gebhart/patrepeval huggingface dataset:
Reevaluation of Fatty Acid Receptor 1 as a Drug Target for the Stimulation of Insulin Secretion in Humans (2013)

The role of free fatty acid receptor 1 (FFAR1/GPR40) in glucose homeostasis is still incompletely understood. Small receptor agonists stimulating insulin secretion are undergoing investigation for the treatment of type 2 diabetes. Surprisingly, genome-wide association studies did not discover diabetes risk variants in FFAR1. We reevaluated the role of FFAR1 in insulin secretion using a specific agonist, FFAR1-knockout mice and human islets. Nondiabetic individuals were metabolically phenotyped and genotyped. In vitro experiments indicated that palmitate and a specific FFAR1 agonist, TUG-469, stimulate glucose-induced insulin secretion through FFAR1. The proapoptotic effect of chronic exposure of β-cells to palmitate was independent of FFAR1. TUG-469 was protective, whereas inhibition of FFAR1 promoted apoptosis. In accordance with the proapoptotic effect of palmitate, in vivo cross-sectional observations demonstrated a negative association between fasting free fatty acids (NEFAs) and insulin secretion. Because NEFAs stimulate secretion through FFAR1, we examined the interaction of genetic variation in FFAR1 with NEFA and insulin secretion. The inverse association of NEFA and secretion was modulated by rs1573611 and became steeper for carriers of the minor allele. In conclusion, FFAR1 agonists support β-cell function, but variation in FFAR1 influences NEFA effects on insulin secretion and therefore could affect therapeutic efficacy of FFAR1 agonists.
A genetic algorithm based recurrent fuzzy neural network for linear induction motor servo drive (2007)

Abstract A genetic algorithm (GA) based recurrent fuzzy neural network (RFNN) is proposed to control the mover of a linear induction motor (LIM) servo drive for periodic motion in this paper. The GA is developed to search the optimal weights between the membership layer and the rule layer of RFNN. First, the dynamic model of an indirect field‐oriented LIM servo drive is derived. Then, an on‐line training RFNN with backpropagation algorithm is introduced as the tracking controller. Moreover, to guarantee the global convergence of tracking error, analytical methods based on a discrete‐type Lyapunov function are proposed to determine the varied learning rates of the RFNN. In addition, a real‐time GA is developed to search the optimal weights between the membership layer and the rule layer of RFNN on‐line. The theoretical analyses for the proposed GA‐based RFNN controller are described in detail. Finally, simulated and experimental results show that the proposed controller provides good control performance dynamic characteristics and is robust with regard to plant parameter variations and external load disturbance.
Custom-modified three-dimensional periodic microstructures by pattern-integrated interference lithography (2014)

By combining interference lithography and projection photolithography concurrently, pattern-integrated interference lithography (PIIL) enables the wafer-scale, rapid, and single-exposure fabrication of multidimensional periodic microstructures that integrate arbitrary functional elements. To date, two-dimensional PIIL has been simulated and experimentally demonstrated. In this paper, we report new simulated results of PIIL exposures for various custom-modified three-dimensional (3D) periodic structures. These results were generated using custom PIIL comprehensive vector modeling. Simulations include mask-integrated and mask-shaped 3D periodic arrangements as well as microcavities on top of or fully embedded within 3D periodic structures. These results indicate PIIL is a viable method for making versatile 3D periodic microstructures.
Protease‐catalyzed peptide synthesis using inverse substrates: The influence of reaction conditions on the trypsin acyl transfer efficiency (1991)

Benzyloxycarbonyl-L-alanine p-guanidinophenyl ester behaves as a trypsin "inverse substrate," i.e., a cationic center is included in the leaving group instead of being in the acyl moiety. Using this substrate as an acyl donor, trypsin catalyzes the synthesis of peptide bonds that cannot be split by this enzyme. An optimal acyl transfer efficiency was achieved between pH 8 and 9 at 30 degrees C.The addition of as much as 50% cosolvent was shown to be of minor influence on the acyl transfer efficiency, whereas the reaction velocity decreases by more than one order of magnitude. The efficiency of H-Leu-NH(2) and H-Val-NH(2) in deacylation is almost the same for "inverse" and normal type substrates.
The almost-invisible perineurioma (2015)

Intraneural perineurioma is a rare, benign slow-growing lesion arising from the perineurial cells that surrounds the peripheral nerve fibers. Typically it presents during childhood and young adulthood as a motor mononeuropathy. MRI plays an essential role in the diagnosis and localization of the lesion, which appears as a fusiform enlargement of the nerve fascicles that enhances intensely with gadolinium. Despite the typical clinical and radiological features, intraneural perineurioma remains largely underdiagnosed because of the lack of familiarity with this entity, but also as a result of technical limitations with conventional MRI that is typically performed as a screening test over a large field of view and without contrast sequences. The purpose of this article is to present the pitfalls and pearls learned from years of experience in the diagnosis and management of this relatively rare condition. Clinical suspicion and detailed neurological examination followed by high-quality electrophysiological studies (EPS) must lead to an adequate preimaging localization of the lesion and narrowing of the imaging area. The use of high-resolution (3-T) MRI combined with gadolinium administration will allow adequate visualization of the internal anatomy of the nerve and help in differentiating other causes of neuropathy. In cases where the lesion is not recognized but clinical suspicion is high, possible errors must be assessed, including the EPS localization, area of imaging, MRI resolution, and slice thickness.
Removal of the Acyl Donor Residue Allows the Use of Simple Alkyl Esters as Acyl Donors for the Dynamic Kinetic Resolution of Secondary Alcohols. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Postprandial Thermic Effect of Chicken Involves Thyroid Hormones and Hepatic Energy Metabolism in Rats (2013)

We investigated the postprandial thermic effect of chicken and its mechanisms in rats. A chicken diet showed a strong thermic effect after consumption, and the removal of fat induced more rapid and stronger thermogenesis. Although thermogenesis induced by a purified chicken protein diet was also strong, the thermic reaction was not so rapid and a remarkable rise of peripheral temperatures was not observed. Defatted chicken and purified chicken protein activated the thyroid hormone system and up-regulated rate-limiting enzyme genes of glucose metabolism and the tricarboxylic acid (TCA) cycle in the liver. Moreover, chicken protein up-regulated the mRNA expression of a rate-limiting enzyme of hepatic lipid metabolism. It is possible that the mechanisms by which body temperature is raised are different between chicken protein and defatted chicken. On the other hand, it is possible that chicken fat suppressed the expression of energy metabolism-related genes that was induced by the consumption of lean chicken. As a result, a rise of postprandial body temperature might not have been induced after consumption of chicken fat. These results suggest that the consumption of lean chicken activates the thyroid hormone system and hepatic energy metabolism and consequently induces the postprandial thermic effect of chicken.
Applying a Spray-jet Method for Measuring Naphthalene Derivatives by Nanosecond Laser MPI TOF-MS (2005)

Abstract A molecular-beam apparatus with a spray-jet method was applied for the laser TOF-MS study of naphthalene derivatives, 2-naphthoic acid (2NA), and 1,5-dihydroxynaphthalene (DHN). The results obtained by this method are compared with those obtained by the traditional sample-heating inlet method. The spray-jet method strongly improved the signal-to-noise ratio (S/N), compared to the traditional method. In addition, the intermolecular clusters due to hydrogen-bond formation were observed in case of the DHN system.
Tricyclic Guanidine Alkaloids from the Marine Sponge Acanthella cavernosa that Stabilize the Tumor Suppressor PDCD4 (2014)

A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.
Identification of a Hydroxypyrimidinone Compound (21) as a Potent APJ Receptor Agonist for the Potential Treatment of Heart Failure (2021)

This paper describes our continued efforts in the area of small-molecule apelin receptor agonists. Recently disclosed compound <b>2</b> showed an acceptable metabolic stability but demonstrated monodemethylation of the dimethoxyphenyl group to generate atropisomer metabolites <i>in vitro</i>. In this article, we extended the structure-activity relationship at the C2 position that led to the identification of potent pyrazole analogues with excellent metabolic stability. Due to the increased polarity at C2, the permeability for these compounds decreased. Further adjustment of the polarity by replacing the N1 2,6-dimethoxyphenyl group with a 2,6-diethylphenyl group and reoptimization for the potency of the C5 pyrroloamides resulted in potent compounds with improved permeability. Compound <b>21</b> displayed excellent pharmacokinetic profiles in rat, monkey, and dog models and robust pharmacodynamic efficacy in the rodent heart failure model. Compound <b>21</b> also showed an acceptable safety profile in preclinical toxicology studies and was selected as a backup development candidate for the program.
Abstract #3252: Effector memory T cells make a major contribution to redirected target cell lysis by T cell-engaging BiTE antibody MT110 (2009)

BiTE antibodies are single-chain bispecific antibody constructs with specificity for CD3 on T cells and a surface antigen on target cells. By transiently bridging T cells and cancer cells, BiTE antibodies are capable to mount a polyclonal T cell response that is no longer limited by T cell receptor specificity, presence of MHC class I, generation and presentation of peptide antigen, or the need for T cell costimulation. An ongoing clinical trial with blinatumomab, a CD19/CD3-bispecific BiTE antibody, in patients with therapy refractory non-Hodgkin\#8217;s lymphoma has shown lasting partial and complete tumor responses. Another BiTE antibody in clinical testing is EpCAM/CD3-bispecific MT110 for the treatment of patients with EpCAM+ cancer. We investigated the contribution of various subpopulations of T cells to the redirected target cell lysis mediated by BiTE antibodies. Naive and effector memory \#945;/\#946; T cells of CD8+ and CD4+ phenotype as well as NKT and \#947;/\#948; \#932; cells were freshly isolated from peripheral blood of healthy donors. T cell subpopulations were used at an effector to target ratio of 10:1 in cytotoxicity assays analyzing dose response of the EpCAM-specific BiTE antibody MT110 and percentage of target cell lysis after 18 h as indicators for the efficacy of redirected target cell lysis. As target for redirected lysis, the EpCAM expressing human KATO III gastric carcinoma cell line was used. The contribution to redirected lysis of central memory \#945;/\#946; T cells was indirectly studied. CD8+ effector memory T cells of CD45RA+ and CD45RO+ phenotype proved to be most efficacious in mediating redirected lysis by BiTE antibodies. CD4+ effector memory T cells were also highly active but with delayed kinetics, apparently, needed to upregulate expression of granzyme B. Naive CD8+ and CD4+ T cells showed very little to no activity. NKT and \#947;/\#948; T cells were also effective in BiTE-induced redirected lysis, however, showed less potency than CD8+ \#945;/\#946; T cells. Our data suggest that, with exception of naive T cells, all other T cell populations currently analyzed can contribute to redirected lysis by BiTE antibodies. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3252.
Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis (2018)

Recent evidence suggests that neutrophil extracellular traps (NETs) play an important role in the development of acute pancreatitis (AP). Herein, we examined the role of peptidylarginine deiminase (PAD), which has been shown to regulate NET formation, in severe AP. AP was induced by retrograde of taurocholate infusion into pancreatic duct in C57BL/6 mice. PAD was pharmacologically inhibited using Cl-amidine, a pan-PAD inhibitor. Pancreata were collected, and histones, citrullinated histone 3, chemokines, myeloperoxidase, and NETs were quantified. Chemokines, matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and DNA-histone complexes were determined in plasma samples. Infusion of taurocholate induced formation of NETs in pancreatic tissues of mice. Pretreatment with Cl-amidine markedly reduced the NET formation in the inflamed pancreas. Moreover, inhibition of PAD decreased the levels of blood amylase as well as edema, acinar cell necrosis, hemorrhage, and neutrophil infiltration in the pancreas of animals with AP. Administration of Cl-amidine attenuated the myeloperoxidase levels in the pancreas and lung of mice exposed to taurocholate. In addition, Cl-amidine decreased pancreatic levels of CXC chemokines, plasma levels of IL-6, and MMP-9 in mice with severe AP. This study shows that Cl-amidine is a potent inhibitor of NET formation in severe AP. Also, our results suggest that PAD regulates pathological inflammation and tissue damage in the inflamed pancreas. Thus, targeting PAD might be a useful strategy to treat patients with severe AP.
<title>Short fiber probe scheme for tapping-mode tuning fork near-field scanning optical microscopy</title> (2002)

Construction of a tapping-mode tuning fork with a short fiber probe as the force sensing element for near-field scanning optical microscopy is reported. This type of near-field scanning optical microscopy provides stable and high Q factor at the tapping frequency of the tuning fork, and thus gives high quality NSOM and AFM images of samples.We present results obtained by using the short tip tapping-mode tuning fork near-field scanning optical microscopy measurements performed on a single mode telecommunication optical fiber and a silica based buried channel waveguide.
Depth‐resolved micro‐Raman spectroscopy of tri‐layer PFSA membrane for PEM fuel cells: how to obtain reliable inner water contents (2012)

Raman depth‐profiling microspectroscopy is currently emerging as a fast and non‐invasive method for the local content measurement of water diffusing across the perfluorosulfonic acid polymer used as electrolyte in low‐temperature fuel cells. However, water depth profiles obtained thereby are affected by the gradual degradation of the Raman signal as the exciting radiation is focused deeper into the sample and, thus, usually exhibit artificial gradients. The appropriate way to rectify raw data, in order to measure reliable inner water contents, is discussed in the case of perfluorosulfonic acid membranes soaked in water. The method is tested on a tri‐layer material composed by stacked ionomers with different chemical composition, ionic exchange capacity and swelling. Comparison of Raman spectra of the different ionomers, obtained under strictly the same hydration and optical conditions, allows critical discussion of previously reported band assignments. It is shown that Raman bands arising from the polymer backbone and from the side chain can be readily discriminated. Reliable water concentration profiles can then be obtained from the ratio between the Raman signal of sorbed water and of the polymer phase. Comparison with depth profiles obtained by using the pure water signal as internal reference shows that quantitative measurement requires the careful choice of the adequate Raman bands for representing the ionomer occupation of the volume probed by the exciting radiation. Different to what usually performed, the ionomer Raman signal to be integrated for compensating optical losses should include both bands arising from the polymer backbone and side chains. Last, obtaining accurate water concentration profiles also needs the knowledge of the so‐called optical factor β , i.e. the ratio between the scattering cross sections of ionomer chemical groups and sorbed water, which has to be measured by independent Raman experiments. Copyright © 2012 John Wiley &amp; Sons, Ltd.
X-ray fabrication of SAW resonators with narrow electrodes in thick high-aspect-ratio polymer templates (2010)

X-ray lithography shadow projection using silicon nitride-based x-ray masks is used to fabricate sub-micron scale, high-aspect-ratio structures in thick polymer templates for surface acoustic wave (SAW) applications. Interdigital electrode patterns with 380 nm wide, free-standing polymer features are fabricated in 2 µm thick templates, representing an aspect ratio of 5.26:1. The tall and narrow polymer 'ribbons' run laterally in a serpentine arrangement of 114 electrodes over a large area of approximately 30 µm × 250 µm. Aluminum deposition and lift-off using the polymer templates are performed to construct metal electrodes for the verification of SAW resonator performance above 2.5 GHz. Environmental scanning electron microscopy and atomic force microscopy are used to inspect the metal electrode edge and surface topology, and demonstrate the feasibility of metal lift-off with highly vertical sidewall polymer templates for SAW applications. Such precise polymer templates could offer interesting possibilities for acoustic applications requiring thick and/or narrow electrodes and reflectors not only through more traditional metal deposition approaches but also as thick etch masks for metal removal.
Cryopreparation and Electron Tomography of Yeast Cells (2017)

Three-dimensional imaging of cells using electron tomography enables analysis of cell structure at unprecedented resolution. The preparation of cells for tomography using rapid freezing followed by freeze-substitution is an essential first step to ensure the optimal preservation of the cell structure for 3D studies. This protocol outlines a method for obtaining well-preserved cells using high-pressure freezing followed by freeze-substitution. We have found that this method is particularly well suited for electron tomography studies and has the added bonus of preserving antigenicity for immuno-electron microscopy. The steps involved in imaging cells and performing tomographic analysis of cellular structures are also outlined.
Validity of additivity approximations used in GAUSSIAN-2 theory (1992)

Three additivity approximations used in GAUSSIAN-2 (G2) theory to compute effective QCISD(T)/6-311+G(3df,2p) energies for molecular systems are investigated by carrying out full QCISD(T)/6-311+G(3df,2p) calculations on the set of 125 systems used for validation [J. Chem. Phys. 94, 7221 (1991)]. The results indicate that the approximations work very well. The average absolute deviation of the full results from experiment is 1.17 kcal/mol which is close to that of G2 theory (1.21 kcal/mol). The average absolute deviation with G2 theory is only 0.30 kcal/mol. However, the cpu cost increases by a factor of 2–3.
Photoanodic pyramid texturization of n-Ge(100) in HCl solution: unexpected anisotropy in the surface chemistry of etching (2019)

Ge pyramid texturization has been demonstrated<italic>via</italic>photoelectrochemical etching in HCl solution.
Pretransitional behavior of viscoelastic parameters at the nematic to twist-bend nematic phase transition in flexiblen-mers (2019)

We report dynamic light scattering measurements of the orientational (Frank) elastic constants and associated viscosities among a homologous series of a liquid crystalline dimer, trimer, and tetramer exhibiting a uniaxial nematic (N) to twist-bend nematic (N<sub>TB</sub>) phase transition. The elastic constants for director splay (K<sub>11</sub>), twist (K<sub>22</sub>) and bend (K<sub>33</sub>) exhibit the relations K<sub>11</sub> > K<sub>22</sub> > K<sub>33</sub> and K<sub>11</sub>/K<sub>22</sub> > 2 over the bulk of the N phase. Their behavior near the N-N<sub>TB</sub> transition shows dependency on the parity of the number (n) of the rigid mesomorphic units in the flexible n-mers. Namely, the bend constant K<sub>33</sub> in the dimer and tetramer turns upward and starts increasing close to the transition, following a monotonic decrease through most of the N phases. In contrast, K<sub>33</sub> for the trimer flattens off just above the transition and shows no pretransitional enhancement. The twist constant K<sub>22</sub> increases pretransitionally in both even and odd n-mers, but more weakly so in the trimer, while K<sub>11</sub> increases steadily on cooling without evidence of pretransitional behavior in any n-mer. The viscosities associated with pure splay, twist-dominated twist-bend, and pure bend fluctuations in the N phase are comparable in magnitude to those of rod-like monomers. All three viscosities increase with decreasing temperature, but the bend viscosity in particular grows sharply near the N-N<sub>TB</sub> transition. The N-N<sub>TB</sub> pretransitional behavior is shown to be in qualitative agreement with the predictions of a coarse-grained theory, which models the N<sub>TB</sub> phase as a "pseudo-layered" structure with the symmetry (but not the mass density wave) of a smectic-A* phase.
Mie Scattering Parameter Estimation in Near-Infrared Tomographic Breast Imaging (2004)

The Mie-type scattering parameters were estimated from NIR tomography of breast tissue. Results show that the average particle size and the number density can be estimated from bulk tissue transport scattering measurements at discrete wavelengths.
NMR Spectra from A Simplified Synthesis of Novel Dictyostatin Analogues with <i>In Vitro</i> Activity against Epothilone B–Resistant Cells and Antiangiogenic Activity in Zebrafish Embryos (2023)

NMR Spectra from A Simplified Synthesis of Novel Dictyostatin Analogues with &lt;i&gt;In Vitro&lt;/i&gt; Activity against Epothilone B–Resistant Cells and Antiangiogenic Activity in Zebrafish Embryos
Ultrasound-Mediated Therapies Using Receptor-Targeted Nanodroplets (2006)

Angiogenic vessels at tumor sites are leaky and allow particles less than 400 nm to pass through. We have developed targeted nanodroplets that are less than 400 nm in size and are capable of encapsulating drug molecules which can be released at the tumor site upon insonation. These nanodroplets are targeted to the α6β1 receptor, which is upregulated in prostate cancer.