gebhart/patrepeval huggingface dataset:
A 0.4-V Miniature CMOS Current Mode Instrumentation Amplifier (2017)

This brief presents a new low-power miniature instrumentation amplifier based on the operational floating current conveyor (OFCC). The OFCC is a general-purpose current mode device capable of realizing all functions as an operational amplifier. The proposed OFCC is designed and implemented in both TSMC low-power 90-nm and UMC high-speed 130-nm CMOS technology for use in low-voltage applications. A single supply of 0.4 V is used to reduce the power consumption. The design utilizes the energy-efficient subthreshold region. A self-cascode technique is used to enhance the tracking capability of the OFCC. Post-layout simulation and Monte Carlo analysis show promising results. The current mode instrumentation amplifier in 90 nm occupies 0.023 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> while consuming 11 μW with 14 kHz gain-independent bandwidth and common mode rejection ratio (CMRR) of 76 dB. The 130-nm design exhibits input referred noise of 1.1 μVRMS for a bandwidth of 0.07-150 Hz while consuming 14 μW and CMRR of 65 dB with 100-kHz bandwidth with chip area 0.021 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Antibodies to Human Thyroid Peroxidase in Autoimmune Thyroid Disease: Studies with a Cloned Recombinant Complementary Deoxyribonucleic Acid Epitope* (1989)

Previous studies carried out by screening a lambda gt11 human thyroid cDNA library with serum samples from selected patients with Hashimoto's thyroiditis and a polyclonal antibody to porcine thyroid peroxidase (TPO) confirmed, at the molecular level, that TPO is a major component of the thyroid microsomal antigen (M). That investigation led to the isolation of a clone (C2) which encodes an 85-amino acid segment of TPO and harbors a major epitope recognized by serum from several patients with autoimmune thyroid disease that contained anti-M autoantibodies (MAb). In this study, C2 antigen that was produced as a beta-galactosidase fusion protein was used to establish an enzyme-linked immunoabsorbent assay for the detection of anti-C2 autoantibodies (C2Ab). C2Ab then were assayed in 191 patients with different autoimmune and nonautoimmune thyroid disorders, and 50 patients with nonthyroidal autoimmune diseases. The results were compared with the titers of anti-TPO antibodies (TPOAb; as detected by monoclonal antibody-assisted RIA) and MAb (as detected by passive hemagglutination). Positive C2Ab was found in the serum of 85 of 136 (63%) patients whose serum contained TPOAb and/or MAb. A significant positive correlation was found between the levels of C2Ab and those of TPOAb (r = 0.76; P less than 0.001) or MAb (r = 0.69; P less than 0.001), which was independent of the type of underlying autoimmune thyroid disorder. Low levels of C2Ab also were found in 10 of 105 (9%) serum samples that did not contain TPOAb. Western blot analysis carried out on the latter samples showed that in 2 samples the apparent C2Ab reactivity was due to the presence of antibodies reacting with beta-galactosidase. In conclusion, we confirmed the validity of screening lambda gt11 cDNA human thyroid libraries to better characterize thyroid autoantigens and demonstrated the feasibility of using recombinant proteins to establish diagnostic assays for autoantibodies.
Polarity Influences the Efficiency of Recombinant Adenoassociated Virus Infection in Differentiated Airway Epithelia (1998)

To better understand mechanisms that limit rAAV transduction in the lung, we have evaluated several unique features of rAAV infection in polarized primary airway epithelial cultures. rAAV was found to transduce the basolateral surface of airway epithelia 200-fold more efficiently than the apical membrane. These differences in membrane infection correlated with the abundance of apical heparan sulfate proteoglycan (AAV-2 receptor) and virus binding. UV irradiation augmented rAAV transduction greater than 20-fold, only when virus was applied to the apical membrane. Ultrastructural analysis of UV-irradiated primary cultures demonstrated significant changes in microvilli architecture following exposure to 25 J/m2 UV. Although virus binding and the abundance of heparan sulfate proteoglycan were not increased at the apical membrane following UV irradiation, increased receptor-independent endocytosis of fluorescent beads was seen at the apical membrane following UV irradiation. We hypothesize that endocytotic processes associated with apical membrane-specific pathways of viral entry, and/or processing of virus to the nucleus, may be altered following UV irradiation. Interestingly, UV irradiation had an inhibitory effect on rAAV transduction from the basolateral membrane, which correlated with a decrease in the abundance of heparan sulfate proteoglycan at the basal membrane. In summary, these findings suggest that independent pathways of viral transduction may occur in the apical and basolateral compartments of polarized airway epithelia.
Mucosal Cytokine Therapy: Marked Antiviral and Antitumor Activity (1999)

Mucosal administration of the Th1 stimulatory cytokines interleukin-2 (IL-2), IL-12, IL-15, IL-18, or granulocyte-macrophage colony-stimulating factor (GM-CSF) induced antiviral activity in mice challenged systemically with a lethal dose of encephalomyocarditis virus (EMCV) similar to that observed following parenteral administration. In contrast, mucosal administration of the Th2 stimulatory cytokines IL-4, IL-5, IL-10, or IL-13 did not affect significantly the survival of EMCV-infected animals. Mucosal administration of IL-2 or IL-12 also exerted a marked antitumor activity in mice inoculated intravenously with Friend erythroleukemia cells. Recombinant IL-2 and IL-18, but none of the other recombinant cytokines tested, induced low levels of IFN in vitro. Polyclonal antibodies to both mouse and human interferon-alpha/beta (IFN-alpha/beta) abrogated the antiviral activity of IL-2 in vivo, even though the anti-human IFN-alpha/beta antibody did not neutralize mouse IFN-alpha/beta, and neither antibody bound to IL-2. IL-15 did not exhibit antiviral activity in IFN-alpha/beta R-/- mice, which are deficient in natural killer (NK) cell activity. These results suggest that mucosal Th1 cytokine therapy induces a soluble factor or activates a specific cell population in the lymphoid or epithelial tissue of the oropharyngeal cavity, which potentiates elimination of virus-infected or neoplasic cells systemically.
Targeting TARP, a novel breast and prostate tumor‐associated antigen, with T cell receptor‐like human recombinant antibodies (2008)

MHC class I molecules are important components of immune surveillance. There are no available methods to directly visualize and determine the quantity and distribution of MHC/peptide complexes on individual cells or to detect such complexes on antigen-presenting cells in tissues. MHC-restricted recombinant antibodies with the same specificity of T cell receptors (TCR) may become a valuable tool to address these questions. They may also serve as valuable targeting molecules that mimic the specificity of cytotoxic T cells. We isolated by phage display a panel of human recombinant Fab antibodies with peptide-specific, MHC-restricted TCR-like reactivity directed toward HLA-A2-restricted T cell epitopes derived from a novel antigen termed TCRgamma alternative reading frame protein (TARP) which is expressed on prostate and breast cancer cells. We have characterized one of these recombinant antibodies and demonstrated its capacity to directly detect specific HLA-A2/TARP T cell epitopes on antigen-presenting cells that have complexes formed by naturally occurring active intracellular processing of the antigen, as well as on the surface of tumor cells. Moreover, by genetic fusion we armed the TCR-like antibody with a potent toxin and demonstrated that it can serve as a targeting moiety killing tumor cells in a peptide-specific, MHC-restricted manner similar to cytotoxic T lymphocytes.
Lyme-Disease: A Multifocal Worldwide Epidemic (1991)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More
Functional Characterization of an Amino-terminal Region of HDAC4 That Possesses MEF2 Binding and Transcriptional Repressive Activity (2003)

Like the full-length histone deacetylase (HDAC) 4, its amino terminus (amino acids 1-208) without the carboxyl deacetylase domain is also known to effectively bind and repress myocyte enhancer factor 2 (MEF2). Within this repressive amino terminus, we further show that a stretch of 90 amino acids (119-208) displays MEF2 binding and repressive activity. The same region is also found to associate specifically with HDAC1 which is responsible for the repressive effect. The amino terminus of HDAC4 can associate with the DNA-bound MEF2 in vitro, suggesting that it does not repress MEF2 simply by disrupting the ability of MEF2 to bind DNA. In vivo, MEF2 induces nuclear translocation of both the full-length HDAC4 and HDAC4-(1-208), whereas the nuclear HDAC4 as well as HDAC4-(1-208) in turn specifically sequesters MEF2 to distinct nuclear bodies. In addition, we show that MyoD and HDAC4 functionally antagonize each other to regulate MEF2 activity. Combined with data from others, our data suggest that the full-length HDAC4 can repress MEF2 through multiple independent repressive domains.
Design and Characterization of Rotational Multicomponent Catalytic Nanomotors (2009)

Multicomponent rotational nanomotors consisting of Pt-coated TiO(2) nanoarms grown upon approximately 2.01-microm-diameter silica microbeads designed by dynamic shadowing growth are presented. When exposed to H(2)O(2), the structures rotate about an axis through the center of the microbead and perpendicular to the TiO(2) nanoarm at a rate of 0.15 Hz per % H(2)O(2) concentration. The rotational frequency increases parabolically when the surface tension of the solution is altered by the addition of sodium dodecyl sulphate; both relationships are explainable by a nanobubble-ejection model.
Transition of Brain Activation from Frontal to Parietal Areas in Visuomotor Sequence Learning (1998)

We studied the neural correlates of visuomotor sequence learning using functional magnetic resonance imaging (fMRI). In the test condition, subjects learned, by trial and error, the correct order of pressing two buttons consecutively for 10 pairs of buttons (2 x 10 task); in the control condition, they pressed buttons in any order. Comparison between the test condition and the control condition revealed four brain areas specifically related to learning: the dorsolateral prefrontal cortex (DLPFC), the presupplementary motor area (pre-SMA), the precuneus, and the intraparietal sulcus (IPS). We found that the time course of activation during learning was different between these areas. To normalize the individual differences in the speed of learning, we classified the performance of each subject into three learning stages: early, intermediate, and advanced stages. Both the relative increase of signal intensity and the number of activated pixels within the four areas showed significant changes across the learning stages, with different time courses. The two frontal areas, DLPFC and pre-SMA, were activated in the earlier stages of learning, whereas the two parietal areas, precuneus and IPS, were activated in the later stages. Specifically, DLPFC, pre-SMA, precuneus, and IPS were most highly activated in the early stage, in both the early and intermediate stages, in the intermediate stage, and in both the intermediate and advanced stages, respectively. The results suggest that the acquisition of visuomotor sequences requires frontal activation, whereas the retrieval of visuomotor sequences requires parietal activation, which might reflect the transition from the declarative stage to the procedural stage.
Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation (2000)

We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease. C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidi no-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. A concentration-dependent decrement in renal and hepatic globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P4. When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg/kg twice daily, renal globotriaosylceramide fell to below starting levels, consistent with an alpha-galactosidase A-independent salvage pathway for globotriaosylceramide degradation. Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. These data suggest that Fabry disease may be amenable to substrate deprivation therapy.
Monoclonal antibody therapies for lymphomas. (2001)

Important advances in molecular biology and chelation chemistry have led to new and improved monoclonal antibody reagents. Rituximab (IDEC-C2B8) was approved by the United States Food and Drug Administration for relapsed CD20-positive lymphomas, and denileukin diftitox was approved (DAB389IL-2) for CTCL. Ibritumomab tiuxetan and iodine 131 anti-B1 have excellent activity and acceptable toxicity and likely higher responses than rituximab. These questions should be answered in phase III trials, and preliminary results from the rituximab versus ibritumomab tiuxetan trial suggest higher responses to the latter. Data on radiolabeled Lym-1, T101, LL2, and anti-Tac also look promising. The therapeutic role of immunotoxins has yet to be determined, but encouraging data with DAB389IL-2 and LMB-2 have been reported. Antibody conjugates with drugs, prodrugs, nonprotein toxins, and other agents are also under investigation. Bispecific antibodies for lymphoma may also have a future role in lymphoma therapy. It is anticipated that many of the major advances in lymphoma therapy will be antibody based.
Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture: direct action of thyroid hormone in vitro. (1979)

We have studied the effect of 3,5,3'-triiodothyronine (T3) on the respiration of adult rat hepatocytes in primary monolayer culture prepared from hypothyroid rat liver. After addition of T3 to the culture medium at a concentration of 2 x 10(-7) M, oxygen consumption of the cultured cells increased detectably at 24 h and was maximal at 72--96 h, relative to control cultures (38.0 +/- 1.8 vs. 25.0 +/- 1.5 microliter/h.mg protein). The thyroid-responsive enzymes, Na+ + K+-activated adenosine triphosphatase (NaK-ATPase) and alpha-glycerophosphate dehydrogenase (GPD), each exhibited increased activity in response to T3, in parallel with the change in oxygen consumption, whereas the activity of Mg-dependent ATPase was unaffected. These responses to T3 were dose dependent over similar concentration ranges, the half-maximal response for each occurring at ca 8 x 10(-10) M. In thyroid-treated cells, the observed increase in respiration was almost completely (90%) inhibited after addition of ouabain (10(-3) M) to the culture medium. It was found also that a 4-h exposure of the cultured hepatocytes to T3 was sufficient to elicit a significant thermogenic response, measured at a time (48 h later) when T3 was no longer present in the medium. The response to T3 occurred in fully defined culture medium and was independent of the presence or absence of hypothyroid rat serum, corticosterone, or insulin, and cellular ATP was unaffected by T3 in concentrations up to 2 x 10(-7) M. The findings document that adult rat hepatocytes in primary monolayer culture respond directly to thyroid hormone; the increases in respiration and NaK-ATPase activity elicited by T3 were cotemporal and apparently coordinate.
Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance (2015)

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.
A study of swing-curve physics in diffraction-based overlay (2016)

With the increase of process complexity in advanced nodes, the requirements of process robustness in overlay metrology continues to tighten. Especially with the introduction of newer materials in the film-stack along with typical stack variations (thickness, optical properties, profile asymmetry etc.), the signal formation physics in diffraction-based overlay (DBO) becomes an important aspect to apply in overlay metrology target and recipe selection. In order to address the signal formation physics, an effort is made towards studying the swing-curve phenomena through wavelength and polarizations on production stacks using simulations as well as experimental technique using DBO. The results provide a wealth of information on target and recipe selection for robustness. Details from simulation and measurements will be reported in this technical publication.
Metabolic Diseases Drug Discovery-Strategic Research Institute's Third International World Summit. Dipeptidyl peptidase-IV inhibitors 26-27 July 2004, San Diego, CA, USA. (2004)

The majority of the presentations a the conference were on three highly sought-after targets for type 2 diabetes mellitus, namely PTP1B, PPARs and DPP-IV, reflecting the current focus and trend in the industry. A couple of novel targets were discussed, including the potential of myostatin as a type 2 diabetes mellitus target and a novel GPCR target. While small molecules were dominant, several biological-based approaches were covered: antibody therapeutics and oligonucleotide-based approaches (ASO and siRNA). In searching for small-molecule leads, structure-based rational design and focused combination chemistry appear to produce better results than a random high-throughput approach over the entire chemical library. The biggest challenges for diabetes and obesity drugs remain similar to those mentioned in previous meetings: increasing specificity to reduce side effects and maintaining long-term effect while maintaining or increasing efficacy. Due to the tremendous interest of the pharmaceutical industry in metabolic disease drug development, our knowledge of food intake and metabolism regulation has increased exponentially. Overall, the prospect of better drugs for, and better control of, type 2 diabetes mellitus and obesity is promising.
The use of stable isotope-labeled glycerol and oleic acid to differentiate the hepatic functions of DGAT1 and -2 (2012)

Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride (TG) synthesis. There are two isoforms, DGAT1 and DGAT2, with distinct protein sequences and potentially different physiological functions. To date, the ability to determine clear functional differences between DGAT1 and DGAT2, especially with respect to hepatic TG synthesis, has been elusive. To dissect the roles of these two key enzymes, we pretreated HepG2 hepatoma cells with (13)C(3)-D(5)-glycerol or (13)C(18)-oleic acid, and profiled the major isotope-labeled TG species by liquid chromatography tandem mass spectrometry. Selective DGAT1 and DGAT2 inhibitors demonstrated that (13)C(3)-D(5)-glycerol-incorporated TG synthesis was mediated by DGAT2, not DGAT1. Conversely, (13)C(18)-oleoyl-incorporated TG synthesis was predominantly mediated by DGAT1. To trace hepatic TG synthesis and VLDL triglyceride (VLDL-TG) secretion in vivo, we administered D(5)-glycerol to mice and measured plasma levels of D(5)-glycerol-incorporated TG. Treatment with an antisense oligonucleotide (ASO) to DGAT2 led to a significant reduction in D(5)-glycerol incorporation into VLDL-TG. In contrast, the DGAT2 ASO had no effect on the incorporation of exogenously administered (13)C(18)-oleic acid into VLDL-TG. Thus, our results indicate that DGAT1 and DGAT2 mediate distinct hepatic functions: DGAT2 is primarily responsible for incorporating endogenously synthesized FAs into TG, whereas DGAT1 plays a greater role in esterifying exogenous FAs to glycerol.
Kinetics of CBD, Δ 9 -THC Degradation and Cannabinol Formation in Cannabis Resin at Various Temperature and pH Conditions (2021)

<b>Introduction:</b> Cannabidiol (CBD), cannabinol (CBN), and Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC) are major cannabinoids in cannabis resin and products. The kinetic of the chemical reaction of resin cannabis is important for product development and storage. A few reports are available in the literature on the rate of CBD and Δ<sup>9</sup>-THC degradation, and CBN formation in dried resin and solutions of various pH. <b>Materials and Methods:</b> Thermal degradation of CBD, Δ<sup>9</sup>-THC, and formation of CBN was studied at 50°C, 60°C, 70°C, and 80°C for dried cannabis resin. The effect of pH and temperature on cannabinoids transformation in cannabis solution was also examined at pH 2, 4, 6, 8, 10, and 12 and at 40°C, 50°C, 60°C, and 70°C. High-performance chromatography coupled with diode-array detection (HPLC-DAD) was used for the analysis of CBD, CBN, and Δ<sup>9</sup>-THC transformation. The values of activation energies (<i>E<sub>a</sub></i>), shelf-life (t<sub>90%</sub> - t<sub>110%</sub>), and rate constant (<i>k</i>) were calculated for the CBD, Δ<sup>9</sup>-THC, and CBN. The effect of temperature and pH on the dried cannabis resin was adequately modeled with the Arrhenius equation. <b>Results:</b> The results indicated that the chemical kinetics in the thermal degradation of CBD, Δ<sup>9</sup>-THC, and formation of CBN were the zero-order, pseudo-zero-order, and first-order reactions, respectively, in cannabis resin. The first-order and pseudo-first-order degradation kinetics were evidenced for CBD and Δ<sup>9</sup>-THC, respectively, in cannabis solutions, whereas the zero-order formation kinetic was detected for the CBN. The transformation rate of the CBD, CBN, and Δ<sup>9</sup>-THC increased with increasing temperature, especially as temperature increased to 70°C at pH 2.0. The optimum pH for CBD stability was between pH 4 and 6, whereas the optimum pH for Δ<sup>9</sup>-THC stability was between pH 4 and 12. <b>Conclusion:</b> The major cannabinoids (CBD, CBN, and Δ<sup>9</sup>-THC) reacted more quickly at high temperature and in an acidic solution. Especially, the minimum transformation of CBD, CBN, and Δ<sup>9</sup>-THC was achieved by using on a low temperature, slightly to moderately acidic pH values, and short-time processing. These results may help to improve the storage condition of CBD, CBN, and Δ<sup>9</sup>-THC products and in the manufacturing process.