gebhart/patrepeval huggingface dataset:
Dietary Phospholipids and Intestinal Cholesterol Absorption (2010)

Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the ability of PLs to inhibit cholesterol absorption is of therapeutic benefit.
Contraindications to Metformin Therapy in Patients With NIDDM (1997)

More than half the patients in our series had concomitant conditions or complications conventionally regarded as cautions or contraindications to metformin; approximately 10% had a multiplicity of such conditions. Regular surveillance is necessary to detect the development of complications such as renal impairment. Vigilance is also required in view of the increased risk of major intercurrent illnesses, which may independently disturb lactate metabolism in patients with NIDDM. Metformin should be withdrawn promptly under such circumstances.
[Lys(B28), Pro(B29)]-Human Insulin: A Rapidly Absorbed Analogue of Human Insulin (1994)

[Lys(B28, Pro(B29)]-human insulin (LYSPRO) is an insulin analogue in which the natural amino acid sequence of the B-chain at positions 28 and 29 is inverted. These changes result in an insulin molecule with a greatly reduced capacity for self-association in solution. These clinical studies were designed to compare LYSPRO with human Regular insulin after subcutaneous injection in humans. We wanted to evaluate the effect of adding zinc to LYSPRO on its pharmacokinetics and pharmacodynamics. In addition, we compared the pharmacokinetics and pharmacodynamics of LYSPRO and human Regular insulin after subcutaneous injection to those of human Regular insulin given intravenously. Thus, we compared four treatments: solutions of zinc-free LYSPRO given subcutaneously (A), zinc-containing LYSPRO given subcutaneously (B), human Regular insulin given subcutaneously (C), and human Regular insulin given intravenously (D). We gave a 10-U dose of each treatment to 10 healthy (nondiabetic) men during glucose clamps. Serum insulin concentrations peaked more than two times higher (maximum serum insulin level [Cmax], 698 vs. 308 pM, A vs. C) and in less than half the time (time to Cmax [Tmax], 42 vs. 101 min, A vs. C) after subcutaneous injection of zinc-free LYSPRO. At the same time, the glucose infusion rate peaked in about half the time (time to maximum glucose infusion rate [TRmax], 99 vs. 179 min, A vs. C) and was slightly but not significantly higher (maximum glucose infusion rate [Rmax], 3.1 vs. 2.2 mmol/min, A vs. C) than that of human Regular insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Human IgG2 Antibodies Display Disulfide-mediated Structural Isoforms (2008)

In this work, we present studies of the covalent structure of human IgG2 molecules. Detailed analysis showed that recombinant human IgG2 monoclonal antibody could be partially resolved into structurally distinct forms caused by multiple disulfide bond structures. In addition to the presently accepted structure for the human IgG2 subclass, we also found major structures that differ from those documented in the current literature. These novel structural isoforms are defined by the light chain constant domain (C(L)) and the heavy chain C(H)1 domain covalently linked via disulfide bonds to the hinge region of the molecule. Our results demonstrate the presence of three main types of structures within the human IgG2 subclass, and we have named these structures IgG2-A, -B, and -A/B. IgG2-A is the known classic structure for the IgG2 subclass defined by structurally independent Fab domains and hinge region. IgG2-B is a structure defined by a symmetrical arrangement of a (C(H)1-C(L)-hinge)(2) complex with both Fab regions covalently linked to the hinge. IgG2-A/B represents an intermediate form, defined by an asymmetrical arrangement involving one Fab arm covalently linked to the hinge through disulfide bonds. The newly discovered structural isoforms are present in native human IgG2 antibodies isolated from myeloma plasma and from normal serum. Furthermore, the isoforms are present in native human IgG2 with either kappa or lambda light chains, although the ratios differ between the light chain classes. These findings indicate that disulfide structural heterogeneity is a naturally occurring feature of antibodies belonging to the human IgG2 subclass.
Synthesis and Metabolic Clearance of 1,25-Dihydroxyvitamin D as Determinants of Serum Concentrations: A Comparison of Two Methods* (1981)

We evaluated endogenous renal 1,25-dihydroxyvitamin D (1,25-OH)2D) synthesis by compartmental analysis of the plasma disappearance of injected [3H]1,25-dihydroxyvitamin D3 in 11 subjects with serum 1,25-(OH)2D concentrations varying from 9-154 pM (normal, 89 +/- 25 pM). Estimated renal synthesis ranged from 2-180 pmol/kg . day. Serum 1,25-(OH)2D concentrations in these subjects best fit a log function of renal synthesis: serum 1,25-(OH)2D, pM = -13 + 74 log renal 1,25-(OH)2D production, picomoles per kg/day (r = 0.91). We also evaluated serum 1,25-(OH)2D concentrations in 6 healthy subjects who had been given 0.6, 1.2, or 1.8 nmol calcitriol every 6 h during a period 6--12 days after hormone administration was begun. Steady serum 1,25-(OH)2D concentrations 2, 4, and 6 h after the last calcitriol dose were achieved in proportion to log dose: serum 1,25-(OH)2D, pM = -12 + 103 log 1,25-dihydroxyvitamin D3 dose, picomoles per kg/day (r = 0.94). Estimated 1,25-(OH)2D production rates using these two methods and assuming a normal serum 1,25-(OH)2D concentration of 89 pM range from 10--24 pmol/kg . day or, for a 70-kg subject, 0.6--1.7 nmol/day or 0.25--0.7 microgram/day. Metabolic clearance of 1,25-(OH)2D appears to be accelerated when production rates are increased.
Isolation of rare cells from cell mixtures by dielectrophoresis (2009)

The application of dielectrophoretic field-flow fractionation (depFFF) to the isolation of circulating tumor cells (CTCs) from clinical blood specimens was studied using simulated cell mixtures of three different cultured tumor cell types with peripheral blood. The depFFF method can not only exploit intrinsic tumor cell properties so that labeling is unnecessary but can also deliver unmodified, viable tumor cells for culture and/or all types of molecular analysis. We investigated tumor cell recovery efficiency as a function of cell loading for a 25 mm wide x 300 mm long depFFF chamber. More than 90% of tumor cells were recovered for small samples but a larger chamber will be required if similarly high recovery efficiencies are to be realized for 10 mL blood specimens used CTC analysis in clinics. We show that the factor limiting isolation efficiency is cell-cell dielectric interactions and that isolation protocols should be completed within approximately 15 min in order to avoid changes in cell dielectric properties associated with ion leakage.
Mass Spectrometry Characterization of Methylphenylsilane‐Hydrogen RF Plasmas (2007)

Abstract The plasmochemistry of methylphenylsilane diluted with hydrogen in radio frequency discharges during the deposition of thin films of plasmatic polysilane is investigated. The plasma reaction system has been examined under conditions identified from previous studies to give the best material. Mass spectrometry is used to follow the monomer fragmentation and to directly (on‐line) analyze the plasma composition under the static and dynamic regimes. The effect of input power is described. The products of the plasma‐induced reactions are collected in a cryogenic trap and then separated and analyzed by gas chromatography with a mass spectrometry analyzer. Organosilicon precursors for the plasma polymerization of one‐dimensional polysilanes are identified together with prevailing reaction pathways in the plasma. A simple method of monomer conversion efficiency is introduced. magnified image
Severe inhibition of maize wall degradation by synthetic lignins formed with coniferaldehyde (1998)

Although the enzymatic or ruminal degradability of plants deficient in cinnamyl alcohol dehydrogenase (CAD) is often greater than their normal counterparts, factors responsible for these degradability differences have not been identified. Since lignins in CAD deficient plants often contain elevated concentrations of aldehydes, we used a cell-wall model system to evaluate what effect aldehyde-containing lignins have on the hydrolysis of cell walls by fungal enzymes. Varying ratios of coniferaldehyde and coniferyl alcohol were polymerised into non-lignified primary walls of maize (Zea mays L) by wall-bound peroxidase and exogenously supplied H2O2. Coniferaldehyde lignins formed fewer cross-linked structures with other wall components, but they were much more inhibitory to cell wall degradation than lignins formed with coniferyl alcohol. This suggests that the improved degradability of CAD deficient plants is not related to the incorporation of p-hydroxycinnamaldehyde units into lignin. Degradability differences were diminished if enzyme loadings were increased and if hydrophobic aldehyde groups in lignins were reduced to their corresponding alcohols by ethanolic sodium borohydride. © 1998 Society of Chemical Industry.
Bariatric Embolization for Suppression of the Hunger Hormone Ghrelin in a Porcine Model (2012)

Bariatric embolization can significantly suppress ghrelin and significantly affect weight gain. Further study is warranted before this technique can be used routinely in humans.
A prospective analysis of cell‐free fetal DNA concentration in maternal plasma as an indicator for adverse pregnancy outcome (2006)

Our results confirm the clinical value of fetal DNA measurement in maternal plasma during the second trimester as a supplement for the diagnosis of aneuploidies. Its use as a screening instrument for complications that develop later in pregnancy seems to be limited but needs further investigation. Although the QF-PCR assay has the advantage of being applicable to both female and male fetuses, this approach cannot be used for quantitation of cff DNA in maternal plasma samples.
Development of a Lung Cancer Therapeutic Based on the Tumor Suppressor MicroRNA-34 (2010)

Tumor suppressor microRNAs (miRNA) provide a new opportunity to treat cancer. This approach, "miRNA replacement therapy," is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that drive a therapeutic response. Here, we describe the development of a therapeutic formulation using chemically synthesized miR-34a and a lipid-based delivery vehicle that blocks tumor growth in mouse models of non-small-cell lung cancer. This formulation is effective when administered locally or systemically. The antioncogenic effects are accompanied by an accumulation of miR-34a in the tumor tissue and downregulation of direct miR-34a targets. Intravenous delivery of formulated miR-34a does not induce an elevation of cytokines or liver and kidney enzymes in serum, suggesting that the formulation is well tolerated and does not induce an immune response. The data provide proof of concept for the systemic delivery of a synthetic tumor suppressor mimic, obviating obstacles associated with viral-based miRNA delivery and facilitating a rapid route for miRNA replacement therapy into the clinic.
Individual variations in structure and function of human eccrine sweat gland (1983)

The mechanisms underlying variations in perspiration rate at the glandular level are still poorly understood. Human eccrine sweat glands were dissected from the back of 12 adults, cannulated, and stimulated in vitro with methacholine (Mch). The maximal sweat rate and pKA for Mch determined from the dose-response curve for each individual were compared with the anatomic dimensions of the isolated secretory tubules. There was significant correlation between Mch sensitivity (pKA) and the size of the sweat gland, sweat rate per gland, sweat rate per unit length of the secretory tubule, and sweat rate per unit glandular volume. The sweat glands from individuals judged to be poor sweaters exhibited smaller size, lower secretory activity both in vivo and in vitro, and decreased Mch sensitivity compared with glands from physically fit individuals. We conclude that the increased Mch sensitivity and glandular hypertrophy are the two important features of functionally active sweat glands and infer that these parameters could improve as a result of acclimatization to physical exercise and/or heat.
Precise robot-assisted guide positioning for distal locking of intramedullary nails (2005)

This paper presents a novel image-guided robot-based system to assist orthopedic surgeons in performing distal locking of long bone intramedullary nails. The system consists of a bone-mounted miniature robot fitted with a drill guide that provides rigid mechanical guidance for hand-held drilling of the distal screws' pilot holes. The robot is automatically positioned so that the drill guide and nail distal locking axes coincide, using a single fluoroscopic X-ray image. Since the robot is rigidly attached to the intramedullary nail or bone, no leg immobilization or real-time tracking is required. We describe the system and protocol and present a method for accurate and robust drill guide and nail hole localization and registration. The in vitro system accuracy experiments for fronto-parallel viewing show a mean angular error of 1.3 degrees (std = 0.4 degrees ) between the computed drill guide axes and the actual locking holes axes, and a mean 3.0 mm error (std = 1.1 mm) in the entry and exit drill point, which is adequate for successfully locking the nail.
Light Emitting Diodes (2006)

Inorganic semiconductor light-emitting diodes (LEDs) are environmentally benign and have found widespread use as indicator lights, mobile displays, large-area displays, signage applications, and lighting applications. The entire visible spectrum can be covered by light-emitting semiconductors: AlGaInP and AlGaInN compound semiconductors are capable of emission in the red-to-yellow wavelength range and violet-to-green wavelength range, respectively. For white light sources based on LEDs, the most common approach is the combination of a blue LED chip with a yellow phosphor. Alternatively, a group of red, green, and blue (RGB) LEDs can be used; such source allows for color tunability. White LEDs are currently used to replace incandescent and fluorescent sources. In this review, the properties of inorganic LEDs will be presented, including emission spectra, electrical characteristics, and current-flow patterns. Structures providing high internal quantum efficiency, namely heterostructures and multiple quantum well structures, will be discussed. Advanced techniques enhancing the external quantum efficiency will be reviewed, including die shaping (chip shaping) and surface roughening. Different approaches to white LEDs will be presented and figures-of-merit such as the color rendering index and luminous efficacy will be explained. Besides visible LEDs, the technical challenges of newly evolving deep ultraviolet (UV) LEDs will be introduced. Finally, the packaging of low-power and high-power LED dies will be discussed.
CD28 and CD3 have complementary roles in T-cell traction forces (2014)

Mechanical forces have key roles in regulating activation of T cells and coordination of the adaptive immune response. A recent example is the ability of T cells to sense the rigidity of an underlying substrate through the T-cell receptor (TCR) coreceptor CD3 and CD28, a costimulation signal essential for cell activation. In this report, we show that these two receptor systems provide complementary functions in regulating the cellular forces needed to test the mechanical properties of the extracellular environment. Traction force microscopy was carried out on primary human cells interacting with micrometer-scale elastomer pillar arrays presenting activation antibodies to CD3 and/or CD28. T cells generated traction forces of 100 pN on arrays with both antibodies. By providing one antibody or the other in solution instead of on the pillars, we show that force generation is associated with CD3 and the TCR complex. Engagement of CD28 increases traction forces associated with CD3 through the signaling pathway involving PI3K, rather than providing additional coupling between the cell and surface. Force generation is concentrated to the cell periphery and associated with molecular complexes containing phosphorylated Pyk2, suggesting that T cells use processes that share features with integrin signaling in force generation. Finally, the ability of T cells to apply forces through the TCR itself, rather than the CD3 coreceptor, was tested. Mouse cells expressing the 5C.C7 TCR exerted traction forces on pillars presenting peptide-loaded MHCs that were similar to those with α-CD3, suggesting that forces are applied to antigen-presenting cells during activation.
Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity. (1990)

We have demonstrated that calf liver protein disulfide-isomerase (Mr 57,000) is a substrate for calf thymus thioredoxin reductase and catalyzes NADPH-dependent insulin disulfide reduction. This reaction can be used as a simple assay for protein disulfide-isomerase during purification in place of the classical method of reactivation of incorrectly oxidized ribonuclease A. Protein disulfide-isomerase contains two redox-active disulfides/molecule which were reduced by NADPH and calf thioredoxin reductase (Km approximately 35 microM). The isomerase was a poor substrate for NADPH and Escherichia coli thioredoxin reductase, but the addition of E. coli thioredoxin resulted in rapid reduction of two disulfides/molecule. Tryptophan fluorescence spectra were shown to monitor the redox state of protein disulfide-isomerase. Fluorescence measurements demonstrated that thioredoxin--(SH)2 reduced the disulfides of the isomerase and allowed the kinetics of the reaction to be followed; the reaction was also catalyzed by calf thioredoxin reductase. Equilibrium measurements showed that the apparent redox potential of the active site disulfide/dithiols of the thioredoxin domains of protein disulfide-isomerase was about 30 mV higher than the disulfide/dithiol of E. coli thioredoxin. Consistent with this, experiments using dithiothreitol or NADPH and thioredoxin reductase-dependent reduction and precipitation of insulin demonstrated differences between protein disulfide-isomerase and thioredoxin, thioredoxin being a better disulfide reductase but less efficient isomerase. Protein disulfide-isomerase is thus a high molecular weight member of the thioredoxin system, able to interact with both mammalian NADPH-thioredoxin reductase and reduced thioredoxin. This may be important for nascent protein disulfide formation and other thiol-dependent redox reactions in cells.
The White-Collar Police Force: "Duty to Report" Statutes in Criminal Law Theory (2002)

and accompanying text. 15Id. 6 See infra notes 207-08 and accompanying text.' Such is the case with some child abuse reporting laws.See Mosteller, supra note 26, at 217 (listing Texas, Rhode Island, Wyoming, Florida, Tennessee, Utah, Delaware, and New Hampshire as states that have varying catch-all provisions that impose the duty to report child abuse on "any person," "any other person," or "any person, including but not limited to [certain categories of reporters]").' See id. at 212
Tyrosine phosphorylation of a 94-kDa protein of human fibroblasts stimulated by streptococcal lipoteichoic acid. (1985)

Lipoteichoic acid (LTA) is an amphipathic component of Gram-positive bacteria. Previous studies from this laboratory have shown that at low concentrations, ranging from 0.1 to 10.0 micrograms/ml, LTA binds to mammalian cells and stimulates mitogenic responses as demonstrated by increased DNA and RNA synthesis. Tyrosine kinase appears to be involved in the action of a number of mitogens including epidermal growth factor, platelet-derived growth factor, and insulin. In the present study, we report the novel finding that tyrosine protein kinase activity is increased in human fibroblasts treated with LTA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of the whole cell lysate of fibroblasts cultured with 32Pi showed increased phosphorylation of a 94-kDa polypeptide. Alkali treatment of the gel resulted in a decreased intensity of the 94-kDa phosphorylated protein in control cells, but not in LTA-treated cells, suggesting the addition of phosphate groups to threonine or tyrosine residues. High voltage electrophoresis of the acid hydrolysate of the excised and eluted 94-kDa protein revealed that LTA stimulated the phosphorylation of tyrosine but not threonine residues. These results suggest that LTA acts on mammalian cells by phosphorylating tyrosine residues of certain proteins and thereby may regulate diverse functions of these cells.
Prospective Phase II Trial of Irinotecan, 5-Fluorouracil, and Leucovorin in Combination as Salvage Therapy for Advanced Colorectal Cancer (2001)

Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. This phase II study was conducted to establish the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil as salvage treatment for this disease. Open phase II trial of CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5-fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. Responders could proceed to surgical resection of residual disease. Thirty-nine patients from 2 institutions received a total of 287 cycles of therapy (median 7 cycles/patient). Eight patients achieved an objective response (7 for liver metastasis and 1 for lung metastasis), and an additional 12 obtained stabilization of disease or minor responses (MR); of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic resection of metastases and all them obtained a complete response. The median duration of response was 14 months, and the median survival was 11 months. Hematologic toxicity (neutropenia) was the most common serious side effect (29% of patients in 2% of cycles), but significant fever developed in only 4 patients. Grade III diarrhea was experienced in at least 1 cycle by 10% of patients. The results of this schedule compare favorably with previously reported experience of a phase I study designed to establish the dose of CPT11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.
Will future RFIC be flexible? (Invited) (2009)

Flexible electronics operating at low frequencies ranging from kilohertz to megahertz have existed for a while. The low carrier mobility of the active materials used in these electronics such as organic polymers, amorphous and polycrystalline silicon essentially limit their operation frequency. While flexible electronics have been desirable for RF for both portable gadget devices and military applications, achieving RF operation in the flexible form has been challenging. In this talk, flexible RFIC fabrication technologies will be presented to show the horizon in this emerging area. In the single-crystal Si nanomembrane-based RFIC technology, the creation and engineering of Si nanomembranes for RFIC applications will be described. The direct fabrication of large-area RF circuits on flexible substrates will be presented in detail. Using this method, over 10 GHz flexible RF devices and GHz flexible RF circuits have been demonstrated. Passive RF components that are directly fabricated on plastic substrate will also be described.