast tumours. Rates of receptor expression were significantly higher in primary than in secondary lesions: for ER 63.3% (n = 689) compared with 45.3% (n = 223), and for PR 53.7% (n = 443) compared with 33.1% (n = 121). The effect of menopausal status was examined by subdividing the patient cohort into those over or under the age of 50 years. In both instances, ER expression in secondary tumours was relatively low; however, only postmenopausal patients had significantly lower rates of PR expression in secondary tumours. Consistent with this, an increase in the ER+PR- profile in secondary tumours compared with primary cases from postmenopausal patients was seen, and in a multivariate analysis, a specific absence of PR expression in secondary tumours was revealed. Comparison of ER and PR expression in simultaneously sampled primary tumours and lymph node metastases from the same patient showed that receptor expression was stable with progression to a metastatic site as results were concordant for ER in 92% (n = 88) and PR in 93.8% of cases (n = 65). These results suggest that absence of PR expression in primary breast cancer is associated with disease progression and may be a marker of an aggressive tumour phenotype.
Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer. (2003)

TM is well tolerated and consistently depletes copper as measured by the serum CP level. Clinical activity was limited to stable disease for a median of 34.5 weeks in this Phase II trial in patients with advanced kidney cancer. Serum levels of proangiogenic factors IL-6, IL-8, VEGF, and bFGF may correlate with copper depletion but not with disease stability in this small cohort. TM may have a role in the treatment of kidney cancer in combination with other antiangiogenic therapies.
Quantification of carboxyl groups in carbodiimide cross‐linked collagen sponges (2007)

Glutaraldehyde (GA) fixation of bioprosthetic tissue is a well adapted technique, with commercial products on the market for almost 40 years. Amine groups present in tissue react with GA to form different types of cross-links. An estimation of the degree of cross-linking of the tissue can be obtained by measuring the concentration of residual amine groups, which is frequently carried out with the 2,4,6 trinitrobenzene sulphonic acid (TNBS) assay. Cross-linked tissue and collagen matrices are usually further characterized by determining their physical properties (such as the shrinkage temperature), biological properties (such as resistance to enzymatic degradation), and mechanical properties before in vivo evaluation takes place. In an effort to improve the properties of cross-linked tissue and collagen, alternative cross-linking methods have been developed. One of these methods is based on the use of water soluble carbodiimides (CDI). It is generally accepted that this cross-linking method leads only to the formation of amide linkages between tissue carboxyl and amine groups. Therefore, until recently the TNBS assay was also used to determine the degree of cross-linking of CDI cross-linked tissue and collagen. However, it cannot be excluded that after activation of carboxyl groups of tissue and collagen by CDI, these groups can react with other nucleophiles (like hydroxyl groups) present in the matrix. To obtain a better insight in the degree of cross-linking of CDI cross-linked matrices a reliable assay for quantification of residual carboxyl groups is required. Up to now such an assay was not available. In this study a new assay to determine residual carboxyl groups in CDI cross-linked collagen matrices is presented. Reconstituted dermal bovine collagen matrices (RDBC) were cross-linked with a water soluble CDI and N-hydroxysuccinimide (NHS) and residual carboxyl groups were labeled using 5-bromomethyl fluorescein. Subsequently, the fluorescent label was released by mild hydrolysis and quantified with capillary zone electrophoresis. A calibration curve relating the concentration of carboxyl groups with peak intensities was obtained using Sephadex standards with known concentrations of carboxyl groups. The concentration of carboxyl groups in unprocessed RDBC as determined with this new technique was equal to the concentration of carboxyl groups measured by amino acid analysis. On the basis of the concentration of residual carboxyl groups determined for CDI/NHS cross-linked RDBC and RDBC, in which the amine groups were blocked with propionaldehyde before CDI/NHS cross-linking, it was concluded that activated carboxyl groups can also react with other groups (such as hydroxyl groups) present in the matrix. This implies that the crosslink density of RDBC matrices after treatment with CDI/NHS is higher than expected on the basis of amide bond formation only, as determined by the TNBS assay.
The effect of n−3 fatty acids on coronary atherosclerosis: Results from SCIMO, an angiographic study, background and implications (2001)

According to the model of "response to injury," the arterial endothelium is occasionally injured in hyperlipidemia, hypertension, diabetes mellitus and in other states known as risk factors. The ensuing inflammatory response is modulated by cytokines and growth factors, among them platelet-derived growth factor (PDGF), and monocyte chemoattractant protein-1 (MCP-1). In two independent studies, we demonstrated that mRNA levels for PDGF-A and -B and for MCP-1 are reduced after ingestion of n-3 fatty acids by human volunteers. This reduction persists after monocyte stimulation/differentiation by adherence. Moreover, the reduction is brought about only by dietary n-3 fatty acids and not by other classes of unsaturated fatty acids (n-6 or n-9). This appears to be one major mechanism of action of reduced progression/increased regression of established coronary artery disease by ingestion of 1.5 g/d n-3 fatty acids, as assessed by coronary angiography in a randomized placebo-controlled double-blind intervention study in 223 patients. The study was conducted according to "Good Clinical Practice," comprehensive rules regulating investigations with pharmaceutical compounds. Together, our investigations lend support to the importance of PDGF-A, PDGF-B, and MCP-1 in the pathogenesis of atherosclerosis, and the beneficial role of n-3 fatty acids therein.
New Human Chromosomal Sites with “Safe Harbor” Potential for Targeted Transgene Insertion (2019)

This study identified 35 new sites for targeted transgene insertion that have the potential to serve as new human genomic "safe harbor" sites (SHS). SHS potential for these 35 sites, located on 16 chromosomes, including both arms of the human X chromosome, and for the existing human SHS <i>AAVS1</i>, <i>hROSA26</i>, and <i>CCR5</i> was assessed using eight different desirable, widely accepted criteria for SHS verifiable with human genomic data. Three representative newly identified sites on human chromosomes 2 and 4 were then experimentally validated by <i>in vitro</i> and <i>in vivo</i> cleavage-sensitivity tests, and analyzed for population-level and cell line-specific sequence variants that might confound site targeting. The highly ranked site on chromosome 4 (SHS231) was further characterized by targeted homology-dependent and -independent transgene insertion and expression in different human cell lines. The structure and fidelity of transgene insertions at this site were confirmed, together with analyses that demonstrated stable expression and function of transgene-encoded proteins, including fluorescent protein markers, selectable marker cassettes, and Cas9 protein variants. SHS-integrated transgene-encoded Cas9 proteins were shown to be capable of introducing a large (17 kb) gRNA-specified deletion in the <i>PAX3/FOXO1</i> fusion oncogene in human rhabdomyosarcoma cells and as a Cas9-VPR fusion protein to upregulate expression of the muscle-specific transcription factor <i>MYF5</i> in human rhabdomyosarcoma cells. An engineering "toolkit" was developed to enable easy use of the most extensively characterized of these new human sites, SHS231, located on the proximal long arm of chromosome 4. The target sites identified here have the potential to serve as additional human SHS to enable basic and clinical gene editing and genome-engineering applications.
Wireless Passive Sensor for Remote pH Monitoring (2011)

In this paper we describe a wireless passive pH sensor for high-resolution remote pH monitoring. The sensor is based on a passive LC coil resonator whose resonant frequency is monitored remotely by measuring the change in impedance of an interrogator coil coupled to the sensor coil. The sensor resonator consists of an inductive coil connected in parallel with a voltage dependent capacitor and a pH combination electrode. Change in the electrode potential in response to variations of the pH of the solution changes the capacitance, and therefore the resonant frequency of the sensor. A linear response with a 0.1 pH resolution is achieved over a 4–10 pH dynamic range. The response time of the sensor is demonstrated to be less than 30 s and is limited by the response time of the pH combination electrode. The described sensor technology is suitable for long-term remote pH monitoring in numerous fields such as biomedical sensing, environmental monitoring, industrial and chemical processing, and structural health monitoring.
Enhanced rate of conversion or recombination of markers within a region of unique sequence in the herpes simplex virus genome (1986)

Insertion mutants of herpes simplex virus type 1, containing a second copy of the sequences of BamHI fragment L (map coordinates 0.706 to 0.744) inserted in inverted orientation into the thymidine kinase gene (at map coordinate 0.315), have been further characterized. We reported previously that, as a result of intramolecular or intermolecular recombination between copies of the BamHI-L sequence at the normal locus and inserted locus, a high proportion of progeny genomes exhibited either inversions of the unique sequence flanked by these inverted repeats or other rearrangements. Now we report that a genetic marker (syn-1 or syn-1+) originally present only in the inserted copy of BamHI fragment L appears in progeny at both the normal and inserted loci, and vice versa, at high frequency. Because these phenomena have not been observed with other insertion mutants containing duplications of other sequences from unique regions of the genome, we conclude that BamHI fragment L contains an element that enhances the rate of homologous recombination in adjacent sequences, resulting in genome rearrangements and gene conversion-like events.
Erenumab in chronic migraine (2019)

This study provides Class II evidence that for patients with CM, erenumab treatment improves HRQoL, headache impact, and disability.