gebhart/patrepeval huggingface dataset:
Optimum Replacement Dose of Thyroid Hormone Assesed by Highly Sensitive TSH Determination in Patients with Congenital Hypothyroidism. (1988)

Serum thyroid hormone concentrations were measured in 100 samples from 25 patients with congenital hypothyroidism who were clinically well while receiving L-T4 therapy. Thyroxine concentrations were significantly higher than those of controls (p<0.01), while triiodothyronine was not significantly different. These samples were divided into four groups according to serum thyroid stimulating hormone concentrations as measured by highly sensitive immunoradiometric assay (IRMA-TSH). Serum thyroid hormone concentrations were compared among groups. The replacement dose of L-T4 and serum thyroid hormone in groups with undetectable IRMA-TSH were significantly higher than those in groups with normal or increased IRMA-TSH.These results show that serum thyroxine concentrations increase in most patients with congenital hypothyroidism on L-T4 therapy. Therefore, thyroxine concentrations above normal are not necessarily of clinical significance if IRMA-TSH is detectable. Undetectable IRMA-TSH might indicate the necessity for a reduction in the L-T4 replacement dose in patients with congenital hypothyroidism.
Mechanisms of Carcinogenicity of Methyl Halides (1993)

Methyl chloride, bromide, and iodide are used as methylating agents. These compounds are mutagenic in short-term tests and do not require activation by exogenous S9 mix. In DNA-binding studies performed in rats and mice, 14C-labeled methyl chloride was given by inhalation, and methylation of DNA bases was examined. The compound did not lead to specific DNA adducts. In particular, methylation of DNA bases was not observed. In contrast, methyl bromide and methyl iodide, upon oral and inhalation administration to rats and mice, caused systemic DNA methylation. Specifically, 3-methyl-adenine, 7-methyl-guanine, and O6-methyl-guanine were formed. Long-term inhalation bioassays have been performed in rats and mice with methyl chloride and methyl bromide. Methyl chloride induced renal tumors, but only in male mice at the highest concentration tested (1000 ppm). Under these special conditions, a number of secondary effects occur subsequent to glutathione depletion in the target tissue, resulting in DNA damage (DNA-protein cross-links and probably DNA single-strand breaks). The particular coincidence of secondary high-dose effects precludes a risk extrapolation to man. Methyl bromide did not induce tumors in rats and mice when administered by inhalation. However, experimental data point to a possible local carcinogenic effect on the rat forestomach when the compound is given by gavage. A factor that accounts for the discrepancy between systemic DNA methylation and apparent noncarcinogenicity upon inhalation might be the preference of 7-N over O6 methylation of guanine. An extrapolation of the negative rodent inhalation bioassay of methyl bromide to man might be problematic because rodents metabolize methyl bromide very quickly whereas in humans there is a particular subpopulation that only poorly metabolizes the compound ("nonconjugators"). Such individuals can be characterized by incubation of erythrocytes with methyl chloride or methyl bromide and measurement of the substrate decline. Methyl iodide has been tested, with positive outcome, in early carcinogenicity bioassays not based on modern methodology. However, these results, along with the proven systemic methylating potency of methyl iodide, argue in favor of a carcinogenic effect of the compound.
Activation of <i>RET</i> as a Dominant Transforming Gene by Germline Mutations of MEN2A and MEN2B (1995)

Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinoma are dominantly inherited cancer syndromes. All three syndromes are associated with mutations in RET, which encodes a receptor-like tyrosine kinase. The altered RET alleles were shown to be transforming genes in NIH 3T3 cells as a consequence of constitutive activation of the RET kinase. The MEN2A mutation resulted in RET dimerization at steady state, whereas the MEN2B mutation altered RET catalytic properties both quantitatively and qualitatively. Oncogenic conversion of RET in these neoplastic syndromes establishes germline transmission of dominant transforming genes in human cancer.
Seprase Promotes Rapid Tumor Growth and Increased Microvessel Density in a Mouse Model of Human Breast Cancer (2004)

Seprase is a cell surface serine protease that is expressed to high levels by invading human breast carcinoma cells. To investigate the role of seprase in breast cancer, MDA MB-231 human mammary adenocarcinoma cells were engineered to express active seprase to high levels. All cells grow rapidly in cell culture. But differences are discovered when the cells are tested for tumorigenicity, growth, and microvessel density by implantation into the mammary fat pads of female severe combined immunodeficient mice. Control transfectants that do not express seprase grow slowly whereas cells that express seprase to high levels form fast-growing tumors that are highly vascular. Microvessel density is elevated in tumors of two different lines of seprase transfectants to 146 +/- 67.4 and 144 +/- 33.42 vessels/mm(2) as compared with 50.5 +/- 12.9 vessels/mm(2) for tumors of control-transfected cells that do not express seprase. Seprase-expressing cells are better able to attract blood vessels and exhibit rapid tumor growth.
Tissue expanders in the gut: a histological and angiographic study. (1992)

A study to assess the effects of an intraluminally placed tissue expander in the rabbit jejunum was performed. Oval expanders (8 cm3) were placed via a midline coeliotomy through an enterotomy on the antimesenteric border of the jejunum. The reservoir was tunnelled subcutaneously through the abdominal wall. Expansion was carried out through this port at 7-10-day intervals using 0.5-cm3 increments. At the end of the experiment, angiography was performed and routine haematoxylin and eosin-stained sections were produced. Angiography revealed an increase in vessel diameter and vascular density of the specimen. Histology showed an increase in villi size, an increase in the number of goblet cells and a marked increase in the thickness of the muscular layer. The possible applications of this technique are discussed.
Design of multi-order diffractive THz lenses (2012)

Quadratic, multi-order diffractive lenses have been designed, fabricated, and demonstrated for the MMW-THz region, with the capability of focusing harmonic wavelengths on to a common focal point. Design wavelength and harmonic spacing can be chosen as design parameters, allowing great flexibility in lens design. Simulations were carried out to determine lens parameters and performance. These lenses reduce both spherical and chromatic aberrations at harmonic wavelengths, and are thinner and lighter than traditional refractive elements. This lens type is potentially useful to sensor fusion architectures.
Decreasing the stability and changing the substrate specificity of the Bacillus stearothermophilus alcohol dehydrogenase by single amino acid replacements (1998)

The gene encoding the alcohol dehydrogenase (adh-hT) from the thermophilic bacterium Bacillus stearothermophilus LLD-R strain has been overexpressed in Escherichia coli and the corresponding recombinant protein purified to homogeneity. Two putative structural determinants contributing to the higher stability of ADH-hT had been identified by comparison with the less thermostable ADH (ADH-T) from the less thermophilic B. stearothermophilus NCA 1503. In order to ascertain their role, mutations were designed to eliminate in ADH-hT a salt bridge at the N-terminus and a proline residue in the coenzyme binding domain replacing the amino acids located at the same positions in ADH-T. Three mutants--Glu11Lys, Pro242Ala, and Glu11Lys/Pro242Ala--were expressed at high level and the proteins purified and characterized. In general, the mutations had little effect on the activity, indicating that they were not disruptive. The thermal resistance was changed displaying quite additive effects.
Molecular basis of <i>Salmonella</i>‐induced enteritis (2000)

Salmonella pathogenesis is a complex and multifactorial phenomenon. Many genes required for full virulence in mice have been identified, but only a few of these have been shown to be necessary for the induction of enteritis. Likewise, at least some of the Salmonella virulence factors affecting enteritis do not appear to be required for infection of systemic sites in mice. This suggests that subsets of virulence genes influence distinct aspects of Salmonella pathogenesis. Recently, considerable progress has been made in characterizing the virulence mechanisms influencing enteritis caused by non-typhoid Salmonella spp. The Salmonella pathogenicity island-1-encoded type III secretion system mediates the translocation of secreted effector proteins into target epithelial cells. These effector proteins are key virulence factors required for Salmonella intestinal invasion and the induction of fluid secretion and inflammatory responses.
100 W/100 μm passively cooled fiber coupled diode laser at 976 nm based on multiple 100 μm single emitters (2009)

We developed a high brightness fiber coupled diode laser module based on single diode lasers providing more than 60 Watts output power from a 100 micron fiber at the optimum fiber laser pump wavelength of 976 nm. The advantage of using multiple single emitters on a submount compared to using bars or mini bars is the direct fiber coupling by use of optical stacking and the fact that no beam transformation is needed. We achieved best brightness with a high fill factor, optical efficiency of more then 80% and wall-plug efficiency of more then 40%. The use of single emitters on a submount also extends the life span due to reduced failure (x<sup>n</sup> vs. x) per device (n individual emitters vs. n emitters on a bar (mini array)). Low drive current enables modulation.
A translational study to investigate the role of carbohydrate sulfotransferase 15 for pancreatic cancer biology from in vitro to first-in-human clinical research. (2015)

e22201 Background: Chondroitin sulfate E (CS-E) is known to promote tumor invasion by cleaving CD44 on pancreatic cancer cells. The biosynthesis of CS-E is mediated by specific enzyme carbohydrate sulfotransferase 15 (CHST15) that is reported to correlate with poor prognosis in several types of cancer. However, the effect of CHST15 blockade in pancreatic cancer has not been investigated. Methods: We synthesized CHST15 dsRNA that selectively inhibits CHST15 genes and tested the effects of CHST15 dsRNA on tumor biology in vitro and in vivo. To translate nonclinical results into clinical practice, we conducted an open-labeled, investigator initiated trial (IIT) through EUS-guided intratumoral injection in patients with unresectable pancreatic cancer to assess the safety in one month-observation as a primary outcome. Results: CHST15 dsRNA inhibited the expression of CHST15 mRNA on PANC-1 cells in vitro, which was associated with reduced secretion of soluble CD44 variant. Intratumoral injection with CHST15 dsRNA inhibited tumor growth and induced necrosis in PANC-1 xenograft model in mice. In IIT, 4 pancreatic cancer patients with a median age of 76.5 years (male: female = 2:2) were completed for one month-observation and approved by monitoring committee. A total of 16 ml of CHST15 dsRNA (250nM) was injected into the tumor under EUS guidance without drug-related adverse events. Mean tumor size changed from 32.2 mm to 30 mm in diameter. In exploratory measures, reduction of CHST15 protein and partial necrosis were detectable in biopsy specimens. Reduction in serum CD44 variant and CA19-9 were also detectable, suggesting the effectiveness of dsRNA injection. Conclusions: This is the first translational document showing the potential of CHST15 as a new therapeutic target for pancreatic cancer at least through mechanism regulating the secretion of soluble CD44 variant. High safety and feasibility were demonstrated, which will contribute to further clinical trials investigating CHST15 dsRNA. Clinical trial information: UMIN000014178.
Collaborative topic modeling for recommending scientific articles (2011)

Researchers have access to large online archives of scientific articles. As a consequence, finding relevant papers has become more difficult. Newly formed online communities of researchers sharing citations provides a new way to solve this problem. In this paper, we develop an algorithm to recommend scientific articles to users of an online community. Our approach combines the merits of traditional collaborative filtering and probabilistic topic modeling. It provides an interpretable latent structure for users and items, and can form recommendations about both existing and newly published articles. We study a large subset of data from CiteULike, a bibliography sharing service, and show that our algorithm provides a more effective recommender system than traditional collaborative filtering.
Specific role of RhoC in tumor invasion and metastasis (2017)

Rho GTPases are regulators of many cellular functions and are often dysregulated in cancer. However, the precise role of Rho proteins for tumor development is not well understood. In breast cancer, overexpression of RhoC is linked with poor prognosis. Here, we aim to compare the function of RhoC and its homolog family member RhoA in breast cancer progression. We established stable breast epithelial cell lines with inducible expression of RhoA and RhoC, respectively. Moreover, we made use of Rho-activating bacterial toxins (Cytotoxic Necrotizing Factors) to stimulate the endogenous pool of Rho GTPases in benign breast epithelial cells and simultaneously knocked down specific Rho proteins. Whereas activation of Rho GTPases was sufficient to induce an invasive phenotype in three-dimensional culture systems, overexpression of RhoA or RhoC were not. However, RhoC but not RhoA was required for invasion, whereas RhoA and RhoC equally regulated proliferation. We further identified downstream target genes of RhoC involved in invasion and identified PTGS2 (COX-2) being preferentially upregulated by RhoC. Consistently, the COX-2 inhibitor Celecoxib blocked the invasive phenotype induced by the Rho-activating toxins.
Results of cavity reconstruction with hydroxyapatite implants after 15 years. (1998)

Long-term results of cavity reconstruction with hydroxyapatite are possible. The main problem is recurrent mucosal disease of the new middle ear-mastoid cleft.
Impact of GLP-1 and GLP-1 Receptor Agonists on Cardiovascular Risk Factors in Type 2 Diabetes (2010)

Type 2 diabetes (T2D) is associated with increased cardiovascular disease and mortality. Most diabetes treatments have not proven to reduce this risk and may be associated with worsening of specific cardiovascular risk factors. GLP-1 receptor agonists (GLP-1R agonists) are new incretin-based therapies for the treatment of T2D. They improve glucose control by stimulating insulin secretion and suppressing glucagon release, both in a glucose-dependent manner. There are two GLP-1R agonists approved for the treatment of T2D: once daily liraglutide and twice daily exenatide, both administered by sc injection. Based on recent clinical trials, GLP-1R agonists suggest having a protective role in cardiovascular risk factors besides improving glycemic control, compared to placebo and to standard diabetes therapies. Both liraglutide and exenatide have demonstrated to induce clinically significant weight loss and to reduce systolic blood pressure. Liraglutide also has a positive effect on the lipid profile and cardiovascular risk biomakers. Furthermore, recent data shows a direct effect of GLP-1 and its metabolites in the vascular endothelium and the myocardium, leading to vasodilator effects and improved cardiac function in humans with acute myocardial infarction or congestive heart failure. GLP-1R agonists have a positive impact on cardiovascular risk factors otherwise not addressed by most standard diabetes therapies. Whether these new compounds actually decrease cardiovascular disease and mortality remains to be demonstrated in outcome studies.
Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of Mesenchymal Stem Cell-Derived Vesicles (2017)

Extracellular vesicles (EVs) are important mediators of cell-to-cell communication pathways via the transport of proteins, mRNA, miRNA and lipids. There are three main types of EVs, exosomes, microparticles and apoptotic bodies, which are classified according to their size and biogenesis. EVs are secreted by all cell types and their function reproduces that of the parental cell. They are involved in many biological processes that regulate tissue homeostasis and physiopathology of diseases. In rheumatic diseases, namely osteoarthritis (OA) and rheumatoid arthritis (RA), EVs have been isolated from synovial fluid and shown to play pathogenic roles contributing to progression of both diseases. By contrast, EVs may have therapeutic effect via the delivery of molecules that may stop disease evolution. In particular, EVs derived from mesenchymal stem cells (MSCs) reproduce the main functions of the parental cells and therefore represent the ideal type of EVs for modulating the course of either disease. The aim of this review is to discuss the role of EVs in OA and RA focusing on their potential pathogenic effect and possible therapeutic options. Special attention is given to MSCs and MSC-derived EVs for modulating OA and RA progression with the perspective of developing innovative therapeutic strategies.
Resource Matching in a Peer-to-Peer Computational Framework. (2007)

The rise in high speed networks has led to an increased interest in the development of grid computing frameworks; the ubiquity of the broadband Internet connection has fostered widespread development and adoption of peer-to-peer applications. These two technologies provide complementary solutions to the inherent problems associated with distributed computations. Various frameworks that combine these two technologies have been proposed and implemented, each with its own strengths and weaknesses. In this paper, we propose and implement a P2P framework with an emphasis on resource management and job deployment to overcome the limitations of existing work. We believe that this will allow our framework to provide higher performance in a heterogeneous environment. We benchmark our framework and provide an analysis of the results.
<i>Echinacea </i>Standardization:  Analytical Methods for Phenolic Compounds and Typical Levels in Medicinal Species (2001)

A proposed standard extraction and HPLC analysis method has been used to measure typical levels of various phenolic compounds in the medicinally used Echinacea species. Chicoric acid was the main phenolic in E. purpurea roots (mean 2.27% summer, 1.68% autumn) and tops (2.02% summer, 0.52% autumn), and echinacoside was the main phenolic in E. angustifolia (1.04%) and E. pallida roots (0.34%). Caftaric acid was the other main phenolic compound in E. purpurea roots (0.40% summer, 0.35% autumn) and tops (0.82% summer, 0.18% autumn), and cynarin was a characteristic component of E. angustifolia roots (0.12%). Enzymatic browning during extraction could reduce the measured levels of phenolic compounds by >50%. Colorimetric analyses for total phenolics correlated well with the HPLC results for E. purpurea and E. angustifolia, but the colorimetric method gave higher values.
Extractive Bioconversion of 2‐Phenylethanol from <scp>l</scp> ‐Phenylalanine by <i>Saccharomyces</i> <i>cerevisiae</i> (2002)

The bioconversion of L-phenylalanine (L-Phe) to 2-phenylethanol (PEA) by the yeast Saccharomyces cerevisiae is limited by the toxicity of the product. PEA extraction by a separate organic phase in the fermenter is the ideal in situ product recovery (ISPR) technique to enhance productivity. Oleic acid was chosen as organic phase for two-phase fed-batch cultures, although it interfered to some extent with yeast viability. There was a synergistic inhibitory impact toward S. cerevisiae in the presence of PEA, and therefore a maximal PEA concentration in the aqueous phase of only 2.1 g/L was achieved, compared to 3.8 g/L for a normal fed-batch culture. However, the overall PEA concentration in the fermenter was increased to 12.6 g/L, because the PEA concentration in the oleic phase attained a value of 24 g/L. Thus, an average volumetric PEA production rate of 0.26 g L(-1) h(-1) and a maximal volumetric PEA production rate of 0.47 g L(-1) h(-1) were achieved in the two-phase fed-batch culture. As ethanol inhibition had to be avoided, the production rates were limited by the intrinsic oxidative capacity of S. cerevisiae. In addition, the high viscosity of the two-phase system lowered the k(l)a, and therefore also the productivity. Thus, if a specific ISPR technique is planned, it consequently has to be remembered that the productivity of this bioconversion process is also quickly limited by the k(l)a of the fermenter at high cell densities.
Parametric excitations of trapped ions in a linear rf ion trap (2002)

The parametric resonant behavior of ions inside a linear rf ion trap is studied both theoretically and experimentally. Theoretically, the resonant motion of ions inside an ideal ion trap is described by approximating the trapping rf field as a harmonic pseudopotential with the ions being excited by an additional quadrupolar ac voltage. The resulting damped Mathieu equation is studied and the regions of resonant instability are predicted by investigating the solutions. Experimentally, the parametric excitation of ${\mathrm{Mg}}^{+}$ ions is observed by subjecting the cloud of trapped ions to an additional quadrupolar ac field. The various ion motion resonances are detected through the disappearance of the laser-induced fluorescence signal. Weak damping is introduced by the presence of a low-pressure buffer gas. The experimental results are compared with the theoretical predictions.
A new fluorescent dye accumulation assay for parallel measurements of the ABCG2, ABCB1 and ABCC1 multidrug transporter functions (2018)

ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent. We found that in cells expressing functional ABCG2, ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. This fluorescence signal in the presence of specific transporter inhibitors is increased to the fluorescence levels in the control cells. Thus the PG accumulation assay is a new, unique tool for the parallel determination of the function of the ABCG2, ABCB1, and ABCC1 multidrug transporters. Since PG has very low cellular toxicity, the PG accumulation assay also allows the selection, separation and culturing of selected cell populations expressing either of these transporters.
Stability of Bacteriophage T4 Short Tail Fiber (2000)

Adsorption of T-even bacteriophages to the E. coli host cell is mediated by long and short tail fibers. Bacteriophage T4 short tail fiber protein p12 was used to investigate the stability against thermal and chemical denaturation. Purified p12 is thermostable with a melting point of 78 degrees C. Guanidinium chloride-induced denaturation displayed strong hysteresis and an intermediate between 2 and 3 M denaturant. The transitions occur at 1.5 and 3.2 M denaturant as revealed by fluorescence spectroscopy and circular dichroism. The data suggest an equilibrium unfolding intermediate with a separate unfolding of the C-terminal knob domain and the shaft region.